UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Synthetic studies using B-keto esters Sum, Phaik-Eng 1976

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata

Download

Media
831-UBC_1976_A6_7 S85.pdf [ 4.11MB ]
Metadata
JSON: 831-1.0060911.json
JSON-LD: 831-1.0060911-ld.json
RDF/XML (Pretty): 831-1.0060911-rdf.xml
RDF/JSON: 831-1.0060911-rdf.json
Turtle: 831-1.0060911-turtle.txt
N-Triples: 831-1.0060911-rdf-ntriples.txt
Original Record: 831-1.0060911-source.json
Full Text
831-1.0060911-fulltext.txt
Citation
831-1.0060911.ris

Full Text

S Y N T H E T I C S T U D I E S USING S-KETO E S T E R S b y P H A I K - E N G SUM B . S c . , F u J e n U n i v e r s i t y , T a i w a n 1972 T H E S I S S U B M I T T E D IN P A R T I A L F U L F I L L M E N T THE REQUIREMENTS FOR THE DEGREE OF MASTER OF S C I E N C E i n THE F A C U L T Y OF GRADUATE S T U D I E S DEPARTMENT OF C H E M I S T R Y We a c c e p t t h i s t h e s i s a s c o n f o r m i n g t o t h e r e q u i r e d s t a n d a r d THE U N I V E R S I T Y OF B R I T I S H COLUMBIA A u g u s t , 1976 (cT) Paik-eng Sum, 1976 In p r e s e n t i n g t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f t h e r e q u i r e m e n t s f o r an a d v a n c e d d e g r e e a t t h e U n i v e r s i t y o f B r i t i s h C o l u m b i a , I a g r e e t h a t t h e L i b r a r y s h a l l make i t f r e e l y a v a i l a b l e f o r r e f e r e n c e a n d s t u d y . I f u r t h e r a g r e e t h a t p e r m i s s i o n f o r e x t e n s i v e c o p y i n g o f t h i s t h e s i s f o r s c h o l a r l y p u r p o s e s may be g r a n t e d by t h e H e a d o f my D e p a r t m e n t o r by h i s r e p r e s e n t a t i v e s . I t i s u n d e r s t o o d t h a t c o p y i n g o r p u b l i c a t i o n o f t h i s t h e s i s f o r f i n a n c i a l g a i n s h a l l n o t be a l l o w e d w i t h o u t my w r i t t e n p e r m i s s i o n . D e p a r t m e n t o f C H E H tij d y The U n i v e r s i t y o f B r i t i s h C o l u m b i a 2075 Wesbrook P l a c e Vancouver, Canada V6T 1WS D a t e ABSTRACT The d i a n i o n s o f g - k e t o e s t e r s have b e e n g e n e r a t e d u s i n g one e q u i v a l e n t o f s o d i u m h y d r i d e and one e q u i v a l e n t o f n - b u t y l 1 i t h i u m o r two e q u i v a l e n t s o f l i t h i u m d i i s o p r o p y l -a m ide. The r e a c t i o n o f t h e s e d i a n i o n s w i t h v a r i o u s e p o x i d e s was s t u d i e d . On t r e a t m e n t o f l i t h i o s o d i o m e t h y l a c e t o -a c e t a t e (55) w i t h one and o n e - h a l f e q u i v a l e n t s o f e t h y l e n e o x i d e and on s u b s e q u e n t t r e a t m e n t w i t h a c i d , a t e t r a h y d r o -f u r y l i d e n e a c e t a t e 9_5_, f o r m e d f r o m t h e c y c l i z a t i o n o f t h e i n t e r m e d i a t e a l c o h o l . M e t h y l a - ( t e t r a h y d r o - 5 - m e t h y 1 - 2 - f u r y 1 i -dene) a c e t a t e (9_6) was a l s o s y n t h e s i z e d by t r e a t i n g t h e d i -a n i o n w i t h p r o p y l e n e o x i d e . The a l k y l a t i o n o f t h e s e d i a n i o n s f r o m 3 - k e t o e s t e r s w i t h a - c h l o r o e t h y 1 e t h y l e t h e r o r a - c h 1 o r o m e t h y 1 m e t h y l e t h e r was a l s o i n v e s t i g a t e d . T h i s p r o v i d e s a c o n v e n i e n t p r e p a r a t i o n o f t h e p r e c u r s o r s t o N a z a r o v ' s r e a g e n t w h i c h a r e v e r y u s e f u l i n t h e R o b i n s o n t y p e a n n e l a t i o n . The p r e p a r a t i o n o f m e t h y l 5 - m e t h o x y - 3 - o x o p e n t a n o a t e (12 0) c o u l d be e a s i l y a c h i e v e d i n a s i n g l e s t e p s y n t h e s i s by t r e a t i n g t h e l i t h i o s o d i o m e t h y l a c e t o a c e t a t e (5_5_) w i t h one e q u i v a l e n t o f c h l o r o m e t h y l m e t h y l e t h e r . S i m i l a r l y , m e t h y l 5 - e t h o x y - 3 - o x o h e x a n o a t e (12 9) and m e t h y l 5 - m e t h o x y - 3 - o x o h e x a n o a t e (130) were p r e p a r e d u s i n g o u r d i a n i o n r e a c t i o n . The s y n t h e s i s o f l a r g e r i n g compounds u s i n g t h e i n t e r n a l d o u b l e a l k y l a t i o n o f t h e s e d i a n i o n s w i t h d i h a l o -a l k a n e s i n a o n e - s t e p r e a c t i o n was f o u n d t o be r a t h e r d i f f i -c u l t . The i s o l a t e d p r o d u c t s were a m i x t u r e o f t h e b i s 3 -d i k e t o e s t e r s and a y - a l k y l a t e d m o n o - h a l o compound i n a p p r o x i -m a t e l y e q u a l a m o u n t s . H o w e v e r , on t r e a t m e n t o f t h e m o n o - h a l o compound w i t h one e q u i v a l e n t o f s o d i u m m e t h o x i d e i n r e f l u x i n g m e t h a n o l , t h e i n t r a m o l e c u l a r c y c l i z a t i o n a t t h e a - c a r b o n was e a s i l y a c h i e v e d . The m o n o - h a l o g - k e t o e s t e r s c o u l d a l s o be c y c l i z e d v i a t h e i r d i a n i o n s t o t h e c y c l i c o r s p i r o S - k e t o e s t e r s . 130 R = C H 3  129 R = C 2 H 5 142a - V -T A B L E OF C ONTENTS P a g e A b s t r a c t i i T a b l e o f C o n t e n t s v L i s t o f S c h e m e s v i i A c k n o w l e d g e m e n t s i x I n t r o d u c t i o n 1 H i s t o r i c a l B a c k g r o u n d T h e D i a n i o n o f g - D i c a r b o n y l C o m p o u n d s 3 R e a c t i o n s o f D i a n i o n s o f g - K e t o E s t e r s 21 R e s u l t s a n d D i s c u s s i o n R e a c t i o n o f D i a n i o n o f M e t h y l A c e t o a c e t a t e w i t h E p o x i d e s 33 R e a c t i o n o f L i t h i o S o d i o M e t h y l A c e t o a c e t a t e w i t h a - c h l o r o e t h e r 38 A l k y l a t i o n o f t h e D i a n i o n o f g - K e t o E s t e r s w i t h D i h a l o a l k a n e s a n d D i h a l o a l k e n e s 46 E x p e r i m e n t a l G e n e r a l 60 R e a c t i o n o f S o d i o L i t h i o M e t h y l A c e t o a c e t a t e w i t h E p o x i d e s 61 R e a c t i o n o f S o d i o L i t h i o M e t h y l A c e t o a c e t a t e w i t h a - C h l o r o - e t h y l e t h e r 63 - v i -T a b l e o f C o n t e n t s - c o n t ' d . P a g e A l k y l a t i o n o f t h e D i a n i o n o f B - K e t o E s t e r s w i t h D i h a l o a l k a n e s 68 R e a c t i o n o f S o d i o L i t h i o M e t h y l A c e t o a c e t a t e w i t h D i h a l o a l k e n e 76 D i a l k y l a t i o n a t t h e y - c a r b o n o f t h e D i a n i o n o f M e t h y l A c e t o a c e t a t e 80 B i b l i o g r a p h y 83 S p e c t r a l A p p e n d i x 90 - v i i -L i s t o f S c h e m e s P a g e S c h e m e I T h e A l k y l a t i o n o f D i s o d i o 2 , 4 - h e x a n e d i o n e 11 I I T h e A l k y l a t i o n o f D i a n i o n s o f g - K e t o A l d e -h y d e s 13 I I I R e a c t i o n o f t h e A n i o n o f D i m e t h y l n i t r o s a m i n e 18 IV D i a l k y l a t i o n o f D i a n i o n o f M e t h y l A c e t o a c e -t a t e 22 V T h e R e a c t i o n o f N i t r i l e s w i t h t h e D i a n i o n o f M e t h y l A c e t o a c e t a t e 30 VI T h e S y n t h e s i s o f E t h y l a - ( t e t r a h y d r o - 2 - f u r y 1 -i d e n e ) A c e t a t e 35 V I I R e a c t i o n o f D i a n i o n o f M e t h y l A c e t o a c e t a t e w i t h E p o x i d e s 36 V I I I T h e S y n t h e s i s o f M e t h y l 3 - o x o - 4 - p e n t e n o a t e 39 I X T h e S y n t h e s i s o f M e t h y l 5 - m e t h o x y - 4 - m e t h y 1 - 3 -o x o p e n t a n o a t e 42 X T h e S y n t h e s i s o f M e d i u m R i n g S i z e C y c l i c g - K e t o E s t e r s 47 XI R e a c t i o n o f S o d i o L i t h i o n M e t h y l A c e t o a c e -t a t e w i t h D i h a l o a l k a n e s 48 X I I T a u t o m e r i z a t i o n o f M e t h y l 2 - o x o c y c 1 o h e p t a n e -c a r b o x y l a t e a n d M e t h y l 2 - o x o c y c 1 o o c t a n e -c a r b o x y l a t e 50 X I I I C o n f i g u r a t i o n s o f e n o l a t e s o f g - K e t o E s t e r 53 - V 1 1 1 cheme XIV D i a l k y 1 a t i o n a t t h e y - c a r b o n o f t h e D i a n i o n o f M e t h y l A c e t o a c e t a t e 57 XV The S y n t h e s i s o f M e t h y l 3 - o x o c y c 1 o a l k y 1 -p r o p a n o a t e 58 A c k n o w l e d g e m e n t s I am much i n d e b t e d t o D r . L a r r y W e i l e r f o r h i s g u i d a n c e a n d k i n d e n c o u r a g e m e n t d u r i n g t h e c o u r s e o f t h i s w o r k . t o F r a n k p r e p a r i n I w o u l d a l s o l i k e W. B. S k i n n e r f o r g t h i s m a n u s c r i p t . t o e x t e n d my s i n c e r e t h a n k s t h e h e l p f u l a d v i c e he g a v e i n - 1 -I N T R O D U C T I O N I n t h e p a s t f o u r o r f i v e d e c a d e s , s y n t h e s i s o f n a t u r a l p r o d u c t s a n d n o v e l o r g a n i c c o m p o u n d s o f c h e m i c a l a n d b i o l o g i c a l i n t e r e s t h a s b e e n t h e m a j o r e f f o r t o f many s y n t h e -t i c o r g a n i c c h e m i s t s . A l t h o u g h a t r e m e n d o u s n u m b e r o f s u c h c o m p o u n d s , n a t u r a l o r s y n t h e t i c , h a v e now b e e n s y n t h e s i z e d , t h e d e v e l o p m e n t , o f m o r e e f f i c i e n t a n d e l e g a n t s y n t h e t i c r o u t e s i s s t i l l a m a i n t h e m e i n o r g a n i c c h e m i s t r y . I n r e c e n t y e a r s , many n a t u r a l p r o d u c t s i n c l u d i n g a l k a l o i d s , t e r p e n e s , p r o s t a g l a n d i n s , i n s e c t i c i d e s a n d c o m p o u n d s o f p h a r m a c e u t i c a l i n t e r e s t h a v e b e e n s y n t h e s i z e d b y e f f i c i e n t a n d w e l l c o n t r o l l e d s y n t h e t i c s e q u e n c e s . Many o f t h e s e s y n -t h e s e s w o u l d n o t be p o s s i b l e w i t h o u t t h e d i s c o v e r y o f new s y n -t h e t i c m e t h o d s . One o f t h e m o s t e x c i t i n g c h a l l e n g e s t o o r g a n i c chem-i s t s i s t h e c o n t r o l o f m o l e c u l a r a r c h i t e c t u r e . T h e p r o b l e m i n v o l v e s c r e a t i n g b o t h t h e p r o p e r f r a m e w o r k a n d s t e r e o c h e m i s t r y . O f t h e v a r i o u s r e a c t i o n t y p e s i n o r g a n i c s y n t h e s i s , n o n e i s m o r e b a s i c t h a n t h e f o r m a t i o n o f c a r b o n - c a r b o n b o n d s , i . e . a l k y l a t i o n w h i c h i s f u n d a m e n t a l i n b u i l d i n g up t h e s k e l e t o n o f o r g a n i c m o l e c u l e s . I n t h e d e v e l o p m e n t o f a new s y n t h e t i c m e t h o d o l o g y , t h e c r i t e r i a o f t h e u s e f u l n e s s o f a s y n t h e t i c m e t h o d l i e i n t h e g e n e r a l i t y , s t e r e o s p e c i f i c i t y a n d t h e o p t i m a l y i e l d o f t h a t p a r t i c u l a r s y n t h e t i c p r o c e s s . 2 -A l k y l a t i o n u s i n g 3 - d i c a r b o n y l compounds have l o n g b e e n known and have f o u n d w i d e s p r e a d a p p l i c a t i o n i n v a r i o u s f i e l d s o f o r g a n i c s y n t h e s i s . H owever, t h e use o f d i a n i o n s o f 3 - d i c a r b o n y l compounds i n a l k y l a t i o n r e a c t i o n s has n o t y e t b e e n f u l l y e x p l o i t e d . I n f a c t , i t has been one o f t h e m a j o r i n t e r e s t s i n o u r l a b o r a t o r y t o d e v e l o p new g e n e r a l and e f f i -c i e n t a l k y l a t i o n r e a c t i o n s b a s e d on t h e d i a n i o n s o f 3 - k e t o e s t e r s , w h i c h h o p e f u l l y w i l l be u s e f u l i n modern s y n t h e t i c c h e m i s t r y . B - K e t o e s t e r s were c h o s e n m a i n l y b e c a u s e i t i s u s u a l l y d i f f i c u l t t o d i f f e r e n t i a t e t h e two c a r b o n y l c a r b o n s i n a 3 - d i k e t o n e , w h i l e i t i s r e l a t i v e l y e a s y t o a c h i e v e r e a c t i o n s p e c i f i c a l l y a t e i t h e r one o f t h e two c a r b o n y l g r o u p s i n a 3 - k e t o e s t e r . 3 -H I S T O R I C A L BACKGROUND T h e D i a n i o n o f g - D i c a r b o n y l C o m p o u n d s g - D i c a r b o n y l c o m p o u n d s c a n u n d e r g o a l k y l a t i o n r e a c -t i o n s o r o t h e r c a r b o n - c a r b o n c o n d e n s a t i o n s a t t h e a - m e t h y l e n e c a r b o n t h r o u g h t h e f o r m a t i o n o f m o n o a n i o n s . F o r e x a m p l e , when a c e t y l a c e t o n e ( 2 ^ i s t r e a t e d w i t h an a l k a l i m e t a l , o r an a l k a l i m e t a l a l k o x i d e o r c a r b o n a t e , a m o n o a n i o n i s f o r m e d w h i c h c a n t h e n be a l k y l a t e d w i t h a l k y l h a l i d e s . T h e s e r e a c t i o n s o f t e n p r o c e e d v e r y s l o w l y e v e n i n r e f l u x i n g s o l v e n t s . I n 1 9 5 8 , H a u s e r a n d H a r r i s r e p o r t e d t h a t i f b e n z o y l -a c e t o n e (1_) o r a c e t y l a c e t o n e {2) i s f i r s t c o n v e r t e d t o t h e d i -p o t a s s i u m s a l t , t h e s a l t u n d e r g o e s a l k y l a t i o n o r o t h e r c a r b o n -c a r b o n c o n d e n s a t i o n a t t h e t e r m i n a l y - c a r b o n r a t h e r t h a n a t t h e a - m e t h y l e n e g r o u p 1 . T h e d i p o t a s s i u m s a l t i s g e n e r a t e d f r o m t h e d i k e t o n e w i t h p o t a s s i u m a m i d e i n l i q u i d a m m o n i a . On t r e a t m e n t w i t h one e q u i v a l e n t o f b e n z y l c h l o r i d e , t h e d i p o t a s -s i u m s a l t s r e a c t r a p i d l y a n d g i v e o n l y y - a l k y l a t e d p r o d u c t s . D i a l k y l a t i j i ' g ' p r o d u c t s w e r e n o t o b s e r v e d . o o p p R ^ v ^ \ KNH 2 R ^ \ < \ C 6 H 5 C H 2 C l R--» NH3 e CH 2 C 6 H 5 1_ R = C 6 H 5 2- R = C 6 H 5 JL R = C 6 H 5 ( 1 ) _2_ R = C H 3 U_ R - C H 3 _6_ R = C H ^ T h e s e a l k y l a t i o n r e s u l t s a r e u s e f u l i n p r e d i c t i n g t h e r e a c t i o n o f t h e d i c a r b a n i o n s o f 3 - d i c a r b o n y l c o m p o u n d s w i t h many o t h e r e l e c t r o p h i l i c a g e n t s . R e a c t i o n s t h a t h a v e b e e n o b s e r v e d i n c l u d e a l k y l a t i o n w i t h a r o m a t i c a n d a l i p h a t i c e s t e r s 3 ' 5 - 7 , c a r b o x y l a t i o n w i t h c a r b o n d i o x i d e 4 , c a r b o n y l a d d i t i o n r e a c t i o n s w i t h k e t o n e s a n d a l d e h y d e s 3 ' 7 - 9 a n d 1,4-a d d i t i o n s t o a , 3 - u n s a t u r a t e d c o m p o u n d s 5 ' 7 ' 9 . T h i s p r o c e d u r e o f g e n e r a t i n g t h e d i c a r b a n i o n s t o f u n c t i o n a l i z e 3 - d i c a r b o n y l c o m p o u n d s a t t h e y - p o s i t i o n h a s a l s o b e e n a p p l i e d t o 3 - k e t o a l d e h y d e 7_ a n d 3 - k e t o e s t e r 3 1 2 ' 31 32 5 -S i n c e a l k y l a t i o n s a t t h e Y - p o s i t i o n a r e n o t o b s e r v e d when 1:1 r a t i o o f d i c a r b o n y l c o m p o u n d a n d b a s e a r e e m p l o y e d , t h e a l k y l a t i o n u s i n g two e q u i v a l e n t s o f b a s e m u s t o c c u r a t t h e s i t e o f s e c o n d a r y i o n i z a t i o n . T r e a t m e n t o f t h e m o n o a n i o n s o f 3 - d i k e t o n e s o r g - k e t o a l d e h y d e s w i t h a s t o i c h i o m e t r i c a m o u n t o f a l k a l i m e t a l a m i d e a f f o r d s e s s e n t i a l l y c o m p l e t e f o r m a t i o n o f t h e d i a n i o n . A t t h e same t i m e a l k y l a t i o n a t t h e a - p o s i t i o n o f d i k e t o n e s h a s n o t b e e n o b s e r v e d d u r i n g t h e d i a n i o n r e a c t i o n s e v e n when e x c e s s a l k y l h a l i d e i s e m p l o y e d . A p p a r e n t l y t h e n u c 1 e o p h i 1 i c i t y o f t h e a - p o s i t i o n o f t h e d i a n i o n i s s u b s t a n -t i a l l y l e s s t h a n t h a t o f t h e y - p o s i t i o n . T h e h i g h r e a c t i v i t y o f t h e s e d i a n i o n s c a n be s h o w n b y c o m p a r i n g t h e r a t e o f d i a n i o n a l k y l a t i o n t o t h a t o f t h e a l k y l a t i o n o f t h e s i m p l e m o n o a n i o n s o f 3 - d i c a r b o n y l c o m p o u n d s . T h e l a t t e r p r o c e e d s v e r y s l o w l y e v e n a t e l e v a t e d t e m p e r a t u r e s w h i l s t r a p i d a l k y l a t i o n o f d i a n i o n s o c c u r s e v e n a t l o w t e m p e r -a t u r e . A h i g h d e g r e e o f s t e r e o s p e c i f i c i t y a l s o a p p e a r s i n t h e s e d i c a r b a n i o n s a l k y l a t i o n r e a c t i o n s . T r e a t m e n t o f t h e d i s o d i u m s a l t o f 1 - p h e n y 1 - 2 , 4 - p e n t a n e d i o n e ( 8 ) w i t h a - p h e n e t h y l c h l o r i d e g a v e e x c l u s i v e l y t h e e r y t h r o p r o d u c t 9^  i n d i c a t i n g t h a t a h i g h d e g r e e o f a s y m m e t r i c i n d u c t i o n o c c u r s d u r i n g t h e r e a c t i o n 1 1 . 9 The d i c a r b a n i o n s o f d i k e t o n e s a r e g e n e r a t e d by a d d i -t i o n o f t h e d i k e t o n e t o two e q u i v a l e n t s o f a l k a l i amide i n l i q u i d ammonia. The a m i d e s o f l i t h i u m , s o d i u m and p o t a s s i u m have been e m p l o y e d i n t h i s r e a c t i o n . The d i a n i o n s o f 3 - k e t o a l d e h y d e s have u s u a l l y b een p r e p a r e d by a d d i t i o n o f t h e mono-s o d i u m s a l t o f t h e k e t o a l d e h y d e t o p o t a s s i u m amide i n l i q u i d a m m o n i a 2 ' 1 2 . K e t o e s t e r d i a n i o n s have been p r e p a r e d p r i n c i -p a l l y by means o f p o t a s s i u m a m i d e 3 ' 1 3 , a l t h o u g h s o d i u m amide may s o m e t i m e s be s a t i s f a c t o r y 1 4 T h e d i c a r b a n i o n s g e n e r a t e d by d i f f e r e n t a l k a l i m e t a l s show c e r t a i n d i s t i n c t d i f f e r e n c e s i n r e a c t i v i t y . A t t h e same t i m e t h e y i e l d s o f a l k y l a t e d p r o d u c t s v a r y w i d e l y . I n g e n e r a l , i t was f o u n d t h a t t h e d i s o d i u m a n d d i p o t a s s i u m s a l t s o f a c e t y l -a c e t o n e (2) g a v e c o m p a r a b l e r e s u l t s 1 6 . T h e d i l i t h i u m s a l t s w e r e f o u n d t o r e a c t s l o w e r a n d p r o d u c e l o w e r y i e l d s t h a n e i t h e r t h e d i s o d i u m o r d i p o t a s s i u m s a l t s . F o r e x a m p l e , t h e a l k y l a t i o n o f d i l i t h i o a c e t y l a c e t o n e (10) w i t h n - b u t y l b r o m i d e was r e p o r t e d t o be o n l y 25% c o m p l e t e a f t e r t w i c e t h e r e a c t i o n p e r i o d e m p l o y e d t o o b t a i n 6 7 - 7 3 % a l k y l a t i o n o f d i s o d i o a c e t y 1 a c e t o n e ( 1 1 ) . 0 0 0 o M + M + 1 ) nBuBr 2) H 3 0 + (5 ) ( C H 2 ) 3 10 M = L i * 12 M = L i + <25% 11 M= N a + 13 M = N a + G 7-73 % T h i s l a c k o f r e a c t i v i t y c a n be e x p l a i n e d b y t h e h i g h e r c o v a l e n t c h a r a c t e r o f t h e 1 i t h i u m - c a r b o n b o n d b u t i t o n l y a p p l i e s t o 8 a l k y l a t i o n r e a c t i o n s b e c a u s e t h e s e d i l i t h i u m s a l t s h a v e b e e n f o u n d t o be v e r y u s e f u l f o r c o n d e n s a t i o n w i t h e n o l i z a b l e e s t e r s a n d k e t o n e s 6 ' 8 . F o r e x a m p l e , d i 1 i t h i o - b e n z o y l a c e t o n e ( 1 4 ) r e a c t s w i t h e t h y l a c e t a t e r a p i d l y a n d a t a r a t e much g r e a t e r t h a n p r o t o n a b s t r a c t i o n f r o m t h e e s t e r 6 , w h i l e t h e d i s o d i o - a n d d i p o t as s i o b e n z o y 1 a c e t o n e (_3) i o n i z e t h e e s t e r s e l e c t i v e l y 6 . Li Li OEt 0 0 0 ( 6 ) 15 0 0 0 3 16 ( 7 ) C 5 H 5 C 0 C H K C 0 C H 3 17 - 9 -Many e x a m p l e s o f a l k y l a t i o n o f t h e d i s o d i u m a n d d i -p o t a s s i u m s a l t s o f a c e t y l a c e t o n e (2_) h a v e a l s o b e e n r e p o r t e d . When p r i m a r y a n d s e c o n d a r y a l i p h a t i c h a l i d e s a r e u s e d a s a l k y l -a t i n g a g e n t s i n t h e a l k y l a t i o n o f d i s o d i o a c e t y 1 a c e t o n e ( 1 1 ) , t h e y i e l d s o f t h e monoa I k y 1 a t i o n p r o d u c t o b t a i n e d u s u a l l y r a n g e f r o m 5 5 % t o 8 0 % . H o w e v e r , o n l y 2 7 % y i e l d i s o b t a i n e d when i s o p r o p y l b r o m i d e i s u s e d 1 6 i n t h e a l k y l a t i o n o f d i p o t a s -s i o a c e t y l a c e t o n e (40 . B u t a y i e l d o f 6 6 % was a c h i e v e d i n t h e a l k y l a t i o n o f d i s o d i o a c e t y l a c e t o n e ( l J J 1 5 w i t h t h e same a l k y l -a t i n g a g e n t . A l k y l a t i o n o f d i s o d i o a c e t y 1 a c e t o n e w i t h s e c -b u t y l b r o m i d e g a v e a 78% y i e l d o f a l k y l a t e d p r o d u c t 1 5 . No a l k y l a t e d p r o d u c t s h a v e b e e n p r o d u c e d w i t h t - b u t y l c h l o r i d e o r 8 - p h e n e t h y l c h l o r i d e 1 6 p r o b a b l y d u e t o t h e i n h e r e n t l a c k o f r e a c t i v i t y o f t e r t i a r y a l k y l h a l i d e s i n d i s p l a c e m e n t r e a c -t i o n s . B i s g - d i k e t o n e s c a n be s y n t h e s i z e d t h r o u g h a l k y l a t i o n o f d i s o d i o a c e t y l a c e t o n e ( _ 1 J J w i t h d i h a l o a Ik a n e s . T r i , t e t r a , n o n a a n d d e c a - m e t h y l e n e b r o m i d e s h a v e b e e n e m p l o y e d s u c c e s s -f u l l y 1 7 . F a i l u r e s h a v e b e e n r e p o r t e d when m e t h y l e n e c h l o r i d e , e t h y l e n e c h l o r i d e , a n d e t h y l e n e b r o m i d e w e r e u s e d i n t h e p r e -p a r a t i o n o f b i s - d i k e t o n e s 18_1 7 . 10 -0 0 ii 1 2 + B r ( C H J n B r • Na + Na+ ^ n n = 3 > 4, 9 or 10 11 0 0 0 0 11 T h e r e g i o s p e c i f i c i t y o f t h e a l k y l a t i o n o f d i c a r b a n -i o n s o f 3 - d i k e t o n e h a s a l r e a d y b e e n d i s c u s s e d t o o c c u r o n l y a t t h e y - p o s i t i o n . I n t h e c a s e o f u n s y m m e t r i c a l g - d i k e t o n e s a l k y l a t i o n o f t h e i r d i a n i o n s i s c a p a b l e , a t l e a s t t h e o r e t i c a l l y , o f p r o d u c i n g two i s o m e r i c p r o d u c t s t h r o u g h t h e f o r m a t i o n o f two d i f f e r e n t d i a n i o n s . T h i s s i t u a t i o n a r i s e s i n u n s y m m e t r i c a l d i k e t o n e s w h e n e v e r b o t h c a r b o n y l g r o u p s a r e f l a n k e d b y c a r b o n a t o m s b e a r i n g o n e o r more h y d r o g e n a t o m s . F o r e x a m p l e , when 2 , 4 - h e x a n e d i o n e (1_9_) was t r e a t e d w i t h t w o e q u i v a l e n t s o f s o d i u m a m i d e , a m i x t u r e o f two d i f f e r e n t d i a n i o n s m i g h t be f o r m e d 1 8 . T r e a t m e n t o f t h e r e a c t i o n m i x t u r e w i t h m e t h y l i o d i d e g a v e an - 1 1 -8 9 : 1 1 m i x t u r e o f t h e m e t h y l 2_1_ a n d t h e m e t h y l e n e a l k y l a t i o n p r o d u c t s 2_2_ r e s p e c t i v e l y . Scheme I 8 9 : 1 1 12 A l k y l a t i o n o f d i p o t a s s i o p r o p i o n y l a c e t o n e g a v e s i m i l a r r e s u l t s 1 8 . I n t h e c a s e o f d i k e t o n e s w i t h c y c l i c s y s t e m , a l k y l a t i o n o f t h e i r d i a n i o n s g a v e o n l y t h o s e p r o d u c t s i n - w h i c h a l k y l a t i o n h a d o c c u r r e d a t t h e m e t h y l g r o u p 1 9 ( e q u a t i o n 9) . 0 0 1) 2 K N H 2 2) C 6 H 5 C H 2 C l 3 ) H + 0 0 6 H 5 ( 9 ) 2 3 n = 0 2U n = 1 25 n = 0 ( 6 2 % ) 26 n = 1 ( 5 o % ) T h e a l k y l a t i o n s o f g - k e t o a l d e h y d e s t h r o u g h d i a n i o n s h a v e a l s o b e e n r e p o r t e d 2 ' 1 3 > 2 0 . A l k y l a t i o n a t t h e y - p o s i t i o n h a s b e e n e f f e c t e d w i t h m e t h y l , n - b u t y l , n - o c t y l a n d b e n z y l h a l i d e s i n g o o d y i e l d 1 2 . T h e p r o d u c t s a r e u n s t a b l e a n d c o n -d e n s e g r a d u a l l y t o g i v e t r i a c y 1 b en z en e s 2_9. T h e i s o l a t i o n d i f f i c u l t y c a n b e o v e r c o m e b y c o n v e r t i n g t h e a l k y l a t e d k e t o -a l d e h y d e s t o m o re s t a b l e c o p p e r c h e l a t e s 2 7 . 13 -Scheme 1 1 Copper chelate 27 COCH9R• R C H ? C O l ^ ^ C O C H 2 R 29 KNH-Q o H RX 0 0 H R H + ( RCH 2COCH 2CHO ) 28 a - F o r m y 1 c y c 1 o p e n t a n o n e a n d a - f o r m y 1 - e y e l o h e x a n o n e h a v e b e e n c o n v e r t e d t o s e c o n d a r y d i a n i o n s b y t r e a t m e n t o f t h e i r m o n o s o d i u m s a l t s w i t h o n e e q u i v a l e n t o f p o t a s s i u m a m i d e i n l i q u i d a m m o n i a 2 1 . A l k y l a t i o n o f t h e s e d i a n i o n s h a v e b e e n e f f e c t e d w i t h s e v e r a l a l k y l h a l i d e s 2 1 >1 3 . 14 A l k y l a t i o n o f 3 - k e t o e s t e r s t h r o u g h t h e f o r m a t i o n o f d i a n i o n s w e r e a l s o s t u d i e d . A l t h o u g h t h e a l k y l a t i o n r e a c -t i o n o c c u r s o n l y a t t h e y - p o s i t i o n , t h e s e r e a c t i o n s w e r e r e p o r t e d t o g i v e p o o r y i e l d s o f a l k y l a t e d e s t e r s 3 . T h e d i -a n i o n o f e t h y l a c e t o a c e t a t e (_3_0) was p r e p a r e d b y a d d i t i o n o f t h e e s t e r t o t w o e q u i v a l e n t s o f p o t a s s i u m a m i d e i n l i q u i d a m m o n i a 3 . A l k y l a t i o n w i t h m e t h y l i o d i d e a n d e t h y l b r o m i d e g a v e t h e y - a l k y l a t e d p r o d u c t s i n y i e l d s o f 3 7 % a n d 2 9 % r e s -p e c t i v e l y . No s i g n i f i c a n t c h a n g e i n y i e l d s was o b s e r v e d e v e n when t h e r e a c t i o n t i m e was v a r i e d f r o m a f e w m i n u t e s t o an h o u r . B e n z y l a t i o n o f e t h y l d i s o d i o a c e t o a c e t a t e (_31_) h a s a l s o b e e n e f f e c t e d i n l o w y i e l d 1 4 . ? o 0 0 OC 2 H 5 2 > A O C 2 H 5 30 31 R 1) RX 2) H + Q 0 •OC 2 H 5 (10) 15 The p o o r r e s u l t s o b t a i n e d i n t h e s e a l k y l a t i o n s may be due t o t h e low t e m p e r a t u r e o f t h e r e a c t i o n and a l s o t h e e t h y l a c e t o a c e t a t e (3_0) may be o n l y p a r t i a l l y c o n v e r t e d t o d i a n i o n by amide i o n due t o a m i n o l y s i s o f t h e e s t e r f u n c -t i o n . Thus a s e a r c h f o r o t h e r r e a c t i o n c o n d i t i o n s t o p r o d u c e t h e d i a n i o n o f 8 - k e t o e s t e r s i s n e c e s s a r y . The b a s e u s e d i n e q u a t i o n (10) s h o u l d be n o n - n u c 1 e o p h i 1 i c , s t r o n g enough t o l e a d t o c o m p l e t e f o r m a t i o n o f t h e d i a n i o n s and i t s h o u l d be u s e f u l i n s o l v e n t s o t h e r t h a n l i q u i d ammonia. The d i l i t h i o s a l t o f e t h y l a c e t o a c e t a t e (3_0) was f i r s t s t u d i e d b e c a u s e o f i t s g r e a t e r s o l u b i l i t y t h a n t h e c o r -r e s p o n d i n g p o t a s s i u m o r s o d i u m s a l t s 2 4 ' 2 5 ' 2 6 . When two e q u i -v a l e n t s o f n - b u t y l 1 i t h i u m were added t o a s o l u t i o n o f e t h y l a c e t o a c e t a t e (30) i n t e t r a h y d r o f u r a n , i t a p p e a r e d t o a t t a c k t h e c a r b o n y l f u n c t i o n s i n s t e a d o f g e n e r a t i n g t h e d e s i r e d d i a n i o n 2 7 ' 2 8 , and t h u s a s e a r c h o f o t h e r b a s e s was i n i t i a t e d . R e c e n t a p p l i c a t i o n o f o t h e r b a s e s o f low n u c 1 e o p h i 1 i c i t y i n -c l u d e use o f t h e s a l t s o f d i a l k y l a m i n e s , s u c h as l i t h i u m d i -e t h y l a m i d e 2 9 , l i t h i u m d i i s o p r o p y l a m i d e 3 0 , l i t h i u m N - i s o p r o p y l -c y c l o h e x y l a m i d e 3 1 , l i t h i u m d i c y c l o h e x y l a m i d e 3 2 , l i t h i u m 2,2,6,6-t e t r a m e t h y l p i p e r i d e 3 2 ' 3 3 and l i t h i u m b i s ( t r i m e t h y 1 s i 1 y 1 ) amide 3 4 . Of a l l t h e s e b a s e s , o n l y l i t h i u m d i i s o p r o p y l a m i d e has been w i d e l y u s e d i n t h e p r e p a r a t i o n o f d i a n i o n s . C r e g e r 3 0 has u s e d l i t h i u m d i i s o p r o p y l a m i d e t o g e n e r a t e t h e d i a n i o n o f - 16 -2 - m e t h y l p r o p a n o i c a c i d (3_3) a n d g o o d r e s u l t s h a v e b e e n o b t a i n e d i n a l k y l a t i n g t h i s d i a n i o n . C0 2H 33 U N HF CO-36 RX R C0 2 H (1D 35 T h e same b a s e h a s a l s o b e e n u s e d t o g e n e r a t e t h e d i a n i o n o f t o l u i c a c i d 3_6_, a n d a l k y l a t i o n o f t h e m e t h y l g r o u p h a s b e e n a c h i e v e d i n m o d e r a t e y i e l d 3 5 . T h e d i a n i o n o f a s e r i e s C0 2 H LiN • C0 2 H R CH. THF. R'X R X CH 2 R' (12) 36 37 17 -o f a l k y l a c e t i c a c i d s 3_8 h a v e a l s o b e e n p r e p a r e d u s i n g l i t h i u m d i i s o p r o p y 1 a m i d e , a n d t h e s e h a v e b e e n shown t o r e a c t w i t h a l k y l h a l i d e s t o g i v e o n l y t h e mono - a - a I k y 1 a t e d p r o d u c t 4 0 3 6 . 0 0 II / 0 ~ R'X RCH 9 C-0H > R-C=CC\_ • > R - C - C - O H 1 I 0 I H R' 38 39 40 (13) T h e s e d i l i t h i o s a l t s w e r e a l s o a l l o w e d t o c o n d e n s e w i t h a l d e -h y d e s a n d k e t o n e s t o g i v e , a f t e r d e h y d r a t i o n , a - a 1 k y 1 a c r y 1 i c a c i d s 3 8 . A o n e - s t e p s y n t h e s i s o f a m i n o a c i d 3 9 c o u l d a l s o be a c h i e v e d when t h e s e s a l t s w e r e a m i n a t e d w i t h 0 - m e t h y l -h y d r o x y l a m i n e . H e x a m e t h y l p h o s p h o r a m i d e was a d d e d i n some r e a c t i o n s t o i n c r e a s e t h e s o l u b i l i t y o f t h e d i a n i o n s . S e e b a c h a n d E n d e r s 4 3 h a v e r e p o r t e d a d i f f i c u l t y , s i m i l a r t o t h a t o f t h e n u c l e o p h i l i c a t t a c k u p o n t h e c a r b o n y l g r o u p s o f e t h y l a c e t o a c e t a t e (_30_) d u r i n g t h e a t t e m p t s t o g e n e r a t e an a n i o n i n t h e a - p o s i t i o n o f d i m e t h y l n i t r o s a m i n e (4 5) w i t h n - b u t y 1 1 i t h i u r n . H o w e v e r , when l i t h i u m d i i s o p r o p y l -a m i d e was u s e d , t h e y w e r e a b l e t o f o r m t h e a n i o n 4_6 a n d a v e r y h i g h y i e l d o f a l k y l a t e d o r a l d o l p r o d u c t s 47 c o u l d be o b t a i n e d . H e n c e i t w o u l d a p p e a r t h a t l i t h i u m d i i s o p r o p y l -- 18 -Scheme III 1) nBuLi/THF > 2) (C 5H 5) 2CO N-N=0 45 Li N • C = NOH (C 6 H 5 ) 2 C' N-N=0 48 OH 49 > - N = 0 C 6 H 5 ° H O , C 6 H 5 Y ^ N - N = 0 ' OH ' 46 47 amide c o u l d a l s o be u s e d t o g e n e r a t e t h e d i a n i o n o f 3 - k e t o e s t e r s . 19 -An i n v e s t i g a t i o n o f o t h e r a l k y 1 - s u b s t i t u t e d l i t h i u m a m i d e s s h o w e d t h a t l i t h i u m b i s ( t r i m e t h y 1 s i 1 y 1 ) a m i d e was e m p l o y e d t o f o r m l i t h i o e t h y l a c e t a t e " , a n d t h a t t h e u s e o f t h i s b a s e c o u l d n o t be e x t e n d e d t o f o r m o t h e r e s t e r e n o -l a t e s . I n was a l s o f o u n d t h a t l i t h i u m N - i s o p r o p y 1 c y c 1 o h e x y 1 -a m i d e was s u p e r i o r t o o t h e r b a s e s i n f o r m i n g t h e e n o l a t e o f e t h y l h e x a n o a t e . Mayo e_t_ a l 4 4 h a v e s u c c e e d e d i n f i r s t g e n e r a t i n g t h e m o n o a n i o n o f p h e n y l a c e t o n e (5_0_) w i t h a m e t a l a m i d e w h i c h p r o t e c t e d t h e c a r b o n y l g r o u p f r o m n u c l e o p h i l i c a t t a c k a n d t h e n t r e a t m e n t o f t h e m o n o a n i o n s o l u t i o n w i t h n - b u t y 1 1 i t h i u m g a v e t h e d i a n i o n 5_2_ i n e x c e l l e n t y i e l d . 0 0 o C 6 H 5 X ^ i J \ M N H 2 C 6 H 5 \ A nBuLi C6H5\A (14) 50 51 52 O u r i n i t i a l a p p r o a c h i n t h e i n v e s t i g a t i o n o f d i a n i o n o f 3 - k e t o e s t e r s was q u i t e s i m i l a r 4 5 . One e q u i v a l e n t o f s o d i u m h y d r i d e s m o o t h l y c o n v e r t e d m e t h y l a c e t o a c e t a t e ( 5 3 ) i n t o i t s m o n o a n i o n 5_4, a n d a d d i t i o n o f o n e e q u i v a l e n t o f n - b u t y l 1 i t h i u m t o t h e m o n o a n i o n 5j4 g a v e t h e d e s i r e d d i a n i o n 5_5_. H o w e v e r , - 20 Q O O / A ^ C 0 2 C H 3 A ^ / C 0 2 C H 3 < 15) NaH - nBuLi --> 53 54 55 i t i s i m p o r t a n t t o n o t e t h a t e x c e s s o f o r g a n o m e t a l 1 i c i s n o t u s e d 2 8 ' 4 5 ' 4 7 . T h i s p r o c e d u r e o f g e n e r a t i n g t h e d i a n i o n o f 3 - k e t o e s t e r s h a s r e c e n t l y b e e n a p p l i e d t o 3 - k e t o p h o s p h o n i u m s a l t s 4 8 a n d 3 - k e t o p h o s p h o n a t e 4 9 . When t h e d i a n i o n o f m e t h y l a c e t o a c e t a t e (5_3) was q u e n c h e d w i t h a s o l u t i o n o f d e u t e r a t e d t r i f 1 u o r o a c e t i c a c i d , i t was f o u n d t h a t t h e r e c o v e r e d m e t h y l a c e t o a c e t a t e s h o w e d i n c o r p o r a t i o n o f d e u t e r i u m a t b o t h t h e a - a n d y - p o s i t i o n s . T h e a - d e u t e r i u m a t o m was e x c h a n g e d b y e x t r a c t i o n o f t h e i s o -l a t e d p r o d u c t w i t h a s o l u t i o n o f s o d i u m b i c a r b o n a t e . A f t e r t h e e x t r a c t i o n , i t was f o u n d , b y nmr a n d mass s p e c t r o s c o p y , t h a t t h e m e t h y l a c e t o a c e t a t e (5>_3) c o n t a i n e d 0.95 ± 0 . 0 3 d e u t e r -i u m a t o m s p e r m o l e c u l e a n d t h i s d e u t e r i u m was l o c a t e d o n l y i n t h e y - p o s i t i o n . 0 0 1) NaH 0 0 0CH 3 2] n B u L i [ / Y X 0 C H 3 D D 3) D 3 0 + 51 56 0 0 1) NaHC03 r ^ ^ 0 C H 3 (16) 2) H 3 0 + D 57 21 R e a c t i o n s o f D i a n i o n s o f 3 - K e t o E s t e r s Some r e a c t i o n s o f d i a n i o n s o f 3 - k e t o e s t e r s h a v e b e e n i n v e s t i g a t e d p r e v i o u s l y i n o u r l a b o r a t o r y . T h e f i r s t s t u d y i n v o l v e d t h e a l k y l a t i o n r e a c t i o n o f t h e d i a n i o n . T h e s e d i a n i o n s c o u l d r e a c t w i t h a r a n g e o f a l k y l a t i n g a g e n t s t o g i v e y - a l k y l a t e d p r o d u c t s i n v e r y g o o d y i e l d s 4 2 . T h e a l k y l a -0 0 0 0 0CH< 53 1) NaH / THF . > 2) nBuLi 3) RX R 0CH 3 (17.) 58 t i o n was f o u n d t o b e v e r y t e m p e r a t u r e d e p e n d e n t a n d t h i s c o u l d be o n e o f t h e r e a s o n s f o r t h e l o w y i e l d r e p o r t e d i n p r e v i o u s a t t e m p t s t o a l k y l a t e t h i s d i a n i o n 3 ' 5 2 ' 5 3 . I t was a l s o f o u n d t h a t d i a l k y l a t e d p r o d u c t s c o u l d be o b t a i n e d b y a d d i n g a n a d d i t i o n a l e q u i v a l e n t o f n - b u t y l - i l i t h i u m a n d a s e c o n d a l k y l a t i n g a g e n t . T h e s p e c t r a l e v i d e n c e c l e a r l y s h o w e d t h a t t h e a l k y l a t i o n h a d a g a i n o c c u r r e d a t t h e y - c a r b o n 5 0 . H o w e v e r , h i g h e r y i e l d s w e r e f o u n d i f t h e mono-a l k y l a t e d p r o d u c t was i s o l a t e d a n d p u r i f i e d b e f o r e p r o c e e d i n g w i t h t h e s e c o n d a l k y l a t i o n . 22 Scheme IV T h e s e r e a c t i o n s w e r e f o u n d t o p r o c e e d v e r y e a s i l y a t 0 - 2 5 ° C a n d w e r e c o m p l e t e i n l e s s t h a n 30 m i n . c o m p a r e d w i t h t h e a - a l k y l a t i o n o f ( 3 - k e t o e s t e r w h i c h t y p i c a l l y r e q u i r e d s e v e r a l h o u r s i n r e f l u x i n g s o l v e n t s . T h i s c o u l d e x p l a i n why no a - a l k y l a t e d p r o d u c t was d e t e c t e d i n t h e a b o v e r e a c t i o n e v e n w i t h an e x c e s s o f a l k y l a t i n g a g e n t . • 23 -T h e r e a c t i o n s o f d i a n i o n s w i t h a , t o - d i h a l o a l k a n e s w e r e a l s o b r i e f l y i n v e s t i g a t e d 5 1 . T h e p r o d u c t s i s o l a t e d w e r e a m i x t u r e o f c y c l i c a l k y l a t e d p r o d u c t s 6_3_ a n d a b i s 3 - k e t o e s t e r s (6_2_) . T h e r a t i o o f t h e s e two p r o d u c t s may 0 0 63 ( n = 3 only ) 5 2 ( n = 3 10 ) d e p e n d on t h e f a t e o f t h e i n t e r m e d i a t e 61_. T h e i n t e r m e d i a t e 61 may r e a c t w i t h a n o t h e r m o l e c u l e o f d i a n i o n t o g i v e \ 2 4 -b i s 3 - k e t o e s t e r 6_2 o r i t may u n d e r g o i n t r a m o l e c u l a r c y c l i z a -t i o n t o g i v e a c y c l i c c o m p o u n d 63_. E q u a l a m o u n t s o f b o t h p r o d u c t s c o u l d be o b t a i n e d when one e q u i v a l e n t o f 1 , 3 - d i b r o m o -p r o p a n e was a d d e d t o a s o l u t i o n o f d i a n i o n 5_5_. H i g h e r y i e l d s o f c y c l i z e d p r o d u c t c o u l d be o b t a i n e d i f e x c e s s d i b r o m o com-p o u n d was a d d e d , w h i l e w i t h o n l y o n e - h a l f e q u i v a l e n t o f t h e d i b r o m o c o m p o u n d , t h e p r e d o m i n a n t p r o d u c t w o u l d be t h e b i s 3 - k e t o e s t e r 6_2. I t was a l s o r e p o r t e d 5 1 t h a t when o n e - h a l f e q u i v a l e n t o f 1 , 1 0 - d i b r o m o d e c a n e was u s e d a s t h e a l k y l a t i n g a g e n t , o n l y b i s 3 - k e t o e s t e r , 3 , 1 6 - d i o x o o c t a d e c a n e d i o a t e was i s o l a t e d i n a l m o s t q u a n t i t a t i v e y i e l d a n d no c y c l i c p r o d u c t was d e t e c t e d . When d i b r o m o m e t h a n e was e m p l o y e d i n t h e a l k y l a t i o n , no e v i d e n c e f o r t h e c y c l i c p r o d u c t o r t h e b i s 3 - k e t o e s t e r was f o u n d . H o w e v e r , a new c o m p o u n d was p r o d u c e d i n r e a s o n a b l e y i e l d , a n d t h e s p e c t r a l a n d a n a l y t i c a l d a t a i n d i c a t e d t h a t t h e c o m p o u n d was i n d e e d t h e p r o d u c t w h i c h a r i s e s f r o m an i n -t e r n a l a l d o l c o n d e n s a t i o n o f t h e e x p e c t e d i n t e r m e d i a t e 6_4 shown i n e q u a t i o n ( 1 9 ) . - 2 5 -0 0 0 0 65 The d i a n i o n s of 3-keto e s t e r s were a l s o found to undergo a l d o l type r e a c t i o n s 5 4 ' 5 5 with ketones and aldehydes to y i e l d <5-hydroxy-3-keto e s t e r s 6_7_. These hydroxy e s t e r s 6 7 could then be dehydrated to the corresponding y , S - u n s a t -urated 3-keto e s t e r s 6 8 . C R R 68 26 When t h e d i a n i o n was t r e a t e d w i t h a c e t a l d e h y d e , p e n t a n a l a n d c y c l o p e n t a n o n e , a l a r g e a m o u n t o f m e t h y l a c e t o -a c e t a t e ( 5 J5 ) was r e c o v e r e d . P r o t o n t r a n s f e r was s u s p e c t e d a s t h e c o m p e t i n g s i d e r e a c t i o n i n t h e s e c a s e s s i n c e s e l f -c o n d e n s a t i o n p r o d u c t s o f c y c l o p e n t a n o n e w e r e a l s o f o r m e d i n t h e r e a c t i o n o f d i a n i o n a n d c y c l o p e n t a n o n e . S i m i l a r d i f f i -c u l t i e s i n v o l v i n g p r o t o n t r a n s f e r h a v e a l s o b e e n r e p o r t e d d u r i n g t h e r e a c t i o n o f d i a n i o n s f r o m g - d i k e t o n e s w i t h k e t o n e s a n d a l d e h y d e s 6 ' 8 . I n t h e c a s e o f a r o m a t i c a l d e h y d e s a n d k e t o n e s t h e p r o d u c t s w e r e f i r s t c o n v e r t e d t o t h e c o r r e s p o n d i n g t r i m e t h y l -s i l y l e t h e r 5 4 p r i o r t o p u r i f i c a t i o n b e c a u s e t h e s e p r o d u c t s u s u a l l y u n d e r w e n t some d e c o m p o s i t i o n , f o r e x a m p l e , r e t r o -a l d o l a n d d e c a r b o x y m e t h y l a t i o n on d i s t i l l a t i o n . I t was f o u n d t h a t no i d e n t i f i a b l e a l d o l p r o d u c t c o u l d be o b t a i n e d when t h e d i a n i o n was t r e a t e d w i t h f o r m a l d e h y d e . T h e a l d o l r e a c t i o n o f t h e d i a n i o n was a l s o f o u n d t o be v e r y t e m p e r a t u r e d e p e n d e n t as was t h e a l k y l a t i o n r e a c t i o n 4 5 . B a s e s o t h e r t h a n s o d i u m h y d r i d e a n d n - b u t y 1 1 i t h i u r n w e r e i n v e s t i g a t e d . I t was f o u n d t h a t two e q u i v a l e n t s o f ' l i -t h i u m d i i s o p r o p y 1 a m i d e 3 7 c o u l d a l s o l e a d t o c o m p l e t e f o r m a t i o n o f t h e d i a n i o n a n d s u b s e q u e n t r e a c t i o n w i t h b e n z o p h e n o n e ( 6 9 ) a t 0° C g a v e t e r m i n a l a l d o l p r o d u c t 7_0 i n 76% y i e l d . H o w e v e r , no t e r m i n a l a l d o l p r o d u c t was d e t e c t e d when two e q u i v a l e n t s 0 0 0 Q 0 0 C 2 H 5 + ph^ ^Ph 31 69 OH " " 7 0 OC 2 H 5 Ph (21) o f l i t h i u m h e x a m e t h y l d i s i l y l a m i d e 5 5 w e r e u s e d a n d i t was s u s p e c t e d t h a t t h i s b a s e m i g h t n o t b e s t r o n g e n o u g h t o g e n e r -a t e t h e d i a n i o n . B e s i d e s t h e r e p o r t e d a l k y l a t i o n s , a m e t h o d f o r t h e s u c c e s s f u l a c y l a t i o n o f t h e d i a n i o n h a s a l s o b e e n d e v e l o p e d 5 7 > 5 8 . W o l f e e_t_ a l _ 3 , h a v e r e p o r t e d t h e f i r s t a c y l a t i o n o f t h e d i a n i o n o f a 3 - k e t o e s t e r w h i c h i n v o l v e d t h e c o n d e n s a t i o n o f t h e d i a n i o n _3_1_ w i t h m e t h y l b e n z o a t e t o g i v e 5 - p h e n y 1 - 3 , 5 - d i o x o • p e n t a n o i c a c i d (7_1_) o r p y r o n e 7_2 i n 4 8 % a n d 1 1 % r e s p e c t i v e l y d e p e n d i n g on t h e r e a c t i o n c o n d i t i o n . - 2 8 0 0 0 0 O C 2 H 5 C 6 H 5 C 0 2 C K H o b 31 or C 6 H 5 ' 0 OH 71 OH I (22) 0 ^ 0 72 E a r l y i n v e s t i g a t i o n i n o u r l a b o r a t o r y d e m o n s t r a t e d t h a t t h e d i a n i o n f r o m m e t h y l a c e t o a c e t a t e (5_3_) r e a c t e d v i o -l e n t l y w i t h a c y l h a l i d e e v e n a t - 7 8 ° C a n d a c o m p l e x m i x t u r e o f p r o d u c t s was o b t a i n e d . H e n c e , l e s s r e a c t i v e a c y l a t i n g a g e n t s w e r e i n v e s t i g a t e d , a n d i t was f o u n d t h a t t r e a t m e n t o f t h e d i a n i o n 5_5_ w i t h m e t h y l a c e t a t e a t 0° C s m o o t h l y g a v e 3 , 6 - d i k e t o e s t e r 73 i n 3 0 - 4 0 % y i e l d . One o f t h e , r e a s o n s f o r 0 0 p o o *0CHo R C 0 2 R ' R- 0 C H 3 ( 2 3 ) 5 5 R = R ' = G H 3 73 - 29 -t h e l o w y i e l d i n t h i s r e a c t i o n c o u l d b e . t h e p r o t o n t r a n s f e r f r o m m o n o a n i o n 7_3 t o d i a n i o n 5_5_. T h e m o s t c o n v e n i e n t p r o c e d u r e t o i m p r o v e t h e y i e l d i n v o l v e d r e a c t i o n o f d i a n i o n w i t h o n e - h a l f e q u i v a l e n t o f e s t e r , a d d i t i o n o f o n e e q u i v a l e n t o f t h e b a s e a n d f i n a l l y t h e r e m a i n i n g o n e - h a l f e q u i v a l e n t o f e s t e r s . U s i n g t h i s p r o c e d u r e , r e a c t i o n o f d i a n i o n 5j>_ f r o m m e t h y l a c e -t o a c e t a t e (5_3) w i t h m e t h y l a c e t a t e g a v e m e t h y l 3 , 5 - d i o x o h e x a n o -a t e (7_3) i n 71% y i e l d a n d t h e d i a n i o n 5_5_ w i t h m e t h y l b u t a n o a t e g a v e m e t h y l 3 , 5 - d i o x o o c t a n o a t e i n 6 7 % y i e l d . T h e r e a c t i o n o f n i t r i l e s w i t h t h e d i a n i o n o f m e t h y l a c e t o a c e t a t e (5_3) h a s a l s o b e e n b r i e f l y i n v e s t i g a t e d 5 0 . I t h a s p r e v i o u s l y b e e n r e p o r t e d 6 1 t h a t e t h y l a c e t o a c e t a t e ( 3 0 ) may be c o n d e n s e d w i t h b e n z o n i t r i l e u s i n g two e q u i v a l e n t s o f s o d i u m a m i d e t o g i v e t h e e n a m i n e 7_4_ ( R 1 = C g H 5 , R = E t ) , b u t 0 0 R 'CN + N a N H 2 / N H 3 31 74 R - C 2 H 5 0 0 R 75 76 3 0 -t h e r e a c t i o n i s c o m p l i c a t e d b y n u c l e o p h i l i c a t t a c k o f t h e a m i d e i o n on t h e n i t r i l e a n d s u b s e q u e n t c o n d e n s a t i o n o f t h e b e n z a m i d i n e w i t h t h e k e t o e s t e r t o g i v e t h e p y r i m i d o n e 75. i n o u r l a b o r a t o r y c o u l d a v o i d t h e c o m p l i c a t i o n o f p y r i m i d o n e 75 f o r m a t i o n . T h e r e a c t i o n b e t w e e n d i a n i o n 5_5 a n d b e n z o -n i t r i l e s was f o u n d t o be s l u g g i s h a n d e x t e n d e d r e a c t i o n t i m e s (12 h o u r s ) g a v e 5 - am i n o - 3 - o x o - 5 - p h e n y 1 - 4 - eno a t e (7_7) (R = C 6 H 5 ) i n 6 6 % y i e l d a n d some h y d r o x y p y r i d o n e 7_8_ ( 2 9 % ) . T h e i s o l a t e d e n a m i n e was f o u n d t o be t h e r m a l l y u n s t a b l e a n d c o n v e r t e d t o a c y c l i c p r o d u c t w h i c h was l a t e r i d e n t i f i e d a s h y d r o x y p y r i d o n e ( 7 8 ) (R = C 5 H 5 ) . T h e a n a l o g o u s t h e r m a l c o n v e r s i o n o f e n a m i n e I t was t h e n f o u n d t h a t u s i n g t h e m e t h o d d e v e l o p e d Scheme V 0 0 RCN 55 77 R = C 6 H 5 R^C 6 H 5 79 R: CH 3 R = CH 3 O H 78 80 31 t o c y c l i c h y d r o x y p y r i d o n e h a s a l s o b e e n r e p o r t e d by S u g i -y a m a 6 1 . T r e a t m e n t o f d i a n i o n 5_5_ w i t h a c e t o n i t r i l e a l s o g a v e t h e e x p e c t e d e n a m i n e p r o d u c t ( 7 9 ) (R = CH 3) i n 86% y i e l d . A f a c i l e a n d new m e t h o d t o a c h i e v e t h e C - a c e t y l a t i o n o f k e t o n e s h a s a l s o b e e n r e p o r t e d 5 0 . T r e a t m e n t o f t h e mono-a n i o n o f s i m p l e g - k e t o e s t e r s w i t h two e q u i v a l e n t s o f m e t h y l -l i t h i u m g a v e t h e g - d i k e t o n e i n g o o d y i e l d . (25) (26) S i m i l a r l y , when t h r e e e q u i v a l e n t s o f me t h y 1 1 i t h i u r n was a d d e d t o t h e m o n o a n i o n t h e m a j o r p r o d u c t ( g r e a t e r t h a n 8 0 % ) was f o u n d t o be t h e e x p e c t e d t e r t i a r y a l c o h o l c o m p o u n d . 84 S3 3 3 -D I S C U S S I O N O u r a i m i n t h i s p r o j e c t was t o f u r t h e r e x p l o r e t h e r e a c t i o n s o f d i a n i o n s o f 6 - k e t o e s t e r s . We w e r e a b l e t o make u s e o f d i a n i o n r e a c t i o n s t o s y n t h e s i z e m e d i u m - s i z e d r i n g com-p o u n d s w h i c h w e r e u s u a l l y q u i t e d i f f i c u l t t o f o r m . O t h e r com-p o u n d s s u c h as some h o m o l o g p r e c u r s o r s t o N a z a r o v ' s r e a g e n t , f u r y l i d e n e c o m p o u n d s a n d s e v e r a l o t h e r new c o m p o u n d s w e r e a l s o p r e p a r e d u s i n g t h e d i a n i o n s . R e a c t i o n o f D i a n i o n o f M e t h y l A c e t o a c e t a t e w i t h E p o x i d e s M e t h y l a - ( t e t r a h y d r o - 2 - f u r y l i d e n e ) a c e t a t e ( 9 5 ) was p r e p a r e d b y t r e a t i n g t h e s o d i o l i t h i o m e t h y l a c e t o a c e t a t e (5 5) w i t h e t h y l e n e o x i d e . I t h a s b e e n r e p o r t e d t h a t t h e p r e p a r a t i o n o f t h e h o m o l o g s o f t h i s c o m p o u n d b y t h e r e d u c t i o n o f f u r a n e s t e r 8_5_ s e e m e d u n l i k e l y . H o w e v e r , t h e f u r y l i d e n e a c e t a t e c o u l d be o b t a i n e d i n 24% y i e l d b y a R e f o r m a t s k y r e a c t i o n w i t h y - b u t y r o l a c t o n e 8 7 5 z . ( 2 7 ) 85 86 34 /fir M k C 0 2 C 2 H 5 C 0 2 C 2 H 5 8 7 8 8 (2ft) C 0 2 C 2 H 5 8 6 R e c e n t l y , T.A. B r y s o n 6 3 r e p o r t e d a p r e p a r a t i o n o f c o m p o u n d 86 u s i n g o u r m e t h o d t o p r e p a r e t h e d i a n i o n . He f i r s t o b t a i n e d t h i s c o m p o u n d i n 34% y i e l d b y t r e a t i n g t h e d i a n i o n o f e t h y l a c e t o a c e t a t e (30_) w i t h t e t r a h y d r o p y r a n y l e t h e r ( T H P ) o f i o d o e t h a n o l , f o l l o w e d b y a q u e o u s e t h a n o l a n d a c i d t o r e m o v e t h e t e t r a h y d r o p y r a n y l a n d f i n a l l y u s i n g b e n z e n e a n d p - t o l u e n e -s u l f o n i c a c i d t o a c h i e v e t h e O - c y c l i z a t i o n . Scheme VI We f o u n d t h a t on t r e a t m e n t w i t h e t h y l e n e o x i d e t h e d i a n i o n o f m e t h y l a c e t o a c e t a t e ( 5 3 ) w o u l d u n d e r g o smooth a d d i t i o n t o t h e e p o x i d e and s u b s e q u e n t t r e a t m e n t w i t h an a c i d gave t h e c y c l i c f u r y l i d e n e 9_5_ i n good y i e l d . Scheme VII Q Q •1) N a H / T H F O C H 3 2 ) n B u L i 0 Q OCH-53 55 o 11 R = H ^ 2 R = C H . R .0. ^ C H C 0 2 C H 3 H + OCH-^ O H R 95 R = H 93 R = H 9 6 R =CH-S i m i l a r l y , t h e d i a n i o n a l s o r e a c t e d w i t h p r o p y l e n e o x i d e t o g i v e m e t h y l a - ( t e t r a h y d r 0 - 5-me t h y 1 - 2 - f u r y 1 i d e n e ) a c e t a t e ( 9 6 ) i n a b o u t 70% y i e l d . T h e i n i t i a l a l c o h o l p r o d u c t 9_4 , (R = CH 3) , was p u r i -f i e d u s i n g p r e p a r a t i v e t . l . c . T h e i r s p e c t r u m o f t h i s a l c o h o l s h o w e d a b s o r p t i o n a t 3550 c m - 1 , i n d i c a t i n g t h e p r e s e n c e o f - 37 -t h e h y d r o x y l g r o u p a n d t h e nmr s p e c t r u m was c o n s i s t e n t w i t h s t r u c t u r e 94. a c e t a t e (9_6_) was p u r i f i e d b y d i s t i l l a t i o n . T h e i r o f 96 s h o w e d a s t r o n g p e a k a t 1640 cm" 1 a n d 1700 cm" 1 i n d i c a t i n g t h e p r e -s e n c e o f a n a 3 g - u n s a t u r a t e d e s t e r g r o u p . F u r t h e r e v i d e n c e f o r s t r u c t u r e 9_6_ was s u p p l i e d b y t h e nmr s p e c t r u m w h i c h h a s a b s o r p t i o n s a t 5 5.2 ( t , I H , J = 0.4 H z , C = C H ) , 5 4.5 (m, I H , 0 - C H ) , 6 3.7 ( s , 3H, - 0 C H 3 ) , 5 3.2 (m, 2H, - C H 2 - ) , 6 2.2 (m, 2H, - C H 2 - ) a n d 6 1.35 ( d , 3H, - C H 3 ) . T h e g e o m e t r y o f t h e d o u b l e b o n d i n b o t h c o m p o u n d 9_5_ a n d 9_6 was _E b y c o m p a r i s o n o f i t s i r a n d nmr w i t h t h o s e o f t h e a u t h e n t i c c o m p o u n d 8_6_6 3 . T h e p r e -f e r e n t i a l f o r m a t i o n o f t h e _E_ i s o m e r o v e r t h e Z i s o m e r i s p r o b -a b l y due t o t h e m o r e f a v o r a b l e o r i e n t a t i o n o f d i p o l e m o m e n t s i n t h e f o r m e r p r o d u c t a n d t h e r e a c t i o n i s an e q u i l i b r i u m m i x t u r e f a v o r i n g t h e _E i s o m e r . T h e m e t h y l a - ( t e t r a h y d r o - 5 - m e t h y 1 - 2 - f u r y l i d e n e ) H £ Z 95 R = H R = 86a R = H R' 86b R = C H 3 R 96 R = CH 3 R = CH 3 38 -R e a c t i o n o f L i t h i o S o d i o M e t h y l A c e t o a c e t a t e w i t h a - c h l o r o - e t h e r S i n c e t h e w o r k o f N a z a r o v a n d Z a v y a l o w 6 5 , t h e u s e -f u l n e s s o f e s t e r s o f 3 - o x o - 4 - p e n t e n o i c a c i d , s u c h as 9_7_ f o r t h e a n n e l a t i o n w i t h a c y c l i c 3 - d i k e t o n e 9_8, i n a R o b i n s o n t y p e a n n e l a t i o n ( e q u a t i o n 2 9 ) 6 6 , a n d f o r a M a n n i c h r e a c t i o n i n t h e c o n s t r u c t i o n o f t h e p i p e r i d o n e r i n g 6 7 h a s b e e n demon-s t r a t e d . H o w e v e r , t h e t e d i o u s n e s s a n d l o w o v e r a l l y i e l d ( 7 - 9 % ) b e l o w , o f t h e c l a s s i c a l s y n t h e s i s o f 106 ( o r 97), o u t l i n e d was a m a j o r d e t e r r e n t t o i t s g e n e r a l u t i l i t y . - 3 9 -65 Scheme VIII 106 - 40 S t o r k a n d G u t h i k o n d a 8 8 h a v e d e v e l o p e d an i m p r o v e d s y n t h e s i s o f 106 w h i c h p a r t i a l l y a l l e v i a t e s t h e a b o v e p r o b l e m s . A n o t h e r a p p r o a c h t o t h e s y n t h e s i s o f c o m p o u n d 97_ h a s a l s o b e e n r e p o r t e d b y P i c h a t a n d B e a u c o u r t 8 9 . T r o s t a n d K u n z 6 4 a l s o r e p o r t e d an i n c r e a s e d y i e l d i n t h e p r e p a r a t i o n o f 1 0 6 . 0 C 2 H 5 0 CI 103 C 0 2 S i ( C H 3 ) 3 L i - ^ — H C 0 2 C 2 H 5 0 0 0 0 H 2 0 OCoH 2 n5 ^ O C 2 H 5 (30) C 0 H c O ' 2 b 107 9 7 L a t e r , H e a t h c o c k e_t a l _ 7 0 , d i s c o v e r e d t h a t t h e p r e c u r s o r t o N a z a r o v ' s r e a g e n t m i g h t be u s e d d i r e c t l y i n t h e a n n e l a t i o n r e a c t i o n , i f a c i d c a t a l y s i s was u s e d . T h e r e f o r e , a n a l t e r n a t i v e s y n t h e s i s o f e t h y 1 - 5 - e t h o x y - 3 - o x o p e n t a n o a t e (10 7) was d e v i s e d . T h i s s u b s t a n c e was o b t a i n e d i n 5 8 % y i e l d b y t r e a t i n g 3 - e t h o x y p r o p a n o y 1 c h l o r i d e ( 1 0 3) w i t h two e q u i -v a l e n t s o f t h e m a g n e s i u m s a l t o f e t h y l h y d r o g e n m a l o n a t e 108 i n T H F 7 1 . - 41 -0 C 2H 50 CI 103 0 0 C 2 H 5 0 OMg2 + 1 0 8 0 0 THF C°C t s» 5 8 % O C 2 H 5 ( 3 1 ) C 2 H 50-107 We f o u n d t h a t t h e p r e p a r a t i o n o f m e t h y l 5 - m e t h o x y -3 - o x o p e n t a n o a t e (12 0) a n d i t s h o m o l o g s w h i c h w e r e p r e c u r s o r s t o N a z a r o v ' s r e a g e n t c o u l d be e a s i l y a c h i e v e d i n a s i n g l e s t e p s y n t h e s i s . On t r e a t m e n t o f l i t h i o s o d i o m e t h y l a c e t o a c e t a t e (5 3) w i t h one e q u i v a l e n t o f c h 1 o r o m e t h y l me t h y 1 e t h e r a t - 5 ° C, t h e c h l o r i d e was s m o o t h l y d i s p l a c e d t o g i v e m e t h y l 5 - m e t h o x y -3 - o x o p e n t a n o a t e (12 0) i n 6 5 % y i e l d . T h i s - c o m p o u n d was e a s i l y p u r i f i e d t h r o u g h p r e p a r a t i v e c o l u m n c h r o m a t o g r a p h y . Nmr s p e c t r u m o f t h i s c o m p o u n d 12 0 s h o w e d a b s o r p t i o n s a t 6 2.6 42 -(m, 2H, 0 C H 2 C H 2 C 0 ) , 5 3.35 ( s , 3H, C H 3 0 ) , 6 3.48 ( s , 2H, C 0 C H 2 C 0 ) , 6 3.35-3.80 (m, 2H, C H 3 0 C H 2 ) , 6 3.7 ( s , 3H , 0 C H 3 ) and 6 5.2 ( e n o l ) w h i c h were c o n s i s t e n t w i t h s t r u c t u r e 12 0. F u r t h e r e v i d e n c e f o r t h i s s t r u c t u r e came f r o m i t s i r , mass s p e c t r u m and m i c r o a n a l y s i s . A n o t h e r h o m o l o g , m e t h y l 5 -methoxy-4-methy1 - 3-oxo-p e n t a n o a t e (12 3) was a l s o e a s i l y p r e p a r e d . The d i a n i o n was Scheme IX - 43 -g e n e r a t e d as b e f o r e and a l k y l a t e d w i t h m e t h y l i o d i d e t o g i v e compound 121; t h e d i a n i o n 12 2 was t h e n g e n e r a t e d and a l l o w e d t o r e a c t w i t h one e q u i v a l e n t o f c h l o r o m e t h y l m e t h y l e t h e r , a t 0° C t o -5° C f o r 45 m i n u t e s t o g i v e compound 12 3 i n good y i e l d . The nmr s p e c t r u m showed s i g n a l s a t 6 1.16 ( d , 3 H ) , 6 3.35 ( s , 3 H ) , 6 3.48 ( s , 2 H ) , 6 2.0-3.0 ( m , l H ) , 6 3.1-3.5 (m, 2H) and 6 3.75 ( s , 3H) i n d i c a t i n g t h e m e t h y l g r o u p C-4, 0-methoxy a t C-5, m e t h y l e n e g r o u p b e t w e e n two c a r b o n y l g r o u p s , m e t h y l e n e , m e t h i n e and 0-methoxy o f t h e e s t e r r e s p e c t i v e l y . The a b s o r p t i o n a t 1715 cm" 1 i n t h e i r s p e c t r u m showed t h e p r e s e n c e o f s a t u r a t e d c a r b o n y l g r o u p and t h e e s t e r g r o u p h a s an a b s o r p t i o n a t 1740 c m - 1 . We were a l s o a b l e t o p r e p a r e m e t h y l 5 - e t h o x y - 3 - o x o -h e x a n o a t e (129) and m e t h y l 5 - m e t h o x y - 3 - o x o h e x a n o a t e ( 130) by o u r d i a n i o n r e a c t i o n . a - C h l o r o e t h y 1 e t h y l e t h e r (12 7) and a - c h l o r o e t h y l m e t h y l e t h e r (12 8) were f i r s t p r e p a r e d i n t h e f o l l o w i n g w a y 7 2 by p a s s i n g a n h y d r o u s h y d r o g e n c h l o r i d e gas i n t o a m i x t u r e o f p a r a l d e h y d e and a b s o l u t e a l c o h o l . 0 CI C H 3 ^ + ROH + HCl * C H 3 ^0R + H^ (33) 125 R = C 2 H 5 127 R = C 2 H 5 126 R = CH 3 128 R = CH 3 T h e l i t h i o s o d i o m e t h y l a c e t o a c e t a t e (5_5) r e a c t e d s m o o t h l y w i t h a - c h l o r o e t h y l e t h y l e t h e r (12 7) t o g i v e m e t h y l 5 - e t h o x y - 3 - o x o h e x a n o a t e ( 1 2 9 ) a n d w i t h a - c h l o r o e t h y l m e t h y l e t h e r (12 8) t o g i v e m e t h y l 5 - m e t h o x y - 3 - o x o h e x a n o a t e ( 1 5 0 ) i n m o d e r a t e y i e l d . A t t h e same t i m e , t h e y w o u l d a l l be 127 R = C 2 H 5 129 R= C 2 H 5 128 R= C H 3 130 R= CH 3 s y n t h e s i z e d f r o m r e a d i l y a v a i l a b l e m a t e r i a l s , t h u s p r o v i d i n g a v e r y c o n v e n i e n t p r e p a r a t i o n o f t h e p r e c u r s o r s t o N a z a r o v ' s r e a g e n t . T h e nmr o f c o m p o u n d 12 9 (R = E t ) s h o w e d a c o m p l i c a t e d a b s o r p t i o n a t 6 2 . 0 - 3 . 0 f o r t h e m e t h y l e n e g r o u p b e t w e e n t h e c a r b o n y l a n d t h e a s y m m e t r i c c e n t e r . I n a d d i t i o n t h e d i a s t e r e o -m e r i c p r o t o n s on t h e e t h o x y g r o u p show a c o m p l e x m u l t i p l e t a r o u n d 6 3.8. R e c e n t l y , i t h a s a l s o b e e n r e p o r t e d 7 3 t h a t t h e R o b i n s o n A n n e l a t i o n r e a c t i o n s c a n be c a r r i e d o u t d i r e c t l y w i t h a 3 - c h l o r o k e t o n e 13 2 i n t h e p r e s e n c e o f an a c i d . We f o u n d t h a t t h e g - c h l o r o k e t o c o m p o u n d c o u l d be e a s i l y o b t a i n e d - 45 i n a l m o s t q u a n t i t a t i v e y i e l d f r o m m e t h y l 5 - e t h o x y - 3 - o x o -h e x a n o a t e (12 9) o r m e t h y l 5 - m e t h o x y - 3 - o x o h e x a n o a t e ( 1 3 0 ) b y s t i r r i n g t h e r e a c t i o n m i x t u r e w i t h h y d r o g e n c h l o r i d e i n c h l o r o f o r m . T h e nmr s p e c t r u m o f m e t h y l 5 - c h l o r o - 3 -0 0 0 C H HCI/CHC13 O C H 3 ( 36) 129 R = C 2 H 5 130 R = CH 3 134 o x o h e x a n o a t e (15 4) s h o w e d a m u l t i p l e t a t 6 4.5 i n d i c a t i n g t h e p r e s e n c e o f -CH--C1 g r o u p a n d a d o u b l e t o f d o u b l e t s a t 5 3.0 due t o t h e m e t h y l e n e g r o u p b e t w e e n t h e s a t u r a t e d c a r b o n y l a n d t h e a s y m m e t r i c c e n t e r . 4 6 -A l k y l a t i o n o f t h e D i a n i o n o f g - k e t o e s t e r s w i t h D i h a l o a l k a n e s  a n d D i h a l o a l k e n e s A s e r i e s o f m e d i u m r i n g s i z e c y c l i c g - k e t o e s t e r s h a v e b e e n p r e p a r e d p r e v i o u s l y u s i n g s e v e r a l d i f f e r e n t m e t h o d s T h e f i r s t r o u t e r e p o r t e d 7 4 i n v o l v e d t h e c a r b o x y 1 a t i o n o f t h e k e t o n e 135 b y means o f e x c e s s d i e t h y l c a r b o n a t e a n d two e q u i -0 (EtO)2CO 2 NaH C 2 H 5 (37) 135 136 v a l e n t s o f s o d i u m h y d r i d e . A l t e r n a t i v e l y , t h e y h a v e a l s o b e e n p r e p a r e d i n a v e r y l e n g t h y r o u t e 7 5 ' 7 6 ' 7 7 . T h e k e t o n e 155 was f i r s t c o n v e r t e d t o i t s c o r r e s p o n d i n g e n a m i n e c o m p o u n d 15 7, f o l l o w e d b y a M i c h a e l t y p e r e a c t i o n , r i n g e x p a n s i o n , h y d r o l y s i s a n d f i n a l l y h y d r o g e n a t e d t o g i v e c o m p o u n d 1 4 0 . On t r e a t m e n t o f t h e s o d i o l i t h i o m e t h y l a c e t o a c e t a t e w i t h o n e e q u i v a l e n t o f d i h a l o a l k a n e , a m i x t u r e o f p r o d u c t s c o n t a i n i n g a p p r o x i m a t e l y e q u a l a m o u n t s o f b i s g - k e t o e s t e r 62 a n d t h e h a l o g e n c o n t a i n i n g c o m p o u n d 141 w e r e f o r m e d . - 47 -Scheme X I f o n l y o n e - h a l f e q u i v a l e n t o f d i h a l o a l k a n e w e r e u s e d , i t f o r m e d e x c l u s i v e l y t h e b i s 3 - k e t o e s t e r 6_2_51 . A l t h o u g h i t h a s b e e n f o u n d 5 1 t h a t when 1 , 3 - d i b r o m o p r o p a n e was u s e d , a c y c l i c 3 - k e t o e s t e r c o u l d be o b t a i n e d t h r o u g h i n t r a m o l e c u l a r r e a c t i o n a t t h e a - c a r b o n , no c y c l i c p r o d u c t s w e r e d e t e c t e d when 1 , 4 - d i b r o m o b u t a n e o r 1 , 5 - d i b r o m o p e n t a n e o r 1 , 1 0 - d i b r o m o -d e c a n e was u s e d a s t h e a l k y l a t i n g a g e n t . One o f t h e r e a s o n s 48 Scheme XI 62a ( n = 3 ) B r ( C H 2 ) 3 B r 55 B r ( C H 2 ) n B r 141 c n = 10 62d n = 10 4 9 -f o r t h e a b s e n c e o f c y c l i c c o m p o u n d s i n t h i s r e a c t i o n m i g h t be t h a t m e d i u m - s i z e d r i n g c o m p o u n d s a r e u s u a l l y m o re d i f f i c u l t t o f o r m t h a n s i x - m e m b e r e d r i n g c o m p o u n d s . E v e n i f t h e p u r i f i e d m o n o h a l o c o m p o u n d was a l l o w e d t o r e f l u x w i t h o n e e q u i v a l e n t o f s o d i u m h y d r i d e i n t e t r a h y d r o f u r a n f o r s e v e r a l h o u r s , no s i g n o f C - a l k y l a t i o n a t t h e a - c a r b o n was o b s e r v e d . T h i s c o r r e -l a t e s w i t h t h e l a c k o f r e a c t i v i t y o f a - c a r b a n i o n a n d t h e f a c t t h a t no d i a l k y l a t i o n was o b s e r v e d i n t h e o r i g i n a l d i a n i o n w o r k . H o w e v e r , on t r e a t m e n t o f t h e m o n o h a l o c o m p o u n d 1 4 1 a (n = 4) w i t h o n e e q u i v a l e n t o f s o d i u m m e t h o x i d e i n r e f l u x i n g m e t h a n o l f o r a b o u t 12 h o u r s t h e c y c l i z a t i o n a t t h e a - c a r b o n p r o c e e d e d s m o o t h l y t o g i v e m e t h y l 2 - o x o c y c l o h e p t a n e c a r b o x y 1 a t e ( 1 4 0 a ) (n = 4) . T h e r e a c t i o n was f o l l o w e d b y t h i n l a y e r c h r o m a t o g r a p h y a n d t h e p r o d u c t was e a s i l y i s o l a t e d . S i m i l a r l y , we w e r e a l s o a b l e t o make m e t h y l 2 - o x o c y c 1 o o c t a n e c a r b o x y 1 a t e ( 1 4 0 b ) (n = 5) b y r e f l u x i n g t h e m o n o h a l o c o m p o u n d 141b (n = 5) w i t h s o d i u m m e t h o x i d e a n d m e t h a n o l . W h i l e no c y c l i c p r o d u c t was o b s e r v e d when t r e a t i n g c o m p o u n d 1 4 1 c ( n = 10) w i t h s o d i u m m e t h o x i d e i n m e t h a n o l a n d t h e m i x t u r e r e f l u x e d f o r 14" h o u r s , t h i s i s p r o -b a b l y d ue t o t h e d i f f i c u l t y i n f o r m i n g 1 3 - m e m b e r e d r i n g . T h e nmr s p e c t r u m o f b o t h c o m p o u n d s 14 0a ( n = 4) a n d 140b (n = 5) s h o w e d a c o m p l i c a t e d a b s o r p t i o n a t 6 3.5 a s s i g n e d t o t h e m e t h i n e g r o u p a t C-2. I n a d d i t i o n , t h e s e c o m p o u n d s - 5 0 OCH- NaOCH-C H 3 O H 0 0 ( C H 2 ) n OCH 3 (38) 141 a n = 4 141b n = 5 140a n =4 140 b n =5 e n o l i z e r e a d i l y t o f o r m 14 0c a n d 1 4 0 d w h i c h h a v e a v e r y l o w a b s o r p t i o n a t 6 1 2 . 6 6 a n d 5 12.34 r e s p e c t i v e l y . Scheme XII 0 P OCH' OCH 140a 140c 140b I40d 51 -An O - c y c l i z e d p r o d u c t 14 2 was f o r m e d b y t r e a t i n g t h e p u r i f i e d m o n o h a l o c o m p o u n d 1 4 1 a (n = 4) w i t h o n e e q u i -v a l e n t o f s o d i u m h y d r i d e i n a m i x t u r e o f t e t r a h y d r o f u r a n a n d h e x a m e t h y l p h o s p h o r a m i d e . I n g e n e r a l when t h e a c t i v e Q 0 NaH THF/HMP • O ^ C H C 0 2 C H 3 T (39) 141a n = 4 142 m e t h y l e n e c o m p o u n d s i n v o l v e d a r e r e l a t i v e l y a c i d i c , O - a l k y l a -t i o n c o m p e t e s s i g n i f i c a n t l y w i t h C - a l k y l a t i o n , a s i n t h i s c a s e ( a 3 - k e t o e s t e r c o m p o u n d ) i n w h i c h t h e e q u i l i b r i u m c o n -c e n t r a t i o n o f t h e e n o l t a u t o m e r i s o f t e n r e l a t i v e l y h i g h . E s p e c i a l l y i n t h e p r e s e n c e o f a p o l a r a p r o t i c s o l v e n t s u c h a s h e x a m e t h y l p h o s p h o r a m i d e , a l k y l a t i o n a t t h e m o re e l e c t r o n e g a t i v e a t o m o f t h e a m b i d e n t a n i o n ( i . e . a t o x y g e n a t o m r a t h e r t h a n a t c a r b o n a t o m f o r an e n o l a t e a n i o n ) i s u s u a l l y f a v o u r e d . T h e s t e r e o c h e m i s t r y a b o u t t h e d o u b l e b o n d o f t h i s O - c y c l i z e d p r o d u c t 14 2 c o u l d be E_ 1 4 2 a o r Z 142b a s s h o w n . Nmr o f t h e c r u d e p r o d u c t s h o w e d p r e d o m i n a n t l y o n e p r o d u c t . 5 2 -C02CH3 U 2 a E ( trans ) U 2 b < cis) T h e p r o d u c t was c h a r a c t e r i z e d a s c o m p o u n d 14 2 a , i . e . t h e _E i s o m e r ( o r t r a n s ) , w h i c h s h o w e d a b s o r p t i o n a t 5 5.25 ( v i n y l h y d r o g e n ) , 6 4.2 ( - C H 2 - 0 - ) , 6 3.7 (-OCH 3) a n d 6 3.2 ( - C H 2 -C = C-) . T h e o b s e r v e d _E i s o m e r i n t h e c y c l i c p r o d u c t c o u l d be d u e t o t h e m o r e f a v o u r a b l e o r i e n t a t i o n o f d i p o l e m o m e n t s as i n c o m p o u n d s -9 5 a n d 9_6_. T h i s c o u l d a l s o be due t o t h e c o n f o r m a t i o n o f t h e i n t e r m e d i a t e . T h e r e a r e t h r e e p o s s i b l e c o n f o r m a t i o n s 14 3 a , 14 3b o r 14 3c t e r m e d u - , w-, a n d s i c k l e -s h a p e d , r e s p e c t i v e l y 8 1 . E v e n t h o u g h o n l y t h e u - s h a p e d e n o -l a t e 1 4 3 a was c a p a b l e o f s e r v i n g a s a b i d e n t a t e l i g a n d f o r a s s o c i a t i o n w i t h a m e t a l i o n a s shown i n s t r u c t u r e 14 3 a , t h e m o s t s t a b l e f o r m o f t h e f r e e e n o l a t e a n i o n was e x p e c t e d t o be t h e w - s h a p e d c o n f o r m e r 1 4 5 b , i n w h i c h d i p o l e - d i p o l e r e p u l -s i o n was m i n i m i z e d . S i n c e a p o l a r a p r o t i c s o l v e n t s u c h a s h e x a m e t h y l p h o s p h o r a m i d e c o u l d s t r o n g l y s o l v a t e t h e m e t a l c a t i o n s , t h e w - s h a p e d c o n f o r m e r 14 3b a p p e a r e d t o be p r e f e r -r e d 8 2 . T h u s t h e i s o l a t e d p r o d u c t 142 s h o u l d be t r a n s o r E i s o m e r 1 4 2 a . - 5 3 -79,81 Scheme XIII 0_ 0 R OCH 3 0_ OCH3 143a U 3 b 143c ( U-shaped) (W-shaped ) ( sickle - shaped ) R - ( C H 2 ) 4 B r 5 A -R e a c t i o n o f d i a n i o n 5_5 w i t h a d i h a l o a l k e n e was a l s o i n v e s t i g a t e d . T h e c i s 1 , 4 - d i c h 1 o r o - 2 - b u t e n e ( 1 4 5 ) was s y n -t h e s i z e d f r o m c i s 1 , 4 - d i o 1 - 2 - b u t e n e ( 1 4 4 ) (>91 % , c i s ) ; i n HO 1 4 4 OH NCS/ Me 2S C H 2 C l 2 C I 145 -CI (40) 0 Q OCH, + CI •ci 55 Q 0 CI 146 OCH--t-145 Q Q OCH-(41) OCH-0 0 147 55 t h i s way, we w e r e a b l e t o o b t a i n m a i n l y c i s 1 , 4 - d i c h l o r o -2 - b u t e n e ( 14 5) 8 0 . I t was f o u n d t h a t when c i s 1 , 4 - d i c h 1 o r o -2 - b u t e n e (14 5) was a l l o w e d t o r e a c t w i t h t h e d i a n i o n , t h e i s o l a t e d p r o d u c t s w e r e a m i x t u r e o f c h l o r o - c o n t a i n i n g mono-a l k y l a t e d c o m p o u n d 146 a n d a b i s 3 - k e t o e s t e r 14 7 i n a p p r o x i -m a t e l y e q u a l a m o u n t s . T h e g e o m e t r y a b o u t t h e d o u b l e b o n d o f c h l o r b p r o d u c t , was f o u n d t o r e m a i n c i s , a n d no i s o m e r i z a t i o n o f t h e d o u b l e b o n d was o b s e r v e d . T h i s was s h o w n b y t h e nmr s p e c t r u m o f the o l e f i n i c p r o t o n s w h i c h h a v e a c h a r a c t e r i s t i c a b s o r p t i o n a t a p p r o x i m a t e l y 6 5.7 w i t h a c o u p l i n g c o n s t a n t J = 12 H z . T h e s e two p r o d u c t s w e r e e a s i l y s e p a r a t e d b y p r e p a r a t i v e t h i n l a y e r c h r o m a t o g r a p h y . On t r e a t m e n t o f t h e i s o l a t e d p u r e m o n o - c h l o r o c o m p o u n d 14 6 w i t h s o d i u m m e t h o x i d e i n r e f l u x i n g m e t h a n o l , i n t r a m o l e c u l a r c y c l i z a t i o n a t a - c a r b o n c o u l d be e a s i l y a c h i e v e d . T h e o n l y p r o d u c t f o r m e d was t h e s e v e n - m e m b e r e d r i n g c o m p o u n d 14 8. T h i s i s v e r y i n t e r e s t i n g b e c a u s e on e m i g h t 56 -e x p e c t t h e m o n o - c h l o r o c o m p o u n d 14 6 w o u l d u n d e r g o an a l l y l i c d i s p l a c e m e n t r e a c t i o n t o g i v e t h e £ i v e - m e m b e r e d c o m p o u n d 14 9 w h i c h m i g h t r e q u i r e l e s s e n e r g y t h a n t h e f o r m a t i o n o f s e v e n -m e m b e r e d r i n g c o m p o u n d 1 4 8 . A s t u d y o f m o l e c u l a r m o d e l s i n -d i c a t e d t h a t i f t h e g e o m e t r y o f t h e d o u b l e b o n d was c i s , t h e m e t h y l e n e g r o u p n e x t t o t h e c h l o r i d e was c l o s e r t o t h e a n i o n a t t h e c t - c a r b o n t h a n t h e m e t h i n e g r o u p a t C - 6 ; t h e r e f o r e , s e v e n - m e m b e r e d r i n g c o m p o u n d 14 8 was f o r m e d i n s t e a d o f f i v e -m e m b e r e d r i n g c o m p o u n d 14 9. T h e p r e s e n c e o f t h e d o u b l e b o n d i n a s e v e n - m e m b e r e d r i n g l o w e r s t h e s t r a i n o f t h i s r i n g a s c o m p a r e d t o t h a t o f c y c l o h e p t a n e a n d t h i s may r e f l e c t t h e e a s e i n f o r m a t i o n o f t h e s e v e n - m e m b e r e d r i n g i n t h i s c a s e . I f t h e g e o m e t r y o f t h e d o u b l e b o n d was t r a n s , t h e m e t h y l e n e g r o u p a t C-8 was k e p t f a r a p a r t f r o m C-2 a n d i t i s i m p o s s i b l e f o r t h e c a r b a n i o n t o r e a c h C-8 a t a l l , s o o n l y t h e m e t h i n e 57 -c a r b o n w o u l d be a t t a c k e d by t h e a n i o n a t C-2. D i a l k y l a t i o n a t t h e y - c a r b o n o f t h e d i a n i o n o f m e t h y l a c e t o a c e t a t e was a l s o i n v e s t i g a t e d i n t h e f o l l o w i n g way. T h e d i a n i o n was f i r s t a l l o w e d t o r e a c t w i t h 1 , 4 - d i b r o m o b u t a n e f o r o n e - h a l f h o u r a t 0 ° C , t h e n one e q u i v a l e n t o f l i t h i u m d i i s o -p r o p y l a m i d e was a d d e d t o r e g e n e r a t e t h e a n i o n a t t h e y - c a r b o n . I n t r a m o l e c u l a r c y c l i z a t i o n o c c u r r e d a t t h e y - c a r b o n t o g i v e m e t h y l 3 - o x o - 3 - c y c l o p e n t y l p r o p a n o a t e ( 1 5 0 a ) . M e t h y l 3 - o x o - 3 -c y c 1 o h e x y 1 p r o p a n o a t e (15 0b) c o u l d a l s o be o b t a i n e d when 1,5-d i b r o m o p e n t a n e was u s e d as t h e a l k y l a t i n g a g e n t . B o t h com-p o u n d s 1 5 0 a a n d 15 0b w e r e o b t a i n e d i n r e a s o n a b l e y i e l d a l o n g w i t h some b i s a l k y l a t i o n p r o d u c t s . T h i s p r o v i d e s a v e r y c o n -Scheme XIV - 58 v e n i e n t m e t h o d f o r t h e p r e p a r a t i o n o f t h e s e c o m p o u n d s 150 a n d 15 0b, when c o m p a r e d w i t h t h e m e t h o d r e p o r t e d 7 8 . I n t h i s p r o c e d u r e m e t h y l o r e t h y l a c e t o a c e t a t e i s t r e a t e d wi s o d i u m e t h o x i d e o r m e t h o x i d e , t h e n an a c y l h a l i d e was a d d a n d t h e r e s u l t i n g p r o d u c t was h y d r o l y z e d t o g i v e c o m p o u n d 150 a s shown i n S c h e m e XV. Scheme XV R = C H 3 or C 2 H 5 59 -1 5 0 60 -E X P E R I M E N T A L G e n e r a l M e l t i n g p o i n t s , w h i c h w e r e d e t e r m i n e d on a K o f l e r h o t s t a g e m i c r o s c o p e , a n d b o i l i n g p o i n t s a r e u n c o r r e c t e d . A l l i r a n d nmr s p e c t r a w e r e r e c o r d e d i n s o l u t i o n , t h e s o l v e n t u s e d i s r e p o r t e d i n p a r e n t h e s e s a t t h e b e g i n n i n g o f e a c h s p e c t r u m . T h e i r s p e c t r a w e r e r e c o r d e d u s i n g a P e r k i n - E l m e r m o d e l 700 s p e c t r o p h o t o m e t e r , a n d w e r e c a l i b r a t e d w i t h t h e 1601 c m - 1 b a n d o f p o l y s t y r e n e . T h e a s s i g n m e n t o f e a c h a b s o r p -t i o n i s i n d i c a t e d i n p a r e n t h e s e s a f t e r e a c h b a n d . T h e 1 H -nmr s p e c t r a w e r e r e c o r d e d on e i t h e r a V a r i a n m o d e l T - 6 0 o r HA-100 s p e c t r o m e t e r . T h e s i g n a l p o s i t i o n s a r e r e p o r t e d u s i n g t h e 6 s c a l e w i t h t e f r a m e t h y 1 s i 1 a n e a s i n t e r n a l s t a n d a r d , e x c e p t w h e r e i n d i c a t e d . T h e m u l t i p l i c i t y , c o u p l i n g c o n s t a n t s , i n t e g r a t e d p e a k a r e a s a n d p r o t o n a s s i g n m e n t s a r e i n d i c a t e d i n p a r e n t h e s e s a f t e r e a c h s i g n a l . T h e mass s p e c t r a w e r e o b -t a i n e d u s i n g an A t l a s CH-4B mass s p e c t r o m e t e r , a n d h i g h r e s o -l u t i o n d e t e r m i n a t i o n s w e r e o b t a i n e d u s i n g an A E I MS-902 o r MS-50 mass s p e c t r o m e t e r . B o t h i n s t r u m e n t s w e r e o p e r a t e d a t a n i o n i s i n g p o t e n t i a l o f 70 e l e c t r o n v o l t s . E l e m e n t a l m i c r o a n a l y s e s w e r e p e r f o r m e d b y Mr. P e t e r B o r d a , U n i v e r s i t y o f B r i t i s h C o l u m b i a . T h e s i l i c a g e l u s e d was o b t a i n e d f r o m E . M e r c k a n d t h a t u s e d f o r t h i n l a y e r c h r o m a t o g r a p h y ( t i c ) was t h e g r a d e P F 2 5 4 , w h i l s t t h a t u s e d f o r c o l u m n c h r o m a t o g r a p h y was t h e g r a d e f i n e r t h a n 200 mesh ASTM. 61 T e t r a h y d r o f u r a n was d r i e d b y r e f l u x i n g o v e r l i t h i u m a l u m i n i u m h y d r i d e f o r a m i n i m u m o f two h o u r s p r i o r t o u s e . R e a c t i o n o f S o d i o L i t h i o M e t h y l A c e t o a c e t a t e ( 5 5 ) w i t h E p o x i d e s . M e t h y l a - ( t e t r a h y d r o - 2 - f u r y 1 i d e n e ) a c e t a t e ( 9 5 ) A p p r o x i m a t e l y 50 ml o f t e t r a h y d r o f u r a n was d i s t i l l e d d i r e c t l y i n t o a 100 ml f l a s k c o n t a i n i n g 1 .0896 g o f s o d i u m h y d r i d e ( a s a 5 0 % m i n e r a l o i l d i s p e r s i o n ) . T h e f l a s k was f i t t e d w i t h m a g n e t i c s t i r r e r , s e p t u m c a p , f l u s h e d w i t h n i t r o -g e n a n d c o o l e d w i t h i c e . M e t h y l a c e t o a c e t a t e ( 2 . 6 4 g, .0 22 m o l e ) was a d d e d d r o p w i s e a n d t h e r e a c t i o n m i x t u r e was s t i r r e d f o r t e n m i n u t e s a t 0° C. n - B u t y 1 1 i t h i u m , as a 2.4 M s o l u t i o n i n h e x a n e , ( 9 . 0 m l , .022 m o l e ) was a d d e d d r o p w i s e a n d t h e r e a c -t i o n m i x t u r e was s t i r r e d f o r an a d d i t i o n a l t e n m i n u t e s . E t h y l -e n e o x i d e ( 1 . 0 g, 0.023 m o l e ) i n 5 ml o f d r y t e t r a h y d r o f u r a n was t h e n a d d e d a n d t h e s o l u t i o n was i m m e d i a t e l y b r o u g h t t o r o o m t e m p e r a t u r e . T h e c o l o r o f t h e r e a c t i o n m i x t u r e c h a n g e d f r o m y e l l o w t o g r e e n . I t was t h e n s t i r r e d f o r o n e - h a l f h o u r , q u e n c h e d w i t h 5 ml o f c o n c e n t r a t e d h y d r o c h l o r i c a c i d p l u s 5 ml o f w a t e r a n d d i l u t e d w i t h e t h e r . T h e c o m b i n e d o r g a n i c p h a s e s w e r e w a s h e d w i t h s a t u r a t e d s o d i u m b i c a r b o n a t e a n d b r i n e u n t i l t h e m i x t u r e was n e u t r a l t o w e a k l y b a s i c . I t was t h e n d r i e d o v e r m a g n e s i u m s u l f a t e , f i l t e r e d , a n d t h e s o l v e n t s w e r e r e m o v e d b y e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e , t o g i v e 2.045 g ( 6 4 % ) o f c r u d e p r o d u c t . D i s t i l l a t i o n ( K u g e l r o h r ) o f t h e r e s u l t i n g o i l a t r e d u c e d p r e s s u r e ( 1 . 0 mm) c a u s e d t h e p r o d u c t - 62 t o s u b l i m e on t h e d i s t i l l a t i n g b u l b . T h e w h i t e c r y s t a l s w e r e i d e n t i f i e d as m e t h y l c c - ( t e t r a h y d r o - 2 - f u r y l i d e n e ) a c e -t a t e (95_) , mp 3 9 - 4 1 ° C; i r ( C H C 1 3 ) 1710 ( e s t e r C=0) a n d 1640 cm" 1 ( C = C - C = 0 ) ; nmr (CDC1 3 ) 6 2.08 (m, 2H, C H 2 ) , 3.15 ( t , J = 7.0 H z , 2H, C H 2 C = C ) , 3.65 ( s , 3H, 0 C H 3 ) , 4.25 ( t , J = 7.0 H z , 2H, C H 2 0 ) a n d 5.35 ppm ( t , J = 0.4 Hz, IH, C = C H ) ; mass s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 1 ( 2 9 ) , 4 2 ( 2 6 ) , 4 3 ( 3 2 ) , 4 4 ( 2 1 ) , 5 3 ( 1 1 ) , 5 5 ( 1 9 ) , 5 9 ( 1 1 ) , 6 9 ( 1 0 0 ) , 8 4 ( 9 ) , 1 1 0 ( 1 2 ) , 1 1 1 ( 6 3 ) , a n d 1 4 2 ( 2 4 ) ; a n a l y s i s c a l c u l a t e d f o r C 7 H i 0 O 3 : C 5 9 . 1 5 H 7.04 f o u n d : C 5 8 . 9 9 H 7.14 M e t h y l a - ( t e t r a h y d r o - 5-me t h y 1 - 2 - f u r y 1 i d e n e) a c e t a t e (SL6_) T h i s c o m p o u n d was p r e p a r e d b y t h e same p r o c e d u r e as t h a t e m p l o y e d i n t h e p r e p a r a t i o n o f m e t h y l a - ( t e t r a h y d r o - 2 -f u r y l i d e n e ) a c e t a t e (9_5_) . T h e r e a g e n t s u s e d w e r e : m e t h y l a c e t o a c e t a t e ( 5 . 8 0 g, 0.05 m o l e ) , s o d i u m h y d r i d e ( 2 . 7 g ) , a s a 5 7 % m i n e r a l o i l d i s p e r s i o n , n - b u t y 1 1 i t h i u m , a s a 1.6 M s o l u t i o n i n h e x a n e (32 m l , 0.05 m o l e ) a n d p r o p y l e n e o x i d e ( 2 . 9 0 g, 0.05 m o l e ) , w h i c h g a v e 6.034 g ( 6 9 % ) o f m e t h y l -3 - o x o - 7 - h y d r o x y - h e p t a n o a t e ( 9 4 ) , i d e n t i f i e d b y i t s i r a n d nmr. C o m p o u n d 9_4 ( 1 . 7 4 g, 0.01 m o l e ) was n o t p u r i f i e d b u t was t r e a t e d w i t h o n e e q u i v a l e n t o f o x a l i c a c i d i n C H 2 C1 2 ; t h e r e a c t i o n m i x t u r e was t h e n s t i r r e d f o r 2h h o u r s , w a s h e d w i t h s o d i u m b i c a r b o n a t e (2 x 50 m l ) , d r i e d o v e r m a g n e s i u m 63 -s u l f a t e , a n d t h e s o l v e n t s r e m o v e d b y e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e t o g i v e 1.4558 g ( 8 4 % ) o f m e t h y l a - ( t e t r a -h y d r o - 5 - m e t h y 1 - 2 - f u r y 1 i d e n e ) a c e t a t e (9_6) . D i s t i l l a t i o n o f t h e c r u d e p r o d u c t a t r e d u c e d p r e s s u r e g a v e 0 . 7 1 9 6 g ( 4 6 % ) o f p u r e c o m p o u n d (9_6_), bp 9 0 ° C, (14 mm); i r ( C H C 1 3 ) 1700 ( e s t e r C=0) a n d 1640 cm" 1 ( C = C - C = 0 ) ; nmr (C DC 1 3) 5 1.35 ( d , J = 7.0 H z , 3H, CH 3) , 2.20 (m, 2H, C H 2 ) , 3.20 (m, 2H, C H 2 C = C ) , 3.70 ( s , 3H, 0 C H 3 ) , 4.5 (m, I H , CH3CHO) a n d . 5 . 2 ppm ( t , J = 0.4 H z , I H , C = CH) ; m a s s s p e c t r u m a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C 8 H 1 2 0 3 : 1 5 6 . 0 7 8 6 amu, f o u n d 1 5 6 . 0 7 6 1 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 1 ( 1 6 ) , 4 3 ( 1 7 ) , 5 3 ( 6 ) , 5 5 ( 1 0 ) , 5 6 ( 9 ) , 5 9 ( 9 ) , 6 9 ( 1 0 0 ) , 8 2 ( 1 5 ) , 1 0 1 ( 3 2 ) , 1 2 4 ( 2 0 ) , 1 2 5 ( 5 8 ) , 1 2 7 ( 9 ) , 1 4 0 ( 5 ) a n d 1 5 6 ( 6 4 ) . R e a c t i o n o f S o d i o L i t h i o M e t h y l A c e t o a c e t a t e ( 5 5 ) w i t h  a - C h 1 o r o - e t h y 1 e t h e r M e t h y l 5 - m e t h o x y - 3 - o x o p e n t a n o a t e ( 1 2 0 ) S o d i u m h y d r i d e , a s a 5 7 % m i n e r a l o i l d i s p e r s i o n , ( 1 . 0 8 9 6 g, 0.02 m o l e ) was w e i g h e d i n t o an o v e n d r i e d f l a s k . I t was w a s h e d w i t h t e t r a h y d r o f u r a n (10 m l ) t o g e t r i d o f m i n e r a l o i l . A f t e r d e c a n t a t i o n o f t h e t e t r a h y d r o f u r a n , f r e s h t e t r a h y d r o f u r a n (50 m l ) was d i s t i l l e d d i r e c t l y i n t o t h e f l a s k . T h e f l a s k was t h e n e q u i p p e d w i t h a m a g n e t i c s t i r r e r , s e p t u m c a p , c o o l e d i n i c e a n d f l u s h e d w i t h n i t r o g e n . M e t h y l a c e t o -- 64 -a c e t a t e ( 2 . 3 2 g, 0.02 mole) was added d r o p w i s e t o t h e c o o l e d s l u r r y , and a f t e r t h e a d d i t i o n , t h e r e a c t i o n m i x t u r e was a l l o w e d t o s t i r f o r t e n m i n u t e s . n - B u t y l 1 i t h i u m , as a 2.4 M s o l u t i o n i n h e x a n e ( 9 . 0 m l , .02 mole) was a d d e d d r o p w i s e t o t h e r e a c t i o n m i x t u r e and i t was a l l o w e d t o s t i r f o r a n o t h e r t e n m i n u t e s . A f t e r a d d i t i o n o f c h l o r o m e t h y l m e t h y l e t h e r ( 1 . 6 1 0 2 g, 0.02 m o l e ) , t h e t e m p e r a t u r e was l o w e r e d t o -15°C ( i c e and a c e t o n e ) , and t h e r e a c t i o n m i x t u r e was a l l o w e d t o s t i r f o r an a d d i t i o n a l 30 m i n u t e s . I t was t h e n q u e n c h e d w i t h d i l u t e a c e t i c a c i d , e x t r a c t e d w i t h e t h e r (2 x 50 m l ) , washed w i t h s o d i u m b i c a r b o n a t e (2 x 50 m l ) , b r i n e (50 ml) and d r i e d o v e r magnesium s u l f a t e . The s o l v e n t s were r e m o v e d by e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e t o g i v e 1.0586 g (66% ) o f c r u d e m e t h y l 5 - m e t h o x y - 3 - o x o p e n t a n o a t e ( 1 2 0') . 150 mg o f compound 12 0 was p u r i f i e d by c o l u m n c h r o m a t o g r a p h y ( s i l i c a g e l 200 mesh ASTM) u s i n g a m i x t u r e o f c a r b o n t e t r a -c h l o r i d e and e t h y l e t h e r ( 8 : 2 v / v ) as e l u e n t . The s o l v e n t s were r e m o v e d by e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e t o g i v e 91 mg ( 4 0 % ) o f compound 1 2 0 ; i r (CHC1 3) 1740 ( e s t e r C = 0) , 1715 (C = 0) and 1630 cm" 1 ( e n o l ) ; nmr ( C D C I 3 ) 6 2.0-3.0 (m, 2H, 0 C H 2 C H 2 C 0 ) , 3.35 ( s , 3H, C H 3 C H 2 ) , 3.48 ( s , 2H, C 0 C H 2 C 0 ) , 3.35-3.80 (m, 2H, C H 3 0 C H 2 ) , 3.75 ( s , 3H, COOCH3) and 5.2 ppm ( e n o l ) ; - 65 -mass s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 3 ( 3 0 ) , 4 5 ( 1 0 0 ) , 5 5 ( 2 4 ) , 5 9 ( 9 ) , 6 9 ( 1 3 ) , 8 5 ( 1 3 ) , 8 7 ( 1 4 ) , 1 2 7 ( 4 ) , 1 2 9 ( 6 ) , 1 4 1 ( 3 ) , 142 (4) , and 1 6 0 ( 2 ) ; a n a l y s i s c a l c u l a t e d f o r C y H i ^ : C 52.49 H 7.55 f o u n d : C 52.70 H 7.47 M e t h y l 5 -methoxy-4-methy 1 - 3 - o x o p e n t a n o a t e (1_2_3) T h i s compound was p r e p a r e d by t h e same p r o c e d u r e as t h a t e m p l o y e d i n t h e p r e p a r a t i o n o f m e t h y l 5 - m e t h o x y - 3 -o x o p e n t a n o a t e ( 1 2 0 ) . The r e a g e n t s u s e d w e r e : s o d i u m h y d r i d e , as a 57% m i n e r a l o i l d i s p e r s i o n ( 0 . 3632 g, 0.007 m o l e ) , m e t h y l 3 - o x o p e n t a n o a t e ( 0 . 8 6 6 7 g, 0.006 m o l e ) , n - b u t y l l i t h i u m , as a 2.2 M s o l u t i o n i n h e x a n e (3 m l , 0.007 mole ) and c h l o r o m e t h y l m e t h y l e t h e r ( 0 . 5 3 6 7 g, 0.007 m o l e ) ; w h i c h gave 1.0109 g ( 8 7 % ) o f c r u d e m e t h y l 5 - methoxy-4-methy1 - 3 - o x o p e n t a n o a t e (12 3 ) . P u r i f i c a t i o n was a c h i e v e d by d i s t i l l a t i o n ( K u g e l r o h r ) t o g i v e 0.5324 g o f 1_2_3 ( 4 6 % ) , bp 60°C,(11.0 mm); i r ( C H C 1 3 ) 1740 ( e s t e r C=0), 1715 (C=0) and 1630 c m - 1 ( e n o l ) ; nmr (CDC13 ) 6 1.16 ( d , J=7.0 Hz, 3H, C H 3 ) , 2.0-3.0 (m,lH , 0CH 2CH) , 3.1-3.5 (m, 2H, C H 3 0 C H 2 ) , 3.35 ( s , 3H, 0 C H 3 ) , 3.48 ( s , 2H, C0CH 2C0) and 3.75 ppm ( s , 3H, C 0 0 C H 3 ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C 8 H 1 1 + 0 4 : 1 74.0892 amu, f o u n d 174.0879 m/e; b) low r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 1 ( 1 9 ) , 4 3 ( 1 5 ) , 4 5 ( 1 0 0 ) , 5 7 ( 1 9 ) , 5 9 ( 1 8 ) , 6 9 ( 2 0 ) , 7 3 ( 2 4 ) , 8 5 ( 1 0 ) , 9 9 ( 1 1 ) , 1 0 1 ( 4 8 ) , 1 2 7 ( 9 ) , 1 4 2 ( 2 0 ) , 1 4 3 ( 1 0 ) , 1 5 6 ( 6 ) , - 6 6 -1 5 8 ( 6 ) a n d 174 ( 2 ) . M e t h y l 5 - e t h o x y - 3 - o x o h e x a n o a t e ( 1 2 9 ) T h i s c o m p o u n d was p r e p a r e d b y t h e same p r o c e d u r e a s t h a t e m p l o y e d i n t h e p r e p a r a t i o n o f m e t h y l 5 - m e t h o x y - 3 -o x o p e n t a n o a t e (12 0 ) . T h e r e a g e n t s u s e d i n t h e p r e p a r a t i o n w e r e : s o d i u m h y d r i d e , a s a 5 7 % m i n e r a l o i l d i s p e r s i o n ( 0 . 2 7 g, 0.005 m o l e ) , m e t h y l a c e t o a c e t a t e ( 0 . 5 8 g, 0.005 m o l e ) , n - b u t y 1 1 i t h i u m , a s a 2.2 M s o l u t i o n i n h e x a n e ( 2 . 4 m l , 0.005 m o l e ) a n d a - c h 1 o r o e t h y 1 e t h y l e t h e r ( 0 . 5 4 g, 0.005 m o l e ) , w h i c h g a v e 0 . 6 8 4 6 g ( 7 3 % ) o f c r u d e m e t h y l 5 - e t h o x y - 3 -o x o h e x a n o a t e (12 9) ; i r (CHC 1 3 ) 1 740 ( e s t e r C = 0) a n d 1 720 c m - 1 ( C = 0 ) ; nmr ( C D C 1 3 ) 5 1.14 ( t , J = 7.0 H z , 3H, O C H 2 C H 3 ) , 1.18 ( d , J = 6.2 H z , 3H, C H 3 C H ) , 2 . 0 - 3 . 0 (m, 2H, C H 2 C 0 ) , 3.7 ( s , 3H, O C H 3 ) , 3 . 2 - 3 . 6 (m, 2H, O C H 2 C H 3 ) a n d 3. 7 - 4 . 0 ppm (m, I H , C H O E t ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C g H i g O ^ : 1 8 8 . 1 0 4 9 amu, f o u n d 1 8 8 . 1 0 5 2 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 1 ( 2 4 ) , 4 3 ( 1 0 0 ) , 4 5 ( 8 4 ) , 5 7 ( 1 3 ) , 5 9 ( 1 3 ) , 6 9 ( 5 5 ) , 7 0 ( 1 4 ) , 7 3 ( 3 3 ) , 8 5 ( 2 8 ) , 9 9 ( 3 3 ) , 1 0 1 ( 1 6 ) , 1 1 1 ( 1 2 ) , 1 1 5 ( 3 1 ) , 1 1 7 ( 1 0 ) , 1 2 7 ( 3 2 ) , 1 4 2 ( 1 0 ) , 1 4 4 ( 2 4 ) , 1 5 7 ( 1 1 ) , 1 5 9 ( 2 5 ) , 1 7 0 ( 7 ) a n d 1 8 8 ( 0 . 3 ) . .. p u r i f i e d by t i c f o r s p e c t r a l data - 67 M e t h y l 5 - n i e t h o x y - 3 - o x o h e x a n o a t e ( 1 3 0 ) T h i s c o m p o u n d was p r e p a r e d by t h e same p r o c e d u r e a s t h a t e m p l o y e d i n t h e p r e p a r a t i o n o f m e t h y l 5 - m e t h o x y - 3 -o x o p e n t a n o a t e (12 0) . T h e r e a g e n t u s e d i n t h e p r e p a r a t i o n w e r e : s o d i u m h y d r i d e , a s a 5 7 % m i n e r a l o i l d i s p e r s i o n ( 1 . 0 8 9 6 g, 0.02 m o l e ) , m e t h y l a c e t o a c e t a t e ( 2 . 3 2 g, 0.02 m o l e ) , n - b u t y 1 1 i t h i u r n , as a 2.2 M s o l u t i o n i n h e x a n e ( 9 . 5 m l , 0.02 m o l e ) a n d a-ch1oroethy1 m e t h y l e t h e r ( 1 . 8 8 g, 0.02 m o l e ) , w h i c h g a v e 3.0882 g ( 8 9 % ) o f c r u d e m e t h y l 5 - m e t h o x y - 3 - o x o -h e x a n o a t e (130)*; i r ( C H C 1 3 ) 1 740 ( e s t e r C = 0) a n d 1720 c m - 1 (C = 0 ) ; nmr ( C D C 1 3 ) 6 1.1 ( d , J = 6.0 H z , 3H, C H 3 - C H ) , 2 . 0 - 3 . 0 (m, 2,-H, 0 - C H C H 2 C 0 ) , 3.30 ( s , 3H, 0 C H 3 ) , 3.5 ( s , 2H, C 0 C H 2 C 0 2 C H 3.20 -4:. 00'(m, III, OCHGH^:) , and 5:76 ppm ( s , 3H, C00CH 3 ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a 1 c u l a t . e d . f o r CsHntOi^: 1 7 4 . 0 8 9 2 amu, f o u n d 1 7 3 . 0 8 1 5 m/e; ( T h e m o l e c u l e l o s e s one h y d r o g e n r e a d i l y . ) b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 3 ( 4 1 ) , 5 9 ( 1 0 0 ) , 6 9 ( 2 9 ) , 8 5 ( 2 5 ) , 1 0 1 ( 4 0 ) , 1 1 0 ( 8 ) , 1 1 1 ( 6 ) , 1 1 6 ( 8 ) , 1 1 7 ( 8 ) , 1 2 7 ( 1 5 ) , 1 4 2 ( 1 2 ) , 1 4 3 ( 8 ) , 1 5 9 ( 6 ) , 1 6 8 ( 3 ) a n d 1 7 3 ( 1 ) . M e t h y l 5 - c h l o r o - 3 - o x o h e x a n o a t e ( 1 5 4 ) C h l o r o f o r m (50 m l ) was s a t u r a t e d w i t h a n h y d r o u s h y d r o g e n c h l o r i d e b y d i r e c t p a s s a g e o f t h e g a s t h r o u g h t h e s o l v e n t . M e t h y l 5 - e t h o x y - 3 - o x o h e x a n o a t e (12 9) ( 0 . 5 5 g, - 68 -0 . 0 0 2 9 m o l e ) was d i s s o l v e d i n t h i s H C I / C H C I 3 s o l u t i o n a n d t h e r e a c t i o n m i x t u r e was s t i r r e d a t r o o m t e m p e r a t u r e f o r two h o u r s . T h e r e a c t i o n m i x t u r e was t h e n w a s h e d w i t h s a t u r -a t e d s o d i u m b i c a r b o n a t e , b r i n e a n d d r i e d o v e r m a g n e s i u m s u l f a t e . T h e s o l v e n t s w e r e r e m o v e d b y e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e t o g i v e 0 . 5 1 6 7 g ( 9 9 % ) o f m e t h y l 5 - c h l o r o -* 3 - o x o h e x a n o a t e ( 1 5 4 ) ; i r ( C H C I 3 ) 1740 ( e s t e r C=0) a n d 1720 cm" 1 ( C = 0 ) ; nmr (CDC 1 3) <5 1.5 ( d , J = 7.0 H z , 3H, C H 3 C H C 1 ) , 3.0 ( d d , J = 7.0 H z , J = 3.0 H z , 2H, C H 2 C = 0 ) , 3.5 ( s , 2H, C 0 C H 2 C 0 2 C H 3 ) , 3.75 ( s , 3H, 0 C H 3 ) a n d 4.5 ppm (m, I H , C H 3 C H C I ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C 7 H n C 1 0 3 : 1 7 8 . 0 3 9 7 amu, f o u n d 1 7 8 . 0 3 9 7 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 1 ( 8 1 ) , 4 3 ( 9 8 ) , 4 4 ( 5 1 ) , 5 9 ( 2 3 ) , 6 9 ( 1 0 0 ) , 1 0 1 ( 3 2 ) , 1 1 0 ( 3 7 ) , 1 1 1 ( 3 5 ) , 1 2 7 ( 3 2 ) , 1 4 2 ( 5 2 ) , 1 4 3 ( 1 6 ) a n d 1 7 8 ( 2 ) . A l k y l a t i o n o f t h e D i a n i o n o f g - K e t o e s t e r s w i t h D i h a l o a l k a n e s R e a c t i o n o f 1 , 4 - d i b r o m o b u t a n e w i t h d i a n i o n 5_5_ S o d i u m h y d r i d e , as a 5 7 % m i n e r a l o i l d i s p e r s i o n ( 1 . 0 8 9 6 g, 0.02 m o l e ) was w e i g h e d i n t o an o v e n - d r i e d 100 ml f l a s k , a n d t e t r a h y d r o f u r a n (50 m l ) was d i s t i l l e d f r o m l i t h i u m a l u m i n i u m h y d r i d e , d i r e c t l y i n t o t h i s f l a s k . T h e f l a s k was f i t t e d w i t h a m a g n e t i c s t i r r e r , s e p t u m c a p , c o o l e d i n i c e t o 0° C a n d f l u s h e d w i t h n i t r o g e n . M e t h y l a c e t o a c e t a t e - 6 9 -( 2 . 3 2 g, 0.02 m o l e ) was a d d e d d r o p w i s e , a n d t h e r e a c t i o n m i x t u r e was s t i r r e d f o r t e n m i n u t e s a f t e r t h e a d d i t i o n was c o m p l e t e . n - B u t y l l i t h i u m , as a 2.2 M s o l u t i o n i n h e x a n e , (9 m l , .02 m o l e ) was a d d e d d r o p w i s e t o t h e r e a c t i o n w h i c h was a l l o w e d t o s t i r f o r a f u r t h e r t e n m i n u t e s b e f o r e t h e a d d i t i o n o f 1 , 4 - d i b r o m o b u t a n e ( 4 . 3 1 8 6 g, 0.02 m o l e ) i n o n e p o r t i o n . T h e r e a c t i o n m i x t u r e was t h e n a l l o w e d t o s t i r f o r an a d d i t i o n a l o n e h o u r a t 0° C. I t was t h e n q u e n c h e d w i t h d i l u t e h y d r o c h l o r i c a c i d , e x t r a c t e d w i t h e t h y l e t h e r (2 x 50 m l ) , w a s h e d w i t h s a t u r a t e d s o d i u m b i c a r b o n a t e (2 x 50 m l ) , s a t u r a t e d s o d i u m c h l o r i d e s o l u t i o n (50 m l ) , d r i e d o v e r mag-n e s i u m s u l f a t e a n d f i l t e r e d . T h e s o l v e n t s w e r e r e m o v e d b y e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e t o g i v e 3 . 2 7 2 9 g o f c r u d e p r o d u c t s . P u r i f i c a t i o n o f t h e s e p r o d u c t s was a c h i e v e d b y t i c : 150 mg o f t h e c r u d e m a t e r i a l was c h r o m a t o g r a p h e d on a 20 cm x 20 cm s i l i c a c o a t e d p l a t e , a d s o r b e n t t h i c k n e s s 0.9 mm, u s i n g a m i x t u r e o f c a r b o n t e t r a c h l o r i d e a n d e t h y l e t h e r ( 7 : 3 v / v ) as e l u e n t . Two c o m p o n e n t s w e r e i s o l a t e d f r o m t h i s c h r o m a t o g r a p h y , a n d t h e s e w e r e , i n o r d e r o f e l u t i o n , m e t h y l 8 - b r o m o - 5 - o x o o c t a n o a t e ( 1 4 1 a ) ( 0 . 0 5 9 8 g, 26%) a n d d i m e t h y l 3 , 1 0 - d i o x o d o d e c a n e d i o a t e ( 6 2 b ) ( 0 . 0 3 9 5 g, 1 5 % ) . M e t h y l 8 - b r o m o - 3 - o x o o c t a n o a t e ( 1 4 1 a ) was c h a r a c t e r -i s e d b y : i r ( C H C 1 3 ) 1745 ( e s t e r C=0) a n d 1720 cm" 1 ( C = 0 ) ; 70 -nmr (CDC 13) 6 1 . 2 5 - 2 . 0 (m, 6H, C O C H 2 C H 2 C H 2 C H 2 C H 2 B r ) , 2.56 ( t , J = 7.0 H z , 2H, C H 2 C O ) , 3.5 ( s , 2H, C 0 C H 2 C 0 ) , ' 3.42 ( t , J = 6.2 H z , 2H, C H 2 B r ) a n d 3.75 ppm ( s , 3H, 0 C H 3 ) ; mass s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 0 ( 4 4 ) , 4 1 ( 1 6 ) , 4 3 ( 5 7 ) , 4 4 ( 1 0 0 ) , 5 5 ( 9 ) , 5 7 ( 9 ) , 5 9 ( 6 ) , 6 9 ( 1 6 ) , 7 3 ( 1 ) , 1 0 1 ( 8 ) , 1 1 3 ( 1 1 ) , 1 16 ( 2 0 ) , 1 29 ( 2 ) , 1 71 (1 1) , 1 77 (5) , 1 79 ( 4 ) , 250 ( 1) a n d 252 ( 1 ) ; a n a l y s i s c a l c u l a t e d f o r C 9 H 1 5 B r 0 3 : C 4 3 . 0 5 H 6.02 B r 31.82 0 19 . 1 1 f o u n d : C 4 2 . 9 6 H 5.93 B r 3 1 . 9 8 0 19 . 13 D i m e t h y l 3 , 1 0 - d i o x o d o d e c a n e d i . o a t e ( 6 2 b ) was c h a r a c -t e r i z e d b y : i r ( C H C I 3 ) 1 745 ( e s t e r C = 0 ) , 1720 cm" 1 (C = 0 ) ; nmr ( C D C 1 3 ) 6 1.1-1.8 (m, 8H, C 0 C H 2 C H 2 C H 2 C H 2 C H 2 C H 2 C 0 ) , 2.52 ( t , J = 6.20 H z , 4H, C 0 C H 2 C H 2 ) , 3.42 ( s , 4H, C 0 C H 2 C 0 ) a n d 3.75 ppm ( s , 6H, 0 C H 3 ) ; m a s s s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 1 ( 2 0 ) , 4 3 ( 2 0 ) , 5 5 ( 2 9 ) , 5 8 ( 2 0 ) , 5 9 ( 3 3 ) , 6 9 ( 2 2 ) , 7 4 ( 1 3 ) , 8 3 ( 1 7 ) , 9 7 ( 4 5 ) , 1 0 1 ( 3 7 ) , 1 1 1 ( 2 2 ) , 1 1 6 ( 6 8 ) , 1 2 9 ( 2 4 ) , 1 3 9 ( 2 7 ) , 1 5 3 ( 1 2 ) , 1 7 1 ( 1 0 0 ) , 1 7 2 ( 1 0 ) , 1 8 1 ( 1 3 ) , 2 1 3 ( 8 ) , 2 5 5 ( 8 ) , 2 6 8 ( 1 1 ) a n d 2 8 6 ( 1 ) ; a n a l y s i s c a l c u l a t e d f o r C i t + H 2 2 0 5 : C 5 8 . 7 3 H 7.74 f o u n d : C 5 8 . 6 7 H 7.66 R e a c t i o n o f 1 , 5 - d i b r o m o p e n t a n e w i t h d i a n i o n 55 T h e p r o c e d u r e u s e d i n t h i s a s t h a t e m p l o y e d i n t h e r e a c t i o n o f r e a c t i o n was t h e same 1 , 4 - d i b r o m o b u t a n e w i t h 71 d i a n i o n 5_5_. T h e r e a g e n t s u s e d w e r e : s o d i u m h y d r i d e , as a 5 7 % m i n e r a l o i l d i s p e r s i o n ( 1 . 0 8 9 6 g, 0.02 m o l e ) , m e t h y l a c e t o a c e t a t e ( 2 . 3 2 g, 0.02 m o l e ) , n - b u t y l l i t h i u m , as a 2.2 M s o l u t i o n i n h e x a n e (9 m l , 0.02 m o l e ) a n d 1 , 5 - d i b r o m o p e n t a n e ( 4 . 6 g, 0.02 m o l e ) , w h i c h g a v e 4 . 1 5 8 0 g o f a m i x t u r e o f c r u d e p r o d u c t s . P u r i f i c a t i o n o f t h e s e p r o d u c t s was a c h i e v e d b y t i c : 150 mg o f c r u d e p r o d u c t s was c h r o m a t o g r a p h e d on a 20 cm x 20 cm s i l i c a c o a t e d p l a t e , a d s o r b e n t t h i c k n e s s 0.9 mm, u s i n g a m i x t u r e o f c a r b o n t e t r a c h l o r i d e a n d e t h y l e t h e r ( 7 : 3 v / v ) a s e l u e n t . Two c o m p o n e n t s w e r e i s o l a t e d f r o m t h i s c h r o m a t o g r a p h y , a n d t h e s e w e r e , i n o r d e r o f e l u t i o n , m e t h y l 9 - b r o m o - 3 - o x o n o n a o a t e ( 1 4 1 b ) ( 0 . 0 4 5 9 g, 25%) a n d d i m e t h y l 3 , 1 1 - d i o x o t r i d e c a n e d i o a t e ( 6 2 c ) ( 0 . 0 3 4 4 g, 1 6 % ) . M e t h y l 9 - b r o m o - 3 - o x o n o n a o a t e ( 1 4 1 b ) was c h a r a c t e r i s e d b y : i r ( C H C 1 3 ) 1745 ( e s t e r C=0) a n d 1720 cm" 1 ( C = 0 ) ; nmr (CDC 13) 6 1.2-2.0 (m, 8H, C 0 C H 2 ( C H 2 ) 4 C H 2 B r ) , 2.55 ( t , J = 7.0 H z , 2H, C H 2 C 0 ) , 3.42 ( t , J = 6.5 H z , 2H, C H 2 B r ) , 3.45 ( s , 2H, C 0 C H 2 C 0 ) a n d 3.72 ppm ( s , 3H, 0 C H 3 ) ; mass s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 3 ( 7 2 ) , 4 4 ( 7 5 ) , 5 5 ( 5 6 ) , 5 8 ( 4 0 ) , 5 9 ( 2 1 ) , 6 9 ( 1 2 ) , 7 4 ( 1 7 ) , 8 3 ( 2 5 ) , 8 4 ( 1 6 ) , 1 0 1 ( 2 5 ) , 1 1 1 ( 1 1 ) , 1 1 6 ( 1 0 0 ) , 1 1 7 ( 1 5 ) , 1 2 7 ( 9 ) , 1 2 9 ( 8 ) , 1 8 5 ( 2 5 ) , 1 9 1 ( 1 5 ) , 1 9 3 ( 1 3 ) , 2 6 4 ( 0 . 1 ) , a n d 2 6 6 ( 0 . 1 ) ; a n a l y s i s c a l c u l a t e d f o r C i 0 H i 7 B r O 3 : C 4 5 . 3 0 H 6.46 B r 30.14 0 1 8 . 1 0 ; f o u n d : C 4 5 . 4 7 H 6.27 B r 2 9 . 9 0 72 D i m e t h y l 3 , 1 1 - d i o x o t r i d e c a n e d i o a t e ( 6 2 c ) was c h a r a c t e r i s e d b y : i r ( C H C I 3 ) 1 745 ( e s t e r C = 0) a n d 1 720 cm" 1 ( O O ) ; nmr ( C D C 1 3 ) 6 1.2-1.8 (m, 10H, C O C H 2 ( C H 2 ) 5 C H 2 C O ) , 2.5 ( t , J = 7.0 H z , 4H, C H 2 C 0 ) , 3.45 ( s , 4H, C 0 C H 2 C 0 ) , a n d 3 . 75 ppm ( s , 6H, OCH 3 ) ; mass s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 3 ( 3 5 ) , 5 5 ( 5 8 ) , 5 9 ( 4 8 ) , 6 9 ( 2 8 ) , 8 1 ( 1 0 ) , 8 4 ( 2 2 ) , 9 7 ( 2 0 ) , 1 0 1 ( 4 7 ) , 1 1 1 ( 4 3 ) , 1 1 6 ( 7 9 ) , 1 2 5 ( 2 3 ) , 1 2 9 ( 2 9 ) , 1 5 3 ( 2 5 ) , 1 6 7 ( 7 6 ) , 1 8 5 ( 1 0 0 ) , 1 9 5 ( 2 0 ) , 2 2 7 ( 1 8 ) , 2 6 7 ( 1 6 ) , 2 6 8 ( 1 6 ) a n d 3 0 0 ( 7 ) ; a n a l y s i s c a l c u l a t e d f o r C 1 5 H 1 1 + 0 6 : C 5 9 . 9 8 H 8.05 0 3 1 . 9 6 ; f o u n d : C 5 9 . 8 7 H 8.05 R e a c t i o n o f 1 , 1 0 - d i b r omo de c an e w i t h d i a n i o n 5JL T h e p r o c e d u r e u s e d i n t h i s r e a c t i o n was t h e same as t h a t e m p l o y e d i n t h e r e a c t i o n o f 1 , 4 - d i b r o m o b u t a n e w i t h d i a n i o n 5_5_. T h e r e a g e n t s u s e d w e r e : s o d i u m h y d r i d e , a s a 5 7 % m i n e r a l o i l d i s p e r s i o n ( 1 . 0 8 9 6 g, 0.02 m o l e ) , m e t h y l a c e t o -a c e t a t e ( 2 . 3 2 g, 0.02 m o l e ) , n - b u t y l l i t h i u m , a s a 2.2 M s o l u t i o n i n h e x a n e (9 m l , 0.02 m o l e ) a n d 1 , 1 0 - d i b r o m o d e c a n e ( 5 . 9 9 6 g, 0.02 m o l e ) , w h i c h g a v e 7.0324 g o f a m i x t u r e o f c r u d e p r o d u c t s . P u r i f i c a t i o n o f t h e p r o d u c t s was a c h i e v e d b y t i c : 150 mg o f c r u d e m i x t u r e o f 6 2 c a n d 1 4 1 c was c h r o m a -t o g r a p h e d on a 20 cm x 20 cm s i l i c a c o a t e d p l a t e , a d s o r b e n t - /s -t h i c k n e s s 0.9 mm, u s i n g a m i x t u r e o f c a r b o n t e t r a c h l o r i d e a n d e t h y l e t h e r ( 7 : 3 v / v ) as e l u e n t . Two c o m p o n e n t s w e r e i s o l a t e d f r o m t h i s c h r o m a t o g r a p h y , a n d t h e s e w e r e , i n o r d e r o f e l u t i o n , m e t h y l 1 4 - b r o m o - 3 - o x o t e t r a d e c a n o a t e ( 1 4 1 c ) ( 0 . 0 5 5 8 g, 39%) a n d d i m e t h y l 3 , 1 6 - d i o x o o c t a d e c a n e d i o a t e ( 6 2 d ) (0 . 0 3 4 1 g , 22%) w h i c h was i d e n t i f i e d b y c o m p a r i s o n o f i t s i r a n d nmr s p e c t r a w i t h t h o s e o f t h e a u t h e n t i c c o m p o u n d . M e t h y l 1 4 - b r o m o - 3 - o x o t e t r a d e c a n o a t e ( 1 4 1 c ) was c h a r a c t e r i s e d b y : i r (CHC1 3 ) 1 745 ( e s t e r C = 0) a n d 1720 cm" 1 ( C = 0 ) ; nmr ( C D C 1 3 ) 6 1 .0-1.6 (m, 18H, C O C H 2 ( C H 2 ) 9 C H 2 B r ) , 2.5 ( t , J = 7.0 H z , 2H, C H 2 C 0 ) , 3.42 ( s , 2H, C 0 C H 2 C 0 ) , 3.42 ( t , J = 6.5 H z , 2H, C H 2 B r ) a n d 3.7 ppm ( s , 3H, O C H 3 ) ; mass s p e c t r u m a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C i 5 H 2 7 B r 0 3 : 3 3 4 . 1 1 4 4 amu, f o u n d 3 3 4 . 1 1 2 0 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 5 5 ( 8 2 ) , 5 8 ( 8 9 ) , 5 9 ( 4 5 ) , 6 9 ( 4 5 ) , 7 1 ( 4 0 ) , 7 4 ( 3 3 ) , 8 1 ( 2 9 ) , 8 3 ( 3 1 ) , 8 5 ( 3 3 ) , 9 7 ( 2 3 ) , 1 0 1 ( 2 6 ) , 1 1 6 ( 1 0 0 ) , 1 2 9 ( 4 1 ) , 1 3 0 ( 1 6 ) , 1 3 8 ( 1 4 ) , 1 4 9 ( 1 1 ) , 1 5 9 ( 9 ) , 1 6 2 ( 1 6 ) , 1 6 3 ( 9 ) , 1 7 9 ( 1 0 ) , 1 8 1 ( 1 1 ) , 1 8 3 ( 1 1 ) , 1 9 3 ( 6 ) , 1 9 5 ( 8 ) , 2 3 6 ( 5 ) , 2 5 2 ( 3 ) a n d 2 5 4 ( 6 ) . M e t h y l 2 - c y c 1 o h e p t a n o n e c a r b o x y l a t e ( 1 4 0 a ) An o v e n - d r i e d 100 ml 3 - n e c k f l a s k was f i t t e d w i t h a c o n d e n s e r p r o t e c t e d b y a c a l c i u m c h l o r i d e t u b e a n d a 10 ml d r o p p i n g f u n n e l . 50 ml o f d r y m e t h a n o l was a d d e d g r a d u a l l y t o t h e f l a s k c o n t a i n i n g s o d i u m ( 0 . 2 3 g, 0.01 m o l e ) . When - 7 4 -t h e s o d i u m h a s d i s s o l v e d , a c r u d e m i x t u r e o f c o m p o u n d 62b a n d m e t h y l 8 - b r o m o - 3 - o x o o c t a n o a t e ( 1 4 1 a ) ( 3 . 5 g, a s s u m i n g 0 . 0052 m o l e o f ( 1 4 1 a ) ) i n 2 ml o f m e t h a n o l was a d d e d d r o p w i s e t o t h e s o d i u m m e t h o x i d e s o l u t i o n . T h e r e a c t i o n m i x t u r e was t h e n h e a t e d t o g e n t l e b o i l i n g a n d r e f l u x e d f o r 13 h o u r s . I t was t h e n a l l o w e d t o c o o l a n d m e t h a n o l was r e m o v e d by e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e . W a t e r (25 m l ) was a d d e d t o d i s s o l v e t h e s o l i d , a n d t h e p r o d u c t was e x t r a c t e d w i t h e t h y l e t h e r (2 x 25 m l ) . T h e o r g a n i c l a y e r was t h e n w a s h e d w i t h w a t e r u n t i l i t was n e u t r a l t o l i t m u s , d r i e d o v e r mag-n e s i u m s u l f a t e a n d t h e s o l v e n t r e m o v e d u n d e r r e d u c e d p r e s s u r e t o g i v e 1.9254 g o f c r u d e p r o d u c t . 90 mg o f c r u d e p r o d u c t was c h r o m a t o g r a p h e d on a 5 cm x 20 cm s i l i c a c o a t e d p l a t e , a d s o r b e n t t h i c k n e s s 0.9 mm, u s i n g a m i x t u r e o f c a r b o n t e t r a -c h l o r i d e a n d e t h y l e t h e r ( 7 : 3 v / v ) a s e l u e n t . T h e t o p f r a c -t i o n i s o l a t e d f r o m t h i s c h r o m a t o g r a p h y was m e t h y l 2 - c y c l o -h e p t a n o n e c a r b o x y l a t e ( 1 4 0 a ) ( 0 . 0 3 0 g, 73% b a s e on b r o m o -c o m p o u n d 1 4 1 a ) w h i c h was c h a r a c t e r i s e d b y : i r (CHC1 3 ) 1 735 ( e s t e r C = 0) a n d 1 700 cm" 1 (C = 0) ; nmr (CDC 1 3) 6 1.2-2.0 (m, 8H, C 0 C H 2 ( C H 2 ) ^ C H ) , 2.5 (m, 2H, C H 2 C 0 ) , 3.5 (m, I H , COCHCO) a n d 3.7 ppm ( s , 3H, O C H 3 ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C 9 H i 4 0 3 : 1 7 0 . 0 9 4 3 amu, f o u n d 1 7 0 . 0 9 4 4 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 1 ( 3 3 ) , 5 5 ( 7 3 ) , 6 8 ( 2 3 ) , 6 9 ( 2 0 ) , 7 4 ( 3 1 ) , 8 2 ( 3 1 ) , 8 7 ( 2 5 ) , 1 1 0 ( 3 7 ) , 1 1 1 ( 6 ) , 1 1 3 ( 2 7 ) , 1 2 8 ( 1 5 ) , 1 3 8 ( 1 0 0 ) , 1 3 9 ( 4 5 ) , 142 ( 4 3 ) a n d 1 70 ( 6 0 ) . 75 M e t h y l 2 - c y c l o o c t a n o n e c a r b o x y l a t e ( 1 4 0 b ) T h i s c o m p o u n d was p r e p a r e d by t h e same p r o c e d u r e a s t h a t e m p l o y e d i n t h e p r e p a r a t i o n o f c o m p o u n d 14 0 a . T h e r e a g e n t s u s e d w e r e : s o d i u m ( 0 . 2 3 g, 0.01 m o l e ) , d r y m e t h a n o l (50 m l ) a n d c r u d e m i x t u r e o f c o m p o u n d 6 2c a n d m e t h y l 9 - b r o m o -3 - o x o n o n a o a t e ( 1 4 1 b ) ( 4 . 2 g, a s s u m i n g 0.005 m o l e o f ( 1 4 1 b ) ) . 150 mg o f c r u d e p r o d u c t was c h r o m a t o g r a p h e d t o g i v e 0.050 g ( 7 3 % b a s e d on c o m p o u n d 1 4 1 b ) o f m e t h y l 2 - c y c l o o c t a n o n e c a r -b o x y l a t e ( 1 4 0 b ) w h i c h was c h a r a c t e r i s e d b y : i r (CHC1 3 ) 1 735 ( e s t e r C = 0) a n d 1700 c m - 1 (C = 0) ; nmr (CDC13 ) <5 1.0-2.0 (m, 10H, C 0 C H 2 ( C H 2 ) 5 C H ) , 2.4 (m, 2H, C O C H 2 ) , 3.38 (m, I H , COCHCO) a n d 3.65 ppm ( s , 3 H , . O C H 3 ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C i 4 H 1 6 0 3 : 1 8 4 . 1 0 9 9 amu, f o u n d 1 8 4 . 1 0 9 8 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 1 ( 5 2 ) , 4 3 ( 3 2 ) , 4 5 ( 2 7 ) , 5 5 ( 9 2 ) , 5 9 ( 1 9 ) , 6 8 ( 3 6 ) , 6 8 ( 3 6 ) , 6 9 ( 4 4 ) , 74 ( 1 0 0 ) , 83 ( 2 3 ) , 84 ( 3 4 ) , 86 ( 1 8 ) , 87 ( 3 1 ) , 96 ( 2 7 ) , 98 ( 2 3 ) , 1 0 9 ( 2 3 ) , 1 2 4 ( 2 7 ) , 1 2 5 ( 4 ) , 1 5 2 ( 6 3 ) , 1 5 3 ( 3 1 ) , 1 5 6 ( 3 6 ) , a n d 184 ( 6 7 ) . M e t h y l 2 - o x a - c y c 1 o h e p t a - e t h y 1 i d e n e c a r b o x y 1 a t e ( 1 4 2 ) H e x a m e t h y l p h o s p h o r a m i d e ( 1 5 m l ) was a d d e d t o an o v e n - d r i e d 25 ml f l a s k c o n t a i n i n g 0 .027 g o f s o d i u m h y d r i d e ( a s a 5 7 % m i n e r a l o i l d i s p e r s i o n ) . T h e f l a s k was f i t t e d w i t h a m a g n e t i c s t i r r e r , a s e p t u m c a p a n d f l u s h e d w i t h n i t r o g e n . - 76 -M e t h y l 8 - b r o m o - 3 - o x o o c t a n o a t e ( 1 4 1 a ) ( 0 . 1 2 5 g, 0 . 0 0 0 5 m o l e ) i n 1 ml o f t e t r a h y d r o f u r a n was a d d e d d r o p w i s e t o t h e s o l u t i o n . T h e r e a c t i o n m i x t u r e was a l l o w e d t o s t i r f o r 1% h o u r . I t was t h e n d i l u t e d w i t h p e n t a n e , w a s h e d w i t h w a t e r a n d d r i e d , o v e r m a g n e s i u m s u l f a t e . T h e s o l v e n t s w e r e r e m o v e d b y e v a p o r a -t i o n u n d e r r e d u c e d p r e s s u r e . P u r i f i c a t i o n was a c h i e v e d b y t i c t o g i v e 0 .0502 g ( 5 9 % ) o f c o m p o u n d 14 2 w h i c h was c h a r a c -t e r i s e d b y : i r (CHC1 3 ) 1 700 ( u n s a t u r a t e d e s t e r ) , 1630 ( O C ) a n d 840 cm" 1 ( t r i s u b s t i t u t e d O C ) ; nmr (C DC 13) 6 1 . 2-1.9 (m, 6H, ( C H 2 ) 3 ) , 3.2 (m, 2H, C H 2 C 0 ) , 3.7 ( s , 3H, O C H 3 ) , 4.2 (m, 2H, C H 2 0 ) , a n d 5.25 ppm ( s , I H , O C H ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u a t e d f o r C 9 H 1 4 O 3 : 1 7 0 . 0 9 4 3 a i m , f o u n d 1 7 0 . 0 9 4 4 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 1 ( 7 3 ) , 4 3 ( 3 6 ) , 4 4 ( 8 2 ) , 5 6 ( 1 0 0 ) , 6 0 ( 2 8 ) , 6 9 ( 3 0 ) , 7 0 ( 8 6 ) , 7 5 ( 3 4 ) , 8 3 ( 3 2 ) , 8 5 ( 8 6 ) , 8 7 ( 5 1 ) , 9 8 ( 3 2 ) , 1 0 2 ( 2 8 ) , 1 1 1 ( 4 1 ) , 1 2 9 ( 3 0 ) , 1 3 4 ( 4 5 ) , 1 3 9 ( 7 7 ) , 1 4 0 ( 6 1 ) , 1 4 3 ( 4 2 ) , a n d 1 7 0 ( 6 6 ) . R e a c t i o n o f S o d i o L i t h i o M e t h y l A c e t o a c e t a t e ( 5 5 ) w i t h  D i h a l o a l k e n e P r e p a r a t i o n o f c i s 1 , 4 - d i c h 1 o r o - 2 - b u t e n e s o l v e d N - c h 1 o r o s u c c i n i m i d e ( 1 1 . 7 4 g, 0.088 m o l e ) i n 400 ml o f a n h y d r o u s m e t h y l e n e c h l o r i d e . was T h e d i s -f l a s k 77 -was f i t t e d w i t h a s e p t u m c a p , m a g n e t i c s t i r r e r , c o o l e d i n i c e a n d f l u s h e d w i t h n i t r o g e n . M e t h y l s u l f i d e ( 5 . 4 5 6 g, 0.088 m o l e ) was a d d e d d r o p w i s e o v e r a few m i n u t e s . I n t e n s e w h i t e p r e c i p i t a t e was o b s e r v e d . T h e r e a c t i o n m i x t u r e was t h e n c o o l e d t o - 2 0 ° C ( c a r b o n t e t r a c h l o r i d e , p l u s d r y i c e ) a n d c i s 2 - b u t e n e 1 , 4 - d i o l ( 3 . 5 2 0 g, 0.040 m o l e ) i n 5 ml o f m e t h y l e n e c h l o r i d e was a d d e d o v e r 10 m i n u t e s . T h e r e s u l t i n g s o l u t i o n was t h e n w armed t o 0 ° C a n d s t i r r e d f o r 50 m i n u t e s . T h e w h i t e p r e c i p i t a t e d i s a p p e a r e d , l e a v i n g a c l e a r c o l o r l e s s s o l u t i o n . T h e m i x t u r e was s t i r r e d f o r an a d d i t i o n a l 70 m i n -u t e s , d i l u t e d w i t h p e n t a n e a n d p o u r e d i n t o 400 ml o f i c e -c o l d b r i n e . T h e a q u e o u s p h a s e was e x t r a c t e d w i t h p e n t a n e (2 x 200 m l ) a n d t h e o r g a n i c l a y e r s w e r e c o m b i n e d . I t was t h e n w a s h e d w i t h c o l d b r i n e (2 x 400 m l ) , a n d d r i e d o v e r m a g n e s i u m s u l f a t e . S o l v e n t s w e r e r e m o v e d b y e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e . T h e r e s u l t i n g c r u d e p r o d u c t was t h e n d i s t i l l e d t o g i v e 3 . 6 104 g ( 7 2 % ) o f c i s 1 , 4 - d i c h 1 o r o - 2 -b u t e n e , bp 1 2 8 ° C ( 7 6 0 mm) ( l i t . , bp 7 2 - 7 5 ° C/4 0mm , m i x t u r e o f c i s a n d t r a n s ) . A l k y l a t i o n o f s o d i o l i t h i o m e t h y l a c e t o a c e t a t e ( 5 5 ) w i t h c i s 1 , 4 - d i c h 1 o r o - 2 - b u t e n e T h e p r o c e d u r e u s e d i n t h i s r e a c t i o n was t h e same a s t h a t e m p l o y e d i n t h e r e a c t i o n o f 1 , 4 - d i b r o m o b u t a n e w i t h d i a n i o n 5_5_. T h e r e a g e n t s i n t h i s p r e p a r a t i o n w e r e : s o d i u m - 78 -h y d r i d e , as a 5 7 % m i n e r a l o i l d i s p e r s i o n ( 1 . 0 8 9 6 g, 0.02 m o l e ) , m e t h y l a c e t o a c e t a t e ( 2 . 3 2 g, 0.02 m o l e ) , n - b u t y l -l i t h i u m , a s a 2.2 M s . o l u t i o n i n h e x a n e (9 m l , 0.02 m o l e ) a n d c i s 1 , 4 - d i c h 1 o r o - 2 - b u t e n e ( 2 . 5 g, 0.02 m o l e ) w h i c h g a v e 2 . 9 9 1 3 g o f c r u d e p r o d u c t . P u r i f i c a t i o n o f t h e p r o d u c t s was a c h i e v e d by t i c : 150 mg o f c r u d e p r o d u c t s was c h r o m a t o -g r a p h e d on a s i l i c a c o a t e d p l a t e , a d s o r b e n t t h i c k n e s s 0.9 mm, u s i n g a m i x t u r e o f c a r b o n t e t r a c h l o r i d e a n d e t h y l e t h e r ( 7 : 3 v / v ) as e l u e n t . Two c o m p o n e n t s w i t h i s o l a t e d f r o m t h i s c h r o m a t o g r a p h y , a n d t h e s e w e r e , i n o r d e r o f e l u t i o n , m e t h y l 3 - o x o - 8 - c h l o r o - 6 - o c t e n o a t e ( 1 4 6 ) ( 0 . 0 3 6 5 g, 18%) a n d d i m e t h y l 3 , 1 0 - d i o x o - 6 - d o d e c e n e d i o a t e ( 1 4 7 ) ( 0 . 0 4 9 4 g, 1 8 % ) . M e t h y l 3 - o x o - 8 - c h l o r o - 6 - o c t e n o a t e ( 1 4 6 ) was c h a r a c t e r i z e d b y : . i r ( C H C 1 3 ) 1 745 ( e s t e r C = 0 ) , 1720 (C = 0) a n d 1660 cm" 1 ( c i s CH = CH) ; nmr ( C D C 1 3 ) 5 2 . 2 - 2 . 8 (m, 4H, C H 2 C H 2 C 0 ) , 3.45 ( s , 2H, C 0 C H 2 C 0 ) , 3.75 ( s , 3H, 0 C H 3 ) , 4.08 ( d , J = 6.5 H z , 2H, C H 2 C 1 ) a n d 5 . 5 - 5 . 8 ppm (m, 2H, CH=CH); mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C 9 H 1 3 C 1 0 3 : 2 0 4 . 0 5 5 3 amu, f o u n d 2 0 4 . 0 5 4 0 m/e; b) low r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 5 3 ( 2 0 ) , 5 5 ( 1 6 ) , 5 9 ( 2 0 ) , 6 7 ( 4 2 ) , 6 9 ( 1 0 0 ) , 8 1 ( 1 4 ) , 9 4 ( 1 3 ) , 95 ( 1 3 ) , 101 ( 7 9 ) , 109 ( 1 3 ) , 127 ( 1 3 ) , 136 ( 2 5 ) , 137 ( 34) , 168 ( 37) , 1 6 9 ( 1 0 ) a n d 204 ( 1 ) . 79 D i m e t h y l 3, 1 0 - d i o x o - 6 - d o d e c e n e d i o a t e (14 7) was c h a r a c t e r i s e d b y : i r (CHC1 3 ) 1 740 ( e s t e r O O ) , 1718 ( O O ) a n d 1660 cm" 1 ( c i s CH = CH) ; nmr (CDC1 3) 6 2 . 1 8 - 2 . 8 (m, 8H, C H 2 C H 2 C 0 ) , 3.45 ( s , 4H, C 0 C H 2 C 0 ) , 3.75 ( s , 3H, 0 C H 3 ) , a n d 5.4 ppm ( t , J = 4.0 H z , 2H, CH=CH); mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C i i + H 2 0 0 6 : 2 8 4 . 1 2 5 9 amu, f o u n d 2 8 4 . 1 3 0 5 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 4 3 ( 3 3 ) , 5 7 ( 1 0 ) , 5 9 ( 1 2 ) , 7 1 ( 2 5 ) , 8 5 ( 1 9 ) , 9 1 ( 1 6 ) , 9 4 ( 2 9 ) , 9 5 ( 3 3 ) , 1 0 1 ( 6 1 ) , 1 0 9 ( 1 3 ) , 1 1 3 ( 1 2 ) , 1 1 6 ( 2 0 ) , 1 2 7 ( 1 9 ) , 1 2 9 ( 1 3 ) , 1 3 6 ( 1 2 ) , 1 3 7 ( 4 5 ) , 1 5 0 ( 1 2 ) , 1 5 5 ( 1 8 ) , 1 5 9 ( 1 2 ) , 1 6 8 ( 4 8 ) , 1 6 9 ( 1 0 0 ) , 1 7 9 ( 1 1 ) , 2 2 1 ( 1 6 ) , 2 5 2 ( 1 1 ) a n d 2 8 4 ( 4 ) . M e t h y l 2 - o x o - 5 - e y e 1 o h e p t e n e c a r b o x y l a t e ( 1 4 8 ) T h i s c o m p o u n d was p r e p a r e d b y t h e same p r o c e d u r e as t h a t e m p l o y e d i n t h e p r e p a r a t i o n o f c o m p o u n d 14 0 a . T h e r e a g e n t s u s e d w e r e : s o d i u m ( 0 . 1 5 7 0 g, 0 .0068 m o l e ) , d r y m e t h a n o l ( 1 0 m l ) a n d p u r e m e t h y l 3 - o x o - 8 - c h l o r o - 6 - o c t e n o a t e ( 1 4 6 ) ( 0 . 1 3 8 3 g, 0 . 0 0 6 8 m o l e ) w h i c h g a v e 0 . 0 4 60 g ( 4 0 % ) o f m e t h y l 2 - o x o - 5 - c y c l o h e p t e n e c a r b o x y l a t e (14 8) c h a r a c t e r i s e d b y : i r ( C H C I 3 ) 1 735 ( e s t e r 0 0 ) , 1700 ( 0 0 ) a n d 1660 cm" 1 ( c i s CH=CH); 80 -nmr ( C D C 1 3 ) 6 2 . 0 - 2 . 8 (m, 4H, C H 2 ) , 3.65 (m, I H , C O C H C O ) , 3.72 ( s , 3H, 0 C H 3 ) a n d 5.78 ppm ( t , J = 4.0 H z , 2H, C H - C H ) ; mass s p e c t r u m : a) h i g h r e s o l u t i o n c a l c u l a t e d f o r C 9 H 1 2 0 3 : 1 6 8 . 0 7 8 7 amu, f o u n d 1 6 8 . 0 7 7 9 m/e; b) l o w r e s o l u t i o n m/e ( r e l i n t e n s i t y ) 3 2 ( 1 0 0 ) , 3 9 ( 3 8 ) , 4 2 ( 4 7 ) , 4 4 ( 2 8 ) , 5 3 ( 2 2 ) , 5 5 ( 2 0 ) , 5 9 ( 2 3 ) , 6 6 ( 2 2 ) , 6 7 ( 6 8 ) , 6 8 ( 3 8 ) , 7 9 ( 2 4 ) , 8 0 ( 3 1 ) , 8 1 ( 4 6 ) , 8 4 ( 3 4 ) , 1 0 1 ( 2 1 ) , 1 0 8 ( 2 3 ) , 1 0 9 ( 2 1 ) , 1 1 0 ( 2 1 ) , 1 3 6 ( 9 5 ) , 1 3 7 ( 4 3 ) a n d 1 6 8 ( 6 0 ) . D i a l k y l a t i o n a t t h e y - c a r b o n o f t h e D i a n i o n o f M e t h y l A c e t o -a c e t a t e . M e t h y l 3 - o xo - 5 - c y c 1 o p e n t y 1 p r o p a n o a t e (l_5_0_a_) S o d i u m h y d r i d e , a s a 5 7 % m i n e r a l o i l d i s p e r s i o n , ( 1 . 0 8 9 6 g, 0.02 m o l e ) was w e i g h e d i n t o an o v e n - d r i e d 100 ml f l a s k , a n d t e t r a h y d r o f u r a n (50 m l ) was d i s t i l l e d , f r o m l i t h i u m a l u m i n i u m h y d r i d e , d i r e c t l y i n t o t h e f l a s k . T h e f l a s k was f i t t e d w i t h a m a g n e t i c s t i r r e r , s e p t u m c a p , c o o l e d i n i c e t o 0 ° C a n d f l u s h e d w i t h n i t r o g e n . M e t h y l a c e t o a c e t a t e ( 2 . 3 2 g, 0.02 m o l e ) was a d d e d d r o p w i s e , a n d t h e r e a c t i o n m i x t u r e was s t i r r e d f o r 10 m i n u t e s a f t e r t h e a d d i t i o n was c o m p l e t e . n -B u t y l l i t h i u m as a 2.2 M s o l u t i o n i n h e x a n e ( 9 . 6 m l , 0.021 m o l e ) was a d d e d d r o p w i s e t o t h e r e a c t i o n w h i c h was a l l o w e d t o s t i r f o r a f u r t h e r 10 m i n u t e s b e f o r e t h e a d d i t i o n o f 1,4-81 d i b r o m o b u t a n e ( 4 . 3 1 8 6 g, 0.02 m o l e ) . T h e r e a c t i o n was t h e n s t i r r e d f o r o n e h o u r a n d l i t h i u m d i i s o p r o p y 1 a m i d e (made b y s t i r r i n g 3.08 ml o f d i i s o p r o p y l a m i n e w i t h 9.9 ml o f n - b u t y l -l i t h i u m a t 0° C f o r 1/2 h o u r ) was a d d e d d r o p w i s e . T h e r e a c -t i o n m i x t u r e was t h e n s t i r r e d f o r an a d d i t i o n a l 30 m i n u t e s . I t was t h e n q u e n c h e d w i t h d i l u t e h y d r o c h l o r i c a c i d , e x t r a c t e d w i t h e t h y l e t h e r (2 x 50 m l ) , w a s h e d w i t h s a t u r a t e d s o d i u m b i c a r b o n a t e , w a t e r a n d d r i e d o v e r m a g n e s i u m s u l f a t e . S o l -v e n t s w e r e r e m o v e d b y e v a p o r a t i o n u n d e r r e d u c e d p r e s s u r e t o g i v e 3 . 2 8 8 7 g o f c r u d e p r o d u c t s . P u r i f i c a t i o n was a c h i e v e d b y t i c : 150 mg o f c r u d e p r o d u c t was c h r o m a t o g r a p h e d on a 20 cm x 20 cm s i l i c a c o a t e d p l a t e , a d s o r b e n t t h i c k n e s s 0.9 mm, u s i n g a m i x t u r e o f c a r b o n t e t r a c h l o r i d e a n d e t h y l e t h e r ( 7 : 3 v / v ) a s e l u e n t t o g i v e 0 . 0 4 0 8 g ( 2 6 % b a s e d on m e t h y l a c e t o a c e t a t e , a b o u t 1 0 0 % b a s e d on t h e r a t i o o f b r o m o - c o m p o u n d 1 4 1 a ) o f m e t h y l 3 - o x o - 3 - c y c 1 o p e n t y 1 p r o p a n o a t e (15 0a) . Com-p o u n d 15 0a was c h a r a c t e r i s e d b y : i r (CHC1 3 ) 1 740 ( e s t e r C = 0) a n d 1710 cm" 1 (C = 0 ) ; nmr ( C D C 1 3 ) 6 1 . 0 5 - 2 . 0 (m, 8H, ( C H 2 ) 4 ) , 3.0 (m, I H , C H C O ) , 3.5 ( s , 2H, C 0 C H 2 C 0 ) a n d 3.75 ppm ( s , 3H, 0 C H 3 ) ; m a s s s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 1 ( 6 4 ) , 4 3 ( 5 0 ) , 4 4 ( 1 9 ) , 5 7 ( 7 ) , 5 9 ( 6 0 ) , 6 9 ( 6 2 ) , 7 4 ( 1 9 ) , 9 6 ( 4 0 ) , 9 7 ( 1 0 0 ) , 1 0 1 ( 7 3 ) , 1 2 9 ( 8 6 ) , 1 3 9 ( 7 ) a n d 1 7 0 ( 5 1 ) ; a n a l y s i s c a l c u l a t e d f o r C 9 H 1 4 O 3 : C 6 3 . 5 1 H 8.29 0 2 8 . 2 0 f o u n d : C 6 3.68 H 8.16 82 -M e t h y l 3 - o x o - 3 - c y c l o h e x y l p r o p a n o a t e (15 0b) T h i s c o m p o u n d was p r e p a r e d b y t h e same p r o c e d u r e as t h a t e m p l o y e d i n t h e p r e p a r a t i o n o f m e t h y l 3 - o x o - 3 - c y c l o -p e n t y l p r o p a n o a t e ( 1 5 0 a ) . T h e r e a g e n t s u s e d w e r e : s o d i u m h y d r i d e , as a 5 7 % m i n e r a l o i l d i s p e r s i o n ( 0 . 5 4 5 g, 0.01 m o l e ) , m e t h y l a c e t o a c e t a t e ( 1 . 1 6 g, 0.01 m o l e ) , n- b u t y l 1 i t h i u m ( 4 . 8 m l , 0.01 m o l e ) , 1 , 5 - d i b r o m o p e n t a n e ( 2 . 3 0 g, 0.01 m o l e ) a n d l i t h i u m d i i s o p r o p y 1 a m i d e (made b y s t i r r i n g 1 . 6678 g, 0.016 m o l e o f d i i s o p r o p y 1 a m i n e w i t h 7.5 ml o f n - b u t y l 1 i t h i u m a t 0 ° C f o r 1/2 h o u r ) , w h i c h g a v e 1 . 7 8 5 8 g o f c r u d e p r o d u c t s . 150 mg o f t h i s c r u d e p r o d u c t was c h r o m a t o g r a p h e d t o g i v e 50 mg ( 3 2 % b a s e d on m e t h y l a c e t o a c e t a t e , a b o u t 1 0 0 % b a s e d o n t h e r a t i o o f i n t e r m e d i a t e b r o m o - c o m p o u n d 1 4 1 b ) o f m e t h y l 3 - o x o - 3 -c y c l o h e x y l p r o p a n o a t e (15 0 b ) . C o m p o u n d 150b was c h a r a c t e r i s e d b y : i r ( C H C 1 3 ) 1740 ( e s t e r C = 0) a n d 1710 cm" 1 (C = 0 ) ; nmr ( C D C 1 3 ) 6 1.8-2.0 (m, 10H, ( C H 2 ) 5 ) , 2 . 3 - 2 . 6 (m, I H , C H C O ) , 3.45 ( s , 2H, C 0 C H 2 C 0 ) , a n d 3.72 ppm ( s , 3H, O C H 3 ) . mass s p e c t r u m m/e ( r e l i n t e n s i t y ) 4 1 ( 6 4 ) , 4 3 ( 2 9 ) , 4 4 ( 5 0 ) , 5 5 ( 7 6 ) , 5 9 ( 2 6 ) , 6 9 ( 4 8 ) , 7 4 ( 2 2 ) , 8 3 ( 1 0 0 ) , 1 0 0 ( 2 5 ) , 1 0 1 ( 3 5 ) , 1 0 6 ( 2 0 ) , 1 2 9 ( 3 3 ) , 1 4 3 ( 8 ) a n d 1 8 4 ( 2 9 ) ; a n a l y s i s c a l c u l a t e d f o r C[ QH\ ^0^: C 6 5 . 1 9 H 8.75 0 2 6 . 0 5 f o u n d : C 6 5 . 1 9 H 8.70 83 -B I B L I O G R A P H Y 1. C. R. H a u s e r a n d . T . M. H a r r i s , J . Am. Chem. S o c . ; 80 , 63 6 0 ( 1 9 5 8 ) . 2. T. M. H a r r i s a n d C. R. H a u s e r , J . Am. Chem. S o c , , 8 4 , 1750 ( 1 9 6 2 ) . 3. J . F. W o l f e , T. M. H a r r i s a n d C. R. H a u s e r , J . O r g .  Chem. , 2_9 , 3 2 4 9 ( 1 9 6 4 ) . 4. T. M. H a r r i s a n d C. M. H a r r i s , J . O r g . Chem., 31 , 1032 ( 1 9 6 6 ) . 5. F. B. K i r b y , T. M. H a r r i s a n d C. R. H a u s e r , J . O r g . Chem'. , 28_, 2266 ( 1 9 6 3 ) . 6. S. D. Work a n d C. R. H a u s e r , J . O r g . Chem., 28, 725 ( 1 9 6 3 ) . 7. T. M. H a r r i s , S. B o a t m a n a n d C. R. H a u s e r , J • Am. Chem. S o c . , 87_, 31 86 ( 1 9 6 5 ) . 8. R. J . L i g h t a n d C.R. H a u s e r , J . O r g . Chem., 26, 716 ( 1 9 6 1 ) . 9. R. L. L i g h t , T. M. H a r r i s a n d C. R. H a u s e r , J . O r g . Chem., 26 , 1344 ( 1 9 6 1 ) . 10. M. L. M i l e s , C. G. M o r e l a n d , D. M. Von S c h r i l t z a n d C.R. H a u s e r , Chem. § I n d . ( L o n d o n ) , 2 0 9 8 ( 1 9 6 6 ) . 1 1 . D. M. V o n S c h r i l t z a n d C. R. H a u s e r , O r g . R e a c t . , 17 , 155 ( 1 9 6 9 ) . 12. T. M. H a r r i s , S. B o a t m a n a n d C. R. H a u s e r , J . Amer. Chem. S o c . , 85_, 3273 ( 1 9 6 3 ) . - 84 -13. V. I . G u n n a r , L. F. K u d r y a v t s e v a a n d S. I . Z a v ' y a l o v , B u l l . A c a d . S c i . USSR, D i v . Chem. S c i . , 1343 [ 1 9 6 2 ) , [ I z v . A k a d . N a u k . SSSR. Q t d . K h i m . N a u k . , 1431 ( 1 9 6 2 ) ] [ C . A . , 5_8, 2578 ( 1963).] 14. R. L. C a r n e y a n d T. M. H a r r i s , O r g . R e a c t . , 1 7 , 155 ( 1 9 6 9 ) . 1 5 . K. G. H a m p t o n , T. M. H a r r i s a n d C. R. H a u s e r , J . O r g . Chem. , 30_, 61 ( 1 9 6 5 ) 1 6 . R. B. M e y e r a n d C. R. H a u s e r , J . O r g . Chem., 2 5 , 158 ( 1 9 6 0 ) . 17. K. G. H a m p t o n , R. J . L i g h t a n d C. R. H a u s e r , J . O r g . Chem. , 3_0, 1 4 1 3 ( 1 9 6 5 ) 18. K. G. H a m p t o n , T. M. H a r r i s a n d C. R. H a u s e r , J . O r g . Chem. , 31_, 6 6 3 ( 1 9 6 6 ) . 19. T. M. H a r r i s a n d C. R. H a u s e r , J . Am. Chem. S o c . , 8 1 , 1 1 6 0 ( 1 9 5 9 ) . 2 0 . S. B o a t m a n a n d C. R. H a u s e r , J . O r g . Chem., 3 1 , 1785 ( 1 9 6 6 ) . 2 1 . S. B o a t m a n , T. M. H a r r i s a n d C. R. H a u s e r , J . Am. Chem. S o c . , 8_7, 82 ( 1 9 6 5 ) . 22. H. D. S e y f e r t h , W. B. H u g h e s , a n d J . H. H e r r n , J . Am. Chem. S o c . , 8 7 , 4 1 4 7 ( 1 9 6 5 ) . 2 3 . G. W i t t i g a n d G. G e i s s i e r , J u s t u s L i e b i g s A n n . Chem., 5 8 6 , 44 ( 1 9 5 3 ) . 24. W. R. D u n n a v a n t a n d C. R. H a u s e r , J . O r g . Chem. , 25 , 503 ( 1 9 6 0 ) . - 85 -2 5 . C. R. M a u s e r a n d W. H. P u t e r b a u g h , J . Am. Chem. S o c . , 75 , 4 756 ( 1 9 5 3 ) . 2 6 a . C. R. H a u s e r a n d W. H. P u t e r b a u g h , J . Am. Chem. S o c . , 73_, 2972 ( 1 9 5 1 ) , b . C. R. H a u s e r a n d W. H. P u t e r b a u g h , J . Am. Chem. S o c . , 75 , 1 0 6 8 ( 195 3) . 2 7 . L. S. W e i l e r , u n p u b l i s h e d r e s u l t s . 2 8 . G. B r i e g e r a n d D. C. S p e n c e r , T e t r a h e d r o n L e t t . , 4 5 8 6 ( 1 9 7 1 ) . 2 9 a . M. H a r n e l l a n d R. L e v i n e , J . O r g . Chem. , 15, 162 ( 1 9 6 0 ) . b . R. L e v i n e , Chem. R e v . , 5 4 , 4 6 7 ( 1 9 5 4 ) . 30. P. L. C r e g e r , J . Am. Chem. S o c . , 89 , 2 5 0 0 ( 1 9 6 7 ) . 31. M. W. R a t h k e a n d A. L i n d e r t , J . Am. Chem. S o c , 9 3, 2318 ( 1 9 7 1 ) . 32. R. A. O l o f s o n a n d C. M. D o u g h e r t y , J . Am. Chem. S o c . , 95 , 582 ( 1 9 7 3 ) . 33. R. A. O l o f s o n a n d C. M. D o u g h e r t y , J . Am. Chem. S o c . , 9_5 , 5 79 ( 1 9 7 3 ) . 34. M. W. R a t h k e , J . Am. Chem. S o c . , 9 2 , 3222 ( 1 9 7 0 ) . 35. P. L . C r e g e r , J . Am. Chem. S o c . , 92 , 1396 ( 1 9 7 0 ) . 3 6 . P. L. C r e g e r , J . Am. Chem. S o c . , 92, 1397 ( 1 9 7 0 ) . 3 7 . G. W. M o e r s c h a n d A. R. B u r k e t t , J . O r g . Chem., 36, 1149 ( 1 9 7 1 ) . 38. P. E . P f e f f e r , E . K i n s e l a n d L. S. S i l b e r t , J . O r g . Chem. , 37 , 1256 ( 1 9 7 2 ) . 8 6 -39. S - I . Y a m a d a , T. O g u r i a n d T. S h i o r i , Chem. Commun., 623 ( 1 9 7 2 ) . 4 0 . P. E . P f e f f e r , L. S. S i l b e r t , J . O r g . Chem. , 36^ 3290 ( 1 9 7 1 ) . 4 1 . Y-N. K u o , F. C h e n a n d C. A i n w o r t h , Chem. Commun., 1 36 ( 1 9 7 1 ) . 4 2 . Y-N. Kuo, J . A. Y a h n e r a n d C. A i n w o r t h , J . Am. Chem. S o c . , 9_3, 6 3 2 3 ( 1 9 7 1 ) . 4 3 . D. S e e b a c h a n d D. E n d e r s , Angew. Chem. I n t . E d . E n g l . , 1 1 , 301 ( 1 9 7 2 ) . 4 4 . C. Mayo, C. R. H a u s e r a n d M. L. M i l e s , J . Am. Chem. S o c . , 89_, 5 3 0 3 ( 1 9 6 7 ) . 4 5 . L. W e i l e r , J . Am. Chem. S o c . , 92 , 6702 (1 9 7 0 ) . 4 6 . R. M. C o a t e s a n d J . E . Shaw, J . Am. Chem. S o c , , 92, 5627 ( 1 9 7 0 ) . 4 7 . E . P i e r s a n d R. D. S m i l l i e , J . O r g . Chem., 3 5 , 3 9 9 7 ( 1 9 7 0 ) . 4 8 . J . D. T a y l o r a n d J . F. W o l f e , J . Chem. S o c . , Chem. Commun., 876 ( 1 9 7 2 ) . 4 9 . P. A. G r e c o a n d C. S. P o g o n o w s k i , J . Am. Chem. S o c . , 95, 3071 ( 1 9 7 3 ) . 5 0 . . L. W e i l e r , C a n . J . Chem. , 50 , 2 707 ( 1 9 7 2 ) . 5 1 . S. N. H u c k i n a n d L. W e i l e r , J . Am. Chem. S o c . , 96, 1 0 8 2 ( 1 9 7 4 ) . 52. N. S u g i y a m a , M. Y a m a m o t o , T. T a k a n o a n d C. K a s h i m a , B u i 1, Chem. S o c . J a p . , 40 , 2 9 0 9 ( 1 9 6 7 ) . 87 -5 3 . J . D. H a g a r t y , U. S. P a t e n t 3 , 5 6 5 , 9 2 8 ( 1971 ) ; Chem. A b s t r . , 74, 1 4 0 9 9 9 ( 1 9 7 1 ) . 54. S. N. H u c k i n a n d L. W e i l e r , T e t r a h e d r o n L e t t . , 4 8 3 5 ( 1 9 7 1 ) . 5 5 . S. N. H u c k i n a n d L. W e i l e r , C a n . J . Chem. , 5 2, 2 1 5 7 ( 1 9 7 4 ) . 5 6 . E . H. A m o n o o - N e i z e r , R. A. Shaw, D. 0. S k o v l i n a n d B.C. S m i t h , J . Chem. S o c . , 2 9 9 7 ( 1 9 6 5 ) . 5 7 . S. N. H u c k i n a n d L. W e i l e r , C a n . J . Chem., 52, 1 3 4 3 ( 1 9 7 4 ) . ' • 5 8 . S. N. H u c k i n a n d L. W e i l e r , T e t r a h e d r o n L e t t . , 2405 ( 1 9 7 2 ) . 5 9 . T. T. H o w a r t h , G. P. M u r p h y a n d T. M. H a r r i s , J . Am. Chem. S o c . , 9 1 , 5 1 7 ( 1 9 6 9 ) . 6 0 . S. N. H u c k i n a n d L . W e i l e r , C a n . J . Chem., 52, 1379 ( 1 9 7 4 ) . 6 1 . N. S u g i y a m a , M. Y a m a m o t o , S. K o b a y a s h i a n d C. K a s h i m a , B u l l , Chem. S o c , J a p . , 4 5 , 296 ( 1 9 7 2 ) . 6 2 . F. F. B l i c k a n d B. A. B r o w n , J . O r g . Chem., 26, 3685 ( 1 9 6 1 ) . 6 3 . T. A. B r y s o n , J . O r g . Chem. , 38 , 3428 ( 1 9 7 3 ) . 6 4 . B. M. T r o s t a n d R. A. K u n z , J . O r g . Chem., 39, 2648 ( 1 9 7 4 ) . 6 5 . I . N. N a z a r o v a n d S. I . Z a v y a l o v , Z h . O b s h c h . K h i m . , 2 3 , 1 7 03 ( 1 9 5 3 ) . 6 6 . E . W e n k e r t , A. A f o n s o , J . B. s o n B r e d e n b e r g , C. K a n e k o a n d A. T a h a r a , J . Am. Chem. S o c . , 86, 2038 ( 1 9 6 4 ) . 88 -K. H o h e n l o h e - O e h r i n g e n , M o n a t s h , Chem. , 9 3, 578 ( 1 9 6 2 ) . G. S t o r k a n d R. N . G u t h i k o n d a , T e t r a h e d r o n L e t t . , 2 755 ( 1 9 72) . L. P i c h a t a n d J - P . B e a u c o u r t , S y n t h e s i s, 557 ( 1 9 7 3 ) . J . E . E l l i s , J . S. D u t c h e r a n d C. H. H e a t h c o c k , S y n t h e t i c Commun., 71 ( 1 9 7 4 ) . R. E . I r e l a n d a n d J . A. M a r s h a l l , J . Am. Chem. S o c . , 8 1 , 2 9 0 9 ( 1 9 5 9 ) . 0. G r u m m i t t , E . P. B u d e w i t z a n d C. C. C h u d d , O r g . S y n . , C o l l . V o l . , £ , 748 ( 1 9 6 3 ) . P. A. Z o r e t i c , B. B r a n c h a u d a n d T. M a e s t r o n e , T e t r a -h e d r o n L e t t . , 527 ( 1 9 7 5 ) . S. J . R h o a d s , J . C. G i l b e r t , A. W. D e c o r a , T. R. G a r l a n d , R. J . S p a n g l e r , a n d M. J . U r b i g k i t , T e t r a h e d r o n , 19 , 1625 ( 1 9 6 3 ) . J . A. H i r s c h a n d F . J . C r o s s , J . O r g . Chem., 36, 955 ( 1 9 7 1 ) . R. B u r p i t t a n d J . T h w e a t t , O r g . S y n . , 4 8 , 56 ( 1 9 6 8 ) . G. A. B e r c h t o l d a n d G. F. U h l i g , J . O r g . Chem. , 28, 1459 ( 1 9 6 3 ) . R. J a c q u i e r , C. P e t r u s , F. P e t r u s a n d J . V e r d u c c i , B u l l . S o c . C h i m . F r . , 1_0 , 3694 ( 1 9 6 9 ) . S-. J . R h o a d s a n d R. W. H a s b r o u c k , T e t r a h e d r o n , 2 2 , 355 7 ( 1 9 6 6 ) . E. J . C o r e y , C. U. K i m a n d M. T a k e d a , T e t r a h e d r o n  L e t t . , 4 5 3 9 (1 9 7 2 ) . 89 -H. E . Z a n g g a n d A. D. S c h a e f e r , J . Am. Chem. S o c . , 87 , 18S7 ( 1 9 6 5 ) . B. M i l l e r , H. M a r g u l i e s , T. D r a b b , J r . a n d R. Wayne T e t r a h e d r o n L e t t . , 43 , 3801 , 3805 ( 19 7 0 ) . - 90 -S p e c t r a l In de x - 91 -O a a _ - 92 -I R A N S M IiF A W C E (•:..) RELATIVE INTENSITY L TkANSMITTANCE (%) RELATIVE INTENSITY 0.0 25.0 50.0 "J5.Q 100.0 1 1 : 1 I m ID ON - 97 -n r o - 103 -- 104 -7 - 107 -- 1 0 8 -

Cite

Citation Scheme:

        

Citations by CSL (citeproc-js)

Usage Statistics

Share

Embed

Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                        
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            src="{[{embed.src}]}"
                            data-item="{[{embed.item}]}"
                            data-collection="{[{embed.collection}]}"
                            data-metadata="{[{embed.showMetadata}]}"
                            data-width="{[{embed.width}]}"
                            async >
                            </script>
                            </div>
                        
                    
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:
http://iiif.library.ubc.ca/presentation/dsp.831.1-0060911/manifest

Comment

Related Items