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UBC Theses and Dissertations

Some novel nucleophilic displacement reactions in the carbohydrate area and N.M.R. studies of their products Miller, Diane Claudia 1977

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SOME NOVEL NUCLEOPHILIC DISPLACEMENT REACTIONS IN THE CARBOHYDRATE AREA AND N.M.R. STUDIES OF THEIR PRODUCTS by DIANE CLAUDIA MILLER B . S c , U n i v e r s i t y of B r i t i s h Columbia, 1973 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in the Department of CHEMISTRY We accept t h i s thesis as conforming to the required standard THE UNIVERSITY OF BRITISH COLUMBIA May, 1977 (c) Diane Claudia M i l l e r , 1977 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 the r e q u i r e m e n t s f o r an advanced d e g r e e at 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 , 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 and 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 the Head o f my Depar tment 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 no 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 . Depar tment o f 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 Place Vancouver, Canada V6T 1W5 ( i i ) ABSTRACT 1 , 2 : 5 , 6 - D i - O - i s o p r o p y l i d e n e - a - D - a l l o f u r a n o s e 1, l , 2 : 5 , 6 - d i -O - i s o p r o p y l i d e n e - a - D - g l u c o f u r a n o s e 2_, and 1 , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i -d e n e - a ~ D - g a l a c t o p y r a n o s e 3_ have been t r e a t e d s e p a r a t e l y i n p y r i d i n e s o l u t i o n w i t h t r i f l u o r o m e t h a n e s u l f o n i c a n h y d r i d e , 2,2,2-t r i f l u o r o e t h a n e s u l f o n y l c h l o r i d e , and p e n t a f l u o r o b e n z e n e s u l f o n y l c h l o r i d e . B oth 1 and 2 a f f o r d e d the a n t i c i p a t e d s u l f o n i c e s t e r s . A l t h o u g h 3_ a l s o gave the 2 , 2, 2 - t r i f l u o r o e t h a n e s u l f o n i c and p e n t a -f l u o r o b e n z e n e s u l f o n i c e s t e r s , t h e r e a c t i o n w i t h t r i f l u o r o m e t h a n e -s u l f o n i c a n h y d r i d e y i e l d e d 6 - d e o x y - l , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i d e n e -6 - p y r i d i n o - a - D - g a l a c t o p y r a n o s e t r i f l u o r o m e t h a n e s u l f onate 1_. I n a second p a r t t o t h i s work t r i p h e n y l t i n l i t h i u m was s e p a r a t e l y r e a c t e d w i t h each o f 1,2:3,4-di-O-methylene-a-D-g l u c o f uranose 2_2, m e t h y l 2 , 3-anhydro-4 , 6-0-benzy l i d e n e - a - D -a l l o p y r a n o s i d e 23 and m e t h y l 2,3-anhydro-4,6-0-benzylidene-a-D-mannopyranoside 24 t o form, i n e v e r y c a s e , a s u g a r - s t a n n a n e d e r i v a -t i v e h a v i n g a s t a b l e c a r b o n - t i n bond. N.m.r. s t u d i e s o f b o t h t h e f l u o r i n a t e d sugar s u l f o n a t e s and, p a r t i c u l a r l y , o f the o r g a n o t i n s u g a r s a r e a l s o r e p o r t e d . ( i i i ) T A B L E O F C O N T E N T S I N T R O D U C T I O N -1-R E S U L T S A N D D I S C U S S I O N -8-C H A P T E R I F l u o r i n a t e d S u l f o n i c E s t e r s o f S u g a r s ( a ) T h e i r s y n t h e s i s a n d r e a c t i o n s w i t h p y r i d i n e -8-T R I F L A T E S -8-T R E S Y L A T E S -18-P E N T A F L A T E S -19-( b ) N . m . r . s p e c t r a a n d c o n f o r m a t i o n a l p r o p e r t i e s o f t h e t r i f l y l p y r i d i n i u m s a l t s -22-C H A P T E R I I C - S t a n n y l a t e d C a r b o h y d r a t e s ( a ) S y n t h e s i s ' -28-( b ) N . m . r . s p e c t r a a n d c o n f o r m a t i o n a l p r o p e r t i e s -35-1 H N . M . R -35-H E T E R O N U C L E A R N . M . R . P A R A M E T E R S -45-(1) 1 H - S n c o u p l i n g s -47-(2) 1 3 C n . m . r -47-( i ) c h e m i c a l s h i f t s -47-13 ( i i ) C - S n c o u p l i n g c o n s t a n t s -54-E X P E R I M E N T A L -62-F l u o r i n a t e d S u l f o n a t e s -62-S t a n n a n e D e r i v a t i v e s o f C a r b o h y d r a t e s -67-APPENDIX -71-R E F E R E N C E S -73-(iv) LIST OF TABLES TABLE 1 -25-Chemical s h i f t s (r-values) and m u l t i p l e t s p l i t t i n g s (Hz) for pyridinium s a l t s i n deuterioacetone solutions. TABLE 2 -26-1 19 H chemical s h i f t s (x-values), F chemical s h i f t s (0 ) and m u l t i p l e t s p l i t t i n g s (Hz) f o r sulfonates i n deuterioacetone s o l u t i o n s . TABLE 3 -37-Chemical s h i f t s (x-values) and m u l t i p l e t s p l i t t i n g s (Hz) for 4,6-0-benzy lidene-a-D-altropyranos ides and 1,2:3,4-di-0-methylene-a-D-glucofuranoses i n deuteriobenzene s o l u t i o n s . TABLE 4 ' -51-13 C chemical s h i f t s (ppm) f o r 4 ,6-0_-benzylidene-a-D-altropyranosides and 1,2: 3,5-di-0_-methylene-a-D-glucofuranoses i n deuteriobenzene solutions. TABLE 5 -53-13 C chemical s h i f t differences (ppm) 6 - 6 ^ for 4,6-0_-benzylidene-a-D-glucofuranoses i n deuteriobenzene s o l u t i o n s . TABLE 6 -56-13 C-Sn coupling constants (Hz) f o r organotin sugars. (v) LIST OF FIGURES FIGURE 1 -4-Hammett plo t f o r the s o l v o l y t i c alkyl-oxygen cleavage of X-SO^R. FIGURE 2 -11-Fluorinated s u l f o n y l and pyridinium t r i f l y l d e r i v a t i v e s synthesized for t h i s work. FIGURE 3 -30-C-Stannylated carbohydrates, synthesized f o r t h i s work, and t h e i r precursors. FIGURE 4 -36-*H n.m.r. spectra of tri p h e n y l [1,2 : 3,5-di-0_-methylene-a-D-glucofuranose) 6-C-stannane 25_ (top) and 1,2 : 3,5-di-0_-methylene-a-D-glucofuranose 22_ (bottom) in deuteriobenzene s o l u t i o n . FIGURE 5 -43-(a) Chair and (b) skew conformations f o r methyl 4,6-0-benzylidene-a-D-altropyranosides . FIGURE 6 -46-13 Natural abundance C n.m.r. spectrum of t r i m e t h y l t i n c h l o r i d e i n deuteriobenzene s o l u t i o n . FIGURE 7 -48-Fourier transform n.m.r. spectrum of triphenyl(4,6-0-benzylidene-a-D-altropyranoside)2-C-stannane 26^  showing sp e c t r a l assignments and' *H-Sn couplings. FIGURE 8 -50-Natural abundance ~^C n.m.r. spectra of |"A*| t r i p h e n y l (1,2 :3 ,5-di-0_-methylene-a-D-glucofuranose) 6-C-stannane 25_ and (_Bj 1,2 : 3 ,5-di-0_-methylene-a-D-glucofuranose 22 i n deuteriobenzene s o l u t i o n . (vi) FIGURE 9 -55-3 119 13 Magnitudes of J ( SnCC C) p l o t t e d against the dihedral angle 0 . ( r e f 59). FIGURE 10 -57-13 Natural abundance C n.m.r. spectrum of triphenyl(methyl 4,6-0-benzylidene-a-D-altropyranoside)2-C-stannane 26 i n deuterioacetone s o l u t i o n (0.3 M) showing the normal resonances and the t i n s a t e l l i t e s of the C - l , C-2, and C-3 resonances. FIGURE 11 -72-13 Natural abundance C n.m.r. spectra, of tr i p h e n y l (methyl 4,6-C^-benzylidene-a-D-altropyranoside) 2-C-stannane 26^  i n deuteriobenzene s o l u t i o n (0.3 M) , from a s e l e c t i v e decoupling experiment, showing how the i n d i v i d u a l resonances are assigned. (vi) ACKNOWLEDGEMENT I wish to thank Dr. L. D. H a l l f o r his help, encouragement and enthusiasm throughout t h i s project. I also wish to thank J . D. A p l i n f o r his competent and, sometimes, rut h l e s s e d i t i n g of t h i s t h e s i s . -1-INTRODUCTION I n common w i t h many a r e a s o f o r g a n i c c h e m i s t r y , c a r b o h y d r a t e c h e m i s t r y has p r o f i t e d by t h e f l e x i b i l i t y o f t h e b i m o l e c u l a r n u c l e o -p h i l i c d i s p l a c e m e n t r e a c t i o n ( S ^ 2 ) . T h i s f l e x i b i l i t y i s d e r i v e d from the c h e m i s t ' s c o n t r o l o v e r t h r e e i m p o r t a n t v a r i a b l e s -- t h e l e a v i n g group, the n u c l e o p h i l e and t h e s o l v e n t . T h i s work d e a l s w i t h some i n n o v a t i o n s i n t h e a r e a o f c a r b o h y d r a t e c h e m i s t r y w h i c h i n v o l v e the f i r s t two o f t h e s e v a r i a b l e s -- t h a t i s , w i t h some n o v e l l e a v i n g groups and n u c l e o p h i l e s . I n many o r g a n i c r e a c t i o n s i t i s c o n v e n i e n t t o employ a h a l o g e n atom (CI, B r , I) as t h e l e a v i n g group. A l t h o u g h c a r b o h y d r a t e c h e m i s t r y f o l l o w s t h i s t r e n d f o r r e a c t i o n s a t the anomeric c e n t r e ( C - l p o s i t i o n ) , i n t h e sense t h a t the g l y c o s y l h a l i d e s a r e u s e f u l and w i d e l y used r e a c t i o n i n t e r m e d i a t e s , a t o t h e r c e n t r e s i t i s g e n e r a l l y more e x p e d i e n t t o use a s u l f o n a t e e s t e r . T h i s i s i n g e n e r a l because many o f t h e s e s u l f o n a t e s a r e r e a d i l y o b t a i n e d i n a c r y s t a l l i n e and e a s i l y p u r i f i e d form from p a r t i a l l y b l o c k e d p r e c u r s o r s ; f u r t h e r m o r e , f o r many n u c l e o p h i l e s t h e r e a c t i v i t y o f the s u l f o n a t e s i s adequate f o r r e a c t i o n s t o p r o c e e d under m i l d c o n d i t i o n s . Even so, i t i s n o t o b v i o u s why so much emphasis has been p l a c e d by c a r b o h y d r a t e c h e m i s t s on j u s t t h r e e c l a s s e s o f s u l f o n a t e s — t o s y l a t e s (OTs), m e s y l a t e s (OMs) and benzene s u l f o n -a t e s (OSO^Ph), e s p e c i a l l y when T i p s o n 1 , i n 195 3 i n a r a t h e r -2-p r e s c i e n t r e v i e w a r t i c l e on s u l f o n a t e e s t e r s o f c a r b o h y d r a t e s , had drawn a t t e n t i o n t o t h e f a c t t h a t e l e c t r o n - w i t h d r a w i n g groups were known t o enhance the l e a v i n g p r o p e r t i e s o f a r y l - s u l f o n a t e e s t e r s : -" F i n a l l y , i t seems a s t o u n d i n g t h a t a g r e a t e r v a r i e t y o f s u l f o n i c r a d i c a l s ( a t t a c h e d t o s u g a r s and a l d i t o l s ) have n o t been t e s t e d i n r e l a t i o n t o ease o f d e s u l f o n y l o x y l a t i o n . There can be l i t t l e doubt t h a t , i n t h i s r e g a r d , p - n i t r o p h e n y l s u l f o n y l groups would prove s u p e r i o r t o t o s y l o r m e s y l groups ( s i n c e , f o r p - s u b s t i t u e n t s on the benzene r i n g , the o r d e r o f i n c r e a s i n g r e a c t i v i t y • o f t h e i r e t h y l e s t e r s i s p-CH 30< p-CH 3< p-H< p-Br <p-N0 2), and 2,4 d i n i t r o -p h e n y l s u l f o n y l groups might p r o v e more e f f i c a c i o u s . " F i f t e e n 2 3 y e a r s l a t e r , a two p a r t r e v i e w a r t i c l e ' , w h i c h summarized the l i t e r a t u r e up t o 1969, showed t h a t , i n s p i t e o f T i p s o n ' s remarks, and the l a r g e number o f a p p l i c a t i o n s for s u l f o n a t e e s t e r s d e s c r i b e d , -t h e r e had been a n o t a b l e l a c k o f i n n o v a t i o n i n the range o f s u l f o n -a t e e s t e r s used. R e c o g n i t i o n o f t h i s s i t u a t i o n prompted us t o i n v e s t i g a t e s e v e r a l f a m i l i e s o f f l u o r i n a t e d s u l f o n a t e s w h i c h o f f e r e d an i d e a l o p p o r t u n i t y t o i n c r e a s e t h e scope o f c a r b o h y d r a t e s u l f o n a t e e s t e r c h e m i s t r y . 4 I n 1957, Gramstad and H a s z e l d i n e f i r s t r e p o r t e d the remark-a b l e 0-, N- and C- a l k y l a t i n g p r o p e r t i e s o f the e t h y l and m e t h y l e s t e r s o f t r i f l u o r o m e t h a n e s u l f o n i c a c i d . They found t h a t m e t h y l t r i f l u o r o m e t h a n e s u l f o n a t e r e a c t e d w i t h d i e t h y l e t h e r t o form e t h y l t r i f l u o r o m e t h a n e s u l f o n a t e and e t h y l m e t h y l e t h e r , and t h a t a l k y l a -t i o n o f benzene was e f f e c t e d by e t h y l t r i f l u o r o m e t h a n e s u l f o n a t e ; b o t h r e a c t i o n s o c c u r r e d a t room t e m p e r a t u r e . S i m i l a r l y , N - a l k y l a -t i o n s o f NHE1 0 t o N E t 0 and o f NH^Ph t o HNPhEt and NPhEt,, were -3-e f f e c t e d r a p i d l y and e s s e n t i a l l y q u a n t i t a t i v e l y a t room tempera-t u r e . 5-10 S i n c e t h e n , s e v e r a l a u t h o r s have p u b l i s h e d s i m i l a r r e s u l t s , a l l a t t e s t i n g t o t h e e x t r a o r d i n a r y r e a c t i v i t y o f t h e t r i f l u o r o m e t h a n e s u l f o n i c a c i d e s t e r s o r " t r i f l a t e s " . S t r e i t w i e s e r e t a l ^ found t h a t a c e t o l y s i s o f e t h y l t r i f l a t e p r o c e e d s about 30,000 ti m e s f a s t e r than t h e a c e t o l y s i s o f e t h y l t o s y l a t e and 5,000 times f a s t e r than t h a t o f e t h y l b r o s y l a t e a t 25°C. I t s e t h a n o l y s i s i n 100% e t h a n o l a t t h a t t e m p e r a t u r e i s about 450,000 times f a s t e r than t h a t o f e t h y l b e n z e n e s u l f o n a t e . I n 80% aqueous e t h a n o l , i t s o l v o l y z e s 150,000 t i m e s f a s t e r t h a n e t h y l bromide. Two l e s s r e a c t i v e s e r i e s o f f l u o r i n a t e d s u l f o n a t e e s t e r s were l a t e r r e p o r t e d — t h e 2 , 2 , 2 - t r i f l u o r o e t h a n e s u l f o n a t e s , o r " t r e s y l a t e s " , by Burdon and M c L o u g h l i n ^ i n 1964, and the p e n t a -f l u o r o b e n z e n e s u l f o n a t e s , o r " p e n t a f l a t e s " , by Connett"*"\ i n 1965. These e s t e r s t y p i c a l l y appear t o be about 100 t i m e s more r e a c t i v e t han the c o r r e s p o n d i n g t o s y l a t e s and about 400 t i m e s l e s s r e a c t i v e t han the c o r r e s p o n d i n g t r i f l a t e s . A Hammett p l o t f o r the s o l -v o l y t i c a l k y l - o x y g e n c l e a v a g e o f X-SO^R i s shown i n f i g u r e 1 . The r e a c t i v i t y range o f t h e s u l f o n a t e e s t e r s , t h e n , has been i n c r e a s e d from a f a c t o r o f a p p r o x i m a t e l y 10 between th e m e s y l a t e , t o s y l a t e and b r o s y l a t e l e a v i n g groups t o about 80,000 between t h e s e and t h e f l u o r i n a t e d s u l f o n a t e e s t e r s . The p o s s i b i l i t i e s a f f o r d e d by t h e s e n o v e l , e x t r e m e l y r e a c t i v e e s t e r s d i d n o t escape our a t t e n t i o n ; w i t h t h e s e as i n t e r m e d i a t e s , r e a c t i o n s on s e n s i t i v e s u g a r s might be c a r r i e d o ut q u i c k l y and a t - 4 -low t e m p e r a t u r e s , thus r e d u c i n g s i d e r e a c t i o n s and/or decomposi-t i o n . F u r t h e r m o r e , n u c l e o p h i l i c d i s p l a c e m e n t r e a c t i o n s might now t a k e p l a c e on systems w h i c h p r e v i o u s l y had been a l m o s t , o r c o m p l e t e l y , u n r e a c t i v e . A t the s t a r t o f t h i s s t u d y , o n l y one exper i m e n t had been done, i n t h e c a r b o h y d r a t e a r e a , w i t h t r i f l a t e s . We d e c i d e d t o make a g e n e r a l i n v e s t i g a t i o n , and t h i s i s d e s c r i b e d i n Chapter one. FIGURE 1 Hammett p l o t f o r t h e s o l v o l y t i c a l k y l - o x y g e n c l e a v a g e o f X - S 0 3 R . W i t h r e s p e c t t o the c h o i c e o f n u c l e o p h i l e s , t h e r e has been a f a r w i d e r range o f s t u d i e s i n c a r b o h y d r a t e c h e m i s t r y . However, t h e r e has been a n o t a b l e l a c k o f s t u d y o f d i s p l a c e m e n t r e a c t i o n s 13 by m e t a l n u c l e o p h i l e s , a l t h o u g h u n p u b l i s h e d work by S t e i n e r s u g g e sted t h a t t h i s m i g h t have p o t e n t i a l . Thus, as t h e second p a r t o f t h i s work, we chose t o s t u d y the s y n t h e s i s o f m e t a l d e r i v --5-a t i v e s w i t h the m e t a l bonded d i r e c t l y t o c a r b o n . There a r e s e v e r a l g e n e r a l methods whereby c a r b o n - t i n bonds are formed. A l k y l and a r y l t i n compounds r e a d i l y undergo m e t a l -h a l o g e n exchange r e a c t i o n s o f t h e t y p e : C-M •Sn-Cl •C-Sn' MCI M = Mg, L i , Al, Na, K, Zn or MgCl The G r i g n a r d method (M=MgCl) can be used t o i n t r o d u c e o r g a n i c groups c o n t a i n i n g f u n c t i o n a l s u b s t i t u e n t s p r o v i d i n g t h a t t h e y do n o t i n t e r a c t w i t h organomagnesium compounds. I n c e r t a i n c a s e s , h i g h e r y i e l d s a r e o b t a i n e d when t h e G r i g n a r d r e a g e n t i s r e p l a c e d by an o r g a n o l i t h i u m compound. However, n e i t h e r o f t h e s e methods seemed f e a s i b l e from t h e c a r b o h y d r a t e c h e m i s t ' s p o i n t o f v i e w , as t h e r e has been no l i t e r a t u r e on t h e f o r m a t i o n o f a s u g a r - G r i g n a r d o r a s u g a r - l i t h i o compound, and i t d i d n o t seem l i k e l y t h a t such a m o iety w o u l d be s t a b l e under normal r e a c t i o n c o n d i t i o n s . A r e l a t e d method o f p r e p a r a t i o n v/hich can be used f o r t h e i n t r o d u c t i o n o f f u n c t i o n a l l y s u b s t i t u t e d groups i s t h e r e a c t i o n -6-between a compound c o n t a i n i n g t i n bonded t o an a l k a l i m e t a l and an a l k y l o r a r y l h a l i d e , o r e q u i v a l e n t l e a v i n g group: R 3SnLi R'X R^SnR1 LiX I n 1962, Tamborski e t al" 1"" 1 p u b l i s h e d t h e s y n t h e s i s o f t r i -p h e n y l t i n l i t h i u m from t r i p h e n y l t i n c h l o r i d e and l i t h i u m m e t a l . I t was r e p o r t e d as b e i n g a f a i r l y s t a b l e compound w h i c h , when r e a c t e d w i t h o r g a n o h a l o g e n compounds, gave f a i r l y h i g h y i e l d s o f the c o r r e s p o n d i n g o r g a n o t i n compounds. I n 19 70, Zimmer and lu'> B a y l e s s s y n t h e s i z e d a number o f o r g a n o t i n and o r g a n o s i l i c o n s t e r o i d s , by r e a c t i n g t r i p h e n y l t i n l i t h i u m and t r i p h e n y l s i l i c o n l i t h i u m w i t h s t e r o i d s , s u b s t i t u t e d a t the 3 - p o s i t i o n by e i t h e r a ha l o g e n (Br, C l or I) or a G r i g n a r d f u n c t i o n a l i t y . A t about t h e same t i m e , i n t h i s department, S t e i n e r d i d some p r e l i m i n a r y e x p e r -* iments w i t h r e a c t i o n s o f some 0^MLi compounds, M = Sn, Pb and S i , on b l o c k e d s u g a r s , w h i c h i n d i c a t e d t h a t t h i s was i n d e e d a f e a s i b l e method f o r f o r m i n g a c a r b o n - t i n bond i n a s u g a r m o l e c u l e . T h e r e f o r e , we d e c i d e d t o i n v e s t i g a t e and document the r e a c t i o n s o f t r i p h e n y l t i n l i t h i u m w i t h some b l o c k e d c a r b o h y d r a t e s . The e x p e r i m e n t s d e s c r i b e d * The symbol 0 w i l l be used t h r o u g h o u t t h i s t h e s i s t o r e p r e s e n t a p h e n y l group. -7-i n C hapter two c o n c e r n our a t t e m p t s i n t h i s a r e a . B e s i d e s t h e i r p o t e n t i a l s y n t h e t i c n o v e l t y , the d e r i v a t i v e s t h a t we hoped t o s y n t h e s i z e were l i k e l y t o be good models f o r n.m.r. s t u d i e s . The s a l i e n t f e a t u r e here i s t h a t sugar d e r i v a -t i v e s can be made c o n f o r m a t i o n a l l y r i g i d , and s i n c e t h e y f r e q u e n t l y g i v e w e l l - d i s p e r s e d ''"H n.m.r. s p e c t r a , i t i s p o s s i b l e t o e v a l u a t e t h e i r f a v o u r e d c o n f o r m a t i o n d i r e c t l y . N.m.r. and c o n f o r m a t i o n a l s t u d i e s o f the t r i f l a t e and, p a r t i c u l a r l y , o f t h e t i n d e r i v a t i v e s w i l l be d e a l t w i t h a t the end o f the a p p r o p r i a t e c h a p t e r s . -8-CHAPTER I F l u o r i n a t e d S u l f o n i c E s t e r s o f Sugars a) T h e i r s y n t h e s i s and r e a c t i o n s w i t h p y r i d i n e . TRIFLATES The f o u r s u l f o n y l a t i n g r e a g e n t s most o f t e n used f o r s y n t h e s i s o f t r i f l u o r o m e t h a n e s u l f o n i c a c i d e s t e r s , o r t r i f l a t e s , a r e t r i -f l u o r o m e t h a n e s u l f o n i c ( " t r i f l i e " ) a n h y d r i d e , t r i f l i e c h l o r i d e o r f l u o r i d e , and s i l v e r t r i f l a t e . T r i f l i e a n h y d r i d e and t r i f l i e c h l o r i d e , o r f l u o r i d e , undergo a s i m i l a r t y pe o f r e a c t i o n w i t h an a l c o h o l , t h u s : ( C F 3 S 0 2 ) 2 0 + ROH + B: + ROH + B + HB+X X= F, Cl = usually a t e r t i a r y organic base e.g. pyridine _ 9 -S i l v e r t r i f l a t e , on t h e o t h e r hand, r e a c t s w i t h an a l k y l h a l i d e , g e n e r a l l y an a l k y l b romide, t o form t h e d e s i r e d e s t e r s : CF 3S0 3Ag + R X _> CF 3S0 3R + AgX X= C l , Br A l l f o u r r e a g e n t s a r e c o m m e r c i a l l y a v a i l a b l e , q u i t e s t a b l e and n o t t o o e x p e n s i v e . The a n h y d r i d e , t h e a c i d c h l o r i d e and t h e s i l v e r s a l t were p u r c h a s e d f o r our work. The a n h y d r i d e and a c i d c h l o r i d e a re v o l a t i l e l i q u i d s (b.p. 80°C and 32°C, r e s p e c t i v e l y ) " ^ , s t a b l e i n d e f i n i t e l y a t -10° - 0°C under anhydrous c o n d i t i o n s . The s i l v e r s a l t i s s t a b l e a t room t e m p e r a t u r e b u t i s u n s t a b l e i n the presence o f l i g h t and was thus k e p t i n a b o t t l e wrapped i n aluminum f o i l i n s i d e a d e s s i c a t o r . P r e l i m i n a r y i n v e s t i g a t i o n s i n d i c a t e d t h a t the t r i f l i c c h l o r i d e was n o t s u f f i c i e n t l y r e a c t i v e f o r our p u r p o s e s . E q u i m o l a r quan-t i t i e s o f t r i f l i c c h l o r i d e , p y r i d i n e and 1 , 2 : 5 , 6 - d i - O - i s o p r o p y l i d e n e -a - D - g l u c o f u r a n o s e , 2_ ( f i g u r e 2) , were s t i r r e d f o r 2 days a t 20°C w i t h no s i g n i f i c a n t r e a c t i o n . S i l v e r t r i f l a t e was found t o be more r e a c t i v e i n a r e l a t e d 17 s e r i e s o f e x p e r i m e n t s by B e r r y , however t h e r e a c t i o n workup was i n c o n v e n i e n t , r e q u i r i n g r e m o v a l o f v e r y f i n e , i n s o l u b l e s a l t s . Moreover, a n o t h e r s t e p was r e q u i r e d i n the r e a c t i o n sequence — t h a t -10-of f o r m a t i o n o f t h e s u g a r h a l i d e . The a n h y d r i d e was f o u n d t o be t h e most u s e f u l r e a g e n t f o r our work. I t was f a r more r e a c t i v e t h a n t h e t r i f l i c c h l o r i d e . Thus, e q u i m o l a r q u a n t i t i e s o f t r i f l i c a n h y d r i d e , p y r i d i n e and 2 r e a c t e d t o g i v e the d e s i r e d t r i f l a t e 5_ i n l e s s t h a n one hour a t -15°C. The a n h y d r i d e i s a l s o more c o n v e n i e n t t h a n the s i l v e r t r i f l a t e i n t h a t a t r i f l a t e c o u l d be formed d i r e c t l y from t h e a l c o h o l . Moreover, i n s o l u b l e s a l t s a r e n o t a p r o b l e m i n the p u r i -f i c a t i o n p r o c e d u r e . Our f i n d i n g s appear t o be v e r i f i e d by t h e l i t e r a t u r e . T r i f l i c a n h y d r i d e has been the most w i d e l y used r e a g e n t f o r t r i f l a t e s y n -t h e s e s 7 " 1 0 ' 1 8 ~ 2 1 ' 2 4 ' 2 5 . S i l v e r t r i f l a t e 5 ' 1 2 ' 2 2 and t r i f l i c 4 2 3 f l u o r i d e ' have been used l e s s f r e q u e n t l y . T h i s a u t h o r found 2 6 o n l y one r e f e r e n c e t o t h e use o f t r i f l i c c h l o r i d e f o r t r i f l a t e s y n t h e s i s , a l t h o u g h no e x p e r i m e n t a l d e t a i l s were g i v e n . However, t r i f l i c c h l o r i d e has been used q u i t e s u c c e s s f u l l y f o r the s y n t h e s i s of " t r i f l a m i d e s " , o r t r i f l u o r o m e t h a n e s u l f o n i c a c i d amides w h i c h have been found t o be v e r y u s e f u l b l o c k i n g groups f o r amine , , . ,... 27-31 f u n c t i o n a l i t i e s The p o s s i b l e h i g h r e a c t i v i t y o f the t r i f l a t e s p r e p a r e d i n t h i s work meant c a r e had t o be t a k e n t o use an i n e r t s o l v e n t , an-hydrous r e a c t i o n c o n d i t i o n s and low t e m p e r a t u r e s . M e t h y l e n e c h l o r i d e , chosen as a c o n v e n i e n t s o l v e n t , was found t o be i n e r t under t h e r e a c t i o n c o n d i t i o n s used. The b e s t r e a c t i o n t e m p e r a t u r e range was t h a t a c h i e v e d by an i c e - m e t h a n o l or i c e - b r i n e b a t h (-10° t o -20°C). Lower t e m p e r a t u r e s were more d i f f i c u l t t o main-t a i n and, a t h i g h e r t e m p e r a t u r e s , some o f the t r i f l a t e s , n o t a b l y 1 , R = OH 2 , R = OH 3 , R = OH 4 , R = 'OTf 5 , R = OTf 6 , R = OTf 8^  , R = OS02CH2CF3 9 , R = OS02CH2CF3 7_ , R = CjHN OTf 11, R = OS0 2C 6F 5 12, R = 0S0 oC,F c — 2 6 5 10, R = OS0 2CH 2CF 3 14, R = OTs 15, R = OTs 17_, R = C 5H 5N OTf" 19, R = C j H N V 13_, R 16, R 18, R 20, R OS0 2C 6F 5 OTs C5H N OTs" c 5H 5 N + r FIGURE 2 Fluorinated sulfonyl and pyridinium t r i f l y l derivatives synthesized for this work. -12-the p r i m a r y ones, tended t o decompose. A l t h o u g h t h e f l u o r i n a t e d s u l f o n y l r e a g e n t s a r e n o t d i f f i c u l t t o h a n d l e , t h e y i e l d s o f t h e p r o d u c t s were s i g n i f i c a n t l y improved by w o r k i n g under anhydrous c o n d i t i o n s i n an atmosphere o f d r y n i t r o g e n . I n i t i a l e x p e r i m e n t s i n d i c a t e d t h a t t h e b e s t s c a v e n g e r base f o r t h i s work was p y r i d i n e , a l t h o u g h i t was d i s c o v e r e d t h a t c a r e had t o be t a k e n , e s p e c i a l l y w i t h t h e s y n t h e s i s o f a p r i m a r y t r i f l a t e , t o add o n l y an e q u i m o l a r q u a n t i t y o f p y r i d i n e t o a v o i d o b t a i n i n g the p y r i d i n i u m s a l t r a t h e r than t h e d e s i r e d t r i f l a t e . I n an i n i t i a l e x p e r i m e n t , 1 , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i d e n e - a - D - g a l a c t o p y r a n o s e , 3_ ( f i g u r e 2 ) , was r e a c t e d w i t h a 1% e x c e s s o f t r i f l i c a n h y d r i d e i n p y r i d i n e . A f t e r a p p r o x i m a t e l y 1/2 hour, t . l . c . ( t o l u e n e : e t h e r - 1 : 2 ) i n d i c a t e d t h a t _3 had r e a c t e d c o m p l e t e l y . Workup o f the r e a c t i o n , as d e s c r i b e d i n the e x p e r i m e n t a l s e c t i o n , y i e l d e d w h i t e c r y s t a l l i n e p l a t e l e t s . Subsequent s p e c t r a l a n a l y s i s p r o v e d t h e compound t o be 6 - d e o x y - l , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i d e n e - 6 - p y r i d i n o - «-D-galactopyranose t r i f l u o r o m e t h a n e s u l f onate 7_. Thus, the p.m.r. spectrum o f t h e substance showed the p r e s e n c e o f a r o m a t i c r e s o n a n c e s , t y p i c a l o f p y r i d i n e , a t T 0.74 ( o ) , 1.68 (m) and 1.18 ( p ) . Comparison o f t h e spectrum w i t h t h a t o f 3^  i t s e l f r e v e a l e d t h e resonance due t o t h e 6-hydroxy group had d i s a p p e a r e d and t h a t the p r o t o n s on C-6 were r e s o n a t i n g now a t l o w e r f i e l d , from T 6 . 1 f o r 3_ t o T4.75 and 5.08 f o r 1_, due, p o s s i b l y , t o t h e f a c t t h a t the c a r b o n i n the 6 - p o s i t i o n was now bound t o an a r o m a t i c s p e c i e s i . e . t h e p y r i d i n e r i n g . The f l u o r i n e n.m.r. of t h i s compound showed a s i n g l e t a t 0 c + 81.2 ppm., a s s i g n e d t o the CF^SO^ m o i e t y . A subsequent attempt t o p r e p a r e , i s o l a t e and i d e n t i f y t h e p r i m a r y t r i f l a t e ' 6_, i t s e l f , u s i n g e q u i --13-molar q u a n t i t i e s o f b l o c k e d s u g a r , t r i f l i c a n h y d r i d e and p y r i -d i n e , however, was u n s u c c e s s f u l , as d e c o m p o s i t i o n o c c u r r e d a t temper a t u r e s much above 5°C. T h e r e f o r e i t i s s u g g e s t e d t h a t £ can be used as r e a c t i o n i n t e r m e d i a t e , b u t wo u l d be i s o l a t e d o n l y w i t h d i f f i c u l t y . I n o r d e r t o compare t h e r e a c t i v i t y o f 6 w i t h t h a t o f 1,2: 3, 4 - d i - 0 - i s o p r o p y l i d e n e - 6 - 0 - t o s y l - a - D - g a l a c t o p y r a n o s e 16_, we r e a c t e d 16 w i t h p y r i d i n e . The r e a c t i o n m i x t u r e was h e a t e d t o r e f l u x t e m p e r a t u r e f o r 25 hours b e f o r e i t was c o m p l e t e l y r e a c t e d . The u s u a l workup y i e l d e d a w h i t e powdery m a t e r i a l i d e n t i f i e d , i n the same manner as 6_, as the t o s y l p y r i d i n i u m s a l t , 6-deoxy-1 , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i d e n e - 6 - p y r i d i n o - a - D - g a l a c t o p y r a n o s e t o l -u e n e - p - s u l f o n a t e 18. A 30% y i e l d o f 18_ was o b t a i n e d , compared to a 9 0% y i e l d o f 1_ o b t a i n e d from the t r i f l a t e r e a c t i o n . Thus, some o f t h e advantages o f the t r i f l a t e m o i e t y over t h e t o s y l a t e m o i e t y as a l e a v i n g group f o r S^2 n u c l e o p h i l i c d i s p l a c e m e n t r e a c -t i o n s were now q u i t e a p p a r e n t . The t r i f l a t e r e a c t i o n was f a s t e r , appeared t o have l e s s d e c o m p o s i t i o n and s i d e r e a c t i o n s a s s o c i a t e d w i t h i t and thus gave a f a r h i g h e r y i e l d t han t h e t o s y l a t e r e a c t i o n . I n o r d e r t o v e r i f y t h a t t h e t r i f l y l p y r i d i n i u m s a l t had i n -deed been formed, b o t h 7_ and 18 were c o n v e r t e d t o t h e i r i o d i d e s a l t s , u s i n g K l i n a c e t o n e , as d e s c r i b e d i n the e x p e r i m e n t a l s e c t i o n . S e p a r a t e and mixed m e l t i n g p o i n t s as w e l l as n.m.r. s p e c t r a l d a t a v e r i f i e d t h a t the same i o d i d e s a l t , 2_0, was o b t a i n e d from 1_ as from 18. ' Hav i n g thus examined t h e enhanced r e a c t i v i t y o f a p r i m a r y -14-s u g a r t r i f l a t e , we t h e n t u r n e d o ur a t t e n t i o n t o sec o n d a r y s u g a r 1 2 3 t r i f l a t e s . I t has been n o t e d by s e v e r a l a u t h o r s ' ' t h a t t o s y l a t e f u n c t i o n a l i t i e s i n s e c o n d a r y p o s i t i o n s on s u g a r s a r e n o t v e r y r e a c t i v e i n S N2 r e a c t i o n s . I t was t h o u g h t t h a t perhaps t h e use o f t r i f l a t e s w o uld a c t i v a t e s e c o n d a r y p o s i t i o n s on sugar m o l e c u l e s enough t o a l l o w f o r r e a c t i o n s w h i c h p r e v i o u s l y d i d n o t o c c u r , o r were v e r y s l o w when u s i n g a t o s y l a t e as t h e l e a v i n g group. T h e r e f o r e , 1, 2 : 5, 6 - d i - 0 - i s o p r o p y l i d e n e - a - D - a l l o f uranose JL, was r e a c t e d w i t h a 10% e x c e s s o f t r i f l i c a n h y d r i d e and 4 e q u i v a -l e n t s p y r i d i n e i n methylene c h l o r i d e s o l u t i o n . A f t e r 1 h o u r , t . l . c . ( t o l u e n e : e t h e r - 1 : 2 ) i n d i c a t e d the r e a c t i o n t o be co m p l e t e . A f t e r t h e u s u a l workup, c o l o u r l e s s n e e d l e - l i k e c r y s t a l s were ob-t a i n e d , w h i c h were i d e n t i f i e d £>y n.m.r. as i , 2 : 5 , b - d i - O - i s o p r o -p y l i d e n e - 3 - O - t r i f l y l - a - D - a l l o f u r a n o s e 4_. Thus, t h e resonance a s s i g n e d t o H-3 ( T ^.p) i s d o w n f i e l d from t h a t o f H-3 o f 1_ ( T"5~7 ) • The f l u o r i n e n.m.r. spe c t r u m o f 4_ showed a s i n g l e t a t 0 C + 78.8, a s s i g n e d t o the t r i f l a t e m o i e t y . The y i e l d o f 4 was e s s e n t i a l l y q u a n t i t a t i v e . More v i g o r o u s r e a c t i o n c o n d i t i o n s were r e q u i r e d t o e f f e c t the c o n v e r s i o n o f 1 o r 4 t o 1 , 2 : 5 , 6 - d i - O - i s o p r o p y l i d e n e - 3 - p y r i d i n o -a - D - g l u c o f u r a n o s e 1_7, t h a n t h o s e r e q u i r e d t o c o n v e r t 3 o r 6 t o _7. Thus, 1 o r 4_ was d i s s o l v e d i n p y r i d i n e and h e a t e d t o r e f l u x t e m p e r a t u r e f o r 25 hours t o o b t a i n , a f t e r t h e u s u a l workup, a v e r y h y g r o s c o p i c , brown, c r y s t a l l i n e m a t e r i a l , w h i c h p r o v e d t o be t h e t r i f l a t e s a l t , 1 7 . The p.m.r. spectrum o f the m a t e r i a l showed t h e c h a r a c t e r i s t i c p y r i d i n o r e s o n a n c e s - T.94(O),T 1.61(m) andx 1.09 (p ) . The J0 ^ c o u p l i n g was ca.0, i n d i c a t i v e o f an e l e c t r o n e g a t i v e -15-s p e c i e s a t the 3 p o s i t i o n o f a g l u c o f u r a n o s e s u g a r , c o n f i r m i n g i n v e r s i o n o f c o n f i g u r a t i o n a t C-3. The F n.m.r. spe c t r u m o f the compound showed a s i n g l e t a t 0 c + 81.6 ppm., a s s i g n e d t o t h e t r i f l a t e m o i e t y . The y i e l d o f 17 from .1 was a p p r o x i m a t e l y 70%. I n c o n t r a s t , under s i m i l a r r e a c t i o n c o n d i t i o n s , 1,2:5,6-di-O-i s o p r o p y l i d e n e - 3 - O - t o s y l - a - D - a l l o f u r a n o s e , 1 4 , d i d n o t r e a c t . S i m i l a r l y , 1 , 2 : 5 , 6 - d i - O - i s o p r o p y l i d e n e - a - D - g l u c o f u r a n o s e 2_, was r e a c t e d w i t h a 10% e x c e s s o f t r i f l i c a n h y d r i d e i n p y r i d i n e t o g i v e , w i t h i n one hour, an a l m o s t q u a n t i t a t i v e y i e l d o f what 1 19 was d e t e r m i n e d , by H and F n.m.r., t o be 1 , 2 : 5 , 6 - d i - O - i s o p r o -p y l i d e n e - 3 - O - t r i f l y l - a - D - g l u c o f u r a n o s e 5_. The p.m.r. spe c t r u m of the p r o d u c t a g a i n showed a l a c k o f a 3-hydroxy r e s o n a n c e as w e l l as a d o w n f i e l d s h i f t o f t h e C-3 p r o t o n from x5.6 f o r 2_ t o 19 T4.66 f o r 5. The F s p e c t r u m showed a s i n g l e t r i f l a t e r e s o n a n c e a t 0 c + 77 ppm. • I t has been found t o be v e r y d i f f i c u l t t o a c h i e v e an S„T2 n u c l e o p h i l i c d i s p l a c e m e n t r e a c t i o n a t t h e C-3 p o s i t i o n o f 2 due, presumably, t o s t e r i c h i n d r a n c e . Only one such r e a c t i o n has been 32 r e p o r t e d . T h i s was t h e d i s p l a c e m e n t o f the t o s y l a t e group o f 1 , 2 : 5 , 6 - d i - O - i s o p r o p y l i d e n e - 3 - 0 - t o s y l - a - D - g l u c o f u r a n o s e , 15, by h y d r a z i n e , perhaps s u c c e s s f u l because the h y d r a z i n e i o n p o s s e s s e s v e r y l i t t l e s t e r i c b u l k . I t was t h o u g h t t h a t the t r i f l a t e group might a c t i v a t e the 3 p o s i t i o n o f 2_ s u f f i c i e n t l y t o a l l o w f o r an S N2 n u c l e o p h i l i c d i s p l a c e m e n t r e a c t i o n . A f t e r r e f l u x i n g i n p y r i -d i n e f o r 5 days, t . l . c . ( t o l u e n e : e t h e r - 2 : 1 ) i n d i c a t e d t h a t a l l o f !5 had r e a c t e d , b u t the p y r i d i n i u m s a l t had n o t been formed. -16-E l i m i n a t i o n was assumed t o have o c c u r r e d , however t h i s r e a c t i o n was not f u r t h e r s t u d i e d . 4_ and 5_ were found t o be s t a b l e f o r up t o 6 months i f k e p t c o l d (-10 - 0°C) and d r y , however a t room t e m p e r a t u r e , open t o the atmosphere, b o t h d e r i v a t i v e s decomposed w i t h i n a few h o u r s . As mentioned i n t h e i n t r o d u c t i o n , a t t h e time o f t h e b e g i n n i n g of t h i s work o n l y one t r i f l a t e e x p e r i m e n t w i t h s u g a r s had been 12 r e p o r t e d i n the l i t e r a t u r e . K r o n z e r and S c h u e r c h r e p o r t e d t h e use o f s i l v e r t r i f l a t e and o t h e r s i l v e r s a l t s i n the m e t h a n o l y s i s of some d e r i v a t i v e s o f 2 , 3 , 4 - t r i - O - b e n z y l - a - D - g l u c o p y r a n o s y l bromide, and p o s t u l a t e d g l u c o s y l t r i f l a t e i n t e r m e d i a t e s f o r t h e s i l v e r t r i f l a t e - a s s i s t e d m e t h a n o l y s e s . Some months a f t e r t h e s t a r t o f t h i s s e r i e s o f e x p e r i m e n t s , 25 Maradufu and P e r l i n p u b l i s h e d the s y n t h e s i s o f m e t h y l 2 , 3 , 6 - t r i -O - b e n z o y 1 - 4 - 0 - t r i f l y l - S - D - g l u c o p y r a n o s i d e 21 u s i n g a method s i m i -l a r t o o u r s . I t was found t o have p h y s i c a l c h a r a c t e r i s t i c s s i m i l a r : H 2 O B Z 21 rfo OBz t o our secondary s u g a r t r i f l a t e s . Thus 2_1 was c r y s t a l l i n e and f a i r l y s t a b l e , a l t h o u g h i t darkened on s t a n d i n g . The y i e l d o f 21 (48%) was f a r l o w e r t h a n any o b t a i n e d by u s , perhaps owing t o t h e method o f p u r i f i c a t i o n w h i c h i n c o r p o r a t e d t h e use o f a s i l i c a g e l column. We do n o t b e l i e v e t h a t t h i s i s a good method f o r p u r i f i -c a t i o n o f such r e a c t i v e e n t i t i e s as t r i f l a t e s , p r e f e r r i n g b o t h f o r -17-t h em and, i n d e e d , f o r a l l t h e c r y s t a l l i n e f l u o r i n a t e d s u l f o n a t e d e r i v a t i v e s made i n t h i s s t u d y , t o s i m p l y wash t h e s y r u p , o b t a i n e d a f t e r removal o f t h e l a s t t r a c e s o f p y r i d i n e , w i t h p e t r o l e u m e t h e r (30-60). A f t e r c o o l i n g t h e w a s h i n g s , t h e f l u o r i n a t e d s u g a r s u l -f o n a t e would i n v a r i a b l y c r y s t a l l i z e . I n the ca s e s o f the t r i f l a t e s and the t r e s y l a t e s , the c r y s t a l s f i l t e r e d o f f from t h i s s o l u t i o n were found t o be a n a l y t i c a l l y p u r e . I n the case o f t h e p e n t a f l a t e s , 1 o r 2 f u r t h e r r e c r y s t a l l i z a t i o n s from p e t r o l e u m e t h e r (30-60) were g e n e r a l l y s u f f i c i e n t t o o b t a i n a n a l y t i c a l l y p ure samples. An e x c e p t i o n was 12, b u t column p u r i f i c a t i o n i n t h i s case was found t o be no b e t t e r t h a n the p e t r o l e u m e t h e r e x t r a c t i o n and r e c r y s t a l -l i z a t i o n method. Maradufu and P e r l i n a l s o r e p o r t e d t h e r e a c t i o n o f 21_ w i t h sodium a z i d e t o form m e t h y l 4 - a z i d o - 2 , 3 , 6 - t r i - O - b e n z o y 1 - 4 -deoxy- 6 - D - g a l a c t o p y r a n o s i d e . A l t h o u g h t h e r e a c t i o n p r o c e e d e d f a s t e r than t h a t o f t h e analogous p - b r o m o p h e n y l s u l f o n a t e a l s o s t u d i e d -- 2 hours as compared t o 12 hours -- t h e y i e l d o b t a i n e d was lower — 75% as compared t o 96%. S u b s e q u e n t l y , Lemieux and K o n d o ^ r e p o r t e d t h e use o f b e n z y l t r i f l u o r o m e t h a n e s u l f o n a t e — s y n t h e s i z e d from t r i f l i c a n h y d r i d e and b e n z y l a l c o h o l — t o p r e p a r e t h e b e n z y l e t h e r s o f some sugar d e r i v a t i v e s . 18 B e r r y and H a l l , as p a r t o f a r e l a t e d s e r i e s o f e x p e r i m e n t s i n t h i s department, r e p o r t e d t h e use o f b e n z y l and m e t h y l t r i -f l a t e i n the s y n t h e s i s o f some O - b e n z y l a t e d and O-methylated c a r -b o h y d r a t e d e r i v a t i v e s . ' -18-TRESYLATES As th e i s o l a t i o n o f a p r i m a r y t r i f l a t e p r o v e d u n s u c c e s s f u l , i t was d e c i d e d t o i n v e s t i g a t e o t h e r , l e s s r e a c t i v e f l u o r i n a t e d s u l f o n a t e e s t e r d e r i v a t i v e s o f s u g a r s i n the hope t h a t a more t r a c t a b l e p r i m a r y f l u o r i n a t e d s u g a r s u l f o n a t e c o u l d be f o u n d . 2 , 2 , 2 - t r i f l u o r o e t h y l s u l f o n a t e e s t e r s , o r " t r e s y l a t e s " , have 6 9 been r e p o r t e d ' as b e i n g l e s s r e a c t i v e l e a v i n g groups t h a n t r i -f l a t e s , b u t more r e a c t i v e than t o s y l a t e s . The a c i d c h l o r i d e (CF^CH^SG^Cl) i s a v a i l a b l e c o m m e r c i a l l y 1 ^ . I t was t h e r e f o r e de-_ c i d e d t o a t t e mpt t o s y n t h e s i z e t h e t r e s y l a t e d e r i v a t i v e s o f 1_, 2_ and 3_. U s i n g a method s i m i l a r t o t h a t f o r the s y n t h e s i s o f t r i f l a t e s , 3_ was r e a c t e d w i t h a 15% e x c e s s o f t r e s y l c h l o r i d e and a 60% excess-o f p y r i d i n e i n methylene c h l o r i d e , a t -15°C f o r 1.5 h o u r s , t o g i v e , a f t e r t h e u s u a l workup, an 89% y i e l d o f what was d e t e r m i n e d t o be 1 , 2 : 3 , 4 - d i - 0 - i s o p r o p y l i d e n e - 6 - 0 - t r e s y l - a - D - g a l a c t o p y r a n o s e . The p.m.r. spectrum o f t h e compound showed no 6-hydroxy r e s o n a n c e , b u t d i d show a q u a r t e t , a t x5.37 (J=9.25 H z ) , a t t r i b u t e d t o the coup-l i n g o f t h e f l u o r i n e w i t h t h e t r e s y l a t e p r o t o n s . A g a i n , th e H-6 p r o t o n resonances were d o w n f i e l d from t h o s e o f the H-6 p r o t o n s o f 19 3_ ( T 5.4 3 and T 5.53 f o r 10; x 6.1 f o r 3_) . The F n.m.r. spe c t r u m o f 10_ showed a t r i p l e t a t 0 + 63.6 ppm., a s s i g n e d t o t h e t r e s y l a t e 6 group. A c c o r d i n g t o the l i t e r a t u r e , 10 c o u l d be up t o 100 t i m e s more r e a c t i v e than 16. The t r e s y l a t e d e r i v a t i v e s of: 1^  and 2_, r e s p e c t i v e l y , 1,2:5,6--19-d i - 0 - i s o p r o p y l i d e n e - 3 - 0 - t r e s y l - a - D - a l l o f u r a n o s e ' 8_, and 1,2:5,6-d l - O - i s o p r o p y l i d e n e - 3 - 0 - t r e s y l - a - D - g l u c o f u r a n o s e 9_ were o b t a i n e d i n a s i m i l a r manner t o t h a t o f 3_, b o t h i n a p p r o x i m a t e l y 90% y i e l d . I d e n t i f i c a t i o n o f the compounds was, as b e f o r e , e f f e c t e d by "*"H 19 and F n.m.r. Thus, the p..m.r. s p e c t r a o f 8_ and 9_ each showed a q u a r t e t a s s i g n e d t o t h e two p r o t o n s o f t h e t r e s y l a t e group ( J p H 9.3 Hz i n b o t h c a s e s ) , as w e l l as t h e c h a r a c t e r i s t i c d o w n f i e l d s h i f t o f t h e H-3 p r o t o n r e s o n a n c e s ( f o r 8^  x4.51 from T 5.7 f o r 1; 19 f o r 9_, T4.81 from T 5.6 f o r 2) . A g a i n , t h e F n.m.r. showed a t r i p l e t a t 0 C + 63.2 ppm., f o r b o t h compounds, due t o t h e t r e s y l a t e group. A l l t h e t r e s y l a t e d e r i v a t i v e s s y n t h e s i z e d i n t h i s s t u d y were c r y s t a l l i n e , s t a b l e i n d e f i n i t e l y , d r y , a t 0°C. However, i f l e f t a t room t e m p e r a t u r e , open t o t h e atmosphere, d e c o m p o s i t i o n o c c u r r e d i n 24 h o u r s . PENTAFLATES The c o n v e r s i o n of: 1, 2_ and 3_ i n t o the c o r r e s p o n d i n g p e n t a -f l u o r o b e n z e n e s u l f o n a t e s , o r " p e n t a f l a t e s " , 1 1 , 12 and 13, r e s -p e c t i v e l y , u s i n g the u s u a l p y r i d i n e - a c i d c h l o r i d e method, was l e s s s a t i s f a c t o r y . Y i e l d s were l e s s t h a n 40% and, f o r t h e con-v e r s i o n o f 2_ t o 12, an a n a l y t i c a l l y pure sample c o u l d n o t be ob-t a i n e d . R e a c t i o n s c o n d u c t e d w i t h a 3-molar e x c e s s o f r e a g e n t gave no s i g n i f i c a n t improvement i n y i e l d , n e i t h e r d i d v a r i a t i o n s i n r e a c t i o n time (3-48 h r s . ) and t e m p e r a t u r e (-20 - +80°C). A l l - 2 0 -p r o d u c t s , a g a i n , were i d e n t i f i e d by H and F n.m.r. T a b l e s 1^  and 2_, i n p a r t (b) o f t h i s c h a p t e r , show t h e s h i f t s and c o u p l i n g s o f the compounds s y n t h e s i z e d i n t h i s s t u d y . As the p e n t a f l u o r o b e n z e n e s u l f o n y 1 c h l o r i d e i s f a i r l y e x p e n s i v e and as the r e a c t i v i t y o f the t r e s y l a t e s i s p u r p o r t e d t o be on a p a r w i t h t h a t o f t h e p e n t a f l a t e s , i t i s recommended here t h a t t h e former be used f o r more r e a c t i v e p r i m a r y s u l f o n a t e e s t e r s w h i c h a r e more t r a c t a b l e and s t a b l e t h a n t r i f l a t e s . F o r s e c o n d a r y s u l -f o n a t e e s t e r s , t h e h i g h r e a c t i v i t y and c o m p a r a t i v e s t a b i l i t y o f the secondary t r i f l a t e s make them a more d e s i r a b l e c h o i c e f o r s y n -t h e t i c work th a n e i t h e r t h e t r e s y l a t e s , p e n t a f l a t e s o r n o n f l u o r -i n a t e d s u l f o n a t e e s t e r s . As p r e v i o u s l y s t a t e d , t r i f l a t e s and o t h e r f l u o r i n a t e d s u l f o n a t e e s t e r s show g r e a t p o t e n t i a l f o r the f i e l d o f s y n t h e t i c c a r b o h y d r a t e c h e m i s t r y , as t h e s e e s t e r s m i g h t a l l o w f o r S^2 d i s p l a c e m e n t on o t h e r w i s e u n r e a c t i v e m o l e c u l e s and a l l o w f o r r e a c t i o n s on v e r y s e n s i t i v e s u g a r s w i t h a minimum o f s i d e - r e a c t i o n s . However, t r i f l a t e s y n t h e s e s and r e a c t i o n s , e s p e c i a l l y i n the a r e a o f c a r b o h y d r a t e c h e m i s t r y s t i l l p r e s e n t a number o f d i f f i c u l -t i e s . Thus, i n r e a c t i o n s where a t r i f l a t e was s y n t h e s i z e d u s i n g p y r i d i n e and t r i f l i c a n h y d r i d e , t h e n r e a c t e d w i t h o u t p r i o r i s o l a -t i o n w i t h a n u c l e o p h i l e such as tetra-n-butylammonium i o d i d e , a number o f u n i d e n t i f i e d p r o d u c t s were o b t a i n e d . I t i s p o s s i b l e t h a t t h e t r i f l a t e s a l t s p r o d u c e d by t h e base and the l i b e r a t e d t r i f l i c - 2 1 -a c i d are r e a c t i v e , and i t may be n e c e s s a r y t o i s o l a t e and p u r i f y t h e t r i f l a t e each t i m e , c a u s i n g problems i n t h e case o f t h e u n s t a b l e p r i m a r y t r i f l a t e s . I n t h e s e c a s e s , perhaps t h e t r i f l i c f l u o r i d e o r s i l v e r t r i f l a t e methods would be b e s t . A l t e r n a t e l y , t h e t r e -s y l a t e c o u l d be used; a l t h o u g h i n t h i s case t h e r e a c t i v i t y o f t h e e s t e r formed w o u l d be d e c r e a s e d by a f a c t o r o f ca.4000, i t c o u l d s t i l l be c a . 100 t i m e s more r e a c t i v e t h a n t h e c o r r e s p o n d i n g t o s y l a t e . Doubt a l s o remains c o n c e r n i n g t h e most s u i t a b l e method o f s c a v e n g i n g l i b e r a t e d t r i f l i c a c i d . I t has been found t h a t t r i f l a t e s 4 9 a l k y l a t e p r e f e r e n t i a l l y a t n i t r o g e n r a t h e r than a t oxygen ' so t h a t a base such as p y r i d i n e o r even l u t i d e n e i s u n a c c e p t a b l e . 3 3 Lemieux has used 2 , 4 , 6 - t r i m e t h y l p y r i d i n e as a t r i f l i c a c i d s c a v e nger, and t h i s may o f t e n be t h e b e s t c h o i c e , b e i n g r e l a t i v e l y 18 i n e x p e n s i v e and q u i t e a poor n u c l e o p h i l e ; however B e r r y has found t h a t , i n c e r t a i n r e a c t i o n s , even t h i s has been N - a l k y l a t e d and t h a t , i n t h e s e c a s e s , 2 , 6 - d i - t e r t - b u t y l p y r i d i n e i s b e t t e r . A l t h o u g h the l a t t e r i s f a i r l y e x p e n s i v e , i t can be r e g e n e r a t e d from the s a l t by a d d i t i o n o f p y r i d i n e t o the r e a c t i o n m i x t u r e a f t e r 34 the workup, f o l l o w e d by d i s t i l l a t i o n . L i n d b e r g and co-workers used 2 , 6 - d i - t e r t - b u t y l ~ 4 - m e t h y l p y r i d i n e , w h i c h i s l e s s e x p e n s i v e than 2 , 6 - d i - t e r t - b u t y l p y r i d i n e . C l e a r l y , t h e r e f o r e , much i n v e s t i g a t i v e work needs t o be done i n the a r e a o f S N2 n u c l e o p h i l i c a t t a c k on s u g a r t r i f l a t e s (or o f t r i f l a t e s on sugars) b e f o r e t r i f l a t e s become as g e n e r a l l y use-f u l i n the a r e a o f s y n t h e t i c c a r b o h y d r a t e c h e m i s t r y as t h e u n f l u o r -i n a t e d s u l f o n a t e e s t e r s c u r r e n t l y i n use. -22-b) N.m.r. sp e c t r a and conformational p r o p e r t i e s of the t r i f l y l p y r i d i n i u m s a l t s . The 100 MHz p.m.r. sp e c t r a of the p y r i d i n i u m s a l t s 1_, 17-20 were s u f f i c i e n t l y w e l l d ispersed i n deuterioacetone s o l u t i o n s to make f i r s t - o r d e r assignments and analyses s t r a i g h t forward. The r e s u l t i n g data are summarized i n Table 1. In every i n s t a n c e , the v i c i n a l ^H-^H c o u p l i n g constants were very s i m i l a r to those of the s u l f o n a t e precursor (Table 2) and i n -di c a t e d t h a t these molecules had the a n t i c i p a t e d s o l u t i o n geometry. Thus, the three d e r i v a t i v e s of 1, 2 : 5, 6 - d i - O - i s o p r o p y l i d e n e - a-D_ galactopyranose (7_, 1 8 / 20_) showed s i m i l a r c o u p l i n g s , a l l i n d i c a -35 txve of the t w i s t - b o a t conformation shown below. -23-I n " l i k e f a s h i o n , i t i s c l e a r t h a t t h e f u r a n o s e d e r i v a t i v e s 3 17 and 19 f a v o u r the a n t i c i p a t e d c o n f o r m a t i o n , t h e z e r o v a l u e o f J 2 ^ b e i n g u n e q u i v o c a l l y i n d i c a t i v e o f t h a t p a r t i c u l a r • c o n f o r -36 m a t i o n A l t h o u g h o f no d i a g n o s t i c p o t e n t i a l i t i s i n t e r e s t i n g t o n o t e t h a t the g e m i n a l c o u p l i n g ( J ^ g') i s s u b s t a n t i a l l y s m a l l e r i n a b s o l u t e terms f o r t h e p y r a n o s e d e r i v a t i v e s (-13.5 Hz) t h a n i t i s f o r t h e f u r a n o s e d e r i v a t i v e s (-8.5 H z ) . The i n t r o d u c t i o n o f the p y r i d i n i u m m o i e t y causes s u b s t a n t i a l changes i n the s h i f t s o f t h o s e p r o t o n s w h i c h a r e c l o s e enough t o be i n f l u e n c e d by the e l e c t r o n w i t h d r a w i n g i n d u c t i v e e f f e c t and/or t h e r i n g c u r r e n t e f f e c t o f the a r o m a t i c r i n g . F o r example, th e H-6, H-6' r e s o n a n c e s o f t h e g a l a c t o p y r a n o s e d e r i v a t i v e s a r e - 2 4 -s h i f t e d d o w n f i e l d by 0.5-0.7 ppm. i n g o i n g from a s u l f o n a t e t o the p y r i d i n i u m s a l t and a s i m i l a r d e s h i e l d i n g o f the H-3 r e s o n -ances o f the f u r a n o s e d e r i v a t i v e s i s o b s e r v e d . The i n d u c e d s h i f t s o f the more remote p r o t o n s (such as H - l and H-2 o f 17 and 19), w h i c h can o n l y be a s c r i b e d t o a r i n g - c u r r e n t e f f e c t , s u g g e s t t h a t i t might be w o r t h w h i l e t o s t u d y some o f t h e s e d e r i v a t i v e s by p r o t o n r e l a x a t i o n methods i n o r d e r t o d e t e r m i n e the r e l a t i v e d i s -p o s i t i o n o f the p y r i d i n i u m r i n g w i t h r e s p e c t t o the sugar r i n g . TABLE 1 CHEMICAL SHIFTS (x-VALUES) AND MULTIPLET SPLITTINGS (Hz) FOR PYRIDINIUM SALTS IN DEUTERIOACETONE SOLUTIONS H-l H-2 H-3 H-4 H-5 H-6 H-6 X o PYRIDINE m P Others / 4.47 5.54 5.22 5.43 5.60 4.75 5.08 0.74 1.68 1.18 a J l , 2 5 J 2 , 3 2 .4 J 3 , 4 7 - 8 J 4 , 5 } ' 6 , J 5 , 6 3 J c A 8.8 5,6 J 6 , 6 V 1 3 ' 6 J 6.6 o,m J 7. m,p .8 Jn „ !• o,p .2 18 4.52 5.59 5.31 5.48 5.60 4.58 5.19 0.59 1.75 1.24 ' b J 1.2 *• 7 J 2 , 3 2 .2 : ° 3 , 4 7 " 6 ° 4 , 5 1 - 6 J 5 , 6 2 - 4 5,6 °6,6y 1 3 ' 6 o ,m J 8. m,p 0 J ~ o o,p .20 4.48 5.54 5.28 5.35 5.56 4.52 5.11 0.54 1.66 1,16 ' c J l , 2 4 - 7 J 2 , 3 2 ' .3 J 3 , 4 8 ' ° J 4 f 5 V - J 5 , 6 2 - 5 °5,6^ 9 - 2 J 6 ,6^ 1 3 ' 4 o ,m J 7. m,p 6 o,p 2 17 3.41 4.44 4.37 5.37 6.53 6.04 5.90 0.94 1.61 1.09 J 3 1 ,2 6 m 5 J 2 , 3 0 J 3 , 4 4 J 4 , 5 9 J 5 , 6 4 - 5 J 5 , 6 V 6 J c c\ 8.5 6,6 J n m 6-8 o ,  8 °o.p 3 l i 3.09 4.35 4,35 5.38 6.54 6.07 5.93 0,75 1,60 1.07 J l , 2 3 - 5 J 2 , 3 0 J 3 , 4 4 J 4 , 5 9 J 5 , 6 4 - 5 °5,6N 6 J 6 , 6 ^ 8 - 5 J o m 6.8 o ,m m,p 6 J o , p 1 ' C F 3 so3 , *c 81 .2 p.p. m. b PhCH 3 , 7 .69; C 6 H 4 , 2 .30 , 2 •90"> J „ m ' 8 . o,m C C F 3 S 0 3 • < j>c 81.6 p. p.m. I I TABLE 2 1 H CHEMICAL SHIFTS ( x-VALUES), 1 9 F CHEMICAL SHIFTS (0C) AND MULTIPLET SPLITTINGS (Hz) FOR SULFONATES IN DEUTERIOACETONE SOLUTIONS COMPOUND H - l H-2 H-3 H-4 H-5 H-6 H-6' 0C (ppm) 4.05 5.05 4.78 5.81 6.12 4 t 5.81 1 +78.8 J l , 2 4 - 0 2 J 2 , 3 4 - 6 9 J 3 , 4 6 ' 7 3.84 5.00 4.66 5 | _ 5 > 9 ( m ) _ ( + 7 7 J l , 2 4 J 2 , 3 0 J 3 , 4 2 4.12 5.1 4.51 5.8 5.64 h-5. 8 — — - 1 a 8 J l , 2 3 " 7 J 2 , 3 4 ' 7 J 3 , 4 7 ' 3 + 63.2 3. 92 5. 11 4. 81 5. 8. 6.04 H 5 . 8 - — j +63.2 9 J l , 2 3 ' 7 J 2 , 3 0 J 3 , 4 2 ' ° b 4.41 5.54 4.26 5.60 4. 80 5.43 5.53 c 10 + 63.6 J l , 2 4 - 8 J 2 , 3 4 ' 6 J 3 , 4 7 - 5 J 4 , 5 1 ' 5 J 5 , 6 4 - 5 J,. 11.5 J c c , 6.5 6,6 5,6 4.17 5.18 5.08 +136 (o) 11 h " 6.08 (m) — • • } +148 (m) J l , 2 3 - 5 J 2 , 3 4 , 6 J 3 , 4 7 * 2 9 + 1 6 3 (P> i ro cn ! TABLE 2 (CON'T) COMPOUND H - l H-2 H-3 H-4 H-5 H-6 H-6' 0c(ppm) 12 3.7 J l , 2 3 - 6 h-—- 4 . 8 — H J 2 , 3 3 ' 6 5.8 (m) -+135 (o) +148 (m) +163 (p) 13 4.78 J l , 2 5.66 . 5.35 J 2 , 3 2 ' 5 J 3 , 4 8 / l 5. 71 J 4 , 5 1 - 8 5.94 5. J 5 , 6 5 - 4 42 J c r I 6.3 b, 6 + 135 (o) +147.2 (m) +162.4 (p) a C F 3 C H 2 x 4 . 9 4 ; J H ^ F 9.3 Hz b C F 3 C H 2 T 5 . 3 4 ; J r ^ f 9.3 Hz C C F 3 C H 2 T 5 . 3 7 ; J r p 9.25 Hz I to I - 2 8 -CHAPTER I I C - S t a n n y T a t e d C a r b o h y d r a t e s a) S y n t h e s i s Many g e n e r a l methods e x i s t f o r t h e s y n t h e s i s o f o r g a n o t i n 37 compounds w h i c h have a s t a b l e c a r b o n - t i n b o n d . Two o f t h e s e a p p e a r e d t o be p a r t i c u l a r l y c o m p a t i b l e w i t h r e a d i l y a v a i l a b l e p r e -c u r s o r s -- h y d r o s t a n n y l a t i o n o f a c a r b o n - c a r b o n d o u b l e b o n d and r e a c t i o n o f an a l k y l h a l i d e o r e q u i v a l e n t w i t h a t i n n u c l e o p h i l e . T h i s c h a p t e r i s c o n c e r n e d o n l y w i t h t h e l a t t e r . 37-39 I n t h e o r g a n o t i n l i t e r a t u r e t h e r e a r e s e v e r a l r e f e r e n c e s t o h a l o g e n - m e t a l e x c h a n g e r e a c t i o n s o f t h e s o r t : R3Sn"M+ + R'X —> R^SnR1 + MX M= Na, K, Li X= halide R= alkyl or aryl group The a t t a c k by t h e R^Sn a n i o n on a c a r b o n b e a r i n g a h a l i d e , o r e q u i v a l e n t l e a v i n g g r o u p , c a n e i t h e r be by an i n v e r s i o n mechanism, w h i c h i s p r o b a b l y an S 2 p r o c e s s , o r by a r e t e n t i o n mechanism, w h i c h -29-i s t h o u g h t t o i n v o l v e some s o r t o f e l e c t r o n t r a n s f e r — most l i k e l y the r e a c t i o n o f R^SnM w i t h R'X t o form R^SnX and R'M, w h i c h t h e n 40 condense t o R^SnR'. In t h i s work, n.m.r. d a t a i n d i c a t e d t h a t a t t a c k o f t h e t i n n u c l e o p h i l e a t a secondary c e n t r e r e s u l t e d i n a n e t i n v e r s i o n a t t h a t c e n t r e . I t i s t h e r e f o r e assumed t h a t r e a c t i o n o f t h e t i n n u c l e o p h i l e w i t h t h e s u g a r s used i s i n d e e d an S N2 n u c l e o p h i l i c d i s -placement. The t i n r e a g e n t used i n t h e s e e x p e r i m e n t s was t r i p h e n y l t i n l i t h i u m , r a t h e r than a t r i a l k y l t i n compound. The r e a s o n s f o r t h i s d e c i s i o n were, i n g e n e r a l , t o do w i t h ease o f h a n d l i n g . W h i l e t r i a l k y l t i n compounds are o f t e n q u i t e v o l a t i l e and p o i s o n o u s , t r i -a r y l t i n compounds are c r y s t a l l i n e and l e s s t o x i c . 41 U s i n g t h e method o f Tamborski and coworkers , t r i p h e n y l t i n l i t h i u m was s y n t h e s i z e d from t r i p h e n y l t i n c h l o r i d e and l i t h i u m m e t a l (see e x p e r i m e n t a l s e c t i o n f o r f u l l d e t a i l s ) . I t was d e c i d e d t o f i r s t a t t e m p t t h e s y n t h e s i s o f a p r i m a r y t i n - s u g a r d e r i v a t i v e , as i t was assumed t h a t t h i s t y p e o f d e r i v a t i v e would be more r e a d i l y o b t a i n e d t h a n a sugar w i t h a c a r b o n - t i n bond i n a secondary p o s i t i o n . Thus, t r i p h e n y l t i n l i t h i u m was r e a c t e d v / i t h 1, 2: 3 , 5 - d i - O - m e t h y l e n e - 6 - O - t o s y l - a - D - g l u c o f u r a n o s e 22. T h i n l a y e r chromatography ( t o l u e n e : e t h e r - 1 : 2 ) i n d i c a t e d the r e a c t i o n t o be e s s e n t i a l l y complete a f t e r two h o u r s . A f t e r the workup, as d e s c r i b e d i n the e x p e r i m e n t a l s e c t i o n , a w h i t e c r y s t a l l i n e m a t e r i a l was o b t a i n e d which p r o v e d , upon p.m.r. s p e c t r a l a n a l y s i s , t o be t r i p h e n y l ( 1,2:3,5-di-O-methylene-a - D - g l u c o f u r a n o s e ) 6 - C - s t a n -nane, 2_5. There were no r e s o n a n c e s w h i c h c o u l d be a s s i g n e d t o a .30-FIGURE 3 C-Stannylated carbohydrates, synthesized for this work, and their precursors. -31-t o s y l a t e s u b s t i t u e n t , a nd t h e a r o m a t i c r e g i o n o f t h e s p e c t r u m now i n t e g r a t e d f o r t h r e e p h e n y l s u b s t i t u e n t s . I t h a s g e n e r a l l y 37-39 b e e n f o u n d t h a t a t t a c h i n g a t i n s u b s t i t u e n t t o a c a r b o n atom c a u s e s t h e p r o t o n ( s ) on t h a t c a r b o n atom t o r e s o n a t e a t q u i t e h i g h f i e l d s — u s u a l l y T 7-9. T h u s , f o r 2_2_, t h e p.m.r. r e s o n a n c e s a s s i g n e d t o t h e H-6 p r o t o n s a r e a t c a . x 6 . 6 5 ( b e n z e n e - d g s o l u t i o n ) , w h e r e a s f o r 25_ t h e y w e r e a t c a . x8.5 (benz e n e - d g s o l u t i o n ) . T h i s l a r g e u p f i e l d s h i f t o f t h e r e s o n a n c e s o f t h e p r o t o n s d i r e c t l y a d j a c e n t t o a t i n s u b s t i t u e n t was t h e r e f o r e u s e d i n t h i s work as a p r e l i m i n a r y " d i a g n o s t i c t e s t " t o d e t e r m i n e w h e t h e r o r n o t a t i n -s u g a r compound h a d a c t u a l l y b e e n o b t a i n e d . H a v i n g s u c c e s s f u l l y o b t a i n e d a p r i m a r y t i n s u g a r , a t t e n t i o n was n e x t t u r n e d t o t h e s y n t h e s i s o f s e c o n d a r y t i n s u g a r s . S t e i n e r " " h a d p e r f o r m e d a number o f s u c c e s s f u l e x p e r i m e n t s i n w h i c h e p o x i d e s c i s s i o n was e f f e c t e d by l i t h i u m d i p h e n y l p h o s p h i n e . I n t h i s manner, a number o f s e c o n d a r y d i p h e n y l p h o s p h i n e o x i d e s u g a r s were o b t a i n e d . He h a d a l s o r e a c t e d t r i p h e n y l t i n l i t h i u m w i t h one e p o x i d e , tntikjl ~ acetyl- 2, 3 - a n h y d r o - 8 - L - r i b o p y r a n o s i d e 2_8, t o f o r m t r i p h e n y l (methyl 4~0 -Acetyl - 3 - L - x y l o p y r a n o s i d e ) 3 - C - s t a n n a n e _29 and s u b s e q u e n t l y f o r m e d t r i p h e n y l ( m e t h y l 2 , 4 - d i - 0 - a c e t y 1 - B - L - x y l o p y r a n o s i d e ) 3 - C - s t a n n a n e 30, u s i n g t h e a c e t i c a n h y d r i d e - p y r i d i n e method — a l b e i t i n r a t h e r low o v e r a l l y i e l d — 21%. -32-28 29_ 30 F o r t h i s work, t h e r e f o r e , i t was d e c i d e d t o a t t e m p t t h e syn-• t h e s i s o f s e c o n d a r y s u g a r - t i n d e r i v a t i v e s toy r e a c t i n g e p o x i d e s w i t h t h e t r i p h e n y l t i n l i t h i u m r e a g e n t . M e t h y l 2,3-anhydro-4,6-O-benzylidene- a - D - a l l o p y r a n o s i d e 2_3 was r e a c t e d w i t h t r i p h e n y l t i n l i t h i u m . The r e a c t i o n appeared t o be complete a l m o s t i n s t a n t a n e o u s l y . A f t e r t h e u s u a l workup, a w h i t e powdery m a t e r i a l was o b t a i n e d and i d e n t i f i e d as t r i p h e n y l ( m ethyl 4 , 6 - O - b e n z y l i d e n e - a - D - a l t r o p y r a n o s i d e ) 2-C-stannane, 26, the p.m.r. sp e c t r u m showing t h e c o r r e c t number o f p r o t o n s f o r an e p o x i d e s c i s s i o n . The a r o m a t i c r e g i o n o f the s p e c t r u m i n t e g r a t e d f o r the Zo p h e n y l p r o t o n s and the resonances a s s i g n e d t o H-2 were a t f a i r l y h i g h f i e l d , T 6.93. E l e m e n t a l a n a l y s i s c o n f i r m e d t h a t 26_ had i n d e e d been o b t a i n e d . S i m i l a r l y , m e t h y l 2 , 3 - a n h y d r o - 4 , 6 - O - b e n z y l i d e n e - a -D-mannopyrano-s i d e 2_4 was r e a c t e d w i t h t r i p h e n y l t i n l i t h i u m t o form t r i p h e n y l ( m ethyl 4 , 6 - O - b e n z y l i d e n e - a - D - a l t r o p y r a n o s i d e ) 3-C-stannarie 27. -33-A g a i n , i d e n t i f i c a t i o n o f t h i s p r o d u c t was e f f e c t e d by p.m.r., i n l i k e manner t o t h a t o f _26. F u r t h e r d i s c u s s i o n o f the "*"H as w e l l 13 as the C s p e c t r a l d a t a o f t h e s e compounds w i l l be found xn p a r t (b) o f t h i s c h a p t e r . Some v e r y p r e l i m i n a r y a t t e m p t s were made t o a s c e r t a i n whether o r n o t t r i p h e n y l t i n s u g ars can be d e r i v a t i z e d . I t was d e c i d e d t o f i r s t attempt the removal o f t h e a c i d - s e n s i t i v e b e n z y l i d e n e b l o c k i n g group o f 26. The t r i p h e n y l t i n - c a r b o n bond, i t was d i s c o v e r e d , i s q u i t e l a b i l e t o a c i d . A number o f a c i d i c systems were t r i e d , i n -c l u d i n g r e s i n s ( a m b e r l i t e IR 120), 5% t r i f l u o r o a c e t i c a c i d i n c h l o r -oform, boron t r i f l u o r i d e i n e t h e r and 10% a c e t i c a c i d i n met h a n o l . I n every c a s e , t . l . c . ( t o l u e n e : e t h e r - 1 : 2 ) i n d i c a t e d t h a t t h e t i n -carbon bond was c l e a v e d t o some e x t e n t , however the l a t t e r system seemed t o be b e s t , i n t h a t r e m o v a l o f the b e n z y l i d e n e group appeared t o be ca. 80%, l e a v i n g a p p r o x i m a t e l y 90% o f the c a r b o n - t i n bonds i n t a c t . However, as the r e a c t i o n had been done on t h e e q u i v a l e n t o f a 2-deoxy s u g a r , the m e t h y l g l y c o s i d e was a l s o removed and, due t o s i d e r e a c t i o n s , p o s i t i v e i d e n t i f i c a t i o n o f t h e main f i n a l p r o d u c t p r o v e d d i f f i c u l t w i t h o u t t i m e consuming p u r i f i c a t i o n p r o -c e d u r e s . F u r t h e r work i s i n t e n d e d i n t h i s a r e a , p o s s i b l y on the 3-deoxy sug a r 27_ i n w h i c h , i t i s hoped, t h e m e t h y l g l y c o s i d e l i n k a g e i s not q u i t e so l a b i l e as t h a t o f 2&. 13 Work by S t e i n e r x n d x c a t e s t h a t t h e t r i p h e n y l t i n - c a r b o n bond i s l e s s l a b i l e i n a b a s i c medium th a n i n an a c i d i c medium. Thus, he was a b l e t o e f f e c t the a c e t i c a n h y d r i d e - p y r i d i n e a c e t y l a t i o n , p r e v i o u s l y mentioned, on 7P[_ t o form 30. -34-T h i s work has d emonstrated t h a t s u g a r - t i n d e r i v a t i v e s h a v i n g a s t a b l e c a r b o n - t i n bond can be s y n t h e s i z e d . I t has a l s o i n d i c a t e d t h a t t h e r e i s p o t e n t i a l f o r d e r i v a t i z i n g t h e s e compounds. T h i s augurs w e l l f o r f u t u r e r e s e a r c h i n t h e a r e a , as o r g a n o t i n d e r i v a -t i v e s have, i n t h e l a s t decade o r s o , become i n c r e a s i n g l y impor-t a n t , i n d u s t r i a l l y . They a r e used, among o t h e r t h i n g s , f o r wood p r e s e r v a t i o n , i n f o o d p a c k a g i n g (as p.v.c. s t a b i l i s e r s ) , i n m a r i n e a n t i f o u l i n g p a i n t s and as f u n g i c i d e s . Sugars have the u s e f u l p r o -p e r t y o f b e i n g w a t e r s o l u b l e , o r when s u i t a b l y d e r i v a t i z e d , s o l u b l e i n o r g a n i c media, and may be e x p e c t e d t o c o n f e r such p r o p e r t i e s on t h e i r o r g a n o t i n d e r i v a t i v e s . They a r e cheap, many a r e b i o -l o g i c a l l y i m p o r t a n t and t h e i r p olymers a r e w e l l known. G i v e n t h i s , i t i s s p e c u l a t e d t h a t o r g a n o t i n s u g a r s c o u l d become i n d u s t r i a l l y and, p e r h a p s , m e d i c a l l y i m p o r t a n t s u b s t a n c e s . -35-b) N.M.R. S p e c t r a and c o n f o r m a t i o n a l p r o p e r t i e s 1 13 H and C n.m.r. d a t a were p r i n c i p a l l y used t o e v a l u a t e the gr o s s and c o n f i g u r a t i o n a l s t r u c t u r e s o f the p r o d u c t s . As w i l l be shown, the i n f o r m a t i o n thus o b t a i n e d p r o v e d i m p o r t a n t i n e v a l u a t i n g 13 the s i g n i f i c a n c e o f the C-Sn c o u p l i n g s . The p.m.r. spectrum o f compound 25 and t h a t o f 22 show a l m o s t i d e n t i c a l c o u p l i n g s and s h i f t s f o r t h e r i n g p r o t o n s . ( S e e T a b l e 3) H N.M.R. H 22 25 -36-—r— 2 H-l 0 H X 0 H 0 H iH-5 H-3 H-2 H-4 H-6's 4 6 9 T C 6 H 6 ~T~ 2 3 H-l 0 H X 0 H - J ro 10 i -OH 9 T FIGURE 4 H n.m.r. spectra of triphenyl(1,2:3,5-di-O-methylene-a-D-glucofuranose) 6-C-stannane 25_ (top) and 1,2 :3 ,5-di-O-methylene-a-D-glucofuranose _3|_ (bottom) in deuteriobenzene solution. C * - impurity) TABLE 3 C h e m i c a l s h i f t s ( T v a l u e s ) and m u l t i p l e t s p l i t t i n g s (Hz) f o r 4 , 6 - 0 - b e n z y l i d e n e -a - D - a l t r o p y r a n o s i d e s and 1,2:3,4-di-0-methylene- a-D-glucofuranoses i n d e u t e r i o -benzene s o l u t i o n s Cornoound H - l H-2 H-3 H-4 H-5 H-6 H-6' OMe A r o m a t i c B e n z y l P r o t o n s P r o t o n 25 26 27 4.14 5.75 6.05 6.32 5.59 8.37 8.68 2.6 J., „3.8 J„ , 0 J , .2.4 J . c2.3 J c c11.3 J , ,,-13.3 J c 6.1 1,2 2,3 3,4 4,5 5, 6 6,6 5,6 4. 82 6.93 5.14 6.01 5. 47 5. 65 6.23 7.35. 2.48 4.64 J n „ .5 J - ,2.6 J , .2.5 J . ,-9.1 J , , 4.7 J , ,,-10.3 J c ,, 8.8 1,2 2,3 3,4 4,5 5,6 6,6 5,6 5.63 8.58 7.26 5.55 6.03 6.45 6.09 7.19 2.80-2.17 4.57 J , 0 0 J„ ,2.1 J , .5.9 J„ .8.8 J _ c11.4 J , ,,-11.8 J c ,, 4.8 1,2 2,3 3,4 4,5 5,6 6,6 5,6 31 32 33 4.14 5.59 5.96 6.21 6.07 6.65 J , -3.75J- , 0 ,2.6 J , c1.9 J c , 5.3 J.. c l - 6 J c c , 0 1,2 2,3 3,4 4,5 5,6 6,6 5,6 6.34- 6.62 5.78 6.11 5.77 5.76 7.07 7.57 2.8 4.55 J , 0 0 J , ,3 J , .2.9 J . c9.2 J _ , 5 J , ,,-11.5 J . c,11.7 1,2 2,3 3,4 4,5 5,6 6,6 5,6 5.48 6.07 6.33 5.9 5.49 6.31 5.71 6.48 2.60 4.56 e i J n _ 0 J 0 - 3 J , . 2 . 9 J , c9.5 J j. c 1 0 . 2 J , ,,-10.2 J _ ,, 5.3 6.71 1,2 2,3 3,4 4,5 5,6 6,6' 5,6' •38-TABLE. 3 CON'T. 0. yW 31 and 5.60. Q / V H x 5 . b , -in -r = 8 . 7 Hz. -OH T 6.38, ^ 0H,3 = 3.6 Hz. c -OH T 5 . 8 4 , J Q H F 2 a °X" ^5.25. 5.33. 5-"' , 2 - 8 3 ' e -OH x5.82, J 0 H f 2 X 4 , 7 " -39-Thus, i t i s assumed t h a t 25 has v e r y n e a r l y t h e same s t r u c t u r e and 43 c o n f o r m a t i o n as 2 2. However, the c h e m i c a l s h i f t s o f the C-6 p r o t o n s and t h e coup-l i n g s J,. ' , J _ ' and J a f o r 22 d i f f e r s i g n i f i c a n t l y from t h o s e o f 2_5. As p r e v i o u s l y d i s c u s s e d , t h e u p f i e l d s h i f t s e x p e r i e n c e d by t h e C-6 p r o t o n resonances o f 25 r e l a t i v e t o t h o s e o f 2_2_, a r e known t o o c c u r when a t i n s u b s t i t u e n t r e p l a c e s a more e l e c t r o n e g a -t i v e s p e c i e s , such as t h e t o s y l a t e m o i e t y o f 22. I n g e n e r a l , o n l y t h e resonances of those p r o t o n s a t o t h e t i n s u b s t i t u e n t e x p e r i e n c e 44 s i g n i f i c a n t changes i n c h e m i c a l s h i f t . A l t h o u g h one may be tempted t o base th e d i f f e r e n c e s between the v i c i n a l c o u p l i n g s , J,- g and J,, g,, o f 22 and 25 s o l e l y on d i f f e r i n g p o p u l a t i o n s o f C ^ - C g ' r o t a m e r s , i t must be remembered t h a t the v i c i n a l p r o t o n c o u p l i n g c o n s t a n t s depend on s e v e r a l f a c -t o r s o t h e r than d i h e d r a l a n g l e — one o f the most i m p o r t a n t , i n t h i s c a s e , b e i n g t h e i n v e r s e v a r i a t i o n o f c o u p l i n g c o n s t a n t s w i t h the e l e c t r o n e g a t i v i t y o f the a t t a c h e d s u b s t i t u e n t s . 4 5 ' S i n c e t h e r e has n o t been found a s i m p l e c o r r e l a t i o n between e l e c t r o n e g a -t i v i t y o f s u b s t i t u e n t s and c o u p l i n g c o n s t a n t s 4 7 , and s i n c e o t h e r f a c t o r s such as C-C bond l e n g t h and H-C-C bond a n g l e may c o n t r i b u t e 4 8 t o the s i z e s o f the c o u p l i n g c o n s t a n t s , i t was d e c i d e d n o t t o attempt the e x a c t c a l c u l a t i o n o f d i h e d r a l a n g l e s from c o u p l i n g c o n s t a n t s , b u t t o s i m p l y e s t i m a t e r o tamer p o p u l a t i o n s on t h e b a s i s o f whether o r not the p r o t o n c o u p l i n g s a r e " l a r g e " o r " s m a l l " . W i t h the a i d o f Newman p r o j e c t i o n s , one may v i s u a l i z e t h r e e n o n - e c l i p s e d rotaraers f o r the C^-C^ bond: -40 A B C I t w i l l be assumed t h a t t h e s e , o r c o n f o r m a t i o n s v e r y c l o s e t o them, are e n e r g e t i c a l l y the most f a v o r e d r o t a m e r s . The l a r g e v a l u e o f g would c o r r e s p o n d , i f one were t o i n v o k e the K a r p l u s 49 e q u a t i o n , t o a t r a n s a n t i - p a r a l l e l r e l a t i o n s h i p between th e C.--HV and t h e C,-H_ bonds, whereas t h e s m a l l e r v a l u e o f J r ,, D O 6 6 5,6 would c o r r e s p o n d t o a gauche r e l a t i o n s h i p f o r t h o s e bonds. From thes e d a t a , i t was t h e r e f o r e assumed t h a t the p r e f e r r e d C^-C^ r o t a mer f o r 25_ i s e i t h e r rotamer A o r C. E x a m i n a t i o n o f m o l e c u l a r models l e a d s t o the c o n c l u s i o n t h a t rotamer A i s p r o b a b l y f a v o r e d w i t h r e s p e c t t o rotamer C, as t h e r e appears t o be a s t e r i c i n t e r -a c t i o n between the b u l k y t r i p h e n y l t i n m o i e t y and the s u g a r r i n g f o r rotamer C, w h i c h does n o t e x i s t i n rotamer A. P r o t o n - p r o t o n v i c i n a l c o u p l i n g c o n s t a n t s and c h e m i c a l s h i f t d a t a were used t o i d e n t i f y t h e s t r u c t u r e and c o n f o r m a t i o n o f the - 4 1 -p r o d u c t o b t a i n e d from the r e a c t i o n o f t r i p h e n y l t i n l i t h i u m w i t h 23. As p r e v i o u s l y s t a t e d , i n t e g r a t i o n o f the p.m.r. spe c t r u m o f 26 as w e l l as t h e f a c t t h a t t h e H-2 resonance l i e s a t h i g h f i e l d i n d i c a t e d t h a t the t r i p h e n y l t i n l i t h i u m had i n d e e d e f f e c t e d an epo x i d e s c i s s i o n and t h a t the t r i p h e n y l t i n m o i e t y was now bonded t o C-2. S i n c e b o t h the a l i o - ( 2 3 ) and manno-(2 4) e p o x i d e d e r i v a t i v e s a r e t r a n s - f u s e d 4 , 6 - 0 - b e n z y l i d e n e - h e x o p y r a n o s i d e systems, they e x i s t i n a r i g i d c o n f o r m a t i o n . As a r e s u l t o f t h i s r i g i d i t y , and the s t e r e o e l e c t r o n i c pathway f a v o u r e d f o r e p o x i d e o p e n i n g , t h e r e a c t i o n p r o d u c t s s h o u l d be t r a n s - d i a x i a l . T h i s was c o n f i r m e d by t h e s m a l l J2 3 v a l u e , o b t a i n e d from the p.m.r. spectrum o f 26, t y p i c a l o f an e q u a t o r i a l - e q u a t o r i a l p r o t o n - p r o t o n c o u p l i n g . -42-A r a t h e r e x t e n s i v e s t u d y o f c o n f o r m a t i o n s and p r o t o n - p r o t o n c o u p l i n g c o n s t a n t s o f some m e t h y l 4,6-0-benzylidene-a-D-hexopyrano-" _ 50 s i d e s , i n c l u d i n g a l t r o p y r a n o s i d e s , has been r e p o r t e d by Coxon The v a l u e s o f 2 , J ] _ 3' J 2 3 a n < ^ J 3 4' w I l ^ c ^ n e o b t a i n e d , sup-p o r t e d the assignment o f the c h a i r c o n f o r m a t i o n t o t h e p y r a n o i d r i n g f o r a l l the c o n f i g u r a t i o n s examined, and a s m a l l J . _ v a l u e 1 , 2 (0.6-1.7 Hz) was found t o be c h a r a c t e r i s t i c o f e q u a t o r i a l H^-equa-t o r i a l H^ p r o t o n arrangements i n t h e s e compounds, whereas a some-what l a r g e r 2 v a l u e (3.3-3.8 Hz) was c h a r a c t e r i s t i c o f the e q u a t o r i a l H ^ - a x i a l H 2 arrangement. T h i s was t r u e f o r t h e a l t r o -p y r a n o s i d e s , even i n t h e 2- and 3-deoxy c a s e s . 2 f o r 2_6_ i s v e r y s m a l l (0.5 Hz) . I n a d d i t i o n , t h e o t h e r c o u p l i n g s o b t a i n e d from t h e p.m.r. spectrum were c o m p a t i b l e w i t h t h e v a l u e s g i v e n by Coxon f o r 2 - d e o x y - 4 , 6 - 0 - b e n z y l i d e n e - a - D - a l t r o -p y r a n o s i d e s and hence w i t h a c h a i r c o n f o r m a t i o n , i l l u s t r a t e d i n f i g u r e 5 ( a ) . D e t e r m i n a t i o n o f t h e c o n f o r m a t i o n o f 21_, however, was n o t q u i t e so s t r a i g h t f o r w a r d . As a n t i c i p a t e d , t h e p.m.r. spectrum o f t h e p r o d u c t o b t a i n e d from t h e r e a c t i o n o f t r i p h e n y l t i n l i t h i u m w i t h 2_4 d i s p l a y e d t h e c o r r e c t number of p r o t o n s t o be the e p o x i d e s c i s s i o n p r o d u c t 2_7. T h a t t h i s was i n d e e d the p r o d u c t was c o n f i r m e d by t h e appearance o f the H-3 resonance a t q u i t e h i g h f i e l d ( T 7 . 2 6 ) , i n d i c a t i n g the t r i p h e n y l t i n group was now bonded t o c a r b o n 3. Owing t o the a f o r e m e n t i o n e d f a c t t h a t o n l y a t r a n s d i a x i a l r i n g o p e n i n g i s p o s s i b l e , i t was assumed t h a t the v i c i n a l ^H-^H c o u p l i n g s would i n d i c a t e H - l , H-2 and H-3 t o be i n e q u a t o r i a l p o s i t i o n s . Indeed, 2 was a p p r o x i m a t e l y z e r o and J-> 3 a p p r o x i m a t e l y 2.1 Hz, -44-compared to J 1 2 of 0.9 to 1.1 Hz and J 2 3 of 2.5 to 2.7 Hz for model 3-deoxy altropyranosides studied by Coxon. Models made of 27, however, indicated that there could be a c e r t a i n amount of s t e r i c i n teraction between the t r i p h e n y l t i n moiety and the monosaccharide. This may account for the s l i g h t l y low value of J , . I t i s assumed that the 3 values f o r Coxon's model altropyranosides indicate a diequatorial arrangement for H-2 and H-3. The value of J , ,, ca 2 Hz, for 27 could indicate this d i e q u a t o r i a l arrangement or an a x i a l H-3 - equatorial H-2 arrangement. If the l a t t e r i s true f o r 27, i n d i c a t i n g a d i s t o r t i o n of the sugar ri n g due to s t e r i c i n t e r -actions, then the dihedral angle between H-3 and H-4, as determined by models, should be quite small and ^ quite large. This appears to be so, J 3 4 being 5.9 Hz for 2_7, compared to a j " 3 4 -45-v a l u e o f 2.5 Hz f o r 26. I t was t h e r e f o r e c o n c l u d e d t h a t 2_7 assumed a skew c o n f o r m a t i o n , as shown i n f i g u r e 5 ( b ) . T h i s c o n c l u s i o n seems t o be i n a c c o r d w i t h t h e p r o t o n s h i f t d a t a d i s c u s s e d e a r l i e r i n t h i s s e c t i o n : t h u s , ' w h e r e a s t h e H-3 r e s o n a n c e o f 26 a p p e a r s t o have a n o r m a l s h i f t , t h e H-2 r e s o n a n c e o f 2_8 i s s h i f t e d s i g n i f i c a n t l y ( c a 2 ppm.) t o h i g h f i e l d . A p l a u s i b l e e x p l a n a t i o n f o r t h i s s h i f t i s b a s e d o n a s t e r i c i n t e r a c t i o n b e t w e e n one o f t h e p h e n y l g r o u p s o f t h e 03Sn m o i e t y w i t h t h e r i n g w h i c h w o u l d p o s i t i o n t h e C-H2 bond above j=>\4ne o~f ~fke -phenyl r i n g and h e n c e a l l o w f o r t h e r i n g c u r r e n t -e f f e c t o f t h e p h e n y l s u b s t i t u e n t . HETERONUCLEAR N;M,R. PARAMETERS 117 T i n has 10 s t a b l e i s o t o p e s and o f t h e s e Sn (7.54%, I=H) 119 a n d Sn (8.62%, l=h) a r e o f p r i n c i p a l i n t e r e s t h e r e . From t h e . n.m.r. s t a n d p o i n t , any o r g a n o t i n d e r i v a t i v e c o n s i s t s o f a m i x t u r e o f t h r e e * s e p a r a t e s p e c i e s w h i c h g i v e o v e r l a p p i n g n.m.r. s p e c t r a . 1 13 The H ( o r C) n.m.r. resonances o f t h o s e m o l e c u l e s (83.28%) w h i c h b e a r a n o n m a g n e t i c t i n i s o t o p e w i l l g i v e a n o r m a l n.m.r. s p e c t r u m . The m o l e c u l e s w h i c h a r e s u b s t i t u t e d by a " ^ 7 S n o r ^"^Sn i s o t o p e w i l l g i v e more comp l e x s p e c t r a i n «->hich 4 he. resonances crfi^ose pfofen: 13 ' ' ( o r C) n u c l e i w h i c h a r e s p i n c o u p l e d w i t h t h e m e t a l w i l l a p p e a r as s a t e l l i t e s l o c a t e d s y m m e t r i c a l l y on e i t h e r s i d e o f t h e c o r r e s -p o n d i n g r e s o n a n c e s o f t h e m o l e c u l e s w h i c h b e a r a n o n m a g n e t i c *Of c o u r s e , t h i s i g n o r e s t h e many i s o t o p e " i m p u r i t i e s " a s s o c i a t e d w i t h t h e n a t u r a l a b u n d a n c e o f ^C, ^11, e t c . -46-FIGURE 6 Natural abundance 1 - 5 C n.m.r. spectrum of t r i m e t h y l t i n c h l o r i d e i n deuteriobenzene s o l u t i o n , (ca 0.1M) (PW 30°; NT 53,000; AT 1.023 sec; PD 0; SE -0.4). The peaks marked * are. spinning side bands. -47-n u c l e u s . Those r e s o n a n c e s w h i c h a r e n o t s p i n c o u p l e d t o the m e t a l w i l l be i d e n t i c a l w i t h t h o s e o f t h e m o l e c u l e s w h i c h have a m a g n e t i c a l l y i n e r t t i n n u c l e u s . (See f i g . 6) (1) ^H-Sn c o u p l i n g s I n g e n e r a l , i n d i r e c t Sn-^H s p i n - s p i n c o u p l i n g c o n s t a n t s , w i t h p r o t o n s i n a l k y l g r o u p s , a r e o f t h e o r d e r o f 50-100 Hz w i t h 37_3i J(Sn-BCH) b e i n g l a r g e r t h a n , and o f o p p o s i t e s i g n t o , J( S n - a C H ) . I t was f o u n d f o r the p r o t o n s p e c t r a o f t h e t h r e e o r g a n o t i n com-pounds examined t h a t t h e low d i s p e r s i o n o f the main band sp e c t r u m 119 117 r e s u l t e d i n o v e r l a p s w h i c h o b s c u r e d t h e Sn and Sn s a t e l l i t e s and, as a r e s u l t , v e r y l i t t l e u s e f u l d a t a c o u l d be o b t a i n e d from t h e ^H-Sn c o u p l i n g s . 13 S i n c e C i n v e s t i g a t i o n s a r e p a r t i c u l a r l y s u i t e d t o the d e t e r -m i n a t i o n o f s t r u c t u r e , c o n f o r m a t i o n , and s t a t e o f t i n h y b r i d i z a t i o n i n o r g a n o t i n s because s i g n a l s o f i n t e r e s t can e a s i l y be r e s o l v e d and no second o r d e r a n a l y s i s i s n e c e s s a r y , i t was d e c i d e d t o exa-13 mine t h e C s p e c t r a o f t h e s e compounds w h i c h happened t o p r o v i d e an i d e a l c o n f o r m a t i o n a l c h a l l e n g e . (2) 1 3 C n.m.r. S p e c t r a l a s s i g n m e n t s were p r i m a r i l y based on s e l e c t i v e p r o t o n d e c o u p l i n g e x p e r i m e n t s . (See Appendix! ( i ) c h e m i c a l s h i f t s 13 C c h e m i c a l s h i f t d a t a f o r d e r i v a t i v e s 25, 26 and 2_7 a r e r e p o r t e d i n T a b l e 4. F o r co m p a r i s o n , the c h e m i c a l s h i f t d a t a f o r -48-H-5 FIGURE 7 Fourier transform H n.m.r. spectrum of triphenyl(4,6-0-benzylidene-a-D-altropyranoside)2-C-stannane 26 showing spectral assignments and *H-Sn couplings. (ca 0.3M) (PW 90°; PD 2 sec; AT 4 sec; NT 100.) -49-compounds 3_1, 1, 2 : 3, 5 - d i - 0 - m e t h y l e n e - a - D - g l u c o f u r a n o s e , 3_2, m e t h y l 4, 6-0-benzylidene-2-O-methy 1 - a - D - a l t r o p y r a n o s i d e and 33_, m e t h y l 4 , 6 - 0 - b e n z y l i d e n e - 3 - 0 - m e t h y l - a - D - a l t r o p y r a n o s i d e , are a l s o i n c l u d e d . Due t o t h e f a c t t h a t . 34, m e t h y l 4, 6-0-benzy l i d e n e - c t - D - a l t r o p y r a n o -s i d e , i s o n l y s l i g h t l y s o l u b l e i n benzene, i t was n o t p o s s i b l e t o 13 o b t a i n a C n.m.r. spe c t r u m w i t h a s u f f i c i e n t s i g n a l - t o - n o i s e r a -13 t i o t o a l l o w f o r assignment o f t h e C s i g n a l s , t h e r e f o r e compounds 32 and 3_3 were used as model compounds. The d i f f e r e n c e i n c h e m i c a l s h i f t between a c a r b o n bonded t o an -OMe group and an e q u i v a l e n t 51 carbon bonded t o a h y d r o x y l group i s ca 10 ppm. U s i n g t h e d a t a 13 13 o b t a i n e d from the C s p e c t r a o f 3_2 and 33, the C c h e m i c a l s h i f t s o f 3_4 were e s t i m a t e d and compared t o t h o s e o f t h e 2-deoxy-(26) and 3-deoxy-(2 7) t i n s u g a r s . As can be seen from t h e d a t a r e p o r t e d i n T a b l e 5, s u b s t i t u t i o n o f a h y d r o x y l group by a t r i a r y l t i n -group r e s u l t s i n s h i f t s o f the a - , o r g e m i n a l , c a r b o n r e s o n a n c e s o f from 32 t o 43 ppm. u p f i e l d . The y- r e s o n a n c e s h i f t s were s m a l l and, w i t h one e x c e p t i o n , t o lower f i e l d . The s h i f t s o f t h e 3 - r e s o n a n c e s were a l s o s m a l l — however, l e s s p r e d i c t a b l e , r a n g i n g i n s i z e from a d o w n f i e l d s h i f t o f 2 ppm. t o an u p f i e l d s h i f t o f 2 ppm. 13 52 53 F o r C s p e c t r a o f o r g a n o t i n d e r i v a t i v e s K u i v i l a ' f o u n d t h a t , i n g e n e r a l , l a r g e c h e m i c a l s h i f t v a r i a t i o n s a r e o n l y o b s e r v e d f o r carbons a t o t h e t i n and t h a t s u b s t i t u t i o n o f a p r o t o n by a t r i a l k y l t i n group produces an u p f i e l d s h i f t f o r the r e s o n a n c e s of t h e d i r e c t l y bonded c a r b o n . The y-nuclei u s u a l l y r e s o n a t e a t lower f i e l d s e x c e p t where t h e r e i s a p p r e c i a b l e s t e r i c s t r a i n , w h i l e th e B resonances undergo r e l a t i v e l y c o n s t a n t s h i f t s o f a p p r o x i m a t e l y 3.5 t o 4.5 ppm. t o lower f i e l d s . J A , p 6 H 5 0 H C-1 C-2 C-3 C-4 C-5 C-6 0 H X 0 H C-l o i ro o i cn •N o I 0~> Si A i 1 i 1 i 1 i 1 i 1 i 1 ! •"' i ' ! 1 i ' j ' | ' i ' i • i ' ; —r~I 150 IOO 5 0 ppm o 13 FIGURE 8. Natural abundance C n.m.r. spectra of A triphenyl(1,2:5,5-di-O-methylene-ct-D-glucofuranose) 6-C-stannane 25_ and B l,2:3,5-di-O-methylene-a-D-gTucofuranosc 3i_ in deuteriobenzene solution. T e a . 0.3M). (PW 30°; NT 53,000; AT 1.023 s e c ; PD 0.) TABLE 4 C c h e m i c a l s h i f t s (p.p.m.) f o r 4 , 6 - O - b e n z y l i d e n e - a - D - a l t r o p y r a n o s i d e s and 1 , 2 : 3 , 4 - d i - 0 - m e t h y l e n e - a - D - g l u c o f u r a n o s e s i n d e u t e r i o b e n z e n e s o l u t i o n s Compound C-•1 C-•2 C-3 C-•4 C-5 C-6 -OCH 3 0- /H O'^H B e n z y l 25 105. 09 83. 59 75. 39 80. 68 71.47 14.95 96.33 85.79 26 101. 91 38. 61 69. 37 79. 19 59. 32 68.64 54. 76 102.41 27 101. 1 70. 81 35. 29 77. 15 64. 32 69.35 53.74 100.56 31 104. 83 84. 16 76.80 75. 90 73.53 62.02 96.37 87.. 32 32 99. 84 80. 03 66. 99 77. 19 58.59 69.43 57. 76 54.93 102.34 33 102. 33 69. 78 78. 78 77. 64 59.18 69. 72 59.45 . .54...9.8 102.62 34 ( e s t i m a t e d ) 102. 33 70. 00 67.00 77. 19 58-59 69.50 • 33 34 Our d a t a appears t o be i n a c c o r d v / i t h K u i v i l a ' s f o r t h e s h i f t s o f t h e a- and Y-carbon r e s o n a n c e s , b u t not f o r t h o s e o f t h e 3 - c a r b o n r e s o n a n c e s . I t i s b e l i e v e d t h a t t h i s l a c k o f agreement d e r i v e s from the f a c t t h a t we used a t r i a r y l t i n , r a t h e r t h a n a t r i a l k y l t i n m o i e t y w h i c h , depending upon the d i s p o s i t i o n o f the 3-carbon w i t h r e s p e c t t o the a r o m a t i c r i n g s o f the t r i p h e n y l t i n group, c o u l d produce an u p f i e l d r a t h e r t h a n a d o w n f i e l d s h i f t o f t h e 3-carbon r e s o n a n c e , by t h e r i n g c u r r e n t e f f e c t . A s t u d y o f t h e s e same s u g a r s s u b s t i t u t e d by t r i m e t h y l t i n , r a t h e r t h a n t r i p h e n y l t i n groups would shed more l i g h t on the e f f e c t o f the r i n g c u r r e n t o f the t r i p h e n y l -t i n group on the c h e m i c a l s h i f t s o f c a r b o n , as w e l l as t h e p r o t o n r e s o n a n c e s . TABLE 5 C c h e m i c a l s h i f t d i f f e r e n c e s (p.p.m.) 6 - 6 f o r Sn OH 4 , 6 - O - b e n z y l i d e n e - a - D - a l t r o p y r a n o s i d e s and 1,2:3,4-di-0-m e t h y l e n e - a - D - g l u c o f u r a n o s e s Compound a 6 Y 25 -47.07 -2. 06 + 4. 78 26 ( v a l u e s t o n e a r e s t ppm) -31 C-1 C-3 0 + 2 + 2 27 ( v a l u e s t o n e a r e s t ppm) -33 C-2 C-4 + 1 0 C-1 -1 C-5 +6 I Cn co l -54-13 ( i x ) C-Sn c o u p l i n g c o n s t a n t s 13 119 Up t o 19 73, the d a t a r e p o r t e d on C c o u p l i n g s t o Sn had 54-56 57 been l i m i t e d m a i n l y t o s i m p l e a l i p h a t i c and p h e n y l d e r i v a t i v e s However, s i n c e t h e n , a number o f r e s e a r c h groups have s y s t e m a t i c a l l y i n v e s t i g a t e d many o t h e r t y p e s o f o r g a n o t i n d e r i v a t i v e s -- i n c l u d i n g 52 53 58 c y c l i c and u n s a t u r a t e d o r g a n o t i n compounds. ' ' C o u p l i n g s t h r o u g h one t o f o u r bonds have been examined, and t h e r o l e o f c a r b o n o r b i t a l h y b r i d i z a t i o n and d i h e d r a l a n g l e (3-bond c o u p l i n g s ) have 52 5 3 been i n v e s t i g a t e d . ' The magnitude o f the d i r e c t bond c o u p l i n g £ ("*""^Sn-^3C) J i s i n f l u e n c e d by the h y b r i d i z a t i o n o f the t i n and o f t h e d i r e c t l y 53 a t t a c h e d c a r b o n atoms. F o r c y c l o a l k y l d e r i v a t i v e s o f t i n , K u i v i l a found t h a t [j 1 J 1 1 9 S n - l 3 C ) J i s g e n e r a l l y l a r g e r (503-390 Hz) th a n f o r a c y c l i c compounds (320-314 H z ) , and t h a t i n a l l c a s e s p"J(Sn-1 3 c ) -P3 3 "1 i s larger than J(Sn- CM which, i n turn, i s larger th an 2 13 J (Sn- C) 55 1 1 3 I t i s known t h a t J ( C-Sn) i s p o s i t i v e and 2 . . . . J (C-Sn) n e g a t i v e , f o r a l l a l k y l t i n compounds. I n r i g i d o r g a n o t m s , t h e v i c i n a l c o u p l i n g c o n s t a n t s show a K a r p l u s t y p e v a r i a t i o n (see F i g u r e 9 ) : J = 30.4 - 7.6 cos 9 + 25.2 cos 2 9 59 where 9 i s t h e d i h e d r a l a n g l e . I n a l i p h a t i c o r g a n o t i n d e r i v a t i v e s , the v a l u e s o f the v i c i n a l "^C-^^Sn c o u p l i n g s i n d i c a t e a f l e x i b l e m o l e c u l a r framework w i t h 5 3 a p r e f e r e n c e f o r c e r t a i n c o n f o r m a t i o n s . 3 13 I t was hoped t h a t one c o u l d p r e d i c t , from t h e J ( C-Sn) coup-13 l i n g s o b t a i n e d from the C s p e c t r a o f 2_5, 26 and 27_, t h e i r s o l u t i o n g e o m e t r i e s t o see i f t h e s e were i n a c c o r d w i t h t h o s e p r e d i c t e d -55-0 20 40 60 80 100 120 140 160 180 DIHEDRAL ANGLE IN DEGREE FIGURE 9 Magnitudes of 3 J ( U 9SnCC 1 3C) plotted against the dihedral angle e. (ref 59) from t h e p r o t o n d a t a ; i f s u c c e s s f u l t h i s w o u l d augur w e l l f o r 13 f u t u r e C s t u d i e s o f o r g a n o t i n s u g a r s . A l t h o u g h s i g n a l - t o - n o i s e l i m i t a t i o n s made i t d i f f i c u l t t o 13 d e t e c t the t i n s a t e l l i t e s i n t h e C s p e c t r a o f 25, 26 and 27, a number o f v a l u e s were o b t a i n e d . • These a r e l i s t e d i n T a b l e 6. The 13 117 13 119 s e p a r a t e magnitudes o f t h e g e m i n a l C- Sn and C- Sn coup-l i n g s were r e a d i l y r e s o l v e d . However, f o r a l l o t h e r c a r b o n s , the 317 119 Sn and Sn s a t e l l i t e s were o b s e r v e d as a s i n g l e , b r o a d , un-r e s o l v e d peak and the numbers g i v e n i n T a b l e 6 r e p r e s e n t an "average" 3 v a l u e . F o r t h e 6-deoxy sug a r 25 t h e J c o u p l i n g between C-4 and Sn i s ca 60 Hz. C o n s u l t i n g f i g u r e 9, one can see t h a t t h i s v a l u e TABLE 6 C-Sn c o u p l i n g c o n s t a n t s (Hz) f o r o r g a n o t i n sugars Compound n n W ^ S n - 1 3 ^ ) n 2 J ( S n - 1 3 C n ) n 3 J ( S n - 1 3 C n ) 25 6 372 6 348 5 -24 4 60 26 2 340 2 323 1 -14.8 4 0 3 - 9.6 27 3 392 3 376 2 -10.1 1 32. 8 2 -32 5 15.7 I cn I -57-Ph-C-H C-1 ,Sn C-2 C-3 C-6 J 3,Sn OCH, 115 105 95 85 75 65 55 45 35 ppm 1 3 F I G U R E l O N a t u r a l a b u n d a n c e C n . m . r . s p e c t r u m o f ( m e t h y l 4 , 6 - O - b e n z y l i d e n e -a - D - a l t r o p y r a n o s i d e ) 2 - C - s t a n n a n e 2 6 _ i n a c e t o n e - d ^ s o l u t i o n ( 0 . 3 M ) s h o w i n g t h e n o r m a l r e s o n a n c e s a n d t h e t i n s a t e l l i t e s o f t h e C - 1 , C - 2 , a n d C - 3 r e s o n a n c e s . ( P W 7 ; P D 0 ; N T 8 0 , 0 0 0 ; A T 1 . 0 2 3 s e c . ) -58-c o r r e s p o n d s t o a l a r g e d i h e d r a l a n g l e -- between 160° and 180°. I f a model i s made o f t h e r o t a m e r , about t h e C-5 - C-6 bond, p r e -v i o u s l y assumed t o be e n e r g e t i c a l l y t h e most f a v o u r e d f o r 25, one can see t h a t the d i h e d r a l a n g l e between C-4 and t h e 0^Sn group i s i n d e e d v e r y l a r g e — a p p r o x i m a t e l y 180°. Thus t h e and h e t e r o n u c l e a r d a t a f o r t h i s d e r i v a t i v e a r e i n agreement. A The " " J ^ c o u p l i n g (between C-4 and t i n ) o f the 2-deoxy s u g a r 26 i s ca. 0 Hz. From f i g u r e 9 and from o t h e r d a t a c o m p i l e d by K u i v i l a 59 and coworkers , a z e r o v i c x n a l c o u p l i n g i n d i c a t e s a d i h e d r a l a n g l e between the t i n group and C-4 o f a p p r o x i m a t e l y 85°. A g a i n , a model made o f the c h a i r form p r o p o s e d e a r l i e r i n t h i s c h a p t e r , on the b a s i s o f p.m.r. d a t a , f o r 26_ d i d i n d e e d show an a n g l e between C-4 -59-F o r the 3-deoxy sugar 27, t h e v i c i n a l c o u p l i n g s a r e = 32.8 Hz, c o r r e s p o n d i n g t o a d i h e d r a l a n g l e between C - l and t h e t i n moiety o f ca. 130° o r 35°, and 3 J , - = 15.7 Hz, c o r r e s p o n d i n g t o a d i h e d r a l a n g l e between C-5 and the t i n of ca 112° o r 58°. Examin-a t i o n o f m o l e c u l a r models i n d i c a t e s t h a t a d i h e d r a l a n g l e o f 35° between C - l and the t i n i s n o t p o s s i b l e . As C-5 i s i n a f i x e d p o s i t i o n w i t h r e s p e c t t o t h e r e s t o f t h e m o l e c u l e , a d i h e d r a l a n g l e o f c a 130° between C - l and t h e t i n f o r c e s t h e ' d i h e d r a l a n g l e between C-5 and the t i n t o be ca 110° — a g a i n deduced from models. T h i s i s v e r y c l o s e t o the v a l u e o f 112° o b t a i n e d from f i g u r e 9. These v a l u e s (130° and 112°) do i n d i c a t e a d i s t o r t i o n o f the sug a r - 6 0 -r i n g , w i t h t h e 03Sn group b e i n g d i s p o s e d towards a more e q u a t o r i a l p o s i t i o n than i t would occupy i n an u n d i s t u r b e d c h a i r . As p r e -v i o u s l y s t a t e d , t h i s c o n c u r s w i t h t h e c o n c l u s i o n s d e r i v e d from the p.m.r. d a t a i n t h a t i t , as w e l l , i n d i c a t e s t h e skew form shown i n f i g u r e 5 ( b ) . 5(b) The weakness o f t h i s method i s t h a t one i s somewhat dependent 13 on making q u a n t i t a t i v e i n t e r p r e t a t i o n s o f v i c i n a l C-Sn c o u p l i n g s and t h e d i f f i c u l t i e s o f so d o i n g have a l r e a d y been a l l u d e d t o . N e v e r t h e l e s s , t h e f a c t t h a t t h e d a t a f o r 25 and f o r 2_6 a r e i n a c c o r d w i t h a n t i c i p a t e d g e o m e t r i e s c l e a r l y i n d i c a t e s t h a t something un-e x p e c t e d o c c u r s i n 27. F u r t h e r m o r e , the f a c t t h a t t h r e e i n d e p e n d e n t s e t s o f n.m.r. d a t a f o r 2_7 a l l i n d i c a t e the p o s s i b i l i t y o f a 13 c o n f o r m a t i o n a l d i s t o r t i o n i m p l i e s t h a t i t i s n o t m e r e l y th e C-Sn d a t a t h a t a re a t y p i c a l . I t i s s u g g e s t e d t h a t f u t u r e n.m.r. e x p e r i m e n t s i n t h i s a r e a i n c l u d e p r o t o n d i f f e r e n c e , t i n INDOR and " t i n - o b s e r v e " s p e c t r a . As p r e v i o u s l y d i s c u s s e d , owing t o t h e l a c k o f s p e c t r a l d i s p e r s i o n i n many o f t h e p.m.r. o f o r g a n o t i n compounds, i t i s d i f f i c u l t t o o b t a i n p r o t o n - t i n c o u p l i n g s . I t may be f e a s i b l e t o use a 119 d i f f e r e n c e t e c h n i q u e whereby a Sn-decoupled p.m.r. spectrum i s 119 " s u b t r a c t e d " from a S n - c o u p l e d p.m.r. sp e c t r u m ( u s i n g computer t e c h n i q u e s ) t o o b t a i n a spectrum d i s p l a y i n g o n l y the re s o n a n c e s 119 due t o p r o t o n s t h a t a r e c o u p l e d t o a Sn n u c l e u s . T i n INDOR o r " t i n - o b s e r v e " e x p e r i m e n t s would a l l o w one t o measure the a c t u a l c h e m i c a l s h i f t s o f the "*"^Sn o r ^"^Sn n u c l e i . " T i n - o b s e r v e " s p e c t r a would a l s o a l l o w f o r measurement o f t i n -p r o t o n c o u p l i n g s when t h e s e a r e n o t r e a d i l y a v a i l a b l e from t h e p.m.r. spectrum. I f such e x p e r i m e n t s were u n d e r t a k e n i t would prove advantageous t o e l i m i n a t e the c o u p l i n g s from the p h e n y l p r o t o n s by s e l e c t i v e i r r a d i a t i o n a t t h e i r r e s o n a n c e f r e q u e n c i e s . - 6 2 -EXPERIMENTAL A l l s o l u t i o n s were c o n c e n t r a t e d under d i m i n i s h e d p r e s s u r e , u s i n g a B u c h i r o t a r y e v a p o r a t o r . M e l t i n g p o i n t s were measured w i t h a Hoover U n i m e l t (64 06-K) i n s t r u m e n t and are u n c o r r e c t e d . O p t i c a l r o t a t i o n s were measured on ace t o n e s o l u t i o n s a t ambient temperature w i t h a P e r k i n - E l m e r 141 p o l a r i m e t e r . T . l . c . was p e r -formed on S i l i c a G e l G (M e r c k ) , u s i n g t o l u e n e - e t h e r (1:2) and d e t e c t i o n by c h a r r i n g w i t h H 2 S 0 4 . A l l r e a c t i o n s were p e r f o r m e d i n anhydrous s o l v e n t s under an atmosphere o f d r y n i t r o g e n ; s o l v e n t s were d r i e d , d i s t i l l e d , and then s t o r e d o v e r m o l e c u l a r s i e v e s . F l u o r i n a t e d S u l f o n a t e s T r i f l u o r o m e t h a n e s u l f o n i c a n h y d r i d e (9 8% by g . l . c . ) and 2,2,2-t r i f l u o r o e t h a n e s u l f o n y l ( t r e s y l ) c h l o r i d e (98%) were o b t a i n e d from W i l l o w - B r o o k L a b o r a t o r i e s I n c . (Waukesha, W i s c o n s i n , U.S.A.), and were use,d w i t h o u t f u r t h e r p u r i f i c a t i o n . B o t h r e a g e n t s appear t o be s t a b l e i n d e f i n i t e l y when k e p t a t -10°. P e n t a f l u o r o b e n z e n e -s u l f o n y l c h l o r i d e (99%) was o b t a i n e d from A l d r i c h C h e m i c a l Co., and was used w i t h o u t p u r i f i c a t i o n ; i t i s s t a b l e f o r a t l e a s t s e v e r a l months a t room t e m p e r a t u r e . N.m.r. d a t a f o r 4, 5, 8-13 a r e r e p o r t e d i n T a b l e 2. N.m.r. d a t a f o r 7 and 1.7-2 0 a re r e p o r t e d i n T a b l e 1. 1,2:5, 6 - D i - 0 - i s o p r o p y l i d e n e - 3 - p ^ - t r i f l y l - a - p - a l l o f u r a n o s e (4J . — To a c o o l e d (/N,-15°) s o l u t i o n o f 1 (0.5 g, 1.92 mmol) i n p y r i d i n e (0.6 m l , 7.43 mmol) and CH 2C1 2 (40 m l ) , t r i f l i c a n h y d r i d e (0.38 m l , 2.3 mmol) was s l o w l y added. A f t e r 1 h, t . l . c . showed t h e r e a c t i o n t o be complete. The r e a c t i o n m i x t u r e was p o u r e d o n t o a m i x t u r e o f i c e and sodium hydrogen c a r b o n a t e . The aqueous l a y e r was ex-t r a c t e d w i t h C H 2 C 1 2 (3 x 50 m l ) , and the combined C H 2 C 1 2 s o l u t i o n s were d r i e d , and r a p i d l y and r e p e a t e d l y c o n c e n t r a t e d w i t h t o l u e n e t o remove any r e s i d u a l p y r i d i n e . The brown r e s i d u e was e x t r a c t e d w i t h l i g h t p e t r o l e u m (b.p. 30-60°) (3 x 50 m l ) , and the combined e x t r a c t s were f i l t e r e d and c o o l e d . The c o l o u r l e s s n e e d l e s w h i c h were c o l l e c t e d , a f t e r c a r e f u l e v a p o r a t i o n o f a d d i t i o n a l s o l v e n t were 4 ( 10 0 % ) , m.p. 40°, ] / \ ^ +64 (c 2.1). A n a l . C a l c . f o r C 1 3 H l g F 3 0 g S : c , 39.80; H, 4.88. Found: C, 40.02 H, 5.00. A s i m i l a r r e s u l t was o b t a i n e d u s i n g o n l y p y r i d i n e as s o l v e n t : t h e r e a c t i o n took ^ 3 h f o r c o m p l e t i o n and the p r o d u c t was o b t a i n e d i n 80% y i e l d . 1 , 2 : 5 , 6 - D i - O - i s o p r o p y l i d e n e - 3 - O - t r i f l y l - a - D - g l u c o f u r a n o s e ( 5 ) . In a manner s i m i l a r t o t h a t d e s c r i b e d above, a s o l u t i o n o f 2_ (1 g, 3.8 mmol) i n p y r i d i n e a t -10° , when t r e a t e d w i t h t r i f l i c a n h y d r i d e (0.7 m l , 4.2 mmol), gave _5 ( 100%). When r e c r y s t a l l i s e d from l i g h t p e t r o l e u m (b.p. 30-60°), t h e p r o d u c t was a w h i t e pow-r -]25 der m.p. 70°, [_ aJ D "35° (c 2) . A n a l . C a l c . f o r c 1 3 H i 9 F 3 ° 3 S : c ' 39.80; H, 4.88. Found: C, 39.71; H, 4.85. 6 - D e o x y - l , 2 : 3 , 4 - d i - O - i s o p r o p y l i d e n e - 6 - p y r i d i n o - a - D - g a l a c t o -p y r anose t r i f l u o r o m e t h a n e s u l p h o n a t e {J) . — A s o l u t i o n o f 3_ (1.75 g, 6.7 mmol) i n C H 2 C 1 2 (15 ml) was added d u r i n g 10 min t o a c o o l e d (*--15°) s o l u t i o n o f t r i f l i c a n h y d r i d e (1.2 m l , 7.2 mmol) i n p y r i d i n e . A f t e r 1.5 h, t h e r e a c t i o n m i x t u r e was worked-up i n t he u s u a l f a s h i o n t o y i e l d 7 (2.83 g, 9 0 % ) . R e c r y s t a l l i s a t i o n from aqueous e t h a n o l - l i g h t p e t r o l e u m gave w h i t e p l a t e l e t s , m.p. 217-218° ( d e c ) , [ a ] 2 5 -35° (c 2.5). A n a l . C a l c . f o r C-^H^F^TOgS: C, 45. 86; H, 5.13; N, 2.97. Found: C, 45.95; H, 5.32; N, 2.96. 1, 2 : 5 , 6-Di-Q-isoprop'y lidene-3-£r-tresy 1 - a - p _ - a l l o f uranose (8_) . — A s o l u t i o n o f 1_ (2 g, 7.7 mmol) i n p y r i d i n e (0.94 m l , 11.6 mmol) and CH2C12 (40 ml) was t r e a t e d w i t h t r e s y l c h l o r i d e (0.94 ml, 9.9 mmol), u s i n g a p r o c e d u r e p a r a l l e l t o t h a t d e s c r i b e d above f o r the p r e p a r a t i o n o f _4. The s t i r r e d m i x t u r e was a l l o w e d t o warm up t o room t e m p e r a t u r e o v e r n i g h t . The u s u a l work-up and r e c r y s t a l -l i s a t i o n o f the p r o d u c t from l i g h t p e t r o l e u m gave v e r y f i n e , w h i t e n e e d l e s o f 8. (3.2 g, 8 9 % ) , m.p. 55-56°, £aj 2 5 +66° (c 2.1). A n a l . C a l c . f o r C ^ H ^ F ^ g S - C, 41.38; H, 5.21. Found: C, 41.73; H, 5.28. 1,2: 5, 6 - D i - 0 - i s o p r o p y l i d e n e - 3 - 0 - t r e s y l - a - D - g l u c o f u r a n o s e (9.) . — The r e a c t i o n o f a s o l u t i o n o f 2 (1 g, 3.9 mmol) i n p y r i d i n e (0.47 m l , 5.8 mmol) and C H 2 C 1 2 (40 ml) w i t h t r e s y l c h l o r i d e (0.47 ml, 5 mmol) was conducted as d e s c r i b e d above t o y i e l d _9 as w h i t e n e e d l e s (1.4 g, 9 0 % ) , m.p. 90-91°, [ a ] ^ -39° (c 2.7). A n a l . C a l c . f o r c 1 4 H 2 l F 3 0 8 S : C ' 4 1 - 3 8 ' H ' 5.21. Found: C, 41.72; H, 5.44. 1 , 2 : 3 , 4 - D i - 0 - i s o p r o p y l i d e n e - 6 - 0 - t r e s y l - a - D - g a l a c t o p y r a n o s e (10) The r e a c t i o n o f a s o l u t i o n o f _3 (2.3 g, 8.9 mmol) i n p y r i d i n e (14 mmol) and C H 2 C 1 2 (40 ml) w i t h t r e s y l c h l o r i d e (1.15 m l , 12 mmol) a t -15° f o r 1.5 h was f o l l o w e d by t h e u s u a l work-up. Re-c r y s t a l l i s a t i o n o f t h e p r o d u c t from l i g h t p e t r o l e u m gave 10 (3.2 g, 89%) as f i n e , w h i t e n e e d l e s , m.p. 93-94°, \_a~\^ -52° (c 1.7) . A n a l . C a l c . f o r C 1 4 H 2 1 F 3 ° 8 S : C ' 4 1 - 3 8 « ' H ' .5.21. Found: C, 41.30; H, 5.10. R e a c t i o n s w i t h p e n t a f l u o r o b e n z e n e s u l p h o n y l c h l o r i d e . — None o f t h e r e a c t i o n s a t t e m p t e d w i t h t h i s r e a g e n t were s a t i s f a c t o r y , t h e y i e l d s b e i n g i n v a r i a b l y low (~40%). R e a c t i o n s c o n d u c t e d w i t h a 3-molar e x c e s s o f r e a g e n t gave no s i g n i f i c a n t improvement i n y i e l d , n e i t h e r d i d v a r i a t i o n s i n r e a c t i o n t i m e (3-48 h ) , n o r te m p e r a t u r e (-20-* +80°) . The c a r b o h y d r a t e (1,2 o r 3) (1.4 g, 4.2 mmol) and p y r i d i n e (0.7 m l , 8.7 mmol) was t r e a t e d w i t h p e n t a f l u o r o b e n z e n e s u l p h o n y l c h l o r i d e (1.57 g, 6.25 mmol) and f o l l o w e d by t h e u s u a l work-up. The f o l l o w i n g compounds were t h e r e b y o b t a i n e d . 1,2:5, 6 - D i - 0 - i s o p r o p y l i d e n e - 3 - 0 - p e n t a f l y l - c t - D - a l l o f uranose f 125 = (11) , m.p. 103-104°, |_a JD +64° (c 1.9). A n a l . C a l c . f o r c i 8 H 1 9 F 5 ° 8 S : C ' 4 4 * 0 9 ; H ' 3 - 9 1 - Found: C, 44.04; H, 3.95. 1,2:5, 6 - D i - 0 - i s o p r o p y l i d e n e - 3 - 0 - p e n t a f l y 1-ct-p-glucof uranose (12) , m.p. 132-136°; an a c c e p t a b l y pure specimen was n o t o b t a i n e d even a f t e r chromatography on a n e u t r a l a l u m i n a column (Brockman I ; 80-200 mesh) u s i n g t o l u e n e - e t h e r . 1 , 2 : 3 , 4 - D i - 0 - i s o p r o p y l i d e n e - 6 - 0 - p e n t a f l y l - a - D - g a l a c t o p y r a -nose ( 1 3 ) , m.p. 103-104°, [ a ] 2 5 -47.5° (c 2.3). A n a l . C a l c . f o r C 1 8 H 1 9 F 5 ° 8 S : C, 44.09; H, 3.91. Found: C, 44.21; H, 3.88. -66-6-Deoxy-l, 2: 3., 4 - d i - O - i s o p r o p y l i d e n e - 6 - p y r i d i n o - a - p - g a l a c t o -pyranose t o l u e n e - p - s u l p h o n a t e (l!3) . — A s o l u t i o n o f t h e 6-0-t o s y l d e r i v a t i v e 16 ( 5 g , 1.2 mmol) i n p y r i d i n e ( 50 ml) was heat e d under r e f l u x f o r 24 h; t . l . c . t hen i n d i c a t e d t h a t 95% o f 16 had r e a c t e d . Work-up i n t h e u s u a l f a s h i o n gave a crude p r o d u c t (2 g, 33%) whi c h was r e c r y s t a l l i s e d from aqueous e t h a n o l t o g i v e 18, m.p. 204-205°, " 2 5 ° ( c 0.5). D A n a l . C a l c . f o r C^H^NOgS: C, 58.28; H, 6.52; N, 2.83. Found: C, 58.37; H, 6.69; N, 2.80. 6 - D e o x y - l , 2 : 3 , 4 - d i - O - i s o p r o p y l i d e n e - 6 - p y r i d i n o - a - D - g a l a c t o -pyranose i o d i d e (20) . -- To a s o l u t i o n o f 7_ o r 18 i n a c e t o n e , a 3-molar.excess o f sodium i o d i d e was added. The m i x t u r e was h e a t e d under r e f l u x f o r 1 h and t h e u s u a l work-up gave 20 ( 100%). Re-c r y s t a l l i s a t i o n from methanol gave 2_0 as a p a l e - y e l l o w powder, 25 m.p. 250° ( d e c ) , [of) -30° (c 0.27). A n a l . C a l c . f o r C ^ H ^ I N O ^ C, 45.45; H, 5.38; N, 3.12. Found: C, 45.47; H, 5.37; N, 3.00. S a l t s o f 3 - d e o x y - l , 2 : 5 , 6 - d i - 0 - i s o p r o p y l i d e n e - 3 - p y r i d i n o - a - Q -g l u c o f u r a n o s e t r i f l u o r o m e t h a n e s u l p h o n a t e . — A s o l u t i o n o f JL (1 g, 2.8 mmol) and t r i f l i c a n h y d r i d e (0.74 m l , 4.4 mmol) i n p y r i -d i n e ( 40 ml) was h e a t e d a t r e f l u x t e m p e r a t u r e f o r 25 h. A f t e r the u s u a l work-up and a s i n g l e t r e a t m e n t w i t h c h a r c o a l - C e l i t e , a v e r y h y g r o s c o p i c , brown, c r y s t a l l i n e m a t e r i a l was o b t a i n e d (1.2 g, 7 1 % ) , w h i c h was p r o v e d t o be t h e t r i f l a t e s a l t 17 by "*"H-n.m.r. and F-n.m.r. s p e c t r o s c o p y ( 0 C + 81.6 p.p.m.). L i k e w i s e , 4 was c o n v e r t e d i n t o 17. A sample of. 17 was q u a n t i t a t i v e l y c o n v e r t e d i n t o t h e i o d i d e 19 as d e s c r i b e d p r e v i o u s l y ; m.p. 190-193^ (from aqueous e t h a n o l ) , D 1 ] " "3° (c 0.39). A n a l . C a l c . f o r ' C 1 7 H 2 4 I N 0 5 : C, 45.45; H, 5.38; N, 3.12. Found: C, 44.96; H, 5.46; N, 3.03. Stannane D e r i v a t i v e s o f C a r b o h y d r a t e s T r i p h e n y l t i n c h l o r i d e (9 5+%) was o b t a i n e d f rom A l f a P r o d u c t s (Danvers, Mass., U.S.A.) and was used a f t e r r e c r y s t a l l i z i n g from m e t h a n o l - c h l o r o f o r m and f r e e z e - d r y i n g , u s i n g " D r i e r i t e " as the d e s s i c a n t , a t c a 0.8 t o r r f o r 2 4 h o u r s . L i t h i u m m e t a l rods ( t e c h . grade) were o b t a i n e d from F i s h e r S c i e n t i f i c Co., Chem. Manufac. D i v . ( F a i r Lawn, N.J., U.S.A.). F o r compounds 25, 26 and 27,- "'"H n.m.r. d a t a a r e r e p o r t e d i n 13 T a b l e 3 and C n.m.r. d a t a a r e r e p o r t e d i n T a b l e s 4 and 6. P r e p a r a t i o n o f T r i p h e n y l t i n L i t h i u m : Note: I t was found t h a t t h e r e a c t i o n t o form t r i p h e n y l t i n l i t h i u m worked w e l l o n l y when the s u r f a c e o f the l i t h i u m m e t a l was v e r y c l e a n . The m e t a l s u r f a c e , t h e r e f o r e , was c l e a n e d , f i r s t , i n d r y methanol and then q u i c k l y r i n s e d i n d r y t e t r a h y d r o f u r a n b e f o r e a d d i n g i t t o t h e s o l v e n t i n t h e r e a c t i o n v e s s e l . 14 -3 F o l l o w i n g t h e p r o c e d u r e o f Tamborski , 2.5 g (6.5 x 10 mol) o f t r i p h e n y l t i n c h l o r i d e i n ca 15 ml t e t r a h y d r o f u r a n were added t o a w e l l - s t i r r e d s o l u t i o n c o n t a i n i n g 0.55 g (0.08 mol) l i t h i u m s h a v i n g s and ca 20 ml t e t r a h y d r o f u r a n . W i t h i n about f i f t e e n min-u t e s , h e a t was e v o l v e d and t h e r e a c t i o n m i x t u r e became a d a r k o l i v e - g r e e n c o l o u r . The s o l u t i o n was s t i r r e d f o r 1-2 h o u r s , a f t e r w h i c h time i t was f i l t e r e d t h r o u g h g l a s s w o o l and i m m e d i a t e l y used f o r t h e f o l l o w i n g r e a c t i o n s . Y i e l d s f o r t h i s r e a c t i o n have been r e p o r t e d 6 0 t o be 50-75' P r e p a r a t i o n o f t r i p h e n y l ( 1 , 2 : 3 , 5 - d i - O - m e t h y l e n e - a - D - g l u c o f u r a n o s e ) 6-C-stannane (2_5) : 2.5 g t r i p h e n y l t i n c h l o r i d e (6.5 x 10 mol) i n t e t r a h y d r o -f u r a n were r e a c t e d w i t h an e x c e s s o f l i t h i u m m e t a l , i n t h e manner d e s c r i b e d a b o v e , f o r 2 h o u r s , f i l t e r e d t h r o u g h g l a s s wool and _ 3 added, d r o p w i s e , t o a s t i r r e d s o l u t i o n o f 1.5 g (4.2 x 10 mol) 61 1 , 2 : 3 , 5 - d i - O - m e t h y l e n e - a - D - g l u c o f u r a n o s e - 6 - O - t o s y l a t e i n 25 ml t e t r a h y d r o f u r a n . A f t e r 4 hour s t . l . c . i n d i c a t e d t h a t a l l t h e t o s y l a t e had r e a c t e d . The r e a c t i o n m i x t u r e was t h e n poured i n t o 25 0 ml w a t e r and n e u t r a l i z e d w i t h ammonium c h l o r i d e . The m i x t u r e was e x t r a c t e d w i t h c h l o r o f o r m (3 x 50 ml) and t h e c h l o r o f o r m s o l -u t i o n d r i e d o v e r magnesium s u l f a t e , a f t e r w h i c h the s o l v e n t was removed under reduced p r e s s u r e . Any c o n t a m i n a t i n g h e x a p h e n y l d i t i n was p r e c i p i t a t e d by a d d i n g c o l d anhydrous e t h e r and f i l t e r i n g o f f the c r y s t a l s . The e t h e r was t h e n f l a s h e v a p o r a t e d t o y i e l d a w h i t e c r y s t a l l i n e m a t e r i a l w h i c h was s u b s e q u e n t l y i d e n t i f i e d as 25. Y i e l d , a f t e r one r e c r y s t a l l i z a t i o n (benzene: (30-60) p e t r o -leum e t h e r ) , was 1 g ( 4 3 . 5 % ) , m.p. 108-110°C, [ a ] 2 5 +60.00 (c 2.37). A n a l . C a l c . f o r C 2 6 H 2 g 0 5 S n : C, 58.13; H, 4.88. Found: C, 57. 90; H, .4.86. -69-P r e p a r a t i o n o f t r i p h e n y l ( m e t h y l 4 , 6 - O - b e n z y l i d e n e - a - D - a l t r o -p y r a n o s i d e ) 2-C-stannane ( 2 6 ) : -3 2.5 g (6.5 x 10 mol) o f t r i p h e n y l t i n c h l o r i d e and .55 g l i t h i u m m e t a l (0.08 mol) were r e a c t e d as d e s c r i b e d above, f i l t e r e d , _3 and added, d r o p w i s e , t o a s t i r r e d s o l u t i o n o f 1.0 g (3.78 x 10 mol) m e t h y l 2 , 3 - a n h y d r o - 4 , 6 - O - b e n z y l i d e n e - a - D - a l l o p y r a n o s i d e i n ca 25 ml t e t r a h y d r o f u r a n . The r e a c t i o n appeared t o be i n s t a n t a n -eous, as the dark o l i v e - g r e e n c o l o u r o f the t r i p h e n y l t i n l i t h i u m d i s a p p e a r e d i m m e d i a t e l y upon a d d i t i o n ; however, t o en s u r e c o m p l e t e r e a c 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 1 hour. A f t e r workup, as d e s c r i b e d f o r 25, 2.6 g (75% y i e l d ) o f a c r y s t a l l i n e compound was 25 o b t a i n e d , s u b s e q u e n t l y i d e n t i f i e d as 2_6, m.p. 67-69°, [] a]n +5.9070 (c 2.15). A n a l . C a l c . f o r C_JH o o0.-Sn: C, 62.47; H, 5.24. Found: C, 63.88, H, 5.31. P r e p a r a t i o n o f t r i p h e n y l ( m e t h y l 4 , 6 - O - b e n z y l i d e n e - a - D - a l t r o p y r a n o -s i d e ) - 3 - C - s t a n n a n e (27): 1.25 g (3.25 x 10 mol) t r i p h e n y l t i n c h l o r i d e was r e a c t e d w i t h 0.55 g (0.08 mol) l i t h i u m m e t a l s h a v i n g s i n the manner des-c r i b e d above, f i l t e r e d , and added, d r o p w i s e , t o a s t i r r e d s o l u t i o n of 0.37 g (0.6 x 1 0 ~ 3 m O l ) m e t h y l 2,3 anhydro-4,6-O-benzylidene-c{-D-mannopyranoside i n ca 25 ml t e t r a h y d r o f u r a n . A f t e r t h e u s u a l workup, as f o r 25, a foamy s y r u p was o b t a i n e d . T h i s s y r u p s o l i d i -f i e d a f t e r 12 hours under vacuum. Y i e l d : .81 g ( 9 4 % ) , m.p. 166-168°C, [ a ] 2 5 +91 (c 1.97) . A n a l . C a l c . f o r C ^ H ^ O ^ S n : C, 62.47; H,. 5.24. F o u n d 62.01; H, 5.40. -71-Appendix 13 Assignment o f C r e s o n a n c e s by s e l e c t i v e p r o t o n d e c o u p l i n g . S e l e c t i v e p r o t o n d e c o u p l i n g p r o v i d e d t h e b e s t method o f 13 a s s i g n i n g a l l o f the C r e s o n a n c e s o f d e r i v a t i v e s 25-27 and 31-33. The 100 MHz p r o t o n spectrum o f each d e r i v a t i v e was f i r s t o b t a i n e d by c o n v e n t i o n a l p.m.r. methods and t h e r e s o n a n c e s a s s i g n e d u s i n g s i m p l e , f i r s t o r d e r a n a l y s i s . The d e c o u p l e d 20 MHz (18.682 KG) 13 C n.m.r. spectrum o f each compound was a l s o r e c o r d e d . C a l c u l a -t i o n s o f t h e f r e q u e n c i e s a t w h i c h the p r o t o n s r e s o n a t e i n a 18.682 KG f i e l d (80 MHz) were made. A H e w l e t t P a c k a r d 5105A f r e q u e n c y s y n t h e s i z e r was c o n n e c t e d t o t h e probe and, t o p r e v e n t f r e q u e n c y d r i f t , t o the i n t e r n a l 1 MHz c l o c k o f the CFT-20 s p e c -t r o m e t e r . 13 C s p e c t r a o f the compounds were th e n o b t a i n e d w h i l s t i n d i -v i d u a l p r o t o n r e s o n a n c e s were s e l e c t i v e l y i r r a d i a t e d . The carbon c o u p l e d to a p r o t o n thus i r r a d i a t e d was seen as a s h a r p s i n g l e t i n t h e spectrum ( f i g u r e 11). I d e a l l y , a l l o t h e r c a r b o n r e s o n a n c e s s h o u l d have appeared as m u l t i p l e t s . However, p r o t o n s r e s o n a t i n g a t f r e q u e n c i e s c l o s e t o t h a t b e i n g i r r a d i a t e d a r e , i n g e n e r a l , 13 p a r t i a l l y d e c o u p l e d and t h i s was seen m t h e C s p e c t r a . T h i s 13 f a c t was sometimes h e l p f u l f o r assignment o f t h e C r e s o n a n c e s . Ph-C-H I in 400 Hz 20 ppm' i i i i i i o o I c_> I 1 I ' I ' I ' I I I I I I. I I I I I I I I I I I I I I ' I I I 1 I ' I I I I I I I I I I I I I I I I I I I I I I I I I I fully decoupled spectrum irradiate H-I ' I i I—i—I—i—I—r I I I I • W > 4 i r r a d i a | e H-2 i i i i i i i ' i i I i I I I i i i i i 1 r~i i i i i i i i i—i—i—i—i—i—i—i—i—i—i—i—i—r 1 ! III. I1', t I i ' i i I "1 TT i I i 1—I—I—I—|—I—|—r I I I I I I I I I Li I I I I I I I I ' I I I I I ' I I I I . • i i II i ' i i i i i i—r -!—i—'—r~!—r~i—i > i 1 i irradiate H-3 irradiate H-4 irradiate H-5 ' '' i r i i : i i 13 Natural abundance 'C n.m.r. spectra, of triphenyl(methyl 4 6-0-benzylidene-a-D-altropyranoside)2-C-stannane 26 i n deuteriobenrene sol u t i o n (0 3 M) , from a s e l e c t i v e decoupling" experiment, she-win? how the ind i v i d u a l resonances are assigned. C-6 undecoupled spectrum i T ~ T — i — i — i — i — i — i — r OMe REFERENCES 1 . R.S. T i p s o n , Advan. Carbohydr. Res. / 8_ .'(1953) 1 0 7 - 2 1 5 . 2 . D.H. B a l l and F.W. P a r r i s h , Advan. Carbohydr. Chem., 23 (1968) 2 3 3 - 2 7 9 . 3 . D.H. B a l l and F.W. P a r r i s h , Advan. Carbohydr. Chem. Biochem. 2j4 (1969) 1 3 9 - 1 6 7 . 4 . T. Gramstad and R.N. H a s z e l d i n e , J . Chem. S o c , (1957) 4 0 6 9 - 4 0 7 9 . 5 . A. S t r e i t w i e s e r , J r . , C L . W i l k i n s and E. Kiehlmann, J . Amer. Chem. S o c , 9_0 (1968) 1 5 9 8 - 1 6 0 1 . 6 . R.K. C r o s s l a n d , W.E. W e l l s and V . J . S h i n e r , J r . , J . Amer. Chem. S o c , 9_3 (1971) 4 2 1 7 - 4 2 1 9 . 7. Tah.- Mun Su, W.J. S l i w i n s k i and P. von R. S c h l e y e r , J . Amer. Chem. S o c , 9JL (1969) 5 3 8 6 - 5 3 8 8 . 8 . C D . Beard, K. Baum and V. Grakauskas, J . Org. Chem., 38 (1973) 3 6 7 3 - 3 6 7 7 . 9 . J . Burdon and V.C.R. McLoughlin, Tetrahedron, 2_1 (1965) 1 - 4 . 1 0 . T.M. Chapman and E.A. Freedman, S y n t h e s i s , (1971) 5 9 1 - 5 9 2 . 1 1 . J.E. Connett, J . Chem. S o c , (1956) 1 7 3 - 1 8 0 . 1 2 . F . J . Kronzer and C. Schuerch, Carbohydr. Res., 27 (1973) 3 7 9 - 3 9 0 . 1 3 . P.R. S t e i n e r , Ph.D. T h e s i s , U n i v e r s i t y of B r i t i s h Columbia, 1 9 7 1 . 1 4 . C. Tamborski, F.E. For d and E . J . S o l o s k i , J . Org. Chem., 2_8, (1962) 1 8 1 - 1 8 4 . 1 5 . H. Zimmer and A.V. B a y l e s s , Tetrahedron L e t t e r s No. 4 , (1970) 2 5 9 - 2 6 2 . 1 6 . Willow-Brook Lab. Inc. (Waukesha, Wisconsin, U.S.A.). 1 7 . J . Berry and L.D. H a l l , Carbohydr. Res., 47_ (1976) 3 0 7 - 3 1 0 . 1 8 . F. E f f e n b e r g e r and K. Huthmacher, Angewandte Chemie, 86 (1974) 4 0 9 - 4 1 0 . -74-19 20, 21. 22. 23. 24. 25, 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. F E f f e n b e r g e r and K.E.. Mack/ Tetrahedron Letters, 4_5 (1970) 3947-3948. T.M. Chapman and E.A. Freedman, J . Org. Chem., 38 (1973) 3908-3911. J. Leroux and A.S. P e r l i n , Carbohydr. Res./ 47 (1976) C8-C10 C C . Lee and D. Unger, Can. J . Chem. / 51 (1973) 1494-1496. R.L. Hansen, J . Org. Chem. 30 (1965) 4322-4344. J . Leroux and A.S. P e r l i n , Carbohydr. Res., 47 (1976) C8-C10. A. Maradufu and A.S. P e r l i n , Carbohydr. Res., 32_ (1974) 261-277. P. Hancock, J . Fluorine Chem. / 4_ (1974) 25-33. J.F. Gerster, Ger. Offen. 2, 118, 192 (Cl. C07c, A61K), 28 Oct. 1971, U.S. Appl. 13 Apr. 1970. R.J. Trancik, R.A. Scherrer, and J.K. Harrington, U.S. 3, 725, 451 (Cl. 260/456 A; C07c) , 03 Apr.. 1973, Appl. 28, 020, 13 Apr. 19 70. J.K. Harrington, and R.D. Treptka, U.S. 3, 865, 844 (Cl. 260-332.5; C 07d), 11 Feb. 1975, Appl. 795, 050, 29 Jan. 1969. J.K. Harrington, and R.D. Treptka, U.S. Publ. Pat. Appl. B. 378, 621 (Cl. 260-347.2: C 07d), 28 Jan. 1975, Appl. 795, 050, 29 Jan. 1969. A v a i l . U.S. Pat. Trademark Off. D i v i s i o n of U.S. 3, 766, 193. J.B. Hendrickson, R. Bergeron, A. Giga and D. Sternbach, J. Amer. Chem. S o c , 95. (1973) 3412-3413. F. Shafizadeh, Methods i n Carbohydr. Chem. I, p. 208. R.U. Lemieux and T. Kondo, Carbohydr. Res./ 35 (1974) C4-C-6. J. Arnapp, L. Kenne, B. Lindberg and J . Lonngren, Carbohydr. Res., 44 (1975) C5-C7. C. Cone and L. Hough, Carbohydr. Res., 1 (1965). 1-9. L.D. H a l l , Ph.D. Thesis, University of B r i s t o l , 1962. R.C P o l l e r , "Chemistry of Organotin Compounds", Academic Press, New York (1970). - 7 5 -38. W.P. Neumann, "The O r g a n i c . C h e m i s t r y o f T i n " , I n t e r s c i e n c e P u b l i s h e r s , John W i l e y and Sons (1970). 39. A.K. Sawyer ( E d . ) , " O r g a n o t i n Compounds", M a r c e l Dekker, I n c . , New York (1971). 40. M a t t e s o n , " O r g a n o m e t a l l i c R e a c t i o n Mechanisms o f the Non-t r a n s i t i o n E l e m e n t s " , Academic P r e s s , New Y o r k (1974). 41. C. Tamborski, E.C. F o r d and E . J . S o l o s k i , J . Org. Chem. 2_8 (1962) 181-184. 42. P. Smith and L. S m i t h , Chem. B r . , 11 (1975) 208-212. 43. L.D. H a l l , S.A. B l a c k , K.N. S l e s s o r and A.S. T r a c e y , Can. J . Chem., 5_0 (1972) 1912-1924. 44. R e f e r e n c e 38 pp. 221-224. 45. K.L. W i l l i a m s o n , J . Amer. Chem. S o c , 85 (1963) 516-519; P. L a s z l o and P. von R. S c h l e y e r , I b i d . , " 85_ (1963) 2709-2712; K.L. W i l l i a m s o n , C A . L a n f o r d and C.R. N i c h o l s o n , I b i d . , 86^  (1964) 762-765. 46. R.J. Abraham and K.G.R. P a c h l e r , M o l . Phys., 7 (1963) 165-182.. 47. A . C H u i t r i c , J.B. C a r r , W.F. Tager and B . J . N i s t , T e t r a -hedron, 19 (1963) 2145-2151. 48. M. K a r p l u s , J . Amer. Chem. S o c , 8_5 (1963) 2870-2871. 49. M. K a r p l u s , J . Chem. Phys., 30_ (1959) 11-15. 50. B. Coxon, T e t r a h e d r o n , 21 (1965)3481-3503. 51. J.B. S t o t h e r s , "Carbon-13 N.M.R. S p e c t r o s c o p y " , Academic P r e s s , New York (1972) pp. 458-468. 52. H.G. K u i v i l a , J . L . C o n s i d i n e , R.J. Mynott and R.H. Sarma, J . Organomet. Chem., 5_5 (1973) C11-C14. 53. H.G. K u i v i l a , J . L . C o n s i d i n e , R.H. Sarma and R.J. My n o t t , J . Organomet. Chem., I l l (1976) 179-196. 54. W. M a c F a r l a n e , J . Amer. Chem. S o c , A, (1967) 528-530, H. Dreeskamp and G. S t e g m e i e r , Z. N a t u r f o r s c h g . A, 22 (1967) 1458-1460; F . J . W e i g e r t , M. Winokur and J.D. R o b e r t s , J . Amer. Chem. Soc.,' 90 (1968) 1566-1569. 55. T.J. W i e g e r t and J.D. R o b e r t s , J . Amer. Chem. S o c , 91 (1969) 4940-4941. -76-Yu. K. G r i s h i n , N.M. Sergeyev and Yu. A. Ustynyuk, Org. Magn. Res., A (1972). 377-390. C. D. S c h a e f f e r , J r . , and J . J . Zuckerman, J . Organomet. Chem. 47 (1973) C1-C4. T.N. M i t c h e l l , J . Organomet. Chem., 59 (1973) 189-197. D. D o d d r e l l , I. B u r f i t t , W. K i t c h i n g , M. B u l l p i t t , R .J. Mynott, J . L . C o n s i d i n e , H.G. K u i v i l a and R.H. Sarma, J . Amer. Chem. S o c , 9_6 (1974) 1640-1642. H. Gilman and G.D. L i c h t e n w a l t e r , J . Amer. Chem. S o c , 8_0 (1958) 608-611; H. G i l m a n , M.V. Georges and D. P e t e r s o n , I b i d . , £2 (1960) 403-406. O.T. Schmidt, A. D i s t e l m a i e r and H. R e i n h a r d , Chem. B e r i c h t e 186 (1953) 741-749. G.J. R o b e r t s o n and C.F. G r i f f i t h , J . Chem. S o c , (1935) 1193-1201; D.A. P r i n s , H e l v . Chim. A c t a . , 29 (1946) 1-8. 

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