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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.Sc,  U n i v e r s i t y o f 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 i n t h e Department o f CHEMISTRY  We accept t h i s  t h e s i s as conforming t o the r e q u i r e d  THE UNIVERSITY OF BRITISH COLUMBIA May, 1977  (c)  Diane C l a u d i a M i l l e r ,  1977  standard  In  presenting  this  thesis  an a d v a n c e d d e g r e e the L i b r a r y I  further  for  of  this  written  the U n i v e r s i t y  s h a l l make i t  agree  scholarly  by h i s  at  freely  that permission  for  It  of  financial  British  2075 Wesbrook P l a c e V a n c o u v e r , Canada V6T 1W5  of  Columbia,  British  by  for  gain shall  Columbia  the  requirements  reference copying  of  I agree and this  that  not  copying  or  for that  study. thesis  t h e Head o f my D e p a r t m e n t  is understood  of  The U n i v e r s i t y  of  for extensive  permission.  Department  fulfilment  available  p u r p o s e s may be g r a n t e d  representatives. thesis  in p a r t i a l  or  publication  be a l l o w e d w i t h o u t  my  (ii)  ABSTRACT 1,2:5,6-Di-O-isopropylidene-a-D-allofuranose 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,  l,2:5,6-di-  1,2:3,4-di-0-isopropyli-  d e n e - ~ D - g a l a c t o p y r a n o s e 3_ h a v e b e e n t r e a t e d s e p a r a t e l y a  pyridine solution with  t r i f l u o r o m e t h a n e s u l f o n i c anhydride,  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 chloride.  B o t h 1 and  2 afforded  A l t h o u g h 3_ a l s o g a v e t h e fluorobenzenesulfonic  in  the  2,2,2-  pentafluorobenzenesulfonyl anticipated sulfonic esters.  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  e s t e r s , the  s u l f onic anhydride y i e l d e d  reaction with  penta-  trifluoromethane-  6-deoxy-l,2:3,4-di-0-isopropylidene-  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 o n a t e 1_. I n a second p a r t to t h i s work t r i p h e n y l t i n separately  reacted w i t h each of  lithium  was  1,2:3,4-di-O-methylene-a-D-  g l u c o f u r a n o s e 2_2, m e t h y l 2 , 3 - a n h y d r o - 4 , 6 - 0 - b e n z y l i d e n e - a - D allopyranoside  23 and  m a n n o p y r a n o s i d e 24 t i v e having  methyl  2,3-anhydro-4,6-0-benzylidene-a-D-  to form, i n every case, a sugar-stannane d e r i v a -  a stable carbon-tin  N.m.r. s t u d i e s o f b o t h t h e p a r t i c u l a r l y , of the o r g a n o t i n  bond. f l u o r i n a t e d sugar s u l f o n a t e s sugars are  also  reported.  and,  (iii)  TABLE  OF  CONTENTS  INTRODUCTION  -1-  R E S U L T S AND CHAPTER (a)  I  Their  (b)  DISCUSSION Fluorinated  synthesis  Sulfonic  Esters  and reactions  o f  with  Sugars  pyridine  -8-  TRIFLATES  -8-  TRESYLATES  -18-  PENTAFLATES  -19-  N.m.r.  spectra  pyridinium CHAPTER  II  Synthesis  (b)  N.m.r. H  and conformational  properties  o f t h e  s a l t s Carbohydrates '  spectra  triflyl -22-  C-Stannylated  (a)  1  -8-  and conformational  properties  N.M.R  -28-35-35-  HETERONUCLEAR (1)  1  H-Sn  (2)  1  3  C  N.M.R.  PARAMETERS  couplings  -45-47-  n.m.r  -47-  (i) chemical  shifts  -47-  13  (ii)  C-Sn  coupling  constants  EXPERIMENTAL Fluorinated  -54-62-  Sulfonates  Stannane Derivatives  -62o f Carbohydrates  -67-  APPENDIX  -71-  REFERENCES  -73-  (iv)  LIST OF TABLES  TABLE 1 Chemical salts  -25shifts  ( r - v a l u e s ) and m u l t i p l e t  i n deuterioacetone  splittings  (Hz) f o r p y r i d i n i u m  solutions.  TABLE 2  -26-  1 H chemical splittings  shifts  (x-values),  19  F chemical  (0 ) and m u l t i p l e t  shifts  (Hz) f o r s u l f o n a t e s i n d e u t e r i o a c e t o n e  solutions.  TABLE 3 Chemical  -37shifts  ( x - v a l u e s ) and m u l t i p l e t  splittings  (Hz) f o r 4,6-0-  benzy 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-Dglucofuranoses TABLE 4  i n deuteriobenzene  solutions.  '  -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 13 C chemical  -53-  shift differences  a-D-glucofuranoses  (ppm) 6  i n deuteriobenzene  TABLE 6 13 C-Sn c o u p l i n g c o n s t a n t s  -  6 ^ f o r 4,6-0_-benzylidene-  solutions. -56-  (Hz) f o r o r g a n o t i n  sugars.  (v)  LIST OF FIGURES FIGURE 1  -4-  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-SO^R. FIGURE 2  -11-  Fluorinated sulfonyl  and p y r i d i n i u m t r i f l y l  derivatives  synthesized  f o r t h i s work. FIGURE 3  -30-  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 , s y n t h e s i z e d f o r t h i s work, and t h e i r precursors. FIGURE 4  -36-  *H n.m.r. s p e c t r a o f t r i 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) 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 . FIGURE 5  -43-  (a) C h a i r and (b) skew c o n f o r m a t i o n s f o r methyl  4,6-0-benzylidene-a-  D-altropyranosides . FIGURE 6  -4613  N a t u r a l abundance deuteriobenzene  C n.m.r. spectrum o f t r i m e t h y l t i n c h l o r i d e i n  solution.  FIGURE 7 Fourier transform  -48n.m.r. spectrum o f t r i p h e n y l ( 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 ) 2 - C - s t a n n a n e 26^ showing s p e c t r a l  assignments a n d '  *H-Sn c o u p l i n g s . FIGURE 8  -50-  N a t u r a l abundance ~^C n.m.r. s p e c t r a o f |"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 d e u t e r i o b e n z e n e s o l u t i o n .  (vi)  FIGURE 9  -55-  Magnitudes o f  3 119 13 J( SnCC C) p l o t t e d  against the dihedral  angle 0 . ( r e f 5 9 ) .  FIGURE 10  -5713  N a t u r a l abundance  C n.m.r. spectrum  a-D-altropyranoside)2-C-stannane showing the normal  resonances  o f t r i p h e n y l ( m e t h y l 4,6-0-benzylidene-  26 i n d e u t e r i o a c e t o n e s o l u t i o n  (0.3 M)  and t h e t i n s a t e l l i t e s o f t h e C - l , C-2,  and C-3 resonances. FIGURE 11  -7213  N a t u r a l abundance  C n.m.r. s p e c t r a , o f t r i p h e n y l (methyl  a - D - a l t r o p y r a n o s i d e ) 2-C-stannane 26^ i n d e u t e r i o b e n z e n e from a s e l e c t i v e d e c o u p l i n g experiment, resonances  are a s s i g n e d .  4,6-C^-benzylidene-  solution  (0.3 M) ,  showing how t h e i n d i v i d u a l  (vi) ACKNOWLEDGEMENT I wish t o thank Dr. L. D. H a l l f o r h i s h e l p , encouragement and enthusiasm throughout t h i s p r o j e c t .  I a l s o wish t o thank J . D. A p l i n f o r  h i s competent and, sometimes, r u t h l e s s  editing of this thesis.  -1-  INTRODUCTION  I n common w i t h many a r e a s o f o r g a n i c chemistry philic  has p r o f i t e d by t h e f l e x i b i l i t y  displacement  from t h e chemist's  reaction  (S^2).  This  c o n t r o l over three  chemistry,  of thebimolecular flexibility  important  l e a v i n g group, t h e n u c l e o p h i l e and t h e s o l v e n t . w i t h some i n n o v a t i o n s involve the f i r s t novel  T h i s work  deals  chemistry  v a r i a b l e s -- t h a t i s , w i t h  reactions i ti sconvenient  (CI, B r , I ) as t h e l e a v i n g group.  chemistry (C-l  i s derived  which  some  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  atom  nucleo-  v a r i a b l e s -- t h e  i n the area o f carbohydrate  two o f t h e s e  carbohydrate  follows this  position),  and w i d e l y  carbohydrate centre  i n t h e sense t h a t t h e g l y c o s y l h a l i d e s a r e u s e f u l  g e n e r a l l y more e x p e d i e n t  centres This  i t i s i s in  sulfonates are readily obtained i n  and e a s i l y p u r i f i e d  furthermore,  a t other  t o use a s u l f o n a t e e s t e r .  g e n e r a l b e c a u s e many o f t h e s e  precursors;  Although  t r e n d f o r r e a c t i o n s a t t h e anomeric  used r e a c t i o n i n t e r m e d i a t e s ,  a crystalline  t o employ a h a l o g e n  form from p a r t i a l l y  blocked  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 conditions.  E v e n s o , i t i s n o t o b v i o u s why s o much e m p h a s i s h a s  been p l a c e d by c a r b o h y d r a t e sulfonates — ates  chemists  on j u s t t h r e e  t o s y l a t e s (OTs), m e s y l a t e s  (OSO^Ph), e s p e c i a l l y when T i p s o n , 1  classes of  (OMs) a n d b e n z e n e s u l f o n i n 195 3 i n a r a t h e r  -2-  prescient  r e v i e w a r t i c l e on  drawn a t t e n t i o n t o t h e known t o e n h a n c e t h e "Finally,  sulfonate  e s t e r s of carbohydrates,  fact that electron-withdrawing  leaving properties  (attached  t o s u g a r s and  alditols)  i n r e l a t i o n to ease of d e s u l f o n y l o x y l a t i o n . doubt t h a t , i n t h i s prove s u p e r i o r on  regard,  the  order  of  3  p-Br  3  and  the  there  part review a r t i c l e  t o 1969,  investigate o f f e r e d an sulfonate  < p - N 0 ) , and  of t h i s  their dinitro-  Fifteen  3  sulfonate i n the  described,  range of  sulfon-  s i t u a t i o n p r o m p t e d us  to increase  the  remarks,  esters  f a m i l i e s of f l u o r i n a t e d s u l f o n a t e s  i d e a l opportunity ester  little  2,4  2  l a c k of i n n o v a t i o n  Recognition  several  be  showed t h a t , i n s p i t e o f T i p s o n ' s  been a n o t a b l e  ate e s t e r s used.  tested  ' , which summarized  l a r g e number o f a p p l i c a t i o n s for  had  been  p-substituents  g r o u p s m i g h t p r o v e more e f f i c a c i o u s . "  a two  l i t e r a t u r e up  There can  (since, for  2 years l a t e r ,  have not  increasing reactivity•of  e t h y l e s t e r s i s p - C H 0 < p-CH < p-H< phenylsulfonyl  v a r i e t y of s u l f o n i c  p - n i t r o p h e n y l s u l f o n y l groups would  to t o s y l or mesyl groups  the benzene r i n g ,  groups were  of a r y l - s u l f o n a t e e s t e r s : -  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  radicals  had  to  which  the  scope of  carbohydrate  first  reported  the  chemistry. 4  I n 1957, a b l e 0-,  N-  G r a m s t a d and and  C-  Haszeldine  alkylating properties  e s t e r s of t r i f l u o r o m e t h a n e s u l f o n i c trifluoromethanesulfonate  reacted  trifluoromethanesulfonate  and  t i o n o f b e n z e n e was  occurred  t i o n s of NHE1  to N E t  0  0  with  e t h y l and  methyl  They f o u n d t h a t  methyl  d i e t h y l ether  ethyl  and  t o form e t h y l that  alkyla-  trifluoromethanesulfonate;  a t room t e m p e r a t u r e . and  the  e t h y l methyl ether,  e f f e c t e d by  both reactions  acid.  of  remark-  Similarly,  o f NH^Ph t o HNPhEt and  N-alkyla-  NPhEt,, w e r e  -  -3-  effected  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 t e m p e r a -  ture. 5-10 Since then, several results,  authors  have p u b l i s h e d  a l l a t t e s t i n g to the e x t r a o r d i n a r y  trifluoromethanesulfonic et a l ^ found  that  acid esters  acetolysis  ethanolysis  i n 100%  reactivity  or " t r i f l a t e s " .  of  about  of e t h y l t o s y l a t e  of e t h y l brosylate  ethanol at that  the  Streitwieser  of e t h y l t r i f l a t e proceeds  30,000 t i m e s f a s t e r t h a n t h e a c e t o l y s i s 5,000 t i m e s f a s t e r t h a n t h a t  similar  and  a t 25°C.  temperature  Its  i s about  450,000  times f a s t e r than that  of e t h y l benzenesulfonate.  ethanol,  i t solvolyzes  150,000 t i m e s f a s t e r t h a n e t h y l  bromide.  Two  less reactive  series  esters  were l a t e r r e p o r t e d —  of f l u o r i n a t e d  fluorobenzenesulf onates, typically  sulfonate  aqueous  the 2,2,2-trifluoroethanesulfonates,  " t r e s y l a t e s " , by B u r d o n and M c L o u g h l i n ^  These e s t e r s  I n 80%  i n 1964,  and  the  penta-  o r " p e n t a f l a t e s " , by Connett"*"\  a p p e a r t o be  than the c o r r e s p o n d i n g t o s y l a t e s  a b o u t 100  and  than the c o r r e s p o n d i n g t r i f l a t e s .  or  in  t i m e s more  a b o u t 400  times  A Hammett p l o t  reactive  less  increased tosylate t h e s e and The esters  reactivity  range  from a f a c t o r of a p p r o x i m a t e l y and b r o s y l a t e  leaving  the f l u o r i n a t e d possibilities  d i d not escape  reactions  of the sulfonate  on  1 .  t h e n , has  10 b e t w e e n t h e  been  mesylate,  g r o u p s t o a b o u t 80,000 b e t w e e n  sulfonate  afforded  esters,  reactive  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 The  1965.  by  esters. these novel,  our a t t e n t i o n ;  with  s e n s i t i v e s u g a r s m i g h t be  extremely  t h e s e as  reactive  intermediates,  c a r r i e d out q u i c k l y  and  at  -4-  low t e m p e r a t u r e s , tion.  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-  Furthermore,  n u c l e o p h i l i c displacement  now t a k e p l a c e o n s y s t e m s w h i c h completely, unreactive. experiment  r e a c t i o n s might  p r e v i o u s l y had been almost, o r  A t the s t a r t  of this  h a d been done, i n t h e c a r b o h y d r a t e  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 ,  s t u d y , o n l y one area, with  and t h i s  triflates.  i s described  i n C h a p t e r one.  FIGURE 1  Hammett p l o t of  for  the  solvolytic alkyl-oxygen  cleavage  X-S0 R. 3  With r e s p e c t t o t h e 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  of studies i n carbohydrate  chemistry.  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 w o r k b y S t e i n e r suggested  t h a t t h i s might 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 w o r k , we c h o s e t o s t u d y t h e s y n t h e s i s o f m e t a l  deriv-  -5-  a t i v e s w i t h t h e m e t a l bonded d i r e c t l y  t o carbon.  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.  Alkyl  and a r y l  t i n compounds r e a d i l y  undergo  metal-  halogen exchange r e a c t i o n s o f t h e t y p e :  MCI  •C-Sn'  •Sn-Cl  C-M  M = Mg, L i , A l , Na, K, Zn or MgCl  The  Grignard  method  (M=MgCl) c a n b e u s e d t o i n t r o d u c e  organic  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 they not  i n t e r a c t w i t h o r g a n o m a g n e s i u m compounds.  higher y i e l d s by  are obtained  an o r g a n o l i t h i u m  seemed f e a s i b l e  when t h e G r i g n a r d  compound.  I n c e r t a i n cases, reagent i s replaced  However, n e i t h e r o f t h e s e  from t h e carbohydrate  do  chemist's  as t h e r e h a s b e e n no l i t e r a t u r e o n t h e f o r m a t i o n  methods  p o i n t of view, of a  o r a s u g a r - l i t h i o compound, a n d i t d i d n o t seem l i k e l y  sugar-Grignard that  such  a m o i e t y w o u l d be s t a b l e u n d e r n o r m a l 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 m e t h o d o f p r e p a r a t i o n v/hich c a n be u s e d f o r t h e introduction of functionally  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-  b e t w e e n a compound c o n t a i n i n g t i n b o n d e d t o an a l k a l i m e t a l a n d 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 g r o u p :  R SnLi  R'X  3  R^SnR  1  I n 1 9 6 2 , T a m b o r s k i e t al" "" p u b l i s h e d 1  1  LiX  the synthesis of 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 I t was r e p o r t e d as b e i n g  a fairly  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, g a v e f a i r l y of the corresponding  organotin  metal.  compounds.  high  I n 19 70,  yields  Zimmer a n d  l '> u  Bayless  s y n t h e s i z e d a number o f o r g a n o t i n a n d 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  triphenylsilicon  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 t h e 3 - p o s i t i o n by e i t h e r a halogen  (Br, C l or I) or a Grignard  same t i m e ,  i n this  functionality.  d e p a r t m e n t , 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 *  i m e n t s w i t h r e a c t i o n s o f some 0 ^ M L i compounds, on b l o c k e d  sugars,  method f o r f o r m i n g we d e c i d e d  M = S n , Pb a n d S i ,  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  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 .  feasible Therefore,  t o i n v e s t i g a t e and document t h e 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 *  A t about the  carbohydrates.  The s y m b o l 0 w i l l be u s e d t h r o u g h o u t t h i s a phenyl group.  The e x p e r i m e n t s  described  thesis to represent  -7-  i n C h a p t e r two c o n c e r n o u r a t t e m p t s i n t h i s Besides t h e i r  potential synthetic novelty,  t h a t we h o p e d t o s y n t h e s i z e n.m.r. s t u d i e s . tives  The s a l i e n t  their  were l i k e l y feature  c a n be made c o n f o r m a t i o n a l l y  give well-dispersed  the derivatives  t o be g o o d m o d e l s f o r  here i s that  rigid,  ''"H n.m.r. s p e c t r a ,  favoured conformation d i r e c t l y .  sugar  and s i n c e they  derivafrequently  i t i s possible t o evaluate N.m.r. a n d  studies o f the t r i f l a t e and, p a r t i c u l a r l y , w i l l be d e a l t w i t h  area.  conformational  of the t i n derivatives  a t the end o f the appropriate  chapters.  -8-  CHAPTER I  Fluorinated  a)  Their  Sulfonic Esters  synthesis  and  reactions  of  with  Sugars  pyridine.  TRIFLATES  The of  four  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  trifluoromethanesulfonic  fluoromethanesulfonic fluoride,  and  a similar  (CF S0 ) 0 2  2  +  X= F, C l  anhydride, t r i f l i e  triflie  reaction with  +  triflates,  synthesis  are t r i -  chloride  or  triflate.  a n h y d r i d e and  type of  3  ("triflie")  silver  Triflie  a c i d e s t e r s , or  used f o r  ROH  ROH  +  +  an  c h l o r i d e , or alcohol,  fluoride,  undergo  thus:  B:  B  + HB X  = u s u a l l y a t e r t i a r y organic base e.g.  +  pyridine  _ 9  Silver  triflate,  halide, generally  on t h e o t h e r h a n d , r e a c t s  an a l k y l b r o m i d e ,  CF S0 Ag 3  3  +  R  _>  X  with  an a l k y l  t o form t h e d e s i r e d  CF S0 R 3  3  esters:  AgX  +  X= C l , Br  All  four  reagents  are commercially a v a i l a b l e , quite  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  s i l v e r s a l t were p u r c h a s e d chloride stable  are v o l a t i l e  indefinitely  silver salt presence foil  inside a  ( b . p . 80°C a n d 32°C, r e s p e c t i v e l y ) " ^ ,  a t room t e m p e r a t u r e  The  but i s unstable i n the  a n d was t h u s k e p t i n a b o t t l e w r a p p e d i n a l u m i n u m  investigations  was n o t s u f f i c i e n t l y of t r i f l i c  reactive  indicated  that  chloride, pyridine  with  reaction.  triflate  was f o u n d  Equimolar  chloride quan-  and 1 , 2 : 5 , 6 - d i - O - i s o p r o p y l i d e n e -  2_ ( f i g u r e 2) , w e r e s t i r r e d  no s i g n i f i c a n t  the t r i f l i c  f o r our purposes.  a -D-glucofuranose,  Silver  and a c i d  dessicator.  Preliminary  tities  liquids  The a n h y d r i d e  and t h e  a t -10° - 0°C u n d e r a n h y d r o u s c o n d i t i o n s .  i s stable  of light  f o r o u r work.  stable  f o r 2 d a y s a t 20°C  t o b e more r e a c t i v e  i n a related  17 s e r i e s of experiments  by B e r r y  inconvenient, r e q u i r i n g removal Moreover, another  , h o w e v e r t h e r e a c t i o n w o r k u p was of very f i n e ,  s t e p was r e q u i r e d  insoluble  i n the reaction  salts.  sequence —  that  -10-  of  formation of the sugar The  a n h y d r i d e was  our work.  I t was  halide.  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  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  Thus, e q u i m o l a r q u a n t i t i e s  of t r i f l i c  reacted t o g i v e the d e s i r e d t r i f l a t e -15°C.  The  triflate  anhydride, pyridine 5_ i n l e s s t h a n one  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 t h e  i n that a t r i f l a t e  alcohol.  Moreover,  fication  procedure.  Our  c o u l d be  insoluble salts  f i n d i n g s appear  formed  7  fluoride  1 0  '  1 8  ~  2 1  '  2 4  '  2 5  .  reference  and  Silver  silver  from  of  5  1  2  '  frequently.  t o t h e use o f t r i f l i c  c h l o r i d e has been used q u i t e  "triflamides",  2  2  and  chloride  for  t h i s w o r k meant c a r e h a d hydrous  t o be  r e a c t i o n c o n d i t i o n s and  c h l o r i d e , chosen  successfully  of the t r i f l a t e s  low t e m p e r a t u r e s .  as a c o n v e n i e n t s o l v e n t , was  (-10°  However,  f o r the s y n t h e s i s which  f o r amine prepared i n an-  Methylene  f o u n d t o be  best reaction  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 o r i c e - b r i n e  t o -20°C).  t a i n and,  The  syn-  found  t a k e n t o u s e an i n e r t s o l v e n t ,  under the r e a c t i o n c o n d i t i o n s used. r a n g e was  Triflic  triflate  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  possible high reactivity  puri-  triflic  This author  h a v e b e e n f o u n d t o be v e r y u s e f u l b l o c k i n g g r o u p s , ,. ,... 27-31 functionalities The  the  i n the  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 w e r e g i v e n . triflic  at  reagent f o r t r i f l a t e  triflate '  less  2  hour  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 .  4 23 ' have been used 26  o n l y one  directly  are not a problem  a n h y d r i d e has been the most w i d e l y used theses "  chloride.  L o w e r t e m p e r a t u r e s w e r e more d i f f i c u l t  a t h i g h e r t e m p e r a t u r e s , some o f t h e t r i f l a t e s ,  inert  temperature bath t o mainnotably  1 , R = OH  2 , R = OH  3 , R = OH  4 , R = 'OTf  5 , R = OTf  6 , R = OTf  8^ , R = OS0 CH CF 2  2  11, R = OS0 C F 2  6  3  5  14, R = OTs  9 , R = OS0 CH CF 2  3  7_ , R = C j H N OTf  12, R = 0S0 C,F — 2 6 5  10, R = OS0 CH CF  15, R = OTs  13_, R  OS0 C F  17_, R = C H N OTf"  16, R  OTs  19, R = C j H N V  18, R  C H N OTs"  20, R  c H N r  o  5  FIGURE 2  2  c  5  2  2  f o r t h i s work.  6  +  5  5  3  5  5  Fluorinated sulfonyl and pyridinium t r i f l y l derivatives synthesized  2  -12-  the primary ones, tended  t o decompose.  s u l f o n y l reagents are not d i f f i c u l t p r o d u c t s were s i g n i f i c a n t l y  Although  to handle,  improved  the  fluorinated  the y i e l d s of  by w o r k i n g  under  the  anhydrous  c o n d i t i o n s i n an a t m o s p h e r e o f d r y n i t r o g e n . Initial  experiments  for  t h i s w o r k was  had  t o be  to  indicated  t h a t the best scavenger  p y r i d i n e , a l t h o u g h i t was  base  discovered that care  taken, e s p e c i a l l y w i t h the s y n t h e s i s of a primary  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  to avoid obtaining  the p y r i d i n i u m s a l t r a t h e r than the d e s i r e d t r i f l a t e . experiment,  I n an  initial  1,2:3,4-di-0-isopropylidene- -D-galactopyranose,  3_  a  ( f i g u r e 2 ) , was pyridine.  triflate,  r e a c t e d w i t h a 1%  excess  A f t e r a p p r o x i m a t e l y 1/2  i n d i c a t e d t h a t _3 h a d  hour,  reacted completely.  of t r i f l i c t.l.c.  anhydride  (toluene:ether-1:2)  Workup o f t h e  reaction,  as d e s c r i b e d i n t h e 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 platelets.  Subsequent s p e c t r a l  a n a l y s i s proved  in  crystalline  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 luoromethanesulf onate substance  7_.  showed t h e p r e s e n c e  pyridine, at  T 0.74  T h u s , t h e p.m.r. s p e c t r u m of aromatic resonances,  ( o ) , 1.68  s p e c t r u m w i t h t h a t o f 3^ i t s e l f 6-hydroxy group had r e s o n a t i n g now for  1_, due,  was  now  (m)  and  possibly,  (p).  due  to  f r o m T 6 . 1 f o r 3_ t o 4 . 7 5 and T  to the f a c t t h a t the carbon  a s s i g n e d t o t h e CF^SO^  moiety.  and  identify  the primary  A subsequent  the  the were 5.08  i n the 6 - p o s i t i o n  b o u n d 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 . compound showed a s i n g l e t  of  Comparison of  t h a t t h e p r o t o n s on C-6  f l u o r i n e n.m.r. o f t h i s  isolate  the  typical  r e v e a l e d the resonance  d i s a p p e a r e d and  at lower f i e l d ,  1.18  of  at 0  attempt  t r i f l a t e ' 6_, i t s e l f ,  c  The  + 81.2  ppm.,  to prepare, using equi-  -13-  molar q u a n t i t i e s  of blocked sugar, 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 , h o w e v e r , was u n s u c c e s s f u l , a s d e c o m p o s i t i o n o c c u r r e d a t temperatures  much a b o v e 5°C.  Therefore i t i s suggested that  £  c a n be u s e d as r e a c t i o n i n t e r m e d i a t e , b u t w o u l d b e i s o l a t e d o n l y with  difficulty. In  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 r e a c t e d 16 w i t h p y r i d i n e . r e f l u x temperature The  16_, we  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  f o r 25 h o u r s 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 .  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  t h e same manner as 6_, a s t h e 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-di-0-isopropylidene-6-pyridino- a-D-galactopyranose t o l uene-p-sulfonate 18. to  a 9 0% y i e l d  A 30% y i e l d o f 18_ was o b t a i n e d , c o m p a r e d  o f 1_ o b t a i n e d f r o m t h e t r i f l a t e  some o f t h e a d v a n t a g e s  o f the t r i f l a t e moiety  reaction.  Thus,  over the t o s y l a t e  m o i e t y a s a l e a v i n g g r o u p 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 w e r e now q u i t e a p p a r e n t . appeared  The t r i f l a t e  order to v e r i f y  deed been formed, salts,  faster,  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 In  r e a c t i o n was  that the t r i f l y l  than the t o s y l a t e  reaction.  p y r i d i n i u m s a l t had i n -  b o t h 7_ a n d 1 8 w e r e c o n v e r t e d t o t h e i r  iodide  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 t h e 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 a n d m i x e d m e l t i n g p o i n t s a s w e l l a s n.m.r. s p e c t r a l verified  t h a t t h e same i o d i d e s a l t ,  2_0, was o b t a i n e d f r o m  data  1_ a s  from 18. ' Having  thus examined t h e enhanced r e a c t i v i t y  of a primary  -14-  sugar t r i f l a t e ,  we t h e n t u r n e d o u r a t t e n t i o n t o s e c o n d a r y 12  triflates.  N  triflates  that  tosylate  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  reactive i n S 2 reactions. of  3  I t has been n o t e d by s e v e r a l a u t h o r s ' '  functionalities  sugar  I t was t h o u g h t t h a t p e r h a p s  t h e use  w o u l d 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 s u g a r  molecules  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 w e r e 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 Therefore,  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 u r a n o s e JL,  was r e a c t e d w i t h a 1 0 % 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 . t.l.c.  group.  (toluene:ether-1:2) indicated  After  the reaction  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  1 hour,  t o be c o m p l e t e .  c r y s t a l s were ob-  t a i n e d , w h i c h w e r e i d e n t i f i e d £>y n.m.r. a s 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_. a s s i g n e d t o H-3  Thus, t h e resonance  ( T ^.p) i s d o w n f i e l d f r o m 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. s p e c t r u m o f 4_ showed assigned t o the t r i f l a t e  moiety.  a singlet at 0  The y i e l d o f 4 was  C  + 78.8,  essentially  quantitative. 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  conversion of 1  o  r  4 to 1,2:5,6-di-O-isopropylidene-3-pyridino-  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.  T h u s , 1 o r 4_ was d i s s o l v e d i n p y r i d i n e a n d h e a t e d t o r e f l u x  temperature  f o r 25 h o u r s 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 triflate  salt,17.  The p.m.r. s p e c t r u m o f t h e 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 resonances (p).  The J  0  - T . 9 4 ( O ) , T 1.61(m) a n d x 1.09  ^ c o u p l i n g was c a . 0 , i n d i c a t i v e o f a n e l e c t r o n e g a t i v e  -15-  species at the 3 p o s i t i o n of a g l u c o f u r a n o s e sugar, 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  compound showed a s i n g l e t  triflate In  moiety.  contrast,  The  under  yield  similar  at 0  o f 17  The  F n.m.r. s p e c t r u m  + 81.6  c  was to  a 10%  g i v e , w i t h i n one  excess of t r i f l i c  70%.  1,2:5,6-di-O-  14,did not  react. 2_,  d e t e r m i n e d , by  anhydride i n p y r i d i n e  h o u r , an a l m o s t q u a n t i t a t i v e y i e l d 1  o f what  19  H and  F n.m.r., t o be  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_. of  assigned to the  1,2:5,6-di-O-isopropylidene- a-D-glucofuranose  reacted with  was  of  approximately  conditions,  isopropy lidene-3-O-tosyl- a-D-allofuranose, Similarly,  ppm.,  f r o m .1 was  reaction  confirming  1,2:5,6-di-O-isoproThe  p.m.r.  t h e p r o d u c t a g a i n showed a l a c k o f a 3 - h y d r o x y  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  spectrum  resonance  p r o t o n f r o m x5.6  as  f o r 2_ t o  19 T  4 . 6 6 f o r 5.  at 0  c  +  77  The  F s p e c t r u m showed a s i n g l e  triflate  resonance  ppm.  • I t h a s b e e n f o u n d t o be v e r y d i f f i c u l t nucleophilic displacement reaction presumably,  to s t e r i c  hindrance.  t o a c h i e v e an S„ 2 T  a t t h e C-3 O n l y one  p o s i t i o n of 2  due,  such r e a c t i o n has  been  32 reported  .  T h i s was  the d i s p l a c e m e n t o f the t o s y l a t e group  1,2:5,6-di-O-isopropylidene-3-0-tosyl- a-D-glucofuranose, by h y d r a z i n e , p e r h a p s very  little  steric  might a c t i v a t e S 2 N  s u c c e s s f u l because  bulk.  I t was  the 3 p o s i t i o n  dine f o r 5 days, t . l . c .  15,  the h y d r a z i n e i o n possesses  thought t h a t the t r i f l a t e  o f 2_ s u f f i c i e n t l y  nucleophilic displacement reaction.  of  group  t o a l l o w f o r an  After refluxing  in pyri-  (toluene:ether-2:1)indicated that a l l of  !5 h a d r e a c t e d , b u t t h e 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 a s s u m e d t o h a v e o c c u r r e d , h o w e v e r t h i s was n o t f u r t h e r  studied.  4_ a n d 5_ w e r e f o u n d t o b e s t a b l e cold  f o r up t o 6 months i f k e p t  (-10 - 0°C) a n d d r y , h o w e v e r a t room t e m p e r a t u r e , o p e n t o t h e  atmosphere, b o t h d e r i v a t i v e s decomposed w i t h i n As m e n t i o n e d of  reaction  i n the introduction,  t h i s w o r k o n l y one t r i f l a t e  a few h o u r s .  a t t h e time o f the beginning  experiment w i t h sugars had been 12  reported i n the l i t e r a t u r e . use o f s i l v e r of  triflate  K r o n z e r and S c h u e r c h  and o t h e r s i l v e r  salts  reported the  i n the methanolysis  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  silver triflate  - assisted  intermediates f o r the  methanolyses.  Some months a f t e r t h e s t a r t o f t h i s  series  of experiments,  25 M a r a d u f u and P e r l i n  published the synthesis o f methyl  O-benzoy1-4-0-triflyl-S -D-glucopyranoside lar  to ours.  2,3,6-tri-  21 u s i n g a m e t h o d  I t was f o u n d t o h a v e p h y s i c a l c h a r a c t e r i s t i c s  simisimilar  :H OBZ 2  21  rfo OBz to  our secondary  fairly  stable,  sugar t r i f l a t e s .  Thus 2_1 was c r y s t a l l i n e a n d  although 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 a n y o b t a i n e d b y u s , p e r h a p s method o f p u r i f i c a t i o n w h i c h column.  We do n o t b e l i e v e  owing t o t h e  i n c o r p o r a t e d the use o f a s i l i c a g e l  that this  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  i s a good method f o r p u r i f i -  as t r i f l a t e s ,  p r e f e r r i n g both f o r  -17-  t h em a n d , 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 d e r i v a t i v e s made i n t h i s  fluorinated  sulfonate  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 petroleum e t h e r (30-60).  A f t e r c o o l i n g the washings,  fonate would  invariably  and t h e t r e s y l a t e s ,  crystallize.  the c r y s t a l s  sugar  sul-  In the cases of the t r i f l a t e s  filtered  were f o u n d t o be a n a l y t i c a l l y p u r e . 1 or 2 further recrystallizations  the fluorinated  o f f from t h i s  solution  I n the case o f t h e p e n t a f l a t e s ,  from petroleum e t h e r  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 pure e x c e p t i o n was 1 2 , b u t c o l u m n p u r i f i c a t i o n  i n this  (30-60) samples.  c a s e was  An  found  t o b e no b e t t e r t h a n t h e p e t r o l e u m e t h e r e x t r a c t i o n a n d r e c r y s t a l lization  method.  Maradufu and P e r l i n sodium  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  a z i d e t o form methyl  4-azido-2,3,6-tri-O-benzoy1-4-  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  proceeded  f a s t e r than t h a t of the analogous p-bromophenylsulfonate s t u d i e d -- 2 h o u r s was l o w e r —  a s c o m p a r e d t o 12 h o u r s  also  -- t h e y i e l d o b t a i n e d  75% a s c o m p a r e d t o 9 6 % .  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 trifluoromethane sulfonate — and b e n z y l a l c o h o l —  s y n t h e s i z e d from t r i f l i c  anhydride  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 s u g a r  derivatives. 18 B e r r y and H a l l in this  department,  , 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 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  tri-  f l a t e i n t h e s y n t h e s i s o f some O - b e n z y l a t e d a n d O - m e t h y l a t e d bohydrate d e r i v a t i v e s .  '  car-  -18-  TRESYLATES  As i t was  the  i s o l a t i o n of  a primary t r i f l a t e  decided to i n v e s t i g a t e  sulfonate  ester  derivatives  other,  of  proved  less reactive  sugars i n the  6 been r e p o r t e d f l a t e s , but  esters,  or  '  be  found.  " t r e s y l a t e s " , have  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  more r e a c t i v e  than t o s y l a t e s .  The  to attempt to synthesize  the  groups than  acid  I t was  1  and  could  a more  9  (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 ^ . cided  fluorinated  hope t h a t  t r a c t a b l e primary f l u o r i n a t e d sugar sulfonate 2,2,2-trifluoroethylsulfonate  unsuccessful,  tri-  chloride therefore  t r e s y l a t e d e r i v a t i v e s of  de-_ 1_, 2_  3_. U s i n g a method s i m i l a r t o t h a t  3_ was  reacted  of p y r i d i n e a f t e r the  with  a 15%  excess of  f o r the  tresyl chloride  i n m e t h y l e n e c h l o r i d e , a t -15°C  usual  w o r k u p , an  89%  d i d show a q u a r t e t , l i n g of  the  the  fluorine with  (J=9.25 H z ) ,  the  triflates,  a 60%  excess-  hours, to  determined to  -D-galactopyranose.  compound showed no  at x5.37  of  and  f o r 1.5  y i e l d o f w h a t was  1,2:3,4-di-0-isopropylidene-6-0-tresyl-a p.m.r. s p e c t r u m o f  synthesis  tresylate protons.  A g a i n , the  be The  6-hydroxy r e s o n a n c e , a t t r i b u t e d t o the  give,  but  coupH-6  p r o t o n resonances were d o w n f i e l d from those o f 3_ ( T 5.4 3 and T 5.53 f o r 1 0 ; o f 10_ showed a t r i p l e t a t 0 group.  A c c o r d i n g t o the  t h e H-6 p r o t o n s o f 19 x 6.1 f o r 3_) . The F n.m.r. s p e c t r u m + 63.6 ppm., a s s i g n e d to the t r e s y l a t e 6  literature  more r e a c t i v e t h a n 16. The t r e s y l a t e d e r i v a t i v e s  , 10  of: 1^ and  could  be  up  to  2_, r e s p e c t i v e l y ,  100  times  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_, a n d 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-glucofuranose  1,2:5,6-  9_ w e r e 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 9 0 % y i e l d . I d e n t i f i c a t i o n o f t h e compounds w a s , as b e f o r e , e f f e c t e d b y "*"H 19 and  F n.m.r.  T h u s , t h e p..m.r. s p e c t r a o f 8_ a n d 9_ e a c h  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 g r o u p ( J 9.3 Hz i n b o t h c a s e s ) , a s w e l l a s 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  ( f o r 8^ x 4 . 5 1 f r o m T 5.7  proton resonances  p  H  f o r 1;  19 f o r 9_, T 4 . 8 1 f r o m triplet  at 0  C  T 5.6 f o r 2) .  + 63.2 ppm.,  Again, the  F n.m.r. s h o w e d a  f o r b o t h compounds, due t o t h e t r e s y l a t e  group. All  the t r e s y l a t e d e r i v a t i v e s  were c r y s t a l l i n e , left  stable  a t room t e m p e r a t u r e ,  synthesized i n this  indefinitely,  d r y , a t 0°C.  open t o t h e atmosphere,  study However, i f  decomposition  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_ a n d 3_ i n t o t h e 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 a n d 1 3 , pectively,  u s i n g t h e 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 m e t h o d , was  less satisfactory.  Y i e l d s were l e s s  t h a n 40% a n d , f o r t h e c o n -  v e r s i o n o f 2_ t o 1 2 , an a n a l y t i c a l l y p u r e tained.  res-  s a m p l e c o u l d n o t be o b -  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 r e a c t i o n time  improvement i n y i e l d ,  neither did variations i n  (3-48 h r s . ) a n d t e m p e r a t u r e  (-20 - + 8 0 ° C ) . A l l  -20-  products,  again,  2_, i n p a r t  and  were i d e n t i f i e d by  (b) o f t h i s  chapter,  o f t h e compounds s y n t h e s i z e d As and  H and  show t h e s h i f t s  i n this  par w i t h  of the t r e s y l a t e s i s purported  esters, the high  reactivity  secondary t r i f l a t e s  inated sulfonate  chemistry, otherwise  make them a more d e s i r a b l e c h o i c e  and o t h e r  p o t e n t i a l f o r the f i e l d  as t h e s e e s t e r s m i g h t a l l o w unreactive  of  f o r syn-  or nonfluor-  of synthetic  carbohydrate  f o r r e a c t i o n s on  very  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 t h e still  p r e s e n t a number o f d i f f i c u l -  Thus, i n r e a c t i o n s where a t r i f l a t e  p y r i d i n e and t r i f l i c  fluorinated sulfonate  a minimum o f s i d e - r e a c t i o n s .  area of carbohydrate chemistry  was s y n t h e s i z e d  anhydride, then reacted without p r i o r  a nucleophile  using isola-  s u c h as t e t r a - n - b u t y l a m m o n i u m 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 w e r e o b t a i n e d . triflate  sul-  f o r S^2 d i s p l a c e m e n t o n  m o l e c u l e s and a l l o w  However, t r i f l a t e  the  which  and c o m p a r a t i v e s t a b i l i t y  stated, t r i f l a t e s  s e n s i t i v e sugars w i t h  tion with  esters  esters.  previously  e s t e r s show g r e a t  ties.  t o be o n a  For secondary  t h e t i c work t h 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  As  expensive  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 h e r e t h a t t h e  a r e more t r a c t a b l e a n d s t a b l e t h a n t r i f l a t e s .  the  couplings  chloride i s fairly  f o r m e r be u s e d 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  fonate  and  study.  the pentafluorobenzenesulfony1  as t h e r e a c t i v i t y  T a b l e s 1^  F n.m.r.  I t i s possible  s a l t s p r o d u c e d by t h e base and t h e l i b e r a t e d  that  triflic  -21-  a c i d a r e r e a c t i v e , and the t r i f l a t e each  In these c a s e s , perhaps  t r i f l a t e m e t h o d s w o u l d be b e s t .  s y l a t e c o u l d be the e s t e r could  be n e c e s s a r y t o i s o l a t e  used;  although i n this  f o r m e d w o u l d be d e c r e a s e d  still  be  and  purify  time, c a u s i n g problems i n the case of the u n s t a b l e  primary t r i f l a t e s . or s i l v e r  i t may  c a . 100  the t r i f l i c  fluoride  A l t e r n a t e l y , the  case the r e a c t i v i t y  by  treof  a f a c t o r of ca.4000, i t  t i m e s more r e a c t i v e t h a n t h e  corresponding  tosylate. Doubt a l s o remains scavenging  c o n c e r n i n g t h e most s u i t a b l e method  liberated t r i f l i c  acid.  I t has been f o u n d  alkylate p r e f e r e n t i a l l y at nitrogen t h a t a base such  rather  of  that  triflates  4 9 than a t oxygen ' so  as p y r i d i n e o r e v e n l u t i d e n e  i s unacceptable.  33 Lemieux  has  scavenger,  used  and  2,4,6-trimethylpyridine  t h i s may  often  as a t r i f l i c  be t h e b e s t c h o i c e ,  acid  being  relatively 18  i n e x p e n s i v e and q u i t e found  a poor  nucleophile;  that, i n certain reactions,  and t h a t , Although  even t h i s has  the l a t t e r  is fairly  e x p e n s i v e , i t c a n be  addition of pyridine  the workup, f o l l o w e d  N-alkylated  by d i s t i l l a t i o n .  2,6-di-tert-butyl~4-methylpyridine,  than  2,6-di-tert-butylpyridine. Clearly, therefore,  the area of S 2 N  of t r i f l a t e s  L i n d b e r g and which  on  before t r i f l a t e s  f u l i n the area o f s y n t h e t i c carbohydrate sulfonate  esters  c u r r e n t l y i n use.  sugar  after 34  co-workers  i s less  expensive  much i n v e s t i g a t i v e w o r k n e e d s t o be  nucleophilic attack  on s u g a r s )  regenerated  to the r e a c t i o n mixture  used  inated  been  has  i n these cases, 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 .  f r o m t h e s a l t by  in  however B e r r y  triflates  done  (or  become as g e n e r a l l y  use-  c h e m i s t r y as t h e  unfluor-  -22-  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 o f 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. s p e c t r a o f t h e p y r i d i n i u m s a l t s 1_, 1 7 - 2 0 were s u f f i c i e n t l y w e l l d i s p e r s e d i n d e u t e r i o a c e t o n e  solutions to  make f i r s t - o r d e r assignments and a n a l y s e s s t r a i g h t f o r w a r d .  The  r e s u l t i n g d a t a a r e summarized i n T a b l e 1. I n every i n s t a n c e , t h e v i c i n a l ^H-^H  c o u p l i n g c o n s t a n t s were  v e r y s i m i l a r t o those o f t h e s u l f o n a t e p r e c u r s o r  (Table 2) and i n -  d i c a t e d t h a t these m o l e c u l e s had t h e a n t i c i p a t e d s o l u t i o n geometry. Thus, the t h r e e d e r i v a t i v e s o f 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  t x v e o f the t w i s t - b o a t c o n f o r m a t i o n  shown below.  -23-  In "like fashion,  i t i s clear that  the furanose  derivatives  3 17  and 19  of J  2  favour the a n t i c i p a t e d  ^ being unequivocally  conformation, the zero value  i n d i c a t i v e of that  particular•confor-  36 mation  A l t h o u g h o f no d i a g n o s t i c t h a t the geminal  coupling  p o t e n t i a l i t i s interesting to  ( J ^ g')  a b s o l u t e terms f o r the pyranose f o r the furanose d e r i v a t i v e s The  introduction  i s s u b s t a n t i a l l y smaller  derivatives  (-8.5  (-13.5 Hz)  by  the r i n g current H-6,  H-6'  of the p y r i d i n i u m  moiety  the e l e c t r o n w i t h d r a w i n g  causes  are close  inductive  e f f e c t of the aromatic r i n g .  resonances  in  than i t i s  Hz).  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 be i n f l u e n c e d  note  substantial enough t o  effect  For example,  of the galactopyranose d e r i v a t i v e s  are  and/or the  -24-  shifted  d o w n f i e l d b y 0.5-0.7 ppm. i n g o i n g f r o m 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 t h e H-3  ances o f t h e furanose d e r i v a t i v e s  i s observed.  s h i f t s o f t h e more r e m o t e p r o t o n s  ( s u c h as H - l a n d H-2 o f 1 7 a n d  19),  which  suggest  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 b y  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 position  The i n d u c e d  c a n 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 ,  t h a t i t m i g h t be w o r t h w h i l e  reson-  the r e l a t i v e  of 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  dis-  ring.  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  PYRIDINE  X  o 4.47  5.54  5.22  5.43  5.60  4.75  5.08  /  l,2  J  5  J  2,3  4.52  18 J  7  J  2,3  4.48 l,2  4  -  7  J  3 5  1 ,2  6 m  J  3.09 J  C F  3  l,2 3  2,3  5  J  2,3  8  J  7  '  .3  J  3,4  0  0  8  3,4  3,4 b  ' , 6  J  6  J  5.35 '°  J  4 5Vf  J  4,5  J  9  J  J  4,5  -  2  4  2  5  J  y  °5,6^  9  -  5  J  5,6  V  -  2  6  4  5  °5,6  N  6  PhCH , 7.69; C H , 2 . 3 0 , 2 • "> „ ' 8 . o,m 3  6  4  J  90  J  m  1  6,6^  '  J  6  J  '  1 3  '  o ,m  6  o ,m  4  0.94  c  no  J  5.93 J  6,6^  C  C F  3  8  S 0  J  3  5  J  J  j>  m  c  no,p„ !•.2  J  8. 0  J  1.66 J  ~ o o,p ' c  1,16  7. 6  o,p  m,p  2  1.09  1.61 8  °o.p  1,60 m,p  'b  1.24  m,p  ,m 6-8  o 6.8 o ,m  • <  7..8  m  0,75 -  m,p  a  1.18  1.75  0.54  \ 8.5 6,6 c  6.6 0.59  3  P  1.68  o,m  5.90  6.07  5,6 -  3  5.11  6.04 4  1  °6,6  4.52  5,6 -  V  0.74  5.19  5,6  6.54 9  6,6  J  5,6 4.58  5,6  5,6  8.8  A  c  6.53  5.38  4  J  3  5.56  5.37  4  5,6 5.60  1  4,35 J  }  °4,5 -  6  4.37 J  4,5 5.48  5.28  81 .2 p.p. m. c  -  °3,4 "  :  4.35  so , * 3  .2  2  2  7  5.31  4.44  li  '  2,3  3.41 J  3,4  5.54  .20  17  J  5.59  1 . 2 *•  J  .4  2  Others  m  3  1.07 6  J  o,p  1  81.6 p. p.m. I I  TABLE 1  H  2  CHEMICAL  SULFONATES  SHIFTS  ( x-VALUES),  IN DEUTERIOACETONE  COMPOUND  H-l  4.05  1  9  F  CHEMICAL  SHIFTS  (0 ) C  AND  MULTIPLET  SPLITTINGS  SOLUTIONS  H-2  H-3  H-4  H-5  H-6  5.05  4.78  5.81  6.12  4  H-6'  t J  l,2  4  -  0  2  J  2,3  3.84  4  -  6  9  J  3,4  5.00  6  '  l , 2  J  2,3  4.12  5.81  1  _  (  +78.8  4.66  | 4  0C (ppm)  7  5 J  ( H z ) FOR  0  J  3,4  5.1  _  5  >  9  (  m  )  +  7  7  2  4.51  5.8  h-5. 8  5.64  —  —-  1 + 63.2  8 J  l,2  "  3  7  J  3. 92  2,3  '  4  7  J  3,4  5. 11  7  '  a  3  4. 81  5. 8.  6.04  5.60  4. 80  H5.8-—  j  +63.2  b  9 J  l , 2  3  '  7  J  2,3  4.41  0  J  3,4  5.54  2  '°  4.26  5.43  10  c  5.53 + 63.6  J  l,2  -  4  8  J  4.17  2,3  4  '  6  J  3,4  5.18  -  7  5  J  4,5  h " l , 2  3  -  5  J  2,3  4  ,  6  '  5  J  5,6  4  -  5  J,. 6,6  11.5 J  , 5,6 c  c  6.5  5.08  11 J  1  J  3,4  7  *  2  9  6.08  (m)  — • •  +136 +148  } +  1  6  3  (o) (m) (P>  i ro cn !  TABLE  2  (CON'T)  H-l  COMPOUND  H-2  h-—-  3.7  H-4  H-3  H-5  H-6  — H  4. 8  12  5.8 J  l,2  3  -  6  J  2,3  4.78  '  3  (m)  -  6  5.66  .  5.35  5. 71  5.94  5. 42  13 J  a  CF CH 3  2  l,2  J  x4.94;J ^ H  F  2,3  9.3  2  Hz  '  5  J  b  3,4  8  CF CH 3  /  2  l  J  4,5  1  T5.34;J ^ r  -  f  8  J  9.3  5,6  Hz  5  C  -  J  4  0c(ppm)  H-6'  r  c  I  6.3  +135 +148 +163  (o) (m) (p)  + 135 +147.2 +162.4  (o) (m) (p)  b, 6  CF CH 3  2  T5.37;J  r  p  9.25  Hz  I  to I  -28-  CHAPTER I I  C-StannyTated  a)  Carbohydrates  Synthesis  Many  general  methods  exist  f o r the synthesis  of  organotin  37 compounds appeared cursors reaction This  which  have  a stable  t o be p a r t i c u l a r l y  compatible  -- h y d r o s t a n n y l a t i o n o f an a l k y l  chapter  carbon-tin  bond  with  only  with  the  Two  readily  of a carbon-carbon  halide or equivalent  i s concerned  .  with  of  these  available  double  bond  pre-  and  a t i nnucleophile.  latter.  37-39 In to  the organotin  halogen-metal  literature  exchange  R Sn"M 3  +  +  reactions  R'X  M= Na, K, L i  The  attack  equivalent which  l e a v i n g group, an S  —>  anion  R^SnR  1  references  +  MX  R= a l k y l or a r y l group  on a carbon  can e i t h e r  2 process,  are several  of the sort:  X= halide  by t h e R^Sn  i s probably  there  bearing  be by an i n v e r s i o n  a halide, or mechanism,  o r by a r e t e n t i o n mechanism,  which  -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 — the  r e a c t i o n o f R^SnM w i t h R'X  t o f o r m R^SnX a n d R'M,  most which  likely then  40 c o n d e n s e 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 at a secondary c e n t r e r e s u l t e d i n a net i n v e r s i o n that centre.  at  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 u s e d i s i n d e e d an S 2 N  nucleophilic  dis-  placement. The  t i n r e a g e n t u s e d i n t h e s e e x p e r i m e n t s was  lithium,  r a t h e r than a t r i a l k y l t i n  compound.  The  triphenyltin reasons f o r t h i s  d e c i s i o n w e r e , i n g e n e r a l , t o do w i t h e a s e o f h a n d l i n g . trialkyltin aryltin  compounds a r e o f t e n q u i t e v o l a t i l e  compounds a r e c r y s t a l l i n e  and  less  While  and p o i s o n o u s , t r i -  toxic. 41  U s i n g t h e method o f Tamborski l i t h i u m was metal  and c o w o r k e r s  s y n t h e s i z e d from t r i p h e n y l t i n  (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 I t was  decided to f i r s t  tin-sugar derivative,  , triphenyltin  c h l o r i d e and details).  attempt the synthesis of a primary  as i t was  assumed t h a t t h i s  w o u l d be more r e a d i l y o b t a i n e d t h a n a s u g a r w i t h a bond i n a s e c o n d a r y p o s i t i o n .  Thus, t r i p h e n y l t i n  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 22.  T h i n l a y e r chromatography  r e a c t i o n t o be e s s e n t i a l l y  lithium  type of  carbon-tin lithium  to  (toluene:ether-1:2) indicated  complete  a f t e r two h o u r s .  After  o b t a i n e d w h i c h p r o v e d , upon p.m.r. s p e c t r a l  be t r i p h e n y l  n a n e , 2_5.  was  -D-glucofuranose  w o r k u p , as d e s c r i b e d i n t h e 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 m a t e r i a l was  derivative  the the  crystalline analysis,  (1,2:3,5-di-O-methylene-a -D-glucofuranose)6-C-stan-  T h e r e w e r e no r e s o n a n c e s w h i c h c o u l d be  assigned to a  .30-  FIGURE 3  C-Stannylated precursors.  carbohydrates,  synthesized f o r t h i s work, and t h e i r  -31-  tosylate now  substituent,  integrated  and thearomatic  f o r three  phenyl  region o f t h e spectrum  substituents.  I t has generally  37-39 been  found  that  causes  theproton(s)  fields  —  usually  assigned whereas large  T 7-9.  f o r 25_ t h e y  upfield  shift  Thus,  were  Having next  turned  had  performed  f o r 2_2_,  t h e p.m.r.  x8.5 (benzene-dg  been  obtained  a primary  of successful by l i t h i u m  a  o f secondary  diphenylphosphine  had also  acetylAcetyl  reacted triphenyltin  i nthis  triphenyl  (methyl  30,  using  low  overall  yield  —  lithium  oxide with  3-C-stannane  attention Steiner"" epoxide  In this  sugars  were  one e p o x i d e ,  tntikjl  triphenyl  -L-xylopyranoside) —  manner,  obtained.  _29 a n d s u b s e q u e n t l y  a n h y d r i d e - p y r i d i n e method 21%.  or nota t i n -  i nwhich  diphenylphosphine.  2,4-di-0-acety1-B  the acetic  work as  t i n sugars.  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 -3-L-xylopyranoside)  directly  t i n sugar,  experiments  was e f f e c t e d  He  This  obtained.  scission number  solution),  solution) .  whether  t o t h e s y n t h e s i s o f secondary  a number  high  resonances  o f theprotons  t o determine  atom  a t quite  (benzene-dg  was t h e r e f o r e u s e d  test"  t o a carbon  t o resonate  a r e a t ca. x6.65  a t ca.  had actually  successfully  was  atom  o f t h e resonances  "diagnostic  compound  a t i n substituent  carbon  to a t i n substituent  preliminary  sugar  on t h a t  t o t h e H-6 p r o t o n s  adjacent a  attaching  (methyl 4~0 formed  3-C-stannane  albeit  ~  i n rather  -32-  28  For  30  29_  t h i s work, t h e r e f o r e ,  i t was  decided t o attempt the 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 the  triphenyltin  l i t h i u m reagent.  Methyl 2,3-anhydro-4,6-O-benzylidenewas  reacted with t r i p h e n y l t i n  lithium.  be complete a l m o s t i n s t a n t a n e o u s l y . w h i t e p o w d e r y m a t e r i a l was  a - D - a l l o p y r a n o s i d e 2_3  The r e a c t i o n a p p e a r e d t o  A f t e r the u s u a l workup, a  o b t a i n e d and i d e n t i f i e d  as  triphenyl  (methyl 4,6-O-benzylidene- a - D - a l t r o p y r a n o s i d e ) 2-C-stannane, the  p.m.r. s p e c t r u m s h o w i n g  epoxide s c i s s i o n . for at had  t h e c o r r e c t number o f p r o t o n s f o r a n  The 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  integrated  t h e Zo p h e n y l p r o t o n s and t h e r e s o n a n c e s a s s i g n e d t o H-2 fairly  h i g h f i e l d , T 6.93.  26,  Elemental analysis  were  c o n f i r m e d t h a t 26_  i n d e e d been o b t a i n e d . S i m i l a r l y , methyl 2,3-anhydro-4,6-O-benzylidene-a  s i d e 2_4 was  reacted with triphenyltin  l i t h i u m t o form  (methyl 4,6-O-benzylidene- a - D - a l t r o p y r a n o s i d e )  -D-mannopyranotriphenyl  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 b y p.m.r., i n l i k e manner t o t h a t o f _26.  Further  discussion  o f t h e "*"H a s 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  (b) o f t h i s  chapter.  Some v e r y p r e l i m i n a r y  a t t e m p t s w e r e made t o a s c e r t a i n  o r n o t t r i p h e n y l t i n s u g a r s c a n be d e r i v a t i z e d . first  labile  cluding  I t was d e c i d e d t o  to acid.  resins  A number o f a c i d i c s y s t e m s w e r e t r i e d , i n -  ( a m b e r l i t e I R 1 2 0 ) , 5% t r i f l u o r o a c e t i c  In every case, t . l . c . c a r b o n b o n d was c l e a v e d seemed t o be b e s t ,  i n ether  acid i n chlor-  a n d 10% a c e t i c a c i d i n m e t h a n o l .  (toluene:ether-1:2) t o some e x t e n t ,  indicated that  the t i n -  however t h e l a t t e r  system  i n t h a t removal o f t h e b e n z y l i d e n e group  t o be ca. 8 0 % , l e a v i n g a p p r o x i m a t e l y intact.  blocking  The t r i p h e n y l t i n - c a r b o n b o n d , i t was d i s c o v e r e d , i s  oform, boron t r i f l u o r i d e  90% o f t h e c a r b o n - t i n  appeared  bonds  H o w e v e r , as t h e r e a c t i o n h a d b e e n done o n t h e e q u i v a l e n t  o f a 2-deoxy s u g a r , t h e m e t h y l g l y c o s i d e due  whether  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  g r o u p o f 26. quite  be f o u n d xn p a r t  was a l s o r e m o v e d a n d ,  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  final  p r o d u c t proved d i f f i c u l t w i t h o u t time consuming p u r i f i c a t i o n p r o cedures.  Further  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 t h e  3-deoxy s u g a r 27_ i n w h i c h , i t i s h o p e d , t h e m e t h y l g l y c o s i d e i s n o t q u i t e s o l a b i l e a s t h a t o f 2&. 13 Work b y S t e i n e r is  less labile  he was a b l e previously  xndxcates that  linkage  the triphenyltin-carbon  i n a b a s i c medium t h a n i n an a c i d i c medium.  to e f f e c t the acetic anhydride-pyridine m e n t i o n e d , on 7P[_ t o f o r m 30.  bond  Thus,  acetylation,  -34-  T h i s w o r k has a stable carbon-tin that there  demonstrated t h a t s u g a r - t i n d e r i v a t i v e s having bond can  be  t i v e s have, i n the  of being  in organic on  it  packaging  and  m e d i a , and  as  may  as  organotin  fungicides.  indicated This deriva-  become i n c r e a s i n g l y i m p o r things,  f o r wood  (as p . v . c . s t a b i l i s e r s ) ,  be  Sugars have the  expected to confer  derivatives.  i m p o r t a n t and  i s speculated  and,  also  i n marine  useful  pro-  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  their organotin  logically  area,  T h e y a r e u s e d , among o t h e r  i n food  antifouling paints  i n the  l a s t decade o r so,  industrially.  preservation,  perty  I t has  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.  augurs w e l l f o r f u t u r e r e s e a r c h  tant,  synthesized.  properties  c h e a p , many a r e  t h e i r p o l y m e r s a r e w e l l known.  that organotin  perhaps, medically  They a r e  such  s u g a r s c o u l d become  important  substances.  bio-  Given  this,  industrially  -35b)  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  1  13  H and  C n.m.r. d a t a w e r e p r i n c i p a l l y  used t o e v a l u a t e t h e  gross 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 . shown, t h e i n f o r m a t i o n t h u s o b t a i n e d p r o v e d 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 .  As w i l l be  important i n evaluating  H N.M.R. The p.m.r. s p e c t r u m  o f compound 2 5 a n d t h a t o f 2 2 show  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 22  almost  25  -36-  0 0  H  X  H  0  H  H-l  H-3 H-2  H-6's  H-4  iH-5  —r—  4  2  6  0 0  X  9  T  H  H  ro  10 C H 6  i  H-l  6  -OH  - J ~T~  2  FIGURE 4  3  9  T  H n.m.r. spectra of triphenyl(1,2:3,5-di-O-methylene-a-Dglucofuranose) 6-C-stannane 25_ (top) and 1,2 :3 ,5-di-O-methylenea-D-glucofuranose _3|_ (bottom) i n deuteriobenzene solution. C * - impurity)  TABLE 3  Chemical 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 - 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 benzene s o l u t i o n s Cornoound  H-l 4.14  25  H-2  H-3  H-4  H-5  H-6  H-6'  5.75  6.05  6.32  5.59  8.37  8.68  J., „3.8 J„ , 0 1,2 2,3  26  27  4. 82 J  „ .5 J - ,2.6 1,2 2,3  n  5.63  8.58  J, 0 1,2  J„ ,2.1 2,3  4.14  5.59  0  31  32  6.93  J , -3.75J- , 0 1,2 2,3 6.34-  6.62  J, 0 1,2  J , ,3 2,3  0  5.48 33  J  _ 0 1,2  n  6.07 J  - 3 2,3 0  J , .2.4 J . 2 . 3 J 1 1 . 3 J , ,,-13.3 J 3,4 4,5 5, 6 6,6 c  5.14  6.01  c  c  5. 47  c  5,6  5. 65  6.23 c  5.55  6.03  6.45  c  5.96  6.21  6.07  5.78  6.11  c  c l  5.77  5.76  J , .2.9 J . 9 . 2 J _ , 5 3,4 4,5 5,6 c  6.33 J , .2.9 3,4  5.9  5.49 c  7.35.  2.48  4.64  7.19 2.80-2.17  4.57  7.57  2.8  4.55  6.48  2.60  4.56  ,, 4.8 5,6  6  J  c  , 0 5,6 c  7.07  J , ,,-11.5 J . , 1 1 . 7 6,6 5,6 c  6.31  5.71  J , 9 . 5 J j. 1 0 . 2 J , ,,-10.2 J _ ,, 5.3 4,5 5,6 6,6' 5,6' c  2.6  6.65  ,2.6 J , 1 . 9 J , 5.3 J . . 3,4 4,5 5,6 6,6 c  c  Benzyl Proton  8.8  6.09  J , .5.9 J„ .8.8 J _ 1 1 . 4 J , ,,-11.8 J 3,4 4,5 5,6 6,6  Aromatic Protons  6.1  J , .2.5 J . ,-9.1 J , , 4.7 J , ,,-10.3 J ,, 3,4 4,5 5,6 6,6 5,6 7.26  OMe  i n deuterio-  6.71  e  i  •38-  T A B L E . 3 CON'T.  0. / V  yW  Q  b  c  a  e  -OH  H  T  x 5 . 31 , -in 6.38,  -OH T 5 . 8 4 ,  °X"  and  5.60.  ^-r H , 3 = 8 . 7 H z . 0  = 3.6 H z . J  Q  H  F  2  ^5.25. 5.33. 5-"'  -OH x 5 . 8 2 , J  X 4 , 7 0  H  f  2  "  , 2  -  8 3  '  -39-  T h u s , i t i s assumed t h a t 25 h a s  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  conformation  as 2 2.  However, the c h e m i c a l l i n g s J,. ' , J _ ' o f 2_5. by  and  J  shifts  o f t h e C-6  f o r 22  a  differ  proton  and  significantly  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  t h e C-6  protons  r e s o n a n c e s o f 25 r e l a t i v e  shifts  the  coup-  from  those  experienced  to those  o f 2_2_,  are  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 , s u c h as t h e t o s y l a t e m o i e t y o f 22. the resonances of those  protons  In general,  a to the t i n s u b s t i t u e n t  only  experience  44  s i g n i f i c a n t changes i n c h e m i c a l Although the v i c i n a l  one  may  be  tempted t o base the d i f f e r e n c e s between  c o u p l i n g s , J,- g a n d  d i f f e r i n g populations  coupling constants —  one  tivity  25  solely  on  remembered  d e p e n d on  several fac-  o f the most i m p o r t a n t ,  the i n v e r s e v a r i a t i o n of c o u p l i n g constants  the e l e c t r o n e g a t i v i t y of the a t t a c h e d t h e r e has  o f 22 and  -  than d i h e d r a l angle  t h i s case, being  J,, g,,  o f C ^ C g ' r o t a m e r s , i t m u s t be  t h a t the v i c i n a l proton tors other  shift.  n o t been found a s i m p l e  o f s u b s t i t u e n t s and  f a c t o r s s u c h as C-C  substituents. '  coupling constants  b o n d l e n g t h and  H-C-C  4 7  ,  and  bond angle  with  Since  4 5  c o r r e l a t i o n between  in  electronegasince may  other  contribute  48  t o the s i z e s of the attempt the exact constants, but  coupling constants  c a l c u l a t i o n of d i h e d r a l angles  to simply estimate  of whether or not  , i t was  the p r o t o n  couplings are  r o t a r a e r s f o r t h e C^-C^  from  rotamer populations  bond:  not  to  coupling on  the  basis  "large" or "small".  W i t h t h e a i d o f Newman p r o j e c t i o n s , one non-eclipsed  decided  may  visualize  three  -40  A  B  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  t o them, a r e e n e r g e t i c a l l y value of  C  the most f a v o r e d r o t a m e r s .  g would correspond,  i f one  were t o i n v o k e  very close The the  large Karplus  49 equation  , to a trans a n t i - p a r a l l e l  C.--HV and  t h e C,-H_ bonds, whereas the s m a l l e r v a l u e o f J ,, 6 6 5,6  D  O  t o a gauche r e l a t i o n s h i p  t h e s e d a t a , i t was  f o r those bonds.  A o r C.  Examination  models l e a d s t o the c o n c l u s i o n t h a t rotamer w i t h r e s p e c t to rotamer  C,  C, w h i c h  and  does n o t e x i s t i n r o t a m e r  vicinal  d a t a were used to i d e n t i f y  rota  molecular  a steric the sugar  favored interring  A.  c o u p l i n g c o n s t a n t s and t h e s t r u c t u r e and  of  A i s probably  as t h e r e a p p e a r s t o be  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 moiety  Proton-proton  From  t h e r e f o r e a s s u m e d t h a t t h e p r e f e r r e d C^-C^  f o r 25_ i s e i t h e r r o t a m e r  f o r rotamer  the r  would correspond  mer  r e l a t i o n s h i p between  chemical  conformation  shift of  the  -41-  product 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 23.  lithium with  A s 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 t h e p.m.r. s p e 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 r e s o n a n c e  lies  at high  field  i n d i c a t e d t h a t t h e t r i p h e n y l t i n l i t h i u m h a d i n d e e d e f f e c t e d an epoxide to  C-2.  s c i s s i o n a n d t h a t t h e t r i p h e n y l t i n m o i e t y was now b o n d e d Since both the a l i o - ( 2 3 )  a n d manno-(2 4) e p o x i d e  are t r a n s - f u s e d 4,6-0-benzylidene-hexopyranoside in  a rigid  conformation.  As a r e s u l t o f t h i s  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 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 . J2  derivatives  systems,  rigidity, opening,  they  exist  and the the reaction  T h i s was c o n f i r m e d b y t h e s m a l l  3 v a l u e , o b t a i n e d f r o m t h e p.m.r. s p e c t r u m  equatorial-equatorial proton-proton coupling.  o f 26, t y p i c a l  o f an  -42-  A r a t h e r e x t e n s i v e study of conformations 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  values of  2  ,  J  ] _ 3' 2 J  p o r t e d the assignment ring  3  a n <  ^  proton-proton  4,6-0-benzylidene-a-D-hexopyrano-  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 The  and  J  3  C o x o n 50  _  b e e n r e p o r t e d by  4'  w I l  ^ ^ c  o b t a i n e d , sup-  n e  of the c h a i r conformation  f o r a l l t h e c o n f i g u r a t i o n s examined, and  to the pyranoid  a small J. _ value 1,2  (0.6-1.7 Hz) t o r i a l H^  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-  p r o t o n a r r a n g e m e n t s i n t h e s e compounds, w h e r e a s a some-  what l a r g e r  2  value  equatorial H^-axial H  ( 3 . 3 - 3 . 8 Hz) arrangement.  2  p y r a n o s i d e s , e v e n i n t h e 2- a n d 2  was  c h a r a c t e r i s t i c of  T h i s was  3-deoxy  pyranosides  In addition,  t h e p.m.r. s p e c t r u m  t h e v a l u e s g i v e n by C o x o n f o r  t r u e f o r the  altro-  cases.  f o r 2_6_ i s v e r y s m a l l (0.5 Hz) .  c o u p l i n g s o b t a i n e d from  the  the  other  were c o m p a t i b l e w i t h  2-deoxy-4,6-0-benzylidene-a-D-altro-  and h e n c e w i t h a c h a i r c o n f o r m a t i o n ,  illustrated  in  figure 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_, h o w e v e r , was q u i t e so s t r a i g h t f o r w a r d . of  As  anticipated,  t h e p.m.r.  s c i s s i o n product by  spectrum  the product o b t a i n e d from the r e a c t i o n of t r i p h e n y l t i n  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 o f p r o t o n s 2_7.  T h a t t h i s was  t h e a p p e a r a n c e o f t h e H-3  indicating  the t r i p h e n y l t i n  t o be  g r o u p was  at quite high f i e l d now  bonded t o carbon  Owing t o t h e a f o r e m e n t i o n e d  fact  opening  assumed t h a t t h e v i c i n a l  i s possible,  i t was  w o u l d i n d i c a t e H - l , H-2 Indeed,  2  was  and H-3  approximately  the  i n d e e d t h e p r o d u c t was  resonance  that only a t r a n s d i a x i a l  t o be  in equatorial  not  ^H-^H  lithium epoxide confirmed (T7.26), 3. ring couplings  positions.  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  model 3-deoxy a l t r o p y r a n o s i d e s  Hz  and J  2  of 2.5  3  s t u d i e d by Coxon.  27, however, i n d i c a t e d t h a t t h e r e c o u l d be  t h a t the  account f o r the s l i g h t l y 3  values  a x i a l H-3 27,  The  .  I t i s assumed indicate  v a l u e of J , ,,  f o r 27 c o u l d i n d i c a t e t h i s d i e q u a t o r i a l arrangement or - e q u a t o r i a l H-2  arrangement.  i n d i c a t i n g a d i s t o r t i o n of the  appears to be so, J  3  4  being  5.9  Hz  an  I f the l a t t e r i s t r u e f o r  sugar r i n g due  a c t i o n s , then the d i h e d r a l angle between H-3 by models, should be q u i t e s m a l l and  steric  the monosaccharide.  value of J ,  and H-3.  for  Models made of  f o r Coxon's model a l t r o p y r a n o s i d e s  a d i e q u a t o r i a l arrangement f o r H-2 ca 2 Hz,  low  Hz  a c e r t a i n amount of  i n t e r a c t i o n between the t r i p h e n y l t i n moiety and T h i s may  to 2.7  to s t e r i c  and H-4,  ^ quite large.  as  inter-  determined This  f o r 2_7, compared to a j "  3  4  -45-  value  of It  as  2.5 was  shown  with  Hz  26.  therefore  in  the  for  figure  proton  concluded  5(b).  shift  data  discussed  resonance  of  field.  plausible explanation  a  high steric  moiety  A  interaction  with  the  ring  of  the  phenyl  H E T E R O N U C L E A R N M,R. ;  appears  is shifted  between which  j=>\4ne o~f ~fke -phenyl r i n g effect  26  one  and  to  skew  to  have  a  phenyl  position  hence  allow  the for  in  accord  section:  normal (ca  for this  the  conformation,  be  in this  significantly  of  would  a  seems  earlier  the  2_8  of  assumed  conclusion  the  to  resonance  2_7  whereas H-2  H-3  This  that  groups C-H2  ppm.) i s based  of  bond  the  shift,  2  shift  ring  thus,'  the  on  03Sn  above  current  -  substituent.  PARAMETERS 117  Tin  has  10  stable  119 and Sn ( 8 . 6 2 % , l=h) n.m.r. s t a n d p o i n t , any of  three* 1  The  and  of  these  Sn  are of p r i n c i p a l i n t e r e s t here. organotin d e r i v a t i v e consists of  species  which  give  overlapping  I=H)  (7.54%,  From the . a mixture  n.m.r.  spectra.  13 H  which  separate  isotopes  (or bear  spectrum.  C) a  n.m.r. resonances o f  nonmagnetic  The  molecules  those  t i n isotope which  are  will  molecules give  a  (83.28%)  normal  s u b s t i t u t e d by  a  with  as  either side  ponding  located  resonances  *Of c o u r s e , t h i s with the n a t u r a l  of  symmetrically  on  the  which  molecules  i g n o r e s t h e many a b u n d a n c e o f ^C,  "^ Sn 7  or  i n «->hich 4 he. resonances  i s o t o p e w i l l g i v e more complex s p e c t r a 13 ' ' (or 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 satellites  n.m.r.  the  bear  metal  a  of  will the  ^"^Sn  crfi^ose appear  corres-  nonmagnetic  isotope "impurities" associated ^11, e t c .  pfofen:  -46-  FIGURE 6  N a t u r a l abundance i n deuteriobenzene AT 1.023  1 - 5  C n.m.r. spectrum solution,  s e c ; PD 0; SE - 0 . 4 ) .  s i d e bands.  (ca 0.1M)  of trimethyltin (PW  3 0 ° ; NT  chloride  53,000;  The peaks marked * are. s p i n n i n g  -47nucleus. will  Those resonances  are not spin coupled  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  magnetically  (1)  which  i n e r t t i n nucleus.  which  t o the metal  have a  (See f i g . 6)  ^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 protons  i n a l k y l groups,  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(Sn-aCH). I t was f o u n d  f o r the proton  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 t h e main band spectrum 119 117 r e s u l t e d i n overlaps which obscured the Sn a n d Sn s a t e l l i t e s a n d , a s 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 f r o m t h e ^H-Sn c o u p l i n g s . 13 Since  C investigations are p a r t i c u l a r l y  mination of structure,  conformation,  suited  to the deter-  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 b e c a u s e s i g n a l s o f i n t e r e s t c a n e a s i l y be r e s o l v e d and no s e c o n d  order analysis i s necessary,  i t was d e c i d e d  toexa-  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 assignments decoupling experiments.  (i)  chemical  were p r i m a r i l y based on s e l e c t i v e  proton  (See Appendix!  shifts  13 C chemical s h i f t reported i n Table  4.  d a t a f o r d e r i v a t i v e s 2 5 , 26 a n d 2_7 a r e  F o r comparison,  the chemical s h i f t data f o r  -48-  H-5  FIGURE 7  Fourier transform  H n.m.r. spectrum o f t r i p h e n y l ( 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 ) 2 - C - s t a n n a n e 26 showing spectral  assignments and *H-Sn c o u p l i n g s .  PD 2 s e c ; AT 4 s e c ; NT 100.)  ( c a 0.3M)  (PW 9 0 ° ;  -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, 4, 6 - 0 - b e n z y l i d e n e - 2 - O - m e t h y  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-benzylidene-3-0-methyl-a-D-altropyranoside, are a l s o Due  methyl  included.  t o t h e f a c t t h a t . 34, m e t h y l 4, 6 - 0 - b e n z y 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  not possible  to  13 obtain a tio  C n.m.r. s p e c t r u m w i t h a s u f f i c i e n t 13  t o allow f o r assignment  32 and  of the  signal-to-noise ra-  C signals,  3_3 w e r e u s e d a s m o d e l compounds.  s h i f t b e t w e e n a c a r b o n b o n d e d t o an -OMe  The  compounds  difference i n chemical  group  and 51  c a r b o n b o n d e d t o a h y d r o x y l g r o u p i s c a 10 ppm. 13 o b t a i n e d from the C s p e c t r a o f 3_2 a n d 33, t h e of  therefore  an  13  equivalent  Using the data C chemical s h i f t s  3_4 w e r e e s t i m a t e d and c o m p a r e d t o t h o s e o f t h e 2 - d e o x y - ( 2 6 )  3 - d e o x y - ( 2 7)  t i n sugars.  As  c a n be  seen from the 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 g r o u p b y results  in shifts  32 t o 43 ppm. w i t h one  The  y- r e s o n a n c e  e x c e p t i o n , t o lower f i e l d .  were a l s o s m a l l —  a triaryltin  -group  of the a-, o r geminal, carbon resonances of  upfield.  and  The  s h i f t s were s m a l l shifts  however, l e s s p r e d i c t a b l e ,  of the 3-  from  and, resonances  ranging i n size  f r o m 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 For C spectra of 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 ' found that, i n general, for  carbons  are only  observed  a t o t h e t i n a n d 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  trialkyltin of  large chemical s h i f t variations  group produces  the d i r e c t l y  lower f i e l d s  an u p f i e l d  bonded carbon.  s h i f t f o r the  The y-nuclei  the  B resonances undergo  relatively  3.5  t o 4.5  fields.  ppm.  to lower  resonances  usually  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  resonate at  steric  constant s h i f t s  a  strain,  while  of approximately  ,p6 5 H  A  0  J  H  C-3  C-C-4 2 C-5  C-1  0  C-6  H  X 0  H o  C-l  i  o  o  cn  i  ro  I  0~>  •N  Si  A i  1  i  1  FIGURE 8.  i  1  i  1  i 150 1  i  1  !  •"'  i  IOO  '  !  1  i  '  j  '  |  '  i  50  '  ppm  i  •  i  ' ;  —r~I  o  13 Natural abundance C n.m.r. spectra of A triphenyl(1,2:5,5di-O-methylene-ct-D-glucofuranose) 6-C-stannane 25_ and B l,2:3,5-diO-methylene-a-D-gTucofuranosc 3i_ i n deuteriobenzene solution. T e a . 0.3M). (PW 30°; NT 53,000; AT 1.023 s e c ; PD 0.)  TABLE 4  C chemical s h i f t s and  Compound  C-•1  (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  1,2:3,4-di-0-methylene-a-D-glucofuranoses  C-•2  C-3  C-•4  C-5  C-6  i n deuteriobenzene  -OCH  3  0- / H O'^H  Benzyl  96.33 85.79  25  105. 09  83. 59  75. 39  80. 68  71.47  14.95  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  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  102. 33  70. 00  67.00  77. 19  58-59  69.50  34 (estimated)  96.37 87.. 32  •  solutions  33  Our of  the  34  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  a- and Y-carbon  resonances.  resonances, but not f o r those o f the 3-carbon  I t i s believed  f r o m t h e f a c t t h a t we u s e d moiety which, depending  that this  l a c k o f agreement  a triaryltin,  r a t h e r than a  upon t h e d i s p o s i t i o n  an u p f i e l d  s u b s t i t u t e d by t r i m e t h y l t i n , s h e d more l i g h t on t h e e f f e c t tin  group  group,  r a t h e r than t r i p h e n y l t i n of the ring  with  could 3-carbon  A s t u d y o f t h e s e same groups  sugars would  current of the t r i p h e n y l -  on t h e c h e m i c a l s h i f t s o f c a r b o n , a s w e l l  resonances.  trialkyltin  rather than a downfield s h i f t of the  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 .  derives  o f the 3-carbon  respect t o the aromatic rings of the t r i p h e n y l t i n produce  f o r the s h i f t s  as t h e p r o t o n  TABLE 5  C chemical s h i f t differences  (p.p.m.)  4,6-O-benzylidene-a-D-altropyranosides methylene-a-D-glucofuranoses  6  - 6 for Sn OH and 1 , 2 : 3 , 4 - d i - 0 -  Compound  a  6  Y  25  -47.07  - 2 . 06  + 4. 78  26 (values t o n e a r e s t ppm)  -31  C-1 C-3  0 +2  +2  27 (values t o n e a r e s t ppm)  -33  C-2 C-4  +1 0  C-1 C-5  -1 +6  I Cn  co l  -54-  (ix)  13  C-Sn  coupling  constants  Up t o 19 73, t h e d a t a r e p o r t e d o n been l i m i t e d m a i n l y  to simple  13  aliphatic  C couplings to  54-56  119  Sn had  and p h e n y l d e r i v a t i v e s  57  However, s i n c e t h e n , a number o f r e s e a r c h g r o u p s h a v e 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 through  o r g a n o t i n compounds.  '  '  Couplings  one t o f o u r bonds h a v e b e e n e x a m i n e d , and t h e r o l e o f  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 52 5 3 been i n v e s t i g a t e d .  (3-bond c o u p l i n g s )  carbon  have  '  The m a g n i t u d e o f t h e d i r e c t b o n d c o u p l i n g £  ("*""^Sn-^ C) J i s 3  i n f l u e n c e d by t h e h y b r i d i z a t i o n o f t h e t i n and o f t h e d i r e c t l y attached carbon found  t h a t [j J 1  atoms. 1 1 9  Sn-  l 3  For c y c l o a l k y l d e r i v a t i v e s of t i n , K u i v i l a  C)J  i s g e n e r a l l y l a r g e r (503-390 Hz)  53  than  13 H"1z ) , a n d t h a t i n a l l c a s e s p"J(Snf o r a c y c l i c compounds P3(320-314 an i s l a r g e r than J(SnCM which, i n t u r n , i s l a r g e r th 1 32 13 55 1 1 3 J (SnC) I t i s known t h a t J ( C-Sn) i s p o s i t i v e a n d c )  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 the v i c i n a l c o u p l i n g constants  .  compounds.  In r i g i d  show a K a r p l u s t y p e  .  .  organotms,  variation  (see F i g u r e 9 ) : J = 30.4 - 7.6  c o s 9 + 25.2 c o s 2 9 59 where 9 i s t h e d i h e d r a l a n g l e . In a l i p h a t i c organotin d e r i v a t i v e s ,  the values of the v i c i n a l  "^C-^^Sn couplings i n d i c a t e a f l e x i b l e molecular a preference  for certain  conformations.  53  I t was h o p e d t h a t one c o u l d p r e d i c t , f r o m t h e 13 lings obtained geometries  from the  framework w i t h  3  J(  13 C-Sn)  C s p e c t r a o f 2_5, 26 a n d 27_, t h e i r  t o see i f these were i n a c c o r d w i t h those  coupsolution  predicted  -55-  0  20  40  60  80  100  120  140  160  180  DIHEDRAL ANGLE IN DEGREE  FIGURE 9 Magnitudes of J ( S n C C C ) p l o t t e d against the d i h e d r a l 3  angle e.  from t h e proton  U 9  1 3  ( r e f 59)  data;  i f s u c c e s s f u l t h i s would augur w e l l f o r  13 future  C studies of organotin  sugars.  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 detect  the t i n s a t e l l i t e s  number o f v a l u e s  i n the  were o b t a i n e d .  C s p e c t r a o f 2 5 , 26 a n d 2 7 , a  • T h e s e a r e l i s t e d i n T a b l e 6.  The  13  117 13 119 separate magnitudes o f t h e geminal CSn and CSn c o u p 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 , t h e 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 p e a k a n d t h e numbers g i v e n value. Sn  i n Table 6 represent 3  F o r t h e 6-deoxy s u g a r 25 t h e  i s c a 60 H z .  Consulting  an " a v e r a g e "  J c o u p l i n g b e t w e e n C-4 a n d  f i g u r e 9, one c a n s e e t h a t t h i s  value  TABLE 6  Compound  C-Sn c o u p l i n g c o n s t a n t s  n  n  (Hz) f o r o r g a n o t i n s u g a r s  W ^ S n -  1  3  ^ )  n  2  J(Sn-  1 3  C ) n  n  3  J(Sn-  1 3  25  6  372  6  348  5  -24  4  60  26  2  340  2  323  1  -14.8  4  0  3  -  2  -10.1  1  32. 8  2  -32  5  15.7  27  3  392  3  376  C ) n  9.6  I  cn I  -57-  C-2  Ph-C-H  C-3  OCH,  C-6 C-1  ,Sn  115  J 3,Sn  105  85  95  75  65  55  35  45  ppm  13 FIGURElO  Natural abundance  C n.m.r.  spectrum  a-D-altropyranoside)2-C-stannane ( 0 . 3 M)  showing  of  the C-1,  AT  1.023  C-2,  sec.)  the normal and  C-3  o f ( m e t h y l  4,6-O-benzylidene-  26_ i n a c e t o n e - d ^  resonances  resonances.  and (PW  the 7;  PD  t i n 0;  solution satellites NT  80,000;  -58corresponds  t o a l a r g e d i h e d r a l a n g l e -- b e t w e e n 160° a n d 180°.  I f a m o d e l i s made o f t h e r o t a m e r , v i o u s l y assumed t o be e n e r g e t i c a l l y one is  a b o u t t h e C-5 - C-6 b o n d , p r e t h e most f a v o u r e d f o r 25,  c a n s e e t h a t t h e d i h e d r a l a n g l e b e t w e e n C-4 a n d t h e 0^Sn g r o u p indeed very large —  a p p r o x i m a t e l y 180°.  heteronuclear data f o rt h i s  Thus t h e  and  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 ( b e t w e e n C-4 a n d t i n ) o f t h e 2-deoxy  26 i s ca. 0 Hz. F r o m f i g u r e  sugar  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 c o w o r k e r s  , a zero 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  b e t w e e n t h e t i n g r o u p a n d C-4 o f a p p r o x i m a t e l y made o f t h e c h a i r f o r m p r o p o s e d  earlier i n this  85°.  angle  A g a i n , a model  c h a p t e r , on t h e  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 a n a n g l e b e t w e e n C-4  -59-  F o r t h e 3-deoxy  sugar  32.8 Hz, c o r r e s p o n d i n g moiety  27, t h e v i c i n a l  couplings are  =  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  o f ca. 130° o r 35°, and  d i h e d r a l a n g l e b e t w e e n C-5  3  J , - = 15.7 H z , c o r r e s p o n d i n g  a n d t h e t i n o f c a 112° o r 58°.  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  to a Examin-  that a d i h e d r a l angle of  between C - l and t h e t i n i s n o t p o s s i b l e .  A s C-5  is in a  p o s i t i o n w i t h respect to the r e s t of the molecule,  35°  fixed  a dihedral  a n g l e o f c a 130° b e t w e e n C - l a n d 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 b e t w e e n C-5  and t h e t i n t o be c a 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 t h e v a l u e o f 112° o b t a i n e d f r o m f i g u r e  9.  These v a l u e s  sugar  (130° a n d 112°)  do i n d i c a t e a d i s t o r t i o n o f t h e  -60-  ring, with  t h e 03Sn g r o u p b e i n g  disposed  p o s i t i o n t h a n i t w o u l d o c c u p y i n an viously stated, this  concurs w i t h  t h e p.m.r. d a t a i n t h a t i t , shown i n f i g u r e  t o w a r d s a more e q u a t o r i a l  undisturbed  the  chair.  conclusions  As  derived  as w e l l , i n d i c a t e s t h e  prefrom  skew f o r m  5(b).  5(b)  The  w e a k n e s s o f t h i s m e t h o d i s t h a t one  i s somewhat d e p e n d e n t 13  on m a k i n g 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 and  the  difficulties  Nevertheless,  the  o f so d o i n g h a v e a l r e a d y  f a c t t h a t the  d a t a f o r 25  with a n t i c i p a t e d geometries c l e a r l y e x p e c t e d o c c u r s i n 27.  C-Sn  couplings  been a l l u d e d  and  f o r 2_6 a r e  to. in  i n d i c a t e s t h a t something  Furthermore, the  f a c t that three  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 t h e p o s s i b i l i t y  accord un-  independent of  a 13  conformational  distortion implies  t h a t i t i s not merely the  C-Sn  data that are 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 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 a n d " t i n - o b s e r v e " As p r e v i o u s l y d i s c u s s e d ,  owing  area  spectra.  to the lack of s p e c t r a l dispersion  i n many o f t h e p.m.r. o f o r g a n o t i n to obtain p r o t o n - t i n couplings.  compounds, i t i s d i f f i c u l t  I t may be f e a s i b l e t o u s e a  119 t e c h n i q u e whereby a S n - d e c o u p l e d p.m.r. s p e c t r u m 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. s p e c t r u m ( u s i n g c o m p u t e r  difference  techniques) t o o b t a i n a spectrum d i s p l a y i n g only  the resonances  119 due  to protons that are coupled t o a T i n INDOR o r " t i n - o b s e r v e "  Sn n u c l e u s .  experiments would  measure t h e a c t u a l c h e m i c a l s h i f t s  a l l o w one t o  o f t h e "*"^Sn o r ^"^Sn n u c l e i .  "Tin-observe" s p e c t r a would a l s o allow  f o r measurement o f t i n -  proton couplings  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 f r o m t h e  p.m.r. s p e c t r u m .  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 eliminate the couplings  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  from the phenyl  a t t h e i r resonance  frequencies.  -62-  EXPERIMENTAL All  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 ,  using a Buchi rotary evaporator. w i t h a Hoover Unimelt  M e l t i n g p o i n t s were measured  (64 06-K) i n s t r u m e n t a n d a r e 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 acetone temperature  with a Perkin-Elmer  formed on S i l i c a  s o l u t i o n s a t ambient  141 p o l a r i m e t e r .  T . l . c . was p e r -  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) a n d  d e t e c t i o n by c h a r r i n g w i t h H S 0 . 2  All  4  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 over m o l e c u l a r  sieves.  Fluorinated Sulfonates Trifluoromethanesulfonic anhydride trifluoroethanesulfonyl from Willow-Brook  (tresyl)  (9 8% b y g . l . c . ) a n d 2,2,2-  chloride  (98%) were o b t a i n e d  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 ,  and w e r e 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 . to  Both reagents  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 - 1 0 ° .  sulfonyl chloride  months a t room  i t i s stable  appear  Pentafluorobenzene-  (99%) was o b t a i n e d f r o m A l d r i c h C h e m i c a l  was u s e d w i t h o u t p u r i f i c a t i o n ;  U.S.A.),  Co., and  f o ra t least several  temperature.  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 a n d 1.7-2 0 a r e 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 To a c o o l e d  (4J . —  (/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) a n d C H C 1 2  2.3 mmol) was s l o w l y a d d e d .  2  (40 m l ) , t r i f l i c  A f t e r 1 h, t . l . c .  anhydride  (0.38 m l ,  showed t h e r e a c t i o n  to  be c o m p l e t e .  The r e a c t i o n m i x t u r e  o f i c e and s o d i u m h y d r o g e n c a r b o n a t e . tracted with CH C1 2  2  remove any r e s i d u a l p y r i d i n e .  with l i g h t petroleum  e x t r a c t s were f i l t e r e d  and c o o l e d .  were c o l l e c t e d , a f t e r w e r e 4 ( 1 0 0 % ) , m.p.  Anal. Calc. f o r C H,  1 3  H  l g  extracted  The c o l o u r l e s s n e e d l e s of additional  which  solvent  +64 (c 2 . 1 ) .  F 0 g S : c , 39.80; H, 4.88. F o u n d : C, 3  40.02  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 :  the r e a c t i o n took ^ 3 h f o r completion in  toluene  (3 x 50 m l ) , a n d t h e c o m b i n e d  careful evaporation 40°, ] / \ ^  solutions  2  concentrated with  The b r o w n r e s i d u e was  ( b . p . 30-60°)  mixture  The a q u e o u s l a y e r was e x -  (3 x 50 m l ) , a n d t h e c o m b i n e d C H C 1  2  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 to  was p o u r e d o n t o a  and t h e p r o d u c t  was  obtained  80% y i e l d . 1,2:5,6-Di-O-isopropylidene-3-O-triflyl-a-D-glucofuranose  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 a b o v e , 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° anhydride  (5).  , when t r e a t e d w i t h  (0.7 m l , 4.2 m m o l ) , g a v e _5 ( 1 0 0 % ) .  When  f r o m 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 r -]25 d e r m.p. 70°, [_ J "35° ( c 2) .  was  triflic  recrystallised a white  pow-  a  D  Anal. Calc. f o r 39.71; H,  c  3 i H  1  F 9  3°3  S :  c  '  39.80; H, 4.88. F o u n d : C,  4.85.  6-Deoxy-l,2:3,4-di-O-isopropylidene-6-pyridino-a-D-galactopyranose t r i f luoromethanesulphonate (1.75 cooled in  g, 6.7 mmol) i n C H C 1 2  2  A s o l u t i o n o f 3_  (15 ml) was a d d e d d u r i n g 10 m i n t o a  (*--15°) s o l u t i o n o f t r i f l i c  pyridine.  {J) . —  anhydride  (1.2 m l , 7.2 mmol)  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 w o r k e d - u p  i n the usual fashion to y i e l d  7 (2.83 g, 9 0 % ) .  Recrystallisation  f r o m aqueous e t h a n o l - l i g h t p e t r o l e u m g a v e w h i t e 217-218° ( d e c ) , Anal.  [a]  platelets,  m.p.  -35° ( c 2 . 5 ) .  2 5  C a l c . f o r C - ^ H ^ F ^ T O g S : C, 45. 86; H, 5.13; N, 2.97.  F o u n d : C, 45.95; H, 5.32; N, 2.96. 1, 2 : 5 , 6 - D i - Q - i s o p r o p ' y lidene-3-£r-tresy 1 - a - p _ - l l o f u r a n o s e  (8_) .  a  —  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  mmol) a n d CH C1 2  (40 m l ) was t r e a t e d w i t h t r e s y l  2  ml,  9.9 mmol),  for  t h e p r e p a r a t i o n o f _4.  using a procedure p a r a l l e l  l i s a t i o n of the product  was a l l o w e d  The u s u a l w o r k - u p  and  from l i g h t p e t r o l e u m gave v e r y  n e e d l e s o f 8. (3.2 g, 8 9 % ) , m.p. Anal.  c h l o r i d e (0.94  to that described  The s t i r r e d m i x t u r e  up t o room t e m p e r a t u r e o v e r n i g h t .  white  (0.94 m l , 11.6  Calc. f o r C ^ H ^ F ^ g S -  55-56°, £ a j  2 5  above t o warm  recrystal-  fine,  +66° ( c 2 . 1 ) .  C, 41.38; H, 5.21.  Found:  C,  4 1 . 7 3 ; 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 —  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) a n d C H C 1  (0.47  m l , 5 mmol) was c o n d u c t e d a s d e s c r i b e d  white  2  needles Anal.  (40 m l ) w i t h t r e s y l  2  (1.4 g , 9 0 % ) , m.p.  Calc. f o r 4 c  1  H  l 3 8 F  2  0  S  :  (9.) .  chloride  a b o v e t o y i e l d _9 a s  90-91°, [ a ] ^ -39° ( c 2 . 7 ) . C  '  4 1  -  3 8  '  H  '  5.21.  F o u n d : C,  41.72; H, 5.44. 1,2:3,4-Di-0-isopropylidene-6-0-tresyl-a-D-galactopyranose 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) a n d C H C 1 2  2  (40 m l ) w i t h t r e s y l  c h l o r i d e ( 1 . 1 5 m l , 12  mmol) a t -15° f o r 1.5 h was f o l l o w e d b y t h e u s u a l w o r k - u p . crystallisation  of the product  f r o m l i g h t p e t r o l e u m g a v e 10  Re-  (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) . Anal. Calc. 41.30; H,  f  o  r  C  14 21 3°8 H  F  S :  C  '  - «'  4 1  3 8  H  ' .5.21.  Found:  C,  5.10.  Reactions with pentafluorobenzenesulphonyl of the r e a c t i o n s attempted  with this  the y i e l d s being i n v a r i a b l y a 3-molar e x c e s s  low  chloride.  r e a g e n t were  (~40%).  None  satisfactory,  Reactions conducted  with  o f r e a g e n t g a v e no s i g n i f i c a n t i m p r o v e m e n t 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 temperature  —  (3-48 h ) , n o r  (-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) a n d p y r i d i n e  (0.7 m l , 8.7 mmol) was  treated with  chloride  mmol) a n d f o l l o w e d by t h e u s u a l w o r k - u p .  (1.57 g, 6.25  pentafluorobenzenesulphonyl  The f o l l o w i n g compounds w e r e t h e r e b y  obtained.  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 u r a n o s e  f  (11) , m.p.  125  =  103-104°, |_a J  +64° (c 1 . 9 ) .  D  Anal. Calc. f o r i c  C, 44.04; H,  H 8  19 5°8 F  S :  C  '  4 4  *  0 9 ;  H  '  3  -  9 1  -  Found:  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 - c t - p - g l u c o f u r a n o s e (12) , m.p.  132-136°; an a c c e p t a b l y p u r e s p e c i m e n was  e v e n a f t e r c h r o m a t o g r a p h y on a n e u t r a l a l u m i n a I;  column  not obtained (Brockman  80-200 mesh) u s i n g t o l u e n e - e t h e r . 1,2:3,4-Di-0-isopropylidene-6-0-pentaflyl-a-D-galactopyra-  nose  ( 1 3 ) , m.p.  103-104°, [ a ]  Anal. Calc. f o r C, 4 4 . 2 1 ; H,  3.88.  C  H 1  8  F 1  9  5  °  2 5  S 8  :  -47.5° (c 2 . 3 ) . C,  4 4 . 0 9 ; H,  3.91.  Found:  -66-  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 - p - g a l a c t o pyranose toluene-p-sulphonate  (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 m l ) was heated  under r e f l u x  16 h a d r e a c t e d .  f o r 24 h ; t . l . c .  indicated  t h a t 95% o f  Work-up i n t h e u s u a l f a s h i o n g a v e a c r u d e  (2 g , 33%) w h i c h was r e c r y s t a l l i s e d 18, m.p.  then  204-205°,  "  2 5  product  from aqueous e t h a n o l t o g i v e  ° ( 0.5). c  D  Anal. Calc. f o r C^H^NOgS:  C, 58.28; H, 6.52; N, 2.83.  F o u n d : C, 58.37; H, 6.69; N, 2.80. 6-Deoxy-l,2:3,4-di-O-isopropylidene-6-pyridino-a-D-galactop y r a n o s e 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 , 3 - m o l a r . e x c e s s o f s o d i u m i o d i d e was a d d e d .  The m i x t u r e was  a heated  u n d e r r e f l u x f o r 1 h a n d t h e u s u a l w o r k - u p g a v e 20 ( 1 0 0 % ) . crystallisation  Re-  f r o m m e t h a n o l g a v e 2_0 as a p a l e - y e l l o w p o w d e r , 25  m.p.  250° ( d e c ) , [of)  -30° (c 0 . 2 7 ) .  Anal. Calc. f o rC ^ H ^ I N O ^  C, 4 5 . 4 5 ; H, 5.38; N, 3.12.  F o u n d : C, 45.47; H, 5.37; N, 3.00. Salts of glucofuranose  3-deoxy-l,2:5,6-di-0-isopropylidene-3-pyridino- -Qa  trifluoromethanesulphonate. —  (1 g, 2.8 mmol) a n d t r i f l i c dine  ( 40 m l ) was h e a t e d  anhydride  A s o l u t i o n o f JL  (0.74 m l , 4.4 mmol) i n p y r i -  a t r e f l u x temperature  the u s u a l work-up and a s i n g l e  treatment w i t h  f o r 25 h .  After  charcoal-Celite,  a v e r y h y g r o s c o p i c , b r o w n , 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, and  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  F-n.m.r. s p e c t r o s c o p y Likewise,  (0  4 was c o n v e r t e d  C  salt  + 81.6 p.p.m.). i n t o 17.  17 b y "*"H-n.m.r.  A s a m p l e of. 17 was 19  q u a n t i t a t i v e l y converted  as d e s c r i b e d p r e v i o u s l y ; m.p.  D ]"  "3°  1  190-193^  iodide  (from aqueous e t h a n o l ) ,  (c 0 . 3 9 ) .  Anal. C a l c . for' C F o u n d : C,  44.96; H,  1 7  H  I N 0 : C,  2 4  5.46;  Stannane D e r i v a t i v e s of  5  N,  5.38;  was  was  obtained  3.12.  from A l f a  Products  used a f t e r r e c r y s t a l l i z i n g  freeze-drying, using f o r 2 4 hours.  "Drierite"  d e s s i c a n t , a t c a 0.8  torr  grade) were o b t a i n e d  f r o m F i s h e r S c i e n t i f i c Co.,  ( F a i r Lawn, N . J . ,  N,  Carbohydrates  ( D a n v e r s , M a s s . , U.S.A.) and m e t h a n o l - c h l o r o f o r m and  4 5 . 4 5 ; H,  3.03.  T r i p h e n y l t i n c h l o r i d e (9 5+%)  For  i n t o the  from  as  the  L i t h i u m metal rods  (tech.  Chem. M a n u f a c .  Div.  U.S.A.).  compounds 25,  26  and  27,-  "'"H n.m.r. d a t a  are r e p o r t e d  in  13  T a b l e 3 and  C n.m.r. d a t a  are  reported  i n Tables  4 and  6.  Preparation of 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 the r e a c t i o n to form t r i p h e n y l t i n  w o r k e d w e l l o n l y when t h e s u r f a c e o f t h e clean.  The  l i t h i u m m e t a l was  m e t a l s u r f a c e , t h e r e f o r e , was  m e t h a n o l and  cleaned,  then q u i c k l y r i n s e d i n dry t e t r a h y d r o f u r a n  adding i t to the s o l v e n t i n the r e a c t i o n v e s s e l . F o l l o w i n g t h e p r o c e d u r e o f T a m b o r s k i 14 , 2.5 g of t r i p h e n y l t i n  c h l o r i d e i n c a 15 ml  g  shavings  Within  c a 20 m l  u t e s , h e a t was  evolved  tetrahydrofuran. and  (6.5  very i n dry  before x 10 -3  t e t r a h y d r o f u r a n were added  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 and  first,  lithium  (0.08  the r e a c t i o n mixture  mol)  mol) to  lithium  about f i f t e e n became a  dark  min-  olive-green colour.  The s o l u t i o n was s t i r r e d  w h i c h t i m e i t was f i l t e r e d  through glass wool  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 . been r e p o r t e d  6 0  after  and i m m e d i a t e l y  f o r this reaction  have  t o be 50-75'  Preparation of triphenyl 6-C-stannane  Yields  f o r 1-2 h o u r s ,  (1,2:3,5-di-O-methylene-a-D-glucofuranose)  (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 described above,for 2 hours, f i l t e r e d added, d r o p w i s e , t o a s t i r r e d  t h r o u g h g l a s s wool and  s o l u t i o n o f 1.5 g  (4.2 x 10 61  1,2:3,5-di-O-methylene-a-D-glucofuranose-6-O-tosylate tetrahydrofuran.  A f t e r 4 hours t . l . c .  t o s y l a t e had r e a c t e d .  _3  mol)  i n 25 m l  indicated that a l l the  The r e a c t i o n m i x t u r e was t h e n p o u r e d  25 0 m l w a t e r a n d n e u t r a l i z e d w i t h ammonium c h l o r i d e .  into  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 m l ) a n d 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 , removed under  reduced p r e s s u r e .  a f t e r which  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 b y a d d i n g c o l d a n h y d r o u s o f f the c r y s t a l s .  t h e s o l v e n t was  e t h e r and f i l t e r i n g  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 a s 25.  Yield,  a f t e r one r e c r y s t a l l i z a t i o n  l e u m e t h e r ) , was 1 g ( 4 3 . 5 % ) , m.p. Anal. Calc. 57. 90; H, .4.86.  forC  2 6  H  2 g  (benzene:  108-110°C, [ ] a  (30-60) 2  5  +60.00  petro(c 2 . 3 7 ) .  0 S n : C, 5 8 . 1 3 ; H, 4.88. F o u n d : C, 5  -69-  Preparation of triphenyl pyranoside)  (methyl  4,6-O-benzylidene-a-D-altro-  2-C-stannane ( 2 6 ) : -3  2.5 g  (6.5 x 10  l i t h i u m metal  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  (0.08 m o l ) w e r e r e a c t e d a s d e s c r i b e d a b o v e ,  filtered, _3  and added, d r o p w i s e , t o a s t i r r e d mol) m e t h y l  s o l u t i o n o f 1.0  g  (3.78 x  2,3-anhydro-4,6-O-benzylidene-a-D-allopyranoside  c a 25 m l t e t r a h y d r o f u r a n .  The r e a c t i o n a p p e a r e d  t o be  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 ; t h e m i x t u r e was  d e s c r i b e d f o r 25, 2.6 g  stirred  (75% y i e l d )  lithium  however, t o ensure  f o r 1 hour.  in  instantan-  e o u s , as t h e d a r k o l i v e - g r e e n c o l o u r o f t h e t r i p h e n y l t i n  reaction,  10  complete  A f t e r workup,  of a c r y s t a l l i n e  as  compound  was  25  obtained, subsequently i d e n t i f i e d +5.9070  C, 6 3 . 8 8 , H,  f o r C_JH 0.-Sn: oo  side)-3-C-stannane  a  g  (3.25 x 10  w i t h 0.55  g  (0.08 m o l )  (methyl  5.24.  Found:  4,6-O-benzylidene-a-D-altropyrano-  l i t h i u m metal  3  O  methyl  2,3  12 h o u r s 2  5  reacted  s h a v i n g s i n t h e manner to a stirred  des-  solution  anhydro-4,6-O-benzylidene-c{-  i n c a 25 m l 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  w o r k u p , as f o r 2 5 , a foamy s y r u p was  166-168°C, [ a ]  c h l o r i d e was  and added, d r o p w i s e ,  (0.6 x 1 0 ~ m l )  D-mannopyranoside  after  62.47; H,  mol) t r i p h e n y l t i n  c r i b e d above, f i l t e r e d , g  C,  (27):  1.25  fied  [] ]n  5.31.  Preparation of triphenyl  0.37  67-69°,  (c 2 . 1 5 ) .  Anal. Calc.  of  as 2_6, m.p.  +91  u n d e r vacuum. (c 1.97) .  obtained.  Yield:  .81 g  This syrup (94%),  m.p.  solidi-  Anal. 62.01;  Calc. H,  for C^H^O^Sn:  5.40.  C,  62.47;  H,. 5 . 2 4 .  Found  -71-  Appendix Assignment of  13  C resonances  by s e l e c t i v e  proton  decoupling. 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 assigning a l l of the  C resonances  The 100 MHz p r o t o n s p e c t r u m  of d e r i v a t i v e s  o f e a c h d e r i v a t i v e was  by c o n v e n t i o n a l p.m.r. m e t h o d s a n d t h e r e s o n a n c e s simple, f i r s t  25-27 a n d 3 1 - 3 3 .  order analysis.  The d e c o u p l e d  first  obtained  assigned  20 MHz  using  (18.682 KG)  13 C n.m.r. s p e c t r u m  o f e a c h compound was a l s o r e c o r d e d .  tions of the frequencies a t which 18.682 KG f i e l d  the protons  (80 MHz) w e r e made.  frequency  s y n t h e s i z e r was  frequency  drift,  connected  t o the i n t e r n a l  resonate  Calculain a  A Hewlett Packard  5105A  t o t h e probe and, t o p r e v e n t  1 MHz  c l o c k o f t h e CFT-20  spec-  trometer. 13 C s p e c t r a o f t h e compounds w e r e t h e n o b t a i n e d w h i l s t v i d u a l proton resonances  were s e l e c t i v e l y  irradiated.  The  indicarbon  c o u p l e d t o a p r o t o n t h u s i r r a d i a t e d was s e e n as a s h a r p  singlet  in  resonances  the spectrum  (figure 11).  Ideally,  s h o u l d h a v e a p p e a r e d as m u l t i p l e t s . at  a l l other carbon  However, p r o t o n s  resonating  frequencies close to that being i r r a d i a t e d  partially  decoupled  a n d t h i s was s e e n m  f a c t was s o m e t i m e s h e l p f u l  are, i n general, 13 the C spectra. This  f o r assignment of the  13  C  resonances.  Ph-C-H I  400 Hz 20 ppm'  in  o o  c_>  fully decoupled spectrum  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  irradiate HI 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  I  I  I  I I  I—i—I—i—I—r  W  >  4  i r r a d i a |  e H-2  I I i  i  i  i ii ' i  i  irradiate H-3 i  1  i I i I I I i i i i r~i i i i i i i i i—i—i—i—i—i—i—i—i—i—i—i—i—r  irradiate H-4 ! III.  1  I i ' i i I "1 T T i I i 1—I—I—I—|—I—|—r  Li I I I  I I I '  I I I  t  I', 1  I  I  I  I I I  I I  I  I I I I I  irradiate H-5 I  ' I I  .  • i i II i ' i i i i i i—r !—i—'—r~!—r~i—i > i -  1  i  undecoupled spectrum ' '' i  r  i  i  : i i  i  C-6  13  T~T—i—i—i—i—i—i—r  OMe  N a t u r a l abundance 'C n.m.r. s p e c t r a , o f t r i p h e n y l ( m e t h y l 4 6-0b 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 26 i n d e u t e r i o b e n r e n e s o l u t i o n (0 3 M) , from a s e l e c t i v e d e c o u p l i n g " experiment, she-win? how the i n d i v i d u a l resonances a r e a s s i g n e d .  REFERENCES  1.  R.S. T i p s o n , Advan. C a r b o h y d r . Res. / 8_ .'(1953)  2.  D.H. B a l l and F.W. (1968) 2 3 3 - 2 7 9 .  3.  D.H. B a l l 2j4 (1969)  4.  T. G r a m s t a d and R.N. 4069-4079.  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 . K i e h l m a n n , J . Amer. Chem. 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