Phosphorane reaction with carbohydrates

Application of the Wittig reaction in the carbohydrate field is accompanied by certain difficulties. A correct choice of the initial sugar components is the main problem, owing to the basicity of phosphoranes and, especially, to the drastically basic conditions employed with phosphonium ylides (2a). It is not surprising, therefore, that protected (acetalated and aeetylated) aldehydo sugars and resonance-stabilized phosphoranes were used at first,3-5 although partially protected, and even unprotected, aldoses were shown to be amenable to the reaction with various resonance-stabilized phosphoranes, thanks to the presence of the carbonyl form in the mobile equilibrium. The latter reactions, however, are extremely complicated (see Section IV, p. 284). 

After these results had established the feasibility of generating and utilizing a carbohydrate phosphorane, the two systems that had been reported earlier were examined in order to determine if similar conditions would allow them to undergo the Wittig reaction. The ylide derived from phosphonium salt I condensed with both benz-aldehyde and U-chlorobenzaldehyde to produce good yields of olefinic products Villa and Vlllb. The ylide derived from phosphonium salt II also was successfully condensed with benzaldehyde, but the yield of IX was only 30 , presumably because of its extremely poor solubility even in an HMPA-THF solvent mixture. Both of these systems supported the tenet that it was possible to use unstabilized carbohydrate phosphoranes if the conditions are proper and if the g-oxygen is attached to the carbohydrate through another set of bonds. 

An important question with regard to the scope of this method for complex carbohydrate synthesis was whether an unstabilized carbohydrate phosphorane might be compatible with a suitably blocked nucleoside aldehyde. Condensation of the ylide derived from XXI with uridine derivative XXIII proceeded under the usual conditions to give a 25% yield of XXIV, from which the N-benzoyl group could be readily removed with methanolic ammonia. The yield from this condensation reaction was not optimized, but its success clearly demonstrated the feasibility of such a transformation, if design considerations dictate the use of a nucleoside directly. 

In the meantime, the Wittig olefination of carbohydrate lactones with stabilized phosphoranes at high temperature was discovered. This was an efficient reaction which worked with y- and 5- lactones in excellent yields. This way another new class of exo-glycals 3 was available, as Z/E mixtures but with an interesting push-pull substitution of the double bond (Scheme 1). ... 

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