THE CATALYTIC ENANTIOSELECTIVE STETTER REACTION

摘要

Transformations that proceed by a reversal in the usual electrophilic and nucleo-philic properties associated with a particular functional group, a concept referred to by the German noun 'Umpolung' (literally, 'polarity reversal'),1 allow for the implementation of unconventional disconnections in retrosynthesis and lead directly to motifs that are difficult to access with traditional chemistries (e.g., 1,4-and 1,6-relationships between oxygenated carbon atoms along an alkyl chain). A commonly explored type of Umpolung reactivity involves the generation of acyl anion equivalents wherein the characteristic electrophilicity of the carbonyl group carbon atom is exchanged for nucleophilicity. This scenario can be effected by multistep tactics involving stoichiometric reagents, for example, via the generation and subsequent metalation of dithianes.2'3 However, a more attractive approach is to generate an acyl anion equivalent in situ by the interaction of a catalyst with the requisite aldehyde. Adding to the allure of this approach, if the catalyst employed is a chiral molecule, then catalytic enantioselective synthesis may be possible. The catalytic generation of acyl anion equivalents is largely limited to transformations of aldehydes mediated by cyanide anion or 7V-heterocyclic carbenes (NHCs).4,5 Examples of such processes of both artificial and natural origin exist and include a slew of biosynthetic pathways mediated by the enzyme cofactor thiamine, the deprotonated form of which is a thiazolylidene carbene.