S-Methylidene agents: preparation of chiral non-racemic heterocycles

Reaction of sulfur ylide with aldehyde, imine, and ketone functionality affords the desired three-membered heterocycle in excellent yield. The sulfur ylide is generated in situ upon decarboxylation of carboxymethylsulfonium betaine functionality. Of the seven carboxymethylsulfonium betaine derivatives surveyed, the highest level of conversion of π-acceptor to heterocycle was obtained with the one having S-methyl and S-phenyl functionality bound to a thioacetate derivative. Methylene aziridinations and epoxidations involving the decarboxylation of carboxymethylsulfonium betaine functionality complements existing technologies with the advantages of the reaction protocol, levels of conversion, and scope. While moderate levels of diastereocontrol were observed in the aziridination of imine functionality, the four oxiranes resolved using Jacobsen's Co(II)-salen complex were obtained in both high yield and enantioselectivity. The isolated chiral non-racemic oxiranes constitute the formal synthesis of chelonin B and combretastatin starting from 3-bromo-4-methoxybenzaldehyde and 3,4,5-trimethoxybenzaldehyde, respectively.