Recent Advances in Heteroatom-Stabilized Carbanion Chemistry

Abstract

An efficient, stereoselective method for the synthesis of α-phosphonoenamines based on a modified Peterson olefination was developed. The carbanion derived from Diethyl 1-dimethylamino-1-trimethylsilylmethanophosphonate reacted with aromatic or aliphatic aldehydes selectively eliminating in Peterson fashion to deliver functionally rich α-phosphonoenamines. A highly efficient method was developed for the one-carbon homologation of aldehydes to carboxylic acid derivatives employing the reaction of a 1, 1-bis-dimethylphosphonate derivative with the aldehyde and controlled acid hydrolysis of the derived α-phosphonoenamine intermediate. The reaction of bis(trimethylsilyl)chloromethane with s-BuLi was found to proceed via transmetallation rather than deprotonation yielding the nucleophilic bistrimethylsilylmethyl anion quantitatively which reacted readily with aldehydes providing a general entry to vinylsilanes. The reaction of α-silylated ylides with non-enolizable aldehydes proceeded via selective Peterson-type elimination, in contrast to prior literature reports, providing a direct route to synthetically useful vinylphosphonium salts. The chemoselective formation of trialkylbenzyl phosphoranes in water and their Wittig reaction with aromatic and aliphatic aldehydes provided a practical, stereoselective and environmentally benign route to valuable trans-stilbenes and alkenes. The synthesis of the phytoalexin resveratrol was described. In addition, the method allowed for a gramscale synthesis of the anticancer agent DMU-212 utilizing no organic solvent at any stage. A direct synthesis of 1,3-dienes and 1,3,5-trienes from the reaction of semi-stabilized ylides and a range of saturated and unsaturated aldehydes was reported in water as solvent, employing sodium hydroxide as base. The water-soluble phosphine oxide side product was removed simply by aqueous partitioning of the organic products.