One-pot synthesis of congested aldol products through in-situ enol silane formation-Mukaiyama aldol reaction promoted by trimethylsilyl trifluoromethanesulfonate

A series of α-disubstituted ketones was shown to undergo in situ enol silane formation followed by Mukaiyama aldol addition to various aldehydes in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) and 2,6-lutidine. Purification by chromatography affords superior yields of the congested aldol products as conveniently protected silyl ethers. The in situ-produced enol silane was also shown to undergo α-alkylation and a Mukaiyama aldol-type reaction with a dimethyl acetal.