Three-Component Coupling Reactions of Silylglyoxylates, Alkynes, and Aldehydes:  A Chemoselective One-Step Glycolate Aldol Construction

A single-pot three-component coupling reaction of silylglyoxylates (1), terminal alkynes, and aldehydes in the presence of ZnI₂ and Et₃N is presented. The products of the reaction, densely functionalized silyl-protected glycolate aldols (2), can be converted to the corresponding acetonides (3) in a one-pot deprotection/ketalization sequence. A variety of terminal alkynes and aldehydes can be successfully employed to give a range of highly functionalized, fully protected 1,2-diols in good yields and moderate diastereoselectivities. Mechanistic experiments suggest that the zinc acetylide reacts with the silylgyloxylate (1) in a chemoselective manner. Using an unoptimized (+)-N-methylephedrine and Zn(OTf)₂ system, silyl-deprotected adduct 2 was formed in 64% ee and 89:11 dr.