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

2005-05-04T00:00:00Z (GMT) by David A. Nicewicz Jeffrey S. Johnson
A single-pot three-component coupling reaction of silylglyoxylates (<b>1</b>), terminal alkynes, and aldehydes in the presence of ZnI<sub>2</sub> and Et<sub>3</sub>N is presented. The products of the reaction, densely functionalized silyl-protected glycolate aldols (<b>2</b>), can be converted to the corresponding acetonides (<b>3</b>) 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 (<b>1</b>) in a chemoselective manner. Using an unoptimized (+)-<i>N</i>-methylephedrine and Zn(OTf)<sub>2</sub> system, silyl-deprotected adduct <b>2</b> was formed in 64% ee and 89:11 dr.