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.
Nicewicz
David A
DA
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA.
Johnson
Jeffrey S
JS
D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D006016:Glycolates / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D014297:Trimethylsilyl Compounds / Q000737:chemistry*
D000447:Aldehydes; D000480:Alkynes; D006016:Glycolates; D014297:Trimethylsilyl Compounds