The Exceptional Chelating Ability of Dimethylaluminum Chloride and Methylaluminum Dichloride. The Merged Stereochemical Impact of α- and β-Stereocenters in Chelate-Controlled Carbonyl Addition Reactions with Enolsilane and Hydride Nucleophiles

• Published in: Journal of the American Chemical Society 2001-11, Vol.123 (44), p.10840-10852
• Main Authors: Evans, David A, Allison, Brett D, Yang, Michael G, Masse, Craig E
• Format: Article
• Language: English
• Subjects: Aldehydes - chemistry; Chelating Agents - chemistry; Models, Molecular; Molecular Conformation; Organometallic Compounds - chemistry; Silanes - chemistry; Stereoisomerism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja011337j

A systematic investigation of the stereoselectivity in Lewis acid-promoted (Mukaiyama) aldol reactions of achiral unsubstituted enolsilanes and chiral β-hydroxy aldehydes proceeding under conditions favoring chelation control is presented. Good stereocontrol can be realized for enolsilane aldol reactions of β-alkoxy and β-silyloxy aldehydes bearing only an α- or a β-stereogenic center. Examination of the chelated intermediates for α,β-disubstituted aldehydes concludes that the syn aldehyde diastereomer possesses the arrangement of stereocenters wherein the α- and β-substituents impart a reinforcing facial bias upon the aldehyde carbonyl. Aldol reactions of syn aldehydes were thus observed to proceed with uniformly excellent diastereofacial selectivity. Aldol reactions of the corresponding anti aldehydes containing opposing stereocontrol elements at the α- and β-positions exhibit variable and unpredictable selectivity.