Germanium(II)-Mediated Reductive Cross-Aldol Reaction of Bromoaldehydes with Aldehydes: NMR Studies and ab Initio Calculations

Abstract

A highly practical reductive cross-aldol reaction of alpha-bromoaldehydes with various aldehydes has been developed using Ge(II)Cl 2 to produce aldehyde germanium(IV) aldolates, which were directly transformed to various multifunctionalized compounds. A remarkable change in stereoselectivity depended on the alpha-bromoaldehydes employed; secondary alpha-bromoaldehydes gave syn selectivities, while tertiary alpha-bromoaldehydes accomplished the synthesis of anti-selective aldol products with a quaternary carbon center. NMR studies and X-ray analysis strongly suggested the formation of germanium enolate in the reaction of alpha-bromoaldehyde 2h with GeCl 2-dioxane. Detailed mechanistic studies, including NMR analysis and ab initio calculations, revealed the generation of stable germanium aldolates, which was due to the remarkably low Lewis acidity of the germanium(IV).