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

A highly practical reductive cross-aldol reaction of α-bromoaldehydes with various aldehydes has been developed using Ge(II)Cl2 to produce aldehyde germanium(IV) aldolates, which were directly transformed to various multifunctionalized compounds. A remarkable change in stereoselectivity depended on the α-bromoaldehydes employed; secondary α-bromoaldehydes gave syn selectivities, while tertiary α-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 α-bromoaldehyde 2h with GeCl2−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).