Catalytic Asymmetric Formal C-C Bond Insertion Reaction of Aldehydes via 1,2-Acyl Shift: Construction of All-Carbon Quaternary Stereocenters with Three Carbonyl Groups

The formal C-H bond insertion reaction into aldehydes via 1,2-hydride shift has been well established; however, the formal C-C bond insertion is more challenging. In the presence of chiral oxazaborolidinium ion (COBI) catalyst, the formal C-C bond insertion into glyoxals was developed via an 1,2-acyl shift for the construction of alpha-alkyl-alpha-formyl-beta-ketoesters in high yield (up to 97%) with high enantioselectivity (up to >99%). Computational evidence indicated that noncovalent interactions (n -> pi*) between substrates stabilized the transition state, thereby resulting in high enantioselectivity. This method enabled the construction of unique acyclic all-carbon quaternary stereocenters containing three different carbonyl groups.