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 α-alkyl-α-formyl-β-ketoesters
in high yield (up to 97%) with high enantioselectivity (up to >99%).
Computational evidence indicated that noncovalent interactions (n
→ π*) 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.