Carbene-Catalyzed Direct Functionalization of the β-sp³-Carbon Atoms of α-Chloroaldehydes

A direct functionalization of the β-sp³ carbon atom of α-chloro aldehyde has been developed. The reaction starts with the addition of a carbene catalyst to α-chloroaldehyde to eventually form the homoenolate intermediate. This overall redox-neutral process successfully converts the otherwise inert β-sp³-carbon atom of the aldehyde substrate to a nucleophilic carbon atom for asymmetric reactions. This study constitutes the first success in activating α-chloroaldehydes to generate homoenolate intermediates by carbene organic catalysis and shall encourage further explorations in using organic catalysis for transforming inert chemical bonds.