Highly enantioselective introduction of bis(alkoxycarbonyl)methyl group into the 2-position of piperidine skeleton

Copper ion catalyzed carbon-carbon bond forming reaction of N-acyliminium ions with diaryl malonates was achieved with high enantioselectivity. The key intermediates in the method were 2-methoxy-3,4-didehydropiperidines, which were easily prepared through electrochemical oxidation of 1-(p-methoxybenzoyl)piperidine in methanol followed by the conversion of the oxidation product to didehydropiperidine derivative, which was subjected to a chiral Cu(II) catalyzed coupling reaction with diaryl malonates affording diaryl 2-piperidylmalonates. The maximum %e.e. (e.e., enantiomeric excess) was 97% when di-p-chlorophenyl malonate was used as a nucleophile.