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 % ee (ee, enantiomeric excess) was 97% when di-p-chlorophenyl malonate was used as a nucleophile.

Graphical abstractA Cu(OTf)2 catalyzed coupling reaction between 1-(p-methoxybenzoyl)-3,4-didehydro-2-methoxypiperidine, which were easily prepared by utilizing electrochemical oxidation, and di-p-chlorophenyl malonate to afford 2-piperidinyl malonate with up to 97% ee in the presence of chiral bisoxazoline ligand.Figure optionsDownload full-size imageDownload as PowerPoint slide