Efficient asymmetric carbon-carbon bond-forming reaction at the 2-position of a piperidine skeleton was achieved through scrutinizing chiral catalysts, copper ions, nucleophiles, and reaction temperatures. The key intermediates in this method were 2-methoxy3,4-didehydropiperidines, which were easily prepared by electrochemical oxidation of 1-protected piperidines in methanol followed by didehydrogenation of the oxidation products. This method involved a chiral Cu(II) catalyzed coupling reaction between 1-(4-methoxybenzoyl)3,4-didehydro-2-methoxypiperidine and nucleophiles such as dimethyl malonate and methyl acetoacetate to afford 2-substituted piperidines with up to 82%e.e. (e.e., enantiomeric excess). (C) 2005 Elsevier Ltd. All rights reserved.