Synthesis of 1,5-methano-3-benzazocines by intramolecular Buchwald-Hartwig arylation of 2-piperidinones

A conceptually novel route to 1,5-methano-3-benzazocines based on an intramolecular Buchwald - Hartwig arylation was developed. The reaction required the use of the zinc enolate of the piperidinone substrates. These substrates, piperidin-2-ones with a 2-bromobenzyl substituent in the 5-position were prepared by reductive amination of 4-formyl esters. The latter could be obtained via Michael addition of enamines, derived from 3-arylpropanals, to ethyl acrylate. (c) 2007 Elsevier Ltd. All rights reserved.