Synthesis of Benzomorphan Analogues by Intramolecular Buchwald—Hartwig Cyclization.

A new strategy toward the important class of benzomorphans is described. The key bond formation is based on an intramolecular Buchwald–Hartwig enolate arylation reaction. Thus, alkylation of piperidones with ortho-bromobenzyl bromides provides the necessary substrates. In the presence of a palladium catalyst, a sterically hindered phosphane ligand, and a base, carbon–carbon bond formation to tricyclic benzomorphan derivatives takes place. After removal of the N-protecting group, derivatization reactions are possible. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)