Cyclic sulfamidates as versatile lactam precursors. An evaluation of synthetic strategies towards (-)-aphanorphine.

A full account of studies which led to the efficient asymmetric synthesis of (-)-aphanorphine is reported. Two routes to the key cyclic sulfamidate intermediate are described, the first was based on a chiral auxiliary approach and the second utilised asymmetric hydrogenation methodology. A range of C(3)-substituted lactams (, and ) were synthesised and evaluated as precursors for Pd(0) catalysed entries (based on (i) alpha-arylation of a lactam enolate and (ii) reductive Heck reaction) to the 3-benzazepine core of . These approaches were less effective than an aryl radical cyclisation which allowed the completion of a synthesis of in 12 steps from anisaldehyde.