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.
Bower
John F
JF
School of Chemistry, University of Bristol, Bristol, United Kingdom.
Szeto
Peter
P
Gallagher
Timothy
T
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D003499:Cyclic S-Oxides / Q000737:chemistry*; D003500:Cyclization; D007769:Lactams / Q000737:chemistry*; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry
D001952:Bridged-Ring Compounds; D003499:Cyclic S-Oxides; D007769:Lactams; D011758:Pyrroles; D013449:Sulfonamides; C434304:aphanorphine