The asymmetric synthesis of (R)-(+)- and (S)-(-)-O-methylbharatamine

The asymmetric syntheses of (R)-(+)- and (S)-(-)-O-methylbharatamine were performed using the lateral metallation strategy, in which (R)- and (S)-phenylalaninol were applied as chiral auxiliaries. The addition reaction of chiral o-toluamide carbanion to 6,7-dimethoxy-3,4-dihydroisoquinoline proceeded with a simultaneous cyclization reaction, giving both enantiomers of 2,3-dimethoxy-8-oxoberbine in good yield (76%) with high enantioselectivity (99% ee). Lithium aluminum hydride reduction of each enantiomer led to (R)-(+)- and (S)-(-)-O-methylbharatamine without loss of enantioselectivity. (C) 2004 Elsevier Ltd. All rights reserved.