Synthesis of (S)-(-)- and (R)-(+)-O-methylbharatamine using a diastereoselective Pomeranz-Fritsch-Bobbitt methodology

Laterally lithiated (S)-(-)- and (R)-(+)-o-toluamides 6 with a chiral auxiliary derived from (S)- and (R)-phenylalaninol, respectively, were used as the building blocks and chirality inductors in the asymmetric modification of the Pomeranz-Fritsch-Bobbitt synthesis of isoquinoline alkaloids. Their addition to imine 2 proceeded with partial cyclization, giving isoquinolones (+)-7 and (-)-7 along with acyclic products, (-)-8 and (+)-8, respectively. LAH-reduction of (+)-7 and (-)-7, followed by cyclization, afforded both enantiomers of the alkaloid, (S)-(-)- and (R)-(+)-O-methylbharatamine 5, in 32% and 40% overall yield and with 88% and 73% ees, respectively. (c) 2005 Elsevier Ltd. All rights reserved.