Stereoselective synthesis of a C1-C6 fragment of pinnatoxin A via a 1,4-addition/alkylation sequence

A C1-C6 fragment of pinnatoxin A, (5S,6R)-5,6-dimethyl-3-methyleneoxepan-2-one, which features a gamma,delta-trans-dimethyl-substituted alpha-methylene lactone, has been synthesized in an enantiomerically pure form from ethyl (E)-4-benzyloxy-2-butenoate through an auxiliary-based conjugate addition and alkylation reaction. The excellent diastereoselectivity (98:2) observed in the alkylation reaction is the result of stereocontrol from both the adjacent stereocenter and the chiral oxazolidinone. (C) 2008 Elsevier Ltd. All rights reserved.