Asymmetric syntheses of a GPR40 receptor agonist via diastereoselective and enantioselective conjugate alkynylation

Two asymmetric methods to synthesize a potent GPR40 receptor agonist are reported. Both synthetic routes utilize readily available, inexpensive starting materials and reagents. The first route relies on a highly diastereoselective conjugate alkynylation of an ephedrine-derived oxazepanedione acceptor. The second route features the enantioselective alkynylation of a Meldrum's acid-derived acceptor mediated by a chiral zinc cinchonidine reagent. (C) 2010 Elsevier Ltd. All rights reserved.