1,4-Addition of arylboronic acids to beta-aryl-alpha,beta-unsaturated ketones and esters catalyzed by a rhodium(I)-chiraphos complex for catalytic and enantioselective synthesis of selective endothelin - A receptor antagonists

摘要

An enantioselective synthesis of acyclic beta-diaryl ketones and esters via 1,4-addition of arylboronic acids to beta-aryl-alpha,beta-unsaturated ketones or esters is described. The complex in situ prepared from [Rh(nbd)(2)]BF4 and chiraphos was found to be an excellent catalyst to achieve high enantioselectivities in a range of 83-89% ee for the ketone derivatives and 78-94% ee for tert-butyl beta-arylacrylate derivatives. The protocol provided a catalytic method for the enantioselective synthesis of selective endothelin A receptor antagonists (7, 8) reported by SmithKline Beecham and Merck-Banyu. The enantioselection mechanism and efficiency of the chiraphos ligand for beta-aryl-alpha,beta-unsaturated ketones and esters are discussed on the basis of results of DFT computational studies on the modes of coordination of the enone substrates to the phenylrhodium(I)-(S,S)-chiraphos complex. (c) 2006 Elsevier Ltd. All rights reserved.