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

Abstract

An enantioselective synthesis of acyclic β-diaryl ketones and esters via 1,4-addition of arylboronic acids to β-aryl-α,β-unsaturated ketones or esters is described. The complex in situ prepared from [Rh(nbd) 2]BF 4 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 β-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 β-aryl-α,β-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.