Synthesis of BMS 184394

Significance

BMS 184394 is α β,γ-selective ligand for the retinoic acid nuclear receptor. Its synthesis is used to showcase the first one-pot method for the catalytic asymmetric addition to aldehydes of organozinc reagents generated in situ to give diarylmethanols. The use of cheap bromo­arenes rather than costly arylzinc or arylboronic acids as starting materials is a significant practical advantage. Kim and Walsh report 14 examples of Ar₂Zn addition (yield typically >90%, er > 9:1) and 17 examples of ArZnBu addition (yields 55-98%, er = 3:1 to 99:1) mediated by Nugent’s MIB ligand (see: Y. K. Chen, S.-J. Jeon, P. J. Walsh, W. A. Nugent Org. Synth. 2005, 82, 87-92).