Deoxycholic acid-based phosphites as chiral ligands in the enantioselective conjugate addition of dialkylzincs to cyclic enones:: preparation of (-)-(R)-muscone

Four phosphites, obtained by linking enantiomerically pure binaphthylchlorophosphite to the two different hydroxy substituted positions of deoxycholic acid, were used as chiral ligands in the enantioselective copper catalysed 1,4-addition of diethylzinc to 2-cyclohexenone and dimethylzinc to 2-cyclopentadecenone. Various reaction parameters were changed in order to select the experimental conditions that would maximise yield and ee. The four ligands were screened for activity and enantioselectivity under the optimised reaction conditions for comparative purposes, in order to establish the influence of the absolute configuration of the binaphthyl moiety as well as the position on the cholestanic backbone of the phosphite moiety. The ligand possessing a (R)-binaphthylphosphite moiety at position 12 of the cholestanic backbone proved to be the most enantioselective affording (-)-(R)-muscone in 63% ee. (C) 2004 Elsevier Ltd. All rights reserved.