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 maximise yield and e.e.. The four ligands were screened for activity and enantioselectivity under the optimised reaction conditions for comparative purposes, in order to establish what is the influence of the absolute configuration of binaphthyl moiety as well as the position on the cholestanic backbone of the phosphite moiety. The ligand possessing a (R)-binaphthylphosphite moiety at the position 12 of the cholestanic backbone resulted the most enantioselective affording (-)-(R)-muscone in 63% e.e.