Isotope effects and the mechanism of chlorotrimethylsilane-mediated addition of cuprates to enones

Kinetic isotope effects were determined for the chlorotrimethylsilane-media ted reactions of cyclohexenone with lithium dibutylcuprate in tetrahydrofur an and with lithium butyl(tert-butylethynyl)cuprate in ether. For the react ion in tetrahydrofuran, the observation of a significant carbonyl oxygen is otope effect ((16)k/(17)k = 1.018-1.019) and small olefinic carbon isotope effects ((12)k/(13)k = 1.003-1.008) is consistent with rate-limiting silyla tion of an intermediate pi-complex. Theoretically predicted isotope effects for model reactions support this conclusion. Rate-limiting silylation is a lso supported by relative reactivity studies of chlorotrimethylsilane versu s chlorodimethylphenylsilane. The absence of a significant butyl-group carb on isotope effect on product formation indicates that the cuprate butyl gro ups are nonequivalent in the intermediate leading to the product-determinin g step. In diethyl ether the isotope effects revert to values similar to th ose found previously in reactions of cyclohexenone with Lithium dibutylcupr ate in the absence of chlorotrimethylsilane, consistent with no change in t he overall mechanism in this solvent. A mechanistic hypothesis For the diff ering effects of TMSCl with changes in solvent and substrate is presented.