| The carbometalations of unactivated and electron-rich alkenes are described using the highly reactive and efficient allyldihaloboranes 32 and 52. These allylborating reagents react with alkenes regio- and stereoselectively in high yields and provide a concise and simple methodology for their synthesis.;A complete mechanistic investigation of organocuprate conjugate additions to enones using kinetic isotope effects (KIEs) is presented. For the prototypical cuprate reaction of Bu2CuLi with cyclohexenone in THF, large experimental KIEs for the beta-carbon of cyclohexenone and a substantial KIE for the incoming butyl group implicate reductive elimination from copper as the rate-determining step in these reactions. For the TMSCl-mediated conjugate addition of Bu 2CuLi to cyclohexenone, the reaction pathway was found to depend on the solvent used in these reactions. For the reaction in tetrahydrofuran, the observation of a significant carbonyl oxygen isotope effect (16 k/17k = 1.018--1.019) and small olefinic carbon isotope effects (12k/13k = 1.003--1.008) is consistent with rate-limiting silylation of an intermediate pi-complex. Theoretically predicted isotope effects for model reactions support this conclusion. Rate-limiting silylation is also supported by relative reactivity studies of chlorotrimethylsilane versus chlorodimethylphenylsilane. In diethyl ether the isotope effects revert to values similar to those found previously in reactions of cyclohexenone with lithium dibutylcuprate in the absence of chlorotrimethylsilane, consistent with no change in the overall mechanism in this solvent. A mechanistic hypothesis for the differing effects of TMSCl with changes in solvent and substrate is presented. Finally, preliminary experimental 13C and 2H KIEs were determined for the reaction of cyanocuprate 150 to cyclohexenone in THF. Again, the results point to reductive elimination from a "Cu(III)" intermediate as rate-limiting implicating that the cyanide ligand has a minor influence on the rate-determining step in cuprate conjugate additions. The above results have broad implications towards synthetic and mechanistic studies of organocuprate 1,4-additions to enones. |
