An enantioselective intramolecular S_N2’ reaction of geometrically defined allylic substrates was developed by introducing a co-catalyst system composed of chiral bisphosphoric acid and phenylboronic acid. In the enantioselective nucleophilic substitution reaction using chiral phosphoric acids and derivatives (CPAs) as the catalyst, the formation of the corresponding CPA ester, which is afforded through the S_N2 reaction of the substrate with the nucleophilic phosphate anion generated during the activation of a leaving group, has been a serious problem because of the catalyst deactivation. The developed co-catalyst system surmounted this fundamental problem by efficiently suppressing the catalyst deactivation process to afford enantioenriched vinyl epoxides in good yields with moderate to high enantioselectivities. Mechanistic elucidation of the present enantioselective intramolecular S_N2’ reaction using the co-catalyst system revealed that the leaving group is involved in the enantio-determining transition states, and the anti-S_N2’ pathway is considered to be the rational mechanism of the present allylic substitution reaction. In addition, the stereospecific Meinwald rearrangement of the thus-formed enantioenriched vinyl epoxide was aided by an equimolar amount of a Lewis acid, affording the corresponding all-carbon quaternary α-vinyl cyclohexanone without marked loss of enantiomeric purity.

通过引入由手性双磷酸和苯基硼酸组成的助催化剂体系，开发了几何定义的烯丙基底物的对映选择性分子内 S _N 2' 反应。在使用手性磷酸及其衍生物 (CPA) 作为催化剂的对映选择性亲核取代反应中，形成相应的 CPA 酯，通过 S _N2 底物与离去基团活化过程中产生的亲核磷酸根阴离子的反应，由于催化剂失活而成为一个严重的问题。开发的助催化剂系统通过有效抑制催化剂失活过程以良好的收率提供对映体富集的乙烯基环氧化物，并具有中等至高的对映体选择性，从而克服了这一基本问题。使用助催化剂系统对本发明的对映选择性分子内 S _N 2' 反应的机理阐明表明，离去基团参与决定对映体的过渡态，而抗S _N2'途径被认为是目前烯丙基取代反应的合理机制。此外，由此形成的对映体富集的乙烯基环氧化物的立体定向 Meinwald 重排由等摩尔量的路易斯酸辅助，提供相应的全碳季铵 α-乙烯基环己酮，而对映体纯度没有明显损失。