A Highly Selective Ferrocene-Based Planar Chiral PIP (Fc-PIP) Acyl Transfer Catalyst for the Kinetic Resolution of Alcohols

Novel planar chiral ferrocene nucleophilic catalysts (Fc-PIP) containing both central and planar chiral elements were designed and synthesized for catalytic enantioselective acyl transfer of secondary alcohols. A remarkably efficient catalyst with high selectivity factors (up to S = 1892) was identified. Comparing the combination of central and planar chirality revealed a strong requirement for the “matched” chiral elements, indicating that the stereogenic center of the imidazole rings should present itself on the same face as the ferrocenyl fragment; otherwise, the catalyst is completely inactive. An exclusively stacked transition state that accounts for the high selectivity of the kinetic resolution of secondary alcohols is proposed. Notably, this newly designed catalyst family is suitable for the catalytic kinetic resolution of bulky arylalkyl carbinols, producing esters with extremely high ee (>99%).

为实现二级醇的催化对映选择性酰基转移反应，研究人员设计并合成了兼具中心手性与平面手性元素的新型平面手性二茂铁类亲核催化剂（Fc-PIP）。最终筛选得到一款催化性能优异的催化剂，其选择性因子最高可达S=1892。通过对比中心手性与平面手性的不同组合模式，发现该催化体系对“匹配型”手性元素具有严格要求：咪唑环的手性中心需与二茂铁片段处于同一平面同侧，否则催化剂将完全丧失活性。本研究提出了一种专属堆叠过渡态模型，可合理解释二级醇动力学拆分过程中的高选择性现象。值得注意的是，这款全新设计的催化剂家族可有效应用于大位阻芳基烷基甲醇的催化动力学拆分反应，所得酯类产物的对映体过量值（ee）高达99%以上。