There are few enantioconvergent reactions in which racemic substrates bearing multiple stereochemical features are converted into products with high levels of diastereo- and enantiocontrol. Here, we disclose a process for the highly enantio- and diastereoselective syntheses of medium ring lactams via an intramolecular counterion-directed C-alkylation reaction. The treatment of racemic biaryl anilides that exist as a complex mixture of enantiomers and diastereoisomeric conformers by virtue of multiple axes of restricted rotation with a quinidine-derived ammonium salt under basic conditions affords medium ring lactams bearing elements of both axial and point chirality via an enolate-driven configurational relaxation process. Thermal equilibration of the syn- and anti-product diasteroisomers has demonstrated that the barriers to bowl inversion are >124 kJ mol^-1. We propose that the chiral ammonium salt differentiates between a complex and rapidly equilibrating mixture of enolate and rotational isomers, ultimately leading to highly enantioselective alkylative ring closure. This dynamic and enantioconvergent process offers an operationally simple approach to the synthesis of valuable chiral medium ring lactams for which there are few catalytic and enantioselective approaches.

中文翻译：

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轴向手性介质环的反离子介导的对映收敛合成

很少有对映收敛反应，其中具有多种立体化学特征的外消旋底物被转化为具有高水平非对映和对映控制的产物。在这里，我们公开了一种通过分子内抗衡离子定向C烷基化反应高度对映和非对映选择性合成中环内酰胺的方法。在碱性条件下用奎尼丁衍生的铵盐处理作为对映异构体和非对映异构体构象异构体的复杂混合物存在的外消旋联芳基苯胺，通过烯醇化物提供具有轴向和点手性的中环内酰胺元素- 驱动的构型松弛过程。顺反的热平衡-产物非对映异构体已证明碗反转的障碍>124 kJ mol ^-1。我们建议手性铵盐区分复杂且快速平衡的烯醇化物和旋转异构体混合物，最终导致高度对映选择性的烷基化闭环。这种动态和对映收敛的过程为合成有价值的手性中环内酰胺提供了一种操作简单的方法，而催化和对映选择性方法很少。