Jang Jiwon, Kim Hanbyul, Shin Seunghoon
Department of Chemistry, Research Institute for Natural Sciences and Center for New Directions in Organic Synthesis (CNOS), Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 04763, Korea.
J Org Chem. 2023 Nov 3;88(21):15437-15443. doi: 10.1021/acs.joc.3c02007. Epub 2023 Oct 18.
Gold-catalyzed enantioselective thioallylation of propiolates proved effective in delivering highly enantio-enriched α-allyl-β-thioacrylates. In this work, we report a revised mechanism for this process based on the new mechanistic experiments and kinetic data in the presence of a competitive inhibitor. The employment of thioethers as nucleophiles inevitably involves their competitive binding to the only catalytic site of the Au(I) catalyst, which may inhibit the activity. We developed a modified Hammett plot in the presence of a dummy thioether inhibitor, which revealed a true kinetic profile, excluding the effect of inhibition. A revised mechanism suggested that the conjugate addition of thioethers to the Au(I)-activated alkynes is the turnover-limiting step, and the subsequent [3,3]-rearrangement occurs quickly, suggesting the efficacy of the sulfonium-based approach in accelerating Claisen rearrangement. In addition, the enantioselectivity was suggested to be determined during the sigmatropic rearrangement by discriminating the prochiral olefin faces of the allyl group in the σ-bound Au(I) complex.
金催化的丙炔酸酯对映选择性硫代烯丙基化反应被证明能有效地生成高度对映体富集的α-烯丙基-β-硫代丙烯酸酯。在这项工作中，我们基于新的机理实验和在存在竞争性抑制剂的情况下的动力学数据，报道了该过程的修正机理。使用硫醚作为亲核试剂不可避免地涉及它们与Au(I)催化剂的唯一催化位点的竞争性结合，这可能会抑制活性。我们在存在虚拟硫醚抑制剂的情况下开发了一种修正的哈米特图，它揭示了真实的动力学概况，排除了抑制作用的影响。一种修正的机理表明，硫醚对Au(I)活化的炔烃的共轭加成是周转限制步骤，随后的[3,3]重排迅速发生，这表明基于锍的方法在加速克莱森重排方面的有效性。此外，有人认为对映选择性是在σ迁移重排过程中通过区分σ键合的Au(I)配合物中烯丙基的前手性烯烃面来确定的。
