College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, PR China.
Org Biomol Chem. 2012 Jun 14;10(22):4417-23. doi: 10.1039/c2ob25316j. Epub 2012 May 8.
The mechanism of the gold-catalyzed annulations of 3-aryloxy alkynyl indoles developed by Tu et al. was studied by DFT calculations. It was found that both indole derivatives of electron-donating and electron-withdrawing protective groups would first undergo the 5-exo-dig cyclization simultaneously upon activation by cationic [PR(3)Au(+)] species. However, divergent reactivity of the resulting spirocyclic intermediate in competitive 1,2-alkenyl migration and nucleophilic water addition reactions towards C3 was predicted. When protected by electron-donating group, the 1,2-alkenyl migration occurs to generate a tricyclic intermediate, from which an aromatic Claisen rearrangement/nucleophilic addition sequence results in the observed 1,2-phenoxy migration. In case of electron-withdrawing group, the 1,2-alkenyl migration would be unfavorable. Instead, the nucleophilic addition of water oxygen to C3 is more facile, and leads to the hemiketal intermediate. The possible roles of water-cluster and OTf anion as proton shuttles in both reactions were also evaluated.
图等人通过 DFT 计算研究了金催化的 3-芳氧基炔基吲哚的环化反应机理。研究发现，具有给电子和吸电子保护基团的吲哚衍生物在阳离子[PR(3)Au(+)]物种的活化下，首先会同时经历 5-endo-dig 环化反应。然而，对于生成的螺环中间体，在竞争性的 1,2-烯基迁移和亲核水加成反应中，对于 C3 的反应活性是不同的。当受到供电子基团保护时，1,2-烯基迁移发生，生成三环中间体，其中芳族 Claisen 重排/亲核加成序列导致观察到的 1,2-苯氧基迁移。对于吸电子基团，1,2-烯基迁移是不利的。相反，水氧对 C3 的亲核加成更容易，生成半缩酮中间体。还评估了水簇和 OTf 阴离子在这两种反应中作为质子穿梭体的可能作用。
