Mechanism of the N-protecting group dependent annulations of 3-aryloxy alkynyl indoles under gold catalysis: a computational studyElectronic supplementary information (ESI) available: Other possible reaction pathways, calculated geometries, energies, and Cartesian coordinates. See DOI: 10.1039/c2ob25316j

• Main Authors: Cheng, Bing, Huang, Genping, Xu, Liang, Xia, Yuanzhi
• Format: Journal Article
• Language: English
• Published: 14.06.2012
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c2ob25316j

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. The mechanism of regiodivergent gold-catalyzed annulations of alkynyl indoles from the Tu group was better understood by DFT calculations.