Brønsted-Acid-Promoted Rh-Catalyzed Asymmetric Hydrogenation of N-Unprotected Indoles: A Cocatalysis of Transition Metal and Anion Binding

• DOI: 10.1021/acs.orglett.8b00312
• Publication Date: 2018-03-30T12:28:26Z
• Authors: Jialin Wen; Xiangru Fan; Renchang Tan; Hui-Chun Chien; Qinghai Zhou; Lung Wa Chung; Xumu Zhang
• Keywords: 01 natural sciences; 0104 chemical sciences

The incorporation of Brønsted acid, thiourea anion binding, and transition metal catalysis enables an efficient method to synthesize chiral indolines via hydrogenation of indoles. Catalyzed by a rhodium/ZhaoPhos complex, asymmetric hydrogenation of unprotected indoles is performed smoothly with excellent enantioselectivities (up to 99% ee, up to 400 TON). Brønsted acid HCl activates indoles to form iminium ion intermediates. Mechanistic studies support the assumption that anion binding plays a crucial role as a secondary interaction. DFT calculations reveal an outer-sphere mechanism in this chemical transformation.