Borane‐Catalyzed Tandem Cyclization/Hydrosilylation Towards Enantio‐ and Diastereoselective Construction of trans‐2,3‐Disubstituted‐1,2,3,4‐Tetrahydroquinoxalines

• Published in: Angewandte Chemie Vol. 135; no. 32
• Main Authors: Luo, Zhenli, Li, Zhewei, Zhao, Haoqiang, Yang, Ji, Xu, Lijin, Lei, Ming, Fan, Qinghua, Walsh, Patrick J.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 07.08.2023
• Subjects: 1,2,3,4-Tetrahydroquinoxaline; Borane; Boranes; Catalysts; Chemistry; Diketones; Frustrated Lewis Pairs; Hydroboration; Hydrosilylation; Quinoxaline; Stereoselectivity; Substrates
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202305449

Recent years have witnessed marked progress in the efficient synthesis of various enantioenriched 1,2,3,4‐tetrahydroquinoxalines. However, enantio‐ and diastereoselective access to trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines remains much less explored. Herein we report that a frustrated Lewis pair‐based catalyst generated via in situ hydroboration of 2‐vinylnaphthalene with HB(C6F5)2 allows for the one‐pot tandem cyclization/hydrosilylation of 1,2‐diaminobenzenes and 1,2‐diketones with commercially available PhSiH3 to exclusively afford trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines in high yields with excellent diastereoselectivities (>20 : 1 dr). Furthermore, this reaction can be rendered asymmetric by using an enantioenriched borane‐based catalyst derived from HB(C6F5)2 and a binaphthyl‐based chiral diene to give rise to enantioenriched trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines in high yields with almost complete diastereo‐ and enantiocontrol (>20 : 1 dr, up to >99 % ee). A wide substrate scope, good tolerance of diverse functionality and up to 20‐gram scale production are demonstrated. The enantio‐ and diastereocontrol are achieved by the judicious choice of borane catalyst and hydrosilane. The catalytic pathway and the origin of the excellent stereoselectivity are elucidated by mechanistic experiments and DFT calculations. A one‐pot tandem cyclization/hydrosilylation process applied to 1,2‐diaminobenzenes and 1,2‐diketones under borane catalysis with PhSiH3 for the enantio‐ and diastereoselective synthesis of trans‐2,3‐disubstituted 1,2,3,4‐tetrahydroquinoxalines is presented. Experimental studies and density functional theory calculations were conducted to explore the reaction mechanism. The diastereoselectivity was found to originate from a C−H/π interaction.