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

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.

Automated summary

Significant progress has been made in the efficient synthesis of enantioenriched 1,2,3,4-tetrahydroquinoxalines in recent years. However, the access to trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines with enantio- and diastereoselectivity remains largely unexplored. In this study, a frustrated Lewis pair-based catalyst was used to achieve the one-pot tandem cyclization/hydrosilylation of 1,2-diaminobenzenes and 1,2-diketones, resulting in high yields of trans-2,3-disubstituted 1,2,3,4-tetrahydroquinoxalines with excellent diastereoselectivities. The reaction can be rendered asymmetric by using an enantioenriched borane-based catalyst, leading to enantioenriched products with high yields and complete diastereo- and enantiocontrol. The mechanistic pathway and the origin of the excellent stereoselectivity were elucidated through experiments and calculations.