CPA-Catalyzed Enantioselective Assembly of Chiral 1,4-Dihydropyridines with Nonadjacent 1,3-Stereocenters

Hao-Wei Peng, Jia-Cheng Wei, Yu-Xun Chen, Shun-Jun Ji(纪顺俊)*, Zhong-Jian Cai(蔡忠建)*

Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China

Org. Lett., 2026, 28,8684-8689

Abstract: Herein, we report a chiral phosphoric acid (CPA)-catalyzed asymmetric Pictet–Spengler type annulation, which enables a rapid desymmetrization of prochiral dialdehydes. The 4,5-dihydropyrrolo[1,2-a]quinoxaline (DHPQ) skeleton and a nonadjacent 1,3-stereocenter are simultaneously established for a new family of potential pharmaceutically active 1,4-dihydropyridine (1,4-DHP) compounds. The developed protocol affords high diastereoselectivity (up to 20:1 dr) and good enantioselectivity (up to 99% ee). In addition, the annulation is amenable to gram-scale operation, and the resulting adducts can be readily elaborated into diverse functional groups without erosion of enantioselectivity.

Article information: https://doi.org/10.1021/acs.orglett.6c02340