Chiral Phosphoric Acid Catalyzed Enantioselective Desymmetrization of 1,4‐Dihydropyridines by C(sp3)−H Bromination

• Published in: Angewandte Chemie International Edition 2022-05, Vol.61 (22), p.e202201418-n/a
• Main Authors: Han, Min, Zhang, Shi‐qi, Cui, Xin, Wang, Qi‐wei, Li, Guang‐xun, Tang, Zhuo
• Format: Article
• Language: English
• Subjects: 1,4-Dihydropyridines; Axial Chirality; Bromination; Catalysis; Chirality; Desymmetrization; Dihydropyridines - chemistry; Enantiomers; Halogenation; Hydrogen bonds; Organocatalysis; Phosphoric acid; Phosphoric Acids; Pyridines; Stereoisomerism; Substrates
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202201418

Described herein is the enantioselective synthesis of Hantzsch‐type 1,4‐dihydropyridines (DHPs), which are frequently contained in pharmaceuticals. Readily available symmetrical 1,4‐DHPs were used as substrates, and the methyl group at the 2‐ or 6‐position of the 1,4‐DHP was selectively monobrominated by desymmetrizing enantioselective bromination. The inert C−H bond was converted into a versatile C−Br bond, which guaranteed the modification of the chiral 1,4‐DHP derivatives with high efficiency. Furthermore, axially chiral 4‐aryl pyridines were accessible by central‐to‐axial chirality conversion. Readily available symmetrical 1,4‐dihydropyridines (1,4‐DHPs) were used as substrates to obtain chiral Hantzsch‐type 1,4‐DHPs, which are frequently contained in pharmaceuticals. The inert C−H bond was converted into a versatile C−Br bond, which enabled the modification of the chiral 1,4‐DHP derivatives with high efficiency by nucleophilic substitution. Furthermore, axially chiral 4‐aryl pyridines were accessible by central‐to‐axial chirality conversion.