Dynamic Asymmetric Diamination of Allylic Alcohols through Borrowing Hydrogen Catalysis: Diastereo‐Divergent Synthesis of Tetrahydrobenzodiazepines

• Published in: Angewandte Chemie 2024-12, Vol.136 (49), p.n/a
• Main Authors: Liu, Yufeng, Ji, Peng, Zou, Gongfeng, Liu, Yongbing, Yang, Bin‐Miao, Zhao, Yu
• Format: Article
• Language: English
• Subjects: 1,3-nonadjacent stereocenters; Alcohols; allylic alcohols; Amination; Asymmetry; borrowing hydrogen; Catalysis; Catalytic converters; Chemical synthesis; dynamic kinetic resolution; Enantiomers; Hydrogen; Iridium; Phosphoric acid; Racemization; Stereoselectivity; tetrahydrobenzodiazepines
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202410351

We present herein a catalytic enantioconvergent diamination of racemic allylic alcohols with the construction of two C−N bonds and 1,3‐nonadjacent stereocenters. This iridium/chiral phosphoric acid cooperative catalytic system operates through an atom‐economical borrowing hydrogen amination/aza‐Michael cascade, and converts readily available phenylenediamines and racemic allylic alcohols to 1,5‐tetrahydrobenzodiazepines in high enantioselectivity. An intriguing solvent‐dependent switch of diastereoselectivity was also observed. Mechanistic studies suggested a dynamic kinetic resolution process involving racemization through a reversible Michael addition, making the last step of asymmetric imine reduction the enantiodetermining step of this cascade process. We present herein an unprecedented, catalytic enantioconvergent diamination of racemic allylic alcohols with the construction of two C−N bonds and 1,3‐nonadjacent stereocenters. This iridium/chiral phosphoric acid cooperative catalytic system operates through an atom‐economical borrowing hydrogen amination/aza‐Michael cascade, and converts readily available phenylenediamines and racemic allylic alcohols to 1,5‐tetrahydrobenzodiazepines in high enantioselectivity. An intriguing solvent‐dependent switch of diastereoselectivity was also observed.