Rhodium‐Catalyzed Asymmetric Hydrogenation and Transfer Hydrogenation of 1,3‐Dipolar Nitrones

• Published in: Angewandte Chemie International Edition 2024-04, Vol.63 (14), p.e202319662-n/a
• Main Authors: Xu, Liren, Yang, Tilong, Sun, Hao, Zeng, Jingwen, Mu, Shuo, Zhang, Xumu, Chen, Gen‐Qiang
• Format: Article
• Language: English
• Subjects: 1,3-dipolar nitrones; 7-membered cyclic transition state; asymmetric (transfer) hydrogenation; Asymmetry; Catalysts; Diamines; Enantiomers; hydrogen-bonding interaction; Hydrogenation; Rhodium
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202319662

Owing to their distinctive 1,3‐dipolar structure, the catalytic asymmetric hydrogenation of nitrones to hydroxylamines has been a formidable and longstanding challenge, characterized by intricate enantiocontrol and susceptibility to N−O bond cleavage. In this study, the asymmetric hydrogenation and transfer hydrogenation of nitrones were accomplished with a tethered TsDPEN‐derived cyclopentadienyl rhodium(III) catalyst (TsDPEN: p‐toluenesulfonyl‐1,2‐diphenylethylene‐1,2‐diamine), the reaction proceeds via a novel 7‐membered cyclic transition state, producing chiral hydroxylamines with up to 99 % yield and >99 % ee. The practical viability of this methodology was underscored by gram‐scale catalytic reactions and subsequent transformations. Furthermore, mechanistic investigations and DFT calculations were also conducted to elucidate the origin of enantioselectivity. The enantioselective reduction of 1,3‐dipolar nitrones to hydroxylamines was achieved by Rh(III)‐catalyzed asymmetric hydrogenation and transfer hydrogenation. A wide range of chiral N,N‐disubstituted hydroxylamines were synthesized with up to 99 % yield and >99 % ee. Mechanistic investigations and DFT calculations were conducted to elucidate the origin of reactivity and enantioselectivity.