Synergistically activating nucleophile strategy enabled organocatalytic asymmetric P-addition of cyclic imines

• Published in: Chemical science (Cambridge) 2024-07, Vol.15 (3), p.1217-1225
• Main Authors: Zhang, Hongkui, Tan, Jian-Ping, Ren, Xiaoyu, Wang, Fan, Zheng, Jia-Yan, He, Jiajia, Feng, Yu, Xu, Zhipeng, Su, Zhishan, Wang, Tianli
• Format: Article
• Language: English
• Subjects: Asymmetry; Catalysis; Chemical synthesis; Chemistry; Enantiomers; Imines; Nucleophiles; Phosphine oxide; Scale (corrosion); Side effects
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d4sc02212b

Herein, we present an attractive organocatalytic asymmetric addition of P-nucleophiles to five-membered cyclic N -sulfonyl imines facilitated by phosphonium salt catalysis, enabling the highly enantioselective synthesis of tri- and tetra-substituted cyclic phosphorus-containing benzosultams. With this protocol, various cyclic α-aminophosphonates were efficiently synthesized with high yields and exceptional enantioselectivities (up to >99% ee) under mild reaction conditions. The utility and practicality of this method were demonstrated through gram-scale reactions and straightforward elaborations. Notably, the success of this approach relies on the deliberate selection of a synergistic organocatalytic system, which helps circumvent foreseeable side effects while handling secondary phosphine oxides (SPOs). Systematic mechanistic studies, incorporating experiments and DFT calculations, have revealed the critical importance of judiciously selecting bifunctional phosphonium salt catalysts for effectively activating P-nucleophiles while stereoselectively controlling the P-attack process. An attractive organocatalytic asymmetric addition of P-nucleophiles with cyclic N -sulfonyl imines by phosphonium salt catalysis has been disclosed, offering a facile way to phosphorus-containing benzosultams in high yields and stereoselectivities.