Stereodivergent Four-Component Reactions via Rh-Carbynoids
Jian Luo, Yinwu Li, Haiqing Wang, Geng-Xin Liu, Zhenghui Kang, Yu Qian, Zhuofeng Ke, Xiang Fu, Wenhao Hu
Abstract
Multicomponent reactions (MCRs) provide a robust platform for the modular assembly of structurally complex molecules, while higher-order MCRs (≥4 components) exponentially expand the accessible chemical space. Although Rh-carbynoids exhibit significant potential for developing higher-order MCRs due to their unique reactivity, their application in asymmetric four-component reactions (4CRs) has been hindered by competing nucleophilic reactivities and stereochemical control. Herein, we overcome these challenges by integrating N - and C -nucleophiles and report an asymmetric 4CR involving hypervalent iodine diazo reagents, carbamates, N,N -dialkylanilines, and imines. This strategy represents the first asymmetric 4CR utilizing Rh-carbynoids, achieving the sequential formation of C(sp 3 )–N, C(sp 3 )–C(sp 2 ), and C(sp 3 )–C(sp 3 ) bonds at a single carbon center. The method provides stereodivergent access to α,β-diamino-3-arylpropanoic acid derivatives bearing two contiguous stereocenters with good yields and exceptional enantioselectivity.