Maji Kakoli, Palai Angshuman, Mallick Dibyendu, Maji Biplab
Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur, 741246, West Bengal, India.
Department of Chemistry, Presidency University, 86/1 College Street, Kolkata, 700073, West Bengal, India.
Angew Chem Int Ed Engl. 2025 Mar 24;64(13):e202424394. doi: 10.1002/anie.202424394. Epub 2025 Jan 21.
Chiral allylamines are important structural components in natural products, pharmaceuticals, and chiral catalysts. Herein, we report a cobalt-catalyzed enantioselective reductive coupling of imines with internal alkynes to synthesize chiral allylamines. The reaction is catalyzed by a cobalt complex derived from commercially available bisphosphine ligand utilizing zinc as the electron donor. The substrate scope is extensive. Symmetric and unsymmetric alkyl and aryl alkynes have been successfully coupled with various imines derived from aryl and alkyl aldehydes. Tri- and tetra-substituted allyl amines were isolated in high yields, with enantiomeric excess surpassing >99.9 % and regioselectivities exceeding >20 : 1. These chiral allyl amines can serve as versatile platforms for subsequent transformations while preserving their stereochemical integrity. Extensive experimental and computational mechanistic studies were performed to elucidate the mechanism. These investigations have indicated that an in situ cobalt(I) catalyst enables the oxidative cyclization of alkynes and imines, and a spin crossover occurs during the enantio-determining step. Zinc plays a pivotal role in facilitating the transmetallation of the resulting azacobaltacycle. The observed enantioselectivity was interpreted by the stabilization of the transition state through higher stabilizing interaction energy from high negative polarization, dispersion, and C-H⋅⋅⋅π interactions.
手性烯丙胺是天然产物、药物和手性催化剂中的重要结构组成部分。在此，我们报道了一种钴催化的亚胺与内炔的对映选择性还原偶联反应，用于合成手性烯丙胺。该反应由一种钴配合物催化，该配合物由市售双膦配体衍生而来，以锌作为电子供体。底物范围广泛。对称和不对称的烷基和芳基炔烃已成功地与各种由芳基和烷基醛衍生的亚胺偶联。三取代和四取代烯丙胺以高产率分离得到，对映体过量超过99.9%，区域选择性超过20:1。这些手性烯丙胺可作为后续转化的通用平台，同时保持其立体化学完整性。进行了广泛的实验和计算机理研究以阐明反应机理。这些研究表明，原位钴(I)催化剂能使炔烃和亚胺发生氧化环化，并且在对映体决定步骤中发生自旋交叉。锌在促进所得氮杂钴环的金属转移中起关键作用。通过来自高负极化、色散和C-H⋅⋅⋅π相互作用的更高稳定相互作用能对过渡态的稳定作用来解释所观察到的对映选择性。
