Hu Hui, Wang Zhaobin
Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province Department of Chemistry School of Science, Westlake University, Hangzhou 310030, China.
Institute of Natural Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China.
J Am Chem Soc. 2023 Sep 27;145(38):20775-20781. doi: 10.1021/jacs.3c08493. Epub 2023 Sep 13.
Chiral β-amino alcohols are crucial structural motifs found in pharmaceuticals, natural products, and chiral ligands in asymmetric catalysis. Despite previous advances, the development of catalytic approaches to access β-amino alcohols bearing vicinal stereocenters from readily available chemicals remains a prominent challenge. Herein, we describe the Cr-catalyzed asymmetric cross aza-pinacol coupling of aldehydes and -sulfonyl imines. This protocol proceeds in a radical-polar crossover manner from the intermediacy of an α-amino radical instead of a ketyl radical. Key to the success is using a chiral chromium catalyst, which plays a triple role in the chemoselective single-electron reduction of the imine, fast radical interception to inhibit radical addition to imines, and chemo- and stereoselective addition to aldehydes instead of imines. This method provides a modular and efficient approach to accessing diverse β-amino alcohols bearing vicinal stereocenters.
手性β-氨基醇是药物、天然产物以及不对称催化中的手性配体中至关重要的结构基序。尽管此前已有进展，但从易得的化学品出发，开发催化方法以获得带有相邻立体中心的β-氨基醇仍然是一个突出的挑战。在此，我们描述了铬催化的醛与磺酰亚胺的不对称交叉氮杂频哪醇偶联反应。该反应以自由基-极性交叉的方式进行，经由α-氨基自由基而非酮基自由基中间体。成功的关键在于使用手性铬催化剂，它在亚胺的化学选择性单电子还原、快速自由基捕获以抑制自由基加成到亚胺以及对醛而非亚胺的化学和立体选择性加成中发挥三重作用。该方法为获得带有相邻立体中心的多种β-氨基醇提供了一种模块化且高效的途径。
