康 · 学术 ｜ Reaction of the Day No. 1035

　　转自：

　　Iridium-Catalyzed Enantioconvergent Borrowing Hydrogen Annulation of Racemic 1,4-Diols with Amines

　　Yongbing Liu,Huanlin Diao,Guorong Hong, Jonathan Edward, Tao Zhang, Guoqiang Yang, Bin-Miao Yang,* and Yu Zhao*

　　Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Fuzhou 350207, China;

　　Department of Chemistry, National University of Singapore, Singapore 117544, Republic of Singapore

　　—J. Am. Chem. Soc. 2023, 145, 9, 5007–5016.

　　Recommended by Shi Li _ MOC

　　

　　KEYWORDS: Iridium catalysis, annulation, amine, diol, pyrrolidine, enantioselective

　　ABSTRACT: B-M. Yang and Y. Zhao et al present an enantioconvergent access to chiral N-heterocycles directly from simple racemic diols and primary amines, through a highly economical borrowing hydrogen annulation. The identification of a chiral amine-derived iridacycle catalyst was the key for achieving high efficiency and enantioselectivity in the one-step construction of two C?N bonds. This catalytic method enabled a rapid access to a wide range of diversely substituted enantioenriched pyrrolidines including key precursors to valuable drugs such as aticaprant and MSC 2530818.

　　Background and this work

　　Scope of Diols for Monosubstituted Pyrrolidines

　　Scope of Aryl Amines for Monosubstituted Pyrrolidines

　　Scope of Disubstituted Pyrrolidines

　　Summary and Comments:

　　B-M. Yang and Y. Zhao et aldeveloped an Iridium-catalyzed enantioconvergent?aminative annulation of racemic diols through borrowing hydrogen catalysis, resulting in a practical access to enantioenriched N-(hetero)aryl pyrrolidines. Key to the success of this transformation is the development of chiral amine-derived iridacycle complexes, which promote the redox-neutral amination with high enantiocontrol in cooperation with a chiral phosphoric acid. Mechanistic understanding of this complex catalytic system involving double redox cycles also provides key information about the kinetics and enantiocontrol of the cooperative catalytic system.

　　B-M.Yang和Y.Zhao等人开发了一种手性Ir和磷酸催化的外消旋二元醇与胺的对映选择性环化反应，制备了丰富的手性N-(杂)芳基吡咯烷类衍生物。该转化成功的关键是开发手性胺衍生的铱环配合物，其与手性磷酸协同促进了具有高对映体控制的氧化还原中性胺化过程。这种涉及双氧化还原循环的复杂催化体系也提供了关于协同催化体系的动力学和对映控制的关键信息。