Mi Ruijie, Ding Zhiying, Yu Songjie, Crabtree Robert H, Li Xingwei
Institute of Molecular Sciences and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao, Shandong 266237, China.
Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian, Liaoning 116024, China.
J Am Chem Soc. 2023 Apr 12;145(14):8150-8162. doi: 10.1021/jacs.3c01162. Epub 2023 Apr 4.
Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design of -protected -allylhydroxyamines as bifunctional olefins that undergo catalytic asymmetric 1,2-carboamidation with three classes of (hetero)arenes to afford chiral amino alcohols via C-H activation. The C═C bond in -allylhydroxyamine is activated by the intramolecular electrophilic amidating moiety as well as a migrating directing group. The asymmetric carboamidation reaction pattern depends on the nature of the (hetero)arene reagent. Simple achiral (hetero)arenes reacted to give centrally chiral β-amino alcohols in excellent enantioselectivity. The employment of axially prochiral or axially racemic heteroarenes afforded amino alcohols with both axial and central chirality in excellent enantio- and diastereoselectivity. In the case of axially racemic heteroarenes, the coupling follows a kinetic resolution pattern with an -factor of up to >600. A nitrene-based reaction mechanism has been suggested based on experimental studies, and a unique mode of induction of enantio- and diastereoselectivity has been proposed. Applications of the amino alcohol products have been demonstrated.
烯烃的双官能团化提供了一种构建复杂手性结构的有吸引力的方法。本文报道了一种α-保护的烯丙基羟胺的设计，该烯丙基羟胺作为双官能烯烃，可与三类（杂）芳烃发生催化不对称1,2-碳酰胺化反应，通过C-H活化生成手性氨基醇。烯丙基羟胺中的C═C键被分子内亲电酰胺化部分以及迁移导向基团活化。不对称碳酰胺化反应模式取决于（杂）芳烃试剂的性质。简单的非手性（杂）芳烃反应生成中心手性β-氨基醇，对映选择性优异。使用轴向前手性或轴向外消旋杂芳烃可得到具有轴向和中心手性的氨基醇，对映和非对映选择性均优异。对于轴向外消旋杂芳烃，偶联反应遵循动力学拆分模式，α-因子高达>600。基于实验研究提出了一种基于氮烯的反应机理，并提出了一种独特的对映和非对映选择性诱导模式。已证明了氨基醇产物的应用。
