Yong Xuefeng, Gao Weiwei, Lin Xiulian, Ho Chun-Yu
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, (150001), Heilongjiang, China.
Shenzhen Grubbs Institute, Guangdong Provincial Key Laboratory of Catalysis, Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen, (518055), Guangdong, China.
Commun Chem. 2020 Apr 30;3(1):50. doi: 10.1038/s42004-020-0299-9.
Diastereodivergent heterocycle synthesis has been recognized as an important tool for drug discovery in recent years, yet strategies based on nickelacycle formation have not been established. Here, we report a NHC-Ni catalyzed highly 1,3- and 1,4-diastereodivergent heterocycle synthesis from enyne, which is achieved by manipulating the enyne N-substituent (allowing switching of selectivity from up to 2:98 to 98:2). The key to success is the efficient diastereodivergent formation of a nickelacyclopentene, with broad enyne scope at mild conditions, which subsequently provides reductive hydroalkenylation, acylation and silylation products on demand. Diastereoisomers which are sterically hard to distinguish or difficult to access by conventional routes are now accessible easily, including those with very similar 4°, contiguous and skipped stereocenters.
近年来，非对映发散性杂环合成已被公认为药物发现的重要工具，但基于镍环形成的策略尚未确立。在此，我们报道了一种由NHC-Ni催化的、从烯炔出发的高度1,3-和1,4-非对映发散性杂环合成方法，该方法通过操纵烯炔的N-取代基实现（选择性可从高达2:98切换至98:2）。成功的关键在于镍环戊烯的高效非对映发散性形成，在温和条件下烯炔适用范围广泛，随后可按需提供还原氢烯基化、酰化和硅基化产物。现在，通过常规途径在空间上难以区分或难以获得的非对映异构体变得易于获得，包括那些具有非常相似的季碳、相邻和间隔立体中心的异构体。
