Zhao Wei, Lin En-Ze, Chen Ke-Zhi, Sun Yu-Wen, Li Bi-Jie
Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
Nat Chem. 2025 Sep 17. doi: 10.1038/s41557-025-01936-3.
Catalytic alkene hydrofunctionalization is arguably one of the most fundamentally important methodologies to construct diverse C-X bonds with concomitant creation of stereogenic centres. While most catalytic hydrofunctionalization methodologies create a single stereocentre or vicinal stereocentres through 1,2-addition, channelling hydrofunctionalization to 1,3-addition mode to create non-adjacent stereocentres with simultaneous controls of both relative and absolute configurations represents a notable challenge. Here we report a catalytic 1,3-hydrofunctionalization of unactivated trisubstituted alkenes to generate enantiopure products containing α and γ stereocentres. An amide group on the alkene first directs the catalyst to cleave the methylene C-H bond enantioselectively, delivering an allylic stereocentre through C-H transposition. The amide remains bound to the metal centre, subsequently directing the catalyst to hydrofunctionalize the resulting alkene with high regiochemical and stereochemical controls. The separate stereocontrols in this 'directing relay' enables stereodivergent access to 1,3-hydroalkynylation products, in which all four possible stereoisomers are obtained with excellent diastereoselectivities and enantioselectivities.
催化烯烃氢官能团化可以说是构建各种碳-杂原子键并同时生成手性中心的最重要的基本方法之一。虽然大多数催化氢官能团化方法通过1,2-加成生成单个手性中心或邻位手性中心，但将氢官能团化导向1,3-加成模式以生成非相邻手性中心并同时控制相对和绝对构型是一项重大挑战。在此，我们报道了未活化的三取代烯烃的催化1,3-氢官能团化反应，以生成含有α和γ手性中心的对映纯产物。烯烃上的酰胺基团首先引导催化剂对亚甲基碳氢键进行对映选择性裂解，通过碳氢键重排产生一个烯丙基手性中心。酰胺仍与金属中心结合，随后引导催化剂对生成的烯烃进行氢官能团化反应，并具有高区域化学和立体化学控制。这种“导向接力”中的独立立体控制使得能够立体发散地获得1,3-氢炔基化产物，其中所有四种可能的立体异构体均以优异的非对映选择性和对映选择性得到。
