Ligand-Promoted,Enantioconvergent Synthesis of Aliphatic Alkanes Bearing Trifluoromethylated Stereocenters via Hydrotrifluoroalkylation of Unactivated Alkenes  

作　　者：Yan He Kang-Jie Bian Bing-Bing Wu Peng Liu Shan-Xiu Ni Xi-Sheng Wang 

机构地区：[1]Department of Chemistry,University of Science and Technology of China,Hefei,Anhui 230026,China

出　　处：《Chinese Journal of Chemistry》2022年第13期1531-1536,I0002,共7页中国化学（英文版）

基　　金：Financial support for this work was provided by the National Key R&D Program of China(2021YFF0701700);the National Natural Science Foundation of China(21971228).

摘　　要：While drug chirality remains one of the most important themes in medicinal chemistry and fluorine-containing drugs have comprised large portion of global pharmaceutical market,the synthesis of fluorine-containing compounds featuring a trifluoromethylated stereogenic carbon center is still underdeveloped.Recent strategy of enantioconvergent cross-coupling of trifluoromethylated alkyl halide has significantly updated previous toolbox that is dependent on additional functional group to achieve desired bond formation and highly enantioselective control.However,evident limitations were present in specific coupling candidate(sp?carbon)and/or prerequisite heteroatom in trifluoroalkyl source for inducing effective stereoconvergent differentiation.Leveraging novel design of sterically hindered bisoxazoline ligand and drastic increase of molecular complexity of in situ generated sp3 coupling partner via metal-hydride atom transfer,herein,we report a nickel-catalyzed,highly enantioselective hydrotrifluoroalkylation of unactivated alkenes for diverse synthesis of enantioenriched aliphatic alkanes featuring trifluoromehylated stereogenic carbon.Excellent stereochemical control(mostly>95:5 er),high catalytic reactivity,mild conditions,and broad substrate scope(40+examples),enable convenient late-stage asymmetric trifluoroalkylation of various biologically active complexmolecules.

关 键 词：Trifluoromethylated stereocenters Hydrotrifluoroalkylation C-Ccoupling Unactivated alkenes CHEMOSELECTIVITY 

分 类 号：O62[理学—有机化学]