Wang Peng-Fei, Yu Jiao, Guo Kai-Xin, Jiang Sheng-Peng, Chen Ji-Jun, Gu Qiang-Shuai, Liu Ji-Ren, Hong Xin, Li Zhong-Liang, Liu Xin-Yuan
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Southern University of Science and Technology, Shenzhen 518055, China.
Shenzhen Grubbs Institute and Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.
J Am Chem Soc. 2022 Apr 13;144(14):6442-6452. doi: 10.1021/jacs.2c00957. Epub 2022 Apr 1.
The enantioconvergent radical C(sp)-C(sp) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.
由于烯基硼酸酯易于获得、低毒且对空气/湿气稳定，卤代烃与烯基硼酸酯的对映汇聚型自由基C(sp)-C(sp)交叉偶联是合成有价值的对映体富集烯烃的一种有吸引力的工具。在此，我们报道了一种铜/手性N,N,N-配体催化体系，用于苄基/炔丙基卤化物与烯基硼酸酯的对映汇聚型交叉偶联（>80个例子），具有良好的官能团耐受性。成功的关键是通过在一个配位喹啉环的邻位引入空间位阻来合理设计半不稳定的N,N,N-配体。因此，新设计的配体不仅可以以三齿形式促进自由基交叉偶联过程，还可以以双齿形式对高活性烷基自由基进行对映体控制。简便的后续转化突出了其在合成各种对映体富集的结构单元以及药物发现的后期官能团化中的潜在用途。
