Chen Zi-Hao, Sun Rui-Ze, Yao Fei, Hu Xu-Dong, Xiang Long-Xue, Cong Hengjiang, Liu Wen-Bo
Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
J Am Chem Soc. 2022 Mar 23;144(11):4776-4782. doi: 10.1021/jacs.2c01237. Epub 2022 Mar 9.
An enantioselective nickel-catalyzed intramolecular reductive cross-coupling of C(sp) electrophiles and cyano groups is reported. Enantioenriched CN-containing all-carbon quaternary stereocenters are assembled by desymmetrizing cyclization of aryl/alkenyl halide-tethered malononitriles. The use of an organic reductant, (EtO)MeSiH, is crucial to the enantioselectivity and reactivity. Applications of the method are demonstrated through the synthesis of bioactive molecules and their cyanated analogues and the total synthesis of the natural product diomuscinone. This study exhibits the potential of desymmetrizing reductive coupling strategies to access structurally rigid and synthetically versatile molecules from readily available starting materials.
报道了一种对映选择性镍催化的C(sp)亲电试剂与氰基的分子内还原交叉偶联反应。通过芳基/烯基卤代连接的丙二腈的去对称环化反应，构建了对映体富集的含氰基全碳季碳立体中心。有机还原剂(EtO)MeSiH的使用对映选择性和反应性至关重要。通过生物活性分子及其氰化类似物的合成以及天然产物二肌松酮的全合成，证明了该方法的应用。这项研究展示了去对称还原偶联策略从易得的起始原料获得结构刚性和合成用途广泛的分子的潜力。
