Zheng Wenrui, Tan Boon Beng, Ge Shaozhong, Lu Yixin
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore.
J Am Chem Soc. 2024 Feb 28;146(8):5366-5374. doi: 10.1021/jacs.3c12675. Epub 2024 Feb 14.
Two enantioselective approaches to synthesize chiral skipped diboronate compounds have been developed, relying on copper-catalyzed one-pot asymmetric ring-opening diboration of arylidenecyclopropanes. A wide range of arylidenecyclopropanes react smoothly with HBpin in the presence of CuOAc and ()-DTBM-Segphos, affording chiral 1,4-diboronates with high enantioselectivity (up to 99% ee). Meanwhile, a variety of arylidenecyclopropanes react selectively with HBpin and Bpin in the presence of CuOAc and (,)-Ph-BPE with the sequential addition of MeOH, providing chiral 1,3-diboronates with high enantioselectivity (up to 98% ee). These enantioenriched 1,3- and 1,4-diboronates can undergo various enantiospecific transformations with minimal loss of their enantiopurity. Mechanistic studies reveal that these two diboration processes start with CuH-catalyzed ring-opening hydroboration of arylidenecyclopropanes to form a mixture of /-homoallyl boronate intermediates, which subsequently undergo enantioselective CuH-catalyzed second hydroboration or Cu-Bpin-catalyzed protoboration to produce chiral 1,4-diboronates or 1,3-diboronates, respectively.
已经开发出两种对映选择性方法来合成手性跳跃二硼酸酯化合物，该方法依赖于铜催化的亚芳基环丙烷的一锅法不对称开环二硼化反应。在醋酸铜和（）-DTBM-联二萘酚存在下，多种亚芳基环丙烷能与频哪醇硼烷顺利反应，以高对映选择性（高达99% ee）得到手性1,4-二硼酸酯。同时，在醋酸铜和（，）-苯基双膦存在下，通过依次加入甲醇，多种亚芳基环丙烷能与频哪醇硼烷和硼酸频哪醇酯选择性反应，以高对映选择性（高达98% ee）提供手性1,3-二硼酸酯。这些对映体富集的1,3-和1,4-二硼酸酯可进行各种对映体特异性转化，且对映体纯度损失最小。机理研究表明，这两种二硼化过程均始于铜氢催化的亚芳基环丙烷的开环硼氢化反应，形成/-高烯丙基硼酸酯中间体混合物，随后该混合物分别经对映选择性铜氢催化的第二次硼氢化反应或铜-硼酸频哪醇酯催化的原硼化反应，生成手性1,4-二硼酸酯或1,3-二硼酸酯。
