C−H Bond Activation for the Synthesis of Heterocyclic Atropisomers Yields Hedgehog Pathway Inhibitors
作者:Gang Shan、Jana Flegel、Houhua Li、Christian Merten、Slava Ziegler、Andrey P. Antonchick、Herbert Waldmann
DOI:10.1002/anie.201809680
日期:2018.10.22
pronounced bioactivity, and methods for their efficient synthesis have gained widespread attention. However, enantioselective synthesis of axially chiral 4‐arylisoquinolones by means of C−H activation has not been reported to date. Described here is a rhodium (III)‐catalyzed C−H bond activation and annulation for the atroposelective synthesis of axially chiral 4‐arylisoquinolones. The method employs
轴向手性4-芳基异喹诺酮具有明显的生物活性,其有效合成方法受到了广泛关注。然而,迄今尚未报道过通过CH活化的轴向手性4-芳基异喹诺酮的对映选择性合成。此处描述了铑(III)催化的CH键的活化和环化反应,用于轴向手性4-芳基异喹诺酮的对映选择性合成。该方法使用体现为哌啶环的手性环戊二烯基配体作为骨架,并以良好或优异的产率和对映选择性产生阻转异构体。4-芳基异喹诺酮类化合物在不同细胞试验中的研究证明了其生物学相关性,从而导致发现了新型的非SMO(SMO =平滑化)刺猬信号通路抑制剂。