Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
J Am Chem Soc. 2023 May 3;145(17):9441-9447. doi: 10.1021/jacs.3c01949. Epub 2023 Apr 22.
Cyclopropanes are common building blocks in pharmaceuticals, agrochemicals, and organic materials. The most general methods for the synthesis of chiral cyclopropanes are catalytic additions of diazoalkanes to alkenes. However, a limitation of this approach is that diazoalkanes can only be safely handled on preparative scales if they possess stabilizing substituents. Here we show that -dichloroalkanes can serve as precursors to nonstabilized carbenes for asymmetric cyclopropanation reactions of alkenes. The process uses a cobalt catalyst and is proposed to involve the formation of a cationic carbenoid species bearing structural resemblance to the Simmons-Smith reagent. High levels of enantioselectivity are observed for monosubstituted, 1,1-disubstituted, and internal alkenes. The reaction is compatible with alkyl-substituted carbenes, which are susceptible to undergoing competing 1,2-hydride shifts.
环丙烷是药物、农用化学品和有机材料中常见的结构单元。合成手性环丙烷最常用的方法是重氮烷烃对烯烃的催化加成。然而，这种方法的一个限制是，如果重氮烷烃没有稳定的取代基，只能在制备规模上安全处理。在这里，我们证明了 -二氯代烷烃可以作为非稳定碳烯的前体，用于烯烃的不对称环丙烷化反应。该过程使用钴催化剂，并提出涉及形成带有类似于 Simmons-Smith 试剂的结构相似的阳离子碳烯物种。观察到单取代、1,1-二取代和内部烯烃的高对映选择性。该反应与烷基取代的碳烯兼容，这些碳烯容易发生竞争的 1,2-氢迁移。
