The direct arylation of allylic sp~3 C-H bonds via organic and photoredox catalysis

摘要

James Cuthbertson和David MacMillan介绍了用于烯丙基sp~3碳-氢键的直接芳基化反应的一个新的通用方法，这为不需要通过引入外来官能团、而只是通过简单的、但却惰性的构造单元的偶联来合成复杂有机分子提供了一个潜在方法。通过与光氧化还原和基于硫醇的有机催化相结合，这个反应只需要温和的条件，并且能够适用于一系列不同的烯烃和缺电子芳烃偶联配体。%The direct functionalization of unactivated sp~3 C-H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts1, the establishment of general and mild strategies for the engagement of sp~3 C-H bonds in C-C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and animation of allylic C-H bonds (that is, C-H bonds where an adjacent carbon is involved in a C=C bond) have become widely established, the engagement of allylic substrates in C-C bond forming reactions has thus far required the use of pre-functionalized coupling partners. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug's action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C-H arylation. This C-C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C-H bonds.