The direct arylation of allylic sp3 C–H bonds via organic and photoredox catalysis

Cuthbertson, James D.; MacMillan, David W. C.

Abstract

The direct functionalization of unactivated sp3 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 sp3 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 amination of allylic C–H bonds (that is, C–H bonds where an adjacent carbon is involved in a C = C bond) have become widely established2,3, the engagement of allylic substrates in C–C bond forming reactions has thus far required the use of pre-functionalized coupling partners4. 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.

Citation

Cuthbertson, J. D., & MacMillan, D. W. C. (2015). The direct arylation of allylic sp3 C–H bonds via organic and photoredox catalysis. Nature, 519(7541), 74-77. https://doi.org/10.1038/nature14255

• Journal Article Type: Article
• Acceptance Date: Jan 22, 2015
• Online Publication Date: Mar 5, 2015
• Publication Date: 2015-03
• Deposit Date: Dec 4, 2018
• Publicly Available Date: Feb 20, 2019
• Journal: Nature
• Print ISSN: 0028-0836
• Electronic ISSN: 1476-4687
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 519
• Issue: 7541
• Pages: 74-77
• DOI: https://doi.org/10.1038/nature14255
• Public URL: https://nottingham-repository.worktribe.com/output/1358710
• Publisher URL: https://www.nature.com/articles/nature14255
• Related Public URLs: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378681/
• Contract Date: Feb 20, 2019