Open AccessCopper-catalysed benzylic C–H coupling with alcohols via radical relay enabled by redox buffering
Author(s) -
Huayou Hu,
Si Jie Chen,
Mukunda Mandal,
Saied Md Pratik,
Joshua A. Buss,
Shane W. Krska,
Christopher J. Cramer,
Shan S. Stahl
Publication year - 2020
Publication title -
nature catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 14.33
H-Index - 65
ISSN - 2520-1158
DOI - 10.1038/s41929-020-0425-1
Subject(s) - chemistry , catalysis , combinatorial chemistry , reagent , coupling reaction , organic synthesis , molecule , aryl , redox , oxidative coupling of methane , copper , photochemistry , organic chemistry , alkyl
Cross-coupling reactions enable rapid, convergent synthesis of diverse molecules and provide the foundation for modern chemical synthesis. The most widely used methods employ sp 2 -hybridized coupling partners, such as aryl halides or related pre-functionalized substrates. Here, we demonstrate copper-catalysed oxidative cross coupling of benzylic C-H bonds with alcohols to afford benzyl ethers, enabled by a redox-buffering strategy that maintains the activity of the copper catalyst throughout the reaction. The reactions employ the C-H substrate as the limiting reagent and exhibit broad scope with respect to both coupling partners. This approach to direct site-selective functionalization of C(sp 3 )-H bonds provides the basis for efficient three-dimensional diversification of organic molecules and should find widespread utility in organic synthesis, particularly for medicinal chemistry applications.