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Copper-catalysed benzylic C-H coupling with alcohols via radical relay enabled by redox buffering.

ABSTRACT: Cross-coupling reactions enable rapid, convergent synthesis of diverse molecules and provide the foundation for modern chemical synthesis. The most widely used methods employ sp2-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(sp3)-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.

SUBMITTER: Hu H

PROVIDER: S-EPMC7197765 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Copper-catalysed benzylic C-H coupling with alcohols via radical relay enabled by redox buffering.

Hu Huayou H Chen Si-Jie SJ Mandal Mukunda M Pratik Saied Md SM Buss Joshua A JA Krska Shane W SW Cramer Christopher J CJ Stahl Shannon S SS

Nature catalysis 20200224 4

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<sup>2</sup>-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 thro ...[more]

PMID: 32368720

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