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Metal-free photoinduced C(sp3)–H borylation of alkanes

Nature volume 586, pages 714–719 (2020)Cite this article

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Abstract

Boronic acids and their derivatives are some of the most useful reagents in the chemical sciences1, with applications spanning pharmaceuticals, agrochemicals and functional materials. Catalytic C–H borylation is a powerful method for introducing these and other boron groups into organic molecules because it can be used to directly functionalize C–H bonds of feedstock chemicals without the need for substrate pre-activation1,2,3. These reactions have traditionally relied on precious-metal catalysts for C–H bond cleavage and, as a result, display high selectivity for borylation of aromatic C(sp2)–H bonds over aliphatic C(sp3)–H bonds4. Here we report a mechanistically distinct, metal-free borylation using hydrogen atom transfer catalysis5, in which homolytic cleavage of C(sp3)–H bonds produces alkyl radicals that are borylated by direct reaction with a diboron reagent. The reaction proceeds by violet-light photoinduced electron transfer between an N-alkoxyphthalimide-based oxidant and a chloride hydrogen atom transfer catalyst. Unusually, stronger methyl C–H bonds are borylated preferentially over weaker secondary, tertiary and even benzylic C–H bonds. Mechanistic studies indicate that the high methyl selectivity is a result of the formation of a chlorine radical–boron ‘ate’ complex that selectively cleaves sterically unhindered C–H bonds. By using a photoinduced hydrogen atom transfer strategy, this metal-free C(sp3)–H borylation enables unreactive alkanes to be transformed into valuable organoboron reagents under mild conditions and with selectivities that contrast with those of established metal-catalysed protocols.

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Fig. 1: Catalytic C–H borylation reactions.
Fig. 2: Photoinduced C–H borylations of alkanes.
Fig. 3: Photoinduced C–H borylations of silanes.
Fig. 4: Mechanistic studies.

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Data availability

Materials and methods, experimental procedures, characterization data, spectra and additional mechanistic discussions are available in the Supplementary Information.

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Acknowledgements

We thank the EPSRC (EP/R004978/1) for funding. We gratefully acknowledge A. Sedikides and A. Lennox (University of Bristol) for performing cyclic voltammetry experiments.

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  1. School of Chemistry, University of Bristol, Bristol, UK

    Chao Shu, Adam Noble & Varinder K. Aggarwal

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  1. Chao Shu
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Contributions

A.N. and V.K.A. conceived the project, directed the research and prepared the manuscript; C.S. performed the experimental work; all authors analysed the results.

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Correspondence to Adam Noble or Varinder K. Aggarwal.

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Supplementary Information

This file contains Supplementary Methods, Supplementary Figures 1-39, Supplementary Tables 1-21, Spectral Data and Supplementary References.

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Shu, C., Noble, A. & Aggarwal, V.K. Metal-free photoinduced C(sp3)–H borylation of alkanes. Nature 586, 714–719 (2020). https://doi.org/10.1038/s41586-020-2831-6

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