Photocatalytic regio- and stereoselective C(sp3)–H functionalization of benzylic and allylic hydrocarbons as well as unactivated alkanes

Abstract

The selective functionalization of inert C(sp3)–H bonds is extremely attractive in organic synthesis and catalysis science, but the conversion of hydrocarbons lacking directing groups into chiral molecules through catalytic C(sp3)–H functionalization is formidably challenging. Here, to address this problem, we have developed a photochemical system consisting of a hydrogen atom transfer organophotocatalyst and a chiral catalyst containing an earth-abundant metal. With the cooperative catalysts and imine partners, a wide range of benzylic, allylic hydrocarbons and unactivated alkanes can be converted to functionalized chiral products. The readily tunable bisoxazoline catalysts of copper or other metals exhibit precise regional recognition and asymmetric induction towards these inert C–H bonds. The reactions are applicable to many compounds including small hydrocarbons, branched alkanes, cycloalkanes and more complex medicinal agents. This method provides an economic and rapid construction of optically active compounds, starting from the most basic chemical feedstocks.

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Fig. 1: Direct and selective C(sp3)–H functionalization of pure hydrocarbons.
Fig. 2: Initial design and mechanistic hypothesis.
Fig. 3: Reaction scope.
Fig. 4: Reaction scope.
Fig. 5: Mechanistic study.
Fig. 6: Synthetic utility of the method.

Data availability

The data supporting the findings of this study are available from the corresponding author upon request.

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Acknowledgements

We gratefully acknowledge funding from the National Natural Science Foundation of China (grant no. 21572184), the Natural Science Foundation of Fujian Province of China (grant no. 2017J06006) and the Fundamental Research Funds for the Central Universities (grant no. 20720190048).

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L.G. and Y.L. conceived and designed the project. Y.L. and M.L. conducted the experiments. Y.L., M.L. and L.G. analysed and interpreted the experimental data. L.G. prepared the manuscript. Y.L. prepared the Supplementary Information.

Corresponding author

Correspondence to Lei Gong.

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Supplementary methods, Supplementary Figs. 1–77, Supplementary Tables 1–3 and Supplementary References.

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Li, Y., Lei, M. & Gong, L. Photocatalytic regio- and stereoselective C(sp3)–H functionalization of benzylic and allylic hydrocarbons as well as unactivated alkanes. Nat Catal 2, 1016–1026 (2019). https://doi.org/10.1038/s41929-019-0357-9

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