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Highly tunable multi-borylation of gem-difluoroalkenes via copper catalysis

Abstract

Multi-borylated compounds are useful starting materials for the construction of complex molecules. Although certain classes of multi-borylated compounds, such as geminal and 1,2-bis(boronates), can now be accessed selectively by several well-established methods, the synthesis of one class—those containing more than two boronate substituents—remains a great challenge. Here, copper catalytic systems were developed for the borylation of gem-difluoroalkenes with B2pin2 via dual C–F bond activation to afford multi-borylate libraries—1,2-alkyldiboronates, 1,1,2-alkyltriboronates and 1,1,1,2-alkyltetraboronates—by slightly tuning the reaction conditions. The advantages of this strategy include not only avoiding the use of different methods and substrates for each type of multi-substituted alkyl boronate, but also the excellent functional group compatibility, readily accessible gem-difluorovinyl group and highly chemoselective process.

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Fig. 1: Development of a highly tunable defluoroborylation protocol to selectively construct 1,2-alkyldiboronates, 1,1,2-alkyltriboronates and 1,1,1,2-alkyltetraboronates.
Fig. 2: Utility of the formed multi-borylation compounds.
Fig. 3: Investigation of gem-dibromoalkene, 15 and deuterium-labelling experiments.
Fig. 4: Detailed mechanistic studies on the intermediates of 5a and 6a.
Fig. 5: Proposed catalytic cycles of the present tunable multi-borylation.

Data availability

Crystallographic data for the structures 5f and 6f reported in this paper have been deposited at the Cambridge Crystallographic Data Centre under deposition numbers 1855882 and 1855883. Copies of the data can be obtained free of charge via www.ccdc.cam.ac.uk/getstructures. All other data supporting the findings of this study, including experimental procedures and compound characterization, are available within the paper and its Supplementary Information, or from the corresponding author upon reasonable request.

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Acknowledgements

We thank A. Lei at Wuhan University for assistance with the operando infrared experiments. This work was supported by the Funding Programs for the ‘1000 Youth Talents Plan’, National Natural Science Foundation of China (grant 2167020084), ‘Jiangsu Specially-Appointed Professor Plan’ and ‘Innovation and Entrepreneurship Talents Plan’ of Jiangsu Province.

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Z.S. conceived the study, supervised the project and wrote the paper. J.H performed the experiments and mechanism study, and analysed the data. Y.Z. performed the crystallographic studies.

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Correspondence to Zhuangzhi Shi.

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Supplementary Information

Supplementary Information

Supplementary Methods, Supplementary References, Supplementary Figures 1–108

Compound 5f

Crystallographic data for compound 5f

Compound 6f

Crystallographic data for compound 6f

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Hu, J., Zhao, Y. & Shi, Z. Highly tunable multi-borylation of gem-difluoroalkenes via copper catalysis. Nat Catal 1, 860–869 (2018). https://doi.org/10.1038/s41929-018-0147-9

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