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Cobalt-electrocatalytic HAT for functionalization of unsaturated C–C bonds

Abstract

The study and application of transition metal hydrides (TMHs) has been an active area of chemical research since the early 1960s1, for energy storage, through the reduction of protons to generate hydrogen2,3, and for organic synthesis, for the functionalization of unsaturated C–C, C–O and C–N bonds4,5. In the former instance, electrochemical means for driving such reactivity has been common place since the 1950s6 but the use of stoichiometric exogenous organic- and metal-based reductants to harness the power of TMHs in synthetic chemistry remains the norm. In particular, cobalt-based TMHs have found widespread use for the derivatization of olefins and alkynes in complex molecule construction, often by a net hydrogen atom transfer (HAT)7. Here we show how an electrocatalytic approach inspired by decades of energy storage research can be made use of in the context of modern organic synthesis. This strategy not only offers benefits in terms of sustainability and efficiency but also enables enhanced chemoselectivity and distinct, tunable reactivity. Ten different reaction manifolds across dozens of substrates are exemplified, along with detailed mechanistic insights into this scalable electrochemical entry into Co–H generation that takes place through a low-valent intermediate.

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Fig. 1: Energy-storage-inspired electrochemical HAT by cobalt catalysis.
Fig. 2: Scope of e-HAT isomerization.
Fig. 3: Scope of e-HAT reduction.
Fig. 4: Selectivity, scalability and HAT reactions of e-HAT.
Fig. 5: Mechanistic study.

Data availability

The data that support the findings of this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

This work was supported by the NSF Center for Synthetic Organic Electrochemistry (grant no. CHE-2002158). S.G. thanks the Council for Higher Education, Fulbright Israel and Yad Hanadiv for their generous fellowships. A.B. thanks the Austrian Science Fund (FWF) for an Erwin Schrödinger Fellowship (J 4452-N). H.-J.Z. thanks the Shanghai Institute of Organic Chemistry (SIOC) fellowship. C.A.M. thanks the National Institute of General Medical Sciences of the National Institutes of Health (grant no. K99GM140249). We are grateful to D.-H. Huang and L. Pasternack (Scripps Research) for assistance with the NMR spectroscopy, to J. Chen, B. Sanchez and E. Sturgell (Scripps Automated Synthesis Facility) for assistance with high-performance liquid chromatography, high-resolution mass spectroscopy and liquid chromatography–mass spectrometry. We thank S. Harwood, Y. Kawamata, K. X. Rodriguez and C. Bi for helpful advice and suggestions. We also thank Q. Liu and X. Liu (Tsinghua University) for helpful discussions.

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S.G., A.B. and P.S.B. developed the concept. S.G., A.B., H.-J.Z. and P.S.B. were responsible for the optimization and scope. L.C., M.Q., S.G. and P.-G.E. performed the flow setup and scale up. C.G., C.A.M., W.D.B., S.G., H.D.A. and S.D.M. carried out the CV studies and analysis. D.V., T.T. and M.S.S. carried out the DFT calculations and analysis. D.E.H., E.K. and S.E.R. carried out the UV–vis studies. R.A.D., W.H. and D.G.B. carried out the kinetic studies. R.Z. and H.D.A. performed the DEMS analysis. S.G., A.B., H.-J.Z., J.C.V., D.G.B., H.D.A., S.E.R., M.S.S. and P.S.B. prepared the manuscript.

Corresponding authors

Correspondence to Hector D. Abruna, Donna G. Blackmond, Shelley D. Minteer, Sarah E. Reisman, Matthew S. Sigman or Phil S. Baran.

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Gnaim, S., Bauer, A., Zhang, HJ. et al. Cobalt-electrocatalytic HAT for functionalization of unsaturated C–C bonds. Nature 605, 687–695 (2022). https://doi.org/10.1038/s41586-022-04595-3

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