A site-selective amination catalyst discriminates between nearly identical C–H bonds of unsymmetrical disubstituted alkenes

Abstract

C–H activation reactions enable chemists to unveil new retrosynthetic disconnections and streamline conventional synthetic approaches. A long-standing challenge in C–H activation is the inability to distinguish electronically and sterically similar C–H bonds. Although numerous synergistic combinations of transition-metal complexes and chelating directing groups have been utilized to distinguish C–H bonds, undirected regioselective C–H functionalization strategies remain elusive. Here we report a regioselective C–H activation/amination reaction of various unsymmetrical dialkyl-substituted alkenes. The regioselectivity of C–H activation is correlated to the electronic properties of allylic C–H bonds indicated by the corresponding 1JCH coupling constants. A linear relationship between the difference in the 1JCH coupling constants of the two competing allylic C–H bonds (Δ1JCH) and the C–H activation barriers (ΔΔG) has also been determined.

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Fig. 1: Site-selective allylic C–H amination.
Fig. 2: Study of regioselectivities in C–H amination of unsymmetrical trans-1,2-disubstituted alkenes.
Fig. 3: Study of the origin of regioselectivities.

Data availability

All data generated or analysed during this study are included in this published article and its Supplementary Information.

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Acknowledgements

We thank NIGMS (GM80442) for support. We thank J. Decatur for assistance with determining 1JCH coupling constants.

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H.L. and T.R. conceived and initiated the study. H.L. designed and conducted the experiments. H.L. and T.R. co-wrote the manuscript.

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Correspondence to Tomislav Rovis.

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Supplementary information

Supplementary Information

Experimental procedures, characterization data and mechanistic studies, Supplementary Fig. 1 and Tables 1 and 2.

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Lei, H., Rovis, T. A site-selective amination catalyst discriminates between nearly identical C–H bonds of unsymmetrical disubstituted alkenes. Nat. Chem. 12, 725–731 (2020). https://doi.org/10.1038/s41557-020-0470-z

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