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


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

Author information




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.

Corresponding author

Correspondence to Tomislav Rovis.

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The authors declare no competing interests.

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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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