In the absence of directing auxiliaries, the catalytic addition of carbogenic groups to unactivated alkenes with control of regioselectivity remains an ongoing challenge in organic chemistry. Here we describe a directing-group-free, nickel-catalysed strategy that couples a broad array of unactivated and activated olefins with aryl-substituted triflates and organometallic nucleophiles to afford diarylation adducts in either regioisomeric form, in up to 93% yield and >98% site selectivity. By switching the reagents involved, the present strategy may be extended to other classes of dicarbofunctionalization reactions. Mechanistic and computational investigations offer insights into the origin of the observed regiochemical outcome and the utility of the method is highlighted through the concise syntheses of biologically active molecules. The catalyst control principles reported are expected to advance efforts towards the development of general site-selective alkene functionalizations, removing the requirement for neighbouring activating groups.
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All data supporting the findings of this study are available within the Article and its Supplementary Information. Crystallographic data for compound 4i have been deposited at the Cambridge Crystallographic Data Centre, under deposition number CCDC 2069191. Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/.
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This research was supported by the National University of Singapore Academic Research Fund Tier 1: R-143-000-B57-114 (M.J.K.) and by the National Institutes of Health R35GM137797 (O.G.). O.G. is grateful to the MARCC/BlueCrab HPC clusters and XSEDE (CHE160082 and CHE160053) for computational resources. We thank G. K. Tan for X-ray crystallographic analysis.
The authors declare no competing interests.
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Supplementary Tables 1–8, Figs. 1–5, experimental data, synthesis and characterization data, NMR spectra, X-ray crystallographic data, DFT calculation data and references.
Supplementary Data 1
Crystallographic data for compound 4i; CCDC reference 2069191.
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Wang, H., Liu, CF., Martin, R.T. et al. Directing-group-free catalytic dicarbofunctionalization of unactivated alkenes. Nat. Chem. 14, 188–195 (2022). https://doi.org/10.1038/s41557-021-00836-6