Two-component C–H bond additions to a large variety of coupling partners have been developed with applications towards materials, natural product and drug synthesis. Sequential three-component C–H bond addition across two different coupling partners potentially enables the convergent synthesis of complex molecular scaffolds from simple precursors. Here, we report three-component Co(iii)-catalysed C–H bond additions to dienes and aldehydes that proceed with high regio- and stereoselectivity, resulting in two new carbon–carbon σ-bonds and four to six new stereocentres. The reaction relies on the synergistic reactivity of the diene and aldehyde, with neither undergoing C–H bond addition alone. A detailed mechanism is supported by X-ray structural characterization of a Co(iii)-allyl intermediate, observed transfer of stereochemical information, and kinetic isotope studies. The applicability of the method to biologically relevant molecules is exemplified by the rapid synthesis of the western fragment of the complex ionophore antibiotic lasalocid A.
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This work was supported by the NIH (R35GM122473).
The authors declare no competing interests.
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Supplementary Methods, Supplementary Figures 1–5, Supplementary Tables 1 & 2, Supplementary References
Crystallographic data for compound 4b, CCDC reference 1812525
Crystallographic data for compound 4ar’, CCDC reference 1826301
Crystallographic data for compound 8a, CCDC reference 1812526
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Boerth, J.A., Maity, S., Williams, S.K. et al. Selective and synergistic cobalt(iii)-catalysed three-component C–H bond addition to dienes and aldehydes. Nat Catal 1, 673–679 (2018). https://doi.org/10.1038/s41929-018-0123-4
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