biostudies-literatureLiu LUniversity of MarylandNational Science Foundation3146-3151https://www.ebi.ac.uk/biostudies/studies/S-EPMC8157325biostudies-literatureUnknown11(12)Design and implementation of the first (asymmetric) Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes (VCPs) with alkyl halides and aryl Grignard reagents has been realized <i>via</i> a mechanistically driven approach. Mechanistic studies support the diffusion of alkyl radical intermediates out of the solvent cage to participate in an intra- or intermolecular radical cascade with a range of VCPs followed by re-entering the Fe radical cross-coupling cycle to undergo (stereo)selective C(sp²)-C(sp³) bond formation. This work provides a proof-of-concept of the use of vinyl cyclopropanes as synthetically useful 1,5-synthons in Fe-catalyzed conjunctive cross-couplings with alkyl halides and aryl/vinyl Grignard reagents. Overall, we provide new design principles for Fe-mediated radical processes and underscore the potential of using combined computations and experiments to accelerate the development of challenging transformations.Chemical scienceIntra- and intermolecular Fe-catalyzed dicarbofunctionalization of vinyl cyclopropanes.PMC81573251751568Acha CLiu LGutierrez OGeherty MBYuan MLee WWilliams BfalseIntra- and intermolecular Fe-catalyzed dicarbofunctionalization of vinyl cyclopropanes.Design and implementation of the first (asymmetric) Fe-catalyzed intra- and intermolecular difunctionalization of vinyl cyclopropanes (VCPs) with alkyl halides and aryl Grignard reagents has been realized <i>via</i> a mechanistically driven approach. Mechanistic studies support the diffusion of alkyl radical intermediates out of the solvent cage to participate in an intra- or intermolecular radical cascade with a range of VCPs followed by re-entering the Fe radical cross-coupling cycle to undergo (stereo)selective C(sp²)-C(sp³) bond formation. This work provides a proof-of-concept of the use of vinyl cyclopropanes as synthetically useful 1,5-synthons in Fe-catalyzed conjunctive cross-couplings with alkyl halides and aryl/vinyl Grignard reagents. Overall, we provide new design principles for Fe-mediated radical processes and underscore the potential of using combined computations and experiments to accelerate the development of challenging transformations.2020-01-01T00:00:00Z2020 Feb2026-05-07T17:05:20.939Z2022-02-10T14:45:43.001ZS-EPMC81573253412281910.1039/d0sc00467g