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 via a mechanistically driven approach. Mechanistic studies support the diffusion of the alkyl radical intermediates out of the solvent cage to participate in an intra- or -intermolecular radical cascade with the VCP followed by re-entering the Fe radical cross-coupling cycle to undergo selective C(sp2)-C(sp3) bond formation. 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.
Intra- 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 via 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(sp 2 )–C(sp 3 ) 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.
- Award ID(s):
- 1751568
- Publication Date:
- NSF-PAR ID:
- 10214127
- Journal Name:
- Chemical Science
- Volume:
- 11
- Issue:
- 12
- Page Range or eLocation-ID:
- 3146 to 3151
- ISSN:
- 2041-6520
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Publisher's Version of Record
- https://doi.org/10.1039/D0SC00467G
