Diastereoselective radical hydroalkylation of cyclopropenes enabled by EDA complexes

Hydroalkylation of cyclopropenes with non-stabilised alkyl radicals remains largely unexplored due to their high reactivity and the propensity of cyclopropyl radicals to undergo ring-opening. Herein, we report a metal-free, visible-light-driven ring-retentive hydroalkylation of cyclopropenes enabled by electron donor–acceptor (EDA) complex-mediated activation of redox-active N-hydroxyphthalimide esters. This strategy enables the controlled decarboxylative generation and direct addition of a broad range of primary, secondary, and tertiary alkyl radicals, affording polysubstituted cyclopropanes bearing two new stereogenic centres with excellent diastereoselectivity. The reaction proceeds under mild conditions with broad functional-group tolerance and is compatible with continuous-flow operation. Mechanistic investigations, including radical trapping, deuterium labelling, UV-Vis studies, and DFT calculations, support a ground-state EDA-initiated radical pathway in which steric effects govern both radical addition and the subsequent hydrogen-atom transfer, accounting for the observed regio- and stereoselectivity.

Equipment used in this paper: UV-150 Photochemical Reactor, SF-10 Laboratory Pump

• Martínez ÁM¹
• García J¹
• Domínguez G¹
• Prats-Colàs P¹
• Alonso I²
• Baumann M³
• Pérez-Castells J¹

•   ¹Department of Chemistry and Biochemistry, School of Pharmacy, Universidad San Pablo-CEU (USP-CEU), CEU Universities, Urbanización Montepríncipe, Boadilla del Monte 28668 Madrid, Spain.
• ²Department of Organic Chemistry, School of Science; Center for Innovation in Advanced Chemistry (ORFEO-CINQA); and Institute for Advanced Research in Chemical Sciences (IAdChem), Universidad Autónoma de Madrid (UAM), Cantoblanco, 28049 Madrid, Spain.
• ³School of Chemistry, University College Dublin (UCD), Science Centre South, Belfield, Dublin 4, Ireland.

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