23:T537,Alkyl cyclopropyl ketones are introduced as versatile substrates for catalytic formal [3 + 2] cycloadditions with alkenes and alkynes and previously unexplored enyne partners, efficiently delivering complex, sp³-rich products. The key to effectively engaging this relatively unreactive new substrate class is the use of SmI₂ as a catalyst in combination with substoichiometric amounts of Sm⁰; the latter likely acting to prevent catalyst deactivation by returning Sm^III to the catalytic cycle. In the absence of Sm⁰, background degradation of the SmI₂ catalyst can outrun product formation. For the most recalcitrant alkyl cyclopropyl ketones, catalysis is "switched-on" using these new robust conditions, and otherwise unattainable products are delivered. Combined experimental and computational studies have been used to identify and probe reactivity trends among alkyl cyclopropyl ketones, including more complex bicyclic alkyl cyclopropyl ketones, which react quickly with various partners to give complex products. In addition to establishing alkyl cyclopropyl ketones as a new substrate class in a burgeoning field of catalysis, our study provides vital mechanistic insight and robust, practical approaches for the nascent field of catalysis with SmI₂.24:T4bc,Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI₂, Kagan's reagent), represent an invaluable platform to generate molecular complexity in a stereocontrolled manner. In addition to classical ketone and aldehyde substrates, recent advances in radical chemistry allow the cyclization of lactone and lactam-type substrates using SmI₂. In contrast, acyclic esters are considered to be unreactive to SmI₂ and their participation in reductive cyclizations is unprecedented. Here, we report a diastereoselective radical 1,4-ester migration process, mediated by SmI₂, that delivers stereodefined alkene hydrocarboxylation products via radical cyclization of acyclic ester groups in α-carbomethoxy δ-lactones. Isotopic labeling experiments and computational studies have been used to probe the mechanism of the migration. We propose that a switch in conformation redirects single electron transfer from SmI₂ to the acyclic ester group, rather than the "more reactive" lactone carbonyl. Our study paves the way for the use of elusive ketyl radicals, derived from acyclic esters, in SmI₂-mediated reductive cyclizations.

#	Concept	H-Index	Publications	Citations
1	Engineering	2	2	314
2	Chemistry	2	2	314
3	Catalysis	2	2	314
4	Natural Sciences	1	1	27
5	Biomolecular Engineering	1	1	27

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