Diastereoselective Radical 1,4-Ester Migration: Radical Cyclizations of Acyclic Esters with SmI 2 .

Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI 2 , 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 SmI 2 . In contrast, acyclic esters are considered to be unreactive to SmI 2 and their participation in reductive cyclizations is unprecedented. Here, we report a diastereoselective radical 1,4-ester migration process, mediated by SmI 2 , 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 SmI 2 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 SmI 2 -mediated reductive cyclizations.