Diastereoselective radical 1,4-ester migration: radical cyclizations of acyclic esters with SmI2

Charlotte Morrill, Áron Péter, Ilma Amalina, Emma Pye, Giacomo Crisenza, Nikolas Kaltsoyannis, David Procter

Research output: Contribution to journalArticlepeer-review

Abstract

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 a-carbomethoxy d-lactones. Isotopic labelling 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.
Original languageEnglish
Pages (from-to)13946-13952
JournalJournal of the American Chemical Society
Volume144
Publication statusPublished - 20 Jul 2022

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