Criegee Intermediate-Enabled Decarboxylative C(sp3)–C(sp3) Cross-Coupling of α,β-Unsaturated Esters with Cyclic Acetals

Abstract

Abstract Ozonolysis and Baeyer–Villiger (BV) rearrangement are among the earliest transformations in which cyclic/acyclic peroxo intermediates, often known as Criegee intermediates, have been detected. Herein, we disclose the merger of a Criegee intermediate with C(sp3)–C(sp3) cross-coupling via a rare anti-Giese addition for a new genre of C–C cross-coupling to access complex chemical libraries. Detailed mechanistic investigation reveals the generation of a cyclic tetrahedral peroxo intermediate (CI), and gas-phase analysis establishes the formation of 16O═C═18O under 18O2 conditions and straightforwardly supports the formation of peroxylactones via a Criegee intermediate under our standard conditions. Importantly, many pharmaceutically active drug-like molecules have been screened thoroughly and have been shown to exhibit excellent tolerance and high regioselectivity for this methodology.