Catalytic Aerobic Carbooxygenation for the Construction of Vicinal Tetrasubstituted Centers: Application to the Synthesis of Hexasubstituted γ‐Lactones

Strategic design for the construction of contiguous tetrasubstituted carbon centers represents a daunting challenge in synthetic organic chemistry. Herein, we report a combined experimental and computational investigation aimed at developing catalytic aerobic carbooxygenation, involving the intramolecular addition of tertiary radicals to geminally disubstituted alkenes, followed by aerobic oxygenation. This reaction provides a straightforward route to various α,α,β,β‐tetrasubstituted γ‐lactones, which can be readily transformed into hexasubstituted γ‐lactones through allylation/translactonization. Computational analysis reveals that the key mechanistic foundation for achieving the developed aerobic carbooxygenation involves the design of endothermic (energetically uphill) C−C bond formation followed by exothermic (energetically downhill) oxygenation. Furthermore, we highlight a unique fluorine‐induced stereoelectronic effect that stabilizes the endothermic stereodetermining transition state.