Factors Controlling Diastereoselectivity and Reactivity in the Catalytic Aerobic Carbooxygenation of (<i>E</i>)‐2‐Fluoro‐3‐aryl‐allyl Nitroacetates

Radical cyclizations are powerful tools for complexity building, providing facile access to functionalized cyclic adducts. However, forging two contiguous tetrasubstituted carbons via radical cyclization through the addition of tertiary radicals to geminally disubstituted sp² carbons has rarely been investigated. Furthermore, the effect of double-bond geometry at the geminally disubstituted sp² carbon on reactivity and stereochemical outcomes remains underexplored. In this study, we present experimental and computational studies on the carbooxygenation of 2-fluoro-3-aryl-allyl nitroacetates to investigate reactivity and selectivity differences between (E)- and (Z)-isomers. First, we identify that (E)-isomers are less reactive than (Z)-isomers. Second, both (E)- and (Z)-isomers undergo conversion to α,α,β,β-tetrasubstituted γ-lactones with high syn-selectivity, despite the absence of putative E/Z isomerization of the alkene unit. Third, incorporating an electron-donating group at the radical acceptor enhances the reactivity of (E)-isomers in catalytic aerobic carbooxygenation. Fourth, computational studies show that syn-selectivity is mainly governed by the fluorine-induced gauche effect, whereas SOMO-HOMO level inversion induced by the electron-donating group at the radical acceptor enhances (E)-isomer reactivity. Based on these mechanistic insights, we develop a diastereoconvergent protocol using the E/Z mixture as a starting material to synthesize a potent antifungal agent.