Unlocking reactivity potential of gem-dihaloolefins: access to Halo-functionalized 1,4-naphthoquinones via intramolecular radical oxidative cyclization

Abstract

Herein, we demonstrate an unprecedented metal-free approach for synthesizing highly functionalized naphthoquinones from gem-dihaloolefins. The reaction proceeds through a one-pot sequence comprising three pivotal steps: an initial oxidation, a 6-endo-dig cyclization, and subsequent oxidation. Here, the combination of diphenyldiselenide and TBHP offered a potent catalytic system for the dual oxidation of gem-dihalovinylbenzene derivatives, enabling the efficient synthesis of 2,3-disubstituted naphthoquinones in good to excellent yields. This developed protocol also facilitates the synthesis of menthol and benzocaine-derived naphthoquinones. Mechanistic insights are provided through control experiments and real-time mass data monitoring using online ESI-MS spectrometry.