Intermediacy of copper(i) under oxidative conditions in the aerobic copper-catalyzed decarboxylative thiolation of benzoic acids

An experimental mechanistic study of the aerobic copper-catalyzed decarboxylative thiolation of benzoic acids with arenethiols is reported. For the model reaction, the findings support the corresponding disulfide (PhSSPh) of the arenethiol (PhSH) as the active thiolating source under reaction conditions. Synthesis and reactivity studies along with kinetic measurements support the chemical and kinetic competence of catalytically active well-defined Cu complexes: (phen)Cu^I(O₂CC₆H₄-o-NO₂) (2), [(phen)Cu^I(μ-SC₆H₅)]₂ (3), (phen)Cu^I(C₆H₄-o-NO₂) (4), and (phen)Cu^II(O₂CC₆H₄-o-NO₂)₂ (5) (phen = 1,10-phenanthroline). The presence of an induction period in the stoichiometric reaction of the copper(II) complex (phen)Cu^II(O₂CC₆H₄-o-NO₂)₂ (5) with PhSSPh and the absence of an induction period in the analogous stoichiometric reaction of the copper(I) complex (phen)Cu^I(O₂CC₆H₄-o-NO₂) (2) suggest that a copper(I) carboxylate is a more likely intermediate than a copper(II) carboxylate. The observation of in situ reduction of Cu^II to Cu^I further supports Cu^I as the primary active catalytic species, and spectroscopic studies also indicate the catalyst resting state to be a Cu^I species. The catalytic reaction exhibits a first-order dependence on [Cu^I] and [2-nitrobenzoic acid] and a zero-order dependence on [PhSSPh] and p(O₂), suggestive of turnover-limiting decarboxylation of a copper(I) carboxylate. Oxygen was found to promote the essential oxidative cleavage of the copper(I) thiolate intermediate [(phen)Cu^I(μ-SC₆H₅)]₂ (3) to regenerate a catalytically active [(phen)Cu^II] (Cu_ox) species with concomitant formation of PhSSPh. On the basis of these findings, a reaction pathway is proposed for the C-S coupling reaction that includes the key Cu^I-based intermediates (phen)Cu^I(O₂CC₆H₄-o-NO₂) (2) and (phen)Cu^I(C₆H₄-o-NO₂) (4). The pathway accounts for the role of O₂ in generating the active thiolating source, PhSSPh, as well as enabling catalytic turnover of in situ generated [(phen)Cu^I(μ-SC₆H₅)]₂ (3).