Intermediacy of Copper(I) under Oxidative Conditions in the Aerobic Copper-Catalyzed Decarboxylative Thiolation of Benzoic Acids

Abstract

An experimental mechanistic study of the aerobic copper-catalyzed decarboxylative thiolation of benzoic acids with aryl thiols is reported. For the model reaction, the findings support the corresponding disulfide (PhSSPh) of the aryl thiol (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 welldefined Cu-complexes; (phen)Cu I (O2CC6H4-o-NO2) (2), (phen)Cu I (C6H4-o-NO2) (4), [(phen)Cu I (µ-SC6H5)]2 (3) and (phen)Cu II (O2CC6H4-o-NO2)2 (5), (phen = 1,10-phenanthroline). The presence of an induction period in the stoichiometric reaction of 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 copper(I) complex (phen)Cu I (O2CC6H4-o-NO2) (2), suggests 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 [2nitrobenzoic acid] and a zero order dependence on [PhSSPh] and pO2, 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(µ-SC6H5)]2 (3) to regenerate a catalytically active [(phen)Cu II ] (Cuox) 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(O2CC6H4-o-NO2) (2), and (phen)Cu(C6H4o-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(µ-SC6H5)]2 (3).

Decarboxylation‐Initiated Intermolecular Carbon‐Heteroatom Bond Formation

“…They also demonstrated that diphenyl diselenide could be an efficient coupling partner, leading to the desired diaryl selenide in 53% yield. Based on mechanistic studies, a pathway was proposed [300] which commences with the decarboxylation of a (Phen)Cu(I)‐carboxylate to form an aryl‐Cu(I) species (Scheme 46B). This intermediate undergoes oxidative addition of the ArSSAr thiolating reagent generated via Cu‐mediated aerobic oxidation of the initial ArSH.…”

Combined Experimental and Computational Mechanistic Investigation of the Palladium-Catalyzed Decarboxylative Cross-Coupling of Sodium Benzoates with Chloroarenes

“…The mechanisms of metal-catalyzed protodecarboxylation and decarboxylative cross-coupling reactions have been studied. ,, In contrast to systems that use Ag ,− or Cu ,− additives, systems utilizing only a Pd catalyst are much less well understood. Unlike decarboxylative Heck reactions or protodecarboxylation reactions, there is minimal experimental mechanistic data on palladium-catalyzed decarboxylative cross-coupling without copper or silver. − A variety of palladium-catalyzed methods have been developed including work by Bilodeau and Forgione on coupling heteroarylcarboxylic acids, , a report by Eli Lilly to synthesize a desired scaffold, , and advancement of intramolecular cyclizations by Shen, , in addition to others. , However, these reactions have not been thoroughly investigated.…”

Recent Metal-Catalyzed Methods for Thioether Synthesis

“…A mechanistic follow-up study suggested that the catalytic cycle proceeds via decarboxylation of the Cu(I) carboxylate complex A to a Cu(I) aryl species B, which undergoes oxidative addition with the in situ formed disulfide. 103 Similar reaction conditions were applied to convert benzylic alcohols to thioethers via oxidative cleavage of the CAr-C(OH) bond and subsequent decarboxylation. 104 Other reported achievements include couplings of alkynyl carboxylic acids, 105 methylthiolations using DMSO, 106 and syntheses of perfluoroalkyl thioethers.…”