Unlock the Potential of Aryl Thiols in Photochemical Carboxylation
Reaction Mechanism
In our mechanistic investigations, we found that both light and tBuOK are crucial for the cleavage of C−S bonds in aryl thioether 3c. The formation of 9 and 10 was determined by GC, suggesting the cleavage of the alkyl C−S bond and the generation of a corresponding alkyl radical. UV-vis spectroscopic measurements showed a bathochromic shift in the spectrum of thioether 3a in the presence of tBuOK, indicating the formation of an electron donor-acceptor (EDA) complex. The radical inhibition experiment with 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) demonstrated the involvement of a radical process. The detection of formate (HCO2−) only in the presence of thiolates and CO2 suggested the generation of CO2•− through single electron transfer (SET) between CO2 and photoactivated thiolate. The reaction profile showed the formation of disulfide 12 and the anionic species p–tBuC6H4SS−, which reacted with iodoethane to produce 13. Computational studies revealed that CO2•− and a thiyl radical are likely generated as key intermediates, and the substitution of CO2•− on the phenyl ring via transition state 3-TS is more favorable than that at the sulfur atom. Further DFT calculations showed that disulfur radical 5-IN could preferentially undergo reduction and S−S bond dissociation to fulfill the carboxylation transformation.
Based on these mechanistic studies and previous reports, a plausible pathway for the cleavage and carboxylation of C(sp2)–S bonds in aryl thiols with CO2 is proposed. Initially, upon irradiation with 365 nm light, a single electron transfer event occurs between the excited thiolate II and CO2 to afford CO2•− and thiyl radical III. The thiyl radical III undergoes dimerization to form the disulfide intermediate 12. Subsequently, the radical addition of CO2•− to disulfide 12 generates the desired carboxylate IV and radical intermediate V. Intermediate V is then reduced by CO2•− via a SET process to produce intermediate VI, which can be trapped by EtI. Finally, intermediate VI is converted to thiolate I under strong basic conditions. However, we cannot exclude other reaction pathways, and further mechanistic studies are ongoing in our laboratory.
Scope of Aryl Thiols
With the optimal reaction conditions in hand, we examined the scope of aryl thiols with different substituents. A broad range of para– and meta-substituted aryl thiols (1a–1q) were effectively transformed with CO2, producing the desired carboxylic acids 2a–2q in moderate to good yields. Diverse functional groups, including ether, amide, boronic ester, ester, thioether, silyloxy, trimethylsilyl, and even unprotected hydroxy group, were well tolerated in the reaction. The aryl thiol 1q bearing an unactivated vinyl group was also competent for this carboxylation reaction, with the vinyl group remaining intact. The sterically hindered aryl thiol 1r bearing ortho methyl group could undergo carboxylation with high efficiency. Di-substituted and tri-substituted aryl thiols were also successfully converted into the corresponding carboxylic acids. Additionally, aryl thiols derived from biologically active molecules were compatible in this reaction, yielding the desired products in good yields.
Scope of Arylthiol Derivatives
We further expanded the substrate scope to arylthiol derivatives. A variety of aryl thioethers, which are challenging substrates in previous photo-induced selective cleavage of C−S bonds, underwent smooth carboxylation with CO2 under the optimized reaction conditions. Different alkylthioarenes bearing primary, secondary, and tertiary alkyl groups were selectively transformed to 2a in 53-95% yields. A thiophenol-derived alkene was also compatible under the present conditions. Diaryl sulfide and thioesters were successfully subjected to the reaction conditions, leading to the corresponding products in good yields. Thiocarbamates could also undergo the C(sp2)–S bond carboxylation smoothly, yielding the corresponding products in high yields.
Synthetic Applications
To further demonstrate the practicality of this strategy, we carried out the carboxylation of analogues of aryl thiols. The carboxylation of benzeneselenol provided the corresponding carboxylic acid in a moderate yield. Diphenyl diselenide, a commonly used radical scavenger, was found to be amenable to Se−Se bond cleavage and carboxylation of C(sp2)–Se bond with CO2. Additionally, we explored the degradation of polyphenylene sulfide (PPS) with CO2. When PPS was subjected to the similar reaction conditions, it could be degraded into product 8 effectively, highlighting the potential applications of this method in material science.