The Formation of Bisaryl-and Arylalkyl-Thioethers

Although thiols are generally stronger nucleophiles than alcohols and amines, the sensitivity of sulfides towards oxidation as well as the formation of disulfide made the cross-coupling between aryl halides and thiols difficult. From all previously reported results, it was foimd that only aryl iodides were suitable for this copper-catalyzed coupling process. 

In 2002, Venkataraman published the synthesis of bisaryl- and arylalkyl-thioethers catalyzed by the Cul/neocuproine system [74]. At the same time, using excess ethylene glycol as a ligand, Cul-catalyzed coupUng of aryl iodides with thiols was found to take place at 80 °C [75]. Soon after, N,N-dimethylglycine (L2) (Table 9.15, entry 1) [76] and L-proline (LI) (entry 2) [77] were revealed to be effective for the same transformation. Recently, CuBr/ 3-keto ester (L19) was reported to be able to promote this cross-coupling reaction to afford the corresponding diaryl thioethers at 60-75 °C (entry 3) [27]. 

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