Efficient Iron/Copper Co-catalyzed S-Arylations of Thiols with Aryl Halides

In the 21st Century, these ancient metals allow fine chemistry.

The formation of aryl–sulfur bonds has emerged as a powerful reaction in the last years, trailing the development of new and powerful C–X couplings. However, the transition-metal-catalyzed cross-coupling reactions of aryl halides with thiols suffer from many limitations, which makes it a relatively less studied transformation. The main reasons are two: First, thiols can act as catalyst poisons and deactivate metal-based catalysts via strong coordination, rendering the catalytic systems totally ineffective. Second, thiols are air-sensitive and prone to form undesired disulfides, so most C–S cross-coupling reactions are performed under inert conditions.

The work by Liu et al. (Shangai, China) focuses on the development of a new catalytic system that overcomes these limitations. The method uses a Fe/Cu catalyst mixture and microwave conditions to enhance the coupling. Thus, in a typical example, catalytic amounts of Fe2O3, Cu(OAc)2, and TMEDA with Cs2CO3 are reacted under microwave irradiation for 10 min to give the desired products in yields ranging from very good to excellent. The catalysts are cheap, user friendly, and the reactions can be done under air without the need for excluding moisture. More than twenty examples are reported, including aromatic and aliphatic thiols, aryl iodides, bromides and chlorides, and even a couple of heterocycles. The aryl iodides are the best substrates, but bromides are good alternatives. An ideal method for drug discovery.

J. Comb. Chem., 2009, 11 (3), pp 338–340. See: 10.1021/cc800182q