ChemCafé

Some time ago came to Lausanne Prof. Lanny S. Liebeskind from Emory University in Atlanta, co-inventor of the Liebeskind-Srogl coupling. This coupling allows the formation of a new C-C bond starting from a thioester and a boronic acid. The reaction usually requires catalytical palladium as well as a copper-based co-catalyst, but a variation using only catalytical copper was developed. Remarkably, the reaction proceeds under mild conditions (no base needed, relatively low temperature) and tolerates a very broad range of reagents. It can be described as in the following scheme:

Mechanistic investigations have shown the importance of the Cu(I) and of the carboxylate anion for the cross-coupling to work efficiently. These two species are therefore clearly involved in the catalytic mechanism, which is shown below. The thiol ester undergoes complexation to the copper(I) carboxylate, followed by oxydative addition of the bound thiol ester to the Pd(0) catalyst (1). A copper-mediated transmetallation then allows to form the organopalladium compound (2) and eliminates the copper thiolate and boron derivative byproducts. The final ketone (3) is obtained by a reductive elimination that also regenerates the palladium catalyst.

The reaction described above uses a stoechiometric amount of the copper(I) carboxylate. To make it catalytic, it is necessary to regenerate the Cu(I) oxygenate from the eliminated Cu-SR. This was achieved by performing the reaction with an excess of boronic acid, and under air. The Cu-SR bond is broken to form a thioether with the excess boronic acid, and a copper oxygenate is made available to the system. A particular thiol ester was necessary to make the reaction work:

Ref: L. S. Liebeskind, J. Srogl, J. Am. Chem. Soc. 2000, 122, 11260;
J. M. Villalobos, J. Srogl, L. S. Liebeskind, J. Am. Chem. Soc. 2007, 129, 15734.