Copper(I) Thiophene-2-carboxylate (CuTC)

(A) Modified Stille Cross-CouplingsIn the presence of CuTC aryl, heteroaryl and alkenylstannates can be cross-coupled with alkenyl iodides under mild conditions and in very good yields. This protocol allows the crosscoupling of thermally sensitive substrates and is highly tolerable towards functional groups compared to palladium catalysts. The usefulness of this method was demonstrated in the coupling of two highly functionalized fragments in the endgame of the total synthesis of apoptolidin. (B) Stereoselective Formation of EnamidesCuTC also promotes formation of enamides from amides and vinyl iodides. Best results were obtained using 30 mol% of CuTC and Cs2CO3 as base. This method yields the enamides with complete E/Z olefin stereoselectivity and also found application in the total synthesis of complex natural products. (C) Ullmann-Type CouplingsAn Ullmann-like reductive coupling of aryl, heteroaryl and alkenyl iodides was recently reported. Typically, the classical Ullmann coupling reactions are conducted above 200 °C, whereas the CuTC-mediated coupling may be performed at room temperature. Notable is the lack of reaction of aromatic substrates not bearing a coordinating ortho substituent. This is explained by the need for a precoordination of the substrate to copper prior to oxidative addition. The alkenyl substrates couple under retention of stereochemistry. (D) Synthesis of AlkynesAn alternative to the Sonogashira protocol is the mild and non-basic palladium-catalyzed, copper carboxylate mediated coupling of thioalkynes and boronic acids. The thioalkynes are reacted with the boronic acids in THF at 45-50 °C and furnish symmetrical as well as unsymmetrical alkynes in moderate to excellent yields. (E) Synthesis of KetonesA general method leading to a variety of ketones is the CuTC-promoted, palladium-catalyzed coupling of thiol esters and boronic acids. Both reaction partners are readily available and the reaction proceeds under non-basic and thus mild conditions to furnish ketones in good yields. (F) Allylic SubstitutionAsymmetric allylic substitution allows the creation of a chiral center in readily available starting materials. So far, there have been great efforts to control the chemo-, regio-, and enantioselectivities of the reaction product. An enantioselective copper-catalyzed allylic alkylation with Grignard and organozinc reagents was recently reported. The products are obtained in very good yields and usually in high enantiomeric excess. (G) 1,4-Addition to EnonesCuTC also promotes the conjugate addition of trimethylaluminum to (beta)-trisubstituted enones, which allows the formation of a quaternary all-carbon center. The use of biphenol- and binaphtholbased ligands afforded very high enantioselectivities, yielding chiral building blocks for more elaborate natural products.