Catalytic, Enantioselective Use Of Organolithiums

A copper-based chiral catalyst is enabling direct use of organolithium reagents to form carbon-carbon bonds enantioselectively, chemists in the Netherlands report (Nat. Chem., DOI: 10.1038/nchem.1009). Although organolithiums are among the most widely used reagents for making C–C bonds, until now there was no general catalytic method for their direct addition with high enantioselectivity. Instead, chemists had to rely on stoichiometric amounts of chiral ligands. Researchers at the University of Groningen, led by Syuzanna R. Harutyunyan and Ben L. Feringa, discovered that a catalyst made from CuBr·S(CH₃)₂ and chiral ferrocenyl diphosphine ligands, such as TaniaPhos, can coax a wide variety of organolithium reagents to react enantioselectively in an S_N2ʹ allylic alkylation (example shown). The reaction tolerates several functional groups, including esters and alcohols. Of utmost importance, the researchers note, are the structure of the active catalyst and the use of dichloromethane as a solvent. “Now that the elusive alkyllithium reagents have finally been tamed for catalytic asymmetric C–C bond formation, the stage is set for the discovery of a myriad of new catalytic applications for organolithium reagents, for the practical synthesis of highly valuable chiral products,” they write.