Chiral Rhodium Complexes Derived From Electron-Rich Phosphine-Phosphites as Asymmetric Hydrogenation Catalysts

Two new chiral cationic rhodium(I) complexes derived from electron-rich dicyclohexylphosphine-phosphite ligands were prepared from enantiopure Sharpless epoxy ethers. The best-performing catalyst system, which bears a less bulky methyl ether moiety, exhibited remarkably high enantioselectivity (up to 99% cc) and reactivity (up to >2500 TON) in asymmetric hydrogenation reactions of various functionalized alkenes (alpha-(acylamino)acrylates, itaconic acid derivatives, a-substituted enol esters and alpha-arylenamides). Our synthetic methodology has been successfully applied to the enantioselective synthesis of the antiepileptic drug (R)-lacosamide (Vimpat).