Cinchona-Alkaloid-Derived NN Ligands and Achiral Phosphines for Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatic and α-Chloroheteroaryl Ketones.

A concise synthesis of cinchona-alkaloid-derived NN ligands bearing alkyl substituents on chiral nitrogen atoms was described. Iridium catalysts containing new chiral NN ligands and achiral phosphines were effective for the asymmetric hydrogenation of heteroaromatic ketones, which afforded corresponding alcohols in up to 99.9% ee. The same protocol was applicable to the asymmetric hydrogenation of α-chloroheteroaryl ketones. Most importantly, the gram-scale asymmetric hydrogenation of 2-acetylthiophene and 2-acetylfuran proceeded smoothly even under 1 MPa of H2.