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

Abstract

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 H 2 .Article pubs.acs.org/joc

Cinchona-alkaloid-derived NN ligands for ruthenium catalyzed asymmetric hydrogenation of ketones

“…The new chiral NN ligand and achiral phosphine modified iridium complex together for asymmetric hydrogenation of heteroaromatic and α-chloroheteroaryl ketones providing the corresponding alcohols in up to 99.9% ee. 31 This result is encouraging as the hydrogenation of aromatic ketones containing heteroatoms is more difficult and therefore less studied. In this context, we are interested in exploring the ruthenium-catalyzed asymmetric hydrogenation of aromatic ketones with cinchona-alkaloid-derived NN ligands in the absence of additional achiral phosphines.…”