Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of ß-Keto Ester.

The Ir-catalyzed asymmetric hydrogenation of ß-keto esters with Cinchona-alkaloid-derived NNP ligands has been developed. ß-Hydroxy esters of opposite configuration were afforded smoothly with 91.5-99.1 and 81.6-99.3% ee, respectively, using NNP L2 and L7 derived from quinidine and quinine separately even on the gram scale. The protocol for the preparation of ß-hydroxy esters of opposite configuration by the simple conversion of ligand configurations offered further opportunities for the synthesis of biologically active molecules and drugs.

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.

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

A range of cinchona-alkaloid-derived NN ligands bearing N-H were employed for the asymmetric hydrogenation of ketones. By substituting N-H of the ligands, we demonstrated that the N-H moiety was essential for asymmetric hydrogenation and that without the N-H moiety asymmetric hydrogenation could not proceed, based on which a proposed mechanism is discussed. The effectiveness of the optimal ligand was evaluated on various aromatic and α,ß-unsaturated ketones, producing the corresponding alcohols with up to 98.8% ee and good yields.