Highly efficient synthesis of enantioenriched β-hydroxy α-amino acid derivatives via Ir-catalyzed dynamic kinetic asymmetric hydrogenation

Asymmetric hydrogenation of aryl alpha-dibenzylamino beta-ketoesters and alpha-dibenzylamino aromatic ketone catalyzed by the Ir/f-phamidol catalytic system through dynamic kinetic resolution was achieved. Asymmetric reduction of aryl alpha-dibenzylamino beta-ketoesters proceeded smoothly to provide the corresponding chiral aryl beta-hydroxy alpha-amino derivatives with excellent diastereo- and enantioselectivities (>99/1 dr, up to >99% ee). The dibenzyl protecting group was easily removed by performing a 10% Pd(OH)(2)-catalyzed hydrogenation under 5 atm of H-2 at room temperature to furnish the syn-aryl beta-hydroxy alpha-amino acid, which is an important drug candidate. A gram-scale experiment demonstrated the synthetic utility of this approach. In addition, the alpha-dibenzylamino aromatic ketone was hydrogenated to the amino alcohol product with excellent enantioselectivity and a high turnover number (S/C up to 10 000). After deprotection of the dibenzyl group, the chiral amino alcohol can serve as a useful scaffold for chiral ligands or auxiliaries in the field of asymmetric synthesis.

Automated summary

Asymmetric hydrogenation of aryldibenzylamino ketones catalyzed by the Ir/f-phamidol system was achieved through dynamic kinetic resolution, producing chiral compounds with high selectivity. This method offers excellent conversion and enantioselectivity, making it applicable in the synthesis of drug candidates and chiral ligands.