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

He，Bin1; Song，Jingyuan1; Yin，Congcong1; Chen，Gen Qiang2; Zhang，Xumu1

2022-09-23

10.1039/d2qo01121b

Organic Chemistry Frontiers   Impact Factor & Quartile

2052-4110

2052-4129

Asymmetric hydrogenation of aryl α-dibenzylamino β-ketoesters and α-dibenzylamino aromatic ketone catalyzed by the Ir/f-phamidol catalytic system through dynamic kinetic resolution was achieved. Asymmetric reduction of aryl α-dibenzylamino β-ketoesters proceeded smoothly to provide the corresponding chiral aryl β-hydroxy α-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)-catalyzed hydrogenation under 5 atm of H at room temperature to furnish the syn-aryl β-hydroxy α-amino acid, which is an important drug candidate. A gram-scale experiment demonstrated the synthetic utility of this approach. In addition, the α-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.

SCI

English

First ; Corresponding

WOS:000865259300001

2-s2.0-85140338018

Scopus

1.Medi-X Pingshan and Department of Chemistry,Southern University of Science and Technology,Shenzhen,518000,China
2.Academy for Advanced Interdisciplinary Studies,Southern University of Science and Technology,Shenzhen,518000,China

He，Bin,Song，Jingyuan,Yin，Congcong,et al. Highly efficient synthesis of enantioenriched β-hydroxy α-amino acid derivatives via Ir-catalyzed dynamic kinetic asymmetric hydrogenation[J]. Organic Chemistry Frontiers,2022,9(22):6247-6251.

He，Bin,Song，Jingyuan,Yin，Congcong,Chen，Gen Qiang,&Zhang，Xumu.(2022).Highly efficient synthesis of enantioenriched β-hydroxy α-amino acid derivatives via Ir-catalyzed dynamic kinetic asymmetric hydrogenation.Organic Chemistry Frontiers,9(22),6247-6251.

He，Bin,et al."Highly efficient synthesis of enantioenriched β-hydroxy α-amino acid derivatives via Ir-catalyzed dynamic kinetic asymmetric hydrogenation".Organic Chemistry Frontiers 9.22(2022):6247-6251.