Carboxyl Group-Directed Iridium-Catalyzed Enantioselective Hydrogenation of Aliphatic γ-Ketoacids
Mao‐Lin Li, Yao Li, Jia‐Bin Pan, Yi-Hao Li, Song Song, Shou‐Fei Zhu, Qi‐Lin Zhou
Abstract
Although the transition metal-catalyzed asymmetric hydrogenation of aromatic ketones has been extensively explored, the enantioselective hydrogenation of aliphatic ketones remains a challenge because chiral catalysts cannot readily discriminate between the re and si faces of these ketones. Herein, we report a carboxyl-directing strategy for the asymmetric hydrogenation of aliphatic γ-ketoacids. With catalysis by iridium complexes bearing chiral spiro phosphino-oxazoline ligands, hydrogenation of aliphatic γ-ketoacids afforded chiral γ-hydroxylacids with high enantioselectivity (up to 99% ee). Mechanistic studies revealed that the carboxyl group of the substrate directs hydrogen transfer and ensures high enantioselectivity. Density functional theory calculations suggested the occurrence of chiral induction involving a hydrogen–hydrogen interaction between a hydride on the iridium atom and the substituent on the oxazoline ring of the ligand, and on the basis of the calculations, we proposed a catalytic cycle involving only Ir(III), which differs from the Ir(III)/Ir(V) catalytic cycle that operates in the hydrogenation of α,β-unsaturated carboxylic acids.