Carboxyl Group-Directed Iridium-Catalyzed Enantioselective Hydrogenation of Aliphatic γ-Ketoacids

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.

Iron/photoredox dual catalysis for acyl nitrene-based C–O bond formation towards phthalides

“…Generally, furan-2-ones could be prepared from carbon-esterification of styrenes 12 and hydrogenation of γ-ketone carboxylic derivatives. 13 The reaction reported herein represents a supplement towards furan-2-ones under mild conditions. To our surprise, 5-arylpentanamides were not compatible, and no corresponding pyrones were afforded under standard conditions (data not shown in Scheme 3).…”

Theoretical Exploration of Mechanism and Ligand Effects of Asymmetric Hydrogenation of β-Amino Ketone Catalyzed by an Iridium-PNN Catalyst

“…All geometries were simulated using the SMD solvation model in i -PrOH based on DFT. , Taking Grimme’s D3 dispersion correction into consideration, the B3LYP functional was used for geometry optimization in combination with SDD effective core potentials for Ir, Fe, and Na and the 6-31G­(d) basis set for other atoms. In terms of the complex catalytic system, the B3LYP-D3 functional has been selected based on the existing theoretical research of the Ir-complex system. ,− In their research studies, the calculation models of different ligand-Ir catalysts were studied by substituents on ligand, central metal, substrate, etc. Frequency calculations were performed at the same level of theory to confirm whether a stationary point was a minimum or a transition state and to acquire corrections to the Gibbs free energy.…”

Reducing Challenges in Organic Synthesis with Stereoselective Hydrogenation and Tandem Catalysis

“…The ligand toolbox for AH continues to grow with greater structural diversity. Some bidentate P,N ligands include PHOX by Pfaltz − (1998) for the AH of unfunctionalized and sterically hindered olefins and SIPHOX by Zhou − (2006) for the AH of ketones and imines. The spiro SDP series by Zhou (2003), when complexed to Ru, can hydrogenate simple ketones with up to 99.5% ee . , Ferrocene backbones such as the C 1 -symmetric planar chiral Josiphos by Togni from Solvias (1990) provide exceedingly high TON and TOF for the AH of olefins, carbonyls, and imines. , Additionally, carbene-based ligands such as CAAC by Bertrand , (2005) have been used for the hydrogenation of aromatic rings.…”