A Computational Study of Asymmetric Hydrogenation of 2‐Phenyl Acrylic Acids Catalyzed by a Rh(I) Catalyst with Ferrocenyl Chiral Bisphosphorus Ligand: The Role of Ion‐Pair Interaction^†

Abstract

Hydrogenation| Enantioselectivity| Reaction mechanism| Density functional theory | Ion-pair interactionAsymmetric hydrogenation reaction is one of the most efficient synthetic methods to form useful chiral compounds for synthetic chemistry, medicinal chemistry and material chemistry. Generally, the enantioselectivity of many hydrogenation reactions is controlled by steric hindrance between the chiral ligand and substrate. Recently, Zhang group developed a highly asymmetric hydrogenation of 2-aryl and 2-alkyl acrylic acids catalyzed by a Rh(I) catalyst with a chiral Wudaphos ligand. The excellent enantioselectivity of this asymmetric reaction was proposed to be controlled by ion-pair interaction between the substrate and chiral ligand. In this study, a systematic density functional theory study has been carried out to investigate the reaction mechanism and origin of the enantioselectivity. Our computational results suggest that this reaction follows the classic mechanism involving oxidative addition of H 2 , migratory insertion and reductive elimination. Different from the C=C coordination to the metal in the common oxidative addition step, our study found that the chelation of the carboxyl group of the substrate to the cationic Rh(I) metal is more favorable in this oxidative addition step. The high enantioselectivity is proposed to be dictated by a better catalyst/substrate geometric complementarity in the major pathway to have less distortion of the catalyst for a strong ion-pair interaction.

A Computational Study on the Reaction Mechanism of Stereocontrolled Synthesis of β-Lactam within [2]Rotaxane

“…All density functional theory (DFT) calculations were performed with the Gaussian 09 program to examine the stereoselectivity of the intramolecular cyclization of N -benzylfumaramide in the presence or absence of the rotaxane. The M06 method combined with mixed basis sets (BS1:6-31G* for the light elements and SDD for the heavy Cs metal) was employed to fully optimize all the structures of reactants, intermediates, transition states (TSs), and products in the gas phase.…”

Nickel-catalyzed asymmetric hydrogenation for the preparation of α-substituted propionic acids

“…Given the very important applications of these compounds, their asymmetric synthesis has long been a prominent research topic for chemists. Among the reported methodologies, asymmetric hydrogenation, as an efficient and easy-to-industrialize preparation method, is one of the most attractive approaches 7 – 35 (Fig. 1b ).…”

Development of C2-Symmetric Chiral Diphosphine Ligands for Highly Enantioselective Hydrogenation Assisted by Ion Pairing

“…Moreover, the hydrogenation of substrates 8 and 9 gave very low ee (Scheme c), indicating that the ion pairing interaction between the ligand and substrate played a very important role in the current reaction . A recent computational study by Chung and Dong as well as their co-workers revealed the role of the ion pairing interaction in a similar reaction …”

“…17 A recent computational study by Chung and Dong as well as their co-workers revealed the role of the ion pairing interaction in a similar reaction. 18 A gram-scale synthesis with a low catalyst loading of 0.05 mol % (S/C = 2000) was then conducted to demonstrate the efficiency of the catalyst system using 4a as the model substrate. To our delight, the product 5a was synthesized with c The enantiomeric excess was determined by HPLC on a Chiralcel chiral OJ-3 column.…”