The enantioselectivity in asymmetric ketone hydrogenation catalyzed by RuH<sub>2</sub>(diphosphine)(diamine) complexes: insights from a 3D-QSSR and DFT study

Li, Longfei; Pan, Yuhui; Lei, Ming

doi:10.1039/c5cy01225b

Cited by 27 publications

(16 citation statements)

References 77 publications

(102 reference statements)

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“…As mentioned in the Introduction, the mechanism of the direct hydrogenation of acetophenone with the achiral precatalyst [FeHBr(CO( 1b )] ( 3b ) in the presence of base has been thoroughly studied by DFT calculations. − As acetophenone is prostereogenic, the use of a chiral pincer ligand introduces additional information concerning the enantiodetermining step of the catalytic cycle, that is, the hydride transfer. − This may allow one to discriminate between the D , I , and O mechanisms (Scheme ) suggested for 3b , provided that they lead to significantly different enantioselectivity and/or different sense of induction. To clarify whether such a discrimination based on the absolute configuration of the product is possible, we performed DFT calculations on the enantiodetermining step of the hydrogenation of acetophenone with complex 3a according to the three different mechanisms (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism

2018

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We report here the tridentate, P-stereogenic, C 2-symmetric PNP pincer ligand (S P,S P)-2,6-bis((cyclohexyl(methyl)phosphanyl)methyl)pyridine (1a) and its iron(II) complexes [FeBr2(CO)(1a)] (2a), [FeHBr(CO)(1a)] (3a), and [FeH2(CO)(1a)] (4a). In the presence of base, bromocarbonylhydride 3a catalyzes the hydrogenation of acetophenone to (S)-1-phenylethanol with 48% ee. The transition states of the enantiodetermining transfer of hydride from 3a to the carbonyl group of acetophenone were studied by density functional theory (DFT) with a full conformational analysis of the PNP ligand for the three different mechanistic models recently proposed for a related achiral catalyst. The DFT calculations show that the outer-sphere monohydride mechanism originally proposed by Milstein reproduces the experimentally observed sense of induction (S) and enantioselectivity, whereas the dihydride and inner-sphere pathways predict the formation of the R enantiomer.

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Section: Resultsmentioning

confidence: 99%

Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism

2018

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“…Recently, the regression analysis of catalytic asymmetric reactions has attracted attention, and several descriptors and protocols have been examined . CoMFA and related methods have also been used for the analysis of such transformations and have provided insights into reactions through the visualization of important molecular structural information .…”

Section: Resultsmentioning

confidence: 99%

“…To support such explorations, regression analyses to extract important structural information from the catalysts have been reported. For example, Lennard‐Jones potentials calculated at probe atoms placed around a catalyst/ligand have been used as steric descriptors . We can extract sterically important regions around the molecules for reactions by QSPR (quantitative structure‐property relationship) modeling between the descriptors and reaction outcomes such as enantiomeric ratios.…”

Section: Introductionmentioning

confidence: 99%

“…This kind of analysis, known as comparative molecular field analysis (CoMFA), was originally developed for the analysis of the interactions between proteins and small molecules. CoMFA and related methods have been used for the analyses of catalytic asymmetric reactions and polymerization reactions . In the analyses, the selection of the important descriptors from among a large number of descriptors is required.…”

Section: Introductionmentioning

confidence: 99%

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Regularized regression analysis of digitized molecular structures in organic reactions for quantification of steric effects

et al. 2017

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In organic chemistry, Comparative Molecular Field Analysis (CoMFA) can be defined as a regression analysis between reaction outcomes and molecular fields, wherein we can extract and visualize important structural information from the coefficients of the constructed regression models. In CoMFA, partial least-squares (PLS) regression, which determines all coefficients in the model, is used for fitting the regression models. However, in organic reactions, steric effects are observed only near the reactive site, indicating that a large number of regression coefficients in the CoMFA of organic reactions should be assigned as 0. The regularized regression method, LASSO/Elastic Net, allows us to fit the regression model while assigning 0 values to unimportant coefficients. Although LASSO/Elastic Net should be suitable for CoMFA, there is no example of its use for organic reaction analysis. Herein, we examine the performance of LASSO/Elastic Net for the quantification of steric effects in CoMFA. We employ digitized molecular structures (the indicator field) as molecular fields that represent steric effects. LASSO/Elastic Net regressions provide highly interpretable models that include less noise than those from PLS regression. © 2017 Wiley Periodicals, Inc.

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“…A representation of the different steps occurring during reaction is shown in Scheme 1 (more details of the catalyzed pathway can be found in reference [21]). Initially, the pre-catalyst 1 is transformed into the catalyst 2.…”

Section: Mechanistic Considerationsmentioning

confidence: 99%

Chiral Catalyst Deactivation during the Asymmetric Hydrogenation of Acetophenone

Ruelas-Leyva

Fuentes

2017

Catalysts

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Asymmetric hydrogenation in solution catalyzed by chiral catalysts is a powerful tool to obtain chiral secondary alcohols. It is possible to reach conversions and enantiomeric excesses close to 99%, but that frequently requires the use of non-optimal amounts of catalysts or long reaction times. That is in part caused by the lack of kinetic information needed for the design of large-scale reactors, including few reported details about catalyst deactivation. In this work, we present a kinetic model for the asymmetric hydrogenation in solution of acetophenone, a prochiral substrate, catalyzed by different bisphosphine-diamine Ru complexes. The experimental data was fitted with a first order model that includes first order deactivation of the catalyst and the presence of residual activity. The fit of the experimental data is very good, and an analysis of the kinetic and deactivation parameters gives further insight into the role of each ligand present in the Ru catalysts. This is the first report of a kinetic analysis of homogenous complexes' catalysis including an analysis of their deactivation.

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The enantioselectivity in asymmetric ketone hydrogenation catalyzed by RuH₂(diphosphine)(diamine) complexes: insights from a 3D-QSSR and DFT study

Abstract: The 3D-QSSR method was carried out to investigate the enantioselectivity of the asymmetric ketone hydrogenation (AKH) catalyzed by RuH2(diphosphine)(diamine) complexes integrating with DFT method, which could provide a way to design homogeneous transition-metal catalysts.

Cited by 27 publications

References 77 publications

Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism

Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism

Regularized regression analysis of digitized molecular structures in organic reactions for quantification of steric effects

Chiral Catalyst Deactivation during the Asymmetric Hydrogenation of Acetophenone

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The enantioselectivity in asymmetric ketone hydrogenation catalyzed by RuH2(diphosphine)(diamine) complexes: insights from a 3D-QSSR and DFT study

Abstract: The 3D-QSSR method was carried out to investigate the enantioselectivity of the asymmetric ketone hydrogenation (AKH) catalyzed by RuH2(diphosphine)(diamine) complexes integrating with DFT method, which could provide a way to design homogeneous transition-metal catalysts.

Cited by 27 publications

References 77 publications

Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism

Iron(II)-Catalyzed Hydrogenation of Acetophenone with a Chiral, Pyridine-Based PNP Pincer Ligand: Support for an Outer-Sphere Mechanism

Regularized regression analysis of digitized molecular structures in organic reactions for quantification of steric effects

Chiral Catalyst Deactivation during the Asymmetric Hydrogenation of Acetophenone

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The enantioselectivity in asymmetric ketone hydrogenation catalyzed by RuH₂(diphosphine)(diamine) complexes: insights from a 3D-QSSR and DFT study