Computing organic stereoselectivity – from concepts to quantitative calculations and predictions

Peng, Qian; Duarte, Fernanda; Paton, Robert S.

doi:10.1039/c6cs00573j

Cited by 210 publications

(185 citation statements)

References 48 publications

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“…52 We found structural differences in the metal π–coordination for these ligands, with Rh12 and Rh22 showing larger variation than Rh1 in the five Rh-C distances associated with the Rh-Cp interaction. These coordination modes thus have greater (η 3 + η 2 ) character than (η 5 ) Rh1 .…”

Section: Resultsmentioning

confidence: 72%

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study

et al. 2017

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CpXRh(III)-catalyzed C-H functionalization reactions are a proven method for the efficient assembly of small molecules. However, rationalization of the effects of cyclopentadienyl (CpX) ligand structure on reaction rate and selectivity has been viewed as a black box, and a truly systematic study is lacking. Consequently, predicting the outcomes of these reactions is challenging because subtle variations in ligand structure can cause notable changes in reaction behavior. A predictive tool is, nonetheless, of considerable value to the community as it would greatly accelerate reaction development. Designing a data set in which the steric and electronic properties of the CpXRh(III) catalysts were systematically varied allowed us to apply multivariate linear regression algorithms to establish correlations between these catalyst-based descriptors and the regio-, diastereoselectivity, and rate of model reactions. This, in turn, led to the development of quantitative predictive models that describe catalyst performance. Our newly-described cone angles and Sterimol parameters for CpX ligands served as highly correlative steric descriptors in the regression models. Through rational design of training and validation sets, key diastereoselectivity outliers were identified. Computations reveal the origins of the outstanding stereoinduction displayed by these outliers. The results are consistent with partial η5−η3 ligand slippage that occurs in the transition state of the selectivity-determining step. In addition to the instructive value of our study, we believe that the insights gained are transposable to other Group 9 transition metals and pave the way toward rational design of C-H functionalization catalysts.

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Section: Resultsmentioning

confidence: 72%

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study

et al. 2017

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“…To our best knowledge, however, very few systematic study of the role of crown ethers for promoting the S N 2 reactions was carried out either experimentally or theoretically. Herein, we pose the following question: Do crown ethers really “separate” the counter‐cation from the nucleophile, helping to form solvent‐separated ion pair(SSIP)?…”

Section: Introductionmentioning

confidence: 99%

Computational study of S_N2 reactions promoted by crown ether: Contact ion pair versus solvent‐separated ion pair mechanism

Lee

Jadhav

Kim

et al. 2017

Int J of Quantum Chemistry

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We examined by quantum chemical methods the mechanism of SN2 reaction using metal bromide MBr (M = Na, K, Cs) and KX (X= F, Cl) in CH3CN promoted by crown ether (18‐crown‐6). We focus on whether the metal salts react as a contact ion pair (CIP; M+ and X– in close contact) or as a solvent‐separated ion pair (SSIP; M+ and X– at large distance). In SSIP mechanism, X– is removed far enough from M+ for the metal salt to be considered as “separated” by the effects of the crown ether and the solvent. In the CIP picture, conversely, the coordination of 18‐crown‐6 to M+ is not sufficient to overcome the powerful Coulombic interactions between M+ and X–. We find that the CIP route is favored for SN2 bromination processes using MBr (M = Na, K, Cs). For SN2 reaction using KF, the feasibility of the two pathways is essentially equal, whereas for SN2 chlorination by KCl the SSIP route is predicted to be favored.

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“…The results provide insight into the origin of enantioselectivity in asymmetric aldol reaction catalyzed by homoboroproline.[a] H. Dulger, Prof. S. S. Erdem differences in Gibbs free energies of the TSs of selectivitydetermining steps. [24]…”

mentioning

confidence: 99%

“…[a] H. Dulger, Prof. S. S. Erdem differences in Gibbs free energies of the TSs of selectivitydetermining steps. [24]…”

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confidence: 99%

Computational Insight Into the Enantioselectivity of Homoboroproline Catalyzed Asymmetric Aldol Reaction

et al. 2019

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Chiral amino boronic acids and their derivatives have a wide range of applications including enzyme inhibitors, anti‐cancer agents and molecular sensors. They also draw attention as effective catalysts. Recently, a new proline based amino boronic acid derivative, homoboroproline, was synthesized and demonstrated to be an efficient catalyst in an asymmetric aldol reaction. The reaction mechanism has been elucidated in the present study for the first time. Considering different orientations of the enamine intermediate and the aldehyde, potential alternative mechanisms were modeled with density functional theory (DFT) calculations via PCM/M06‐2X/6‐31G(d,p) method in acetone. The potential energy surface of each mechanism was explored to establish the rate‐determining and enantioselectivity‐determining steps. The calculated enantiomeric excess values (>99%) were found to be in agreement with the experimental values (93%, 95%). The detailed investigation of the transition state structures of the selectivity‐determining step has revealed that attractive interactions between boron and aldehyde oxygen are responsible for the selectivity confirmed by natural bond orbital (NBO) analysis. The results provide insight into the origin of enantioselectivity in asymmetric aldol reaction catalyzed by homoboroproline.

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Computing organic stereoselectivity – from concepts to quantitative calculations and predictions

Cited by 210 publications

References 48 publications

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study

Computational study of S_N2 reactions promoted by crown ether: Contact ion pair versus solvent‐separated ion pair mechanism

Computational Insight Into the Enantioselectivity of Homoboroproline Catalyzed Asymmetric Aldol Reaction

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Computing organic stereoselectivity – from concepts to quantitative calculations and predictions

Cited by 210 publications

References 48 publications

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study

Correlating Reactivity and Selectivity to Cyclopentadienyl Ligand Properties in Rh(III)-Catalyzed C–H Activation Reactions: An Experimental and Computational Study

Computational study of SN2 reactions promoted by crown ether: Contact ion pair versus solvent‐separated ion pair mechanism

Computational Insight Into the Enantioselectivity of Homoboroproline Catalyzed Asymmetric Aldol Reaction

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Computational study of S_N2 reactions promoted by crown ether: Contact ion pair versus solvent‐separated ion pair mechanism