Unraveling the Mechanism of the Cinchoninium Ion Asymmetric Phase-Transfer-Catalyzed Alkylation Reaction

Martins, Ernane de Freitas; Pliego, Josefredo R.

doi:10.1021/cs400021r

Cited by 40 publications

(16 citation statements)

References 47 publications

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“…Phase-selective sampling has been achieved by carefully aliquoting a stirred solution and then allowing the immiscible solvents to separate to enable manual sampling from the desired phase. − Given that mass transfer between heterogeneous liquids governs the rate of many phase-transfer reactions, arresting agitation may provide a means to “pause” the reaction and allow for sampling. While this approach can facilitate reaction time course analysis, the data acquired may not be reflective of the operational catalytic system under continuous agitation.…”

Section: Introductionmentioning

confidence: 99%

Using an Automated Monitoring Platform for Investigations of Biphasic Reactions

et al. 2019

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Insights and mechanistic studies into biphasic reactions are often challenging due to difficulty in deploying in situ reaction-monitoring or sampling procedures. Herein, we describe the development and application of an automated monitoring platform capable of delineating time course reaction progress of biphasic reactions. The system was applied toward a case study of an enantioselective biphasic spirocyclization catalyzed by a doubly quaternized cinchona alkaloid. A combination of heterogeneous and phase-selective sampling, coupled with high-performance liquid chromatography–mass spectrometry (HPLC–MS), allowed for the detection, quantification, and identification of reactive species in either the heterogeneous liquid–liquid mixture or isolated organic phase throughout the reaction. The data gathered using this method allowed for valuable insight into catalyst phase-transfer behavior, elucidation of catalyst decomposition pathways, and the determination of rate laws governing the reaction. This method is adaptable and will provide a robust means for the investigation of biphasic reactions.

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Section: Introductionmentioning

confidence: 99%

Using an Automated Monitoring Platform for Investigations of Biphasic Reactions

et al. 2019

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“…The quinuclidine moiety is able to activate a nucleophile, and the hydroxyl group can activate an electrophile or assist in the orientation of the substrates via hydrogen bonding. Despite the large number of mechanistic studies by means of nuclear magnetic resonance (NMR), reaction kinetics, and computational techniques, the understanding of the overall mechanisms of Cinchona alkaloid-catalyzed reactions remains limited. ,,− In particular, experimental observation of the reaction intermediates is challenging because of the transient and noncovalent nature of the interactions between the catalyst and the substrates.…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic Study of a Cinchona Alkaloid-Catalyzed Henry Reaction

2018

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A spectroscopic study of an organocatalytic Henry reaction between nitroalkanes and aldehydes catalyzed by a quinidine-derived Cinchona alkaloid is described. The binding modes of the reaction substrates are investigated using electronic absorption and fluorescence spectroscopy and further corroborated by nuclear magnetic resonance measurements. Aldehydes are shown to associate with both the 6′-OH group and the basic quinuclidine nitrogen of the catalyst, whereas nitroalkanes do not exhibit a clear binding mode. Reaction progress kinetic analysis reveals that the reaction is first-order in both of the substrates and the catalyst. Second, the reaction proceeds approximately five times faster in the excess of the nitroalkanes than in the excess of the aldehydes, suggesting that binding of the aldehydes results in the inhibition of the catalyst. Aldehydes deactivate the basic quinuclidine site, thus suppressing the deprotonation of the nitroalkanes which is the proposed initial step in the reaction cycle.

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“…The use of multiple hydrogen bonds to stabilize the anion‐molecule S N 2 transition state (Scheme ) has been envisioned and computationally supported as a promising strategy in supramolecular catalysis . An a posteriori theoretical study of a classical asymmetric phase‐transfer catalyzed process has found this kind of mechanism is operating . In this point, it is important to mention that this kind of activation has not been fully appreciated and its potential use remains poorly explored.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of nucleophilic fluorination promoted by bis‐tert‐alcohol‐functionalized crown‐6‐calix[4]arene

Pliego

2018

Int J of Quantum Chemistry

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Theoretical calculations were performed to elucidate the ability of the recently reported bis-tertalcohol-functionalized crown-6-calix[4]arene (BACCA) molecule to promote nucleophilic fluorination of alkyl mesylates with cesium fluoride reagent. It was found that a similar structure, named BACCAt, can separate the cesium fluoride ion pair in tert-butanol solution. This separation has a free energy cost, even considering the double hydrogen bonds with the fluoride ion. The solvent has an important effect on the stabilization of this complex, due to interaction with the high dipole moment of the separated ion pair. The observed rate acceleration effect involves a structure with double hydrogen bonds between the BACCAt and the centers of negative charges of the S N 2 transition state. The predicted free energy barrier of 27.3 kcal mol 21 is in excellent agreement with the estimated experimental value of 26.2 kcal mol 21 . K E Y W O R D S cation-binding catalysis, nucleophilic fluorination, phase-transfer catalysis, solvent effect, supramolecular catalysis

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Unraveling the Mechanism of the Cinchoninium Ion Asymmetric Phase-Transfer-Catalyzed Alkylation Reaction

Cited by 40 publications

References 47 publications

Using an Automated Monitoring Platform for Investigations of Biphasic Reactions

Using an Automated Monitoring Platform for Investigations of Biphasic Reactions

Spectroscopic Study of a Cinchona Alkaloid-Catalyzed Henry Reaction

Mechanism of nucleophilic fluorination promoted by bis‐tert‐alcohol‐functionalized crown‐6‐calix[4]arene

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