Hydrophobic Amplification of Noncovalent Organocatalysis.

Kleiner, Christian M.; Schreiner, Peter R.

doi:10.1002/chin.200709041

Cited by 3 publications

(3 citation statements)

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“…For instance, reaction rates have beenrather counterintuitivelyshown to be enhanced in hydrogen-bonded water, which has been ascribed to 'hydrophobic hydration'. 2,15 Thus, to understand catalytic activity and to allow for a rational catalyst design, it is vital to understand solvation and study binding strength in solution.…”

Section: Introductionmentioning

confidence: 99%

CF3-groups critically enhance the binding of thiourea catalysts to ketones – a NMR and FT-IR study

Ehrhard

Jäger

Malm

et al. 2019

Journal of Molecular Liquids

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Substituted phenylthioureas have been established as efficient organocatalysts and substituents containing electron withdrawing CF 3 groups have been shown to enhance catalytic efficiency. The effect of the CF 3 groups on binding of catalysts to substrates in solution has however remained elusive. Here, we report on the effect of CF 3 substituted diphenylthioureas on the association with the substrate 1,3-diphenyl-2propenone in solution by using a combination of nuclear magnetic resonance (NMR) and Fourier-transform infrared (FT-IR) spectroscopy. We use the ensemble-averaged chemical shift of the thiourea proton as function of substrate concentration to determine the association constants between catalyst and substrate. To experimentally discriminate between free and bound catalyst we use infrared absorption spectra, which show a red-shift of thiourea's N-H stretching vibration upon association with the substrate. With both methods, we find the association constant K to increase from ~1 L/mol to ~20 L/mol with increasing number of CF 3 substituents. This enhanced binding can explain the increased reaction rates observed for CF 3 substituted diphenylthiourea catalysts. For the efficient catalyst containing four CF 3groups (Schreiner's catalyst), the strongest association is observed in toluene as a solvent, while the binding strength is somewhat weaker in dichloromethane, and association to the substrate is not detectable in acetonitrile. Our results thus demonstrate that even weak association between the thiourea catalysts and the ketone can facilitate efficient catalytic conversion. However, the association with the ketone substrates is very susceptible to competing interactions with the solvent.

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Section: Introductionmentioning

confidence: 99%

CF3-groups critically enhance the binding of thiourea catalysts to ketones – a NMR and FT-IR study

Ehrhard

Jäger

Malm

et al. 2019

Journal of Molecular Liquids

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“…An alternative possibility, also consistent with the structural evidence, is that the activation energy of the chemical reaction of making the covalent bond with the ( R )‐GOP reactant is higher than for the ( S )‐GOP reactant for stereoelectronic reasons. The ring opening of the epoxide is subject to general acid catalysis 24, 25. The complexed active site is very tight,12, 17 suggesting that there will not be a major conformational rearrangement of the suicide inhibitor on ring opening.…”

Section: Resultsmentioning

confidence: 99%

High resolution crystal structures of triosephosphate isomerase complexed with its suicide inhibitors: The conformational flexibility of the catalytic glutamate in its closed, liganded active site

et al. 2011

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The key residue of the active site of triosephosphate isomerase (TIM) is the catalytic glutamate, which is proposed to be important (i) as a catalytic base, for initiating the reaction, as well as (ii) for the subsequent proton shuttling steps. The structural properties of this glutamate in the liganded complex have been investigated by studying the high resolution crystal structures of typanosomal TIM, complexed with three suicide inhibitors: (S)-glycidol phosphate ((S)-GOP, at 0.99 Å resolution), (R)-glycidol phosphate, ((R)-GOP, at 1.08 Å resolution), and bromohydroxyacetone phosphate (BHAP, at 1.97 Å resolution). The structures show that in the (S)-GOP active site this catalytic glutamate is in the well characterized, competent conformation. However, an unusual side chain conformation is observed in the (R)-GOP and BHAP complexes. In addition, Glu97, salt bridged to the catalytic lysine in the competent active site, adopts an unusual side chain conformation in these two latter complexes. The higher chemical reactivity of (S)-GOP compared with (R)-GOP, as known from solution studies, can be understood: the structures indicate that in the case of (S)-GOP, Glu167 can attack the terminal carbon of the epoxide in a stereoelectronically favored, nearly linear OACAO arrangement, but this is not possible for the (R)-GOP isomer. These structures confirm the previously proposed conformational flexibility of the catalytic glutamate in its closed, liganded state. The importance of this conformational flexibility for the proton shuttling steps in the TIM catalytic cycle, which is apparently achieved by a sliding motion of the side chain carboxylate group above the enediolate plane, is also discussed.

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“…Inzwischen sind wir in der Lage, eine Reihe weiterer synthetisch wertvoller Reaktionen mit diesen kleinen, organischen Molekülen zu beschleunigen oder überhaupt erst möglich zu machen (Taylor/Jacobsen 2006). Hierzu zählen zum Beispiel die Schützung von Carbonylgruppen als Acetale, Epoxidöffnungen mit Aminen in Wasser, die Transferhydrierung sowie die Schützung von Alkoholen als THP-Ether (Kotke/Schreiner 2006und 2007Kleiner/Schreiner 2006;Zhang/Schreiner 2007). Dieses katalytische Konzept wird nunmehr weltweit untersucht und zur Beschleunigung einer Vielzahl von Reaktionen angewandt.…”

Section: Organokatalyse Als Ressourcenschonende Alternativeunclassified

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Kleiner¹,

Schreiner²

2007

ÖW

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Hydrophobic Amplification of Noncovalent Organocatalysis.

Cited by 3 publications

References 1 publication

CF3-groups critically enhance the binding of thiourea catalysts to ketones – a NMR and FT-IR study

CF3-groups critically enhance the binding of thiourea catalysts to ketones – a NMR and FT-IR study

High resolution crystal structures of triosephosphate isomerase complexed with its suicide inhibitors: The conformational flexibility of the catalytic glutamate in its closed, liganded active site

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