Density Functional Theory Study of the <i>Cinchona</i> Thiourea‐ Catalyzed Henry Reaction: Mechanism and Enantioselectivity

Hammar, Peter; Marcelli, Tommaso; Hiemstra, Henk; Himo, Fahmi

doi:10.1002/adsc.200700367

Cited by 100 publications

(76 citation statements)

References 49 publications

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“…The resulting protonated amino group together with the thiourea moiety can then bind the ketoenolate and activate the imine electrophile. Two pre-transition-state models of different reactant arrangements derived from theoretical investigations have been proposed in the literature (Figure 3)31323334353637383940. Our initial efforts were thus focused on the identification of the pre-transition-state complex between the substrate and catalyst.…”

Section: Resultsmentioning

confidence: 99%

Kinetic Evidence of an Apparent Negative Activation Enthalpy in an Organocatalytic Process

Xiao

Lee

Chen

et al. 2013

Sci Rep

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A combined kinetic and computational study on our tryptophan-based bifunctional thiourea catalyzed asymmetric Mannich reactions reveals an apparent negative activation enthalpy. The formation of the pre-transition state complex has been unambiguously confirmed and these observations provide an experimental support for the formation of multiple hydrogen bonding network between the substrates and the catalyst. Such interactions allow the creation of a binding cavity, a key factor to install high enantioselectivity.

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Section: Resultsmentioning

confidence: 99%

Kinetic Evidence of an Apparent Negative Activation Enthalpy in an Organocatalytic Process

Xiao

Lee

Chen

et al. 2013

Sci Rep

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“…However, in line with the pragmatic aim claimed above, the discussion will be focused on how the SIE affects DFT calculations at the level of theory commonly used for constructing potential energy surfaces, and exploring chemical reactivity in the type of systems indicated by the title. 30,31 Therefore, since all results rely on the basic gas phase calculations, the main part of the present investigation of SIE effects is carried out for gas phase results. Optimized values of the most important structural and electronic parameters are given in Table II. vestigations, geometries are optimized at a double-Z level in gas phase.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the effects of the self-interaction error in density functional theory: When do the delocalized states appear? II. Iron-oxo complexes and closed-shell substrate molecules

Johansson

Blomberg

Siegbahn

2008

The Journal of Chemical Physics

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Effects of the self-interaction error (SIE) in approximate density functional theory have several times been reported and quantified for the dissociation of charged radicals, charge transfer complexes, polarizabilities, and for transition states of reactions involving main-group molecules. In the present contribution, effects of the SIE in systems composed of a catalytic transition metal complex and a closed-shell substrate molecule are investigated. For this type of system, effects of the SIE have not been reported earlier. It is found that although the best density functionals (e.g., B3LYP) are capable of accurate predictions of structure, thermodynamics, and reactivity of such systems, there are situations and systems for which the magnitude of the SIE can be large, and for which the effects can be severe for the modeling of chemical reactivity. The largest energetic effect reported here is the artificial stabilization of a catalyst-substrate complex by as much as 18 kcal/mol. Also, the disappearance of significant energy barriers for hydrogen atom transfer in certain systems are reported. In line with earlier work, it is found that the magnitude of the SIE is related to the energetics of electron transfer between the metal catalyst and the substrate molecule. It is suggested that these problems might be circumvented by the inclusion of counterions or point charges that would alter the energetics of electron transfer. It is also pointed out that the effects of SIE in the modeling of transition metal reactivity need to be investigated further.

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“…The pyridyl substituent offers the possibility of protonation at the pyridine N; behavior analogous to the bifunctional role of thiourea derivatives recently studied by computational methods. [31,35,36] The corresponding TSC3 certainly has the thiourea in the tautomeric form ( Figure 5), and the energy of 17.4 kcal mol À1 with respect to reactants is lower than that of TSB3. The route via TSC3 is, however, still unable to compete with the rate-limiting energy in the absence of thiourea, which was 16.7 kcal mol À1 .…”

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confidence: 97%

Brønsted Acid Catalyzed Morita–Baylis–Hillman Reaction: A New Mechanistic View for Thioureas Revealed by ESI‐MS(/MS) Monitoring and DFT Calculations

Amarante

Benassi

Milagre

et al. 2009

Chemistry A European J

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A Morita-Baylis-Hillman (MBH) reaction catalyzed by thiourea was monitored by ESI-MS(/MS) and key intermediates were intercepted and characterized. These intermediates suggest that thiourea acts as an organocatalyst in all steps of the MBH reaction cycle, including the rate-limiting proton-transfer step. DFT calculations, performed for a model MBH reaction between formaldehyde and acrolein with trimethylamine as base and in the presence or the absence of thiourea, suggest that thiourea accelerates MBH reactions by decreasing the transition-state (TS) energies through bidentate hydrogen bonding throughout the whole catalytic cycle. In the rate-limiting proton-transfer step, the thiourea acts not as a proton shuttle, but as a Brønsted acid stabilizing the basic oxygen center that is formed in the TS.

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Density Functional Theory Study of the Cinchona Thiourea‐ Catalyzed Henry Reaction: Mechanism and Enantioselectivity

Cited by 100 publications

References 49 publications

Kinetic Evidence of an Apparent Negative Activation Enthalpy in an Organocatalytic Process

Kinetic Evidence of an Apparent Negative Activation Enthalpy in an Organocatalytic Process

Quantifying the effects of the self-interaction error in density functional theory: When do the delocalized states appear? II. Iron-oxo complexes and closed-shell substrate molecules

Brønsted Acid Catalyzed Morita–Baylis–Hillman Reaction: A New Mechanistic View for Thioureas Revealed by ESI‐MS(/MS) Monitoring and DFT Calculations

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