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Kinetic evidence of an apparent negative activation enthalpy in an organocatalytic process.

Han X, Lee R, Chen T, Luo J, Lu Y, Huang KW - Sci Rep (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: KAUST Catalysis Center and Division of Physical Science and Engineering, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.

ABSTRACT
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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Proposed models for catalyst-substrate complex.
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f3: Proposed models for catalyst-substrate complex.

Mentions: This reaction was modeled with DFT calculations to elucidate the observed enantioselectivity and to appraise the energetics. It is well-accepted that the pendent amine on the catalyst can first act as a base to assist the formation of the ketoenolate from the β-ketoester substrate. 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. Hydrogen bonding is believed to be the keystone interaction for the binding of catalyst and substrates leading to a spatially preferred conformation dictated by the catalyst, a phenomenon that is a reminiscence of enzyme-substrate(s) complexation in biological systems.


Kinetic evidence of an apparent negative activation enthalpy in an organocatalytic process.

Han X, Lee R, Chen T, Luo J, Lu Y, Huang KW - Sci Rep (2013)

Proposed models for catalyst-substrate complex.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757351&req=5

f3: Proposed models for catalyst-substrate complex.
Mentions: This reaction was modeled with DFT calculations to elucidate the observed enantioselectivity and to appraise the energetics. It is well-accepted that the pendent amine on the catalyst can first act as a base to assist the formation of the ketoenolate from the β-ketoester substrate. 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. Hydrogen bonding is believed to be the keystone interaction for the binding of catalyst and substrates leading to a spatially preferred conformation dictated by the catalyst, a phenomenon that is a reminiscence of enzyme-substrate(s) complexation in biological systems.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: KAUST Catalysis Center and Division of Physical Science and Engineering, King Abdullah University of Science and Technology, Thuwal, Kingdom of Saudi Arabia.

ABSTRACT
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.

Show MeSH