Limits...
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.

Show MeSH
Mannich reaction of fluorinated ketoester and imine.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3757351&req=5

f1: Mannich reaction of fluorinated ketoester and imine.

Mentions: We recently demonstrated that tryptophan-based bifunctional thiourea derivatives are capable of efficiently promoting the asymmetric Mannich reaction of fluorinated ketoesters to afford highly optically enriched fluorine-containing molecules with adjacent quaternary and tertiary stereocenters (Figure 1)24. High enantioselectivity and diastereoselectivity were observed with a wide range of aromatic and heteroaromatic ketoesters with an optimal bifunctional thiourea-based organocatalyst. Preliminary computational studies also suggested the involvement of a “pre-transition-state complex” with multiple hydrogen bonding interactions, and in turn could be responsible for the excellent stereochemical control. In a bid to further deepen our mechanistic understanding of such a catalytic system, we attempted kinetic studies in which experimental data revealed an uncommon apparent negative activation enthalpy. Even though there is precedence of experimentally observed negative activation enthalpy in reactions2526272829, the phenomenon in organocatalytic systems is nascent revealing insightful chemical behavior. Concomitant computational studies supported experimental findings and from a theoretical viewpoint we were able to elucidate the origin of the stereochemical outcome and to deduce that the observed apparent negative activation enthalpy arose from a highly extensive and favorable H-bonding effect.


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)

Mannich reaction of fluorinated ketoester and imine.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Mannich reaction of fluorinated ketoester and imine.
Mentions: We recently demonstrated that tryptophan-based bifunctional thiourea derivatives are capable of efficiently promoting the asymmetric Mannich reaction of fluorinated ketoesters to afford highly optically enriched fluorine-containing molecules with adjacent quaternary and tertiary stereocenters (Figure 1)24. High enantioselectivity and diastereoselectivity were observed with a wide range of aromatic and heteroaromatic ketoesters with an optimal bifunctional thiourea-based organocatalyst. Preliminary computational studies also suggested the involvement of a “pre-transition-state complex” with multiple hydrogen bonding interactions, and in turn could be responsible for the excellent stereochemical control. In a bid to further deepen our mechanistic understanding of such a catalytic system, we attempted kinetic studies in which experimental data revealed an uncommon apparent negative activation enthalpy. Even though there is precedence of experimentally observed negative activation enthalpy in reactions2526272829, the phenomenon in organocatalytic systems is nascent revealing insightful chemical behavior. Concomitant computational studies supported experimental findings and from a theoretical viewpoint we were able to elucidate the origin of the stereochemical outcome and to deduce that the observed apparent negative activation enthalpy arose from a highly extensive and favorable H-bonding effect.

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