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Transition state analysis of enantioselective Brønsted base catalysis by chiral cyclopropenimines.

Bandar JS, Sauer GS, Wulff WD, Lambert TH, Vetticatt MJ - J. Am. Chem. Soc. (2014)

Bottom Line: Experimental (13)C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst.The reaction is found to proceed via rate-limiting carbon-carbon bond formation.The origins of enantioselectivity and a key noncovalent CH···O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027, United States.

ABSTRACT
Experimental (13)C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting carbon-carbon bond formation. The origins of enantioselectivity and a key noncovalent CH···O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies. The resulting high-resolution experimental picture of the enantioselectivity-determining transition state is expected to guide new catalyst design and reaction development.

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Transition structures leading to minor (R) enantiomerof product 4a that utilize monocoordinated binding modes 5a and 5b. Most hydrogen atoms have been removedfor clarity. All transition structures are oriented with the acrylatein the foreground and the enolate in the background.
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fig5: Transition structures leading to minor (R) enantiomerof product 4a that utilize monocoordinated binding modes 5a and 5b. Most hydrogen atoms have been removedfor clarity. All transition structures are oriented with the acrylatein the foreground and the enolate in the background.

Mentions: Shown in Figure 4 (S transitionstructures) and Figure 5 (R transition structures) are the eight transition structures correspondingto the eight geometries shown in Figure 3 formonocoordinated binding modes 5a and 5b.Two features are common to all eight transition structures namely(1) strong H-bonding interactions between both reactants(2 and 3a) and the two H-bond donors inthe catalyst, and (2) an s-cis conformation of 3a.16 The lowest energy transitionstructures leading to each enantiomer, TS5bSE (Erel = 0.0 kcal/mol, Figure 4) and TS5aRZ (Erel = 1.7 kcal/mol, Figure 5), are highlightedusing green and red boxes, respectively. This energy difference (1.7kcal/mol) corresponds to a predicted 89% ee. Consideration of a contributingsecond transition structure leading to the major enantiomer (TS5aSE, Erel = 0.9 kcal/mol; whichis still lower in energy than TS5aRZ by 0.8 kcal/mol)gives an altered prediction of 92% ee. This is in good agreement withthe experimental 98% ee.17


Transition state analysis of enantioselective Brønsted base catalysis by chiral cyclopropenimines.

Bandar JS, Sauer GS, Wulff WD, Lambert TH, Vetticatt MJ - J. Am. Chem. Soc. (2014)

Transition structures leading to minor (R) enantiomerof product 4a that utilize monocoordinated binding modes 5a and 5b. Most hydrogen atoms have been removedfor clarity. All transition structures are oriented with the acrylatein the foreground and the enolate in the background.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230825&req=5

fig5: Transition structures leading to minor (R) enantiomerof product 4a that utilize monocoordinated binding modes 5a and 5b. Most hydrogen atoms have been removedfor clarity. All transition structures are oriented with the acrylatein the foreground and the enolate in the background.
Mentions: Shown in Figure 4 (S transitionstructures) and Figure 5 (R transition structures) are the eight transition structures correspondingto the eight geometries shown in Figure 3 formonocoordinated binding modes 5a and 5b.Two features are common to all eight transition structures namely(1) strong H-bonding interactions between both reactants(2 and 3a) and the two H-bond donors inthe catalyst, and (2) an s-cis conformation of 3a.16 The lowest energy transitionstructures leading to each enantiomer, TS5bSE (Erel = 0.0 kcal/mol, Figure 4) and TS5aRZ (Erel = 1.7 kcal/mol, Figure 5), are highlightedusing green and red boxes, respectively. This energy difference (1.7kcal/mol) corresponds to a predicted 89% ee. Consideration of a contributingsecond transition structure leading to the major enantiomer (TS5aSE, Erel = 0.9 kcal/mol; whichis still lower in energy than TS5aRZ by 0.8 kcal/mol)gives an altered prediction of 92% ee. This is in good agreement withthe experimental 98% ee.17

Bottom Line: Experimental (13)C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst.The reaction is found to proceed via rate-limiting carbon-carbon bond formation.The origins of enantioselectivity and a key noncovalent CH···O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, Columbia University , 3000 Broadway, New York, New York 10027, United States.

ABSTRACT
Experimental (13)C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting carbon-carbon bond formation. The origins of enantioselectivity and a key noncovalent CH···O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies. The resulting high-resolution experimental picture of the enantioselectivity-determining transition state is expected to guide new catalyst design and reaction development.

Show MeSH
Related in: MedlinePlus