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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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Division oflayers for the ONIOM method used for initial explorationof transition structures.
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fig2: Division oflayers for the ONIOM method used for initial explorationof transition structures.

Mentions: A detailed investigation of the catalyst geometry revealed a preferencefor a conformation wherein the cyclohexyl rings are geared in thesame direction and the hydrogen atom at the chiral center is orientedanti to the NH proton (the H–C–N–H dihedral angleis −146°; B3LYP/6-31+G**).11 The next step in the study was the identification of carbon–carbonbond forming transition structures leading to the major and minorenantiomers of product 4a and the theoretical predictionof enantioselectivity. Owing to the large size of the system, initialexplorations of transition structures were performed using the hybridONIOM12 (B3LYP/6-31+G**:AM1) method asimplemented in Gaussian 09.13 The ONIOMmethod treats the key bond-forming and H-bonding portions of the transitionstate using the high-level DFT method (B3LYP/6-31+G**) and the stericbulk of the catalyst and reactants using the semiempirical method(AM1). The division of layers for the ONIOM calculations is shownin Figure 2. The time efficiency of the ONIOMmethod allowed us to explore a range of transition structures, includingthose involving higher energy catalyst conformations, those involvingdifferent H-bonding scenarios, and those lacking multiple H-bondinginteractions. The summary of the results from the ONIOM study is presentedin the Supporting Information.


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)

Division oflayers for the ONIOM method used for initial explorationof transition structures.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Division oflayers for the ONIOM method used for initial explorationof transition structures.
Mentions: A detailed investigation of the catalyst geometry revealed a preferencefor a conformation wherein the cyclohexyl rings are geared in thesame direction and the hydrogen atom at the chiral center is orientedanti to the NH proton (the H–C–N–H dihedral angleis −146°; B3LYP/6-31+G**).11 The next step in the study was the identification of carbon–carbonbond forming transition structures leading to the major and minorenantiomers of product 4a and the theoretical predictionof enantioselectivity. Owing to the large size of the system, initialexplorations of transition structures were performed using the hybridONIOM12 (B3LYP/6-31+G**:AM1) method asimplemented in Gaussian 09.13 The ONIOMmethod treats the key bond-forming and H-bonding portions of the transitionstate using the high-level DFT method (B3LYP/6-31+G**) and the stericbulk of the catalyst and reactants using the semiempirical method(AM1). The division of layers for the ONIOM calculations is shownin Figure 2. The time efficiency of the ONIOMmethod allowed us to explore a range of transition structures, includingthose involving higher energy catalyst conformations, those involvingdifferent H-bonding scenarios, and those lacking multiple H-bondinginteractions. The summary of the results from the ONIOM study is presentedin the Supporting Information.

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