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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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Experimental 13C KIEs for reaction of 2 and 3b catalyzed by 1. The twosets ofKIEs for each carbon represent two independent experiments and thenumbers in parentheses represent the standard deviation in the lastdigit as determined from six measurements. KIEs for the bond-formingcarbon atoms are shown in red.
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fig1: Experimental 13C KIEs for reaction of 2 and 3b catalyzed by 1. The twosets ofKIEs for each carbon represent two independent experiments and thenumbers in parentheses represent the standard deviation in the lastdigit as determined from six measurements. KIEs for the bond-formingcarbon atoms are shown in red.

Mentions: We chose the reactionof the glycine imine 2 and benzyl acrylate 3b catalyzed by 1 for the measurement of 13C KIEs using NMR methodology at natural abundance.7 Complementary approaches were used for the determinationof 13C KIEs for the two reaction components 2 and 3b. The KIEs for 2 were determinedby analysis of product samples.8 Thus,the isotopic composition of 4b was measured from twoindependent experiments taken to 21 ± 2% and 22 ± 2% conversionin 2 and compared to samples of 4b isolatedfrom reactions taken to 100% conversion. The KIEs for 3b were determined by analysis of recovered starting material:9 samples of 3b were reisolated fromtwo independent experiments taken to 72 ± 2% and 74 ± 2%conversion (with respect to 3b) and were compared tosamples of unreacted 3b. The experimental KIEs calculatedfrom the change in 13C isotopic composition and the fractionalconversion are shown in Figure 1.10


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)

Experimental 13C KIEs for reaction of 2 and 3b catalyzed by 1. The twosets ofKIEs for each carbon represent two independent experiments and thenumbers in parentheses represent the standard deviation in the lastdigit as determined from six measurements. KIEs for the bond-formingcarbon atoms are shown in red.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4230825&req=5

fig1: Experimental 13C KIEs for reaction of 2 and 3b catalyzed by 1. The twosets ofKIEs for each carbon represent two independent experiments and thenumbers in parentheses represent the standard deviation in the lastdigit as determined from six measurements. KIEs for the bond-formingcarbon atoms are shown in red.
Mentions: We chose the reactionof the glycine imine 2 and benzyl acrylate 3b catalyzed by 1 for the measurement of 13C KIEs using NMR methodology at natural abundance.7 Complementary approaches were used for the determinationof 13C KIEs for the two reaction components 2 and 3b. The KIEs for 2 were determinedby analysis of product samples.8 Thus,the isotopic composition of 4b was measured from twoindependent experiments taken to 21 ± 2% and 22 ± 2% conversionin 2 and compared to samples of 4b isolatedfrom reactions taken to 100% conversion. The KIEs for 3b were determined by analysis of recovered starting material:9 samples of 3b were reisolated fromtwo independent experiments taken to 72 ± 2% and 74 ± 2%conversion (with respect to 3b) and were compared tosamples of unreacted 3b. The experimental KIEs calculatedfrom the change in 13C isotopic composition and the fractionalconversion are shown in Figure 1.10

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