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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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Possible binding modes of the catalyst–enolatecomplex 5.
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fig3: Possible binding modes of the catalyst–enolatecomplex 5.

Mentions: The exploratory ONIOM study led to the identification ofa subsetof viable transition structures arising from four distinct bindingmodes (5a–d, Figure 3) of the catalyst–enolate complex 5. Asimple template that can be used to describe these “most likely”transition state assemblies is shown in Figure 3. After initial deprotonation of 2 by 1, the resulting catalyst-bound enolate 5 can adopt eitherthe E or Z geometry. In monocoordinatedbinding mode 5a, the enolate is held by a single H-bondinginteraction between the hydroxyl group on the catalyst and the enolateoxygen. The NH moiety of protonated 1 presumably directs 3a for conjugate attack by H-bonding to the oxygen atom of 3a at the transition state. Four possible orientations ofbinding mode 5a that allow for this combination of H-bondinginteractions are shown in Figure 3. They arelabeled 5aRE, 5aRZ, 5aSE, and 5aSZ based on the binding mode 5a, the enantiomerof product formed (R or S), and the enolategeometry (E or Z). A similar (and complementary)situation arises when the enolate oxygen is H-bonded to the NH moietyof catalyst 1—binding mode 5b. Inthis monocoordinated binding mode, the enolate can once again adopteither a E or Z conformation andthe hydroxyl group directs 3a for conjugate attack viaH-bonding to the oxygen atom. Four additional conformations, 5bRE, 5bRZ, 5bSE, and 5bSZ, can be envisioned from binding mode 5b.


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)

Possible binding modes of the catalyst–enolatecomplex 5.
© Copyright Policy
Related In: Results  -  Collection

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

fig3: Possible binding modes of the catalyst–enolatecomplex 5.
Mentions: The exploratory ONIOM study led to the identification ofa subsetof viable transition structures arising from four distinct bindingmodes (5a–d, Figure 3) of the catalyst–enolate complex 5. Asimple template that can be used to describe these “most likely”transition state assemblies is shown in Figure 3. After initial deprotonation of 2 by 1, the resulting catalyst-bound enolate 5 can adopt eitherthe E or Z geometry. In monocoordinatedbinding mode 5a, the enolate is held by a single H-bondinginteraction between the hydroxyl group on the catalyst and the enolateoxygen. The NH moiety of protonated 1 presumably directs 3a for conjugate attack by H-bonding to the oxygen atom of 3a at the transition state. Four possible orientations ofbinding mode 5a that allow for this combination of H-bondinginteractions are shown in Figure 3. They arelabeled 5aRE, 5aRZ, 5aSE, and 5aSZ based on the binding mode 5a, the enantiomerof product formed (R or S), and the enolategeometry (E or Z). A similar (and complementary)situation arises when the enolate oxygen is H-bonded to the NH moietyof catalyst 1—binding mode 5b. Inthis monocoordinated binding mode, the enolate can once again adopteither a E or Z conformation andthe hydroxyl group directs 3a for conjugate attack viaH-bonding to the oxygen atom. Four additional conformations, 5bRE, 5bRZ, 5bSE, and 5bSZ, can be envisioned from binding mode 5b.

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