Secondary Deuterium Isotope Effects on Reactions Proceeding Through Carbocations

Sunko, Dionis E.; Hehre, Warren J.

doi:10.1002/9780470171936.ch5

Cited by 25 publications

(11 citation statements)

References 62 publications

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“…The observed effect on k cat establishes that chemistry is significantly rate determining for the enzyme. Moreover, the magnitude of the isotope effect is consistent with considerable C−H bond cleavage in the transition state (Scheme b or 1d), but would be unprecedentedly large for a β-secondary effect in an ion pair mechanism (Scheme c) . The somewhat smaller isotope effect observed on k cat / K m indicates a significant forward commitment to catalysis for IPL …”

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confidence: 66%

“…Moreover, the magnitude of the isotope effect is consistent with considerable C-H bond cleavage in the transition state (Scheme 1b or 1d), but would be unprecedentedly large for a β-secondary effect in an ion pair mechanism (Scheme 1c). 11 The somewhat smaller isotope effect observed on k cat /K m indicates a significant forward commitment to catalysis for IPL. 12 The fate of the deuterium atom at C2 was determined directly by 2 H NMR spectroscopy.…”

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confidence: 93%

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Isochorismate Pyruvate Lyase: A Pericyclic Reaction Mechanism?

et al. 2005

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Isochorismate pyruvate lyase (IPL) catalyzes the cleavage of isochorismate to give salicylate and pyruvate, a key step in bacterial siderophore biosynthesis. We investigated the enzyme from Pseudomonas aeruginosa using isochorismate selectively deuterated at C2 as a substrate. Monitoring the reaction by 2H NMR spectroscopy revealed that the label is quantitatively transferred from C2 to C9, producing stoichiometric amounts of [3-2H]pyruvate as product. Moreover, the deuterium kinetic isotope effect of 2.34 +/- 0.08 on kcat indicates that C-H cleavage is significantly rate limiting. Consistent with these data, hybrid density functional theory (HDFT) calculations at the Becke3LYP/DZ+(2d,p) level of theory predict a concerted but highly asynchronous pericyclic transition structure, in which carbon-oxygen bond cleavage is more advanced than hydrogen atom transfer from C2 to C9; the calculated 2H isotope effect of 2.22 at C2 is in excellent accord with the experimental value. Together, these findings indicate that IPL should be added to the small set of proteins that are known to catalyze pericyclic reactions. They also raise the possibility that enzymes, such as chorismate pyruvate lyase, salicylate synthase, 4-amino-4-deoxychorismate lyase, and anthranilate synthase, which accelerate formally similar reaction steps, may also exploit pericyclic mechanisms.

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confidence: 66%

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confidence: 93%

Isochorismate Pyruvate Lyase: A Pericyclic Reaction Mechanism?

et al. 2005

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“…While, it is too small to represent a primary kinetic isotope effect, the observed KIE is notably higher than k H / k D = 1.00−1.04 as found by Singleton and Hang for a stepwise ene reaction. Also, hyperconjugation cannot explain a k H / k D = 1.17, though it is generally accepted as the major contributor to β-deuterium secondary kinetic isotope effects for reactions with radicaloid transition states and for equilibrium isotope effects involving radicals. 15b, To understand this discrepancy, we have analyzed the bona fide diradical C 2 −C 6 cyclization of 1 (R 1 = Ph, R 2 = R 3 = H) as described in a computational study by Engels ).…”

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confidence: 99%

Kinetic Isotope Effects in the Thermal C²−C⁶ Cyclization of Enyne-allenes: Experimental Evidence Supports a Stepwise Mechanism

Schmittel

Vavilala

2005

J. Org. Chem.

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“…As a result, a typical secondary KIE was observed since the k H / k D = 1.19 (see Supporting Information). It suggests that a carbocation intermediate should be involved in this reaction and the C−H bond cleavage is not the rate-determining step . With these results in hand, a plausible mechanism for this catalytic coupling reaction is depicted in Scheme .…”

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Iron-Catalyzed Stereospecific Olefin Synthesis by Direct Coupling of Alcohols and Alkenes with Alcohols

et al. 2011

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An efficient Fe(III)-catalyzed direct coupling of alkenes with alcohols and cross-coupling of alcohols with alcohols to give the corresponding substituted (E)-alkenes stereospecifically is demonstrated. Additionally, this reaction could be scaled up. The kinetic isotope effect (KIE) experiments indicated a typical secondary isotope effect in this process. Although benzylic alcohols were effective substrates, mild conditions, atom efficiency, environmental soundness, and stereospecificity are features that make this procedure very attractive.

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Secondary Deuterium Isotope Effects on Reactions Proceeding Through Carbocations

Cited by 25 publications

References 62 publications

Isochorismate Pyruvate Lyase: A Pericyclic Reaction Mechanism?

Isochorismate Pyruvate Lyase: A Pericyclic Reaction Mechanism?

Kinetic Isotope Effects in the Thermal C²−C⁶ Cyclization of Enyne-allenes: Experimental Evidence Supports a Stepwise Mechanism

Iron-Catalyzed Stereospecific Olefin Synthesis by Direct Coupling of Alcohols and Alkenes with Alcohols

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Secondary Deuterium Isotope Effects on Reactions Proceeding Through Carbocations

Cited by 25 publications

References 62 publications

Isochorismate Pyruvate Lyase: A Pericyclic Reaction Mechanism?

Isochorismate Pyruvate Lyase: A Pericyclic Reaction Mechanism?

Kinetic Isotope Effects in the Thermal C2−C6 Cyclization of Enyne-allenes: Experimental Evidence Supports a Stepwise Mechanism

Iron-Catalyzed Stereospecific Olefin Synthesis by Direct Coupling of Alcohols and Alkenes with Alcohols

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Kinetic Isotope Effects in the Thermal C²−C⁶ Cyclization of Enyne-allenes: Experimental Evidence Supports a Stepwise Mechanism