Thermodynamic and kinetic secondary isotope effects in the Cope rearrangement

Sunko, Dionis E.; Humski, K.; Malojcic, Rajko; Borčić, S.

doi:10.1021/ja00725a026

Cited by 53 publications

(10 citation statements)

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“…The allyl radical pathway via 1AL seemed with 59.7 kcal mol −1 too endothermic to be competitive for the parent system. Furthermore, no crossover products that would argue for two free allyl radicals had been found 38. The evidence for a concerted pathway in the parent Cope reaction seemed to be clear and the occurrence of a biradical in the Cope reaction as a function of substitutents remained challenging.…”

Section: Historical Survey Of the Cope Rearrangementmentioning

confidence: 99%

The Cope rearrangement—the first born of a great family

Graulich

2011

WIREs Comput Mol Sci

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This review takes the experimental and theoretical discussions on the Cope rearrangement as the basis to emphasize its tight connection to many closely related pericyclic reactions. The Cope reaction, which is rather simple in a formal sense, has led to a plethora of mechanistic discussions to determine the nature of biradical-like intermediates or transition structures. After intense experimental and theoretical investigations starting in the late 1960s, the Cope rearrangement turned out to be a multifaceted reaction with a 'chameleonic' nature, ranging from homoaromatic transition structures to biradical intermediates in substituted cases, and six-electron transition states in the parent system. Additionally, the Cope rearrangement served as an excellent example to probe theoretical methods for the computations of a variety of pericyclic reactions. However, the relationship of the Cope rearrangement with analogous reactions has been hampered by the notion that pericyclic reactions typically are assumed to proceed in a concerted fashion. Only in the past 10 years, the Cope reaction, with its 1,5hexadiene unit, emerged as the structural and mechanistic prototype of a large family, including sigmatropic, cycloaddition, and other electrocyclic reactions as well as thermal rearrangements of polyunsaturated systems, enediynes, eneyneallenes, and many others. The recurrent and interconnecting motif in this family of reactions is the questions regarding cyclic aromatic transition states and the possible involvement of biradical intermediates.

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Section: Historical Survey Of the Cope Rearrangementmentioning

confidence: 99%

The Cope rearrangement—the first born of a great family

Graulich

2011

WIREs Comput Mol Sci

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“…It is expected to fall in the range from unity to EIE. When it is closer to unity, the TS is reactant-like; when it is closer to EIE, the TS is product-like. ,− This empirical prediction, however, often fails for H-transfer reactions, especially in enzymes. One of the earliest observations was by Cleland and co-workers who found a normal α-2° KIE of 1.23 at the 4-H/D position of NAD + in its oxidation of the formate ion via hydride transfer catalyzed by a formate dehydrogenase .…”

Section: Introductionmentioning

confidence: 99%

Imbalanced Transition States from α-H/D and Remote β-Type N-CH/D Secondary Kinetic Isotope Effects on the NADH/NAD⁺ Analogues in Their Hydride Tunneling Reactions in Solution

Sakhaee

Jafari

et al. 2019

J. Org. Chem.

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The α-H/D (if available) and remote β-type N-CH 3 /CD 3 2°kinetic isotope effects (KIEs) on 10-methylacridine (MAH), 9,10-dimethylacridine (DMAH), 1,3-dimethyl-2-phenylbenzimidazoline (DMPBIH) and on the oxidized forms MA + and DMA + , in their hydride transfer reactions with several hydride acceptors/donors in acetonitrile, were determined. The corresponding equilibrium isotope effects (EIEs) were computed. Hammett correlations of several closely related hydride transfer reactions were constructed using the literature data. The α-2°KIEs on both MAH and MA + are inflated relative to the semiclassical prediction on the basis of the KIE/EIE comparison and Hammond's postulate. This together with previously published unusual 1°and 2°K IE behaviors strongly suggest a H-tunneling mechanism. By comparing with the EIEs, the α-2°KIEs were used to analyze the rehybridization of the reaction center C and the N-CH 3 /CD 3 2°KIEs to calculate the charge distribution on the structure containing N during H-tunneling. The rehybridization appears to lag behind the charge development in the donor moiety. The charge distribution at the tunneling ready transition state is in agreement with the Hammett correlations; the donor is productlike, and the acceptor is reactant-like, indicative of a partial negative charge borne by the "in-flight" nucleus being "hydridic" in character. Results were compared with the α-2°KIEs on NADH/NAD + and the Hammett correlations in closely related enzymes. The comparison implicates that the H-tunneling probability would be enhanced by these enzymes.

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“…late TS). 1,[3][4][5] While such correlation between 21 KIE and EIE has been well applied to the mechanistic understanding of the reactions involving heavy atom bond changes, 3,4,[6][7][8] its application in the study of the light H particle transfer reactions has been challenging. 9,10 Since the early 1980's, 21 deuterium or tritium (H/D or H/T) KIEs for many H-transfer reactions, both in solution and in enzymes, have been observed to be larger than the value predicted by the classical TS, and even outside of the range between unity and 21 EIEs.…”

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Imbalanced tunneling ready states in alcohol dehydrogenase model reactions: rehybridization lags behind H-tunneling

et al. 2012

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The secondary kinetic isotope effects for the hydride transfer reactions from aliphatic alcohols to two carbocations (NAD(+) models) in acetonitrile were determined. The results suggest that the hydride transfer takes place by tunneling and that the rehybridizations of both donor and acceptor carbons lag behind the H-tunneling. This is quite contrary to the observations in alcohol dehydrogenases where the importance of enzyme motions in catalysis is manifested.

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Thermodynamic and kinetic secondary isotope effects in the Cope rearrangement

Cited by 53 publications

References 1 publication

The Cope rearrangement—the first born of a great family

The Cope rearrangement—the first born of a great family

Imbalanced Transition States from α-H/D and Remote β-Type N-CH/D Secondary Kinetic Isotope Effects on the NADH/NAD⁺ Analogues in Their Hydride Tunneling Reactions in Solution

Imbalanced tunneling ready states in alcohol dehydrogenase model reactions: rehybridization lags behind H-tunneling

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Thermodynamic and kinetic secondary isotope effects in the Cope rearrangement

Cited by 53 publications

References 1 publication

The Cope rearrangement—the first born of a great family

The Cope rearrangement—the first born of a great family

Imbalanced Transition States from α-H/D and Remote β-Type N-CH/D Secondary Kinetic Isotope Effects on the NADH/NAD+ Analogues in Their Hydride Tunneling Reactions in Solution

Imbalanced tunneling ready states in alcohol dehydrogenase model reactions: rehybridization lags behind H-tunneling

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Imbalanced Transition States from α-H/D and Remote β-Type N-CH/D Secondary Kinetic Isotope Effects on the NADH/NAD⁺ Analogues in Their Hydride Tunneling Reactions in Solution