Kinetics of the cope rearrangement of 1,1-dideuteriohexa-1,5-diene

Doering, W. von E.; Toscano, Vicente G.; Beasley, G. H.

doi:10.1016/s0040-4020(01)91694-1

Cited by 157 publications

(4 citation statements)

References 16 publications

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“…The Cope rearrangement of 1,5-hexadienes (Scheme ) is a reaction of both theoretical and practical significance in organic chemistry. , Like the closely related Claisen rearrangement, the Cope rearrangement is a prototypical [3,3]-sigmatropic shift that, in most cases, proceeds through a concerted, well-ordered chairlike transition state. Simple substrates possess a high activation barrier, often exceeding 30 kcal/mol, thus requiring reaction temperatures approaching or even exceeding 200 °C . However, substrate modifications can significantly reduce the barrier to rearrangement.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of an Organocatalytic Cope Rearrangement Involving Iminium Intermediates: Elucidating the Role of Catalyst Ring Size

Sanders

Jun

et al. 2020

J. Am. Chem. Soc.

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The mechanism of the organocatalytic Cope rearrangement is elucidated through a combined computational and experimental approach. As reported previously, hydrazides catalyze the Cope rearrangement of 1,5-hexadiene-2-carboxaldehydes via iminium ion formation, and seven- and eight-membered ring catalysts are more active than smaller ring sizes. In the present work, quantum mechanical computations and kinetic isotope effect experiments demonstrate that the Cope rearrangement step, rather than iminium formation, is rate-limiting. The computations further explain how the hydrazide catalyst lowers the free-energy barrier of the Cope rearrangement via an associative transition state that is stabilized by enehydrazine character. The computations also explain the catalyst ring size effect, as larger hydrazide rings are able to accommodate optimal transition-state geometries that minimize the unfavorable lone-pair repulsion between neighboring nitrogen atoms and maximize the favorable hyperconjugative donation from each nitrogen atom into neighboring electron-poor sigma bonds, with the seven-membered catalyst achieving a nearly ideal transition-state geometry that is comparable to that of an unconstrained acyclic catalyst. Experimental kinetics studies support the computations, showing that the seven-membered and acyclic hydrazide catalysts react 10 times faster than the six-membered catalyst. Unraveling the mechanism of this reaction is an important step in understanding other reactions catalyzed by hydrazides, and explaining the ring size effect is critical because cyclic catalysts provide a constrained scaffold, enabling the development of asymmetric variants of these reactions.

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Section: Introductionmentioning

confidence: 99%

Mechanism of an Organocatalytic Cope Rearrangement Involving Iminium Intermediates: Elucidating the Role of Catalyst Ring Size

Sanders

Jun

et al. 2020

J. Am. Chem. Soc.

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“…To better understand this Au‐Claisen rearrangement in the [4+2] reaction, activation free energies for several reference reactions were calculated (Figure 1). The parent Cope rearrangement in DCM (dichloromethane) is difficult with a computed activation free energy of 38.7 kcal mol −1 [15] . When a cyclopropane tether is introduced, the Cope rearrangement becomes easier with a computed activation free energy of 23.1 kcal mol −1 , due to the strain release from the cyclopropane tether.…”

Section: Resultsmentioning

confidence: 99%

Metalla‐Claisen Rearrangement in Gold‐Catalyzed [4+2] Reaction: A New Elementary Reaction Suggested for Future Reaction Design

et al. 2023

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We report here computational evidence for a metalla-Claisen rearrangement (MCR) in the case of gold-catalyzed [4+2] cycloaddition reaction of ynedienes. The [4+2] reaction starts from exo cyclopropanation, followed by MCR and reductive elimination. The cyclopropane moiety formed in the first step is crucial for a low barrier of the MCR step. In addition, the importance of an appropriate combination of the tether group and the terminal substituent on alkyne in the ynediene substrates was studied. The mechanism of rhodium-catalyzed [4+2] reaction of yne-dienes was also investigated to see whether an MCR mechanism is involved or not. The findings and new understanding hereby reported represent an important advance in the catalysis field.

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“…According to meeting notes kept by Robert Kohler, Doering gave the invited talk at Woodward's Thursday evening seminar on March 9, 1961 [88] . Doering spoke on A Stereospecific Cope Rearrangement , the reaction that Doering studied extensively in the early 1960s [12,20,111,112] . This reaction was also a key example of no‐mechanism reactions.…”

Section: Prefacementioning

confidence: 99%