Theoretical Study of the Mechanism of an Inverse-Demand Diels–Alder Reaction

Shihab, Mehdi Salih

doi:10.1007/s13369-011-0167-0

Cited by 3 publications

(3 citation statements)

References 36 publications

(39 reference statements)

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“…Shihab et al later studied a related reaction of a series of dienophiles with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate by theoretical methods [52]. Their results are in agreement with the catalytic cycle presented in Scheme 1.…”

Section: Introductionsupporting

confidence: 52%

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

Schnell

Willms

Nozinovic

et al. 2019

Beilstein J. Org. Chem.

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The mechanism of an L-proline-catalyzed pyridazine formation from acetone and aryl-substituted tetrazines via a Diels–Alder reaction with inverse electron demand has been studied with NMR and with electrospray ionization mass spectrometry. A catalytic cycle with three intermediates has been proposed. An enamine derived from L-proline and acetone acts as an electron-rich dienophile in a [4 + 2] cycloaddition with the electron-poor tetrazine forming a tetraazabicyclo[2.2.2]octadiene derivative which then eliminates N2 in a retro-Diels–Alder reaction to yield a 4,5-dihydropyridazine species. The reaction was studied in three variants: unmodified, with a charge-tagged substrate, and with a charge-tagged proline catalyst. The charge-tagging technique strongly increases the ESI response of the respective species and therefore enables to capture otherwise undetected reaction components. With the first two reaction variants, only small intensities of intermediates were found, but the temporal progress of reactants and products could be monitored very well. In experiments with the charge-tagged L-proline-derived catalyst, all three intermediates of the proposed catalytic cycle were detected and characterized by collision-induced dissociation (CID) experiments. Some of the CID pathways of intermediates mimic single steps of the proposed catalytic cycle in the gas phase. Thus, the charge-tagged catalyst proved one more time its superior effectiveness for the detection and study of reactive intermediates at low concentrations.

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Section: Introductionsupporting

confidence: 52%

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

Schnell

Willms

Nozinovic

et al. 2019

Beilstein J. Org. Chem.

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show abstract

“…However, calculations that showed that the activation energy of the one-step pathway is almost 50 kcal mol −1 higher than that for the stepwise pathway later dismissed this view and predicted that a stepwise mechanism was preferred. 107 More recently, it was computationally determined that the barrier for the loss of nitrogen from the tetraazabarrelene intermediate is essentially nonexistent. Therefore, there are two sequential transition states, the first for the cycloaddition, and the second for the loss of N 2 to generate a pyridazine.…”

Section: 11mentioning

confidence: 94%

“…Therefore, they hypothesized that the cycloaddition and elimination of nitrogen occurred in a single asynchronous step, wherein the C–C bonds form and C–N bonds break simultaneously. However, calculations that showed that the activation energy of the one-step pathway is almost 50 kcal mol –1 higher than that for the stepwise pathway later dismissed this view and predicted that a stepwise mechanism was preferred . More recently, it was computationally determined that the barrier for the loss of nitrogen from the tetraazabarrelene intermediate is essentially nonexistent.…”

Section: Inverse-electron Demand Diels-alder Cycloaddition Reactionsmentioning

confidence: 99%

Mechanisms and Substituent Effects of Metal-Free Bioorthogonal Reactions

Deb

Franzini

2021

Chem. Rev.

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Reactions that occur under physiological conditions find diverse uses in the chemical and biological sciences. However, the limitations that biological systems place on chemical reactions restrict the number of such bioorthogonal reactions. A profound understanding of the mechanistic principles and structure−reactivity trends of these transformations is therefore critical to access new and improved versions of bioorthogonal chemistry. The present article reviews the mechanisms and substituent effects of some of the principal metal-free bioorthogonal reactions based on inverse-electron demand Diels−Alder reactions, 1,3-dipolar cycloadditions, and the Staudinger reaction. Mechanisms of modified versions that link these reactions to a dissociative step are further discussed. The presented summary is anticipated to aid the advancement of bioorthogonal chemistry. CONTENTSReview pubs.acs.org/CR

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1,2,4,5-Tetrazines

Chaitanya

Anbarasan

2022

Comprehensive Heterocyclic Chemistry IV

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Theoretical Study of the Mechanism of an Inverse-Demand Diels–Alder Reaction

Cited by 3 publications

References 36 publications

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

Mechanistic studies of an L-proline-catalyzed pyridazine formation involving a Diels–Alder reaction with inverse electron demand

Mechanisms and Substituent Effects of Metal-Free Bioorthogonal Reactions

1,2,4,5-Tetrazines

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