Generation of Cyclopentadienones from 2-Bromocyclopentenones

Harmata, Michael; Barnes, Charles L.; Brackley, James; Bohnert, Gary; Kirchhoefer, Patrick; Kürti, László; Rashatasakhon, Paitoon

doi:10.1021/jo015671+

Cited by 21 publications

(16 citation statements)

References 19 publications

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“…Substituted cyclopentadienones are less reactive and have longer lifetimes in solution 19,22,23,24. Recently, Harmata has reported numerous examples of periselective Diels-Alder reactions using 1 as a precursor to cyclopentadienone 2 in the presence of a base.…”

Section: Introductionmentioning

confidence: 99%

Control Elements in Dynamically Determined Selectivity on a Bifurcating Surface

et al. 2008

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The mechanism and the nature of the dynamically-determined product selectivity in Diels-Alder cycloadditions of 3-methoxycarbonylcyclopentadienone (2) with 1,3-dienes was studied by a combination of product studies, experimental kinetic isotope effects, standard theoretical calculations, and quasiclassical trajectory calculations. The low-energy transition structures in these reactions are structurally balanced between [4π diene + 2π dienone ] and the [2π diene + 4π dienone ] modes of cycloaddition. The accuracy of these structures and their bispericyclic nature is supported by the experimental isotope effects. Trajectories passing through these transition structures can lead to both [4π diene + 2π dienone ] and [2π diene + 4π dienone ] cycloadducts, and the mixture of products obtained varies with the structure of the diene. The factors affecting this selectivity are analyzed. The geometry of the transition structure is a useful predictor of the major product, but the selectivity is also guided by the shape of the energy surface as trajectories approach the products and by how trajectories cross the transition state ridge.

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Section: Introductionmentioning

confidence: 99%

Control Elements in Dynamically Determined Selectivity on a Bifurcating Surface

et al. 2008

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“…We recently reported the generation of cyclopentadienones from 2-bromocyclopentenones by treatment of the latter with triethylamine in refluxing trifluoroethanol (TFE) (Scheme 1). [1] Scheme 1. Formation of a cyclopentadienone dimer.…”

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Intermolecular [4+2] Cycloadditions of a Reactive Cyclopentadienone

Harmata

Gomes

2006

Eur J Org Chem

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“…Mass spectrometry does not rigorously define the regiochemistry of thiol attachment in the products 6 , but two lines of evidence lead us to suggest that this product is formed predominantly with the sulfide residue in the α-position relative to the carbonyl (Scheme 2). First, this is the regiochemistry observed for the analogous elimination/ring-opening reaction of a presumed bromonium ion intermediate generated in the reaction of Br 2 with cyclopentenone (50). Second, we find that this regioisomer is the major isolable product arising from a model reaction of 2-mercaptoethanol with 1 (Scheme 2).…”

Section: Discussionmentioning

confidence: 89%

Thiol-Activated DNA Damage by α-Bromo-2-cyclopentenone

Fekry

Price

Hong

et al. 2011

Chem. Res. Toxicol.

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Some biologically active chemicals are relatively stable in the extracellular environment but, upon entering the cell, undergo biotransformation into reactive intermediates that covalently modify DNA. The diverse chemical reactions involved in the bioactivation of DNA-damaging agents are both fundamentally interesting and of practical importance in medicinal chemistry and toxicology. The work described here examines the bioactivation of α-haloacrolyl-containing molecules. The α-haloacrolyl moiety is found in a variety of cytotoxic natural products including clionastatin B, bromovulone III, discorahabdins A, B, and C, and trichodenone C, in mutagens such as 2-bromoacrolein and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), and in the anticancer drug candidates brostallicin and PNU-151807. Using α-bromo-2-cyclopentenone (1) as a model compound, the activation of α-haloacrolyl-containing molecules by biological thiols was explored. The results indicate that both low molecular weight and peptide thiols readily undergo conjugate addition to 1. The resulting products are consistent with a mechanism in which initial addition of thiols to 1 is followed by intramolecular displacement of bromide ion to yield a DNA-alkylating episulfonium ion intermediate. The reaction of thiol-activated 1 with DNA produces labile lesions at deoxyguanosine residues. The sequence specificity and salt-dependence of this process is consistent with involvement of an episulfonium ion intermediate. The alkylated guanine residue resulting from the thiol-triggered reaction of 1 with duplex DNA was characterized using mass spectrometry. The results provide new insight regarding the mechanisms by which thiols can bioactivate small molecules and offer a more complete understanding of the molecular mechanisms underlying the biological activity of cytotoxic, mutagenic, and medicinal compounds containing the α-haloacrolyl group.

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Generation of Cyclopentadienones from 2-Bromocyclopentenones

Abstract: Generation of Cyclopentadienones from 2-Bromocyclopentenones. -Treatment of 2-bromocyclopentenones with NEt 3 leads to cyclopentadienones which spontaneously undergo dimerization in a regio-and completely diastereoselective manner. The dimers can easily be transformed into indanones.

Cited by 21 publications

References 19 publications

Control Elements in Dynamically Determined Selectivity on a Bifurcating Surface

Control Elements in Dynamically Determined Selectivity on a Bifurcating Surface

Intermolecular [4+2] Cycloadditions of a Reactive Cyclopentadienone

Thiol-Activated DNA Damage by α-Bromo-2-cyclopentenone

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