Abnormal Nazarov Reaction. A New Synthetic Approach to 2,3-Disubstituted 2-Cyclopentenones

Abstract

Acid-catalyzed reaction of β,β′-disubstituted cross conjugated dienones or the corresponding ethylene acetals gives mainly 2,3-disubstituted 2-cyclopentenones in stead of the simple Nazarov cyclization products, 3,4-disubstituted 2-cyclopentenones. This transformation is explained in terms of electrocyclic ring-closure, addition of hydroxylic solvent(s), tautomerization of the resulting 2-hydroxycyclopentanone intermediates, followed by solvolysis and isomerization. Based on this working hypothesis a new route to jasmonoids is disclosed which involves acid-treatment of the acyloin disilyl ethers derived from substituted glutarates.

Understanding the Fate of the Oxyallyl Cation following Nazarov Electrocyclization: Sequential Wagner−Meerwein Migrations and the Synthesis of Spirocyclic Cyclopentenones

“…Trapping with heteroatomic solvents such as methanol, acetic acid, trifluoroacetic acid, or formic acid has been observed in photo-Nazarov cyclizations, 17 and in cyclizations promoted by protic acids. 18 Intramolecular oxygen interruption is also possible during Lewis acid-promoted cyclization, 19 as well as intermolecular trapping with azides, 20 halides 21 or amines. 12b, 22 In addition to hydride shift and methyl shift, a vinyl migration following electrocyclization of a linear dienyl ketone was also reported by Denmark and coworkers.…”

Production of 2,5-hexanedione and 3-methyl-2-cyclopenten-1-one from 5-hydroxymethylfurfural

“…In the early stage, Piancatelli et al synthesized cyclopentenones from furans, where the reaction was catalyzed by a homogeneous strong acid in an acetone/water system. 5 Synthetic methods using other starting materials such as alkynes, alkenes, carbon monoxide, 3,6 dienones, 7 1,3-dicarbonyl compounds, 8 isoprene, 9 mesyltriflone, 10 diazo ketones, 11 alkynones, 12 and HDN (2,5-hexanedione) 13,14 were also developed. It is worth mentioning that HDN can be obtained by the hydrolysis of a HMF-derived product, 2,5-dimethylfuran (DMF).…”

Unusual Nazarov Cyclization in Near-Critical Water

“…The Nazarov reaction is an acid-catalyzed cyclization of divinyl ketones to 2-cyclopentenones . The reaction has been used in construction of many complex, natural, and biologically important target molecules and their synthetic intermediates possessing the cyclopentenone moiety, such as jasmonoids and prostanoids . The Nazarov reaction involves a conrotatory 4π electrocyclization of the pentadienyl cation, and it is therefore considered as a pericyclic reaction.…”

“…The Nazarov reaction produces normally 3,4-disubstituted 2-cyclopentenones 2 from β,β‘-disubstituted cross conjugated divinyl ketones 1 (Scheme ). However, Hirano et al have reported about the abnormal Nazarov reaction, in which the main product is a 2,3-disubstituted 2-cyclopentenone 3 . , They postulated that this unexpected product is formed by the addition of a hydroxylic solvent, such as water or carboxylic acid, to the oxyallyl cation 5 after the electrocyclic ring closure of the protonated divinyl ketone 4 (Scheme ). This would give rise to the hydroxy- or acyloxycyclopentenone intermediate 6 , which isomerises to 7 .…”

“…The normal 3,4-substituted Nazarov product 2 would be obtained after direct deprotonation of the oxyallyl cation 5 . In fact, Hirano et al observed also formation of the conventional 3,4-disubstituted 2-cyclopentenones in the presence of less nucleophilic solvent, where deprotonation can compete with the nucleophilic substitution by the solvent 1

2

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