Nazarov cyclization reaction

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A Nazarov cyclization is an organic reaction converting a divinylketone into a cyclopentenone under the influence of a Brønsted acid such as sulfuric acid or a Lewis acid such aluminum chloride [1]. The key intermediate in this reaction is a hydroxypentadienyl cation and the key reaction step is a thermally allowed electrocyclic ring closure which in accordance with the Woodward-Hoffmann rules as a 4n π system is conrotatory.

Scheme 1. Nazarov cyclization

The reaction was first reported by I.N. Nazarov in 1949.

Contents

[edit] Mechanism

The reaction mechanism for this reaction is outlined in scheme 2. Divinylketone 1 is protonated with a proton donor to the pentadienyl cation 2 in which a positive charge is delocalized over 6 positions, a hybrid of 4 mesomers 2a to 2d. An electrocyclic ring closure takes place to the cyclopentenyl cation 3 and after an elimination reaction the proton is released again. The enol 4 rearranges to the ketone tautomer 5.

Scheme 2. Nazarov reaction mechanism

[edit] Scope

In one study the Nazarov cyclization is paired with a Michael reaction [2]. In this tandem reaction (scheme 3) the iridium catalyst is required for both conversions: it acts as the Lewis acid in the nazarov cyclization and in the next step the nitro group of nitrostyrene first coordinates to iridium in a ligand exchange with the carbonyl ester oxygen atom before the actual Michael addition takes place to the opposite face of the methoxybenzene group.

Scheme 3. Nazarov-Michael tandem (Ph = phenyl)

In an extension any pentadienyl cation regardless of its origin is capable of bringing about Nazarov reaction. In one study this species is obtained from an alkenyl-substituted dihalocyclopropane [3] [4]:

Scheme 4. Nazarov variation

[edit] External links

[edit] References

  1. ^ Named Organic Reactions, 2nd Edition, Thomas Laue and Andreas Plagens, John Wiley & Sons: Chichester, England, New York, 2005. 320 pp. ISBN 0-470-01041-X
  2. ^ Tandem Nazarov Cyclization-Michael Addition Sequence Catalyzed by an Ir(III) Complex Mesfin Janka, Wei He, Inga E. Haedicke, Frank R. Fronczek, Alison J. Frontier, and Richard Eisenberg J. Am. Chem. Soc.; 2006; 128(16) pp 5312 - 5313; Graphical abstract
  3. ^ A New Approach to the Nazarov Reaction via Sequential Electrocyclic Ring Opening and Ring Closure Tina N. Grant and F. G. West J. Am. Chem. Soc.; 2006; 128(29) pp 9348 - 9349; (Communication) DOI:10.1021/ja063421a
  4. ^ The silyl enol ether 2-triisopropylsilyloxydiene 1 reacts with dichlorocarbene and a phase transfer catalyst to the dichlorocyclopropane 2. Reaction with silver tetrafluoroborate of 2 strips a chlorine anion forming a cyclopanyl cation 3a which rearranges to a cyclopropenyl cation 3b and onwards to the Nazarov adduct 3c. Proton elimination (3d) and desilylation gives the cyclopentadienone 4
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