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Nazarov Cyclization
Nazarov Cyclization
By:
Atul C. Yelpale
Under the guidance of:
Prof. K. G. Akamanchi
Nazarov Cyclization
• Nazarov discovered in 1
̴ 950.
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• A broader definition of the Nazarov cyclization includes a
variety of precursors that under specific reaction conditions
also produce 2-cyclopentenones via divinyl ketones or their
functional equivalents.2
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conrotation of pentadienyl cation 2, which is formed by proton
transfer to the dienone . The allyl cation 3 is formed as an
intermediate. Proton loss from 3 terminates the reaction and
leads to cyclopentenone 4.4
5. Tius, M. “Some New Nazarov Chemistry,” Eur. J. Org. Chem. 2005, 2193–2206.
Synthetic utility of Nazarov reaction2
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employed in synthesis endeavors. e.g.
Simple cyclopentanoids such as cis-jasmone.
Prostaglandin analogs, (±)-valleranal, (±)-methylneomycin B,
and (±)-xanthocin.
More recently the Nazarov cyclization has been used in the
synthesis of polyquinane natural products such as (±)-
hirsutene, (±)-modhephene, (±)-siliphinene, (±)-
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pentalenene, (±)-capnellene and (±)-cedrene.
2. Habermas, K. L.; Denmark,S.; Jones, T. K. In Organic Reactions; Paquette, L. A., Ed.; John Wiley & Sons: New
York, 1994; Vol. 45, pp 1.
Cont..
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Nazarov cyclization employing propargyl alcohols has been
successfully applied to synthesis of (±)-strigol, (±)-nor-
sterepolide, (±)-nookatone, (±)-muscone, and (±)-
muscopyridine.
Industrially, an aromatic nazarov cyclization is used in the
synthesis of (+)-indacrinone.
The cyclization has been postulated in the biosynthetic
pathways for cis-jasmonic acid, and marine derived prostanoids
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such as preclavulone A.
About the paper
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process (a).
• The PdCl2-catalyzed cyclization of α-alkoxy dienones
leads to 2-hydroxycyclopentenones (b).
6
Important features of the paper
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cyclisation of divinyl ketones.3
• Depending upon the choice of catalyst, simple hydrolysis
of an intermediate Pd-enolate leads to 2-
hydroxycyclopentenones, 2a, or β-hydride elimination
leads to cross-conjugated cyclopentenones, 12a.
• This paper revealed enhanced reactivity in substrates
with α-alkoxy substituents.4
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3. Pellissier, H. “Recent developments in the Nazarov process,” Tetrahedron 2005, 61, 6479–6517.
4. Frontier, A. J.; Collison, C. “The Nazarov cyclization in organic synthesis. Recent advances,” Tetrahedron,
2005, 61, 7577–7606.
Review points for the paper
• Title:
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The title The Palladium(II)-Catalyzed Nazarov
Reaction seem very general instead of this
Abstract
About present abstract:
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1. Length of abstract is satisfactory.
Suggestions:
1. The abstract should also include yield, and other
conditions such as temperature, solvent, time etc.
9
Review points for the paper
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Kocienski6); but the result obtained were totally
different; here
i. Author does not summarizes the reason for formation of α-
diketone(3) rather than formation of 2-hydroxycyclopentenone.
10
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author uses chemical equation (Scheme 2a); whereas for
the dienone starting materials 1a-i, author gives text.
It Prevented needless duplication.
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Review points for the paper
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stereochemistry of 2g is cis, upon standing, slow
isomerization to the trans isomer takes place. Author
does not comment on
standing time for total conversion.
12
Review points for the paper
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8- Conformational preferences
9- The electron-withdrawing effect of fluorine.
A more extensive examination of a withdrawing substituent
effects is necessary (and ongoing).3
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10, 11- α-alkoxy group is required
3.Frontier, A. J.; Collison, C. “The Nazarov cyclization in organic synthesis. Recent advances,” Tetrahedron, 2005, 61,
7577–7606.
Review points for the paper
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Reaction products of 1c, 1f, 1g, 1h, 1j, 1k and 1l author
neither illustrates product in scheme nor in text.
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3.Frontier, A. J.; Collison, C. “The Nazarov cyclization in organic synthesis. Recent advances,” Tetrahedron, 2005, 61,
7577–7606.
Review points for the paper
Technical usefulness
• These Cyclizations studies by revealed enhanced reactivity in
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substrates with α-alkoxy substituents
Since these early findings the Tius group, in particular, has
developed synthetically valuable cyclopentannulation
methodology based on α-oxygen substitutedpentadienyl cation
precursors.5
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Alternative interpretations
• The point is not discussed
Why are substrates with α-oxygen substitution so reactive?3
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The electron-donating substituent is thought to increase electron
density on the terminal carbon of the pentadienyl cation
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