Nazarov cyclization

Educt
Divinyl ketone R 1 = H, alkyl, aryl R 2 = H, alkyl, aryl

The Nazarov cyclization , also known as the Nazarov reaction , is a name reaction of organic chemistry and was discovered in the 1940s by the Russian chemist Ivan Nikolaevich Nazarov (1906–1957). The reaction is a synthesis reaction for cyclopentenones from divinyl ketones and their precursors .

The term Nazarov cyclization covers further reactions with other substrates but with a similar reaction mechanism.

Overview reaction

In the cyclization originally described by Nazarov, stoichiometric amounts of a Lewis acid are used to activate the divinyl ketone. The following overview shows a variant with hydrogen as a substituent (R ¹ = H and R ² = H):

In addition to hydrogen, a large number of other organyl groups can be used. Both for R ¹ and R ² , alkyl and aryl groups are possible.

If asymmetrical divinyl ketones (R ¹ ≠ R ² ) are used in the Nazarov cyclization , the reaction proceeds according to the following reaction scheme:

This creates a mixture of two regioisomeric α, β-unsaturated ketones.

mechanism

The mechanism of the Nazarov cyclization has been very well researched. It is essentially an electrocyclic mechanism with a conrotatory ring closure.

In the first reaction step, the divinyl ketone 1 is protonated under the influence of an acid to form the hydroxypentadienyl cation 2 . Subsequently, substance 2 reacts by ring closure to form the cyclopentenyl cation 3 . Subsequent deprotonation of the cation 3 first forms the enol 4 , which then reacts to the α, β-unsaturated ketone 5 through keto-enol tautomerism .

The formation of a product mixture in the reaction of asymmetrical divinyl ketones is due to the following mesomeric limit formulas of the cyclopentenyl cation occurring in the mechanism:

Both mesomeric limit formulas can, as shown in the mechanism, be deprotonated. As a result, two reaction products arise.

application

The product mixtures resulting from the reaction represent a major disadvantage when used in the chemical industry. This is prevented by using the following trimethylsilyl-substituted carbonyl compounds:

This method was first published by the chemist Scott Denmark . Since divinyl ketones with a wide variety of substituents can be synthesized relatively easily, the Nazarov cyclization has various possible uses. In particular, the use of silylated carbonyl compounds plays an important role in the synthesis of cyclopentanoid systems in natural product chemistry .

literature

• Tülay A Ateşin: Nazarov Cyclization Reaction. Challenges and Opportunities . In: Organic Chemistry. Current Research . tape 03 , no. 01 , January 13, 2014, doi : 10.4172 / 2161-0401.1000e130 .
• Christiane Santelli-Rouvier, Maurice Santelli: The Nazarov Cyclization . In: Synthesis . tape 1983 , no. 06 , 1983, p. 429-442 , doi : 10.1055 / s-1983-30367 .

Individual evidence

1. ^ ^{A b} I. N. Nazarov, II Zaretskaya: Derivatives of acetylene. XXVII. Hydration of divinylacetylene. In: Bull. Acad. sci. URSS , Classe sci. chim. 1942, pp. 200-209.
2. ^ ^{A b} I. N. Nazarov, II Zaretskaya: Structure of products of hydration of divinylethynyl hydrocarbons. In: Zh. Obshch. Khim. 27, 1957, pp. 693-713.
3. ^ ^{A b c} I. N. Nazarov, II Zaretskaya, TI Sorkina: Cyclopentanolones from the cyclization of divinyl ketones. In: Zh. Obshch. Khim. 30, 1960, pp. 746-754.
4. ^ Zerong Wang: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, New Jersey 2009, ISBN 978-0-471-70450-8 , pp. 2011–2015 , doi : 10.1002 / 9780470638859 .
5. ↑ ^{a b c d e} Thomas Laue, Andreas Plagens: Name and catchword reactions of organic chemistry . Vieweg + Teubner Verlag, Wiesbaden 2006, ISBN 3-8351-0091-2 , Nazarov cyclization, p. 240-242 , doi : 10.1007 / 978-3-322-94726-0_73 (first edition: 1994, here pp. 230-232).
6. ↑ ^{a b} László Kürti, Barbara Czakó .: Strategic Applications of Named Reactions in Organic Synthesis. Background and Detailed Mechanisms , Elsevier Academic Press, 2005, pp. 304-305, ISBN 978-0-12-429785-2 .