Povarov reaction

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The Povarov reaction is an organic reaction described as a formal cycloaddition between an aromatic imine and an alkene. The imine in this organic reaction is a condensation reaction product from an aniline type compound and a benzaldehyde type compound.[1][2][3] The alkene must be electron rich which means that functional groups attached to the alkene must be able to donate electrons. Such alkenes are enol ethers and enamines. The reaction product in the original Povarov reaction is a quinoline. Because the reactions can be carried out with the three components premixed in one reactor it is an example of a multi-component reaction.

Povarov reaction

Reaction mechanism[edit]

The reaction mechanism for the Povarov reaction to the quinoline is outlined in scheme 1. In step one aniline and benzaldehyde react to the Schiff base in a condensation reaction. The Povarov reaction requires a lewis acid such as boron trifluoride to activate the imine for an electrophilic addition of the activated alkene. This reaction step forms an oxonium ion which then reacts with the aromatic ring in a classical electrophilic aromatic substitution. Two additional elimination reactions create the quinoline ring structure.

Scheme 1. The Povarov reaction

The reaction is also classified as a subset of aza Diels-Alder reactions [4]

Examples[edit]

The reaction depicted in scheme 2 illustrates the Povarov reaction with an imine and an enamine in the presence of yttrium triflate as the lewis acid.[5] This reaction is regioselective because the iminium ion preverentially attacks the nitro ortho position and not the para position. The nitro group is a meta directing substituent but since this position is blocked, the most electron rich ring position is now ortho and not para. The reaction is also diastereoselective because the enamine addition occurs with a preference for trans addition without formation of the cis isomer.

Scheme 2 regio- and diastereoselective Povarov reaction

Variations[edit]

One variation of the Povarov reaction is a four component reaction.[6] Whereas in the traditional Povarov reaction the intermediate carbocation gives an intramolecular reaction with the aryl group, this intermediate can also be terminated by an additional nucleophile such as an alcohol. Scheme 3 depicts this 4 component reaction with the ethyl ester of glyoxylic acid, 3,4-dihydro-2H-pyran, aniline and ethanol with lewis acid scandium(III) triflate and molecular sieves.

Scheme 3 Four component Povarov reaction. In order to clarify the role of the lewis acid, a solid scandium nitrogen bond is drawn. Reaction conditions 2 days in acetonitrile at room temperature

References[edit]

  1. ^ Povarov, L. S.; Mikhailov, B. M. Izv. Akad. Nauk SSR, Ser. Khim. 1963, 953–956.
  2. ^ Povarov, L. S.; Grigos, V. I.; Mikhailov, B. M. Izv. Akad. Nauk SSR, Ser. Khim. 1963, 2039–2041.
  3. ^ Povarov, L. S. Russian Chem. Rev. 1967, 36, 656.
  4. ^ Recent synthetic developments in a powerful imino Diels–Alder reaction (Povarov reaction): application to the synthesis of N-polyheterocycles and related alkaloids Vladimir V. Kouznetsov Tetrahedron 65 (2009) 2721–2750 doi:10.1016/j.tet.2008.12.059
  5. ^ Unprecedented regio and stereocontrol in Povarov reaction of benzylidene-(3-nitrophenyl)amine Paul J. Stevenson and Isla Graham Arkivoc AM-717D 2003. (Article)
  6. ^ Straightforward Access to a Structurally Diverse Set of Oxacyclic Scaffolds through a Four-Component Reaction Oscar Jiménez, Guillermo de la Rosa, Rodolfo Lavilla Angewandte Chemie International Edition Volume 44, Issue 40 , Pages 6521 - 6525 2005 Abstract

Glushkov, V. A.; Tolstikov, A G. Synthesis of substituted 1,2,3,4-tetrahydroquinones by the Povarov reaction. New potentials of the classical reaction. Russian Chem. Rev., Vol. 77(2008), No 2, P. 137–159.

See also[edit]