Povarov reaction
{{Short description|Chemical reaction}}
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.Povarov, L. S.; Mikhailov, B. M. Izv. Akad. Nauk SSR, Ser. Khim. 1963, 953–956.Povarov, L. S.; Grigos, V. I.; Mikhailov, B. M. Izv. Akad. Nauk SSR, Ser. Khim. 1963, 2039–2041.{{cite journal | last1 = Povarov | first1 = L. S. | year = 1967 | title = αβ-UNSATURATED ETHERS AND THEIR ANALOGUES IN REACTIONS OF DIENE SYNTHESIS| doi = 10.1070/rc1967v036n09abeh001680 | journal = Russian Chemical Reviews | volume = 36 | issue = 9| page = 656 | bibcode = 1967RuCRv..36..656P | s2cid = 250825235 }} 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.
Reaction mechanism
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.
The reaction is also classified as a subset of aza Diels-Alder reactions;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}} however, it occurs by a step-wise rather than concerted mechanism.
Examples
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.Unprecedented regio and stereocontrol in Povarov reaction of benzylidene-(3-nitrophenyl)amine Paul J. Stevenson and Isla Graham Arkivoc AM-717D 2003. ([http://www.arkat-usa.org/ark/journal/2003/I07_McKervey/AM-717D/717D.asp Article]) This reaction is regioselective because the iminium ion preferentially 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 stereoselective because the enamine addition occurs with a diastereomeric preference for trans addition without formation of the cis isomer. This is in contrast to traditional Diels–Alder reactions, which are stereospecific based on the alkene geometry.
Image:Povarov example.svgIn 2013, Doyle and coworkers reported a Povarov-type, formal [4+2]-cycloaddition reaction between donor-acceptor cyclopropenes and imines (Scheme 3). In the first step, a dirhodium catalyst effects diazo decomposition from silyl enol ether diazo compound to yield a donor/acceptor cyclopropene. The donor/acceptor cyclopropene is then reacted with an aryl imine under scandium(III) triflate catalyzed conditions to yield cyclopropane-fused tetrahydroquinolines in good yields and diastereoselectivities. Treatment of these compounds with TBAF invokes a ring-expansion that provides the corresponding benzazepines.{{Cite journal|title = Tetrahydroquinolines and Benzazepines through Catalytic Diastereoselective Formal [4 + 2]-Cycloaddition Reactions between Donor–Acceptor Cyclopropenes and Imines|journal = Organic Letters|date = 2013-07-05|issn = 1523-7060|pages = 3278–3281|volume = 15|issue = 13|doi = 10.1021/ol401308d|first1 = Phong M.|last1 = Truong|first2 = Michael D.|last2 = Mandler|first3 = Peter Y.|last3 = Zavalij|first4 = Michael P.|last4 = Doyle|pmid=23777207}}
File:-4+2- cycloaddition of donor-acceptor cyclopropenes with aryl imines.png
Variations
One variation of the Povarov reaction is a four component reaction.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 [https://archive.today/20110812233512/http://www3.interscience.wiley.com/cgi-bin/abstract/112092897/ABSTRACT Abstract] 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 4 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.
References
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