ThePovarov reaction is anorganic reaction described as a formalcycloaddition between anaromaticimine and analkene. Theimine in thisorganic reaction is acondensation reaction product from ananiline type compound and abenzaldehyde type compound.[1][2][3] Thealkene must be electron rich which means thatfunctional groups attached to the alkene must be able to donate electrons. Such alkenes areenol ethers andenamines. The reaction product in the original Povarov reaction is aquinoline. Because the reactions can be carried out with the three components premixed in one reactor it is an example of amulti-component reaction.
Thereaction mechanism for the Povarov reaction to thequinoline is outlined in Scheme 1. In step oneaniline andbenzaldehyde react to theSchiff base in acondensation reaction. The Povarov reaction requires aLewis acid such asboron trifluoride to activate theimine for anelectrophilic addition of the activatedalkene. This reaction step forms anoxonium ion which then reacts with thearomatic ring in a classicalelectrophilic aromatic substitution. Two additionalelimination reactions create the quinoline ring structure.
The reaction is also classified as a subset ofaza Diels-Alder reactions;[4] however, it occurs by a step-wise rather than concerted mechanism.
The reaction depicted in Scheme 2 illustrates the Povarov reaction with animine and anenamine in the presence ofyttriumtriflate as theLewis acid.[5] This reaction isregioselective because theiminium ion preferentially attacks thenitroortho position and not thepara position. The nitro group is ameta directing substituent but since this position is blocked, the most electron rich ring position is now ortho and not para. The reaction is alsostereoselective because the enamine addition occurs with adiastereomeric preference fortrans addition without formation of thecis isomer. This is in contrast to traditionalDiels–Alder reactions, which arestereospecific based on the alkene geometry.
In 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.[6]
One variation of the Povarov reaction is a four component reaction.[7] Whereas in the traditional Povarov reaction the intermediatecarbocation gives anintramolecular reaction with the aryl group, this intermediate can also be terminated by an additionalnucleophile such as analcohol.Scheme 4 depicts this 4 component reaction with theethylester ofglyoxylic acid, 3,4-dihydro-2H-pyran,aniline andethanol withlewis acidscandium(III) triflate andmolecular sieves.
