Dienophiles, Povarov reaction

A subset of imino-Diels-Alder cycloadditions involving reactions between N-aryl imines and electron-rich dienophiles is the Povarov reaction [75]. 

The Povarov reaction is the inverse electron-demand aza-Diels-Alder reaction, a [4 + 2] cycloaddition between an A -aiylimine (as the diene) and an electron-rich olefin (as the dienophile), which gives tetiahydroquinolines or substituted quinolines as the product. 

A one-pot multicomponent cascade reaction of arylamines, aldehydes, and electron-deficient dienophiles on a soluble support under microwave conditions has been reported to involve a base-catalysed Povarov reaction and a [l,3]-sigmatropic rearrangement leading to 4,10-dihydropyrimido[l,2-fl]benzimidazoles (Scheme 17). ... 

The Povarov reaction is the inverse electron-demand aza-Diels-Alder reaction, a [4 + 2] cycloaddition between an A-arylimine (as the diene) and an electron-rich olefin (as the dienophile), which gives tetrahydroquinolines 3 or substituted quinolines 4 as the product. This reaction also called as imino-Diels-Alder reaction, usually catalyzed by Lewis or Bronsted acids. Since the jV-arylimine can be prepared in situ from aniline and aldehyde, thus the Povarov reaction can be performed in a one-pot fashion. ... 

Normally, the A-arylimine is obtained by reaction of aldehyde and aniline in acidic condition. Either tetrahydroquinoline or its corresponding substituted quinoline can be generated in the Povarov reaction, depending on the reaction conditions. For instance, DDQ-promoted dehydrogenation, vacuum distillation under acidic condition, oxidation by air or Mn(OAc)3, and Pd/C-catalyzed aromatization of tetrahydroquinoline, provides the corresponding substituted quinolines in good to excellent yield. Since some tetrahydroquinolines are unstable under the reaction conditions, the corresponding substituted quinolines could be isolated as the sole products. Electron-rich olefin, such as vinyl enol ethers, vinyl sulfides, and silyl enol ethers, are widely used as dienophiles in the cycloaddition of A-aryl aldimines to obtain substituted tetrahydroquinolines. To access natural... 

Using Ln(OTf)3 catalyst, Batey demonstrated that the three-component Povarov reaction generated highly functionalized C-2 aliphatic-substituted tetrahydroquinolines 45, which were inaccessible previously using the traditional Povarov reaction, due to the instability of the aliphatic iV-arylaldimine. It is interesting that cyclopentadiene was used as the dienophile in this new process. ... 

G. Dagousset, P. Retailleau, G. Masson, J. Zhu, Chem.-Eur. J. 2012, 18, 5869-5873. Chiral phosphoric acid-catalyzed enantioselective three-component Povarov reaction using cyclic enethioureas as dienophiles stereocontrolled access to enantio-enriched hexahydropyrroloquinolines. 

C. D. Smith, J. I. GavrUyuk, A. J. Lough, R. A. Batey, J. Org. Chem. 2010, 75, 702—715. Lewis acid catalyzed three-component hetero-Diels-Alder (Povarov) reaction of N-arylimmes with strained norbomene-derived dienophiles. 

In 2009, Masson, Zhu and coworkers reported a sequential inverse-electron-demand aza-Diels-Alder reaction (Povarov reaction) [105]. They prepared imines in situ from the corresponding aldehydes 211 and anilines 210 and reacted them with enecarbamates 212 as electron-rich dienophiles with excellent enantioselectivity using phosphoric acid 99c (Scheme 42.49). The practicality of their approach was highlighted by its application in an efficient synthesis of the drug torcetrapib [106]. 

After Akiyama et al. reported the first organocatalzyed inverse electron-demand aza-Diels-Alder reaction (Povarov reaction) between o-hydroxyaniline-derived imines and alkyl vinyl ethers [6], Liu et al. developed a three-component Povarov reaction of aldehydes 3, anilines 7, and benzyl A-vinylcarbamates 8a that efficiently afforded enantioenriched (2,4-c )-4-amino-l,2,3,4-terahydroquinoline 35 with a wild substrate scope (Scheme 2.9) [15a], Subsequently, a full study of the mechanism, substrate scope, and catalyst loading of this transformation was made, which revealed that this type of three-component Povarov reaction underwent a stepwise mechanism [15b]. Very recently, He, Shi, and others proved independently that the hydroxystyrenes 8b or 8c can also act as good dienophiles in asymmetric three-component Povarov reactions, thus providing efficient methods to access structurally diverse multisubstituted tetrahydroquinolines 35a or 35b in high stereoselectivities [16]. 

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