Reactions Povarov

SCHEME 2.9 Phosphoric acid-catalyzed asymmetric three-component Povarov reaction. 

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Glushkov VA, Tolstikov AG (2007) Synthesis of substituted 1,2,3,4-tetrahydroquinones by the povarov reaction new potentials of the classical reaction. Russ Chem Rev 77 137-159... 

Sridharan V, Avendano C, Menendez JC (2008) New findings on the cerium(IV) ammonium nitrate catalyzed Povarov reaction stereoselective synthesis of 4-alkoxy-2-aryl-l,2,3,4-tetrahydroquinoline derivatives. Synthesis 1039-1044... 

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

Kouznetsov VV (2009) Recent synthetic developments in a powerful imino Diels-Alder reaction (Povarov reaction) application to the synthesis of V-polyheterocycles and related alkaloids. Tetrahedron 65 2721-2750... 

Inverse Electron-Demand Aza-Diels Alder Reaction (Povarov Reaction)... 

Scheme 3.26 Inverse electron demand aza D A reaction (Povarov reaction).

An inverse electron demand aza D A reaction of electron rich alkenes with N aryl imines as 2 azadiene (Povarov reaction) provides tetrahydroquinolines. Reactions catalyzed by chiral phosphoric acids yielded different absolute ste reochemical outcomes when ethyl vinyl efher and enecarbamate are employed as electron rich alkenes, although chiral phosphoric acids have the same axial chirality in both cases (see Scheme 3.26). 

The catalytic, enantioselective and three-component Povarov reaction with the phosphoric acid derivative (225) has been successfully developed by Zhu and co-workers (Scheme 63). A wide variety of aromatic and aliphatic aldehydes as well as anilines featuring different electronic properties were tolerated. 

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. 

Zhu demonstrated that arynes (generated from 153 with fluoride) smoothly annulate 2-acyl-substituted tetrahydroisoquinolines in moderate to excellent yields at room temperature. The starting tetrahydroisoquinolines (e.g., 154) were prepared via a Lewis acid-catalyzed, three-component Povarov reaction (9 examples, 21-75% yield) (140L1756). 

Dysprosium(III) catalysis in organic synthesis (Friedel—Crafts alkylation, Mannich-type, Diels—Alder, and Povarov reactions) 12T2015. Enamides and related functional groups as nucleophihc components in ring-forming processes catalyzed by electrophihc metal salts 12SL814. 

The asymmetric Povarov-reaction of A-arylimines 99 with 2- and 3-vinylindoles (100 and 103) was developed by Bemardi, Ricci and co-workers with a chiral phosphoric acid catalyst ((5)-TRIP, 101) and provided highly enantioenriched indole derivatives (Scheme 3.36) [51],... 

Scheme 3,36 Organocatalytic Povarov reactions of 4-methoxyaniline derived imines with 2- and...

Dione 112 was obtained from 10 (Jones oxidation, 56%), 11 (Se02 oxidation, 42%), and 113 (ozonolysis, 63%). One-pot synthesis of 26 from 10 is devised also [277]. Intramolecular hetero Diels-Alder (Povarov) approach has been developed by Twin and Batey [280]. Intramolecular Povarov reaction between aldehyde precursor 116 prepared from acetate 115 with aniline under the shown conditions afforded 26 in 51% yield presumably after in situ oxidation of the initially formed 1,2-dihydroquinoline (Scheme 27). 

Another application of this concept, in this case to an intermolecular process, the Povarov reaction, was reported by Jacobsen s group in 2010 [150]. The reaction was efficiently catalyzed by o-nitrobenzenesulfonic acid in the presence of a chiral urea derivative. The authors performed a detailed experimental and computational analysis of this catalyst system, which supported the mechanism shown in... 

Zhu and co-workers [77] have successfully developed the first organocatalytic enantioselective three-component Povarov reaction for the efficient synthesis of enantiomerically enriched (2,4-cis)-4-amino-2-aryl(alkyl)-tetrahydroquinolines. To illustrate the power of this novel catalytic enantioselective three-component Povarov reaction, they applied this methodology to the short and efficient synthesis of torcetrapib (188), a potent cholesteryl ester transfer protein (CETP) inhibitor (Scheme 17.31). Reaction of 4-trifluoromethylaniline 184, propionaldehyde 18, and enecarbamate 185 using phosphoric acid catalyst 186 afforded tetrahydroquino-line 187 in 57% yield with 93% ee. Ethoxycarbonylation, deprotection/acylation, and benzylation provided torcetrapib (188) in four steps with 32% overall yield. 

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... 

The mechanism of tetrahydroquinoline formation by the Povarov reaction has been debated. A stepwise mechanism involves ionic intermediate 13, followed by an intramolecular electrophilic substitution. A concerted hetero Diels-Alder reaction was proposed where a concerted asynchronous transition state 14 was suggested. 

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