One-pot aza-Diels-Alder reactions

Diels-Alder reactions mediated by FeCh-Nal <2004TL3507> or sulfamic acid <2004S69, 2004S949> yield tetrahydroquinolines while the use of polyethylene glycol 4000 (PEG 4000) as a soluble polymer support in a three-step one-pot aza-Diels-Alder reaction also gives tetrahydroisoquinolines <2004SL1175>. 

To avoid the use of organic solvents in Diels-Alder reactions, ionic liquid was recognized as a promising alternative solvent because its specific features of excellent solubility, lack of volatility, tunable polarity, and stable reusability [27]. 8-Ethyl-1,8-diazabicyclo[5,4,0]-7-undecenium trifiuoromethanesulfonate ([Et-DBUjOTf) was utilized as a recoverable medium for Sc(OTf)3-catalyzed one-pot aza-Diels-Alder reactions of aromatic aldehydes, anilines and Danishefsky s diene (Scheme 12.15) [28]. In this reaction system, Sc(OTf)3 is recovered smoothly in... 

IL [emim][Pro] induced a one-pot aza-Diels-Alder reaction between cyclic a,(3-unsaturated ketones, formaldehyde, and aniline derivatives [69]. Bicyclic ketones 44 having high diastereomeric and enantiomeric purity were readily produced from in situ generated dienols 42 and methylene-imines 43 under the proposed conditions (Scheme 22.17). The catalyst was recovered and reused in the same reaction six times, although the enantioselectivity decreased somewhat. 

Scheme 22.17 [Emim][Pro]

Zulfiqar, F., Kitazume, T. (2000). One-pot aza-Diels-Alder reactions in ionic liquids. Green Chem., 2,137-139, Qune 2000) 1463-9262, ISSN 1463-9262... 

The fluoboric acid-catalyzed aza-Diels-Alder reaction of aldimine and Danishefsky s diene proceeds smoothly to afford dihydro-4-pyridones in high yields [90] (Equation 4.16). Unstable aldimines generated from aliphatic aldehydes can be prepared in situ and allowed to react under one-pot reaction conditions. This one-pot Bronsted acid-catalyzed three-component aza-Diels-Alder reaction affords the adducts in good to high yields. 

Savitha G, Perumal PT (2006) An efficient one-pot synthesis of tetrahydroquinoline derivatives via an aza Diels-Alder reaction mediated by CAN in an aqueous medium and oxidation to heteroaryl quinolines. Tetrahedron Lett 47 3589-3593... 

Substituted tetrahydropyridines 134 have been recently prepared via an interesting one-pot transformation involving the Aza Diels-Alder reaction of imines 132 with enamines 133 (Scheme 26) [62]. The enamine adducts were prepared from the reaction of anilines 129 with the Knoevenagel products of 130 and 131. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Bearing in mind the usefulness and efficiency of one-pot procedures, three-component coupling reactions between aldehydes, amines, and alkenes via imine formation and aza Diels-Alder reactions were examined using the Ln(OTf)3 as a catalyst. 

Cdrdova, et al. reported a one-pot three component direct catalytic enantioselective aza-Diels-Alder reaction of a,p-unsaturated ketones, Scheme 3.39 [54], The reaction was catalyzed by proline with excellent regio-, and stereoselectivity. The... 

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. ... 

Mediated by CF3SO3H, ethynyl ketene-5,5-acetals 66 and 69, the highly reactive dienophiles can react in a one-pot condition with various arylamines and aldehydes, giving the corresponding quinolines in good yield via regiospecific aza-Diels-Alder reaction. ... 

An efficient approach toward the synthesis of dihydropyrido[4,3-(/] pyrimidines 97 via a one-pot, microwave-promoted three-component aza-Diels—Alder reaction was developed by Prajapati and collaborators (Scheme 48) (13TL267). 

The first one-pot three-component enantioselective organocatalyzed aza-Diels-Alder reaction was published in 2005 by Cordova and coworkers [45], The reaction... 

S. Samai, G. Chandra Nandi, S. Chowdhury, M. S. Singh, Tetrahedron 2011, 67, 5935-5941. L-Proline catalyzed synthesis of densely functionalized pyrido[2,3-d]pyrimidines via three-component one-pot domino Knoevenagel aza-Diels-Alder reaction. 

Synthetic strategy One-pot three-component aza-Diels-Alder reaction... 

A one-pot, three-component asymmetric aza-Diels-Alder reaction using S-proline as the organocatalyst was developed by Cordova et al. 2-cyclohexene-1-one 313, aqueous formaldehyde 314, and / -anisidine 315 were mixed with catalytic amount of proline to get the aza-Diels-Alder adduct 316 with excellent enantiomeric excess (Scheme 40.68). 

An extensive review of the one-pot inverse-electron-demand aza-Diels-Alder reaction between A-arylimine and -rich olefins (Povarov reaction) has been presented. " A chiral phosphoric acid-catalysed inverse-electron-demand aza-Diels-Alder reaction... 

An efficient one pot three component aza-Diels-Alder reaction for the synthesis of some complex spiroquinoline derivatives has been carried out under microwave irradiation and solvent-free condition (Bhuyan et al., 2012). 

Highly enantioselective, three-component, inverse electron-demand aza-Diels-Alder reaction of aldehydes, anilines, and isoeugenol derivatives (129) catalysed by a phosphoric acid (119) has been reported by Masson and co-workers. A wide variety of 2,3,4-trisubstituted tetra-hydroquinolines (130) containing an aryl group at the 4-position were obtained in a one-pot process with good to high yields and excellent enantioselectivities (up to >99% ee) (Scheme 45). ... 

Intermolecular cycloaddition reactions of 1-aza- and 2-azadienes are generally sluggish and therefore the intramolecular reaction, in which the entropy factor is more favourable, can lead to a more efficient cycloaddition of these heterodienes. Acylation of A-silyl-a,p-unsaturated imines provides a convenient one-pot method for the formation of 1-azadienes required for the Diels-Alder reaction. For example, addition of allyl chloroformate to the A-trimethylsilyl imine of acrolein gave, after heating, the cycloadduct 99 (3.81). 

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