Recent advances of the Povarov reaction in medicinal chemistry

Ghashghaei, Ouldouz; Masdeu, Carme; Alonso, C.; Palácios, Francisco

doi:10.1016/j.ddtec.2018.08.004

Cited by 73 publications

(39 citation statements)

References 56 publications

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“…First, the aza-Diels-Alder reaction (Povarov reaction) [ 42 ] activated by Lewis acid has been studied theoretically and experimentally for the synthesis of 1,2,3,4-tetrahydro-1,5-naphthyridine derivatives 37a and 37b ( Scheme 12 ), which can be obtained through endo intermediates in a regio- and stereoselective manner [ 43 ]. In the same way, glyoxalate derived 1,5-naphthyridine 37c was prepared through a [4+2] cycloaddition process via endo transition states [ 44 ].…”

Section: Synthesis Of 15-naphthyridinesmentioning

confidence: 99%

Synthetic Strategies, Reactivity and Applications of 1,5-Naphthyridines

et al. 2020

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This review covers the synthesis and reactivity of 1,5-naphthyridine derivatives published in the last 18 years. These heterocycles present a significant importance in the field of medicinal chemistry because many of them exhibit a great variety of biological activities. First, the published strategies related to the synthesis of 1,5-naphthyridines are presented followed by the reactivity of these compounds with electrophilic or nucleophilic reagents, in oxidations, reductions, cross-coupling reactions, modification of side chains or formation of metal complexes. Finally, some properties and applications of these heterocycles studied during this period are examined.

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Section: Synthesis Of 15-naphthyridinesmentioning

confidence: 99%

Synthetic Strategies, Reactivity and Applications of 1,5-Naphthyridines

et al. 2020

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“…As a well‐known structural skeleton, the tetrahydroquinoline (THQ) scaffold has wide application in numerous bioactive molecules, for example, as antitubercular agent and receptor agonist of Parkinson's disease [1, 2]. Among various synthetic methods for this scaffold [3–5], the Povarov reaction has gained considerable attention due to the facility and efficiency in synthesis also with high structural diversity [6]. In terms of catalyst selection, besides transition metal [7], Lewis acids [8], and chiral Brønsted acids [9], a series of organocatalysts have been reported including bifunctional phosphoric acid and chiral urea for asymmetric Povarov reaction [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Theoretical investigation on the mechanism and enantioselectivity of organocatalytic asymmetric Povarov reactions of anilines and aldehydes

Liang

Qian

et al. 2020

Int J of Quantum Chemistry

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The mechanism is investigated for organocatalytic asymmetric Povarov reaction of anilines and aldehydes using M06‐2X functional. Two molecule of aldehyde condense with aniline and catalyst giving N‐arylimine and enamine. The reaction is stepwise involving [2 + 2] cycloaddition and ring‐opening/cyclization. Four competitive paths exist in step 1 leading to isomers of quaternary nitrogen heterocycle as cycloadduct. Step 2 is sequential with proton transfer and concerted ring‐opening/cyclization in two feasible orders. Each path in step 1 divides into two in step 2 producing isomers of tetrahydroquinoline (THQ) bonded with catalyst as cyclization product. The reactive nucleophilic adduct with two charge centers in step 1 supports the recovery of catalyst and generation of aldehyde assisted by water. THQ alcohol is obtained in the following intramolecular Friedel–Crafts reaction. The enantio‐ and diastereoselectivity are both thermodynamic control with preferred path yielding the most stable isomer with 2S3S or 1R2S3S configuration. The path bias is in line with the reduction degree of energy barrier in solvent compared with gas phase. Our conclusion is verified by Multiwfn analysis and the predicted ee, dr value of THQ scaffold in experiment.

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“…15 This type of DAR is a bulk synthetic tool since it is possible to use different commercial starting materials, catalysts, promoters, solvents; in general, a great variety of conditions. 16 Moreover, this reaction has shown the importance of several activated alkenes, as their structural features allow to act as dienes or dienophiles, depending on the established reaction conditions and molecular energy barriers. Among the different dienes reported, the 1,3butadiene derivatives have served as ideal precursors in natural products synthesis.…”

Section: Introductionmentioning

confidence: 99%