Showing papers by "J. Carlos Menéndez published in 2016"
TL;DR: A highly efficient synthesis of 5,6-dihydrodibenzo[b,h][1,6]naphthyridines was achieved by reaction between 2-(N-propargylamino)benzaldehydes and arylamines in the presence of CuBr2.
Abstract: A highly efficient synthesis of 5,6-dihydrodibenzo[b,h][1,6]naphthyridines was achieved by reaction between 2-(N-propargylamino)benzaldehydes and arylamines in the presence of CuBr2. The in situ generated electron-deficient heterodienes bearing a tethered alkyne partner underwent an intramolecular inverse electron-demand hetero-Diels–Alder reaction followed by air oxidation to furnish the products in high yields. This reaction tolerated a large number of substituents to afford diverse products under mild conditions. This strategy was also successfully extended to the synthesis of 12,13-dihydro-6H-benzo[h]chromeno[3,4-b][1,6]naphthyridin-6-ones starting from 3-amino-2H-chromen-2-one, again in high yields.
38 citations
TL;DR: The aza-vinylogous Povarov reaction between α-ketoimines and α,β-unsaturated dimethylhydrazones in the presence of indium trichloride affords 2-acyl-4-alkyl- 4-dimethylHydrazonomethyl-1,2,3,4-tetrahydroquinolines with good cis/trans diastereoselectivities.
Abstract: The aza-vinylogous Povarov reaction between α-ketoimines and α,β-unsaturated dimethylhydrazones in the presence of indium trichloride affords 2-acyl-4-alkyl-4-dimethylhydrazonomethyl-1,2,3,4-tetrahydroquinolines with good cis/trans diastereoselectivities. These compounds were readily transformed into highly substituted 2-acylquinolines using a two-reaction sequence involving the oxidative generation of a C-4 nitrile group, followed by its elimination under thermal conditions. Alternatively, a one-pot protocol based on the reaction of hydrazones with magnesium monoperoxyphthalate hexahydrate in refluxing methanol afforded the target 2-acylquinolines in good to excellent yields. This methodology was also extended to the preparation of 2-arylquinolines.
33 citations
TL;DR: In this paper, the use of solvent-free, high-speed vibration milling conditions has allowed the development of a one-pot telescoped process for the synthesis of pyrroles starting from ketones, primary amines, and β-dicarbonyl compounds and comprising an initial α-iodination followed by a three-component Hantzsch-type reaction.
30 citations
TL;DR: Tetrahydroisoquinoline derivatives containing embedded urea functions were identified as selective TRPM8 channel receptor antagonists and found to be active in reducing the growth of LNCaP prostate cancer cells, suggesting that the activity against prostate cancer is linked toTRPM8 inhibition.
Abstract: Tetrahydroisoquinoline derivatives containing embedded urea functions were identified as selective TRPM8 channel receptor antagonists. Structure–activity relationships were investigated, with the following conclusions: (a) The urea function and the tetrahydroisoquinoline system are necessary for activity. (b) Bis(1-aryl-6,7dimethoxy-1,2,3,4-tetrahydroisoquinolyl)ureas are more active than compounds containing one tetrahydroisoquinoline ring and than an open phenetylamine ureide. (c) Trans compounds are more active than their cis isomers. (d) Aryl substituents are better than alkyls at the isoquinoline C-1 position. (e) Electron-withdrawing substituents lead to higher activities. The most potent compound is the 4-F derivative, with IC50 in the 10–8 M range and selectivities around 1000:1 for most other TRP receptors. Selected compounds were found to be active in reducing the growth of LNCaP prostate cancer cells. TRPM8 inhibition reduces proliferation in the tumor cells tested but not in nontumor prostate ...
29 citations
TL;DR: This experimentally simple protocol provides good yields of structurally complex, biologically relevant heterocycles in a single operation by the three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the condensation of isatins and secondary amino acids.
Abstract: A library of novel dispiro compounds containing oxindole pyrrolidine/oxindolopyrrolothiazole-thiochroman-4-one hybrid frameworks has been synthesized in a fully regio- and stereoselective fashion by the three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the condensation of isatins and secondary amino acids (sarcosine/l-thioproline) with 3-arylidenethiochroman-4-ones. This experimentally simple protocol provides good yields of structurally complex, biologically relevant heterocycles in a single operation.
18 citations
TL;DR: The Hantzsch-type microwave-assisted, solvent-free sequential three-component reaction between primary amines, β-dicarbonyl compounds and α-bromoesters in the presence of indium trichloride afforded 2-pyrrolin-5-ones, which are difficult to access by alternative methods as mentioned in this paper.
Abstract: The Hantzsch-type microwave-assisted, solvent-free sequential three-component reaction between primary amines, β-dicarbonyl compounds and α-bromoesters in the presence of indium trichloride afforded 2-pyrrolin-5-ones, which are difficult to access by alternative methods. Ready access to these compounds allowed their use as synthetic building blocks in a target-oriented project aimed at the synthesis of a compound that had previously been postulated as a candidate for HIV integrase inhibition on the basis of computational studies. The versatility of 2-pyrrolin-5-ones was further verified by their use in a diversity-oriented synthesis context, leading to a library of highly functionalized bispiro compounds. The overall process leading to these compounds involved the generation of six bonds and two cycles over three steps, two of which are multicomponent, and the fully controlled generation of up to four stereocenters, including two quaternary ones.
18 citations
TL;DR: An efficient and selective procedure for the synthesis of epiminodibenzo[b,f][1,5]diazocines involving a AB2 three-component reaction is developed, affording arylamine-derived products that could not be accessed previously.
Abstract: An efficient and selective procedure for the synthesis of epiminodibenzo[b,f][1,5]diazocines involving a AB2 three-component reaction is developed. Two equivalents of suitably substituted 2-aminoarylaldehydes reacted with arylamines in the presence of Yb(OTf)3 to afford the desired products in high yields. The reaction is highly atom-economic and waste-free, in addition to allowing the generation of two heterocyclic rings and four C–N bonds in a single operation. Significantly, this approach is complementary to the existing literature procedures, affording arylamine-derived products that could not be accessed previously. A plausible mechanism is proposed involving an imine formation-intermolecular annulation-intramolecular iminium ion cyclization sequence.
18 citations
TL;DR: A series of pyrrolo[3,4-b]quinolines have been synthesized from N-alkynyl aldehydes and various substituted arylamines in good to excellent yields utilizing an intramolecular Povarov reaction catalyzed by boron trifluoride diethyl etherate as the key final step.
Abstract: A series of novel pyrrolo[3,4-b]quinolines have been synthesized from N-alkynyl aldehydes and various substituted arylamines in good to excellent yields utilizing an intramolecular Povarov reaction catalyzed by boron trifluoride diethyl etherate as the key final step.
6 citations
TL;DR: This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions and transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was achieved in a single step.
Abstract: A sequential three-component process is described, starting from 3-arylmethylene-2,5-piperazinediones and involving a one-pot sequence of reactions achieving regioselective opening of the 2,5-diketopiperazine ring and diastereoselective generation of an aziridine ring. This method allows the preparation of N-unprotected, trisubstituted aziridines bearing a peptide side chain under mild conditions. Their transformation into β-trifluoroacetamido-α-ketoamide and α,β-diketoamide frameworks was also achieved in a single step.
4 citations
TL;DR: In this paper, two libraries of bifunctional polycyclic cage structures have been synthesized for the first time in an ionic liquid, 1-butyl-3methylimidazolium bromide ([bmim]Br), employing a sustainable microwave-assisted, one-pot, three-component [3+2] cycloaddition-annulation protocol in good to excellent yields.
Abstract: Two libraries of novel, bifunctional polycyclic cage structures have been synthesized for the first time in an ionic liquid, 1-butyl-3-methylimidazolium bromide ([bmim]Br), employing a sustainable microwave-assisted, one-pot, three-component [3+2] cycloaddition–annulation protocol in good to excellent yields. The ring systems thus generated contain as structural elements bridged, fused and spiro rings and were obtained with complete regio- and stereoselectivity through the creation of two C–C and two C–N bonds, which led to the generation of two azaheterocyclic rings and five adjacent stereogenic carbons, three of which are quaternary.
1 citations
TL;DR: A catalyst-free, three-component reaction between amino alcohols, 1,3-dicarbonyl compounds and α,β-unsaturated aldehydes was developed for the synthesis of fused tetrahydropyridines in water as discussed by the authors.
Abstract: A catalyst-free, three-component reaction between amino alcohols, 1,3-dicarbonyl compounds and α,β-unsaturated aldehydes was developed for the synthesis of fused tetrahydropyridines in water. The β-enaminone formation-initiated domino sequence afforded oxazolo[3,2-a]pyridines and pyrido[2,1-b][1,3]oxazines diastereoselectivity in good yields involving Michael addition, intramolecular cyclization and iminium ion cyclization steps. This environmentally benign protocol is highly atom-economical where the only side product was two molecules of water and no catalyst or reagent was employed. Besides, in a single operation, four new bonds including two C–N, one C–O and one C–C bonds and two heterocyclic rings were created. The reaction was also effective in various green solvents such as glycerol, PEG-200 and lactic acid.
TL;DR: In this article, the aza-vinylogous Povarov reaction between α-ketoimines and α,β-unsaturated dimethylhydrazones in the presence of indium trichloride affords 2-acyl-4-alkyl-4dimethylhexonomethyl-1,2,3,4-tetrahydroquinolines with good cis/trans diastereoselectivities.
Abstract: The aza-vinylogous Povarov reaction between α-ketoimines and α,β-unsaturated dimethylhydrazones in the presence of indium trichloride affords 2-acyl-4-alkyl-4-dimethylhydrazonomethyl-1,2,3,4-tetrahydroquinolines with good cis/trans diastereoselectivities. These compounds were readily transformed into highly substituted 2-acylquinolines using a two-reaction sequence involving the oxidative generation of a C-4 nitrile group, followed by its elimination under thermal conditions. Alternatively, a one-pot protocol based on the reaction of hydrazones with magnesium monoperoxyphthalate hexahydrate in refluxing methanol afforded the target 2-acylquinolines in good to excellent yields. This methodology was also extended to the preparation of 2-arylquinolines.
TL;DR: In this paper, a microwave-assisted, solvent-free sequential three-component reaction of primary amines, β-carbonyl compounds, and α-bromoester was used as synthetic building blocks in a target-oriented project for the synthesis of compound (VI) that is postulated as a candidate for HIV increase inhibition on the basis of computational studies.
Abstract: New 2-pyrrolin-5-ones (IV) are prepared by Hantzsch—type microwave-assisted, solvent-free sequential three-component reaction of primary amines, β-carbonyl compounds, and α-bromoester and utilized e.g. as synthetic building blocks in a target-oriented project for the synthesis of compound (VI) that is postulated as a candidate for HIV increase inhibition on the basis of computational studies.
TL;DR: In this article, a highly efficient synthesis of 5,6-dihydrodibenzo[b,h][1,6]naphthyridines was achieved by reaction between 2-(N-propargylamino)benzaldehydes and arylamines in the presence of CuBr2.
Abstract: A highly efficient synthesis of 5,6-dihydrodibenzo[b,h][1,6]naphthyridines was achieved by reaction between 2-(N-propargylamino)benzaldehydes and arylamines in the presence of CuBr2. The in situ generated electron-deficient heterodienes bearing a tethered alkyne partner underwent an intramolecular inverse electron-demand hetero-Diels–Alder reaction followed by air oxidation to furnish the products in high yields. This reaction tolerated a large number of substituents to afford diverse products under mild conditions. This strategy was also successfully extended to the synthesis of 12,13-dihydro-6H-benzo[h]chromeno[3,4-b][1,6]naphthyridin-6-ones starting from 3-amino-2H-chromen-2-one, again in high yields.
TL;DR: In this article, the use of solvent-free, high-speed vibration milling conditions has allowed the development of a one-pot telescoped process for the synthesis of pyrroles starting from ketones, primary amines, and β-dicarbonyl compounds and comprising an initial α-iodination followed by a three-component Hantzsch-type reaction.
Abstract: The use of solvent-free, high-speed vibration milling conditions has allowed the development of a one-pot telescoped process for the synthesis of pyrroles starting from ketones, primary amines, and β-dicarbonyl compounds and comprising an initial α-iodination followed by an in situ three-component Hantzsch-type reaction. This method was compared with a solution-based protocol from α-iodoketones, primary amines, and β-dicarbonyl compounds. Although both protocols were far more general than previous Hantzsch-type pyrrole syntheses, the mechanochemical method was superior in that it afforded considerably higher yields in spite of comprising an additional step. The stereochemical integrity of the pyrroles obtained from chiral α-aminoesters was maintained. This solvent-free method was also used for the efficient preparation of ter- and quater-aryl/heteroaryl frameworks containing two pyrrole units and a variety of fused pyrrole systems, including benzo[g]indoles, indeno[1,2-b]pyrroles, indoles, and homoindoles.