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See, for example: a Pyrroles, The Synthesis Reactivity and Physical Properties of Substituted Pyrroles, Part II (Ed.: R. A. Jones), Wiley, New York, 1992;
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See, for example: a) Pyrroles, The Synthesis Reactivity and Physical Properties of Substituted Pyrroles, Part II (Ed.: R. A. Jones), Wiley, New York, 1992;
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Black, D.S.C.1
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0001426611
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Sundberg, R.J.1
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Kel'in, A.V.1
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e) K. Hiroya, S. Matsumoto, M. Ashikawa, K. Ogiwara, T. Sakamoto, Org. Lett. 2006, 8, 5349-5352;
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24944474895
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g) R. Martín, M. R. Rivero, S. L. Buchwald, Angew. Chem. 2006, 118, 7237-7240;
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Angew. Chem
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Martín, R.1
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33750623389
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Angew. Chem. Int. Ed. 2006, 45, 7079-7082.
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Chem. Int. Ed
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For recent reviews and highlights on pyrrole syntheses through MCRs, see: a
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For recent reviews and highlights on pyrrole syntheses through MCRs, see: a) G. Balme, Angew. Chem. 2004, 116, 6396-6399;
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Angew. Chem
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Balme, G.1
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Angew. Chem. Int. Ed. 2004, 43, 6238-6241;
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V. Cadierno, J. Gimeno, N. Nebra, Adv. Synth. Catal. 2007, 349, 382-394.
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Adv. Synth. Catal
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Cadierno, V.1
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Nebra, N.3
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33645069129
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Brønsted acid catalysed propargylations of several organic substrates, including 1,3-dicarbonyl compounds, with alkynols have been reported: a R. Sanz, A. Martínez, J. M. Álvarez-Gutiérrez, F. Rodríguez, Eur. J. Org. Chem. 2006, 1383-1386;
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Brønsted acid catalysed propargylations of several organic substrates, including 1,3-dicarbonyl compounds, with alkynols have been reported: a) R. Sanz, A. Martínez, J. M. Álvarez-Gutiérrez, F. Rodríguez, Eur. J. Org. Chem. 2006, 1383-1386;
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35
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33847795994
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R. Sanz, D. Miguel, A. Martínez, J. M. Álvarez- Gutiérrez, F. Rodríguez, Org. Lett. 2007, 9, 727-730. In these works, only 5mol% of the acid is required to promote the propargylation process efficiently. In our case, the use of larger quantities of acid (50 mol%) is imperative in order to avoid the Meyer-Schuster isomerisation of the propargylic alcohol catalysed by ruthenium complex 1;
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b) R. Sanz, D. Miguel, A. Martínez, J. M. Álvarez- Gutiérrez, F. Rodríguez, Org. Lett. 2007, 9, 727-730. In these works, only 5mol% of the acid is required to promote the propargylation process efficiently. In our case, the use of larger quantities of acid (50 mol%) is imperative in order to avoid the Meyer-Schuster isomerisation of the propargylic alcohol catalysed by ruthenium complex 1;
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36
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31544473149
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c) V. Cadierno, S. E. García-Garrido, J. Gimeno, Adv. Synth. Catal. 2006, 348, 101-110;
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Adv. Synth. Catal
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Cadierno, V.1
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Gimeno, J.3
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33750524263
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d) V. Cadierno, J. Díez, S. E. García-Garrido. J. Gimeno, N. Nebra, Adv. Synth. Catal. 2006, 348, 2125-2132.
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Adv. Synth. Catal
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Cadierno, V.1
Díez, J.2
García-Garrido, S.E.3
Gimeno, J.4
Nebra, N.5
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38
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37249091068
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This unusual transformation has been previously observed by us while studying the coupling process depicted in Scheme 1 see reference [7, The intermediate carboxylic acid 5 could not be detected by GC/MS, which indicates that its decarboxylation is a highly favoured process
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This unusual transformation has been previously observed by us while studying the coupling process depicted in Scheme 1 (see reference [7]). The intermediate carboxylic acid 5 could not be detected by GC/MS, which indicates that its decarboxylation is a highly favoured process.
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39
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37249084977
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The enantiomeric excess of 7q (> 99% ee; determined by chiral HPLC analysis) was identical to that of the starting amine, a result that confirms the complete stereospecificity of the reaction sequence.
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The enantiomeric excess of 7q (> 99% ee; determined by chiral HPLC analysis) was identical to that of the starting amine, a result that confirms the complete stereospecificity of the reaction sequence.
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40
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24944579952
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Metal-mediated cleavage of propargylic C-N bonds is a well-documented process. For a review on this topic, see
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Metal-mediated cleavage of propargylic C-N bonds is a well-documented process. For a review on this topic, see: S. Escoubet, S. Gastaldi, M. Bertrand, Eur. J. Org. Chem. 2005, 3855-3873.
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(2005)
Eur. J. Org. Chem
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Escoubet, S.1
Gastaldi, S.2
Bertrand, M.3
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41
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0000078290
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2 with primary amines to produce 1,2,3,5-substituted pyrroles: a) A. Arcadi, S. D. Giuseppe, F. Marinelli, E. Rossi, Adv. Synth. Catal. 2001, 343, 443-446;
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2 with primary amines to produce 1,2,3,5-substituted pyrroles: a) A. Arcadi, S. D. Giuseppe, F. Marinelli, E. Rossi, Adv. Synth. Catal. 2001, 343, 443-446;
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42
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0035976093
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A. Arcadi, S. Di Giuseppe, F. Marinelli, E. Rossi, Tetrahedron: Asymmetry 2001, 12, 2715-2720. The intermediate β-enamino ester 11 was not detected by GC/MS, which indicates its great tendency to undergo the annulation.
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b) A. Arcadi, S. Di Giuseppe, F. Marinelli, E. Rossi, Tetrahedron: Asymmetry 2001, 12, 2715-2720. The intermediate β-enamino ester 11 was not detected by GC/MS, which indicates its great tendency to undergo the annulation.
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26444601347
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We have observed that transformation of 10 into 3d is a highly favoured process that can be exclusively promoted by CF 3CO2H (50 mol, in THF at 75°C, Nevertheless, under these conditions, the sequential amination/annulation reaction takes place very slowly and yields 3d in only 43% yield (as determined by GC) after 24 h compare with entry 4 in Table 1, This fact clearly indicates an active role of the Lewis acid-ruthenium species in the reaction sequence. We note that related sequential amination/annulation reactions of 2-propynyl-1,3-dicarbonyl compounds with amines catalysed by trifluoroacetic acid have been described: A. S. Demir, A. Aybey, M. Kayalar, ARKlVOC 2005, 15, 105-116. It is also interesting to note that treatment of 10 with aniline, in THF at 75°C, in the absence of both CF3CO2H and complex 1 leads directly to pyrrole 3d without detection of the intermed
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2H and complex 1 leads directly to pyrrole 3d without detection of the intermediate β-enamino ester 11, albeit in very low yield (approximately 20%; as determined by GC) after 24 h (compare with the catalysed reaction in entry 4 in Table 1; 2 h, 94% yield of isolated product).
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0035909591
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A one-pot four-component synthesis of 1,2,3,5-tetrasubstituted pyrroles from secondary propargylic alcohols, aryl halides, aldehydes and primary amines has been reported. The process, which is catalysed by a Pd/Cu/thiazolium salt/acetic acid system, generates the corresponding tetrasubstituted pyrroles only in moderate yields (49-59%): R. U. Braun, K. Zeitler, T.J.J. Müller, Org. Lett. 2001, 3, 3297-3300.
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A one-pot four-component synthesis of 1,2,3,5-tetrasubstituted pyrroles from secondary propargylic alcohols, aryl halides, aldehydes and primary amines has been reported. The process, which is catalysed by a Pd/Cu/thiazolium salt/acetic acid system, generates the corresponding tetrasubstituted pyrroles only in moderate yields (49-59%): R. U. Braun, K. Zeitler, T.J.J. Müller, Org. Lett. 2001, 3, 3297-3300.
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37249013735
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A closely related one-pot three-component synthesis of fully substituted pyrroles from alkynol 2a, aniline and enolisable ketones, employing [Cp*RuCl(μ2-SMe)2RuCp*Cl, Cp: pentamethylcyclopentadienyl; 10 mol, NH4BF4 (20mol, and PtCl2 (20 mol, has been described. We note that 1) no 1,3-dicarbonyl compounds were used as substrates in this catalytic reaction, 2) large excesses of both the ketone (used as solvent) and aniline (5 equiv relative to 2 a) are required and 3) only moderate yields 44-58, are attained after 100 h under refluxing conditions: Y. Nishibayashi, M. Yoshikawa, Y. Inada, M. D. Milton, M. Hidai, S. Uemura. Angew. Chem. 2003, 115, 2785-2788;
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2 (20 mol%), has been described. We note that 1) no 1,3-dicarbonyl compounds were used as substrates in this catalytic reaction, 2) large excesses of both the ketone (used as solvent) and aniline (5 equiv relative to 2 a) are required and 3) only moderate yields (44-58%) are attained after 100 h under refluxing conditions: Y. Nishibayashi, M. Yoshikawa, Y. Inada, M. D. Milton, M. Hidai, S. Uemura. Angew. Chem. 2003, 115, 2785-2788;
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Chem. Int. Ed
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V. Cadierno, J. Diez, S. E. García-Garrido, J. Gimeno, Chem. Commun. 2004, 2716-2717.
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Chem. Commun
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Cadierno, V.1
Diez, J.2
García-Garrido, S.E.3
Gimeno, J.4
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