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Volumn 133, Issue 4, 2011, Pages 740-743

An atom-economic synthesis of nitrogen heterocycles from alkynes

Author keywords

[No Author keywords available]

Indexed keywords

AMBIENT TEMPERATURES; CASCADE REACTIONS; HETEROCYCLES; NITROGEN HETEROCYCLES; REACTION CONDITIONS;

EID: 79851505291     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja110117g     Document Type: Article
Times cited : (110)

References (39)
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    • (c) For a general review of pyrrole heterocycle syntheses see: Bergman, J.; Janosik, T. In Comprehensive Heterocyclic Chemistry III; Jones, G., Ramsden, C. A., Eds.; Elsevier: Amsterdam, 2008; Vol. 3, pp 269-351. For reviews regarding the prevalence and biological importance of pyrrole heterocycles see:
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    • A reviewer has suggested that coupling of 1 and 2 may involve allene tautomer 1a see below. Our previous success utilizing acceptors 1b and 1d, where competitive formation of 1c was not observed and where formation of an allene intermediate is not possible, respectively, suggests that allene intermediates are not involved. For the use of 1b see reference 2a, and for the use of 1d see
    • A reviewer has suggested that coupling of 1 and 2 may involve allene tautomer 1a (see below). Our previous success utilizing acceptors 1b and 1d, where competitive formation of 1c was not observed and where formation of an allene intermediate is not possible, respectively, suggests that allene intermediates are not involved. For the use of 1b see reference 2a, and for the use of 1d see: Trost, B. M.; Gunzner, J. L.; Yasukata, T. Tetrahedron Lett. 2001, 42, 3775.
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    • Isopyrroles related to 4 have been reported:, In addition, isofurans were observed as intermediates in previous work see ref 2a. In both cases, however, the reactivity of these intermediates was not explored
    • Isopyrroles related to 4 have been reported: Larock, R. C.; Doty, M. J.; Han, X. Tetrahedron Lett. 1998, 39, 5143. In addition, isofurans were observed as intermediates in previous work (see ref 2a). In both cases, however, the reactivity of these intermediates was not explored.
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    • Acceptor 1 is prepared in two steps from commercially available Boc-propargyl amine. See Supporting Information for details
    • Acceptor 1 is prepared in two steps from commercially available Boc-propargyl amine. See Supporting Information for details.
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    • reaction is tolerant of a variety of solvents. In this study PhMe displayed the best compromise between reaction time and yield
    • The reaction is tolerant of a variety of solvents. In this study PhMe displayed the best compromise between reaction time and yield.
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    • Attempts to isomerize 3k or 4k to 5k under basic and acidic conditions returned low isolated yields of the desired product. 3k could be cyclized to 5k under thermal conditions but required unacceptably high temperatures >100 °C and reaction times >48 h
    • Attempts to isomerize 3k or 4k to 5k under basic and acidic conditions returned low isolated yields of the desired product. 3k could be cyclized to 5k under thermal conditions but required unacceptably high temperatures (>100 °C) and reaction times (>48 h).
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    • Following complete conversion, the reaction mixture is filtered through a short column of fluorosil to provide analytically pure samples of the isopyrrole. See Supporting Information for details
    • Following complete conversion, the reaction mixture is filtered through a short column of fluorosil to provide analytically pure samples of the isopyrrole. See Supporting Information for details.
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    • 4 simplified product mixtures which were typically composed of alcohol 6c and the corresponding ketone
    • 4 simplified product mixtures which were typically composed of alcohol 6c and the corresponding ketone.
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    • Functionalization of 5k would require stoichiometric amounts of activating agents and would reduce the overall atom economy of this process
    • Functionalization of 5k would require stoichiometric amounts of activating agents and would reduce the overall atom economy of this process.
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    • 2 in the conversion of 3k to 5k Table 2. Nevertheless, under the conditions described in Scheme 3, substituted isopyrrole products were not detected. We speculate that the additional additives present under these conditions promote the isomerization of ispoyrrole intermediates into the corresponding pyrrole products
    • 2 in the conversion of 3k to 5k (Table 2). Nevertheless, under the conditions described in Scheme 3, substituted isopyrrole products were not detected. We speculate that the additional additives present under these conditions promote the isomerization of ispoyrrole intermediates into the corresponding pyrrole products.


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