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DOI: 10.1055/s-0033-1341193
Pyrroles via Copper-Promoted Oxidative Coupling of Enamides with Alkynes
Publication History
Publication Date:
17 April 2014 (online)
Significance
Reported is the synthesis of pyrroles by the reaction of enamides with alkynes in the presence of Cu(OAc)2, K2CO3 as base, Et3N as an additive, and under oxygen (balloon pressure). In optimization studies, combinations of organic and inorganic bases were tested; use of organic base ( Et3N) in the absence of inorganic base (K2CO3) led to N-acetylated pyrroles. Enamides bearing electron-rich [e.g., R1 = 3-MeOC6H4, 4-MeOC6H4, 3,4-(MeO)2C6H4] and electron-deficient (e.g., 4-ClC6H4, 4-FC6H4, 4-O2NC6H4) groups form the NH pyrroles in 32–82% yield. In addition, fused and cyclic enamides were successful reaction partners. Ethyl-3-phenylpropiolate afforded the desired product in lower yield (28%).
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Comment
Pyrroles are an important class of heterocyclic compounds and building blocks for synthetic pharmaceutical agents, natural products, and materials science (see Review below). Various synthetic methods have been developed for the construction of pyrroles including four component coupling reactions of aldehydes, amines, dialkyl acetylenedicarboxylates, and nitromethane in the presence of molecular iodine (B. Das, N. Bhunia, M. Lingaiah Synthesis 2011, 3471). The present method involves C–H and N–H bond functionalization of enamides.
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Review
V. Estévez, M. Villacampa, J. C. Menéndez Chem. Soc. Rev. 2010, 39, 4402–4421.
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