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Synlett 2011(8): 1133-1136  
DOI: 10.1055/s-0030-1259945
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Synthesis of 2-Aminofuran-3-carbonitriles via Cascade Stetter-γ-Ketonitrile Cyclization Reaction Catalyzed by N-Heterocyclic Carbene

Peng Liua, Min Leia, Lei Ma*a, Lihong Hu*a,b
a School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. of China
Fax: +86(21)64253691; e-Mail: malei@ecust.edu.cn;
b Shanghai Research Center for Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Shanghai, 201203, P. R. of China
e-Mail: simmhulh@mail.shcnc.ac.cn;
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Publication History

Received 14 January 2011
Publication Date:
07 April 2011 (online)

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Abstract

An efficient method for the synthesis of 4,5-disubstituted 2-aminofuran-3-carbonitriles via a cascade Stetter-γ-ketonitrile ­cyclization reaction of aromatic aldehydes with acylidenemalono­nitriles, catalyzed by N-heterocyclic carbenes, has been developed. This procedure provides the corresponding products in moderate to high yields under mild conditions.

Key words

N-heterocyclic carbenes (NHCs) - umpolung - cascade reaction - Stetter reaction - 2-aminofuran

    Primary data for this article are available online and can be cited using the following DOI: 10.4125/pd0010th:
  • Primary Data

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18

General procedure for the synthesis of 4,5-disubstituted 2-aminofuran-3-carbonitriles 3: A flame-dried, round-bottom flask was charged with thiazolium salt 4c (0.5 mmol), aromatic aldehyde 1 (1.0 mmol), acylidenemalononitrile 2 (1.0 mmol), and EtOH (5 mL) under a positive pressure of nitrogen, followed by addition of t-BuOK (1.0 mmol).
The resulting solution was stirred for 0.5-2 h at r.t. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether-EtOAc, 6:1) to afford the product 3.