You Wang, Lanting Xu, D. Ma
Jan 4, 2010
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Influential Citations
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Chemistry, an Asian journal
Abstract
The synthesis of substituted furans is an old but still active research area in organic chemistry. The continuing interest in this topic stems from the fact that these heterocycles play an important role in many aspects. For example, furan is the key structural subunit in an enormous number of bioactive natural products and pharmaceutically important substances, and forms the skeleton of many flavor and fragrance compounds. Additionally, substituted furans are useful and versatile intermediates in synthetic organic chemistry. Among the existing methods for synthesizing substituted furans, cycloisomerization of (Z)-2-en-4-yn-1-ols is one of the most attractive approaches because of the potential to form polysubstituted furans with great diversity. For this transformation, the often-used promoters or catalysts are strong bases (such as KOtBu) or transition-metal (like ruthenium, palladium, e] and gold ) complexes. In 1990, V gh and co-workers disclosed that copper(II) could catalyze the conversion of (Z)-3-methyl-2-penten-4yn-1-ol into 3,3-dimethylfuran. Although only this one example has been examined, the potential of copper salts as the catalysts for the cycloisomerization of (Z)-2-en-4-yn-1ols prompted us to develop a cascade process to synthesize substituted furans from substituted 3-iodoprop-2-en-1-ols 2 and 1-alkynes 1. As outlined in Scheme 1, we envisaged that after CuI/amino acid catalyzed cross-coupling of 1 and 2 to afford substituted (Z)-2-en-4-yn-1-ols 3, the free hydroxyl group would attack the C C triple bond under the assistance of the copper salt (complex 4) to give cyclization products 5. From the intermediates 5, substituted furans 7 could be formed through two possible pathways. One is protonation of 5 and subsequent isomerization of the heterocycles 6. The other possible pathway involves isomerization of 5, followed by protonation of the resultant intermediates 8. With this idea in mind, we conducted a CuI/amino acid catalyzed reaction of 1-ethynylbenzene 1 a with (Z)-3-iodo2-phenylbut-2-en-1-ol 2 a. It was found that under our previous reaction conditions for cross-coupling of vinyl iodides and terminal alkynes (N,N-dimethylglycine as the ligand, Cs2CO3 as the base, dioxane as the solvent, 80 8C) [6a] the desired furan 7 a was isolated in 70 % yield (Table 1, entry 1). Encouraged by this result, we attempted to improve the yield by changing the reaction conditions. It was found that a better yield could be obtained by using l-proline as a ligand (Table 1, entry 2), which is consistent with results observed in our indole formation. Switching the base to K2CO3 and K3PO4 failed to give better results (Table 1, en[a] Y. Wang, L. Xu Department of Chemistry Fudan University Shanghai 200433 (China) [b] Prof. Dr. D. Ma State Key Laboratory of Bioorganic & Natural Products Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai 200032 (China) Fax: (+86) 21-64166128 E-mail : madw@mail.sioc.ac.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/asia.200900523. Scheme 1. Coupling/cycloisomerization cascade process to polysubstituted furans from substituted 3-iodoprop-2-en-1-ols and 1-alkynes.