Addition/Oxidative Rearrangement of 3-Furfurals and 3-Furyl Imines: New Approaches to Substituted Furans and Pyrroles
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- 作者：Ann Rowley Kelly ; Michael H. Kerrigan ; Patrick J. Walsh
- 刊名：Journal of the American Chemical Society
- 出版年：2008
- 出版时间：March 26, 2008
- 年：2008
- 卷：130
- 期：12
- 页码：4097 - 4104
- 全文大小：131K
- 年卷期：v.130,no.12(March 26, 2008)
- ISSN：1520-5126
文摘
Furans and pyrroles are important synthons in chemical synthesis and are commonly found innatural products, pharmaceutical agents, and materials. Introduced herein are three methods to prepare2-substituted 3-furfurals starting from 3-furfural, 3-bromofuran, and 3-vinylfurans. Addition of a variety oforganolithium, Grignard, and organozinc reagents (M-R) to 3-furfural provides 3-furyl alcohols in high yields.Treatment of these intermediates with NBS initiates a novel oxidative rearrangement that results in theinstallation of the R group in the 2 position of the 2-substituted 3-furfurals. Likewise, metalation of3-bromofuran with n-BuLi and addition to benzaldehyde provides a furyl alcohol that is converted to 2-phenyl3-furfural upon oxidative rearrangement. Enantioenriched disubstituted furans can be prepared startingwith the Sharpless asymmetric dihydroxylation of 3-vinylfurans. The resulting enantioenriched diols undergothe oxidative rearrangement to furnish enantioenriched 2-substituted 3-furfurals with excellent transfer ofasymmetry. This later method has been applied to the enantioselective preparation of an intermediate inHonda's synthesis of the natural product (-)-canadensolide. Mechanistic studies involving deuterium-labeledfuryl alcohol suggest that the oxidative rearrangement proceeds through an unsaturated 1,4-dialdehydeintermediate. The alcohol then cyclizes onto an aldehyde, resulting in the elimination of water andrearomatization. On the basis of this proposed mechanism, we found that 3-furyl imines undergo the additionof organometallic reagents to provide furyl sulfonamides. Under the oxidative rearrangement conditions,2-substituted 3-formyl pyrroles are formed, providing a novel route to these heterocycles. In contrast to themetalation of heterocycles, which often lead to mixtures of regioisomeric products, these new oxidativerearrangements of furyl alcohols and furyl sulfonamides generate only one regioisomer in each case.