Iodine-Mediated Electrophilic Cyclization of 2-Alkynyl-1-methylene Azide Aromatics Leading to Highly Substituted Isoquinolines and Its Application to the Synthesis of Norchelerythrine

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• 作者：Dirk Fischer ; Hisamitsu Tomeba ; Nirmal K. Pahadi ; Nitin T. Patil ; Zhibao Huo ; Yoshinori Yamamoto
• 刊名：Journal of the American Chemical Society
• 出版年：2008
• 出版时间：November 19, 2008
• 年：2008
• 卷：130
• 期：46
• 页码：15720-15725
• 全文大小：215K
• 年卷期：v.130,no.46(November 19, 2008)
• ISSN：1520-5126

文摘

The reaction of 2-alkynyl-1-methylene azide aromatics 1 with iodine and/or other iodium donors, such as the Barluenga reagent (Py₂IBF₄/HBF₄) and NIS, gave highly substituted cyclization products, namely, the 1,3-disubstituted 4-iodoisoquinolines 2, in good to high yields. Not only simple 2-alkynyl benzyl azides 1a−j and their substituted analogues 1k−u and 6 but also heteroaromatic analogues, including pyridine 8, pyrroles 10a−c, furane 10d, and thiophenes 10e-g, gave the corresponding isoquinoline derivatives in excellent to allowable yields. Electron-donating and electron-accepting substituents on the aromatic ring were equally tolerated, and either acidic or basic (or even neutral) reaction conditions, depending on the reactivity of the substrate, could be applied to smoothly convert the azide starting materials into the desired isoquinoline products in moderate to good yields. Limits were found only in connection with the substituent at the alkyne terminus, where electron-neutral or electron-donating substituents are clearly favored. The iodine-mediated electrophilic cyclization of 1 most probably proceeds through the iodonium ion intermediate 4 followed by nucleophilic cyclization of the azide and subsequent elimination of N₂. This new methodology was successfully applied to the short synthesis of norchelerythrine.