Synthesis of Indolo[2,1-a]isoquinolines via a Triazene-Directed C鈥揌 Annulation Cascade

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• 作者：Huan Sun ; Chengming Wang ; Yun-Fang Yang ; Ping Chen ; Yun-Dong Wu ; Xinhao Zhang ; Yong Huang
• 刊名：Journal of Organic Chemistry
• 出版年：2014
• 出版时间：December 19, 2014
• 年：2014
• 卷：79
• 期：24
• 页码：11863-11872
• 全文大小：568K
• ISSN：1520-6904

文摘

Indole-containing polyaromatic scaffolds are widely found in natural products, pharmaceutical agents, and 蟺-conjugated functional materials. Often, the synthesis of these highly valuable molecules requires a multistep sequence. Therefore, a simple, one-step protocol to access libraries of polyaromatic indole scaffolds is highly desirable. Herein we describe the direct synthesis of polysubstituted indolo[2,1-a]isoquinoline analogues via a double C鈥揌 annulation cascade using triazene as an internally cleavable directing group. Evidence from HRMS and theoretical calculations suggests that an unprecedented 1,2-alkyl migration might be responsible for the in situ cleavage of the directing group. Both kinetic isotope effects and DFT calculations suggested that the alkyne insertion step is rate-limiting for the second C,N annulation reaction.