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

Indole-containing polyaromatic scaffolds are widely found in natural products, pharmaceutical agents, and π-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 polyaromat...

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Bibliographic Details
Published in:Journal of organic chemistry 2014-12, Vol.79 (24), p.11863-11872
Main Authors: Sun, Huan, Wang, Chengming, Yang, Yun-Fang, Chen, Ping, Wu, Yun-Dong, Zhang, Xinhao, Huang, Yong
Format: Article
Language:English
Subjects:
Catalysis
Indoles - chemical synthesis
Indoles - chemistry
Isoquinolines - chemical synthesis
Isoquinolines - chemistry
Molecular Structure
Triazenes - chemistry
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Summary:Indole-containing polyaromatic scaffolds are widely found in natural products, pharmaceutical agents, and π-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–H 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.
ISSN:0022-3263
1520-6904
DOI:10.1021/jo500807d