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Chemodivergent Tandem Cyclizations of 2‑Indolylmethanols with Tryptophols: C–N versus C–C Bond Formation

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journal contribution
posted on 07.05.2018, 00:00 by Jing-Yi Wang, Ping Wu, Jia-Le Wu, Guang-Jian Mei, Feng Shi
A chemodivergent reaction of 2-indolylmethanols with tryptophols has been established via an interrupted Nazarov-type cyclization in the presence of Brønsted acid, leading to the efficient synthesis of two series of cyclopenta­[b]­indole derivatives in a broad substrate scope with high yields and excellent diastereoselectivities (42 examples, up to 99% yield, all >95:5 dr). It was found that the presence or absence of molecular sieves played an important role in controlling the chemoselectivity of the reaction. In the presence of 3 Å molecular sieves, tryptophol would utilize the nucleophilicity of its nitrogen atom to form a new C–N bond, while, in the absence of molecular sieves, tryptophol would utilize the nucleophilicity of its C2-position to generate a new C–C bond. Therefore, this reaction will provide a good example for additive-controlled chemoselectivity. In addition, this approach not only provides a useful strategy for the synthesis of structurally diversified cyclopenta­[b]­indoles but also demonstrates the practicability of 2-indolylmethanols in organic synthesis.