Chemodivergent Tandem Cyclizations of 2-Indolylmethanols with Tryptophols: C-N versus C-C Bond Formation.

ABSTRACT

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 >955 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.