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

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.