Cooperative Catalysis-Enabled (4 + 3) Cycloaddition of 2-Indolylmethanols with In Situ- Generated ortho -Naphthoquinone Methides.

A cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols with ortho -naphthoquinone methides ( o -NQMs), which were in situ- generated from enynones, has been established in the presence of silver/Brønsted acid cocatalysts. In the reaction pathway, the key o -NQM intermediates were formed through Ag(I)-catalyzed cyclization of enynones, while the indole-based carbocation intermediates were generated via Brønsted acid-catalyzed dehydration of 2-indolylmethanols. By this approach, a wide range of seven-membered cyclohepta[ b ]indoles were synthesized in good yields with high efficiency under mild reaction conditions, which serves as a useful strategy toward constructing indole-fused seven-membered rings. Moreover, the catalytic asymmetric version of this (4 + 3) cycloaddition has been realized under the cooperative catalysis of Ag(I) with chiral phosphoric acid, which offered chiral cyclohepta[ b ]indole with a good enantioselectivity (75% ee). This work not only represents the first cooperative catalysis-enabled (4 + 3) cycloaddition of 2-indolylmethanols but also provides a good example for o -NQM-involved cycloadditions, which will contribute to the chemistry of 2-indolylmethanols and enrich the research contents of cooperative catalysis.