Concise Synthesis of Furo[2,3-b]indolines via [3,3]-Sigmatropic Rearrangement of N-Alkenyloxyindoles

A concise new synthetic route to furo[2,3-b]indolines has been developed by taking advantage of the reactivity of N-alkenyloxyindole intermediates. These compounds spontaneously undergo [3,3]-sigmatropic rearrangement followed by cyclization to form hemiaminals as single diastereomers. Tin-promoted N-hydroxyindole formation followed by conjugate addition to activated alkynes provides simple and modular access to a diverse array of N-alkenyloxyindoles and their corresponding furo[2,3-b]indolines. Microscale high-throughput experimentation was used to facilitate investigation of the scope and tolerance of this transformation and related studies on the nucleophilic aromatic substitution and rearrangement of N-hydroxyindoles with halogenated arenes have also been evaluated.

Automated summary

A concise new synthetic route to furo[2,3-b]indolines has been developed by utilizing the reactivity of N-alkenyloxyindole intermediates. These compounds undergo spontaneous [3,3]-sigmatropic rearrangement followed by cyclization to form hemiaminals as single diastereomers. The tin-promoted formation of N-hydroxyindole followed by conjugate addition to activated alkynes provides simple and modular access to a diverse array of N-alkenyloxyindoles and their corresponding furo[2,3-b]indolines.