Development of a Non‐Directed Petasis‐Type Reaction by an Aromaticity‐Disrupting Strategy

The Petasis-type reaction, which couples an imine and boronic acid, is an important tool for C−C bond formation in organic synthesis. However, the generality of this transformation has been limited by the requirement for a directing heteroatom to enable reactivity. Herein, we report the development of a non-directed Petasis-type reaction that allows for the coupling of trifluoroborate salts with α-hydroxyindoles. By disrupting aromaticity to generate a reactive iminium ion, in conjunction with using trifluoroborate nucleophiles, the method generates a new C−C bond without the need for a directing group. This reaction is operationally simple, providing α-functionalized indoles in up to 99 % yield using sp, sp², and sp³-hybridized trifluoroborate nucleophiles. Finally, this reaction is applied as a novel bioconjugation strategy to link biologically active molecules and toward the convergent synthesis of non-natural heterodimeric bisindole alkaloid analogs.