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

Abstract

The Petasis-type reaction, which couples an imine and boronic acid, is an important tool for CÀ 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 nondirected 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 CÀ 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, sp 2 , and sp 3 -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.

Streamlined Strategy for Scalable and Enantioselective Total Syntheses of the Eburnane Alkaloids

“…Reduction of the lactam to the corresponding hemiaminal with DIBAL-H delivered (+)-eburnamine 2 in an 86% yield as a 7.5:1 mixture of diastereoisomers at C16. Dehydration of (+)-eburnamine by exposure to MsCl in the presence of triethylamine furnished (−)-eburnamenine 1 in an 87% yield. We envisioned completing the synthesis of (−)-dihydroeburnamenine 33 by direct catalytic reduction of the lactam moiety in (−)-eburnamonine 3 (Scheme b).…”