A Bioinspired Synthesis of Polyfunctional Indoles

Abstract

Polyfunctional indoles bearing substituents at C5 and C6 are prevalent in natural products, pharmaceuticals, agrochemicals, and materials. Owing to the remoteness of the C5 and C6 positions, indoles of this family can be difficult to prepare, and often require multistep syntheses. Herein, we describe a concise process that converts simple derivatives of tyrosine into 5,6‐difunctionalized indoles by direct oxidation of C−H, N−H, and O−H bonds. Our work draws inspiration from the biosynthetic polymerization of tyrosine to make melanin pigments, but makes an important departure to provide well‐defined indole heterocycles.

Copper(II)-Catalyzed Direct C–H (Hetero)arylation at the C3 Position of Indoles Assisted by a Removable N,N-Bidentate Auxiliary Moiety

“…Indole has been deemed a critical and privileged structural scaffold in drug discovery and is frequently encountered in bioactive natural products and drug candidates, such as the compounds listed in Figure . This moiety therefore occupies a principal position in the production of functional group-substituted indoles in organic synthesis and medicinal chemistry . In this context, a growing number of important studies have explored indole C3 functionalization .…”