Chiral Phosphoric Acid-Catalyzed Enantioselective Synthesis of Axially Chiral Compounds Involving Indole Derivatives.

Abstract

Indoles are one of the most ubiquitous subclass of N-heterocycles and are increasingly incorporated to design new axially chiral scaffolds. The rich profile of reactivity and N-H functionality allow chemical derivatization for enhanced medicinal, material and catalytic properties. Although asymmetric C-C coupling of two arenes gives the most direct access of axially chiral biaryl scaffolds, this chemistry has been the remit of metal catalysis and works efficiently on limited substrates. Our group has devoted special interest in devising novel organocatalytic arylation reactions to fabricate biaryl atropisomers. In this realm, indoles and derivatives have been reliably used as the arylation partners in combination with azoarenes, nitrosonapthalenes and quinone derivatives. Their efficient interaction with chiral phosphoric acid catalyst as well as the tunability of electronics and sterics have enabled excellent control of stereo-, chemo- and regioselectivity to furnish diverse scaffolds. In addition, indoles could act as nucleophiles in desymmetrization of 1,2,4-triazole-3,5-diones. This account provides a succinct illustration of these developments.