Design and synthesis of axially chiral aryl-pyrroloindoles via the strategy of organocatalytic asymmetric (2 + 3) cyclization

Abstract

The catalytic asymmetric construction of axially chiral indole-based frameworks is an important area of research due to the unique characteristics of such frameworks. Nevertheless, research in this area is still in its infancy and has some challenges, such as designing and constructing new classes of axially chiral indole-based scaffolds and developing their applications in chiral catalysts, ligands, etc. To overcome these challenges, we present herein the design and atroposelective synthesis of aryl-pyrroloindoles as a new class of axially chiral indole-based scaffolds via the strategy of organocatalytic asymmetric (2 + 3) cyclization between 3-arylindoles and propargylic alcohols. More importantly, this new class of axially chiral scaffolds was derived into phosphines, which served as efficient chiral ligands in palladium-catalyzed asymmetric reactions. Moreover, theoretical calculations provided an in-depth understanding of the reaction mechanism. This work offers a new strategy for constructing axially chiral indole-based scaffolds, which are promising for finding more applications in asymmetric catalysis.

Keywords

• Asymmetric organocatalysis
• Axial chirality
• Indole
• Atroposelectivity
• Enantioselectivity
• Cyclization