Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles

Abstract

AbstractThis study establishes the first organocatalytic enantioselective synthesis of axially chiralN,N′‐bisindoles via chiral phosphoric acid‐catalyzed formal (3+2) cycloadditions of indole‐based enaminones as novel platform molecules with 2,3‐diketoesters, where de novo indole‐ring formation is involved. Using this new strategy, various axially chiralN,N′‐bisindoles were synthesized in good yields and with excellent enantioselectivities (up to 87 % yield and 96 % ee). More importantly, this class of axially chiralN,N′‐bisindoles exhibited some degree of cytotoxicity toward cancer cells and was derived into axially chiral phosphine ligands with high catalytic activity. This study provides a new strategy for enantioselective synthesis of axially chiralN,N′‐bisindoles using asymmetric organocatalysis and is the first to realize the applications of such scaffolds in medicinal chemistry and asymmetric catalysis.