Organocatalytic Enantioselective Synthesis of Axially Chiral N,N′‐Bisindoles

Abstract This study establishes the first organocatalytic enantioselective synthesis of axially chiral N , 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 chiral N , N′ ‐bisindoles were synthesized in good yields and with excellent enantioselectivities (up to 87 % yield and 96 % ee). More importantly, this class of axially chiral N , 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 chiral N , N′ ‐bisindoles using asymmetric organocatalysis and is the first to realize the applications of such scaffolds in medicinal chemistry and asymmetric catalysis.