Catalytic Heteroannulation for the Synthesis of Quinoline-4-Carboxamides Bearing Axial Chirality

An iron(III) triflate catalyzed Friedlander-type heteroannulation of 2-(2-aminophenyl)-N,N-dialkyl-2-oxoamides with alpha-methylene carbonyl derivatives has been established, allowing facile access to a range of biologically interesting quinoline-containing tertiary amides in good yields. Investigations into the configurational stability of products led to the identification of a new type of stable axially chiral quinoline-4-carboxamide bearing a sterically demanding phenylsulfonyl C3-substituent. Subsequently, an enantioselective catalytic variant was attempted. The employment of copper(II) catalysis using a chiral bisoxazoline ligand was found to be capable of providing moderate enantiocontrol.

Automated summary

An iron(III) triflate catalyzed Friedlander-type heteroannulation method has been developed for the synthesis of various quinoline-containing tertiary amides. The study also identified a stable axially chiral quinoline-4-carboxamide and attempted an enantioselective catalytic reaction.