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

Abstract

An iron(III) triflate catalyzed Friedländer-type heteroannulation of 2-(2-aminophenyl)-N,N-dialkyl-2-oxoamides with α-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 C3substituent. 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.

Organocatalytic Atroposelective Construction of Axially Chiral Compounds Containing Benzimidazole and Quinoline Rings

“…Therefore, the development of convenient and efficient methods for the construction of diverse axially chiral biaryls has attracted considerable attention over the past decades . In comparison with typical aromatic axially chiral compounds, such as biphenyls and binaphthyls, examples of heteroaromatic axially chiral compounds, particularly benzimidazole and quinoline ring-containing axially chiral compounds, have rarely been reported. , The synthesis of 2-, 4-, 5-, and 8-aryl axially chiral quinolines has been accomplished through the kinetic resolution of axially chiral 5- or 8-aryl quinolines via asymmetric transfer hydrogenation, the enantioselective modification of 8-aryl quinolines by aromatic electrophilic halogenation or aromatic C–H olefination, the enantioselective Suzuki–Miyaura cross-coupling reaction of aryl boronic acids with 5- or 8-bromoquinolines, and the organocatalytic atroposelective heterocycloaddition of 2-aminoaryl ketones/aldehydes with 1,3-dicarbonyl compounds or alkynes (Scheme a) . To the best of our knowledge, only a few studies on the synthesis of 1-aryl axially chiral benzimidazoles, which involved organocatalytic atroposelective heterocycloaddition or enantioselective intramolecular Buchwald–Hartwig reaction, have been reported (Scheme b) .…”