Bendazac

Carboxylic acids are readily available chemicals with broad applications in chemistry‐related areas, and their coupling with amines and alcohols is a fundamental transformation in organic synthesis. However, the catalytic enantioselective coupling of carboxylic acids remains elusive, especially for the atroposelective reaction. Here we report a chiral Brønsted acid (CBA)‐catalyzed atroposelective coupling of carboxylic acids with amines and alcohols using ynamides as coupling reagents. The novel enantiocontrol involving CBA‐catalyzed ester addition enables the straightforward construction of axially chiral amides and planar‐chiral esters with high enantioselectivities through atroposelective intermolecular amidation and intramolecular macrolactonization. Diverse medicinally relevant carboxylic acids can undergo direct late‐stage modification by this method. Importantly, this reaction represents the first atroposelective coupling of carboxylic acids with amines, as well as the first chemocatalytic atroposelective coupling of carboxylic acids with alcohols. The resulting atropisomeric skeletons can be readily derivatized to chiral ligands and catalysts for asymmetric catalysis.

Decarboxylative alkylation of carboxylic acids with easily oxidizable functional groups such as phenol and indole functionalities was achieved using a catalytic amount of basic iron(III) acetate, Fe(OAc)2(OH), in the presence of benzimidazole under 427 nm LED irradiation. Kinetic analyses of this catalytic reaction revealed that the reaction rate is first‐order in alkenes and is linearly correlated with the light intensity; the faster reaction rate for the benzimidazole‐ligated species was consistent with the increased absorbance in the visible light region. Wide functional group tolerance for the easily oxidizable groups is ascribed to the weak oxidation ability of the in situ‐generated oxo‐bridged iron clusters compared with other iron(III) species.