Stereoselective synthesis of atropisomeric amides enabled by intramolecular acyl transfer.

ABSTRACT: C-N atropisomeric amides are important compounds in medicinal chemistry and agrochemistry. Atropselective methods for their synthesis are therefore important. In this study, a novel strategy to make C-N atropisomeric amides based on intramolecular acyl transfer via a tethered Lewis basic pyridine or tertiary amine group is reported. The reactions operate under kinetic control and in most cases are highly atropselective, with the products isolable as pure, single diastereoisomers following chromatography. The kinetically favored atropisomer can also be isomerised into the alternative thermodynamically favored atropisomer upon heating. The kinetic and thermodynamic outcomes are supported by computational studies, while additional mechanistic studies support operation via initia

SUBMITTER: Wootton JM 

PROVIDER: S-EPMC11776508 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature