Cu-catalyzed N-arylation of oxazolidinones: an efficient synthesis of the kappa-opioid receptor Agonist CJ-15161.

An efficient method for intermolecular N-arylation of oxazolidinones using catalytic copper in the presence of a bidentate ligand is reported. The conditions allow the use of copper and can be used to prepare enantiopure N-aryl beta-amino alcohols. A short, scalable synthesis of CJ-15,161 is also reported. The required amines were obtained from the precursor alpha-amino acids or, more conveniently, from the corresponding 1,2-amino alcohols.

Palladium-catalyzed synthesis of N-aryloxazolidinones from aryl chlorides.

An efficient method for intermolecular N-arylation of oxazolidinones using Pd(2)dba(3) and various phosphine ligands in the presence of a weak base is reported. The conditions allow the use of cheaper aryl chlorides containing functionalities such as enolizable ketones, amides, etc., which would be incompatible with other coupling methods. The coupling reaction can be used to prepare enantiopure N-aryl beta-amino alcohols. Depending on the stereoelectronic nature of the aryl chloride, careful choice of ligand was necessary for the success of these reactions. [reaction: see text]

Synthesis of the kappa-agonist CJ-15,161 via a palladium-catalyzed cross-coupling reaction.

Syntheses of CJ-15,161 (1) involving intermolecular N-arylation of an appropriately functionalized diamine, obtained from the precursor alpha-amino acids or, more conveniently, from the corresponding 1,2-amino alcohols via 1,2,3-oxathiazolidine-2,2-dioxide 22, are reported.