Palladium-catalyzed double and single carbonylations of beta-amino alcohols. Selective synthesis of morpholine-2,3-diones and oxazolidin-2-ones and applications for synthesis of alpha-oxo carboxylic acids

Catalytic cross double carbonylation of secondary amines and alcohols proceeds in the presence of [PdCl2(MeCN)(2)] and CuI under carbon monoxide (80 arm) and oxygen (5 atm). Catalytic intramolecular double carbonylation of beta- amino alcohols gives morpholine-2,3-diones, which are excellent protecting compounds of amino alcohols and important precursors for biologically active nitrogen compounds. In contrast, catalytic single carbonylation of B-amino alcohols under a mixture (1:1) of carbon monoxide and oxygen (1.0 atm) proceeds to give oxazolidin-2-ones selectively. The reaction can be explained by assuming a mechanism which includes intramolecular nucleophilic attack of the hydroxy group of (hydroxyethyl)aminocarbonyl ligands on the CO ligand of the carbamoylpalladium(II) complexes, followed by reductive elimination to give morpholine-2,3-diones. In contrast, direct nucleophilic attack of the hydroxy group to the carbamoyl group affords oxazolidin-2-ones. As a common intermediate for the double and single carbonylations, carbamoylpalladium(II) complex has been isolated by the reaction of [PdCl2(PMe(e))(2)] with beta-amino alcohol under CO. The present double carbonylation of amino alcohols provides a novel and convenient method for synthesis of alpha-oxo carboxylic acids. Thus, the morpholine-2,3-diones obtained undergo reaction with Grignard reagents chemoselectively at the ester positions to give 2-substituted 2-hydroxymorpholin-3-ones, which undergo acid hydrolysis to give alpha-oxo carboxylic acids.