Acylation of pyrrolidine-2,4-diones: a synthesis of 3-acyltetramic acids. X-Ray molecular structure of 3-[1-(difluoroboryloxy)ethylidene]-5-isopropyl-1-methyl-pyrrolidine-2,4-dione

Abstract

Pyrrolidine-2,4-diones, prepared from the corresponding α-amino acid esters by condensation with ethoxycarbonylacetic acid, Dieckmann cyclisation, and hydrolysis–decarboxylation, are acylated at C-3 by the acid chlorides of saturated, unsaturated, and arenecarboxylic acids in the presence of Lewis acids. The most efficient protocol involves boron trifluoride–diethyl ether as Lewis acid, isolation of the neutral boron difluoride complexes of the 3-acyltetramic acids, and their subsequent methanolysis. The quaternary ammonium enolates of 5-substituted pyrrolidine-2,4-diones undergo isomerisation to the exocyclic Δ^5,6-isomers during O-acylation with acid chlorides.