Novel synthesis of 2-iminooxazolines from α-hydroxy ketones by using Lewis acid catalyst

Abstract

Synthetic methods available for the construction of heterocyclic molecules can be used to affect a number of valuable synthetic transformations. We recently reported a synthesis of 2-imino-1,3-thiazolines 3 which showed antifungal¬¬1 ¬¬and T-type calcium channel inhibitory activities.2 2-Imino-1,3-thiazolines are isoform of 2-amino-1,3-thiazole, which known to be privileged structure in the medicinal chemistry for development of new pharmaceuticals.3 2-Imino-1,3-oxazolines are oxygen analogue of the 2-imino-1,3-thiazolines and expected to show biological activity. While 2-imino-1,3-thiazolines were synthesized by the reaction of α-halo ketone and thiourea in quantitative yield the oxygen analogue, 2-imino-1,3-oxazolines could not prepared by the reaction of α-halo ketone and urea. As an extension of our studies of lead optimization of this series, we now report here a novel synthesis of 2-imino-1,3-oxazolines 2 from the reaction of α-hydroxy ketone 1 and imide in the presence of Lewis acid catalyst. The synthetic methodology report here is convenient for preparation of 2-imino-1,3-oxazoline derivatives. We will discuss the possible reaction mechanism and the regiochemistry of the products.