Synthesis and oxidation of chiral 2-thiazolines (4,5-dihydro-1,3-thiazoles)

Abstract

Eight new chiral 2-thiazolines (4,5-dihydro-1,3-thiazoles) 2 have been prepared by treatment of the 2-methyloxazolines 1, the benzoylamino alcohols 4 or the trimethylacetylamino alcohols 5 with P₂S₅. With a 2-methyl substituent, reaction with Oxone^® results in ring-opening to give the acetylamino disulfides 9 and with MCPBA there is also ring-opening with incorporation of a m-chlorobenzoyl group to give 12. Treatment of the 2-phenyl compounds with a variety of oxidants gives the benzoylamino sulfonic acids 10 and the disulfides 9 together with the thiazoles 11 in varying proportions. The sulfonic acids and thiazoles are obtained in pure form by reaction with 3 equiv. of peracetic acid and with sulfur, respectively. Although reaction of 2d–f with KMnO₄ under phase-transfer conditions gives the thiazoles 11, addition of 1 equiv. of benzoic acid results in a complete change in selectivity to afford the thiazoline 1,1-dioxides 3d–f in excellent yield. These compounds prove to be exceptionally moisture-sensitive and readily hydrolyse to give the benzoylamino sulfinic acids 8 whose further oxidation and disproportionation probably explains the formation of the sulfonic acids and disulfides with the other oxidants. The high reactivity of the sulfones 3 towards nucleophilic ring-opening precludes their deprotonation and alkylation. Upon flash vacuum pyrolysis at 600 °C, they fragment to give SO₂, benzonitrile and the alkenes 16 in high yield. Fully assigned ¹³C NMR spectra are presented for the 18 heterocyclic compounds prepared and for 17 acyclic derivatives.