Titanium(IV)-mediated tandem deprotection-cyclodehydration of protected cysteine N-amides: Biomimetic syntheses of thiazoline- and thiazole-containing heterocycles

[GRAPHICS] The scope and limitations of TiCl4-mediated Delta(2)-thiazoline synthesis v ia tandem deprotection-dehydrocyclization of trityl-protected cysteine N-am ides is presented. While chemical yields are acceptable (53-96%), the stere ochemical outcomes vary on the basis of structural considerations and react ion conditions (22-99% ee). Racemization at the C(2)-exomethine position li mits the utility of this method for the formation of a thiazoline within a peptide. Treatment of a tritylated Cys-Cys dipeptide with TiCl4 afforded th e corresponding thiazole-thiazoline heterocycle 12 (38% yield, 97% ee).