Readily switchable one-pot 5-exo-dig cyclization using a palladium catalyst

Abstract

A convenient, ligand-free, Pd(OAc)₂-catalyzed one-pot reaction has been developed for the synthesis of oxazolines and oxazoles from easily available acid chlorides and propargylamine. The reaction pathways could be easily modulated to selectively obtain oxazolines or oxazoles by merely changing the additives. This method proceeds via in situ sequential nucleophilic addition/elimination reactions followed by an intramolecular 5-exo-dig cycloisomerization reaction. An interesting observation in this case is the effect of an additive: a basic additive such as triethylamine resulted in the formation of 5-methylene oxazolines, while an acidic additive such as acetic acid resulted in the formation of 5-methyloxazoles. With the current protocol we are able to obtain good to moderate yields of the desired product without the need for the isolation of intermediates.