Zn(OTf)2-Promoted Isocyanide-Based Three-Component Reaction: Direct Access to 2-Oxazolines and β-Amino Amides

An efficient one-pot reaction of propargylamides, isocyanides, and water catalyzed by zinc was developed for the rapid construction of 2-oxazolines with a wide functional group tolerance. The methylene-3-oxazoline was proven to play a vitally important role to start the tandem cascade transformation through unfunctionalized alkynes with sequential nucleophilic addition approaches of isocyanide and water. Notably, with a slight alteration of the reaction temperature and the addition of one molecule of water, various beta-amino amide derivatives were synthesized in good to excellent yields.

Automated summary

An efficient one-pot reaction using zinc as catalyst was developed for the rapid synthesis of 2-oxazolines with a wide range of functional groups. Methylene-3-oxazoline was found to play a vital role in initiating the tandem cascade transformation through unfunctionalized alkynes by sequentially adding isocyanide and water. By slightly adjusting the reaction temperature and adding one molecule of water, various beta-amino amide derivatives were synthesized in good to excellent yields.