Gold-Catalyzed [2+2+1] Synthesis of 2,5-Disubstituted Oxazoles

Significance

Reported is the synthesis of 2,5-disubstituted oxazoles 3 via the gold-catalyzed oxidation of alkynes 1 followed by reaction with ­nitriles 2. Due to the mild reaction conditions, a broad range of functional groups are tolerated on the alkyne component, including aldehydes, halides, protected amines, alcohols, and thiols. Both aliphatic and aromatic alkynes participate equally well in the reaction. The nitrile is typically used as the solvent (0.1 M concentration). However, for expensive nitriles, only three equivalents are sufficient to obtain decent yields in the absence of another solvent (using 1 mol% BrettPhosAuNTf₂ as catalyst).