Silver-Mediated Synthesis of Oxazoles

Significance

Reported is a straightforward silver-mediated synthesis of oxazoles from the reaction of primary amides with bromopyruvates (one example from α-bromoacetophenone). The method is an improvement on the Blümlein-Lewy method, which uses the same starting materials, but in refluxing alcoholic solvent, often resulting in low conversions and undesired byproducts. The addition of silver salts was postulated to drive the reaction by formation of AgBr. While optimizing the reaction, AgSbF₆ was comparable to AgClO₄, but the latter led to product decomposition on prolonged heating. The substrate scope was reasonably well studied; however, the reaction fails with alkyl amides, which is attributed to the ability of the oxazoline intermediate to tautomerize to an enamine species, which is prone to degradation under the reaction conditions. A single example of the synthesis of a trisubstituted oxazole was presented.