Transition-metal-free synthesis of oxazoles: valuable structural fragments in drug discovery

Oxazole, a central structural motif of numerous complex natural products and pharmaceuticals, is closely associated with the development of contemporary drug discovery research due to a diverse portfolio of biological functions. The remarkable medicinal potential and ubiquitous prevalence of oxazoles in synthetic drugs have provided an impetus for their easy accessibility and much effort has been exerted to develop new and efficient methods. In this regard, metal-free reactions for the synthesis of oxazole heterocycles have emerged as an eminent concept over the years due to the toxicity, price or scarcity of some transition-metal- catalyzed reactions. In this review, the various concepts that have proved useful for the development of robust and transition-metal-free methodologies for the construction of oxazole skeleton are presented. A brief description of mechanistic investigations and synthetic utility of these motifs have also been discussed.