Modular Synthesis of Trisubstituted 3-Oxazol-5(2H)-ones from α-Keto Acids, Ketones, and Ammonium Salt by Multicomponent Strategy

In this report, we describe a direct and mild three-component reaction for the modular synthesis of 2,2,4-trisubstituted 3-oxazol-5(2H)-ones from ubiquitous α-keto acids, ketones, and ammonium salt. Significantly, a diverse library of trisubstituted 3-oxazol-5(2H)-ones (120 examples), including pharmaceutical derivatives, was efficiently obtained without the need for any extra catalysts or additives. The scalability of this method was demonstrated on a 200 mmol scale in 87% yield. Mechanistically, two possible reaction paths were proposed. Additionally, herbicidal activity and crop safety were tested to evaluate the biological activity of the title compounds, providing a promising platform for the design of herbicides.