Photoinduced [3+2] Cycloaddition of Carbenes and Nitriles: A Versatile Approach to Oxazole Synthesis

Abstract

We have developed a photoinduced protocol for the synthesis of pharmaceutically important oxazole molecules using diazo- and nitrile-containing reactants. The process involves the initial photolysis of the diazo compound to afford singlet carbenes, which are tapped by nitriles in a [3+2] cycloaddition fashion to give substituted oxazoles. With di-nitrile compounds, useful bis-oxazoles were obtained. The applicability of the transformation is showcased through the expedient synthesis of small-molecule drugs and biologically relevant molecules such as felbinac, pimprinine, texamine, ugnenenazole etc. The protocol is also useful for the generation of ² H and ¹³ C isotope labelled oxazoles. Merging photolysis with continuous-flow chemistry was demonstrated for scaling up the reaction. The non-requirement of metal catalysis or photosensitizers to harness the light energy with blue light sufficing the execution of the reaction makes it a versatile and general protocol for the synthesis of structurally diverse oxazoles.