Unlocking Indazole Synthesis from α-Diazo-β-Ketoesters via Aryne Trapping: A Streamlined Approach

Abstract

Indazoles are high-value chemical building blocks used in medicinal chemistry and materials science for their distinct structural and functional features. This study details a [3 + 2]-cycloaddition reaction between various aryl-ketodiazoesters and ortho-(trimethylsilyl)aryl triflates under mild conditions, leading predominantly to 1-acyl-1H-indazoles. N-aryl-1H-indazoles and aryl benzoates are also observed as other products. The reaction exhibits broad functional group tolerance and scalability, making it a valuable synthetic approach. Mechanistic insights, derived from control experiments and density functional theory calculations, elucidate the cycloaddition pathway and rationalize the formation of the products. Collectively, these findings underscore the method's potential for synthesizing complex indazole derivatives, which hold significant promises for applications in pharmaceutical development and advanced materials research.