Catalyst Free Chemoselective Carbene Insertion Into COO─H Bond Over ─OH of Salicylic Acid

The α- salicylate esters are found in natural products and play a vital role in biological processes. Understanding their structures and functions can provide insights into biochemical pathways and potential therapeutic targets. Herein, we have developed a strategy without the use of metal catalysts or additives for the chemoselective carbene insertion into COO─H bond over ─OH of salicylic acid. Salicylic acids were reacted with diazo compounds to yield α-salicylate esters at 150 °C. Having realized the importance of α-salicylate esters, we have generalized our strategy to various diazo compounds as well as salicylic and thiosalicylic acids. All the reactions produced expected products in good to excellent yields. It has been observed that salicylic acid reacted with diazo compounds in a chemoselective manner while thiosalicylic acid produced a mixture of products. The plausible mechanism of the reaction has been supported by DFT calculations and the origin of the chemoselectivity has been realized with the help of local Fukui functions. All the synthesized α- salicylate esters were isolated and characterized by sophisticated analytical and spectroscopic techniques including single crystal X-ray analysis.