Additive‐Free Phosphonylation of Chloroheteroarenes via S _N Ar–Arbuzov Reaction: Scope and Limitations

The phosphonylation of electron‐deficient alpha‐chloro‐substituted nitrogen‐containing heteroarenes with triethyl phosphite and triisopropyl phosphite using microwave‐assisted S _N Ar–Arbuzov reaction was studied. The reaction proceeds at 200–270°C in 30–75 min. The efficiency of the method depends on the relationship between substrate reactivity and the product stability against decomposition under the reaction conditions. It was shown that less reactive pyridine and pyrazine derivatives give low yields due to the insufficient stability of the substrates and products. In the case of 1,10‐phenanthroline, quinoline, isoquinoline, quinoxaline, and pyrimidine derivatives, the phosphonylation products were obtained in 40–95% yields due to their higher stability under reaction conditions. An approach to assessing substrate reactivity using quantum chemical calculations is proposed. The reaction does not require transition metals or any other additives. Moreover, it does not affect halogen atoms at other positions of the heterocyclic system, which is beneficial for further modification of the reaction products.