A green, transition-metal-free synthetic strategy was developed for the efficient construction of endocyclic urea-containing heterocycles, opening a novel avenue for the targeted synthesis of these high-value molecular frameworks. Serving as key regulatory media, fluorinated alcohol solvents can drive the in situ conversion of bench-stable dioxazolones into highly reactive isocyanate intermediates that participate in subsequent cyclization reactions. Characterized by high atom economy and excellent substrate generality. It not only enables the efficient preparation of a series of quinazolinone derivatives via a skeletal recasting strategy of isatoic anhydrides but also facilitates the synthesis of hydantoins using amino acid esters as starting materials, while achieving precise structural modification of diverse pharmaceutical molecules. Boasting broad functional group tolerance, the reaction system obviates the need for catalysts, harsh reaction conditions, and redundant additives. Fully aligned with the core principles of green chemistry, this protocol provides a new paradigm for the sustainable synthesis of heterocyclic compounds and the efficient creation of functional drug derivatives.
Cai et al. (Fri,) studied this question.