Synthesis of Molecular Hybrids Based on Nucleophilic Heterocycles Mediated by HAT Processes

Hydrogen Atom Transfer processes represent one of the most efficient strategies for the direct functionalization of sp² and sp³ carbons¹. Phenolic compounds methylated at the ortho or para positions generate quinone methides (QMs) — highly electrophilic intermediates² that readily react with nucleophiles, such as nitrogen-containing heterocycles, which are widely recognized for their biological relevance³. This work aims to develop an efficient synthetic protocol for obtaining molecular hybrids derived from uracils and other heterocycles conjugated to 1,2-di-tert-butyl-4-methylphenol (BHT). To this end, the TEMPO radical will be employed as catalyst together with Na₂S₂O₈ to promote the formation of the BHT-derived QM, in the presence of uracil. After some preliminary tests, the target product was obtained in 24% yield using 20 mol% TEMPO and 1 equiv. Na₂S₂O₈. After complete optimization, this strategy will enable the synthesis of a wide variety of substituted and biologically active products based on uracils and other nitrogen-containing heterocycles.