Hydrazones as Productive Dienophiles in the Inverse Electron Demand Diels-Alder Reactions of 1,3,5-Triazines

Enamines, ynamines and amidines are common dienophiles for inverse electron demand Diels-Alder (IEDDA) reactions of 1,3,5-triazines, however, their wide utilization may be limited due to their poor stability to conventional purification methods such as silica gel chromatography. To address this limitation, oximes and hydrazones are envisioned as potential alternative dienophiles, even though they are primarily used as protecting groups due to their excellent stability or lack of reactivity. Through investigation of substituent effects and optimization of reaction conditions, oximes and hydrazones were developed as productive dienophiles for 1,3,5-triazine IEDDA reactions, leading to the desired IEDDA products in moderate (for oximes) to excellent (for hydrazones) yields. Hydrazones are air-stable and can be conveniently purified by conventional methods, therefore the introduction of hydrazones as productive dienophiles further expanded the scope of 1,3,5-triazine IEDDA reactions.