Synthesis of Imidazolidinone-Fused 3,1-Benzoxazines via One-Pot Multicomponent Reactions

A novel palladium-catalyzed one-pot multicomponent reaction has been developed for the efficient synthesis of imidazolidinone-fused 3,1-benzoxazine derivatives from simple and readily available starting materials, including 2-aminoarylmethyl alcohols, ethyl glyoxylate, and amines. Notably, this transformation proceeds under mild conditions with a broad substrate scope, high <i>trans-</i>selectivity, and operational simplicity. The method enables the efficient construction of five new bonds and two ring moieties in one pot process, offering straightforward access to structurally diverse polycyclic fused 3,1-benzoxazine derivatives. Density functional theory (DFT) calculations were employed to elucidate the reaction mechanism and rationalize the observed <i>trans</i>-selectivity. Preliminary biological evaluations revealed promising antifungal activity in selected derivatives.