Microwave assisted N-directed Pd-catalyzed direct ortho-acyloxylation, and ortho-hydroxylation of benzo[b][1,4]oxazin- 2-ones via C–H activation

Abstract

A novel and highly efficient microwave-assisted palladium-catalyzed method has been developed for the regioselective ortho-acyloxylation, and ortho-hydroxylation of 3-phenyl-2H-benzo[b][1,4]oxazin-2-ones. Utilizing the C–H activation strategy, this protocol exploits the directing effect of nitrogen within the heterocyclic framework, enabling selective introduction of acetoxyl, butoxyl, and hydroxyl groups with excellent regioselectivity and moderate to good yields. The method exhibits broad substrate compatibility and impressive tolerance to various functional groups, offering significant advantages in cost-effectiveness and time efficiency, with reactions completed within minutes and easily scalable to gram quantities. Additionally, late-stage functionalization of hydroxylated compounds via the Suzuki reaction demonstrates the method's utility in drug discovery, facilitating further functionalization of biologically active molecules with outstanding regioselectivity.