Kathiravan Subban, Dhillon Prakriti, Zhang Tianshu, Nicholls Ian A
Bioorganic & Biophysical Chemistry Laboratory, Linnaeus University Centre for Biomaterials Chemistry, Department of Chemistry & Biomedical Sciences, Linnaeus University, SE-39182 Kalmar, Sweden.
Molecules. 2024 Nov 29;29(23):5669. doi: 10.3390/molecules29235669.
Unsymmetrical urea derivatives are essential structural motifs in a wide array of biologically significant compounds. Despite the well-established methods for synthesizing symmetrical ureas, efficient strategies for the synthesis of unsymmetrical urea derivatives remain limited. In this study, we present a novel approach for the synthesis of unsymmetrical urea derivatives through the coupling of amides and amines. Utilizing hypervalent iodine reagent PhI(OAc) as a coupling mediator, this method circumvents the need for metal catalysts, high temperatures, and inert atmosphere. The reaction proceeds under mild conditions and demonstrates broad substrate scope, including various primary and secondary amines and primary benzamides. This protocol not only offers a practical and versatile route for synthesizing unsymmetrical ureas but also shows significant potential for the late-stage functionalization of complex molecules in drug development.
不对称脲衍生物是众多具有生物学意义的化合物中的重要结构基序。尽管合成对称脲已有成熟的方法，但合成不对称脲衍生物的有效策略仍然有限。在本研究中，我们提出了一种通过酰胺与胺的偶联来合成不对称脲衍生物的新方法。利用高价碘试剂PhI(OAc)作为偶联介质，该方法无需金属催化剂、高温和惰性气氛。反应在温和条件下进行，并显示出广泛的底物范围，包括各种伯胺、仲胺和伯苯甲酰胺。该方案不仅为合成不对称脲提供了一条实用且通用的途径，而且在药物开发中对复杂分子的后期功能化也显示出巨大潜力。
