Wang Linxuan, Qi Jialin, Li Haoyu, Xu Zhenghu
School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China.
Dongguan Key Laboratory of Interdisciplinary Science for Advanced Materials and Large-Scale Scientific Facilities, School of Physical Sciences, Great Bay University (Great Bay, Institute for Advanced Study), Dongguan, 523000, China.
Chemistry. 2025 Jan 27;31(6):e202403722. doi: 10.1002/chem.202403722. Epub 2024 Nov 21.
The β-lactam scaffolds are the prevalent structural units in antibiotics and natural products. Herein, three-component asymmetric Kinugasa/aldol and Kinugasa/Mannich cascade reactions have been developed for constructing α-quaternary chiral β-lactams. This method involved the tandem reaction of alkynes, nitrones and aldehydes (or imines), resulting in the formation of three sequential stereocenters controlled by copper(I) catalysts and chiral bis(oxazolidine) ligands. The developed protocol features high enantioselectivity, good reaction efficiency, and mild operational conditions, representing a practical and sustainable synthetic tool for the construction of functionalized chiral β-lactams.
β-内酰胺骨架是抗生素和天然产物中普遍存在的结构单元。在此，已开发出三组分不对称衣笠反应/羟醛缩合反应和衣笠反应/曼尼希串联反应来构建α-季碳手性β-内酰胺。该方法涉及炔烃、硝酮和醛（或亚胺）的串联反应，通过铜（I）催化剂和手性双（恶唑烷）配体控制形成三个连续的立体中心。所开发的方案具有高对映选择性、良好的反应效率和温和的操作条件，是构建功能化手性β-内酰胺的实用且可持续的合成工具。
