一种简单、高效合成α-卤代甲基酮化合物的新方法

Mild and Efficient Method for Synthesis of α-Halomethylketones

发展了一种简单、高效、温和的卤代炔烃水合反应体系.在阳离子金催化剂的催化作用下,以二氯乙烷为溶剂,室温下卤代炔烃发生水合反应,高收率、高区域选择性地得到单一的α-卤代甲基酮化合物(收率≥91%).该方法具有底物适用范围广、反应条件温和和环境友好等优点,为含α-卤代甲基酮结构单元的天然产物及复杂药物分子的合成提供了新方法.

α-Halomethylketones are building blocks for the synthesis of various compounds due to their selective transformations with different reagents. Moreover, a wide range of α-halomethylketone derivatives at-tract increasing interests in pharmaceutical chemistry. α-Halomethylketones are also widespread used as inter-mediates in organic synthesis, such as in Favorskii rearrangement and Reformatsky reaction. However, their direct synthesis from the corresponding methylktones by N-halosuccinimides, molecular halogen and metal halides has been plagued by poor regioselectivity and over-halogenation. For the above reasons, a simple, convenient and environmentally benign protocol to synthesize the α-halomethylketones was developed by cata-lytic hydration of haloalkynes, which can be easily prepared in one step from commercial terminal alkynes. In the presence of 3% （molar fraction） BrettPhosAuNTf2 and 3 mmol H2 O in dichloroethane at room temperature, a broad range of haloalkynes were converted into α-halomethylketones in excellent yield through gold-catalyzed hydration reaction. The presented methodology will provide new strategies for α-halomethylketones-type drug design and synthesis, which has important academic significance and application value.