甲基酮的二氟同系化-卤化反应:一锅法合成β-卤代-α,α-二氟代酮  

Difluorohomologization-Halogenation of Methyl Ketones: One-Pot Synthesis of β-Halo-α,α-Difluoroketones

作　　者：宋晓宁 杨杉 汪欣[2] 王芒[1] Song Xiaoning;Yang Shan;Wang Xin;Wang Mang(Faculty of Chemistry,Northeast Normal University,Changchun 130024;First Hospital of Bethune,Jilin University,Changchun 130021)

机构地区：[1]东北师范大学化学学院,长春130024 [2]吉林大学白求恩第一医院,长春130021

出　　处：《化学学报》2018年第12期983-987,共5页Acta Chimica Sinica

基　　金：国家自然科学基金(No.21672032)资助~~

摘　　要：以(溴二氟甲基)三甲基硅烷(TMSCF2Br)为二氟卡宾源,利用其兼具TMS转移特性及自活化特性,仅在催化量的n-Bu4NBr的催化启动下,直接完成甲基酮的烯醇化-二氟环丙烷化反应以及与卤正离子的开环卤化反应,并使用卤负离子作为卤源,采用其原位氧化形成卤正离子的方法实现了偕二氟环丙烷硅醚的开环-卤化,合成了β-卤代-α,α-二氟代酮类物质.α,α-Difluoroketones represent an important subclass of organofluorine compounds, and have been widely applied in medicinal chemistry, particularly as enzyme inhibitors. Efficient use of organofluorine reagents plays a key role for the synthesis of fluorine-containing organic compounds. As an environmental and efficient difluorocarbene reagent, TMSCF2Br has been well utilized in synthetic applications. In 2013, Hu first utilized TMSCF2Br as a general difluorocarbene source for the difluoromethylenation of alkenes/alkynes as well as the difluoromethylation of O-, S-, N-, and P-nucleophiles. Moreover, Dilman realized the rapid assembly of various CF2-containing products by using TMSCF2Br as a difluorocarbene source, which depended on the concept of three independent components: difluorocarbene, nucleophile, and electrophile. Compared with the previous works, we recently reported a catalytic difluorocyclopropanation of enolizable ketones by using TMSCF2Br reagent, which acts as not only the difluorocarbene source but also the TMS transfer agent. The in situ generated siloxydifluorocyclopropanes were used for the synthesis of α-fluoroenones, o-fluoronaphthols, α,α-difluorocyclopentenones and α,α-difluorocyclopentanones compounds. Here, we report a simple and effective method for the conversion of enolizable ketones to α,α-difluoro-β-halo-substituted ketones. The whole process involves the in situ formation and regioselective ring opening halogenation of siloxydifluorocyclopropanes. The reaction features easily available raw materials, simple operation and practical method. A representative procedure for this reaction is as following: To a dried polytetrafluoroethene (PTFE) sealed pressure tube were added ketone 1 (0.5 mmol), n-Bu4NBr (0.05 mmol, 10 mol%), TMSCF2Br (0.75 mmol) and toluene (2.5 mL) in sequence. The reaction mixture was stirred at 110 ℃ for 2 h, followed by adding an additional amount of TMSCF2Br (0.5 mmol) for another 4 h. Removal of toluene under reduced pressure delivered a mixture mainly

关 键 词：酮 α α-二氟代酮 偕二氟环丙烷硅醚 多米诺反应 

分 类 号：O621.3[理学—有机化学] TQ460.1[理学—化学]