自由基Brook重排调控的α-氟烷基-α-硅基甲醇参与的烯烃双官能团化反应  

Radical Brook Rearrangement Mediated Olefin Difunctionalization Involvingα-Fluoroalkyl-α-silyl Methanols

作　　者：邓沈娜 彭常春 牛云宏 许云 张云霄 陈祥 王红敏 刘珊珊 沈晓 Deng Shenna;Peng Changchun;Niu Yunhong;Xu Yun;Zhang Yunxiao;Chen Xiang;Wang Hongmin;Liu Shanshan;Shen Xiao(The Institute for Advanced Studies,Wuhan University,Wuhan 430072;Shenzhen Research Institute of Wuhan University,Shenzhen 518057;Jiangxi Jemincare Pharmaceutical Co.,Ltd,Yichun 336000)

机构地区：[1]武汉大学高等研究院,武汉430072 [2]武汉大学深圳研究院,深圳518057 [3]江西济民可信药业有限公司,宜春336000

出　　处：《化学学报》2024年第2期119-125,共7页Acta Chimica Sinica

基　　金：国家重点研发计划(No.2022YFA1506100);广东省基础与应用基础研究基金(Nos.2021A1515010105,2021A1515110248);国家自然科学基金(No.21901191);江西济民可信药业有限公司(No.YC-RD-202111-0005)资助。

摘　　要：α-氟烷基醇是药物分子的重要结构单元.以锰络合物为催化剂,以α-氟烷基-α-硅基甲醇为试剂,通过自由基Brook重排,对烯烃进行双官能团化的三组分反应模块化合成了α-氟烷基醇化合物.该反应操作简单,底物普适性良好,能够进行克级规模的制备,有一定的应用潜力.Incorporation of fluorine has always been a conventional strategy for designing new drugs and materials because it can usually improve the physiochemical and physiological properties of organic molecules.Among various organofluorine compounds,α-fluoroalkyl alcohols are of particular importance and they are important skeletons of bioactive molecules.Herein,we report a three components olefin difunctionalization reaction for the synthesis ofα-fluoroalkyl alcohols through manganese-catalyzed radical Brook rearrangement ofα-fluoroalkyl-α-silyl methanols.The operationally simple reaction showed broad substrate scope,and the product could be prepared on gram scale.Twenty-fiveα-fluoroalkyl alcohols have been synthesized in 44%~86%yields.It is compatible with a variety of halogen substituents(F,Cl,Br),electron donating OMe and naphthalenyl groups and is also suitable for different symmetrical aryl olefins,asymmetric aryl olefins and alkoxyl olefins.The reaction is also compatible with different nucleophiles such as aryl carboxylic acids and anilines.Besides,the reaction is compatible with aα-alkyl alcohol which afford the desired olefin difunctionalization product in 36%yield.A rep-resentative procedure is described as follows.In the glovebox,α-difluoromethyl-α-dimethylphenylsilyl methanol(64.8 mg,0.3 mmol),1,1-stilbene(223 mg,0.3 mmol),benzoic acid(110 mg,0.9 mmol),Mn(OAc)_(2)(2.6 mg,0.015 mmol),tert-butyl peroxybenzoate(TBPB,175 mg,0.9 mmol),4ÅMS(30 mg)and dry dichloromethane(DCM,0.5 mL)were added to a dry 10 mL reaction tube equipped with a magnetic agitator.The reaction mixture was then removed from the glove box,stirred at 70℃for 1 h.Then tetrabutylammonium fluoride(TBAF,0.36 mmol)was added at 0℃.After 30 min,the reaction mixture was quenched with saturated sodium bicarbonate aqueous solution(10 mL),extracted with ethyl acetate(10 mL×3).The organic phase was combined,washed with saturated NaCl aqueous solution and dried with anhydrous sodium sulfate and concentrated under vacuum.Then the crude product

关 键 词：自由基Brook重排 烯烃双官能团化 三组分反应 锰催化 

分 类 号：O621.251[理学—有机化学]