Acta Chimica Sinica ›› 2024, Vol. 82 ›› Issue (2): 119-125.DOI: 10.6023/A23110487 Previous Articles     Next Articles

Special Issue: 有机氟化学合集



邓沈娜a,b, 彭常春c, 牛云宏a,b, 许云c, 张云霄a,b, 陈祥a,b, 王红敏c, 刘珊珊a,b, 沈晓a,b,*()   

  1. a 武汉大学 高等研究院 武汉 430072
    b 武汉大学深圳研究院 深圳 518057
    c 江西济民可信药业有限公司 宜春 336000
  • 投稿日期:2023-11-02 发布日期:2023-12-20
  • 基金资助:
    国家重点研发计划(2022YFA1506100); 广东省基础与应用基础研究基金(2021A1515010105); 广东省基础与应用基础研究基金(2021A1515110248); 国家自然科学基金(21901191); 江西济民可信药业有限公司(YC-RD-202111-0005)

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

Shenna Denga,b, Changchun Pengc, Yunhong Niua,b, Yun Xuc, Yunxiao Zhanga,b, Xiang Chena,b, Hongmin Wangc, Shanshan Liua,b, Xiao Shena,b()   

  1. a The Institute for Advanced Studies, Wuhan University, Wuhan 430072
    b Shenzhen Research Institute of Wuhan University, Shenzhen 518057
    c Jiangxi Jemincare Pharmaceutical Co., Ltd, Yichun 336000
  • Received:2023-11-02 Published:2023-12-20
  • Contact: E-mail:
  • Supported by:
    National Key Research and Development Program of China(2022YFA1506100); Guangdong Basic and Applied Basic Research Foundation(2021A1515010105); Guangdong Basic and Applied Basic Research Foundation(2021A1515110248); National Natural Science Foundation of China(21901191); Jiangxi Jemincare Pharmaceutical Co., Ltd(YC-RD-202111-0005)

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 of α-fluoroalkyl alcohols through manganese-catalyzed radical Brook rearrangement of α-fluoroalkyl-α-silyl methanols. The operationally simple reaction showed broad substrate scope, and the product could be prepared on gram scale. Twenty-five α-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 a α-alkyl alcohol which afford the desired olefin difunctionalization product in 36% yield. A representative 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), 4Å MS (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 was purified by silica gel column chromatography to obtain corresponding target product.

Key words: radical Brook rearrangement, olefin difunctionalization, three component reaction, Mn-catalysis