Acta Chimica Sinica ›› 2013, Vol. 71 ›› Issue (11): 1488-1491.DOI: 10.6023/A13060581 Previous Articles     Next Articles



于海昕a,b, 万春云b, 韩静a, 李昂b   

  1. a 沈阳药科大学制药工程学院 沈阳 110016;
    b 中国科学院上海有机化学研究所 生命有机化学国家重点实验室 上海 200032
  • 投稿日期:2013-06-01 发布日期:2013-08-14
  • 通讯作者: 韩静, 李昂;
  • 基金资助:

    项目受科技部973计划(No. 2013CB836900)、国家自然科学基金(Nos. 21172235, 21222202, 21290180)、上海市浦江人才计划(12PJ1410800)和中国科学院资助.

A Protocol for α-Bromination of β-Substituted Enones

Yu Haixina,b, Wan Chunyunb, Han Jinga, Li Angb   

  1. a School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China;
    b State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
  • Received:2013-06-01 Published:2013-08-14
  • Supported by:

    Project supported by National Basic Research Program of China (973 program, 2013CB836900), the National Natural Science Foundation of China (Nos. 21172235, 21222202, and 21290180), Shanghai Pujiang Plan (12PJ1410800), and Chinese Academy of Sciences.

α-Haloenone is an important building block in organic synthesis, especially in natural product synthesis. There are at least 4 different reaction modes of this class of compounds: 1, crossing coupling reactions at the α-position; 2, conjugate additions at the β-position; 3, deprotonation at the α'-position; 4, deprotonation at the γ-position. Representative examples of the utilities of α-haloenone include the syntheses of diversonol and the core structures of lomaiviticins and guanacastepenes. From a mechanistic perspective, two types of α-halogenation methods have been developed previously: one through a sequential Baylis-Hillman-type Michael addition/α-halogenation/β-elimination process; the other one involving an electrophilic bromination followed by a β-elimination. The success of the former type of reactions highly depends on the formation of the transient enolate; the β-substituent on the enone substrates drastically slows down the rate of the first Michael addition step which is responsible for the enolate formation. The latter takes advantage of the strong electrophilicity of molecular bromine to overcome the steric effect of the substrates. However, quite a few side reactions including non-selective bromination often occur, resulting in modest to low yield and poor reproducibility of the desired product on a large scale. Here, we report a protocol for α-bromination of β-substituted enones using pyridine hydrobromide perbromide as a brominating reagent. Cyclic enones prove to be suitable substrates for this reaction, and the corresponding products were obtained in >80% yield in general. Notably, β-phenyl cyclohexenone, a rather unreactive substrate due to both steric and electronic reasons, was brominated smoothly. These bromination products may serve as useful synthon in organic synthesis. For acyclic enones and enoates, the reaction has to be performed at elevated temperature, which may be attributable to the rather poor acidity of the α-proton of the dibromo intermediate. The reaction is reliable on a large scale, and the reagents used are safe and low-toxic.

Key words: conjugated enones, α-bromination, addition-elimination mechanism, pyridine hydrobromide perbromide, natural product synthesis