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2012 , Vol. 70 >Issue 18: 1917 - 1922

DOI: https://doi.org/10.6023/A12080542

研究论文

仲酰胺经酰胺活化直接合成酮的普适性方法

  • 肖开炯 ,
  • 黄应红 ,
  • 黄培强
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  • 化学生物学福建省重点实验室 厦门大学化学化工学院化学系 厦门 361005

收稿日期: 2012-08-11

  网络出版日期: 2012-08-31

基金资助

项目受国家重点基础研究发展计划(973 计划)(No. 2010CB833200)、国家自然科学基金(Nos. 21072160, 20832005)和教育部博士研究生学术新人奖(2010)资助.

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General Direct Transformation of Secondary Amides to Ketones via Amide Activation

  • Xiao Kaijiong ,
  • Huang Yinghong ,
  • Huang Peiqiang
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  • Fujian Provincial Key Laboratory of Chemical Biology, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005

Received date: 2012-08-11

  Online published: 2012-08-31

Supported by

Supporting information for this article is available free of charge via the Internet at http://sioc-journal.cn. Project supported by the National Basic Research Program (973 Program) of China (No. 2010CB833200), the National Natural Science Foundation of China (Nos. 21072160, 20832005), and a Scholarship Award for Excellent Doctoral Student granted by Ministry of Education of China (2010).

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摘要

本文报道仲酰胺经去胺基烷基化反应直接合成酮的通用性方法. 这一新的C-C 键形成方法是基于Tf2O 对仲酰胺的活化及有机铈试剂对活化所形成活性中间体的加成而实现的. 该方法可用于各种酮的合成, 包括烷基-烷基酮、烷基-芳基酮、芳基-芳基酮、α,β-不饱和酮以及β-氯-α,β-不饱和酮等, 收率65%～90%. 研究表明, 除了有机铈试剂外, 碱性较弱的炔基硼试剂、温和亲核性的烯丙基三甲基硅烷以及低亲核性的苯乙烯均可与仲酰胺的活化中间体进行加成反应, 水解后生成相应的酮. 因此, 该方法具有较好的普适性和重要的合成应用价值. 基于实验结果和验证实验, 提出经由腈鎓中间体的可能反应机理. 本法使仲酰胺成为形式上的酰化试剂, 不但可与有机金属试剂反应, 还可与烯丙基三甲基硅烷和苯乙烯进行还原酰化反应.

关键词： 仲酰胺; 酮; 有机铈试剂; 分子活化; C-C 键形成; 还原酰化

本文引用格式

肖开炯 , 黄应红 , 黄培强 . 仲酰胺经酰胺活化直接合成酮的普适性方法[J]. 化学学报, 2012 , 70(18) : 1917 -1922 . DOI: 10.6023/A12080542

Abstract

Carbon-carbon bond formation and functional group transformation are two cornerstones of organic synthesis. Generally, most of the established methods involve the transformation of a more reactive molecule to a more stable one, while the inverse transformation from a more stable molecule to a more reactive one is challenging. Secondary amides are a class of quite stable compounds, and ketones are a class of extremely versatile compounds enabling a number of fundamental transformations. The direct transformation of secondary amides into ketones is of high relevance in organic synthesis. Nonetheless, no such method has been reported when this work was disclosed. Here, we report in detail the general direct transformation of secondary amides into ketones by Tf2O-mediated deaminative alkylation with organocerium reagents. The influence of the base additive and the organometallic reagent on this transformation was investigated. It was found that 2-fluoropyridine gave the best results of the bases screened, and both organocerium reagents (RCeCl2) generated in situ from RLi and CeCl3 and cerium complexes generated in situ from RMgX and CeCl3 are superior to organomagnesium, organolithium and organozinc reagents. The optimum reaction condition was thus determined as successive treatment of a dichloromethane (0.25 mol/L) solution of secondary amide (1.0 equiv.) and 2-fluoropyridine (1.2 equiv.) with 1.1 molar equivalents of Tf2O (-78℃, then 0℃), and 3.0 molar equivalents of RM/CeCl3 (-78℃), followed by hydrolysis with 2 mol/L aqueous HCl solution. This protocol shows wide substrate applicability. Using the developed method, a variety of ketones including alkyl-alkyl ketones, alkyl-aryl ketones, aryl-aryl ketones, α,β-unsaturated ketones, and β-chloroenones have been synthesized in 65%～90% yields. It should be noted that the reaction of α,β-unsaturated amides led to a highly selective 1,2-addition and the use of alkynyl cerium reagents generated from lithium acetylides yielded β-chloroenones. Moreover, weakly basic alkynylborane reagents and allyltrimethyl silane, and even weakly nucleophilic styrene can also be applied as nucleophiles for the deaminative alkylation of secondary amides. On the basis of the experimental results, a plausible mechanism involving nitrilium ion intermediate and ketimine is proposed. As one significance of these transformations, secondary amides successfully serve as effective acylating reagents in the intermolecular reactions with organometallic reagents, allyltrimethyl silane and styrene (reductive acylation).

Key words： secondary amides; ketones; organocerium reagents; molecular activation; C-C bond formation; reductive acylation

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