Acta Chim. Sinica ›› 2018, Vol. 76 ›› Issue (6): 440-444.DOI: 10.6023/A18030083 Previous Articles     Next Articles



关弘浩a, 陈磊b, 刘磊a,b   

  1. a 山东大学药学院 济南 250012;
    b 山东大学化学与化工学院 济南 250100
  • 投稿日期:2018-03-01 发布日期:2018-05-09
  • 通讯作者: 刘磊,
  • 基金资助:


Oxidative C—H Alkynylation of Unactivated Acyclic Ethers

Guan Honghaoa, Chen Leib, Liu Leia,b   

  1. a School of Pharmaceutical Science, Shandong University, Jinan 250012;
    b School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100
  • Received:2018-03-01 Published:2018-05-09
  • Contact: 10.6023/A18030083
  • Supported by:

    Project supported by the National Natural Science Foundation of China (Nos. 21722204, 21472112) and Fok Ying Tung Education Foundation (No. 151035).

C—C bond forming reactions through cross-dehydrogenative coupling (CDC) of two readily available C—H components under oxidative conditions have emerged as one of the most straightforward and economical approaches for increasing molecular complexity and functional group content with minimal waste generation. CDC reactions involving oxidative functionalization of sp3 C—H bonds of both cyclic and acyclic amines with diverse partners have been extensively explored. In sharp contrast, the CDC of corresponding ether substrates remains relatively underdeveloped. Current approaches predominantly focus on cyclic ethers as well as acyclic benzylic ethers. The CDC reaction of extensively existing unactivated acyclic ethers proved to be much more challenging, which might be ascribed to their inherent low reactivity. On the other hand, the existing protocols for unactivated ethers rely heavily on peroxide-mediated oxidation systems, which typically required high temperature and a large excess of ether substrates as the solvent. Accordingly, coupling partners that can be compatible with such harsh conditions are largely restricted to sp2 or sp3 C—H reagents with relatively low manipulation capability, such as arenes, heteroarenes, and 1,3-dicarbonyl moieties. Alkynes represent common structural motifs spread across the fields of biology, chemistry, material science, and medicine, and act as global handles for diverse functionalities. Therefore, the development of a mild approach for CDC of unactivated acyclic ethers with terminal alkynes is highly desired. In 2014, our group developed a mild Ph3CCl/GaCl3 mediated oxidation system, allowing to achieve the oxidative C—H alkynylation of tetrahydrofuran with organoboranes. Herein, we reported the first CDC of unactivated acyclic ethers with terminal alkynes promoted by Ph3CCl/GaCl3. The reaction proceeded at room temperature in CH2Cl2, thus avoiding the employment of excess ether as the solvent. The typical procedure is as follows:a mixture of unactivated acyclic ether (2.0 mmol), terminal alkyne (0.1 mmol), Ph3CCl (0.1 mmol), and CuI (0.03 mmol) in CH2Cl2 at r.t. was added GaCl3 (0.1 mmol) in a glove box to afford the expected coupling products in moderate to good yields. The Ph3CCl/GaCl3 mediated oxidative C—H alkynylation of unactivated acyclic ethers with alkyl substituted alkynylboranes was further established to overcome the relative low efficiency for the CDC reaction involving alkyl substituted terminal alkynes.

Key words: acyclic ether, unactivated ether, terminal alkyne, cross-dehydrogenative coupling, carbocation