Ring-closing C–O/C–O metathesis of ethers with primary aliphatic alcohols

• Published in: Nature communications 2023-04, Vol.14 (1), p.1883-1883, Article 1883
• Main Authors: Liu, Hongmei, Huang, Qing, Liao, Rong-zhen, Li, Man, Xie, Youwei
• Format: Article
• Language: English
• Subjects: 639/638/549; 639/638/77/888; Alcohol; Alcohols; Aliphatic alcohols; Chemical reactions; Computer applications; Ethers; Humanities and Social Sciences; Metathesis; multidisciplinary; Organic chemistry; Science; Science (multidisciplinary); Substrates; Textbooks
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-37538-1

In canonical organic chemistry textbooks, the widely adopted mechanism for the classic transetherifications between ethers and alcohols starts with the activation of the ether in order to weaken the C–O bond, followed by the nucleophilic attack by the alcohol hydroxy group, resulting in a net C–O/O–H σ-bond metathesis. In this manuscript, our experimental and computational investigation of a Re 2 O 7 mediated ring-closing transetherification challenges the fundamental tenets of the traditional transetherification mechanism. Instead of ether activation, the alternative activation of the hydroxy group followed by nucleophilic attack of ether is realized by commercially available Re 2 O 7 through the formation of perrhenate ester intermediate in hexafluoroisopropanol (HFIP), which results in an unusual C–O/C–O σ-bond metathesis. Due to the preference for the activation of alcohol rather than ether, this intramolecular transetherification reaction is therefore suitable for substrates bearing multiple ether moieties, unparalleled by any previous methods. Transetherifications between ethers and alcohols are fundamental organic reactions that are frequently used for the preparations of unsymmetrical ethers. In this article, the authors challenge the fundamental tenets of the traditional transetherification mechanism via systematic experimental and computational investigations of a Re 2 O 7 -mediated annulation.