Silver-catalyzed site-selective C(sp3)−H benzylation of ethers with N-triftosylhydrazones

• Main Authors: Anderson, E.A (Author), Bi, X. (Author), Jiang, X. (Author), Liu, Z. (Author), Nolan, S.P (Author), Sivaguru, P. (Author), Song, Q. (Author), Wang, H. (Author), Yu, W. (Author)
• Format: Article
• Language: English
• Published: Nature Research 2022
• Subjects: anesthetic agent; Anesthetics, General; catalysis; Catalysis; ether; ether derivative; Ethers; explosive; silver; Silver
• Online Access: View Fulltext in Publisher
• ISBN: 20411723 (ISSN)
• DOI: 10.1038/s41467-022-29323-3

The insertion of carbenes into the α-C–H bonds of ethers represents one of the most powerful approaches to access polysubstituted α-branched ethers. However, intermolecular carbene insertions remain challenging, since current approaches are generally limited to the use of toxic and potentially explosive α-diazocarbonyl compounds. We now report a silver-catalyzed α-C–H benzylation of ethers using bench-stable N-triftosylhydrazones as safe and convenient carbene precursors. This approach is well suited for both inter- and intramolecular insertions to deliver medicinally relevant homobenzylic ethers and 5–8-membered oxacycles in good yields. The synthetic utility of this strategy is demonstrated by its easy scalability, broad scope with valuable functional groups, high regioselectivity, and late-stage functionalization of complex oxygen-containing molecules. The relative reactivities of different types of silver carbenes and C−H bonds were also investigated by experments and DFT calculations. © 2022, The Author(s).