2-Methyltetrahydrofuran (2-MeTHF): A Green Solvent for Pd−NHC-Catalyzed Amide and Ester Suzuki-Miyaura Cross-Coupling by N−C/O−C Cleavage

Peng Lei, Yun Ling, Jie An, Steven P. Nolan, Michal Szostak

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

The palladium-NHC-catalyzed (NHC=N-heterocyclic carbene) Suzuki-Miyaura cross-coupling of amides and esters via highly chemoselective N−C(O) and O−C(O) cleavage with aryl boronic acids using green, sustainable and eco-friendly 2-methyltetrahydrofuran (2-MeTHF) is reported. A variety of amides and aryl esters were coupled with aryl boronic acids in high to excellent yields. This method employs commercially-available, air- and moisture-stable Pd(II) −NHC precatalysts. Crucially, the use of 2-MeTHF leads to the highest TON reported to date in amide N−C(O) bond cross-coupling. This operationally-simple protocol was utilized in the synthesis a bioactive ketone intermediate, emphasizing the potential of 2-MeTHF as a green solvent in unconventional amide bond disconnection. Given the tremendous importance of amide bond cross-coupling strategies and the drive to maintain full sustainability in cross-coupling processes, we expect that the synthetic method will be of broad interest. (Figure presented.).

Original languageEnglish (US)
Pages (from-to)5654-5660
Number of pages7
JournalAdvanced Synthesis and Catalysis
Volume361
Issue number24
DOIs
StatePublished - Dec 17 2019

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Organic Chemistry

Keywords

  • 2-MeTHF
  • C−N activation
  • C−O activation
  • Pd−NHCs
  • Suzuki-Miyaura
  • cross-coupling

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