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

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.