Synthesis of Arylacetamides via Benzylic C-H Bond Activation using a Palladium Catalyst

Huang et al. have reported the palladium-catalyzed oxidative aminocarbonylation via benzylic C-H bond activation. According to their results, under the presence of CO and di-tert-butyl peroxide (=TBP), benzylic C-H bonds of alkyl aromatics are selectively activated by the action of Pd(Xantphos)Cl₂ catalyst. Subsequent aminocarbonylation with amines successfully proceeds to afford the corresponding arylacetamides. This reaction can be applied to substrates bearing a halogen substituent, and a subsequent cross-coupling reaction facilitates expedient synthesis of complex arylacetamides. By using this protocol, the marketed drug ibuprofen can be easily obtained.