Useful Palladium Catalyst for C(sp³)–H Activation

Dichloro[9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene]palladium(II) (1) is a useful catalyst for benzylic C(sp³)–H bond activation. For example, 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 1. Subsequent aminocarbonylation with amines successfully proceeds to afford the corresponding arylacetamides.¹⁾ 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 anti-inflammatory agent ibuprofen can be easily obtained. As a similar synthetic manner, alkoxycarbonylations also proceed by using alcohols instead of amines.²⁾

Typical Procedure:
A mixture of Pd(Xantphos)Cl₂ (7.6 mg, 5 mol%), toluene derivative (20.0 mmol), amine (0.2 mmol) and TBP (53.0 mg, 0.36 mmol) is added into an autoclave. Then the autoclave is purged and charged with CO at 10 atm. The reaction mixture is stirred at 120 °C for 16 h, and then CO is carefully released. The corresponding reaction mixture is purified by flash column chromatography on silica gel to give the desired product.