Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates at the C-Cl site

This study described palladium-catalyzed chemoselective direct alpha-arylation of carbonyl compounds with chloroaryl triflates in the Ar-Cl bond. The Pd/SelectPhos system showed excellent chemoselectivity toward the Ar-Cl bond in the presence of the Ar-OTf bond with a broad substrate scope and excellent product yields. The electronic and steric hindrance offered by the -PR2 group of the ligand with the C2-alkyl group was found to be the key factor affecting the reactivity and chemoselectivity of the alpha-arylation reaction. The chemodivergent approach was also successfully employed in the synthesis of flurbiprofen and its derivatives (e.g., -OMe and -F).

Automated summary

This study described a selective palladium-catalyzed direct α-arylation reaction using chloroaryl triflates and carbonyl compounds. The reaction exhibited excellent chemoselectivity towards the Ar-Cl bond with a broad substrate scope and high product yields. The electronic and steric effects of the -PR2 group and C2-alkyl group were found to be crucial for the reactivity and selectivity of the α-arylation reaction. This chemodivergent approach was also successfully applied in the synthesis of flurbiprofen and its derivatives (-OMe and -F).