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

• Published in: Chemical science (Cambridge) Vol. 13; no. 17; pp. 4762 - 4769
• Main Authors: Chen, Zicong, Gu, Changxue, Yuen, On Ying, So, Chau Ming
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 04.05.2022; The Royal Society of Chemistry
• Subjects: Carbonyl compounds; Carbonyls; Chemistry; Palladium; Steric hindrance; Substrates
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d1sc06701j

This study described palladium-catalyzed chemoselective direct α-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 -PR 2 group of the ligand with the C2-alkyl group was found to be the key factor affecting the reactivity and chemoselectivity of the α-arylation reaction. The chemodivergent approach was also successfully employed in the synthesis of flurbiprofen and its derivatives ( e.g. , -OMe and -F). Palladium-catalyzed chemoselective direct α-arylation of carbonyl compounds with chloroaryl triflates in the Ar-Cl bond is reported. The effects of -PR 2 and C2-alkyl groups of the ligands are investigated using experimental and computational methods.