Structural effects of arsine ligands on C–H difunctionalization of thiophene

Abstract

Despite their significant potential in organometallic chemistry, the utility of arsines as ligands in transition-metal catalysis remains underexplored relative to their phosphine counterparts. Although the Pd-catalyzed C–H difunctionalization of thiophene proceeds efficiently with triphenylarsine (AsPh₃) but fails with conventional phosphine ligands, the synthetic utility of arsine ligands other than AsPh₃ has not been explored. In this study, the steric and electronic requirements of the Pd-catalyzed C–H difunctionalization of thiophene are explored using 36 synthesized arsines and nine phosphines. Ligand parameterization reveals that arsines with moderate electron-donating abilities and sufficient steric accessibility were preferred. Notably, the identified steric demand is more readily met by arsines than by phosphines. Furthermore, arsines exhibit superior oxidative stability under reaction conditions that typically oxidize phosphines owing to the high oxophilicity of phosphorus. These experimental and computational findings demonstrate that the use of arsines can expand the scope of transition metal catalysts by enabling access to catalytic spaces that are less accessible with traditional phosphines.