Electronic and steric effects of phosphine ligands on the linear regioselectivity of propylene methoxycarbonylation

The propylene methoxycarbonylation is a potential atom-economical reaction for the synthesis of butyrate esters, which minimizes wastewater discharge and alleviates subsequent separation difficulties. However, to the best of our knowledge, the mechanism of this reaction has not been thoroughly investigated, and the regioselectivity enhancement remains challenging. Herein, we studied the structure-performance relationship of Palladium-based homogeneous catalysts with different monophosphine and bisphosphine ligands by combining experiments and theoretical calculations. The ligands primarily influence the catalytic activity through electronic effects, while regulating product regioselectivity through steric effects. Using an optimized catalyst, the turnover frequency reaches 12,500 h-1 with a normal-to-iso selectivity ratio of 15.8, representing 13.9-fold and 6.6-fold improvements over a conventional palladium–phosphine catalyst. Mechanistic calculations reveal that regioselectivity is determined by the hydrogen insertion position in the first elementary step. Our work fills a gap in propylene methoxycarbonylation research and provides a basis for rational design of regioselective catalysts. Propylene methoxycarbonylation offers an atom-economical route to synthesize butyrate esters, yet its mechanism and regioselectivity remain underexplored. Here, the authors investigate the structure–performance relationship of Pd-based catalysts with various monophosphine and bisphosphine ligands, revealing that electronic and steric effects enhance catalytic activity and regioselectivity.