Understanding Catalyst Structure Selectivity Relationships in Pd-Catalyzed Enantioselective Methoxycarbonylation of Styrene

Catalyst-controlled regioselectivity in palladium, catalyzed carbonylation of allteries has been a long-standing goal of homogeneous catalysis. In general, monophosphines do favor branched regioselectivity, but lead to poor enanticrselectivity, while diphosphines give mainly linear products. Previously, Ave reported the simultaneous control of regio- and enantioselectitity in the hydrolcy- and methoxycarbonylation of vinyl arenes with Pd complexes of the Phanephos ligand. Herein, we present a density functional theollr study (B3PW9I-D3 level of tlieciry) of the catalytic cycle, supported by deuterium labeling studies, to understand its mechanism. Alkene coordination to a Pd-hydride species was identified as the origin of, asymmetric induction and regioselectivity in both the parent Pd/Xylyl-Phanephos catalyst and electron-deficient analogue, and rationalized according to a quadrant-diagram representation. The mechanism by which preferentially formed pro-(S) Pd-alkene complex can isomerize via rotation around the palladium-(C=C) bond was investigated. In the parent system, this process is in competition with the methanolysis step that leads to the ester product and is responsible the overall loss of regiciselectivity. On the other hand, the introduction of;electron-withdrawing substituents on the catalyst frarnework results in the reduction of the methanolysis barriers, making the isomerizatiori pathway energetically unfavorable and so leading simultaneously to high regiocontrol and good enantiomeric ratios.