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

Catalyst-controlled regioselectivity
in palladium-catalyzed carbonylation
of alkenes has been a long-standing goal of homogeneous catalysis.
In general, monophosphines do favor branched regioselectivity, but
lead to poor enantioselectivity, while diphosphines give mainly linear
products. Previously, we reported the simultaneous control of regio-
and enantioselectivity in the hydroxy- and methoxycarbonylation of
vinyl arenes with Pd complexes of the Phanephos ligand. Herein, we
present a density functional theory study (B3PW91-D3 level of theory)
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 the 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 for the overall loss of regioselectivity. On the other
hand, the introduction of electron-withdrawing substituents on the
catalyst framework results in the reduction of the methanolysis barriers,
making the isomerization pathway energetically unfavorable and so
leading simultaneously to high regiocontrol and good enantiomeric
ratios.