Electrostatic Control of Regioselectivity in Au(I)-Catalyzed Hydroarylation

Competing pathways
in catalytic reactions often involve transition
states with very different charge distributions, but this difference
is rarely exploited to control selectivity. The proximity of a counterion
to a charged catalyst in an ion paired complex gives rise to strong
electrostatic interactions that could be used to energetically differentiate
transition states. Here we investigate the effects of ion pairing
on the regioselectivity of the hydroarylation of 3-substituted phenyl
propargyl ethers catalyzed by cationic Au­(I) complexes, which forms
a mixture of 5- and 7-substituted 2H-chromenes. We
show that changing the solvent dielectric to enforce ion pairing to
a SbF6– counterion changes the regioselectivity
by up to a factor of 12 depending on the substrate structure. Density
functional theory (DFT) is used to calculate the energy difference
between the putative product-determining isomeric transition states
(ΔΔE‡) in both the
presence and absence of the counterion. The change in ΔΔE‡ upon switching from the unpaired transition
states in high solvent dielectric to ion paired transition states
in low solvent dielectric (Δ­(ΔΔE‡)) was found to be in good agreement with the
experimentally observed selectivity changes across several substrates.
Our calculations indicate that the origin of Δ­(ΔΔE‡) lies in the preferential electrostatic
stabilization of the transition state with greater charge separation
by the counterion in the ion paired case. By performing calculations
at multiple different values of the solvent dielectric, we show that
the role of the solvent in changing selectivity is not solely to enforce
ion pairing, but rather that interactions between the ion paired complex
and the solvent also contribute to Δ­(ΔΔE‡). Our results provide a foundation for exploiting
electrostatic control of selectivity in other ion paired systems.