The enantioselective Pd-catalyzed
redox-relay Heck arylation of
acyclic alkenyl alcohols allows access to various useful chiral building
blocks from simple olefinic substrates. Mechanistically, after the
initial migratory insertion, a succession of β-hydride elimination
and migratory insertion steps yields a saturated carbonyl product
instead of the more general Heck product, an unsaturated alcohol.
Here, we investigate the reaction mechanism, including the relay function,
yielding the final carbonyl group transformation. M06 calculations
predict a ΔΔ<i>G</i><sup>⧧</sup> of 1
kcal/mol for the site selectivity and 2.5 kcal/mol for the enantioselectivity,
in quantitative agreement with experimental results. The site selectivity
is controlled by a remote electronic effect, where the developing
polarization of the alkene in the migratory insertion transition state
is stabilized by the C–O dipole of the alcohol moiety. The
enantioselectivity is controlled by steric repulsion between the oxazoline
substituent and the alcohol-bearing alkene substituent. The relay
efficiency is due to an unusually smooth potential energy surface
without high barriers, where the hydroxyalkyl-palladium species acts
as a thermodynamic sink, driving the reaction toward the carbonyl
product. Computational predictions of the relative reactivity and
selectivity of the double bond isomers are validated experimentally
