The Reaction Mechanism of the Enantioselective Tsuji Allylation: Inner-Sphere and Outer-Sphere Pathways, Internal Rearrangements, and Asymmetric C–C Bond Formation

We use first principles quantum mechanics (density functional
theory) to report a detailed reaction mechanism of the asymmetric
Tsuji allylation involving prochiral nucleophiles and nonprochiral
allyl fragments, which is consistent with experimental findings. The
observed enantioselectivity is best explained with an inner-sphere
mechanism involving the formation of a 5-coordinate Pd species that
undergoes a ligand rearrangement, which is selective with regard to
the prochiral faces of the intermediate enolate. Subsequent reductive
elimination generates the product and a Pd0 complex. The
reductive elimination occurs via an unconventional seven-centered
transition state that contrasts dramatically with the standard three-centered
C–C reductive elimination mechanism. Although limitations in
the present theory prevent the conclusive identification of the enantioselective
step, we note that three different computational schemes using different
levels of theory all find that inner-sphere pathways are lower in
energy than outer-sphere pathways. This result qualitatively contrasts
with established allylation reaction mechanisms involving prochiral
nucleophiles and prochiral allyl fragments. Energetic profiles of
all reaction pathways are presented in detail.