Mechanism of the Palladium-Catalyzed Asymmetric Borylative
Migration of Enol Perfluorosulfonates: Insights into an Enantiofacial-Selective
Transmetalation
posted on 2021-07-07, 08:14authored byHelen
A. Clement, Mohamad Estaitie, You-Ri Kim, Dennis G. Hall, Claude Y. Legault
In
2009, one of our laboratories described a palladium-catalyzed
enantioselective borylative migration reaction of heterocyclic enol
perfluorosulfonates that provides ready access to optically enriched,
synthetically useful dihydropyranyl and dehydropiperidinyl allylic
boronates 3 and 4. However, several aspects
of the catalytic cycle and the mechanism of enantiomeric induction
of the anomalous borylation reaction that produces 3 and 4 remain unknown or ambiguous. Herein, a combination of experimental
and computational studies suggests that the reaction is initiated
by a Miyaura-type borylation, followed by an alkene isomerization
pathway involving an electrophilic cationic palladium species. According
to reaction kinetics analysis and computations, the first step of
oxidative addition to afford the alkenylpalladium(II) triflate complex Int-2 is the rate-determining step of the overall reaction.
Following the complexation of pinacolborane to the cationic alkenylpalladium Int-4 to form the hydride complex Int-5, a face-selective
enantio-determining transmetallation via σ-bond metathesis affords
the η-2 alkenylboronate-bound palladium(II) hydride Int-6. While formation of this chiral intermediate is key, the calculations
suggest that the stereoinduction process is further complicated by
a possible reversibility in formation of the intermediate Int-5 preceding the σ-bond metathesis. Moreover, the enantioselectivity
is inversely proportional to the pKaH of
the amine base owing to protonation of the dimethylamine moiety on
the Taniaphos ligand. From Int-6, alkene insertion, β-hydride
elimination, and subsequent deprotonation and decomplexation lead
to the allylboronate product with regeneration of the palladium(0)
catalyst. The ratio of allylboronate to alkenylboronate products depends
primarily on the presence of the heteroatom, which provides relative
π-stabilization of the palladium hydride complex obtained after
alkene isomerization.