Mechanism of the Palladium-Catalyzed Asymmetric Borylative Migration of Enol Perfluorosulfonates: Insights into an Enantiofacial-Selective Transmetalation

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 pK_aH 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.