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

Abstract

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.

Chromium-Catalyzed Selective Borylation of Vinyl Triflates and Unactivated Aryl Carboxylic Esters with Pinacolborane

“…17−19 It has been reported that the reaction of vinyl triflates with HBpin by palladium catalysis mainly led to allylic borylation. 20,21 Because of these competing reactions, the use of HBpin as an atomefficient boron source in the borylation of esters is underdeveloped and remains chemoselectively challenging. Studies in the field currently focus on the use of precious palladium and rhodium as catalysts.…”

“…The borylation of these esters provides a useful tool in forming vinylated and arylated boron feedstocks, which are currently dominated by using diborons such as B 2 pin 2 and B 2 nep 2 as boron reagents via loss of one boron functionality (Figure a). − Compared with diboron-based ester borylation, the use of pinacolborane (HBpin) as a boron source for borylation is of interest because of the atom efficiency, and it usually occurs along with evolution of hydrogen. However, ester scaffolds can be hydrided by the hydrogen or HBpin formed in situ, giving reduced side compounds of de-esterificated olefins, reduced alkanes, arenes, or arenols (Figure b). − It has been reported that the reaction of vinyl triflates with HBpin by palladium catalysis mainly led to allylic borylation. , Because of these competing reactions, the use of HBpin as an atom-efficient boron source in the borylation of esters is underdeveloped and remains chemoselectively challenging. Studies in the field currently focus on the use of precious palladium and rhodium as catalysts.…”