(49b) Isomerization of Epoxides By Tris(Pentafluorophenyl)Borane (BCF): Investigation of Solvent Effects and Induction Period

Epoxides are important intermediates in organic synthesis due to their high reactivity, yielding valuable products which are essential in medicinal and petrochemical industries. They can be easily converted into chemicals with functional groups such as aldehydes, ketones, or alcohols. In particular, the rearrangement of epoxides is an efficient approach to synthesizing aldehydes, where the regioselectivity of this reaction is of great synthetic interest to get the desired carbonyl compound. The isomerization of epoxides has been catalyzed by Lewis acid catalysts (AlCl₃ and BF₃) as well as solid acid catalysts like Al₂O₃, Al₂O₃-SiO₂, ZnO and zeolites. However, each catalytic system had its own limitations, including low efficiency, low aldehyde selectivity, generation of by-products, or hazardous catalysts. Here, we report the isomerization of propylene oxide catalyzed by tris(pentafluorophenyl)borane, also known as BCF. Our previous investigations into BCF-mediated epoxide alcoholysis revealed the existence of multiple catalytic pathways resulting in a complex reaction network. In this work, we explore the isomerization of propylene oxide as a function of reactant concentration, temperature, water level and solvents. We find particularly interesting solvent effects in glycol ethers that are structurally similar to the products of epoxide alcoholysis. As such, we have studied the formation of strong complexes among the catalyst, water, reactants, and glycol ethers, which can influence product selectivity and are slow to convert into the active form of the catalyst. We combine experimental results from heteronuclear Overhauser effect NMR spectroscopy (HOESY) and variable temperature NMR with density functional theory calculations to gain insights on the complexes that are relevant to catalysis. Our findings provide valuable insights into the mechanistic intricacies of epoxide isomerization catalyzed by BCF, offering a deeper understanding of the reaction pathways, and highlighting opportunities for optimizing process conditions in industrial applications.