Sinead T. Keaveney

Towards reaction control using an ionic liquid: biasing outcomes of reactions of benzyl halides

The effect of the ionic liquid 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide on substitution and elimination reactions of benzyl halides is examined and solvent control of the reaction outcome demonstrated. In competing reactions, the ionic liquid is shown to favour unimolecular processes over bimolecular processes and substitution over elimination, irrespective of the mole fraction of ionic liquid used. Temperature dependent analyses, where possible, are used to determine the microscopic origins of these effects.

Effect of Modifying the Anion of an Ionic Liquid on the Outcome of an SN2 Process

The effect of a series of ionic liquids containing different anions (bis(trifluoromethanesulfonyl)imide, dicyanimide, hexafluorophosphate, tetrafluoroborate, and bromide) on the rate constant of a bimolecular substitution process was investigated. A general ionic liquid effect was noted, with increases in the rate constant observed in all ionic liquids used when compared with that in acetonitrile. Temperature-dependent kinetic data allowed calculation of activation parameters in each of the reaction mixtures considered; these parameters showed that the microscopic origins of the rate enhancements observed were not the same for all of the ionic liquids used, demonstrating the importance of the nature of the anion.

Computational approaches to understanding reaction outcomes of organic processes in ionic liquids

This review considers how various computational methods have been applied to explain the changes in reaction outcome on moving from a molecular to an ionic liquid solvent. Initially, different conceptual approaches to modelling ionic liquids are discussed, followed by a consideration of the limitations and constraints of these approaches. A series of case studies demonstrating the utility of computational approaches to explain processes in ionic liquids are considered; some of these address the solubility of species in ionic liquids while others examine classes of reaction where the outcome in ionic liquids can be explained through the application of computational approaches. Overall, the utility of computational methods to explain, and potentially predict, the effect of ionic liquids on reaction outcome is demonstrated.

Ionic liquid solvents: the importance of microscopic interactions in predicting organic reaction outcomes

Abstract Ionic liquids are attractive alternatives to molecular solvents as they have many favourable physical properties and can produce different organic reaction outcomes compared to molecular solvents. Thus far, interactions between the ionic liquid components and specific sites (such as charged centres, lone pairs and π systems) on the reagents and transition state have been identified as affecting reaction outcome; a comprehensive understanding of these interactions is necessary to allow prediction of ionic liquid solvent effects. This manuscript summarises our recent progress in the development of a framework for predicting the effect of an ionic liquid solvent on the outcome of organic processes. There will be a particular focus on the importance of the different interactions between the ionic liquid components and the species along the reaction coordinate that are responsible for the changes in reaction outcome observed in the cases described.

Palladium-Catalyzed Decarbonylative Trifluoromethylation of Acid Fluorides

Abstract While acid fluorides can readily be made from widely available or biomass‐feedstock‐derived carboxylic acids, their use as functional groups in metal‐catalyzed cross‐coupling reactions is rare. This report presents the first demonstration of Pd‐catalyzed decarbonylative functionalization of acid fluorides to yield trifluoromethyl arenes (ArCF3). The strategy relies on a Pd/Xantphos catalytic system and the supply of fluoride for transmetalation through intramolecular redistribution to the the Pd center. This strategy eliminated the need for exogenous and detrimental fluoride additives and allows Xantphos to be used in catalytic trifluoromethylations for the first time. Our experimental and computational mechanistic data support a sequence in which transmetalation by R3SiCF3 occurs prior to decarbonylation.

Modular Functionalization of Arenes in a Triply Selective Sequence: Rapid C(sp2) and C(sp3) Coupling of C−Br, C−OTf, and C−Cl Bonds Enabled by a Single Palladium(I) Dimer

Abstract Full control over multiple competing coupling sites would enable straightforward access to densely functionalized compound libraries. Historically, the site selection in Pd0‐catalyzed functionalizations of poly(pseudo)halogenated arenes has been unpredictable, being dependent on the employed catalyst, the reaction conditions, and the substrate itself. Building on our previous report of C−Br‐selective functionalization in the presence of C−OTf and C−Cl bonds, we herein complete the sequence and demonstrate the first general arylations and alkylations of C−OTf bonds (in <10 min), followed by functionalization of the C−Cl site (in <25 min), at room temperature using the same air‐ and moisture‐stable PdI dimer. This allowed the realization of the first general and triply selective sequential C−C coupling (in 2D and 3D space) of C−Br followed by C−OTf and then C−Cl bonds.