Developing simple boranes as phase transfer catalysts for nucleophilic fluorination using CsF

Abstract

Despite the general high fluorophilicity of boron, simple organoboranes such as BEt3 and 3,5-(CF3)2C6H3–BPin are shown herein for the first time, to our knowledge, to be effective phase-transfer catalysts for the fluorination of organohalides with CsF. Significant chiral induction during nucleophilic fluorination to form -fluoroamines using oxazaborolidine (CBS) (pre)catalysts and CsF also can be achieved. Screening different boranes revealed a correlation between calculated fluoride affinity of the borane and nucleophilic fluorination reactivity, with sufficent fluoride affinity required for boranes to react with CsF and form Cs[fluoroborate] salts, but too high a fluoride affinity leading to fluoroborates that are poor at transferring fluoride to an electrophile. Fluoride affinity is only one component controlling reactivity in this context; effective fluorination also is dependent on the ligation of Cs+ which effects the [Cs⋯F⋯BR3] interaction and thus the B–F bond strength. Effective ligation of Cs+ (such as by [2.2.2]-cryptand) weakens the Cs⋯FB interaction which strengthens the B–F bond - thus disfavours fluoride transfer to an electrophile. Combined these findings enables optimal fluorination outcomes to be expected using robust (to the fluorination conditions) boranes with fluoride affinity of ca. 110 kJ mol-1 (relative to Me3Si+) under conditions where a signficant Cs⋯F–B interaction persists.