Tetramethylammonium Fluoride : Fundamental Properties and Applications in C-F Bond-Forming Reactions and as a Base

Nucleophilic ionic sources of fluoride are essential reagents in the synthetic toolbox to access high added-value fluorinated building blocks unattainable by other means. In this review, we provide a concise description and rationale of the outstanding features of one of these reagents, tetramethylammonium fluoride (TMAF), as well as disclosing the different methods for its preparation, and how its physicochemical properties and solvation effects in different solvents are intimately associated with its reactivity. Furthermore, herein we also comprehensively describe its historic and recent utilization, up to December 2021, in C-F bond-forming reactions with special emphasis on nucleophilic aromatic substitution fluorinations with a potential sustainable application in industrial settings, as well as its use as a base capable of rendering unprecedented transformations. Keywords: tetramethylammonium fluoride; TMAF; solvation effects; nucleophilic fluorination; sustainable industrial fluorination; SNAr; [18F]-radiolabelling; superbases; selective methylation; fluorinated excited speciesPeer reviewe