Microwave-assisted rapid electrophilic fluorination of 1,3-dicarbonyl derivatives with Selectfluor®

Enolization rates control mono- versus di-fluorination of 1,3-dicarbonyl derivatives

“…1a), that do not present any handling problems, numerous reports followed regarding the electrophilic uorination of 1,3-dicarbonyl derivatives. Procedures include catalyst-free reactions, 19 microwave-assisted methods, 20 transition metal (Ti and Ru) catalysed methods, [21][22][23] solvent-free reactions assisted by milling, 24,25 uorinations in ionic liquids, 26 and reactions conducted in water. 27,28 In many cases, difficulties in controlling mono-versus diuorination were reported, leading to challenging separations of the product mixtures.…”

Solvent‐Free Fluorination of Electron‐Rich Aromatic Compounds with F‐TEDA‐BF4: Toward “Dry” Processes

“…[8a], [8b], The replacement of volatile organic solvents with more “green” alternatives is one of the most demanding areas of research , . Recent advances in “green” fluorination with NF reagents includes reactions in room‐temperature ionic liquids (ILs), IL/alcohol mixtures,, supercritical carbon dioxide, water,, poly(ethylene glycol) 400 (PEG‐400), and H 2 O/PEG‐400, as well as the use of microwave irradiation for low energy consumption . However, the most significant decrease of the environmental footprint of most industrial processes would be the complete elimination of the solvent.…”

Towards Greener Fluorine Organic Chemistry: Direct Electrophilic Fluorination of Carbonyl Compounds in Water and Under Solvent‐Free Reaction Conditions

“…Selective mono-fluorofunctionalization of acyclic 1,3-dicarbonyls bearing a methylene carbon atom between two carbonyl functional groups is not an easy task and often strict control of the reaction conditions is necessary in order to diminish over-fluorination to 2,2-difluoro-substituted products, while for complete difluorination the presence at least equivalent amounts of a strong base was reported to be necessary. [16] In our case, the fluorination of a group of acyclic 1,3-dicarbonyl compounds (9a-d, Table 1) with F-TEDA-BF 4 in water could also not be selectively stopped at the monofluorination stage, but by using a two-fold excess of the reagent efficient formation of the 2,2-difluoro-substituted products 10a-d was established without any additional activation of the starting material. We also tested two examples of less active 1,3-dicarbonyl compounds 3-oxobutyric acid ethyl ester (9e, entry 10, Table 1) and diethyl malonate, and found that fluorination of 9e with F-TEDA-BF 4 in water gave a complex reaction mixture of mono-and difluoro products, hydrolyzed products and hydrates, while the reaction under SFRC with NFSi selectively and efficiently yielded 2,2-difluoro-3-oxobutyric acid ethyl ester 10e.…”