Mechanochemical electrophilic fluorination of liquid beta-ketoesters

Mechanochemistry as an emerging tool for molecular synthesis: what can it offer?

“…When using the less reactive β-keto ester, solvent based reactions take five days to complete, whereas under ball-milling conditions reaction is complete within two hours. 53 …”

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.…”

Mechanochemical Friedel–Crafts acylations

“…When the catalyst amount was decreased to one equivalent, a significant decrease of yield was attained (Table 1, entry 2). Addition of various grinding additives to improve mass transfer and prevent pasting of the reaction mixture [26–28] (Table 1, entries 5–8) was detrimental to reaction yields. The addition of a small amount of solvents which was reported to facilitate several ball milling reactions (liquid assisted grinding, LAG) [29–32], also decreased yields (Table 1, entries 9 and 10).…”