Abstract
An improved substrate scope for the mechanochemical electrophilic fluorination of dicarbonyls is reported. The applicable substrates have now been broadened to include liquid β-ketoesters. Key to this capability is the inclusion of a grinding auxiliary (NaCl) to improve mass transfer and prevent pasting or gumming of the reaction mixture. Notably, the use of a small amount of acetonitrile is critical to increasing the rate of reaction, ensuring complete consumption of starting materials during the short reaction times as well as improving the selectivity for the monofluorinated product in the mill.
Highlights
Mechanochemistry is an emerging tool for organic synthesis, with a variety of synthetically important transformations reported as possible under milling conditions in the absence of solvent.[1]
One such phenomenon is liquid assisted grinding (LAG), whereby the addition of a small quantity of liquid can lead to significant changes in the outcome of a mechanochemical reaction.[6]
It was found that under LAG conditions, the selectivity of fluorination was significantly improved compared to neat reaction conditions
Summary
Mechanochemistry is an emerging tool for organic synthesis, with a variety of synthetically important transformations reported as possible under milling conditions in the absence of solvent.[1]. There are several examples in which LAG enhances the rate of reaction, and it has been demonstrated that both the quantity and identity of the added liquid can be used to switch between polymorphic forms.[8] A further consideration is in the physical state of the reagents, where liquid and solids behave differently, which is not normally an important factor in solution-based reactions Under mechanochemical milling, this can have a significant effect on the performance of the reaction, possibly due to changes in the mixing or energy transfer through the reaction mixture. We report the modification of our reaction conditions to allow the fluorination of less reactive, liquid substrates, improving the overall scope of the solventless process.[13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
