Ring Synthesis Incorporating Fluorinated Starting Materials

4 Ring Synthesis Incorporating Fluorinated Starting Materials 

The most promising approach for the efficient preparation of fluoro-heterocycles is by ring synthesis from fluorine-containing starting materials and intermediates. 

CAUTION Monofluoroacetates are intermediates for some literature syntheses of fluorinated heterocycles. Fluoroacetic acid and its derivatives, such as fluoroacetamide and ethyl fluoroacetate, and compounds which could be metabolically converted into fluoroacetate, such as 2-fluoroethanol, are extremely toxic and have no antidote. A lethal dose of the acid in humans may be as low as 100 mg. They should be avoided if at all possible, but if their use is essential, they must only be used under rigorous control. 

There are, perhaps surprisingly, many complex polyfluorinated starting materials available commercially and some apparently quite exotic reagents and intermediates can be easily (and often cheaply) prepared from these. These intermediates may simply be the fluorinated analogues of standard intermediates, for example, 1,3-dicarbonyl compounds or their equivalents, such as an iminium salt synthon for fluoromalonaldehyde.  

A related method giving oxy compounds involves displacement of the activated flnorine in 2,3 -diflnoroacry lates.  

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