Synthesis and Comparison of the Reactivity of Allyl Fluorides and ...

1.4 Building Block Approach to Organofluorine Compounds
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Chapter One
Fluorinated building blocks are small readily available materials that already contain
fluorine atoms, and for this reason they are extremely valuable in synthetic chemistry as
they negate the use of hazardous fluorinating reagents such as DAST. There are numerous
papers that discuss their uses and a selective review of mono-, di- and tri-fluorinated
building blocks will be presented here.
Chlorofluorocarbenes are extremely useful building blocks due to the fact that they react
with electron rich alkenes, such as enol ethers and the corresponding products,
alkoxycyclopropanes, can undergo solvolysis reactions leading to �-fluoro-Z-enals. These
are extremely valuable and have been utilised by Johnson et al. in the synthesis of steroid
analogues. [51-54]
Fluoroalkenes and gem-difluoroalkenes are highly reactive towards nucleophilic attack at
the fluorinated sp 2 carbon due to 3 factors, i) high electron deficiency on the gem-
difluoromethylene carbon, ii) thermodynamic instability of sp 2 hybridised fluoroalkenes in
comparison with sp 3 hybridised fluoroalkanes and iii) the formation of stable sp 3 hybridised
�-fluorocarbanions (Figure 1.10).
Figure 1.10 Stable sp 3 hybridised �-fluorocarbanion
Hence, nucleophiles attack exclusively at the gem-difluoromethylene carbon atoms of
difluoroalkenes to form the corresponding �-fluorocarbanions. The subsequent reaction
pathways can be classified into three groups:
(i) Addition-elimination, which is conducted with metal nucleophiles in aprotic
solvents. Here, the carbanion undergoes defluorination affording the product as
an �-substituted monofluoroalkene.
(ii) 1,2 addition, which can be conducted with any nucleophile in a protic solvent or
with protic nucleophiles (amines and alcohols) or electrophiles in aprotic
solvents, where the carbanion can be trapped by either an electrophile or proton
in order to yield the addition product.