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

5.2.5 Metal-mediated synthesis of 3,3-difluoro-2-phenylpent-4-en-2-ol (181)
128
Chapter Five
After the successful synthesis of several novel difluoro compounds derived from aldehydes,
the reaction of acetophenone with 3-bromo-3,3-difluoropropene was examined. Previously
acetophenone has been successfully reacted with 3-bromo-3,3-difluoropropene in zinc
mediated reactions, however, there were no reports in the literature where indium has
successfully been used to catalyse the reaction. Therefore, a flask was charged with
acetophenone, 3-bromo-3,3-difluoropropene, indium and water and the reaction mixture
was sonicated for 24 hours, however, work up and analysis of the crude reaction mixture by
1 H and 19 F NMR spectroscopy showed that no product was present. This agreed with the
report of Kirihara where it had been stated that when catalysed by indium no reaction
occurred and that if a compound had both aldehyde and ketone functionalities, the reaction
would occur at the carbonyl of the aldehyde preferentially. Hence, the reaction was
repeated using the method outlined by Burton, acid washed zinc powder, acetophenone and
DMF were cooled to 0 ºC, whilst a solution of 3-bromo-3,3-difluoropropene in THF was
added dropwise, the reaction mixture was then warmed to room temperature and stirred
overnight, after which workup, drying over magnesium sulphate and removal of solvent in
vacuo afforded the crude product. However, 1 H and 19 F NMR spectroscopy demonstrated
that only 4 % conversion to product had occurred, analysis by TLC also showed that the
product and starting material had very similar Rf values and, therefore, would be difficult to
separate even after trying several different solvent systems.
Scheme 5.14 Synthesis of (181)
The reaction was then repeated however, THF was used as the solvent. After stirring the
reaction mixture overnight a small aliquot was analysed by 1 H and 19 F NMR spectroscopy
which exhibited that once again only a small amount of product had formed, therefore, the
reaction mixture was heated to 45 ºC for 24 h. After which another aliquot was removed
from the reaction mixture and analysed exhibiting that 10 % conversion to product had
occurred. Therefore, in order to further encourage the formation of desired product the
reaction mixture was sonicated for 60 h, after which workup, drying over magnesium
sulphate and removal of solvent in vacuo afforded the crude product. 1 H and 19 F NMR
spectroscopy of the crude product exhibited 20 % conversion to desired product, which is
lower than the 45 % reported by Burton.