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

120
Chapter Five
benzaldehyde, 3-bromo-3,3-difluoropropene, indium and water were sonicated at room
temperature for 3 hours, after which work up of the mixture and analysis of the crude
reaction mixture by 1 H and 19 F NMR spectroscopy confirmed that the desired product had
formed. In particular, 19 F NMR spectroscopy revealed a diagnostic AB pattern
characteristic of diastereotopic fluorine atoms in the product. However, the presence of
benzoic acid was also observed. The crude mixture was purified by column
chromatography [diethyl ether: petroleum ether (15:85)] and the product isolated in a
moderate 54 % yield, in keeping with the yield obtained by Percy. In a series of
experiments, the reaction conditions were varied in an attempt to reproduce the excellent
yields claimed by Kirihara. Using the molar ratio of reagents, indium: 3-bromo-3,3-
difluoropropene: benzaldehyde [(2):(2):(1)], the desired product was afforded in an
excellent 99 % yield after purification by column chromatography using the solvent system
[diethyl ether: petroleum ether (15:85)].
Scheme 5.7 Synthesis of (158)
Kirihara postulated that there may be two possible mechanistic pathways by which the
reaction was proceeding. Firstly through a sesqui(difluoroallyl) indium (III) sesqui bromide
species, or secondly by formation of difluoroallyl indium (I). In the former, nucleophilic
addition of 3-bromo-3,3-difluoropropene occurs across the indium, whilst in the latter case a
transmetallation reaction occurs to afford the desired product.
Figure 5.1 Sesqui(difluoroallyl)indium(III) sesquibromide and Difluoroallylindium (I)
5.2.2 Synthesis of difluoroallylic esters
Once the reaction conditions for the synthesis of (158) had been optimised and a substantial
amount of (158) had been formed it was reacted further to form difluoroallylic esters using
the method outlined by Nakamura. [37] The product (159) was synthesised by charging a
reaction flask with (158) and pyridine and cooling to 0 ºC, after which benzoyl chloride was
added and the reaction mixture warmed to room temperature and stirred for 2 hours.