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

Scheme 1.25 Synthesis of (41)-(44)
26
Chapter One
Saeki et al. [73] following on from their work on cross-coupling reactions with
fluorobenzenes, applied the same protocol to gem-difluoroalkenes, however, in conjunction
with the palladium catalyst it was found that the arylzinc reagent was more effective than
the Grignard reagent, and reflux for 48 hours in THF afforded the mono-coupled product in
70 % yield, with 23 % of the di-coupled product also forming. When the Ni catalyst
[NiCl2(dppp)] was employed with Grignard the di-coupled product was obtained as the
major product in 58 % yield (Scheme 1.26).
Scheme 1.26 Cross-coupling of gem-difluoroalkenes
More recently Yamada et al. have reported how copper (I) salts promote the fluorine-metal
exchange reactions of fluoroalkenes with Grignard reagents, and that the selective
replacement of fluorine in (45) by the organocuprate takes place efficiently to generate the
corresponding �-metallated tetrafluorocuprate intermediate which then reacts with allyl
bromide to give (Z)-benzyl 2-fluoro-3-(trifluoromethyl)hexa-2,5-dienoate in 67 % yield as
virtually all the cis isomer (E/Z = 0:99) (Scheme 1.27). [77]