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

25
Chapter One
method is employed by industry in order to synthesise the commercially available
Levofloxacin and Sparfloxacin (Figure 1.11).
1.5.2 Alkenyl fluorides
Figure 1.11 Levofloxacin and Sparfloxacin
Recently Ichikawa investigated nucleophilic 5-endo-trig cyclisations of 1,1-difluoro-1-
alkenes. [76] ���-difluorostyrene and 1,1-difluoro-1-butene derivatives with a nucleophilic
oxygen, nitrogen, sulphur or carbon atom at the ortho/homoallylic position were utilised in
order for substitution to proceed in a 5-endo-trig manner. Para-toluenesulfonamides when
reacted with NaH in DMF afforded the desired cyclic products ((41) and (42)) in excellent
yields (84 and 81 %). Similarly the reaction proceeded equally well with an intramolecular
oxygen nucleophile affording the corresponding product (43) in 80 % yield, under the same
reaction conditions. The utilisation of a sulphur nucleophile was also successful though
slightly different reaction conditions were employed, firstly 1-(1,1-difluorohex-1-en-2-yl)-2-
(methylsulfinyl)benzene was treated with trifluroacetic anhydride and triethylamine in
DCM, followed by reaction with potassium carbonate in methanol to afford the desired
product, 2-fluroobenzol[b]thiophene (44) in 82 % yield (Scheme 1.25).