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

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Chapter Five
Gem(difluoroallyl) lithium in solution is best described by (157). The inductive effect of the
fluorine substituents is expected to stabilise the carbanion centre, however, this effect is
cancelled by destabilising repulsion between the lone pair of electrons on fluorine
substituents and electrons in the carbanion orbital. Therefore, a possible mechanistic
pathway for the reaction of gem-(difluoroallyl) lithium with a carbonyl is illustrated in
Scheme 5.5. Allylic lithium reagents exist in ether solvents in tight ion pairs. Where there
is a considerable covalent bonding contribution lithium is expected to coordinate at the site
of greatest negative charge thereby blocking the CH2 terminus from attack by electrophiles.
Scheme 5.5 Mechanistic pathway for the reaction of gem-(difluoroallyl) lithium
with a carbonyl
Following on from Seyferth’s work, Burton [33, 34] developed a route to the direct allylation
of aldehydes and ketones via the in situ reaction of 3-bromo-3,3-difluoropropene with acid
washed zinc powder and carbonyl substrates. This method circumvented issues such as the
use of thermally unstable intermediates as well as competitive reactions of the carbonyl
substrates with n-butyllithium. Products were obtained in moderate to good yields (45-73
%) (Table 5.2).
R R’ Product Yield (%)
C6H5 H C6H5CH(OH)CF2CH=CH2 67
n-C6H13 H n-C6H13CH(OH)CF2CH=CH2 53
n-C5H11 H n-C5H11CH(OH)CF2CH=CH2 47
C6H5CHMe H C6H5CHMeCH(OH)CF2CH=CH2 47
i-Bu Me i-BuC(OH)(Me)CF2CH=CH2 55
C6H5 Me C6H5C(OH)(Me)CF2CH=CH2 45
C6H5 CF3 C6H5C(OH)(CF3)CF2CH=CH2 73
p-MeC6H4 CF3 p-MeC6H4C(OH) (CF3)CF2CH=CH2 69
Table 5.2 Reactions of aldehydes and ketones with Zn activated
3-bromo-3,3-difluoropropene