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

Scheme 1.6 Synthesis of F-CD-BF4 (13)
9
Chapter One
The enantioselective fluorinating ability of the new [N-F] + reagents was tested with 2-
methyl-1-tetralone. Initially, only moderate yields (40–50 %) were obtained of the 2-fluoro
compound, due to the protonation of the enolate by the free hydroxyl group, this was
rectified by using two equivalents of base (Scheme 1.7). After which, all four [N-F] +
reagents afforded the desired fluorinated product in high yield (70–98 %), though moderate
enantioselectivities were obtained (20–50 % ee), with the highest enantioselectivity induced
by F-CD-BF4 (50 % ee).
Scheme 1.7 Fluorination of the Enolate of 2-Methyl-1-tetralone.
The fluorinating ability of F-CD-BF4 (13) was tested with various substrates. Although the
enantioselectivities obtained were moderate and not always an improvement on previous
results using neutral [N-F] reagents, the yields were substantially higher (80-98 %),
suggesting that charged [N-F] + reagents had a greater fluorinating ability. Additionally,
[N-F] + reagents are less substrate dependent and therefore allow the trimethyl silyl enol
ether of 2-methyl-1-tetralone to be fluorinated. Higher enantioselectivity was obtained than
that for the fluorination of enolates, with addition of sodium hydroxide to the fluorinating
agent aiding reactivity and stereoselectivity. F-CD-BF4 afforded the fluorinated product in a
93 % yield and 61 % ee which was the highest of the [N-F] + reagents.
In 2001, Cahard further utilised the [N-F] + reagents by achieving the first enantioselective
�-fluorination of �-amino acid derivatives. The synthesis was based upon reacting the
preformed ester enolate or nitrile anion with the modified N-fluoro cinchona alkaloids.
However, the [N-F] + reagents based upon naturally occurring cinchona alkaloids afforded