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

1.3 Enantioselective Nucleophilic Fluorination
16
Chapter One
Enantioselective nucleophilic fluorination was first attempted in 1989 by Hann and
Sampson. [37] Their aim was to develop homochiral aminofluorosulphuranes as potential
enantioselective fluorinating agents. A homochiral anologue of DAST was therefore
synthesised where R= CH2OMe (27) (Scheme 1.14).
Scheme 1.14 Homochiral anologue of DAST (27)
Fluorination of racemic 2-(trimethylsiloxy)octane using 1.1 equivalents of (27) in DCM for
5 hours at -78 °C, yielded a 74/26 mixture of 2-fluorooctane and alkenes. In order to
evaluate the enantiodiscriminating ability of (27), kinetic resolution studies were conducted.
The reaction of 2-(trimethylsiloxy)octane with 0.5 equivalents of (27), afforded an 8 %
kinetic resolution. Whilst the reaction of racemic ethyl-2-(trimethylsiloxy)propanoate with
0.5 equivalents of (27) at 0 °C for 4 hours afforded ethyl 2-fluoropropanoate in a
disappointing 16 % ee.
Beaumont et al. took a similar approach and synthesised two chiral quaternary phosphonium
fluorides with chiral alkyl groups and asymmetric phosphonium centres in 2000 (Figure
1.11). [38] It was proposed that chiral quaternary ammonium and phosphonium fluorides
would have interesting properties as novel reagents for simple asymmetric nucleophilic
fluorination. Initial studies showed that the phosphonium compounds were more effective
reagents than the ammonium salts and were therefore considered in more detail.
Figure 1.11 Diastereomeric benzylmenthylmethylphenylphosphonium fluorides (28) & (29)
Diastereomeric benzylmenthylmethylphenylphosphonium fluorides (28) and (29), with R
and S configuration at phosphorus were synthesised from the diastereomers of menthyl-
methylphenylphosphine. In order to test the abilities of (28) and (29) as asymmetric
nucleophilic fluorinating reagents, a two-fold excess of (28) was reacted with racemic 2-