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

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Chapter Two
In dehydroxyfluorinations undesired side products can be formed via carbonium ion type
rearrangements and dehydration. The former, carbonium ion type rearrangements, are less
likely to occur when DAST is used as a reagent in comparison to other sources of
nucleophilic fluorine such as SeF4.pyridine. This has been exemplified through the
fluorination of isobutyl alcohol, when DAST was used the ratio of products was 2:1 of
isobutyl fluoride to tert-butyl fluoride, whereas the same reaction with SeF4.pyridine has
reportedly only afforded the rearranged tert-butyl fluoride. [3] Dehydration is also less
problematic with DAST as a fluorinating agent, with Middleton reporting that cyclooctanol
reacts with DAST to yield a 70:30 ratio of cyclooctyl fluoride to cyclooctene, whereas the
use of Et2NCF2CHClF afforded only cyclooctene. [2]
Many groups have studied at length the structural features of the starting allylic alcohol and
their influence on regioselectivity in reactions with DAST. [4-8] In 1991 Mann reported that
regioselectivity is poor when the allylic alcohol is substituted with alkyl groups, which was
found to be a significant disadvantage in the fluorination of squalene derivatives, where a
3:7 mixture of primary and secondary allylic fluorides was obtained. When DAST was
modified from trifluoride to difluoride, reaction with the allylic alcohol was wholly selective
with the desired fluorinated squalene as the only product. [9] Conversely, Grée and co-
workers found that when allylic alcohols were substituted with phenyl groups or strongly
[4, 5]
electron-withdrawing groups regioselectivity was high (Scheme 2.3).
R 1 = R 3 = H, R 2 = Me, R 4 = Ph 0 : 1 71 % yield
R 1 = R 3 = H, R 2 = CO2Me, R 4 = Me 1 : 0 80 % yield
R 1 = R 3 = H, R 2 = COPh, R 4 = Me 1 : 0 70 % yield
Scheme 2.3 Fluorination of allylic alcohols by Grée
Further work by Grée et al. demonstrated how selectivity could be controlled by
complexing the allylic alcohol to a metal prior to fluorination. With rhenium complexing to
the substrate nucleophilic displacement of the hydroxyl group occurred with complete
regiocontrol affording the allylic fluoride, in moderate to good yields (40-76 %), as a single
diastereoisomer with retention of configuration. [10] It was also found that Fe(CO)3
complexes of dienyl alcohols could be used to control diastereoselectivity (Scheme 2.4).
Retention of configuration was achieved when secondary alcohols were used, affording the
corresponding fluorinated products in good yields (76 – 86 %). [11]