Angewandte
Chemie
on the formate ester. Reaction with 2 equiv of tBuLi under
the same conditions resulted in the same product mixture: 2
(43%), 10 (22%), and 5 (15%). However, with MeLi
(1 equiv), 78% of 2 was obtained with only trace amounts
of 10 present, and with no 5 observed at all. Finally, the
deprotected pentose was obtained by hydrogenolysis of the
benzyl group, and was isolated as the pyranose 11 as
evidenced by 1H NMR spectroscopy (DMSO) and
HMBC NMR experiments (see the Supporting Information).
An anomeric ratio of 2.6:1 was observed.
nose structure. Finally, we have achieved a fully regioselec-
tive, high-yielding monoalkylation protocol for terminal 1,2-
diols substituted by a perfluoroalkyl chain, with complemen-
tary selectivity to existing methods. The short, high-yielding
sequence for the synthesis of 2 and 3 should make such IPF-
modified monosaccharides easily accessible building blocks.
Further research on the reactivity of the monosaccharides/
glycal in glycosylation reactions is in progress.
Received: May 21, 2004
The synthesis of tetrafluoropyranose 3 and glycal 4 is
shown in Scheme 4. The ring formation was envisaged to
Keywords: asymmetric dihydroxylation · carbohydrates ·
fluorine · perfluoro compounds · synthetic methods
.
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Scheme 4. Synthesis of fluorinated pyranose 3 and glycal 4.
=
a) Na2S2O4, NaHCO3, DMSO, H2C CHOR, RT, 16 h. b) H2SO4 (25%
aq.), dioxane, reflux, 4 h. c) Pd(OH)2/C, EtOAc, RT, 12 h. d) o-NO2C6H4-
SeCN, PBu3, THF, RT, 1 h, then H2O2 (30% aq.), NaHCO3, RT, 1.5 h.
occur by a domino sequence as follows: perfluoroalkyl radical
generation to initiate intermolecular addition onto ethyl vinyl
ether, followed by atom transfer to give the a-bromoether 12,
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the ethyl glycoside 13. For this transformation the solvent
proved to be of importance. With MeCN/H2O mixtures,
typically used for dithionite-mediated perfluoroalkyl radical
generation,[16] the reaction proved quite capricious, with a
maximum yield of 44% of 13 (after 16 h at reflux).
Conversely, the reaction in DMSO[17] proved much faster,
even at room temperature, and reliably afforded 13 in
significantly better yields.
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Using benzyl vinyl ether, the dibenzyl-protected 14 was
synthesized in good yield under identical reaction conditions.
The fully deprotected pyranose 15 could now be obtained in a
single step by hydrogenolysis (1.4:1 mixture of anomers).
Anomeric deprotection of 13 gave the 6-O-benzyl pyranose 3,
and subsequent subjection to Grieco elimination conditions[18]
resulted in the formation of glycal 4.
In summary we have reported a short enantioselective
synthesis of a tetrafluorinated pentose and hexose, and of a
tetrafluorinated
glycal.
A
fluorinated-building-block
approach was followed, using a SAD reaction on a terminal
a-perfluorinated alkene to introduce chirality. A very high ee
value for this class of alkenes (78%) was obtained. The key
operation in the synthesis of 2 and 3 was the ring formation.
We report the first cyclization involving perfluoroalkyl
lithium species and demonstrate that the rate of 5-exo
cyclization is faster than that of the competing fluoride
elimination under the conditions used. We have also estab-
lished a novel domino perfluoroalkyl radical addition/atom
transfer/nucleophilic cyclization approach to obtain a pyra-
Angew. Chem. Int. Ed. 2004, 43, 5677 –5679
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5679