conditions are sufficiently mild that the very acid sensitive
glycal 15 can be glycosylated efficiently. Owing to the poor
solubility of 13 under the reaction conditions (-78 °C, CH2-
Cl2), the coupling of 13 and 8 did not go to completion and
26% of 13 was recovered. Nevertheless, the successful use
of 13 as a glycosyl acceptor attests to the significantly greater
reactivity of the 2-deoxy-2-iodoglycosyl imidates compared
to the 2-deoxy-2-iodoglycosyl acetates, thereby enabling the
synthesis of disaccharides (e.g., 14) already suitably activated
for a subsequent glycosidation reaction at higher reaction
temperature.2
Glycosyl donors 8 and 9 containing strong electron
withdrawing C(4)-acyl substituents are considerably more
stable and less reactive than 10, which is quite sensitive to
handling and decomposes readily even upon attempted
storage. Because we anticipated the need to use glycosyl
donors containing C(4)-silyloxy or C(4)-ether protecting
groups, it was desirable to develop a more stable glycosyl
donor as an equivalent of 10. We anticipated that the
analogous 2-bromo-2-deoxyglycosyl imidate 22 would be
less reactive and more stable than 10, due to the greater
electronegativity of the 2-bromo substituent which should
inductively destabilize the transition state leading to oxonium
ion intermediates. Thiem has previously demonstrated that
2-bromo-2-deoxyglycosyl bromides are useful precursors to
2-deoxy-â-glycosides via silver silicate promoted glycosi-
dations (although the stereoselectivity of these reactions is
generally e 6:1).14,15
Figure 4. Synthesis and â-selective glycosidation reactions of
2-deoxy-2-bromo-R-glucosyl trichloroacetimidate 22.
In summary, we have demonstrated that 2-deoxy-2-
iodoglycosyl imidates 8-10 and 2-deoxy-2-bromoglycosyl
imidate 22 are highly reactive glycosyl donors. These donors
undergo highly stereoselective glycosidation reactions with
a range of monosaccharide acceptors to give 2-deoxy-2-iodo-
and 2-deoxy-2-bromo-â-glycosides, precursors of 2-deoxy-
â-glycosides, with g 19:1 selectivity. It is noteworthy that
the 2-deoxy-2-iodoglycosyl imidates are substantially more
reactive than the 2-deoxy-2-iodoglycosyl acetates previously
reported from our laboratory.2 Application of this methodol-
ogy to the synthesis of biologically relevant 2-deoxy-â-
glycosides is in progress and will be reported in due course.
2-Bromo-2-deoxyglycosyl imidate 22 was synthesized
starting from tri-O-acetyl-D-glucal, 20. Anhydro sugar 21 was
prepared by methanolysis of 20 followed by intramolecular
bromoetherification (NBS, (Bu3Sn)2O, CH3CN; 64% from
21) and then selective protection of the C(4)-OH as a TBS
ether. The bromoetherification sequence employed here is
an improvement over the literature procedure that involves
the reaction of the stannylated glucal with Br2 in CHCl3 and
provides a 9:1 mixture of the 1,6-anhydro-2-bromo-gluco-
and -manno isomers.10 Acetolysis of the anhydro linkage of
21 followed by deprotection of the anomeric acetate and then
activation of the pyranose gave the imidate 22 in ca. 40%
overall yield using the conditions described for the synthesis
of 8 from 7. Imidate 22 indeed proved to be more robust
than 10 and underwent highly â-selective glycosidation
reactions with acceptors 2 and 24, as summarized in Figure
4.
Acknowledgment. This research was supported by a
grant from the NIH (GM 38907).
Supporting Information Available: Representative ex-
perimental procedures for synthesis of the 2-deoxy-2-iodo-
and 2-deoxy-2-bromo-R-glucosyl trichloroacetimidates and
their glycosidation reactions; spectroscopic data for 8-10,
12, 14, 16, 18, 19, 21-23, and 25. This material is available
(14) Thiem, J.; Gerken, M.; Boch, K. Liebigs Ann. Chem. 1983, 462.
(15) Thiem, J.; Gerken, M. J. Org. Chem. 1985, 50, 954, and references
therein.
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