Abstract
Chlorodifluoromethyl groups were introduced into the 2-position
of the glycals 1 , 5 , 8 , and 11 by dithionite-mediated
addition of CF2 ClBr. The reaction proceeded stereoselectively,
i.e. the CF2 Cl-group is always found trans to
the neighbouring substituent at C-3 in the products. Because the
primarily formed glycosyl bromides hydrolyse easily, the corresponding
2-chlorodifluoromethyl-2-deoxypyranoses 3 , 6 , 9 , and 12 were isolated. Only 3,4,6-tri-O -acetyl-2-chlorodifluoromethyl-2-deoxy-d -glucopyranosyl bromide (2 )
was stable enough for chromatographic separation. The unprotected
anomeric pyranoses 3 , 6 , 9 , and 12 were
acetylated by acetic anhydride/pyridine yielding the 1-O -acetyl derivatives 4 , 7 , 10 , and 13 . These compounds are suitable glycosyl
donors, just as the anomeric phenyl thioglycosides 16 and 17 generated from 1,3,4-tri-O -acetyl-2-chlorodifluoromethyl-2-deoxy-d -arabinopyranside (7 )
and thiophenol (BF3 -catalysis). Furthermore, the reactivity
of glucosyl bromide 2 , 6-deoxy-l -glucose derivative 13 and
thioglycosides 16 , 17 was
investigated. On treatment of glucosyl bromide 2 with
pyridine, the 2-chlorodifluoromethyl substituted glycal 14 is formed as the result of HBr elimination.
Furthermore, the chlorodifluoromethyl group of compounds 14 and 16 was
converted into a methoxycarbonyl group by refluxing in methanolic
sodium methoxide (products 15 and 19 , respectively). Finally, the thioglycosides 16 and 17 were
subsequently deacetylated by CsF on alumina (yielding the dihydroxy
derivatives 18 and 20 )
and acetalized with chloral/DCC (18 forming
acetal 21 and carbonate 22 )
and acetone (20 forming acetal 23 ), respectively. X-ray analyses are given
for the 1-O -acetate 4 and
the thioglycosides 21 and 24 .
Key words
carbohydrates - glycals - difluoromethylation - radical addition reactions - eliminations
- acetals
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