Ferric chloride, an anomerization catalyst for the preparation of alkyl α-glycopyranosides

Dealkylatior The
occurred with 4 and 6 because of the acid lability of their ethereal G-C bonds.' Ferric chloride has been used fo 5 appears decomposition. 4-methoxycinnamate derivative 9 was decomposed by this reagent, presumably by oxidation of the aromatic ring. The stability of other groups was tested. Protecting groups such as acetonidesg and benzylidine acctals are labile to FeC13. The benzoate group was stable, and derivatives 8 and 13 yielded a-glycosides. Thl reactions were, however, slower than the acetate derivative 1. The benzoate derivative of methyl xyloside 1: was sensitive to decomposition presumably due to the greater acid lability of the xylose ring; the correspondin! acetate derivative 11 was less sensitive to decomposition and gave good results. The methyl-protected glycosidl 10 was easily hydrolyzed, yielding the corresponding lactol and glycosyl chloride. The Zdeoxy derivative 11 gave high a-selectivity comparable to the oxygen sugars. Anomerization of the methoxyl group of 15 wa achieved, but the reaction was slow and decomposition products were also obtained; anomerization of the seconr : anomeric center was not observed. The acetate derivative of glucosamine 16 afforded a complex mixture of 0: glycoside and decomposition products resulting from the cleavage of the anomeric methoxyl group; a sohtbilit: problem also arose presumably from the complexation of FeC13 to the basic acetylamino group. Thl bromobenzoate derivative 17 gave better results, but the anomerization was slow and significant amounts of thl bicyclic oxazoline derivative, resulting from the displacement of the anomeric methoxyl group by the C-: aminoacyl carbonyl group, was isolated. Anomerization was attempted with the furanoside derivatives, methy 8-ribofuranoside triacetate and methyl B-fructofuranoside tetrabenzoate, but was unsuccessful. Product resulting from exocyclic bond cleavage were observed, consistent with the greater lability of the glycosidic bonr of furanosides compared to those of pyranosides.10 The anomerization may occur by two pathways, involving endccyclic bond cleavage (Path A) or exocyclil bond cleavage (Path B).ll Path A may predominate for acylated oxygen sugars, since side products resultin! from the exocyclic C-O bond cleavage (lactols and chlorides) are not observed. Path B may be more prcvalen with the nitrogen sugars (16 and 17), which possess the cation-stabilizing C-Z aminoacyl groups.
imp. SM decomp. a
lh lh 15 min 85%
92:8
4.5 h lh Me (10) lactol a 'OR
OBz-Br
89%
92 :8 __ __
20 min
85%
lh lh
83%
89:11 __
4-BrBz (12)
decomp.
0CH3
`OBz-Br
(13)
a
5h
88%
Tcmihedmn Lettax. Vol. 33. No. 30, pp. 4295-4298.1992 Priited in Grest Britain
oo404039/92
$5.00. ,013
Pergamon Press Ltd
Ferric Chloride, an Anomerization Catalyst for the Preparation of Alkyl a-Glycopyranosides
I
OCHB
Thus,
this reagent
offers a simple
route for the preparation
of a-glycopyranosides
from
P-glycopyranosides
or a mixture of a-and P-glycopyranosides.
Ferric chloride is an inexpensive and easilyvarious
The tetra-0-acetyl oxidation of phenol
glucoside derivatives (l-3,7) ethers,8 and the glycoside
gave good yields and
4295
4296
Table I. Anomerization Results:6 A&rPmd
R-
Time
1.5h 45 min Ih 20 min
%Ma
83% 84% 90% 82%
a/B Ratb b
90 : 10
Me (1)
a
94 :6 95:s __ -__
Ph (5) cholesteryl (6) cholestanyl (7)
Anomerically pure glycosides are prepared from glycosyl halides by two strategies1 An acyloxy group a the C-Z position directs the incoming glycopyranosides preparation of 1,2-cis glycopyranosides nucleophile via neighboring group participation to give 1,2-tram (p-glycoside for the &co and galacto series, and a-glycoside is more difficult for the ~URPZD series). The The disadvantages of the
selectivity (a: p cu. 95 : 5)s A mixture of a-and p-glycosides afforded similar results.
BnQ 1. Fe&, OCH ' CH.$$ fl, 1 h RO do R = 4-MeOCinn RO
2.
-
4-MeOCinnCl, AgOTf PY, a 1 h (90%)
Summary:
Anhydrous FeC$ in CHzClz has been found to readily anomerize P-glycopyranosides
to their
corresponding u-anomers in good yields and selectivities at room temperature. Acetyl- and benzoyl-protected oxygen sugars yielded the best results.