Regioselective monoacetylation of methyl pyranosides of pentoses and 6-deoxyhexoses by acetic anhydride in the presence of MoCl5

Article abstract of DOI:10.1080/00397910600591565

Convenient regioselective syntheses of 3-acetates of methyl pyranosides of α-L-rhamnose, α- and β-L-arabinose, α-D-fucose, α-D-lyxose, and β-D-ribose with good yields have been attained using MoCl₅ as catalyst. Methyl β-L-rhamnopyranoside under this conditions gave 2-acetate. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600591565

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Regioselective Monoacetylation of Methyl
Pyranosides of Pentoses and 6‐Deoxyhexoses
by Acetic Anhydride in the Presence of MoCl5
Evgeny V. Evtushenko a
a Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian
Academy of Sciences, Vladivostok, Russia
Published online: 21 Aug 2006.
To cite this article: Evgeny V. Evtushenko (2006) Regioselective Monoacetylation of Methyl Pyranosides of
Pentoses and 6‐Deoxyhexoses by Acetic Anhydride in the Presence of MoCl5 , Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:11, 1593-1599
To link to this article: http://dx.doi.org/10.1080/00397910600591565
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Synthetic Communicationsw, 36: 1593–1599, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600591565
Regioselective Monoacetylation of Methyl
Pyranosides of Pentoses and 6-Deoxyhexoses
by Acetic Anhydride in the Presence of
MoCl5
Evgeny V. Evtushenko
Pacific Institute of Bioorganic Chemistry, Far East Branch of the Russian
Academy of Sciences, Vladivostok, Russia
Abstract: Convenient regioselective syntheses of 3-acetates of methyl pyranosides of
a-L-rhamnose, a- and b-L-arabinose, a-D-fucose, a-D-lyxose, and b-D-ribose with
good yields have been attained using MoCl5 as catalyst. Methyl b-L-rhamnopyranoside
under this conditions gave 2-acetate.
Keywords: Methyl glycopyranosides, regioselective acetylation, transition metals
Partially acetylated carbohydrates have been useful as reference compounds in
the analysis of certain natural products containing carbohydrates and are used
as versatile intermediates in other synthesis.
Earlier studies on partial acylation of carbohydrates[1] were not always
successful from the preparative point of view because of small differences
in reactivity of hydroxyl groups. Therefore, regioselective acylation and
acetylation, in particular, of carbohydrates is a difficult challenge for
chemists. In the past few years, enzymatic[2] and chemical approaches[3–8]
for regioselective acetylation of monosaccharides have been developed.
Transition metals,[3] some amines,[4] and molecule sieves[5] were used as
Received in Poland October 6, 2005
Address correspondence to Evgeny V. Evtushenko, Pacific Institute of Bioorganic
Chemistry, Far East Branch of the Russian Academy of Sciences, Pr Stoletiya
Vladivostoka 159, 690022, Vladivostok, Russia. Tel.: 7-4232-311430; Fax: 7-4232-
314050; E-mail: evt@piboc.dvo.ru
1593

1594
E. V. Evtushenko
Scheme 1.
catalysts; tin organic compounds,[6] copper,[7,8] and mercury[7] chelats were
also used.
Sugars are known to form complexes with transition metals,[9] and the
cyclic complexes are more thermodynamically preferable than acyclic ones.
In a previous work[10] we have shown that the results of methylation of
methyl glycopyranosides by diazomethane in the presence transition-metal
chlorides may be interpreted as a consequence of intermediate cyclic
bidentate complexes with the participation of two vicinal hydroxyl groups
of glycopyranosides and transition-metal atom.
In this article we report the catalytic influence of transition-metal salts on
regioselectivity of acetylation of methyl pyranosides of pentose and 6-deoxy
hexoses. Our preliminary experiments demonstrated high efficiency of MoCl5
as catalyst under regioselective acetylation of methyl glycosides (Scheme 1).
Table 1 shows that using 1,2-dimethoxyethane (DME) as solvent results
in the greatest selectivity at replacement OH-3 in methyl a-L-rhamnopyrano-
side. The results of acetylation of methyl glycopyranosides by acetic
anhydride in DME are given in Table 2. Data of the acetylation of methyl
glycosides in basic conditions are given for comparison.
As can be seen from Table 2, use of cerium(III) and yttrium(III) chloride
as well as copper(II) and mercuric(II) trifluoroacetates practically does not
give 4-acetate in acetylation of methyl a-L-rhamnopyranoside. Probably
these transition-metal atoms form intermediate bidentate complexes with
Table 1. Acetylation of methyl a-L-rhamnopyranoside by acetic anhydride in the
a
presence MoCl5
Acetates (%)b
Solvent
Glycoside (%)
2-Ac
3-Ac
4-Ac
Di þ tri-Ac
DME
9
72
22
48
4
4
81
24
44
43
6
1,4-Dioxane
CH3CN
EtOAc
10
5
16
4
8
aReaction conditions: methyl a-L-rhamnopyranoside (0.5 mmol), solvent (3 ml),
23
Ac2O (1.5 ml), MoCl5 (5 10 mmol); 24 h.
.
1
bDetermined by H NMR analysis of monoacetate fractions.

Regioselective Monoacetylation of Methyl Pyranosides
1595
Table 2. Regioselective acetylation of methyl glycopyranosides by acetic anhydride
in DME in the presence of transition-metal saltsa
Acetates %b
No.
Methyl pyranoside
Catalyst
2-Ac
3-Ac 4-Ac Di þ Tri-Ac
1
2
3
4
5
6
CeCl3
YCl3
Cu(CF3COO)2 44
36
42
35
22
18
11
8
46
1
45
83
Hg(CF3COO)2
MoClc5
Pyrd
9
91 (87)
22
9
14
8
14
20
7
8
MoClc5
Pyr
81 (78)
14
19
15
13
9
10
MoClc5
Pyr
94 (91)
26
6
12
17
1
11
12
MoClc5
Pyr
67 (63)
15
4
12
29
18
20
13
13
14
MoClc5
Pyr
77 (75)
17
2
16
21
17
15
16
MoCle5
Pyr
29
13
1
16
21
14
49
12
17
18
MoClc5
Pyr
9
12
70 (66)
18
21
17
18
11
19
20
MoClf5
Pyr
2
13
98 (96)
23
20
(continued)

1596
E. V. Evtushenko
Table 2. Continued
Acetates %b
No.
21
Methyl pyranoside
Catalyst
2-Ac
3-Ac 4-Ac Di þ Tri-Ac
11 31
c
MoCl5
c
22
MoCl5
8
46
aReaction conditions: methyl glycopyranoside (1 mmol), DME (6 ml), Ac2O (3 ml),
catalyst (0.2 mmol), 48 h.
bDetermined by 1H NMR analysis of monoacetate fractions, isolated yields in
brackets.
cMoCl5—0.01 mmol, 48 h.
dReaction conditions: methyl glycopyranoside (0.5 mmol), pyridine (0.5 ml), Ac2O
(1 mmol), rt, 24 h.
eMoCl5—0.05 mmol, 48 h.
fMoCl5—0.001 mmol, 24 h.
cis-vicinal hydroxyl groups of methyl a-L-rhamnopyranoside; with sub-
sequent acetylation involved in complexation the hydroxyl groups.
Using MoCl5 as catalyst leads to regioselective synthesis of 3-acetate of
methyl a-L-rhamnopyranoside—91% from total mixture and 100% from
fraction mono-substituted esters. Under the same conditions methyl b-L-
rhamnopyranoside forms 2-acetate with a high yield (81%) that perhaps is a
result of the anomeric effect. The acetylation of methyl pyranosides of a- and
b-L-arabinose, a-D-fucose, and a-D-lyxose led to 3-acetate as the main product
in the monoacetates fraction. It is interesting that methyl b-D-xylopyranoside,
which has no cis-vicinal hydroxyl groups, does not form 3-acetate.
The acetylation of methyl 2-O-methyl-a-L-rhamnopyranoside in the
presence of MoCl5 proceeded slower than parent methyl a-L-rhamnopyrano-
side and gives a mixture of 3- and 4-acetates with a preponderance of the
latter. This indicates a possibility of such complexation between methyl
a-L-rhamnopyranoside and MoCl5. On the acetylation of 4-methyl ether of
rhamno-pyranoside, 3-acetate predominated in the reaction mixture, but the
lower reaction rate and the presence of 2-acetate in mixture support the possi-
bility of the formation of an intermediate tridentate complex between rhamno-
pyranoside and MoCl5 with participation of three hydroxyl groups. The almost

Regioselective Monoacetylation of Methyl Pyranosides
1597
quantitative yield of 3-acetate (96%) under acetylation of methyl b-D-
ribopyranoside is probably due to the participation of three neighboring
hydroxyl groups in complexation with the molybdenum atom.
This article suggests the simple and effective method of C-3-O-acety-
lation of methyl pyranosides of pentoses and 6-deoxyhexoses. The progress
of this methodology and study of this reaction mechanism will be continued
further.
EXPERIMENTAL
Melting points were determined on a Boethius micro-hot-stage apparatus and
are uncorrected. Optical rotations were measured with a Perkin-Elmer model
141. Chloroform was used as a solvent. 1H NMR spectra were recorded on a
Bruker WM-250 spectrometer. CDCl3 was used as a solvent. Chemical shifts
(d) are reported in ppm related to Me4Si. TLC was performed on silica gel L
(5–40 mm; Chemapol) with 95 : 5 CHCl3–MeOH solvent and detection by
charring with sulfuric acid. Column chromatography was performed on
silica gel (100–160 mm; Chemapol).
General Procedure for the Monoacetylation of Methyl Glycosides
The solution of methyl glycoside (1 mmol), MoCl5 (0.01 mmol); for methyl
b-D-ribopyranoside, 0.001 mmol), and Ac2O (3 ml, 32 mmol) in DME (6 ml)
was allowed to stir at room temperature for 48 h and was monitored by
TLC. Cold water (3 ml) was added. After 1 h, the mixture was concentrated
to a syrup under reduced pressure at room temperature. The product
was isolated by flash chromatography on a column of silica gel using
CHCl3–EtOH, 50 : 1.
Data
Methyl 3-O-acetyl-a-L-rhamnopyranoside. Yield 191 mg (87%). Rf 0.42, mp
1
44–468C (from EtOAc–hexane), [a]2D0 288.28 (c 0.7, CHCl3). H NMR
d: 5.02 (dd, 1H, J2,3 ¼ 3.2 Hz, J3,4 ¼ 9.4 Hz, H-3), 4.67 (d, 1H,
J1,2 ¼ 1.9 Hz, H-1), 4.02 (m, 1H, H-5), 3.65 (m, 2H, H-2, H-4), 3.40 (s, 3H,
OCH3), 2.17 (s, 3H, Ac), 1.36 (d, 3H J5,6 ¼ 6.3 Hz, CH3). Anal. calcd. for
C9H16O6: C, 49.09; H, 7.32. Found: C, 48.96; H, 7.16.
Methyl 2-O-acetyl-b-L-rhamnopyranoside. Yield 172 mg, (78%). Rf 0.44, mp
1
134–1358C (from EtOAc–hexane), [a]2D0 þ57.38 (c 0.5, CHCl3). H NMR
d: 5.36 (dd, 1H, J1,2 ¼ 1.1 Hz, J2,3 ¼ 3.5 Hz, H-2), 4.47 (d, 1H, H-1), 3.69
(dd, 1H, J3,4 ¼ 9.0 Hz, H-3), 3.52 (s, 3H, OCH3), 3.46 (t, 1H, J4,5 ¼ 9.0 Hz,

1598
E. V. Evtushenko
H-4), 3.37 (m, 1H, H-5), 2.18 (s, 3H, Ac), 1.41 (d, 3H, J5,6 ¼ 6.1 Hz, CH3).
Anal. calcd. for C9H16O6: C, 49.09; H, 7.32. Found: C, 48.84; H, 7.40.
Methyl 3-O-acetyl-a-L-arabinopyranoside. Yield 130 mg, (63%). Rf 0.39, mp
130–1318C (from EtOAc–hexane), [a]2D0 þ44.38 (c 0.6, CHCl3). 1H NMR d:
4.86 (dd, 1H, J2,3 ¼ 9.8 Hz, J3,4 ¼ 3.2 Hz, H-3), 4.19 (d, 1H, J1,2 ¼ 7.3 Hz,
H-1), 4.06 (m, 1H, H-4), 4.02 (dd, 1H, J4,5a ¼ 2.5 Hz, J5a,5b ¼ 12.8 Hz,
H-5a), 3.82 (m, 1H, H-2), 3.62 (dd, 1H, J4,5b ¼ 1.4 Hz, H-5b), 3.57 (s, 3H,
OCH3), 2.18 (s, 3H, Ac). Anal. calcd. for C8H14O6: C, 46.60; H, 6.84.
Found: C, 46.49; H, 6.77.
Methyl 3-O-acetyl-b-L-arabinopyranoside. Yield 154 mg, (75%). Rf 0.49, mp
1
126–1278C (from EtOAc–hexane), [a]2D0 þ231.48 (c 0.6, CHCl3). H NMR
d: 5.10 (dd, 1H, J2,3 ¼ 10.0 Hz, J3,4 ¼ 3.2 Hz, H-3), 4.83 (d, 1H,
J1,2 ¼ 3.9 Hz, H-1), 4.08–3.92 (m, 2H, H-2, H-4), 3.85 (dd, 1H,
J4,5a ¼ 1.4 Hz, J5a,5b ¼ 12.5 Hz, H-5a), 3.70 (dd, 1H, J4,5b ¼ 2.2 Hz, H-5b),
3.46 (s, 3H, OCH3), 2.18 (s, 3H, Ac). Anal. calcd. for C8H14O6: C, 46.60;
H, 6.84. Found: C, 46.42; H, 6.94.
Methyl 3-O-acetyl-a-D-lyxopyranoside. Yield 136 mg (66%). Rf 0.38, syrup,
[a]2D0 þ74.68 (c 0.4, CHCl3). 1H NMR d: 5.05 (dd, 1H, J2,3 ¼ 3.2 Hz,
J3,4 ¼ 8.8 Hz, H-3), 4.65 (d, 1H, J1,2 ¼ 2.7 Hz, H-1), 4.10–3.90 (m, 2H,
H-2, H-4), 3.82 (dd, 1H, J4,5a¼ 5.3, J5a,5b ¼ 11.3 Hz, H-5a), 3.58 (dd, 1H,
J4,5b ¼ 9.3 Hz, H-5b), 3.43 (s, 3H, OCH3), 2.18 (s, 3H, Ac). Anal. calcd. for
C8H14O6: C, 46.60; H, 6.84. Found: C, 46.44; H, 6.89.
Methyl 3-O-acetyl-a-D-fucopyranoside. Yield 200 mg (91%). Rf0.52, mp
1
117.5–118.58C (from EtOAc–hexane), [a]2D0 þ239.88 (c 0.4, CHCl3). H
NMR d: 5.07 (dd, 1H, J2,3 ¼ 10.3 Hz, J3,4 ¼ 3.1 Hz, H-3), 4.79 (d, 1H,
J1,2 ¼ 4.0 Hz, H-1), 4.02 (m, 1H, H-5), 3.94 (dd, 1H, H-2), 3.85 (m, 1H,
H-4), 3.44 (s, 3H, OCH3), 2.17 (s, 3H, Ac), 1.29 (d, 3H, J5.6 ¼ 6.7 Hz,
CH3). Anal. calcd. for C9H16O6: C, 49.09; H, 7.32. Found: C, 48.90; H, 7.20.
Methyl 3-O-acetyl-b-D-ribopyranoside. Yield 198 mg (96%). Rf 0.58, mp 111–
1128C (from EtOAc–hexane), [a]2D0 –158.18 (c 0.4, CHCl3). 1H NMR d: 5.01
(t, 1H, J2,3 ¼ J3,4 ¼ 3.2 Hz, H-3), 4.78 (d, 1H, J1,2 ¼ 2.0 Hz, H-1), 4.03 (m, 1H,
H-4), 3.93 (dd, 1H, J4,5a ¼ 1.7, J5a,5b ¼ 12.4Hz, H-5a), 3.89 (m, 1H, H-2), 3.81
(dd, 1H, J4,5b ¼ 2.3 Hz, H-5b), 3.42 (s, 3H, OCH3), 2.19 (s, 3H, Ac). Anal.
calcd. for C8H14O6: C, 46.60; H, 6.84. Found: C, 46.72; H, 6.96.
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