Studies on the regioselective reductive ringcleavage reactions of 3,5-O-arylidene-D-xylofuranosides

Article abstract of DOI:10.1081/SCC-120021517

Reductive ring cleavage of 3,5-O-arylidene-D-xylofuranosides using LiAlH₄-AlCl₃ and NaBH₃CN-BF₃ proceeded regioselectively to provide secondary alcohol as the major product. The effect of the substitutents on th

Full text of DOI:10.1081/SCC-120021517

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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ISSN: 0039-7911 (Print) 1532-2432 (Online) Journal homepage: http://www.tandfonline.com/loi/lsyc20
Studies on the Regioselective Reductive
Ringcleavage Reactions of 3,5-O-Arylidene- d-
xylofuranosides
Ching-Yun Hsu & Chia-Chun Chen
To cite this article: Ching-Yun Hsu & Chia-Chun Chen (2003) Studies on the Regioselective
Reductive Ringcleavage Reactions of 3,5-O-Arylidene- d-xylofuranosides, Synthetic
Communications, 33:13, 2349-2363, DOI: 10.1081/SCC-120021517
To link to this article: http://dx.doi.org/10.1081/SCC-120021517
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Date: 18 February 2016, At: 23:34

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SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 13, pp. 2349–2363, 2003
Studies on the Regioselective Reductive
Ringcleavage Reactions of 3,5-O-Arylidene-
D-xylofuranosides
*
Ching-Yun Hsu and Chia-Chun Chen
Department of Chemical Engineering, Cheng Shiu
Institute of Technology Kaohsiung, Taiwan, ROC
ABSTRACT
Reductive ring cleavage of 3,5-O-arylidene-D-xylofuranosides using
LiA1H4–A1C13 and NaBH3CN–BF3 proceeded regioselectively to
provide secondary alcohol as the major product. The effect of the
substitutents on the selectivity is examined.
Key Words: Regioselective reductive cleavage; Xylofuranosides;
Benzylidene ketals; Projective groups; Hydride reducing agents.
*Correspondence: Ching-Yun Hsu, Department of Chemical Engineering,
Cheng Shiu Institute of Technology Kaohsiung, Taiwan, 833 ROC; E-mail:
erichsu@cc.csit.edu.tw.
2349
DOI: 10.1081/SCC-120021517
Copyright & 2003 by Marcel Dekker, Inc.
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com

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2350
Hsu and Chen
INTRODUCTION
Recent advances made in the field of oligosaccharide synthesis can be
attributed to the improved methods for the construction of the glycosidic
bond, whose success depends on the selective protection and deprotection
of sugar hydroxyl groups.[1] Benzylidene acetal is one of the extensively
used protective groups, which provides selective protection of the 4- and
6-hydroxyl groups of gluco, manno, and galactopyranoses and other
related sugars.[2,3] Methodologies for the regioselective reductive cleavage
of the benzylidene acetal, allowing selective formation of benzyl ether at
either the C4 or C6 hydroxyl moieties enhanced the utility of this protec-
tive group.[4,5]
RESULTS AND DISCUSSION
Though regioselective reduction of benzylidene acetals of pyranoses
is extensively studied, selective deprotection of this function is less
explored in furanose derivatives.[6] LiA1H4-A1C13
and NaBH3CN-
[7,8]
[5]
BF3 were quite often used as reagents to cleave the acetal function.
In the case of 4,6-O-benzylidene hexopyranosides, the direction of the
ring opening depends on the bulkiness of the C3-substituent.[6,8–10]
Although there are couple reports that dealt with the reductive ring open-
ing of 3,5-O-benzylidene-D-xylofuranoside, only one furanosyl sugar was
studied.[11] We have carried out a detailed study of the regioselective ring
opening reactions of 3,5-O-benzylidene-D-xylofuranosides 1 and results
are presented in this article.
When either anomer of 3,5-O-benzylidene-D-xylofuranoside la was
treated with NaBH3CN-BF3 or LiA1H4-A1C13 in THF, the correspond-
ing 5-O-benzyl-D-xylofuranoside 2a was obtained as the major product
(Sch. 1). The reductive cleavage was highly regioselective and only trace
amountof 3- O-benzyl-D-xylofuranoside 3a was formed. The yield of the
productwas relaitvely more when NaBH 3CN-BF3 was used as the
reagent.
To study the effect of the substituents on the regioselectivity of the
ring opening,3,5-O-arylidene-D-xylofuranosides were subjected to reduc-
tion under similar experimental conditions. Benzylidene acetals contain-
ing electron donating substituents such as 40-methoxy benzylidene and
20,40-dimethoxy benzylidene derivatives of D-xylofuranosides, 1b and 1c
on treatment with NaBH3CN-BF3 or LiAlH4-A1C13 in THF furnished
the corresponding 5-O-benzyl-D-xylofuranosides 2b and 2c respectively as
the major products in these reactions. However, the selectivity was

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Ringcleavage Reactions of 3,5-O-Arylidene-D-xylofuranosides
2351
significantly low when compared to simple benzyl derivative. On the
other hand, benzylidene acetals of furanosides with electron withdrawing
substituents in the benzene ring such as 20,60-difluorobenzylidene and
20,60-dichlorobenzylidene acetals, 1d and 1e, afforded a single product 4
in each case. However, the 1H NMR spectrum of 4 was devoid of the C1
anomeric proton signal corresponding to xylofuranoside (5.36 ppm).
Compound 4 was characterized as diol based on its spectral data. Thus
1d and 1e underwent initial reductive cleavage of benzylidene moiety to
5-O-benzyl derivative which suffered subsequent furanose ring cleavage
to yield 1, 2-diols 4a and 4b respectively. Though the reaction was very
slow, the selectivity was good in these cases.
Table 1. Ratio and yields of secondary (2) and primary alcohols (3).
Productraito
(2ꢀOH:1ꢀOH)
Compound
Reagent
Yield (%)
1a a
LAH/AlCl3
NaBH3CN/BF3
LAH/AlCl3
26:1
41:1
38:1
31:1
6:1
69
86
70
88
83
80
91
78
73
78
70
83
1a b
1b a
1b b
1c a
1c b
NaBH3CN/BF3
LAH/AlC13
NaBH3CN/BF3
LAH/AlCl3
4:1
5:1
NaBH3CN/BF3
LAH/AlCl3
3:1
3:1
NaBH3CN/BF3
LAH/AlCl3
NaBH3CN/BF3
4:3
2:1
7:6
Scheme 1.

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2352
Hsu and Chen
Thus electron donating groups in the benzylidene ring diminished the
regioselectivity while presence of an electron withdrawing group led to
enhanced selectivity, although reaction did not stop with the opening of
arylidene acetal ring in the latter case.
The mixture of the isomeric alcohols 2 and 3 could be separated by
1
using HPLC, and H NMR helped in the differentiation of primary and
secondary alcoholic products. Thus in moderately dilute solution, OH
proton of primary and secondary alcohols appeared as triplet and
doublet respectively. Esterification of the hydroxyl group using acetyl
chloride under basic conditions also served in distinguishing the isomeric
products which was based on the relative downfield shift in signal
positions of proton(s) attached to the hydroxyl group containing carbon.
The possible mechanistic pathways leading to both primary and
secondary alcohols are depicted in Sch. 2. Chelation of the oxygen
Scheme 2.

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Ringcleavage Reactions of 3,5-O-Arylidene-D-xylofuranosides
2353
atoms of substrate with the electron deficient A1 of the reagent leads to
the intermediates A and B. Intermediate A in which C2 oxygen is coor-
dinated to the electron deficient A1 leads to secondary alcohol 2 while
primary alcohol 3 results from intermediate B.
Formation of 2 as the major product in these reductive ring cleavage
reactions indicated the prominent role played by the C2 oxygen in chela-
tion with Al and this was proved by 13C NMR study carried out at low
temperatures. Thus, when an equimolar reaction of 1a and trimethylalu-
minium hexane solution was studied by 13C NMR at À78ꢀC in 1:1
CD2Cl2 and CDCl3 mixture as the solvent, a significant shift was
observed in the signals at 108.4 (CH), 88.6 (CH), 72.8 (CH), 56.0
(CH3) corresponding to C2, C3, C7, and C2-methoxy carbons of 1a
respectively. Shift in these signals may be obviously attributed to the
participation of the C2 oxygen in the chelation which will affect the
environmentof ht ese carbons.
Subsequently we have modified the oxygen function at C2 in the
substrate to find out its effect on the extent of chelation with the reagent.
Reaction of the 2-hydroxy compound 5 with benzyl bromide in the pres-
ence of NaH afforded the corresponding benzyle derivative 6 which on
treatment with LAH/AlCl3 afforded the secondary alcohol 7 along with
the corresponding open chain vicinal diol 8 as the minor product (Sch. 3).
Thus, in spite of the presence of a relatively bulkier benzyl substituent,
the C2 oxygen could participate in chelation.
In order to study the effect of an electron withdrawing group on the
ability of the C2 oxygen to participate in chelation, a mesyl group was
Scheme 3.

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2354
Hsu and Chen
Scheme 4.
Scheme 5.
introduced on it. Thus reaction of the methyl furanoside 5 with mesyl
chloride in the presence of triethylamine in dichloromethane furnished
the corresponding mesylate 9 as a white solid. Treatment of 9 with two
equiv. of BF3ÁEt2O at 0ꢀC followed by the addition of a THF solution of
NaBH3CN yielded the secondary alcohol 10 as the sole product (Sch. 4).
Formation of the epoxide 11 from 10 in the presence of NaH through an

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Ringcleavage Reactions of 3,5-O-Arylidene-D-xylofuranosides
2355
intramolecular substitution of mesyl group proved the assigned structure
of 10.
Finally it was planned to examine the regioselectivity of the reductive
ring cleavage in the absence of C2 oxygen and C2 OH group of 5 was
replaced by a methyl group. Swern oxidation of the alcohol 5 yielded
ketone 12 in 87% yield. As ketone was prone to undergo epimerization
readily, it was as such used in the subsequent laboratory operation with
out further chromatographic purification. Thus Wittig reaction of the
ketone 12 with CH3BrPPh3/BuLi at0 ꢀC yielded alkene 13 which on
catalytic hydrogenation afforded 14 as an inseparable mixture of a, b
isomers in 10:1 ratio.
Reductive cleavage of 14 using LAH/AlCl3 proceeded very slowly
and afforded a mixture of open chain diols 15 and 16 corresponding to
primary and secondary alcohols, respectively in 1:1 ratio (Sch. 5). Thus
no selectivity was observed in the absence of C2 oxygen.
In conclusion, reductive ring opening of acetals of xylofuranosides
with mixed hydride reagents, LiA-H4–AlCl3 and NaBH3CN–BF3 pro-
ceeded regioselectively to provide secondary alcohol as the major prod-
uct. Electron donating substituents in the arylidene moiety decreased the
selectivity, while electron withdrawing groups enhanced the selectivity,
though reduction led to furanose ring opening in the latter case. The
role of the C2 oxygen in providing the regioselectivity was studied by
modifying the oxygen functionality at C2 of the substrate.
EXPERIMENTAL SECTION
All the melting points were determined on a Buchi 512 melting point
apparatus and are uncorrected. Infra red spectra were recorded on Perkin
1
Elmer 781 and Bomern B-100 Infrared Spectrophotometers. H NMR
spectra were run on a Bruker AM-400 NMR spectrometer. Low
Resolution Mass spectra and High Resolution Mass Spectra were mea-
sured on Jeol TMS-D-100 and Jeol TMS-HX spectrometers, respectively.
Elemental analyseswereperformed onaHeraeusCHN-O-Rapid Analyzer.
Specific rotations were determined on Jasco DIP-360 polarimeter.
General Procedure for the Reductive Cleavage of 3,5-O-
Arylidene-2-O-methyl-a(b)2-O-D-xylofuranoses (1a–e)
To a solution of AlCl3 (0.88 b, 6.60 mmol) in anhydrous ether (8 mL)
at0 C was added 1M solution of LAH (1.70 mL, 1.70 mmol, THF) and
ꢀ

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Hsu and Chen
the reaction mixture was stirred for 20 min. A solution of compound 1
(3.30 mmol) in of ether (3 mL) was added slowly to the above reagent
solution and the reaction mixture was warmed to room temperature and
stirred for 4 h.
In case of xylofuranoses 1d and 1e, the reaction mixture was heated
ꢀ
at55 C for 50 h. The reaction was quenched with saturated NaCl solu-
tion (10 mL) and the mixture was extracted with ethyl acetate
(3 Â 15 mL). The combined organic extracts were dried (Na2SO4) and
concentrated, and the residue was purified by flash column chromatogra-
phy (EtOAc/hexanes). Xylofuranoses 1a–c yielded a mixture of corre-
sponding alcohols 2 and 3 in each case, which was separated by HPLC
using hexane/EtOAc/isopropanol (2:4:1) as the mobile phase.
Compounds 1d and 1e afforded the diols 4a and 4b, respectively.
20
Compound 2a. ½aŠ 18.2 (c 2.5, CHC13). IR (CHC13): 3600–3200
D
(OH), 2890, 1480, 1170, 1110 cmÀ1
.
1H NMR (CDC13, 400 MHz):
ꢀ 7.39–7.28 (m, 5H), 4.97 (d, 1H, J ¼ 4.4 Hz.), 4.62, 4.57 (ABq, 2H,
J ¼ 12.0 Hz), 4.44 (m, 1H), 4.29 (m, 1H), 3.74 (m, 3H), 3.49 (s, 3H),
3.43 (s, 3H), 3.17 (d, OH, J ¼ 8 Hz). 13C NMR (CDC13, 100 MHz):
ꢀ 137.3 (C), 128.5 (CH), 127.7 (CH), 127.6 (CH), 100.4 (CH), 87.1
(CH), 76.0 (CH), 75.4 (CH), 73.8 (CH2), 69.2 (CH2), 58.0 (CH3), 55.1
(CH3). HRMS (EI, 70 eV): Calcd. for C14H20O5: 268.1311. Found:
268.1318.
20
Compound 3a. ½aŠ À26.73 (c 2.0, CHC13). IR (CHC13): 3600–3300
D
(OH), 2940, 1510, 1200, 1120 cmÀ1
.
1H NMR (CDC13, 400 MHz): ꢀ
7.37–7.29 (m, 5H), 4.84 (d, 1H, J ¼ 1.6 Hz), 4.70, 4.54 (ABq, 2H,
J ¼ 12 Hz), 4.31–4.26 (m, 1H), 4.10 (dd, 1H, J ¼ 6.8, 4.0 Hz), 3. 87 (dd,
1H, J ¼ 3.6, 2.0 Hz), 3.97 (1H), 3.42 (s, 3), 3.37 (s, 3H), 2.58 (br, OH).
13C NMR (CDCl3, 100 MHz): ꢀ 137.4 (C), 128.5 (CH), 128.0 (CH), 127.8
(CH), 107.6 (CH), 89.1 (CH), 82.6 (CH), 80.6 (CH), 72.5 (CH2), 62.2
(CH2), 57.8 (CH3), 55.6 (CH3). MS (12eV, m/z): 237 (Mþ-31, 4), 177
(52), 117 (20), 91 (100). HRMS (EI, 70 eV). Calcd. for C14H20O5:
268.1311. Found: 268.1299.
20
Compound 2b. ½aŠ 93 (c 0.5, CHCl3); IR (CHC13) 3700–3150, 2940,
D
1620, 1515, 1260, 1040 cmÀ1. 1H NMR (CDCl3, 400 MHz): ꢀ 7.23 (d, 2H,
J ¼ 8.8 Hz), 6.87 (d, 2H, J ¼ 8.8 Hz), 4.95 (d, 1H, J ¼ 4.4 Hz), 4.54, 4.46
(ABq, 2H, J ¼ 11.6 Hz), 4.42 (m, 1H), 4.26 (dt, 1H, J ¼ 7.2, 3.6 Hz), 3.79
(s, 3H), 3.72–3.69 (m, 3H), 3.48 (s, 3H), 3.41 (s, 3H), 3.14 (d, OH,
J ¼ 8.4 Hz). 13C NMR (CDCl3, 100 MHz): ꢀ 159.5 (C), 130.0 (CH),
129.5 (C), 114.0 (CH), 100.5 (CH), 87.5 (CH), 76.5 (CH), 75.5 (CH),
73.5 (CH), 68.5 (CH2), 58.5 (CH2), 55.5(CH2), 55.4 (CH2). MS (12 eV,
m/z) 298 (Mþ, 6), 266 (17), 179 (41), 164 (100). HRMS (EI, 70eV). Calcd.
for C15H22O6: 298.1433. Found: 298.1425.

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Ringcleavage Reactions of 3,5-O-Arylidene-D-xylofuranosides
2357
20
D
Compound 3b. ½aŠ À2.9 (c. 1, CHCl3). IR (CHCl3): 3600–3200, 2920,
1610, 1510, 1250, 1120 cmÀ1. 1H NMR (CDCl3, 400 MHz): ꢀ 7.26 (d, 2H,
J ¼ 8.4 Hz), 6.88 (d, 2H, J ¼ 8.4 Hz), 4.83 (d, 1H, J ¼ 1.6 Hz), 4.64, 4.46
(ABq, 2H, J ¼ 11.6 Hz), 4.26 (m, 1H), 4.08 (dd, 1H, J ¼ 4.4, 3.6 Hz), 3.86
(d, 1H, J ¼ 3.6 Hz), 3.08, (m, 3H), 3.76 (m, 2H), 3.42 (m, 3H), 3.37 (m,
3H). MS (12 eV, m/z): 298 (Mþ, 1), 235 (10), 151 (15), 121 (100). HRMS
(EI, 70 eV). Calcd. for C15H22O6: 298.1404. Found: 298.1398.
20
Compound 2c. ½aŠ À54(c 1, CHCl3). IR (CHCl3): 3550–3400 (OH),
D
1
3020, 1615, 1510, 1220 cmÀ1. H NMR (CDCl3, 400 MHz), ꢀ 7.2 (d, 1H,
J ¼ 8.8 Hz), 6.44–6.42 (m, 2H), 4.85 (s, 1H), 4.53, 4.47 (ABq, 2H,
J ¼ 11.2 Hz), 4.34 (dt, 1H, J ¼ 11.2, 5.6 Hz), 4.19 (dd, 1H, J ¼ 6.0,
6.0 Hz), 3.92–3.69 (m, 3H), 3.79 (s, 3H), 3.78 (s, 3H), 3.39 (s, 3H), 3.35
(s, 3H), 3.28 (d, OH, J ¼ 8.0 Hz). MS (12 eV, m/z): 328 (Mþ, 78), 296 (87),
167 (81), 166 (100), 151 (89). HRMS (EI, 70 eV). Calcd. for C16H24O7:
328.1522. Found: 328.1526.
20
Compound 3c. ½aŠ À51.9 (c 1, CHCl3). IR (CHCl3): 3600–3400
D
(OH), 3020, 2940, 1620, 1510, 1300, 1220 cmÀ1
.
1H NMR (CDCl3,
400 MHz): ꢀ 7.15 (d, 1H, J ¼ 8.0 Hz), 6.44 (dd, 1H, J ¼ 8.0, 2.4 Hz),
6.41 (d, 1H, J ¼ 2.4 Hz), 4.94 (d, 1H, J ¼ 4.4 Hz), 4.66, 4.50 (ABq, 2H,
J ¼ 10.8 Hz), 4.32 (dd, 1H, J ¼ 6.8, 7.2 Hz), 4.17 (m, 1H), 3.88 (dd, 1H,
J ¼ 6.0, 4.0 Hz), 3.79 (s, 3H), 3.78 (s, 3H), 3.69 (dd, 2H, J ¼ 6.8, 4.8 Hz),
3.45 (s, 3H), 3.41 (s, 3H), 2.89 (t, OH, J ¼ 6.8 Hz). MS (12 eV, m/z): 328
(Mþ, 17), 296 (13), 265 (21), 167 (31), 151 (100). HRMS (EI, 70 eV).
Calcd. for C16H24O7: 328.1522. Found: 328.1528.
20
Compound 4a. Yield 50%; ½aŠ À13.23 (c 5, CHCl3): IR (neat).
D
3600–3200 (OH), 2940, 1540, 1440, 1200 cmÀ1
.
1H NMR (CDCl3,
400 MHz): ꢀ 7.29 (d, 1H, J ¼ 7.6 Hz), 7.17 (d, 1H, J ¼ 7.6 Hz), 7.15 (d,
1H, J ¼ 7.6 Hz), 4.82, 4.79 (ABq, 2H, J ¼ 10.8 Hz), 3.88 (bs, 1H), 3.75-
3.55 (m, 6H), 3.41 (s, 3H), 3.34 (s, 3H), 3.06 (d, OH, J ¼ 4.0 Hz), 2.84 (d,
OH,. J ¼ 5.2 Hz). 13C NMR (CDCl3, 100 MHz): ꢀ 136.8 (C), 133.0 (C),
130.0 (CH), 128.4 (CH), 81.0 (CH), 72.3 (CH2), 71.2 (CH2), 71.0 (CH),
69.9 (CH), 67.6 (CH2), 59.3 (CH3), 58.3(CH3). MS (12 eV, m/z): 305 (Mþ-
33, 8), 303 (Mþ-35, 9), 249 (27), 247 (45), 177 (64), 175 (100), 87 (78). MS
(FAB, 70 eV): 339.
20
D
Compound 4b. Yield 56%; ½aŠ À4.80 (c 5, CHC13): IR (neat).
3600–3200 (OH), 2950, 1630, 1605, 1480, 1240, 1100 cmÀ1
.
1H NMR
(CDC13, 400 MHz): ꢀ 7.23–7.19 (m. 1H), 6.85-6.80 (m, 2H), 4.58 (s,
2H), 3.82 (bs, 1H), 3.66 (bs, 1H), 3.60–3.48 (m, 4H), 3.39–3.37 (m,
1H), 3.38 (s, 3H), 3.29 (s, 3H), 3.20 (bs, OH), 2.94 (bs, OH). 13C NMR
(CDC13, 100 MHz), ꢀ 163 (C), 160.5 (C), 130.1 (CH), 113.4 (C), 111.1
(CH), 80.8 (CH), 71.9 (CH2), 71.1 (CH2), 70.8 (CH), 69.8 (CH), 60.3
(CH20), 59 (CH3), 58.1 (CH3); Mass (12 eV, m/z): 261 (Mþ-45, 25), 255

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2358
Hsu and Chen
(18), 171 (31), 127 (100), 88 (81). MS (FAB, 70 eV): 307. Anal. calcd. for
C14H16F2O5: C, 55.63; H, 5.23. Found: C, 55.65; H, 5.27.
Preparation of Methyl 3,5-O-Benzylidene-2-O-benzyl-
a-D-xylofuranose (6)
NaH (60%, 0.64 g, 16 mmol) was washed with hexane (3 Â 10 mL),
dried in vacuo and THF (10 mL) was added to it under N2 atmosphere. A
solution of alcohol 5 (2.5 g, 9.92 mmol) in THF (10 mL) was added slowly
to the above mixture and stirred vigorously for 15 min. Benzyl bromide
(1.43 mL, 11.9 mmol) was added and reaction mixture was stirred at
room temperature for 6 h. Reaction was quenched with saturated NaCl
solution (20 mL) and the mixture was extracted with ethyl acetate
(3 Â 15 mL). The combined organic extracts were dried (Na2S04) and
concentrated, and the residue was purified by flash column chromatogra-
phy (EtOAc/hexanes 4:1) to frunish compound 6 (3.08 g, 91%) as a white
solid. M.p. 114ꢀC. ½aŠ À74.96 (c 5, CHCl3). IR (CHCl3): 3030, 1230,
20
D
1
940, 750 cmÀ1. H NMR (CDCl3, 400 MHz): ꢀ 7.48–7.30 (m, 10H), 5.43
(s, 1H), 5.28 (d, 1H, J ¼ 4.4 Hz), 4.75, 4.64 (ABq, 2H, J ¼ 12.0 Hz), 4.43
(d, 1H, J ¼ 2.8 Hz), 4.41 (d, 1H, J ¼ 13.6 Hz), 4.15–4.10 (m, 3H), 3.54 (s,
3H); 13C NMR (CDCl3, 100 MHz), ꢀ 137.7 (C), 137.5 (C),129.0 (CH),
128.3 (CH), 128.1 (CH), 127.9 (CH), 127.8 (CH), 126.0 (CH), 104.4
(CH), 99.2 (CH), 83.3 (CH), 80.0 (CH), 73.2 (CH), 70.7 (CH), 67.0
(CH2), 56.5 (CH3). HRMS (EI, 70 eV). Calcd. for C20H22O5: 342.1467.
Found: 342.1477. Anal. calcd. for C20H22O5: C, 70.17; H, 6.43. Found: C,
69.96; H, 6.52.
Reductive Cleavage of 3,5-O-Benzylidene-2-
O-benzyl-a-D-xylofuranose (6)
To a solution of AlCl3 (1.76 g, 13.2 mmol) in anhydrous ether
(16 mL) at0 ꢀC was added 1M solution of LAH (3.4 mL, 3.4 mmol,
THF) and the reaction mixture was stirred for 20 min. A solution of
compound 6 (2.12 g, 6.20 mmol) in 5 mL of ether was added slowly to
the above reagent solution and the reaction mixture was warmed to room
temperature and stirred for 10 h. The reaction was quenched with satu-
rated NaCl solution (10 mL) and mixture was extracted with ethyl acetate
(4 Â 20 mL). The combined organic extracts were dried (Na2S04) and
concentrated, and the residue was purified by flash column chromatogra-
phy (EtOAc/hexanes 1:3) to provide alcohols 7 and 8.

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Ringcleavage Reactions of 3,5-O-Arylidene-D-xylofuranosides
2359
20
Compound 7. Yield 38%; ½aŠ À35 (c 1, CHCl3). IR (CHCl3):
D
3600–3400 (OH), 3020, 2940, 1470, 960 cmÀ1
.
1H NMR (CDCl3,
400 MHz): ꢀ 7.37–7.25 (m, 5H), 4.78 (d, 1H, J ¼ 4.4 Hz), 4.70, 4.67
(ABq, 2H, J ¼ 14.4 Hz), 4.57, 4.51 (ABq, 2H, J ¼ 14.8 Hz), 4.50(m, 1H),
4.28 (m, 1H), 3.86 (dd, 1H, J ¼ 6.0, 4.4 Hz), 3.73 (dd, 1H, J ¼ 3.2, 2.0 Hz),
3.37 (s, 3H), 2.98 (d, OH, J ¼ 8.0 Hz). 13C NMR (CDC13, 100 MHz): ꢀ
138 (C), 137.5 (C, 128.5 (CH), 128.4 (CH), 128.2 (CH), 128.0 (CH), 127.7
(CH), 101 (CH), 85.1 (CH), 76.0 (CH), 75.7 (CH), 74.0 (CH2), 72.5
(CH2), 69.4 (CH2), 55.5 (CH3). Mass (12 eV, m/z): 312 (Mþ-32,6),193
(34), 163 (61),91 (100).
20
D
Compound 8: Yield 13%; ½aŠ À40 (c 1, CHCl3). IR (CHCl3):
3600–3300 (OH), 3020, 2940, 1460, 1100 cmÀ1
.
1H NMR (CDCl3,
400 MHz) ꢀ: 7.35–7.27 (m, 5H), 4.75, 4.55 (ABq, 2H, J ¼ 11.6 Hz), 4.53,
4.51 (ABq, 2H, J ¼ 11.6 Hz), 3.92 (bs, 1H), 3.77 (dd, 1H, J ¼ 4.4, 2.4 Hz),
3.69–3.51 (m, 5H), 3.37 (s, 3H), 3.11 (d, OH, J ¼ 3.6 Hz), 2.83 (d, OH,
J ¼ 5.6 Hz). 13C NMR (CDCl3, 100 MHz), ꢀ 137.9 (C), 128.5 (CH), 128.1
(CH), 128.0 (CH), 78.9 (CH), 73.5 (CH2), 72.6 (CH2), 72.0 (CH2), 71.8
(CH2), 71.1 (CH), 70.1 (CH), 59.3 (CH3). MS (FAB, 70 eV): 347.
Preparation of Methyl 3,5-O-Benzylidene-2-
O-mesyl-a-D-xylofuranose (9)
To a solution of alcohol 5 (1.60 g, 6.35 mmol) and triethylamine
(1.80 mL, 13.7 mmol) in dry dichloromethane at 0ꢀC was added mesyl
chloride (0.54 mL, 6.98 mmol) and the reaction mixture was stirred at
room temperature for 8 h. The reaction was quenched with 5% HCl
(10 mL) and the mixture was extracted with dichloromethane
(3 Â 15 mL). The combined organic extracts were dried (Na2S04) and
concentrated, and the residue was purified by flash column chromatogra-
phy (EtOAc/hexanes 1:6) to provide compound 9 (1.84 g, 88%) as a white
20
solid. M.p. 116ꢀC. ½aŠD À115.87 (c 3.2, CHCl3). IR (CHCl3): 3020, 1450,
1350, 1210, 1180, 1075, 1020 cmÀ1 1H NMR (CDCl3, 400 MHz): ꢀ
.
7.48–7.44 (m, 2H), 7.39-7.34 (m, 3H), 5.47 (s, 1H), 5.41 (d, 1H, J ¼ 3.
6 Hz), 4.61 (d, 1H, J ¼ 2.0 Hz), 4.42 (dd, 1H, J ¼ 13.2, 1.2 Hz), 4.17 (bs,
1H), 4.12 (dd, 1H, J ¼ 13.6, 2.0 Hz), 3.54 (s, 3H), 3.09 (s, 3H). 13C NMR
(CDCl3, 100 MHz), ꢀ 137.2 (C), 129.2 (CH), 128.3 (CH), 126.0 (CH),
103.4 (CH), 99.3 (CH), 81.9 (CH), 75.2 (CH), 71.2 (CH), 66.9 (CH2),
57.0 (CH3), 38.7 (CH3). MS (12 eV, m/z): 330 (Mþ, 42), 329 (Mþ-1,
36), 251 (63), 191 (42), 121 (100). HRMS (EI, 70 eV). Calcd. for
C14H18O7S: 330.0725. Found: 330.0740. Anal. calcd. for C14H18O7S: C,
50.91; H, 5.45; S, 9.70. Found: C, 50.46; H, 5.40; S, 9.86.

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2360
Hsu and Chen
Reductive Cleavage of 3,5-O-Benzylidene-2-
O-mesyl-a-D-xylofuranose (9)
To a solution of BF3ÁEt20 (1.60 mL, 1.60 mmol) in THF (5 mL) at
0ꢀC was added compound 9 and the reaction mixture was stirred for
10 min. A solution of NaBH3CN (0.12 g, 1.92 mmol) dissolved in THF
(10 mL) was added slowly to the above mixture and the contents were
stirred at room temperature for 40 h. Reaction mixture was poured in to
saturated NaHCO3 solution (20 mL) and was extracted with ethyl acetate
(3 Â 15 mL). The combined organic extracts were dried (Na2SO4) and
concentrated, and the residue was purified by flash column chromatogra-
phy (EtOAc/hexanes 1:2) to provide secondary alcohol 10 (0.13 g, 92%).
M.p. 134ꢀC. ½aŠ À128.4 (c 9.2, CHCl3). IR (CHCl3): 3680–3300 (OH),
20
D
3030, 2950, 1365, 1220, 1185 cmÀ1
.
1H NMR (CDCl3, 400 MHz): ꢀ
7.35–7.28 (m, 5H), 5.01 (d, 1H, J ¼ 4.4 Hz), 4.83 (dd, 1H, J ¼ 6.4,
4.4 Hz), 4.61, 4.55 (ABq, 2H, J ¼ 12 Hz), 4.59–4.57 (m, 1H), 4.30–4.28
(m, 1H), 3.74, 3.73 (ABq, 2H, J ¼ 1.6 Hz), 3.41(s, 3H), 3.34 (d, OH,
J ¼ 8.4 Hz), 3.10 (s, 3H). 13C NMR (CDCl3, 100 MHz), ꢀ 137.0 (C),
128.6 (CH), 128.0 (CH), 127.7 (CH), 99.6 (CH), 84.1 (CH), 75.3 (CH),
74.0 (CH2), 73.9 (CH), 68.9 (CH2), 55.4 (CH3), 58.5 (CH3). MS (12 eV,
m/z): 332 (Mþ, 5), 221 (18), 193 (26), 91 (56), 87 (100). HRMS (EI,
70 eV). Calcd. for C14H20O7S: 332.0905. Found: 332.0917.
Preparation of Methyl 5-Benzyl-2,3-
anhydro-a-D-xylofuranose (11)
NaH (60%, 0.08 g, 1.93 mmol) was washed with hexane (3 Â 10 mL),
dried in vacuo and THF (10 mL) was added to it under N2 atmosphere.
A solution of alcohol 10 (0.16 g, 0.48 mmol) in THF (5 mL) was added
slowly to the above mixture and stirred for 4 h. The reaction was
quenched with saturated NaCl solution (5 mL) and the mixture was
extracted with ethyl acetate (3 Â 10 mL). The combined organic extracts
were dried (Na2SO4) and concentrated, and the residue was purified by
flash column chromatography (EtOAc/hexanes 1:6) to furnish epoxide 11
20
(0.091 g, 80%). ½aŠ 24.11 (c 0.9, CHC13). IR (CHCl3): 3680–3300 (OH),
D
3020, 1523, 1450, 1353, 1215 cmÀ1
.
1H NMR (CDCl3, 400 MHz): ꢀ
7.34–7.25 (m, 5H), 4.93 (s, 1H), 4.60, 4.56 (ABq, 2H, J ¼ 12 Hz), 4.19
(dd, 1H, J ¼ 6.4, 6.4 Hz), 3.74 (d, 1H, J ¼ 2.8 Hz), 3.65–4.62 (m, 3H), 3.40
(s, 3H). 13C NMR (CDCl3, 100 MHz): ꢀ 137.8 (C), 128(CH), 127.8 (CH),
127.7 (CH), 102.3 (CH), 75.1 (CH), 73.7 (CH2), 68.5 (CH2), 56.2 (CH),
55.6 (CH), 54.3 (CH2), 58.5 (CH3). MS (FAB, m/z) 235.

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Ringcleavage Reactions of 3,5-O-Arylidene-D-xylofuranosides
2361
Swern Oxidation of Methyl 3,5-D-Benzylidene-
a(b)-D-xylofuranose (5)
To a solution of oxalyl chloride (3.00 mL, 34.2 mmol) in CH2Cl2
(20 mL) under N2 atmosphere at À78ꢀC was added DMSO (5.30 mL,
68.4 mmol) and the mixture was stirred for 5 min. A solution of alcohol
5 (4.30 g, 17.1 mmol) in CH2Cl2 (10 mL) was slowly added to the above
reagent and the reaction mixture was stirred at À78ꢀC for 1h. The reac-
tion was quenched with triethylamine (14.3 mL, 102 mmol) and warmed
to room temperature. Ether (100 mL) was added and the precipitate was
filtered off. The filtrate was diluted with H2O (30 mL) and extracted with
ether (3 Â 20 mL). The combined organic extracts were dried (Na2SO4)
and concentrated, and the residue was purified by flash column chroma-
tography (EtOAc/hexanes 1:3) to furnish ketone 12 (3.70 g, 87%). IR
1
(CHCl3): 3010 (OH), 1725 (C ¼ 0), 1220, 1045 cmÀ1. H NMR (CDC13,
400 MHz): ꢀ 7.50–7.45 (m, 2H), 7.37–7.33 (m, 3H), 5.52 (d, 1H,
J ¼ 5.2 Hz), 5.00 (d, 1H, J ¼ 4.4 Hz), 4.51–4.06 (m, 4H), 3.56 (s, 3H).
MS (12 eV, m/z): 249 (Mþ-1, 5), 162(95), 145 (15), 105 (100).
Preparation of Methyl 3,5-O-Benzylidene-2-
deoxy-2-C-methylene-a-D-xylofuranose (13)
At À78ꢀC, CH3BrPPh3 (15.9 g, 45.0 mmol) was dissolved in THF
(25 mL) under N2 atmosphere and BuLi (2.2 M, 19.0 mL, 41.80 mmol)
was slowly added to this solution. The reaction mixture was warmed to
0ꢀC and stirred for 30 min, then was lowered to À78ꢀC and a solution of
12 (3.55 g, 14.2 mmol) in THF (10 mL) was slowly added. The reaction
mixture was stirred at room temperature for 24 h, and quenched with
saturated NaCl solution (20 mL). The mixture was extracted with ethyl
acetate (3 Â 20 mL). The combined organic extracts were dried (Na2SO4)
and concentrated, and the residue was purified by flash column chroma-
tography (EtOAc/hexanes 1:5) to furnish alkene 13 (1.93 g, 55%). M.p.
20
135ꢀC. ½aŠ 177.5 (c 2, CHC13). IR (CHCl3): 3020, 1515, 1215, 1050, 925:
D
1H NMR (CDCl3, 400 MHz): ꢀ 7.47 (dd, 1H, J ¼ 8.0, 2.0 Hz), 7.36–7.31
(m, 3H), 5.63 (d, 1H, J ¼ 1.6 Hz), 5.55 (s, 1H), 5.49 (s, 2H), 4.70 (d, 1H,
J ¼ 2.0 Hz), 4.47 (d, 1H, J ¼ 13.2 Hz), 4.19 (dd, 1H, J ¼ 13.2 Hz), 3.98 (d,
1H, J ¼ 2.0 Hz), 3.47 (s, 3H). 13C NMR (CDCl3, 100 MHz): ꢀ 147.8 (C),
137.7 (CH), 129.0 (CH), 128.2 (CH), 126.2 (CH), 116.7 (CH2), 103.9 (C),
99.2 (CH), 77.1 (CH), 72.0 (CH), 66.9 (CH2), 55.6 (CH3). MS (12 eV,
m/z): 248 (Mþ, 8), 247 (Mþ-1, 100), 171 (46), 149 (42), 99 (100). (HRMS:
EI, 70 eV) Calcd. for C14H16O4: 248.1011. Found: 248.1006.

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2362
Hsu and Chen
Preparation of Methyl 3,5-O-Benzylidene-2-C-
methyl-2-deoxy-a-D-xylofuranose (14)
A solution of alkene (1.05 g, 1.23 mmol) and Pd-C (10%, 0.05 g) in
MeOH (20 mL) was subjected to hydrogenation at 1 atm pressure for 5 h.
The reaction mixture was filtered through celite and the precipitate was
washed with methanol (2 Â 5 mL). The combined methanolic solution
was dried (Na2SO4) and concentrated, and the residue was purified by
flash column chromatography (EtOAc/hexanes 1:4) to furnish 14 (1.01 g,
95%) as a white solid. M.p. 74ꢀC. IR (CHCl3): 3020, 1520, 1420, 1210,
1
930 cmÀ1. H NMR (CDCL3, 400 MHz): 7.50–7.46 (m, 2H), 7.36–7.31
(m, 3H), 5.44 (s, 1H), 4.95 (d, 1H, J ¼ 5.6 Hz), 4.3 8 (d, 1H, J ¼ 13.2 Hz),
4.26 (dd, 1H, J ¼ 4.0, 2.0 Hz), 4.09 (dd, 1H, J ¼ 13.2, 2.4 Hz), 4.00 (m,
1H), 3.44 (s, 3H), 2.34–2.25 (m, 2H), 1.24–1.10 (m, 2H). MS (12 eV, m/z):
248 (Mþ, 57), 250 (Mþ-l, 39), 190 (21), 144 (48), 101 (100). HRMS (EI,
70 eV). Calcd. for C14H18O4: 250.1209. Found: 250.1207.
Reductive Cleavage of Methyl 3,5-O-Benzylidene-
2-C-methyl-2-deoxy-a-D-xylofuranose (14)
To a solution of LAH (1 M, 1.70 mL, 1.70 mmol, THF) in THF
(5 mL), was added a suspension of AlCl3 (0.56 ꢁ g, 4.20 mmol) in THF
ꢀ
(5 mL) at0 C under N2 atmosphere and the reagent mixture was stirred
for 20 min. A solution of compound 14 (0.51 g, 2.10 mmol) in 5 mL of
THF was added slowly to the above reagent solution and the reaction
mixture was warmed to room temperature and stirred for 18 h. The reac-
tion was quenched with saturated NaCl solution (10 mL) and the mixture
was extracted with ethyl acetate (3 Â 10 mL). The combined organic
extracts were dried (Na2S04) and concentrated, and the residue was pur-
ified by flash column chromatography (EtOAc/hexanes 1:2) to furnish
alcohols 15 and 16.
Compound 15. Yield 0.17 g, 34%. IR (CHCl3): 3393, 2909, 1496,
1454, 1391, 1079; 1H NMR (CDCl3, 400 MHz), 7.41–7.29 (m, 5H),
4.64, 4.52 (ABq, 2H, J ¼ 11.2 Hz), 3.75 (bs, 1H), 3.61 (m 2H), 3.51-3.35
(m, 4H), 3.30 (s, 3H), 2.85 (bs, OH), 2.15 (m, 1H), 1.71 (bs, OH), 1.02 (d,
3H, J ¼ 7.2 Hz). MS (FAB, 70 eV): 255.
Compound 16. Yield 0.18 g, 33%. IR (CHCl3): 3600–3400, 3020,
2920, 1230, 1050; 1H NMR (CDCl3, 400 MHz): 7.38–7.26 (m, 5H),
4.55, 4.53 (ABq, 2H, J ¼ 13.2 Hz), 3.73 (bs, OH), 3.64–3.33 (m, 6H),
3.31 (s, 3H), 3.21 (bs, OH), 2.55–1.89 (m, 1H), 0.96 (d, 3H, J ¼ 7.2 Hz).
HRMS (EI, 70 eV). Calcd. for C14H23O4: 255.1612. Found. 255.1604.

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Ringcleavage Reactions of 3,5-O-Arylidene-D-xylofuranosides
2363
ACKNOWLEDGMENT
We thank the National Science Council of the Republic of China for
the Financial support. (NSC 85-2113-M-230-0027). We also thank our
research students—Li-Wen Wang, Ti-Chung Huang, and Hsiao-Ting
Huang.
REFERENCES
1. Sakagami, M.; Hamana, H. Tetrahedron Lett. 2000, 41, 5547.
2. Garegg, P. J. Pure Appl. Chem. 1984, 845.
3. Preparative Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel
Dekker, Inc.: New York, 1997; 53–65.
4. Garegg, P.J.; Hultberg, H. Carbohydrate Res. 1981, 93, C10.
5. Garegg, P.J.; Hultberg, H.; Wallin, S. Carbohydrate Res. 1982,
108, 97.
6. Liptak, A.; Neszmelyi, A.; Kovac, P.; Hirsch, J. Tetrahedron 1981,
37, 2379.
7. Bhattacharjee, S.S.; Gorin, P.A. J. Can. J. Chem. 1969, 47, 1195.
8. Liptak, A. Tetrahedron Lett. 1976, 16, 3551.
9. Liptak, A.; Jodal, I.; Nanasi, P. Carbohydrate Res. 1975, 44, 1.
10. Liptak, A.; Fugedi, P.; Nanasi, P. Carbohydrate Res. 1978, 65, 209.
11. (a) Marwood, R.D.; Shuto, S.; Jenkins, D.J.; Potter, B.V.L. Chem.
Commun. 2000, 219; (b) Marwood, R.D.; Jenkins, D.J.; Correa, V.;
Taylor, C.W.; Potter, B.V.L. J. Med. Chem. 2000, 43, 4278.
Received in the Netherlands October 24, 2002

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