1→2 Migration and concurrent glycosidation of phenyl 1-thio-α-mannopyranosides via 2,3-O-cyclic dioxonium intermediates

Article abstract of DOI:10.1016/S0040-4020(02)01452-7

Treatment of phenyl 2,3-O-cyclic ketene acetal- and 2,3-O-thionocarbonyl-1-thio-mannopyranosides with TMSOTf and MeOTf, respectively, gave the corresponding 2,3-O-cyclic dioxonium intermediates, which proceeded via 1→2 migration and concurrent glycosidation in the presence of alcohols to provide the corresponding 2-S-phenyl glycosides stereoselectively. While the former donors were too labile, the latter donors have proved superior for the present purpose. The X-ray crystallographic structures of phenyl 4-O-methyl-2,3-O-thiocarbonyl-1-thio-α-L-rhamnopyranoside (1), a typical donor for the present reaction, and its anomeric azide analogue (6), which could not undergo the present reaction under similar conditions, are provided.

Full text of DOI:10.1016/S0040-4020(02)01452-7

Tetrahedron 59 (2003) 249–254
1!2 Migration and concurrent glycosidation of phenyl 1-thio-a-
mannopyranosides via 2,3-O-cyclic dioxonium intermediates
Zunyi Yang,a Hongzhi Cao,a Jie Hu,a Renli Shanb and Biao Yua
,
*
aState Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, People’s Republic of China
bShanghai University and Goodway Chemicals Joint Research Centre, Shanghai 200436, People’s Republic of China
Received 27 August 2002; revised 18 October 2002; accepted 7 November 2002
Abstract—Treatment of phenyl 2,3-O-cyclic ketene acetal- and 2,3-O-thionocarbonyl-1-thio-mannopyranosides with TMSOTf and MeOTf,
respectively, gave the corresponding 2,3-O-cyclic dioxonium intermediates, which proceeded via 1!2 migration and concurrent
glycosidation in the presence of alcohols to provide the corresponding 2-S-phenyl glycosides stereoselectively. While the former donors were
too labile, the latter donors have proved superior for the present purpose. The X-ray crystallographic structures of phenyl 4-O-methyl-2,3-O-
thiocarbonyl-1-thio-a-L-rhamnopyranoside (1), a typical donor for the present reaction, and its anomeric azide analogue (6), which could not
undergo the present reaction under similar conditions, are provided. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
protocol has been successfully applied to the synthesis of
the hexadeoxysaccharide fragment of Landomycine A, i.e.,
a-L-rhodinose-(1!3)-b-D-olivose-(1!4)-b-D-olivose-
(1!4)-a-L-rhodinose-(1!3)-b-D-olivose-(1!4)-b-D-
olivose!OMP.4 Here we report the experimental results
which have not been mentioned previously for the
development of this successful glycosidation method.
Based on the incidental finding that ethyl 1-thio-a-L-
rhamnopyranoside 2,3-O-orthoesters undergo a 1!2
migration and concurrent glycosidation under the action of
acids,1,2 we developed a facile approach for the stereo-
selective syntheses of 2-thio-b-glucopyranosides by using
ethyl(phenyl) 1-thio-a-mannopyranoside 2,3-O-ethoxy-
ethylidenes as donors and TMSOTf as a promoter.2 The
resulting products are ready precursors to 2-deoxy-b-
glycosides, which are important structural components in
many natural products, and are otherwise difficult to
synthesize. Although this method possess such advantages
as easy accessibility of donors, convenient reaction
conditions, and tolerance towards a variety of alcohol
acceptors, an inherent drawback is that the ethoxy group
resulting from the 2,3-O-ethoxyethylidene competes for
glycosidation.2 On mechanistic consideration (Scheme 1),
2,3-O-cyclic dioxonium IV was the key intermediate from
2,3-O-orthoester I, which then transformed into an 1,2-
episulphonium, and finally led to the stereoselective 1!2
migration and concurrent glycosidation upon nucleophilic
attack of an alcohol on the anomeric carbon. Therefore, any
1-thio-a-mannopyranosides which could generate 2,3-O-
cyclic dioxonium IV would be possible donors. We have
recently disclosed that phenyl 2,3-O-thionocarbonyl-1-thio-
a-mannopyranosides (III) were ideal for this purpose.3 This
2. Results and discussion
Shown in Scheme 2 is a representative example using
phenyl 2,3-O-thionocarbonyl-1-thio-a-mannopyranosides
for 1!2 migration and concurrent glycosidation.3,4 While
the expected product 2 was produced in excellent yield, a
variable amount of 3 was always detected, which was
conceivably produced via attack of the corresponding 2,3-
O-cyclic dioxonium intermediate (IV) by any moisture that
remains in the reaction, or water introduced in the workup
procedure.
Nicolaou et al. disclosed that the 1!2 migration of an
anomeric N3 group took place as readily as that of the
anomeric PhS group on the relevant 2-OH sugars under the
promotion of DAST.5 We thus explored the possibility of N3
migration and concurrent glycosidation within the present
subject (Scheme 3). Unfortunately, treatment of 2,3-O-
thionocarbonyl azide 6, which was readily prepared from 4,6
under similar conditions for the glycosidation of the
1-phenylthio counterpart 1, did not produce the desired
product 7. In fact, no products other than the hydrolysis
product 8 were detected.
Keywords: glycosidation; phenyl 1-thio-a-mannopyranoside; 2,3-O-cyclic
dioxonium.
*
Corresponding author. Tel.: þ86-21-6416-3300; fax: þ86-21-6416-6128;
e-mail: byu@mail.sioc.ac.cn
0040–4020/03/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)01452-7

250
Z. Yang et al. / Tetrahedron 59 (2003) 249–254
Scheme 1.
Scheme 2.
The single crystals of 1, a typical donor, and the anomeric
azide analogue 6 were obtained, which led to the X-ray
structures as shown in the ORTEP drawings.7 The fused-
ring bicyclic systems of these two compounds adopt very
similar conformations. The C9–S2–C1–C2–O2–C8–S1
atoms on 1 are orientated in such a way (i.e., the torsion
angles of C9–S2–C1–C2, S2–C1–C2–O2, C1–C2–O2–
C8, and C2–O2–C8–S1 are 2163.5(2)8, 2158.98(19)8,
2147.3(2)8, and 2171.5(2)8, respectively) that a ready 1!2
PhS migration would be facilitated. The similar confor-
mation of 6 therefore could not explain why a 1!2 N3
migration did not take place, the reason must lie in the
different nuleophilicity of the phenylthio and the azide
group.
In the previous reports,3,4 all the phenyl 2,3-O-thiono-
carbonyl-1-thio-a-mannopyranosides employed as donors
were 6-deoxy derivatives. Thus, we further explored the
utility of 6-hydroxylated sugars for glycosidation
(Scheme 4). Subjecting phenyl 4,6-di-O-acetyl-2,3-O-thio-
nocarbonyl-1-thio-a-D-mannopyranoside (10), which was
readily prepared from diol 9,8 to the typical glycosidation
˚
conditions (1.2 equiv. MeOTf, alcohol 13, 4 A MS, CH2Cl2,
room temperature, with or without 2,6-di-tert-butyl-4-
methylpyridine (DTBMP))3,4 produced complex products.

Z. Yang et al. / Tetrahedron 59 (2003) 249–254
251
Scheme 3. Reagents and conditions: (a) MeI, NaH, DMF, room temperature; (b) p-TsOH·H2O, 308C, 92% (for two steps); (c) Im2CS, THF, 608C, 90%.
˚
Scheme 4. Reagents and conditions: (a) Im2CS, THF, 608C, 80% (for 10); 87% (for 12); (b) 13 or BnOH, MeOTf (1.2 equiv.), DTBMP, 4 A MS, CH2Cl2, room
temperature, 85% (for 14); 73% (for 15).
The complexity might arise from the competitive attack on
the nascent 2,3-O-cyclic dioxonium (IV) by the proximal
carbonyl oxygen in the 6-OAc function. Thus, 4,6-di-O-
methyl derivative 12 was prepared from diol 118 and
subjected toward glycosidation under similar conditions.
Indeed, the expected glycosides 14 and 15 were obtained in
satisfactory yields (89 and 73%, respectively) when sugar
alcohol 13 and benzyl alcohol were used as acceptors,
respectively.
bromination of 17 under the action of bases (KOH or
t-BuOK) in the presence or absence of phase transfer agents
(TBAB or Aliquat 336) in THF or DMF at various
temperatures led to no product or complex products,12,13
including the decomposed product 16. Thus bromide 17 was
converted into the corresponding iodide 18 (KI, Aliquat 336
(2%), DMF, 808C, 90%). Applying the iodide 18 to the
typical elimination conditions (KOBut, DMF, room tem-
perature) gave clean reaction as monitored by TLC; the
starting iodide disappeared within 2 h and two new spots
appeared. However, flash chromatography on a silica gel
column, even using Et3N containing elutes, only afforded
the more polar product. The 1H NMR spectrum of the
resulting product correlated clearly to a mixture of the
2-OAc and 3-OAc derivatives, which are conceivably
derived from the desired 2,3-cyclic ketene acetal.12 There-
fore, the reaction mixture, after concentration under
vacuum, was passed through a short basic alumina column
(pH,9.5) with 15:1 petroleum ether–Et3N as elutes.
Removal of the elutes under vacuum provided a white
Hecht and co-workers have reported the preparation of
sugar 1,2-O-cyclic ketene acetals (1,2-O-vinylidene acetals)
and the reaction of the resulting 1,2-O-cyclic acetoxoniums
upon treatment with proton donors.9 The 1,2-O-cyclic
acetoxoniums are always the putative key intermediates in
the glycosylation reaction employing sugar donors with a
neighbouring acetyl group.10 We thus envisioned phenyl
1-thio-a-L-rhamnopyranoside 2,3-O-cyclic ketene acetals,
which would readily lead to 2,3-O-cyclic dioxoniums (IV),
as good donors for the present 1!2 migration and
concurrent glycosidation (Scheme 5). Treatment of 2,3-
diol 163,11 with 2-bromo-1,1-dimethoxyethane in the
presence of a catalytic amount of 10-camphorsulphonic
acid (CSA) gave 2,3-O-acetal 17 in 81% yield.12 Dehydro-
1
syrup, whose H NMR spectrum was still complicated due
to the appearance of the mono-acetyl derivatives.
Fortunately, direct utilization of the resulting syrup for the
glycosidation conditions (cholesterol, 0.2 equiv. TMSOTf,

252
Z. Yang et al. / Tetrahedron 59 (2003) 249–254
Scheme 5. Reagents and conditions: (a) BrCH2CH(OMe)2, CSA (cat.), 608C, 81%; (b) KI, Aliquat 336, DMF, 808C, 90%; (c) KOBut, DMF, room temperature;
˚
(d) cholesterol, TMSOTf (0.2 equiv.), 4 A MS, CH2Cl2, room temperature, 76%.
˚
4 A MS, CH2Cl2, room temperature) afforded the desired
1!2 migration and concurrent glycosidation product 20 in
satisfactory yield (78%).
After evaporation of the solvent, the residue oil was
dissolved in MeOH (30 mL), and p-TsOH·H2O (210 mg,
1.2 mmol) was added to the solution. The mixture was
stirred at 308C for 5 h, and then quenched with Et3N. After
concentration the residue was purified by flash silica gel
column chromatography (1:2 hexane–EtOAc) to afford 5
(1.54 g, 92%) as a white solid mp 93.38C; [a]2D0¼2262.1 (c
In conclusion, under the scope of 2,3-O-cyclic dioxonium
initiated 1!2 migration and concurrent glycosidation of
1-thio-a-mannopyranosides, we developed 2,3-O-ortho-
esters,2 2,3-O-ketene acetals, and 2,3-O-thionocarbonates
as donors. While the 2,3-O-orthoesters inhere a competing
glycosidation of the ethoxy group and the 2,3-O-ketene
acetals are unstable, the 2,3-O-thionocarbonates demon-
strate optimal donor characteristics.3,4
1
1.0, CHCl3). H NMR (300 MHz, CDCl3): d 5.32 (s, 1H,
H-1), 3.85 (br s, 1H, H-2), 3.76 (m, 2H, H-3, H-5), 3.56 (s,
3H, OMe), 3.12 (t, 1H, J¼9.1 Hz, H-4), 2.51 (m, 2H, OH),
1.38 (d, 3H, J¼6.1 Hz, H-6). 13C NMR (75 MHz, CDCl3): d
89.4, 82.4, 70.6, 70.3, 69.6, 60.6, 17.8. ESIMS (m/z): 226.0
(MþNaþ). IR (nmax): 3261 (br), 2120 (N3) cm21. Anal.
calcd for C7H13N3O4: C, 41.38; H, 6.45; N, 20.68. Found: C,
41.39; H, 6.39; N, 20.53.
3. Experimental
3.1. General remarks14
3.1.3. 4-O-Methyl-2,3-O-thionocarbonyl-a-L-rhamno-
pyranosyl azide (6). To a solution of the diol 5 (200 mg,
0.98 mmol) in dry THF (5 mL) was added a solution of 1,10-
thiocarbonyl diimidazole (234 mg, 1.18 mmol) in dry THF
(5 mL). The mixture was stirred at reflux under an
atmosphere of Ar for 3.5 h. TLC indicated completion of
the reaction. Then the mixture was concentrated and
purified by a silica gel column chromatography (6:1
hexane–EtOAc) to provide 6 (227 mg, 94%) as a white
solid. Recrystallization in petroleum ether and CH2Cl2 gave
6 as colourless prisms.7 mp 76.88C; [a]2D0¼2176.7 (c 1.0,
3.1.1. Phenyl 2,3-O-carbonyl-4-O-methyl-1-thio-a-L-
rhamnopyranoside (3). Trace amount of 3 was obtained
as a white amorphous solid in the glycosidation reaction of
2,3-O-thionocarbonyl donor 1,3,4 under similar conditions
for preparation of 14 and 15. 3: [a]2D0¼2248.5 (c 1.0,
CHCl3); 1H NMR (300 MHz, CDCl3): d 7.46–7.34 (m, 5H,
Ph), 5.77 (s, 1H, H-1), 4.86 (d, 1H, J¼6.9 Hz, H-2), 4.75 (t,
1H, J¼6.9 Hz, H-3), 4.15 (m, 1H, H-5), 3.57 (s, 3H, OMe),
3.14 (dd, 1H, J¼9.7, 6.9 Hz, H-4), 1.28 (d, 3H, J¼6.2 Hz,
H-6). 13C NMR (75 MHz, CDCl3): d 153.26 (CvO),
132.56, 131.67, 129.33, 128.43, 82.66, 82.22, 78.81, 77.56,
65.66, 59.62, 17.54; EIMS (m/z, %): 296 (Mþ, 25.6), 187
(100), 110 (38.0). IR (nmax): 2979, 2939, 2897, 1805
(CvO) cm21. Anal. calcd for C14H16O5S: C, 56.72; H,
5.44. Found: C, 56.83; H, 5.62.
1
CHCl3). H NMR (300 MHz, CDCl3): d 5.70 (s, 1H, H-1),
4.87 (t, 1H, J¼7.0 Hz, H-3), 4.60 (d, 1H, J¼7.0 Hz, H-2),
3.81 (m, 1H, H-5), 3.57 (s, 3H, OMe), 3.10 (dd, 1H, J¼9.9,
7.0 Hz, H-4), 1.39 (d, 3H, J¼6.3 Hz, H-6). 13C NMR
(75 MHz, CDCl3): d 189.3, 84.6, 82.8, 81.1, 79.7, 66.2,
59.8, 17.5. ESIMS (m/z): 246.0 (MþHþ). IR (nmax): 2164,
2121, 1328 cm21. Anal. calcd for C8H11N3O4S: C, 39.18;
H, 4.52; N, 17.13; S, 13.07. Found: C, 39.19; H, 4.50; N,
17.19; S, 13.03.
3.1.2. 4-O-Methyl-a-L-rhamnopyranosyl azide (5). To a
solution of 2,3-O-isopropylidene-a-L-rhamnopyranosyl
azide (4)6 (1.89 g, 8.23 mmol) in DMF was added NaH
(0.82 g, 20.5 mmol, 60% suspension in paraffin oil). After
stirring at room temperature for 0.5 h, MeI (2.6 mL,
41.15 mmol) was added to the suspension at 08C. The
mixture was stirred for an additional 3.5 h at room
temperature. TLC (3:1 hexane–EtOAc) indicated com-
pletion of the reaction. The mixture was quenched with
water and diluted with CH2Cl2 (80 mL). The organic layer
was washed successively with 2 M HCl (20 mL), aq.
NaHCO3 (20 mL), and brine, and then dried over MgSO4.
3.1.4. 2,3-O-Carbonyl-4-O-methyl-a-L-rhamnopyrano-
syl azide (8). Trace amount of 8 was obtained as a white
solid in the attempted glycosidation reaction of 2,3-O-
thionocarbonyl azide 6 under the similar conditions for the
preparation of 14 and 15; mp 78.88C; [a]2D0¼2204.8 (c 1.0,
1
CHCl3). H NMR (300 MHz, CDCl3): d 5.63 (s, 1H, H-1),
4.66 (t, 1H, J¼7.0 Hz, H-3), 4.48 (d, 1H, J¼7.0 Hz, H-2),
3.83–3.78 (m, 1H, H-5), 3.54 (s, 3H, OMe), 3.09 (dd, 1H,
J¼9.6, 7.0 Hz, H-4), 1.38 (d, 3H, J¼6.3 Hz, H-6). ESIMS

Z. Yang et al. / Tetrahedron 59 (2003) 249–254
253
(m/z): 252.1 (MþNaþ). IR (nmax): 2121, 1847
(CvO) cm21. Anal. calcd for C8H11N3O5: C, 41.92; H,
4.84; N, 18.33. Found: C, 42.36; H, 5.03; N, 17.96.
OMe), 3.34–3.28 (m, 1H), 3.07 (dd, 1H, J¼11.4, 8.7 Hz,
H-2), 2.40 (s, 3H, MeS), 1.50, 1.36 (s each, 3H each, Me2C),
1.07 (d, 3H, J¼6.0 Hz, H-6); IR (nmax): 2986, 2935, 1722,
1144, 1122 cm21; ESIMS (m/z): 670.3 (MþNHþ4 ). Anal.
calcd for C31H40O9S3: C, 57.03; H, 6.18. Found: C, 56.61;
H, 6.19.
3.1.5. Phenyl 4,6-di-O-acetyl-2,3-O-thionocarbonyl-1-
thio-a-D-mannopyranoside (10). To the diol 98 (1.12 g,
3.14 mmol) in dry tetrahydrofuran (8 mL) was added a
solution
of
1,10-thiocarbonyldiimidazole
(840 mg,
3.2.2. Benzyl 4,6-di-O-methyl-3-O-(methylthio)carbonyl-
2-S-phenyl-b-D-glucopyranosides (15). [a]2D0¼214.4 (c
0.9, CHCl3); 1H NMR (300 MHz, CDCl3): d 7.52–7.20 (m,
10H, Ph), 5.11 (dd, 1H, J¼11.4, 8.7 Hz, H-3), 4.91 (d, 1H,
J¼12.0 Hz), 4.60 (d, 1H, J¼12.0 Hz), 4.34 (d, 1H,
J¼9.0 Hz, H-1), 3.64–3.61 (m, 2H), 3.47, 3.42 (s each,
3H each, 2£OMe), 3.40–3.27 (m, 2H), 3.05 (dd, 1H,
J¼11.4, 8.7 Hz, H-2), 2.40 (s, 3H, MeS); IR (nmax): 2934,
2839, 1720, 1146, 1112 cm21; ESIMS (m/z): 482.2
(MþNHþ4 ); HRMS (m/z): calcd for C23H28O6S2:
464.1327. Found: 464.1345.
4.72 mmol) in THF (8 mL) while at reflux under an
atmosphere of Ar. After being stirred for 2 h, the reaction
mixture was diluted with EtOAc. The organic layer was
washed with brine, dried over MgSO4, and then filtered and
concentrated in vacuum. The residue was purified by flash
chromatography (10:1 petroleum ether–EtOAc) to give 10
(1.0 g, 80%) as a white amorphous solid. [a]2D0¼162.2 (c
1.0, CHCl3); 1H NMR (300 MHz, CDCl3): d 7.51–7.36 (m,
5H, Ph), 5.93 (s, 1H, H-1), 5.20–5.05 (m, 3H), 4.52–4.44
(m, 1H), 4.26 (dd, 1H, J¼12.4, 5.5 Hz, H-6), 4.09 (dd, 1H,
J¼12.4, 2.5 Hz, H-60), 2.16, 2.02 (s each, 3H each, 2 Ac).
ESIMS (m/z, %): 338 (Mþ260, 0.6), 261 (12.6), 247 (16.3).
IR (nmax): 1751, 1737, 1319, 1302, 1242 cm21. Anal. calcd
for C17H18O7S2·1/2H2O: C, 50.11; H, 4.70. Found: C,
50.29; H, 4.79.
3.2.3. Phenyl 2,3-O-bromoethylidene-4-O-methyl-1-thio-
a-L-rhamnopyranoside (17). In a 25 mL flask fitted with a
Claisen distillation apparatus were heated diol 163,11
(344 mg, 1.27 mmol), bromoacetaldehyde dimethyl acetal
(0.3 mL, 2.54 mmol), and CSA (89 mg, 0.38 mmol) at 708C
for 7 h while being stirred. The methanol was continuously
removed during the reaction by distillation into a receiver.
The crude product was purified by a silica gel column
chromatography (12:1 petroleum ether–EtOAc) to give 17
(387 mg, 81%) as a yellow syrup. [a]2D0¼2153.8 (c 1.1,
CHCl3); 1H NMR (300 MHz, CDCl3): d 7.56–7.28 (m, 5H,
SPh), 5.79 (s, 1H, H-1), 5.22 (dd, J¼4.7, 3.6 Hz, 1H),
4.34–4.22 (m, 2H), 4.06–4.02 (m, 1H), 3.56 (s, 3H, OMe),
3.54–3.44 (m, 2H), 3.18–3.12 (m, 1H), 1.25 (d, J¼6.3 Hz,
3H, H-6). EIMS (m/z, %): 374 (Mþ21, 3.0), 265
(Mþ2SPh21, 99.6).
3.1.6. Phenyl 4,6-di-O-methyl-2,3-O-thionocarbonyl-1-
thio-a-D-mannopyranoside (12). A similar procedure for
the preparation of 10 from diol 9 was employed for the
synthesis of 12 from diol 11.8 Compound 12 was obtained as
a white solid (87%); mp 92.98C; [a]2D0¼203.0 (c 1.0,
CHCl3); 1H NMR (300 MHz, CDCl3): d 7.55–7.38 (m, 5H,
Ph), 5.93 (s, 1H, H-1), 5.05–5.03 (m, 2H), 4.24–4.18 (m,
1H), 3.71–3.54 (m, 6H), 3.40 (s, 3H, OMe). 13C NMR
(75 MHz, CDCl3): d 189.6, 132.5, 131.2, 129.3, 128.5, 83.0,
82.1, 81.1, 75.9, 70.4, 68.9, 59.5, 59.2. IR (nmax): 3004,
2968, 2931, 1368, 1377, 1345, 1302, 1285, 1101 cm21
;
ESIMS (m/z): 360.1 (MþNHþ4 ). Anal. calcd for
C15H18O5S2·1/2H2O: C, 51.26; H, 5.45. Found: C, 51.51;
H, 5.43.
3.2.4. Phenyl 2,3-O-iodoethylidene-4-O-methyl-1-thio-a-
L-rhamnopyranoside (18). To a mixture of 17 (893 mg,
2.38 mmol) and KI (4.74 g, 28.55 mmol) in dry DMF
(2 mL) at 808C under Ar, was added phase-transfer catalyst
Aliquat 336 (1.1 mL). After being stirred for two days, the
mixture was diluted with EtOAc, and then filtered through a
pad of Celitee. The filtrates were concentrated. The residue
was purified by a silica gel column chromatography (16:1
petroleum ether–EtOAc) to give 18 (800 mg, 90%) as a
yellow syrup. [a]D20¼2142.3 (c 0.9, CHCl3); 1H NMR
(300 MHz, CDCl3): d 7.56–7.28 (m, 5H, SPh), 5.79 (s, 1H,
H-1), 5.03 (t, J¼4.7 Hz, 1H), 4.34–4.27 (m, 2H), 4.12–4.04
(m, 1H), 3.56 (s, 3H, OMe), 3.38–3.18 (m, 3H), 1.25 (d,
J¼6.1 Hz, 3H, H-6); EIMS (m/z, %): 422 (Mþ, 0.4), 313
(Mþ2SPh, 100); HRMS calcd for C15H19O4IS: 422.0049.
Found: 422.0013.
3.2. Typical procedure for the glycosidation reaction of
phenyl 2,3-O-thionocarbonyl-1-thio-a-mannopyrano-
side donors with alcohols
To a stirred solution of an alcohol (1.0 equiv.), 2,6-di-tert-
˚
butyl-4-methylpyridine (1.5 equiv.), and 4 A MS in
anhydrous CH2Cl2 at room temperature under argon, was
added a solution of the donor in CH2Cl2 (1.2 equiv.),
followed by the addition of a solution of MeOTf (1.2 equiv.)
in CH2Cl2. After being stirred for 6 h, the mixture was
quenched with Et3N, and then filtered through a pad of
Celitee. The filtrates were concentrated. The residue was
applied to a silica gel column chromatography (5:1
petroleum ether–EtOAc) to give the corresponding 2-thio-
glycosides as amorphous solids.
3.2.5. Cholesteryl 3-O-acetyl-6-deoxy-4-O-methyl-2-S-
phenyl-b-L-glucopyranoside (20). In a conical flask
potassium t-butoxide (50 mg, 0.45 mmol) was dissolved in
anhydrous DMF (2 mL) at 08C under Ar. After being stirred
for 0.5 h, a solution of iodide 18 (190 mg, 0.45 mmol) in
DMF (1 mL) was added, the reaction mixture was then
allowed to warm to room temperature. After 2 h, TLC
showed the reaction to be complete. After the solvent had
been removed by evaporation, the residue was applied to a
basic alumina column (pH,9.5) chromatography (15:1
3.2.1. Phenyl 4,6-di-O-methyl-3-O-(methylthio)carbo-
nyl-2-S-phenyl-b-D-glucopyranosyl-(1!4)-2,3-O-isopro-
pylidene-1-thio-a-L-rhamnopyranoside (14). [a]2D0¼
1
2159.7 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): d
7.56–7.25 (m, 10H, 2£S0Ph), 5.70 (s, 1H, H-1), 5.12 (d0d,
1H, J¼11.4, 8.7 Hz, H-3 ), 4.95 (d, 1H, J¼9.0 Hz, H-1 ),
4.31–4.29 (m, 2H), 3.90–3.82 (m, 1H), 3.76–3.70 (m, 1H),
3.68–3.54 (m, 2H), 3.46 (s, 3H, OMe), 3.44–3.36 (m, 4H,

254
Z. Yang et al. / Tetrahedron 59 (2003) 249–254
212, 13–24. (b) Pozsgay, V. Carbohydr. Res. 1992, 235,
295–302.
petroleum ether–triethylamine) to give the crude ketene
acetal 19 (119 mg) as a colourless syrup, which was used
immediately in the next step without characterization. To a
2. (a) Yu, B.; Yang, Z. Tetrahedron Lett. 2000, 41, 2961–2964.
(b) Yang, Z.; Yu, B. Carbohydr. Res. 2001, 333, 105–114.
3. Yu, B.; Yang, Z. Org. Lett. 2001, 3, 377–379.
4. Yu, B.; Wang, P. Org. Lett. 2002, 4, 1919–1922.
5. Nicolaou, K. C.; Ladduwahetty, T.; Randall, J. L.;
Chucholowski, A. J. Am. Chem. Soc. 1986, 108, 2466–2467.
˚
stirred solution of cholesterol (65 mg, 0.17 mmol) and 4 A
MS (200 mg) in anhydrous CH2Cl2 (2 mL) at room
temperature under argon was added a solution of TMSOTf
in CH2Cl2 (0.1 M, 0.2 equiv.), followed by the addition of a
solution of the crude ketene acetal 19 (119 mg, 0.40 mmol)
in CH2Cl2 (1 mL). After being stirred for 2 h, the mixture
was quenched with Et3N, and then filtered through a pad of
Celitee. The filtrates were concentrated. The residue was
applied to a silica gel column chromatography (10:1
petroleum ether–EtOAc) to provide 20 (87 mg, 76%) as a
¨
6. Gyorgydeak, Z.; Szilagyi, L. Liebigs Ann. Chem. 1985,
103–112.
7. Full crystallographic details of compounds 1 and 6 have been
deposited with the Cambridge Crystallographic Data Centre
(CCDC 190419 and 191703, respectively). Copies of these
data may be obtained free of charge from the director, CCDC,
12 Union Road, Cambridge, CB2 1EZ, UK (fax: þ44-1223-
336033; e-mail: deposit@ccdc.cam.ac.uk or www: http://
www.ccdc.cam.ac.uk).
1
white amorphous solid. [a]2D0¼229.0 (c 1.1, CHCl3); H
NMR (300 MHz, CDCl3): d 7.58–7.27 (m, 5H, SPh), 5.34
(m, 1H), 5.05 (dd, 1H, J¼11.3, 9.1 Hz), 4.45 (d, 1H,
J¼8.8 Hz, H-1), 3.58–3.46 (m, 1H), 3.44 (s, 3H, OMe),
3.42–3.33 (m, 1H, H-5), 3.13 (dd, 1H, J¼11.3, 8.8 Hz),
2.93 (t, 1H, J¼9.1 Hz, H-2), 2.40–2.20 (m, 2H), 2.07 (s, 3H,
OAc), 2.06–0.64 (m, 44H); EIMS (m/z, %): 680 (Mþ2H),
369 (100). IR: (nmax) 2937, 2868, 1750, 1238 cm21. Anal.
calcd for C42H64O5S: C, 74.07; H, 9.47. Found: C, 74.16; H,
9.42.
8. Similar procedure for the preparation of ethyl 4,6-di-O-acetyl-
1-thio-a-D-mannopyranoside was used for the preparation of
diols 9 and 11, see Ref. 2b.
9. Sznaidman, M. L.; Johnson, S. C.; Crasto, C.; Hecht, S. M.
J. Org. Chem. 1995, 60, 3942–3943.
10. Yang, Z.; Lin, W.; Yu, B. Carbohydr. Res. 2000, 329,
879–884, and references cited therein.
11. Nicolaou, K. C.; Li, Y.; Fylaktakidou, K. C.; Mitchell, H. J.;
Wei, H. X.; Weyershausen, B. Angew. Chem. Int. Ed. 2001,
40, 3849–3854.
Acknowledgements
The work was supported by the National Natural Science
Foundation of China (29925203) and the Committee of
Science and Technology of Shanghai (01JC14053).
12. Zhu, P. C.; Lin, J.; Pittman, Jr. C. U. J. Org. Chem. 1995, 60,
5729–5731.
13. (a) Bailey, W. J.; Zhou, L.-L. Tetrahedron Lett. 1991, 32,
´ ´
1539–1540. (b) Dıez-Ortiz, A.; Dıez-Barra, E.; de la Hoz, A.;
Prieto, P. Synth. Commun. 1993, 23, 1935–1942.
14. Yu, B.; Zhu, X.; Hui, Y. Tetrahedron 2001, 57, 9403–9413.
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