Protection of Hydroxy Groups with Diphenylmethyl and 9-Fluorenyl Trichloroacetimidates - Effect on Anomeric Stereocontrol

Article abstract of DOI:10.1002/ejoc.200300323

The use of O-diphenylmethyl (DPM) and the O-(9-fluorenyl) (Fl) trichloroacetimidates permitted efficient protection of alcohols. The compatibility of these groups with other chemical manipulations is demonstrated. Glucosylation of typical acceptors with a

Full text of DOI:10.1002/ejoc.200300323

FULL PAPER
Protection of Hydroxy Groups with Diphenylmethyl and 9-Fluorenyl
Trichloroacetimidates ؊ Effect on Anomeric Stereocontrol
Ibrahim A. I. Ali,[a] El Sayed H. El Ashry,[b] and Richard R. Schmidt*[a]
Keywords: Carbohydrates / Glycosidation / Protecting groups / Stereoselectivity / Trichloroacetimidates
The use of O-diphenylmethyl (DPM) and the O-(9-fluorenyl)
(Fl) trichloroacetimidates permitted efficient protection of al-
cohols. The compatibility of these groups with other chemical
manipulations is demonstrated. Glucosylation of typical ac-
ceptors with an O-glucopyranosyl trichloroacetimidate as
ides, thus demonstrating anchimeric assistance of the DPM
group in the anomeric stereocontrol. This effect was also ob-
served in mannopyranoside synthesis.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
donor having a DPM group at 2-O afforded β-glucopyranos- Germany, 2003)
Introduction
has been carried out by treatment of 9-bromo- or 9-diazo-
fluorene with alcohols.[23Ϫ25] As would be expected, the sol-
volysis of 9-fluorenyl ethers under acidic conditions is
slower than that of the corresponding diphenylmethyl de-
rivatives, reflecting the different stabilities of the di-
phenylmethyl and the fluorenyl carbenium ion
intermediates.[20Ϫ22] It therefore appears worthwhile to in-
vestigate the properties of these two structurally related
compounds, which might exhibit different protecting group
characteristics due to their different carbenium ion stabilis-
ation and steric demands.
Protection/deprotection methodologies are of great sig-
nificance in organic synthesis. As a consequence of the
extensive use of the benzyl group as a protecting group, the
diphenylmethyl (DPM) group has also found use for the
protection of hydroxy groups, its hydrogenolytic cleavage
being as cleanly achievable as in the case of benzyl ethers.[1]
The synthesis of DPM ethers can be carried out by use of
DPM chloride and bromide in the presence of a base,[2]
diphenyldiazomethane,[3,4] diphenylmethyl phosphate in the
presence of trifluoroacetic acid[3,4] or of diphenylmethanol
in the presence of various acids such as xenon difluoride,[5]
p-toluenesulfonic acid,[6] concentrated sulfuric acid,[7] ytter-
bium() triflate/ferric chloride,[8] ferric chloride or ferric
perchlorate,[9] and ferric nitrate.[10] Direct transformation of
silyl ethers or alkyl tetrahydropyranyl ethers into the corre-
sponding DPM alkyl ethers has also been reported to take
place with DPM formate in the presence of trimethylsilyl
trifluoromethanesulfonate (TMSOTf).[11] The DPM group
was generated when orthoesters of myo-inositol were
treated with Grignard reagents.[12] As well as for alcohol
protection, the DPM group has also been used for the pro-
tection of acids.[13Ϫ15] Moreover, DPM ethers are also valu-
able as therapeutic agents.[16Ϫ18]
As a consequence of the interest in the DPM and Fl
groups and the need for efficient methods for their intro-
duction onto alcohols, their trichloroacetimidates were con-
sidered as donors of the DMP[26] and Fl groups, respec-
tively. Obviously, we also had the importance of O-glycosyl
trichloroacetimidates as glycosyl donors in mind.[27Ϫ29]
Moreover, the ready formation of the trichloroacetimidates
from DPMϪOH and 9-FlϪOH, as well as the mild con-
ditions usable for the introduction of these groups in the
presence of acid- and base-sensitive groups should be of
significance. The introduction of the DPM group and the
Fl group as protecting groups, particularly in the carbo-
hydrate field, as well as their effects on the anomeric ratios
in glycosidation reactions have therefore been investigated.
9-Fluorenyl (Fl) ethers, on the other hand, have attracted
comparatively less attention, studies on them being mainly
concerned with photolytic reactions.[19Ϫ22] Their synthesis
Results and Discussion
[a]
Fachbereich Chemie, Universität Konstanz,
The required O-DPM[26] and O-Fl trichloroacetimidates
2a and 2b, respectively, were prepared by treatment of di-
phenylmethanol (1) and 9-fluorenol (1b) with trichloroace-
tonitrile in the presence of 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) as catalyst (Scheme 1). Their formation was
confirmed spectroscopically [δ(NH) ϭ 8.4, 8.6 ppm]. The
Fach M 725, 78457 Konstanz, Germany
Fax: (internat.) ϩ 49-7531/88-3135
E-mail: Richard.Schmidt@uni-konstanz.de
[b]
Department of Chemistry, Faculty of Science, University of
Alexandria,
Alexandria, Egypt
E-mail: eelashry@link.net
eelashry60@hotmail.com
Eur. J. Org. Chem. 2003, 4121Ϫ4131
DOI: 10.1002/ejoc.200300323
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I. A. I. Ali, E. S. H. El Ashry, R. R. Schmidt
FULL PAPER
trichloroacetimidates 2a and 2b are crystalline compounds,
characterized by their stabilities at room temperature for
long periods of time without detection of any decompo-
sition. Reactions between trichloroacetimidate 2a and 2b
and typical alcohols containing primary and secondary
hydroxy groups, such as 3Ϫ6, readily afforded the corre-
sponding DPM ethers 3aϪ6a and Fl ethers 3b, 4b and 6b
in high yields (Table 1). The reactions with 2a were per-
Table 1. Treatment of alcohols 3Ϫ13 with O-DPM and O-Fl trich-
loroacetimidates 2a and 2b[a]
Scheme 1
formed at room temperature and those with 2b at Ϫ40 °C.
The etherification of primary and secondary hydroxy
groups in various types of partially protected carbohydrates
7Ϫ13 was successfully carried out in similar fashion
(Table 1). Thus, treatment of 2a or 2b with 6-O-unprotected
glucoside 7,[30] possessing a primary hydroxy group, gave 7a
or 7b, respectively. The carbohydrate derivatives
8Ϫ10,[31Ϫ33] with secondary hydroxy groups at positions 4,
3 and 2, gave the DPM and Fl derivatives 8aϪ10a and
8bϪ10b, respectively, under similar conditions. Ready intro-
duction of the DPM and Fl protecting groups was even
possible at the anomeric hydroxy group; thus, 11[34] gave the
corresponding α-glycosides 11a and 11b, while 12[35] gave
α-glycoside 12b in high yield. For these derivatives α con-
figurations could be assigned with the aid of NMR spectro-
scopic data [11a: δ(1-H) ϭ 5.15 ppm, J ϭ 3.7 Hz; 11b: δ(1-
H) ϭ 5.30 ppm, J ϭ 3.7 Hz]. Even regioselective introduc-
tion of DPM was possible, treatment of 4,6-O-unprotected
glucoside 13 with DPM donor 2a,[36] for instance, giving
only 6-O-protected glucoside 13a in high yield.
The DPM and Fl groups can be readily removed by hy-
drogenolysis, as shown for compounds 7a and 7b, which
upon deprotection and acetylation gave the known O-ace-
tyl-protected methyl glucoside 14 (Scheme 2).[37]
Stereoselective glycoside bond formation is a subject still
attracting many investigators. In this respect, it was of inter-
est to study the effects of the DPM and Fl groups on the
stereoselectivity obtained during glycosylation reactions. To
this end, 1-O-deallylation of 10a and 10b, with DPM and Fl
groups at 2-O, was performed with Wilkinson’s catalyst,[38]
[a]
[b]
For details see Scheme 1 and Exp. Sect.
The carbohydrate
[c]
acceptors were obtained by literature procedures; see references.
Not investigated.
cleanly furnishing 1-O-unprotected compounds 15a and the glycosyl acceptor 7,[30] with 2-O-DPM-protected 16a
15b, respectively (Scheme 3). Activation of their anomeric gave exclusively the corresponding β-glucosides 17aϪ19a in
centres by treatment with trichloroacetonitrile in the pres- good yields, without any detection of the α anomers.
ence of DBU as base gave trichloroacetimidates 16a and
The analogous glucosyl donor 16b, possessing an Fl
16b. Glycosylation of methyl and octyl alcohols, as well as group, however, predominantly gave the respective β-gluco-
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Protection of Hydroxy Groups with Diphenylmethyl and 9-Fluorenyl Trichloroacetimidates
FULL PAPER
Scheme 2
Scheme 4. Reagents and conditions: (a) 2a, TMSOTf, CH2Cl2; (b)
(Ph3P)RhCl, Tol, EtOH, H2O; (c) CAN; (d) CCl3CN, DBU
Treatment of these with 2a in the presence of TMSOTf
as catalyst afforded 2-O-DPM-protected intermediates 22
and 23 in high yields. Removal of the 1-O-allyl group in
22 or the 1-O-MP group in 23 under standard conditions
afforded 1-O-unprotected mannose derivative 24 without
Scheme 3
sides 17bβϪ19bβ on treatment with the same acceptors, but the DPM group being affected. Treatment of 24 with trich-
the β products were accompanied by the corresponding α- loroacetonitrile in the presence of DBU as base furnished
glucosides 17bαϪ19bα, the product ratio depending on the the desired mannopyranosyl donor 25a in high yield. From
structure of the acceptor. The presence of a DPM group at the NMR spectroscopic data, only the α anomer was ob-
2-O thus has a particularly favourable effect. The DPM tained. For comparison, the corresponding known 2-O-
group exhibits the desired stability under glycosylation con- benzyl-protected mannopyranosyl donor 25b[42] was also
ditions and, presumably thanks to its steric demand on the investigated.
α side of the molecule, it strongly favours β-glucopyrano-
The results of the glycosylation reaction with 25a and
side formation. This is particularly worth mentioning be- 25b and different acceptors in dichloromethane at Ϫ40 °C
cause the corresponding 2-O-benzyl-protected glucosyl do- in the presence of TMSOTf as catalyst are summarized in
nor (16: R ϭ Bn) provides α/β mixtures under these Table 2.
conditions.[27Ϫ29]
As expected, treatment of donor 25b with octanol, 6-O-
It was recently observed that the presence of sterically unprotected glucopyranoside 7[30], 6-O-unprotected manno-
demanding 2-O substituents at mannopyranosyl donors en- pyranoside 28[39] and 4-O-unprotected glucopyranoside 8[31]
forces β-mannopyranoside formation rather than inhibiting preferentially afforded α-mannopyranosides 26bα,[43]
it, because bulky substituents at 2-O support generation of 27bα[44] and 28bα. The result with the 2-O-DPM-protected
a twist-boat intermediate, which should be preferentially at- mannosyl donor 25a, however, was quite different. For the
tacked from the β side.[39] It was therefore of interest to acceptors with primary hydroxy groups (7, 26, 28) a clear
investigate a 2-O-DPM-protected mannopyranosyl donor preference for the formation of β products 26aβϪ28aβ was
in glycosylation reactions (Scheme 4). To this end, mannose observed. With less reactive acceptor 8,[31] with a less ac-
was transformed into the known allyl and 4-methoxyphenyl cessible secondary hydroxy group, only the α-linked disac-
(MP) mannopyranosides 20[40] and 21,[41] respectively charide 29aα[44] was obtained. Obviously, this is due to
(Scheme 4).
some as yet unexplainable change in mechanism.
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I. A. I. Ali, E. S. H. El Ashry, R. R. Schmidt
FULL PAPER
ternal standard. The assignments of 13C NMR spectra were based
on carbon-proton shift-correlation heteronuclear multiple quantum
coherence (HMQC). MALDI-MS: Kratos Compact Maldi 1; 2,5-
dihydroxybenzoic acid was used as matrix. FAB-MS: Finnigan
MAT 312/AMD 5000, 790 eV, 70 °C. Microanalyses were per-
formed in the Microanalysis Unit at the Department of Chemistry,
Universität Konstanz.
Table 2. Glycosylation results with mannosyl donors 25a and 25b[a]
O-Diphenylmethyl Trichloroacetimidate (2a): A mixture of di-
phenylcarbinol (0.92 g, 5.0 mmol), trichloroacetonitrile (5 mL,
50 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (71 µL) in dry di-
chloromethane (10 mL) was stirred under nitrogen at room tem-
perature for 3 h. The reaction mixture was then concentrated in
vacuo and the residue was purified by flash chromatography (3%
triethylamine in petroleum ether/ethyl acetate, 80:1) to give 2a
(1.5 g, 94%) as a white powder. TLC (3% triethylamine in toluene)
1
Rf ϭ 0.70; m.p. 85 °C, ref.[26] 85 °C. H NMR (250 MHz, CDCl3):
δ ϭ 6.94 (s, 1 H, CH), 7.29Ϫ7.44 (m, 10 H, Ar-H), 8.40 (br. s, 1
H, NH) ppm. 13C NMR (62.8 MHz, CDCl3): δ ϭ 81.4 (CH), 91.6
(CCl3), 126.9, 127.9, 128.5, 139.8 (C-Ar), 161.3 (CNH) ppm. EI-
MS: m/z ϭ 328.0.
[a]
For details see Scheme 5 and Exp. Sect.
O-(9-Fluorenyl) Trichloroacetimidate (2b): A stirred solution of 9-
hydroxyfluorene (0.91 g, 5.0 mmol) in dry dichloromethane
(10 mL) and trichloroacetonitrile (5 mL, 50 mmol) was treated with
DBU (71 µL) at room temperature and the mixture was then left
to stand for 0.5 h. The solvent was evaporated and the product was
purified by column chromatography (3% triethylamine in toluene)
to give 2b (1.4 g, 86%) as a white powder. TLC (3% triethylamine
in toluene) Rf ϭ 0.56; m.p. 59 °C. 1H NMR (250 MHz, CDCl3):
δ ϭ 6.99 (s, 1 H, CH), 7.25Ϫ7.67 (m, 8 H, Ar-H), 8.67 (br. s, 1 H,
NH) ppm. 13C NMR (62.5 MHz, CDCl3): δ ϭ 79.6 (CH), 91.5
(CCl3), 120.0, 126.0, 127.8, 129.6, 141.9, 141.7 (C-Ar), 163.6
(CNH) ppm. EI-MS: m/z ϭ 326.0.
In conclusion, O-DPM and O-Fl protection can readily
be carried out with the aid of the O-DPM and O-Fl trichlo-
roacetimidates. These protecting groups are compatible
with quite a few manipulations: at other functional groups
of a sugar molecule, for instance, and also with glycoside
bond formation. Of particular interest is the behaviour of
DPM groups at 2-O of glucopyranosyl donors, which sup-
port β-glucopyranoside formation. The steric bulk of the
DPM group thus exerts anchimeric assistance on the anom-
eric stereocontrol[45] through neighbouring group partici-
pation, as a 2-O-acyl group does. A 2-O-DPM group, how-
ever, affects activation of a glycosyl donor much less than
a 2-O-acyl group. The 2-O-DPM group also strongly affects
stereocontrol of mannopyranoside synthesis. For reactive
acceptors a clear preference for β-glycoside formation is ob-
served.
General Procedure for the Reactions between Trichloroacetimidate
2a and Alcohols: A solution of 2a (0.2 g, 0.6 mmol) and the appro-
priate alcohol (0.6 mmol) in dry dichloromethane (10 mL) was
stirred under nitrogen at room temperature for 5 min, and
TMSOTf (13 µL, 0.06 mmol) was then added. After 45Ϫ150 min,
the reaction mixture was neutralized with solid sodium hydrogen-
carbonate, filtered and concentrated in vacuo. The residue was
purified by column chromatography.
General Procedure for the Reactions between Trichloroacetimidate
2b and Alcohols: A solution of 2b (0.46 g, 1.4 mmol) and the appro-
priate alcohol (1.6 mmol) in dry dichloromethane (10 mL) was co-
oled to Ϫ40 °C, treated with TMSOTf (26 µL, 0.14 mmol), and the
mixture was then stirred for 10Ϫ120 min. The reaction mixture was
quenched by the addition of solid sodium hydrogencarbonate, fil-
tered and concentrated. The crude residue was purified by column
chromatography on silica gel with petroleum ether/ethyl acetate as
eluent.
Scheme 5
Experimental Section
3,5-Dinitrobenzyl Diphenylmethyl Ether (3a): Yellow powder (0.2 g,
91%); Rf ϭ 0.66 (petroleum ether/ethyl acetate, 5:1); m.p. 127 °C.
1H NMR (250 MHz, CDCl3): δ ϭ 4.71 (s, 2 H, CH2), 5.50 (s, 1 H,
CH), 7.31Ϫ7.40 (m, 10 H, Ar-H), 8.52 (m, 2 H, Ar-H), 8.91 (t, J ϭ
2.1 Hz, 1 H, Ar-H) ppm. 13C NMR (62.8 MHz, CDCl3): δ ϭ 68.7
(CH2), 84.3 (CH), 117.8, 126.9, 127.1, 128.0, 128.7, 141.0, 143.3,
148.6 (C-Ar) ppm. EI-MS: m/z ϭ 364.0. C20H16N2O5 (364.36):
calcd. C 65.93, H 4.43, N 7.68; found C 65.80, H 4.60, N 7.40.
General Remarks: Melting points are uncorrected. Thin layer chro-
matography (TLC) was performed on silica gel 60 F254 plastic
plates (E. Merck, layer thickness 0.2 mm). Detection was achieved
by treatment either with a solution of 20 g of ammonium molyb-
date and 0.4 g of cerium() sulfate in 400 mL of 10% H2SO4 or
with 15% H2SO4, and heating at 150 °C. Flash chromatography
was carried out on silica gel (Baker, 30Ϫ60 µm). Optical rotations
were determined at 20 °C with a PerkinϪElmer 241 MC polar-
imeter (1-dm cell). NMR spectra were recorded with Bruker AC
250 and 600 DRX instruments, with tetramethylsilane as an in-
9-(3,5-Dinitrobenzyloxy)fluorene (3b): Yellow powder (0.45 g, 88%);
Rf ϭ 0.47 (petroleum ether/ethyl acetate, 4:1); m.p. 108 °C. 1H
NMR (250 MHz, CDCl3): δ ϭ 4.26 (s, 2 H, CH2), 5.89 (s, 1 H,
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Protection of Hydroxy Groups with Diphenylmethyl and 9-Fluorenyl Trichloroacetimidates
CH), 7.25Ϫ8.89 (m, 11 H, Ar-H) ppm. 13C NMR (62.8 MHz, Methyl 2,3,6-Tri-O-benzyl-4-O-diphenylmethyl-α-
FULL PAPER
D-glucopyranoside
CDCl3): δ ϭ 63.8 (CH2), 81.0 (CH), 117.6, 120.3, 125.5, 127.1,
127.9, 129.7, 141.1, 141.5, 143.7, 148.4 (C-Ar) ppm. EI-MS: m/z ϭ
362.0. C20H14N2O5 (362.34): calcd. C 66.29, H 3.89, N 7.73; found
C 66.61, H 4.06, N 7.97.
(8a): Colourless oil (0.32 g, 83%); Rf ϭ 0.63 (petroleum ether/ethyl
acetate, 4:1). [α]D ϭ Ϫ35.0 (c ϭ 1.0, CH2Cl2). 1H NMR (250 MHz,
CDCl3): δ ϭ 3.2 (dd, J5,6 ϭ 5.1, J6,6Ј ϭ 10.6 Hz, 1 H, 6-H), 3.44
(s, 3 H, OCH3), 3.55 (dd, J1,2 ϭ 3.6, J2,3 ϭ 9.6 Hz, 1 H, 2-H), 3.70
(m, 1 H, 6-H), 3.81 (m, 1 H, 5-H), 4.04 (dd, J3,2 ϭ 9.6, J3,4
9.6 Hz, 1 H, 3-H), 4.14 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.23 (d,
gem ϭ 10.6 Hz, 1 H, CHPh), 4.49 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh),
4.63 (d, J1,2 ϭ 3.6 Hz, 1 H, 1-H), 4.65 (d, Jgem ϭ 10.6 Hz, 1 H,
CHPh), 4.78 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.95 (d, Jgem
ϭ
Diphenylmethyl Isopropyl Ether (4a): Colourless oil (0.1 g, 73.5%);
Rf ϭ 0.76 (petroleum ether/ethyl acetate, 5:1). Compound 4a was
synthesized by a published procedure. The analytical data are
identical with the published values.[46]
J
ϭ
10.6 Hz, 1 H, CHPh), 5.91 (s, 1 H, CH) ppm. MS (MALDI, posi-
tive mode, matrix: DHB): m/z ϭ 653.0 [M ϩ Na]ϩ, 669.0 [M ϩ
K]ϩ. C41H42O6 (630.78): calcd. C 78.07, H 6.71; found C 78.03,
H 6.50.
9-Isopropoxyfluorene (4b): White powder (0.28 g, 88.5%); Rf ϭ 0.64
(petroleum ether/ethyl acetate, 10:1); m.p. 44 °C, refs.[23,24]: 43Ϫ44
°C.
Cyclohexyl Diphenylmethyl Ether (5a): Colourless oil (0.12 g, 75%);
Rf ϭ 0.66 (petroleum ether/ethyl acetate, 6:1). Compound 5a was
synthesized by a published procedure. The analytical data are
identical with the published values.[47]
Methyl 2,3,6-Tri-O-benzyl-4-O-(9-fluorenyl)-α-D-glucopyranoside
(8b): White foam (0.54 g, 61%); Rf ϭ 0.48 (petroleum ether/ethyl
acetate, 4:1). [α]D ϭ ϩ13.3 (c ϭ 1.0, CH2Cl2). 1H NMR (600 MHz,
CDCl3): δ ϭ 3.29 (m, 1 H, 6-H), 3.34 (s, 3 H, OCH3), 3.38 (dd,
J6,5 ϭ 3.3, Jgem ϭ 10.2 Hz, 1 H, 6Ј-H), 3.50 (m, 2 H, 2-H, 5-H),
3.63 (dd, J4,3 ϭ 9.1, J4,5 ϭ 9.5 Hz, 1 H, 4-H), 3.73 (dd, J3,2 ϭ 9.2,
J3,4 ϭ 9.1 Hz, 1 H, 3-H), 4.60 (d, J1,2 ϭ 2.8 Hz, 1 H, 1-H), 4.62
(d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.64 (d, Jgem ϭ 12.1 Hz, 1 H,
Cholesteryl Diphenylmethyl Ether (6a): White powder (0.31 g, 92%);
Rf ϭ 0.42 (petroleum ether/ethyl acetate, 10:1); m.p. 136 °C. 1H
NMR (250 MHz, CDCl3): δ ϭ 0.64Ϫ2.28 (m, 43 H, cholesterol),
3.31 (m, 1 H, CH), 5.30 (d, 1 H, CH), 5.61 (s, 1 H, CH), 7.20Ϫ7.52
(m, 10 H, Ar-H) ppm. EI-MS: m/z ϭ 552.0. C40H56O (552.88):
calcd. C 86.80, H 10.21; found C 87.04, H 9.82.
CHPh), 4.66 (d, Jgem ϭ 11.6 Hz, 1 H, CHPh), 4.73 (d, Jgem
ϭ
11.6 Hz, 1 H, CHPh), 4.76 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.97
(d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 5.68 (s, 1 H, CH), 7.21Ϫ7.60 (m,
23 H, Ar-H) ppm. 13C NMR (150.8 MHz, CDCl3): δ ϭ 55.1,
(OCH3), 63.5 (C-6), 69.8 (C-5), 70.6 (C-4), 73.1, 75.4, 77.2 (3 CH2),
79.4 (C-2), 80.7 (CH), 81.5 (C-3), 98.1 (C-1), 119.8, 119.9, 120.2,
125.2, 125.4, 125.6, 127.3, 127.7, 127.9, 128.0, 128.4, 128.5, 129.1,
140.8, 140.9, 142.4 (C-Ar) ppm. MS (MALDI, positive mode, ma-
trix: DHB): m/z ϭ 629.0 [M ϩ H]ϩ. C41H40O6 (628.77): calcd. C
78.32, H 6.41; found C 78.51, H 6.49.
Cholesteryl Fluorenyl Ether (6b): Colourless oil (0.70 g, 91%); Rf ϭ
0.80 (petroleum ether/ethyl acetate, 20:1). 1H NMR (250 MHz,
CDCl3): δ ϭ 0.64Ϫ2.40 (m, 43 H, cholesterol), 3.4 (m, 1 H, CH),
5.22 (d, 1 H, CH), 5.60 (s, 1 H, CH), 7.21Ϫ7.72 (m, 8 H, Ar-H)
ppm. EI-MS: m/z ϭ 550.0. C40H54O (550.86): calcd. C 87.21, H
9.88; found C 87.15, H 9.81.
Methyl 2,3,4-Tri-O-benzyl-6-O-diphenylmethyl-α-D-glucopyranoside
3-O-Diphenylmethyl-1:2,5:6-di-O-isopropylidene-α-D-glucofuranose
(7a): Colourless oil (0.30 g, 78%); Rf ϭ 0.51 (petroleum ether/ethyl
(9a): White foam (0.20 g, 77%); Rf ϭ 0.67 (petroleum ether/ethyl
acetate, 4:1). [α]D ϭ Ϫ21.1 (c ϭ 1.0, CH2Cl2). 1H NMR (250 MHz,
CDCl3): δ ϭ 1.22, 1.30, 1.35, 1.40 (4 CH3), 3.96 (m, 2 H, 6-H, 6Ј-
H), 4.09Ϫ4.20 (m, 2 H, 4-H, 3-H), 4.31 (m, 1 H, 5-H), 4.51 (d,
1
acetate, 5:1). [α]D ϭ Ϫ8.6 (c ϭ 1.0, CH2Cl2). H NMR (250 MHz,
CDCl3): δ ϭ 3.40 (s, 3 H, OCH3), 3.57 (dd, J1,2 ϭ 3.6, J2,3
ϭ
9.3 Hz, 1 H, 2-H), 3.60Ϫ3.71 (m, 3 H, 4-H, 6-H, 6Ј-H), 3.80 (m, 1
H, 5-H), 4.04 (dd, J3,2 ϭ 9.3, J3,4 ϭ 9.2 Hz, 1 H, 3-H), 4.50 (d,
Jgem ϭ 10.8 Hz, 1 H, CHPh), 4.67 (d, J1,2 ϭ 3.6 Hz, 1 H, 1-H),
4.69 (m, 2 H, 2 CHPh), 4.73 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.81
(d, Jgem ϭ 10.8 Hz, 1 H, CHPh), 4.86 (d, Jgem ϭ 12.1 Hz, 1 H,
CHPh), 5.40 (s, 1 H, CH), 7.23Ϫ7.40 (m, 25 H, Ar-H) ppm. MS
(MALDI, positive mode, matrix: DHB): m/z ϭ 653.0 [M ϩ Na]ϩ,
669.0 [M ϩ K]ϩ. C41H42O6 (630.78): calcd. C 78.07, H 6.71; found
C 78.04, H 6.61.
J2,1 ϭ 3.7 Hz, 1 H, 2-H), 5.60 (s, 1 H, CH), 5.87 (d, J1,2 ϭ 3.7 Hz, 1
H, 1-H), 7.11Ϫ7.50 (m, 10 H, Ar-H) ppm. 13C NMR (150.8 MHz,
CDCl3): δ ϭ 25.5, 26.3, 26.7, 26.9 (4 CH3), 67.6 (C-6), 72.7 (C-5),
80.0 (C-3), 81.6 (C-4), 82.6 (CH), 83.0 (C-2), 105.4 (C-1), 109.0,
111.8, 126.9, 127.4, 127.7, 128.4, 128.5, 141.3, 142.1 (C-Ar) ppm.
MS (MALDI, positive mode, matrix: DHB): m/z ϭ 449.0 [M ϩ
Na]ϩ, 465.0 [M ϩ K]ϩ. C25H30O6 (426.51): calcd. C 70.40, H 7.01;
found C 70.26, H 7.02.
Methyl 2,3,4-Tri-O-benzyl-6-O-fluorenyl-α-D-glucopyranoside (7b):
3-O-(9-Fluorenyl)-1:2,5:6-di-O-isopropylidene-α-D-glucofuranose
White foam (0.69 g, 79%); Rf ϭ 0.52 (petroleum ether/ethyl acetate,
5:1). [α]D ϭ 25.5 (c ϭ 2.0, CH2Cl2). 1H NMR (600 MHz, CDCl3):
δ ϭ 3.44 (s, 3 H, OCH3), 3.51 (m, 2 H, 6-H, 6Ј-H), 3.60 (dd, J4,3 ϭ
9.3, J4,5 ϭ 9.6 Hz, 1 H, 4-H), 3.63 (dd, J1,2 ϭ 3.1, J2,3 ϭ 9.2 Hz, 1
H, 2-H), 3.74 (m, 1 H, 5-H), 4.02 (dd, J3,2 ϭ 9.2, J3,4 ϭ 9.3 Hz, 1
(9b): Colourless oil (0.49 g, 82.5%); Rf ϭ 0.38 (petroleum ether/
ethyl acetate, 5:1). [α]D ϭ ϩ9.8 (c ϭ 2.0, CH2Cl2). 1H NMR
(600 MHz, CDCl3): δ ϭ 1.22, 1.42, 1.44, 1.64 (4 CH3), 4.05 (dd,
J6,5 ϭ 5.7, Jgem ϭ 8.6 Hz, 1 H, 6-H), 4.17 (m, 2 H, 4-H, 6Ј-H),
4.42 (d, J ϭ 2.9 Hz, 1 H, 3-H), 4.52 (dd, J5,6 ϭ 5.7, J5,4 ϭ 8.4 Hz,
1 H, 5-H), 4.55 (d, J2,1 ϭ 3.6 Hz, 1 H, 2-H), 5.66 (s, 1 H, CH),
5.88 (d, J1,2 ϭ 3.6 Hz, 1 H, 1-H), 7.27Ϫ7.70 (m, 8 H, Ar-H) ppm.
13C NMR (150.8 MHz, CDCl3): δ ϭ 24.1, 25.4, 27.0 (4 CH3), 67.7
(C-6), 72.5 (C-5), 81.7 (C-3), 81.9 (C-4), 82.1 (CH), 84.1 (C-2),
105.4 (C-1), 109.0, 111.7, 119.8, 119.9, 125.1, 125.7, 127.3, 127.6,
129.0, 129.3, 140.3, 140.8, 142.6, 143.1 (C-Ar) ppm. MS (MALDI,
positive mode, matrix: DHB): m/z ϭ 447.0 [M ϩ Na]ϩ. C25H28O6
(424.49): calcd. C 70.73, H 6.65; found C 70.92, H 6.70.
H, 3-H), 4.50 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh), 4.72 (d, J1,2
3.1 Hz, 1 H, 1-H), 4.74 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh), 4.83 (d,
gem ϭ 11.3 Hz, 1 H, CHPh), 4.86 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh),
ϭ
J
4.88 (d, Jgem ϭ 11.3 Hz, 1 H, CHPh), 5.05 (d, Jgem ϭ 11.3 Hz, 1
H, CHPh), 5.74 (s, 1 H, CH), 7.05Ϫ7.42 (m, 8 H, Ar-H) ppm. 13C
NMR (150.8 MHz, CDCl3): δ ϭ 54.9 (OCH3), 63.4 (C-6), 70.0 (C-
5), 73.1, 74.7, 75.6 (3 CH2), 77.5 (C-4), 79.7 (C-2), 80.8 (CH), 82.0
(C-3), 97.8 (C-1), 119.8, 125.4, 127.1, 127.2, 127.4, 128.2, 129.1,
137.9, 138.6, 140.7, 142.2, 142.4 (C-Ar) ppm. MS (MALDI, posi-
tive mode, matrix: DHB): m/z ϭ 650 [M ϩ Na]ϩ. C41H40O6 Allyl 3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α-
(628.76): calcd. C 78.32, H 6.41; found C 78.71, H 6.37. (10a): Colourless oil (0.30 g, 76%); Rf ϭ 0.72 (petroleum ether/ethyl
D-glucopyranoside
Eur. J. Org. Chem. 2003, 4121Ϫ4131
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4125

I. A. I. Ali, E. S. H. El Ashry, R. R. Schmidt
FULL PAPER
acetate, 4:1). [α]D ϭ 25.0 (c ϭ 1.0, CH2Cl2). H NMR (600 MHz, 551.0 [M ϩ K]ϩ. C27H28O10·0.5H2O (521.51): calcd. C 62.18, H
CDCl3): δ ϭ 3.62 (m, 3 H, 4-H, 5-H, 6Ј-H), 3.73 (dd, J2,1 ϭ 3.5, 5.75; found C 61.87, H 5.77.
J2,3 ϭ 10.5 Hz, 1 H, 2-H), 3.80 (m, 1 H, 6-H), 3.91 (dd, J ϭ 6.3,
1
9-Fluorenyl 2:3,5:6-Di-O-isopropylidene-α-D-mannofuranoside (12b):
J ϭ 12.9 Hz, 1 H, CH2CHϭCH2), 4.10 (m, 2 H, 3-H, CH2CHϭ
CH2), 4.44 (d, Jgem ϭ 11.8 Hz, 1 H, CHPh), 4.48 (d, Jgem
White foam (0.33 g, 56%); Rf ϭ 0.43 (petroleum ether/ethyl acetate,
ϭ
5:1). [α]D ϭ Ϫ3.5 (c ϭ 1.0, CH2Cl2). 1H NMR (250 MHz, CDCl3):
10.5 Hz, 1 H, CHPh), 4.58 (d, Jgem ϭ 11.8 Hz, 1 H, CHPh), 4.69
(d, J1,2 ϭ 3.5 Hz, 1 H, 1-H), 4.81 (d, Jgem ϭ 10.5 Hz, 1 H, CHPh),
4.86 (d, Jgem ϭ 10.5 Hz, 1 H, CHPh), 4.95 (d, Jgem ϭ 10.5 Hz, 1 H,
CHPh), 5.21 (m, 2 H, CHϭCH2), 5.61 (s, 1 H, CH), 5.92 (m, 1 H,
CHϭCH2), 7.14Ϫ7.39 (m, 25 H, Ar-H) ppm. 13C NMR
(150.8 MHz, CDCl3): δ ϭ 68.3 (CH2), 68.4 (C-6), 70.1 (CH2ϪCHϭ
CH2), 73.4 (C-5), 74.9, 75.7 (2 CH2), 78.6 (C-4), 79.7 (C-2), 82.5
(C-3), 84.9 (CH), 96.3 (C-1), 117.7 (CHϭCH2), 126.7, 127.2, 127.3,
127.4, 127.6, 127.8, 127.9, 128.3, 128.4, 133.9, 138.3, 142.1, 142.7
(HCϭ, C-Ar) ppm. MS (MALDI, positive mode, matrix: DHB):
m/z ϭ 680.0 [M ϩ Na]ϩ. C43H44O6 (656.81): calcd. C 78.63, H
6.75; found C 78.46, H 6.63.
δ ϭ 1.30, 1.36, 1.43, 1.47 (4 CH3), 3.71 (dd, J6,5 ϭ 4.4, Jgem
ϭ
8.6 Hz, 1 H, 6-H), 3.90 (dd, J6,5 ϭ 6.3, Jgem ϭ 8.6 Hz, 1 H, 6Ј-H),
4.11 (dd, J4,3 ϭ 3.6, J4,5 ϭ 7.3 Hz, 1 H, 4-H), 4.29 (m, 1 H, 5-H),
4.67 (d, J2,3 ϭ 5.9 Hz, 1 H, 2-H), 4.77 (dd, J3,4 ϭ 3.6, J3,2 ϭ 5.9 Hz,
1 H, 3-H), 5.41 (s, 1 H, 1-H), 5.63 (s, 1 H, CH), 7.20Ϫ7.71 (m, 8
H, Ar-H) ppm. 13C NMR (150.8 MHz, CDCl3): δ ϭ 66.4 (C-6),
73.2 (C-5), 79.5 (C-3), 80.3 (C-4), 85.5 (C-2), 105.8 (C-1), 109.1,
112.6, 119.9, 120.0, 125.2, 126.1, 127.6, 127.7, 129.0, 129.2, 140.2,
140.9, 142.0, 143.7 (C-Ar) ppm. MS (MALDI, positive mode, ma-
trix: DHB): m/z ϭ 447.0 [M ϩ Na]ϩ. C25H28O6 (424.49): calcd. C
70.73, H 6.65; found C 70.91, H 6.87.
3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α/β-
Wilkinson’s catalyst (342 mg, 0.36 mmol) was added to a solution
of 10a (1.2 g, 1.85 mmol) in toluene/EtOH/H2O mixture
D-glucopyranose (15a):
Allyl
3,4,6-Tri-O-benzyl-2-O-(9-fluorenyl)-α-D-glucopyranoside
(10b): Colourless oil (0.27 g, 66.5%); Rf ϭ 0.54 (petroleum ether/
ethyl acetate, 4:1). [α]D ϭ Ϫ5.7 (c ϭ 2.0, CH2Cl2). 1H NMR
(600 MHz, CDCl3): δ ϭ 3.50 (m, 3 H, 6-H, 4-H, 2-H), 3.64 (dd,
J6Ј,5 ϭ 3.2, Jgem ϭ 10.5 Hz, 1 H, 6Ј-H), 3.69 (m, 1 H, 5-H), 3.78
a
(40:40:2 mL) and the reaction mixture was heated at reflux at 110
°C. After 10 h, the solvent was evaporated in vacuo and the residue
was purified by flash chromatography (petroleum ether/ethyl acet-
ate, 10:1) to give an α/β mixture of 15a (0.80 g, 71%) as a colourless
oil; Rf ϭ 0.45 (petroleum ether/ethyl acetate, 3:1).[α]D ϭ 17.8 (c ϭ
(dd, J ϭ 6.1, J ϭ 12.1 Hz, 1 H, CH2CHϭCH2), 3.97 (dd, J3,4
ϭ
9.2, J3,3 ϭ 9.4 Hz, 1 H, 3-H), 4.01 (m, 1 H, CH2CHϭCH2), 4.31
(d, J1,2 ϭ 2.9 Hz, 1 H, 1-H), 4.36 (d, Jgem ϭ 10.5 Hz, 1 H, CHPh),
4.38 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.54 (d, Jgem ϭ 12.1 Hz, 1
1
1.0, CH2Cl2). H NMR (600 MHz, CDCl3): δ ϭ 3.08 (br. s, 1 H,
α-OH), 3.53 (br. s, 1 H, β-OH), 3.53 (m, 2 H, β-4-H, β-5-H), 3.63
(m, 2 H, α-4-H, α-6-H), 3.72 (m, 2 H, α-2-H, β-3-H, α-6-H), 4.04
(m, 2 H, α-3-H, α-5-H), 4.46 (d, Jgem ϭ 9.6 Hz, 1 H, CHPh), 4.48
(d, Jgem ϭ 9.6 Hz, 1 H, CHPh), 4.51 (d, Jgem ϭ 12.2 Hz, 1 H,
CHPh), 4.75 (d, J1,2 ϭ 8.2 Hz, 1 H, β-1-H), 4.83 (d, Jgem ϭ 9.6 Hz,
H, CHPh), 4.77 (d, Jgem ϭ 12.5 Hz, 1 H, CHPh), 4.87 (d, Jgem
ϭ
11.2 Hz, 1 H, CHPh), 5.15 (d, Jgem ϭ 11.2 Hz, 1 H, CHPh), 5.19
(d, J ϭ 10.2 Hz, 1 H, CH2ϭCH), 5.30 (d, J ϭ 18.5 Hz, 1 H, CH2ϭ
CH), 5.78 (s, 1 H, CHϭCH2), 6.01 (m, 1 H, CHϭCH2), 7.04Ϫ7.64
(m, 23 H, Ar-H) ppm. MS (MALDI, positive mode, matrix: DHB):
m/z ϭ 677.0 [M ϩ Na]ϩ, 693.0 [M ϩ K]ϩ. C43H42O6 (654.80):
calcd. C 78.87, H 6.46; found C 78.61, H 6.50.
1 H, CHPh), 4.86 (d, Jgem ϭ 9.6 Hz, 1 H, CHPh), 4.99 (d, Jgem
ϭ
12.2 Hz, 1 H, CHPh), 5.07 (d, J1,2 ϭ 2.9 Hz, 1 H, α-1-H), 5.72 (s,
1 H, CH), 7.16Ϫ7.38 (m, 25 H, Ar-H) ppm. 13C NMR (150.8 MHz,
CDCl3): δ ϭ 67.0 (CH2), 68.4 (C-6), 70.2 (C-5), 73.4, 74.7 (2 CH2),
77.7 (C-4), 78.2 (C-2), 81.8 (C-3), 82.9 (CH), 91.1 (α-1-C), 97.6 (β-
1-C), 126.6, 127.1, 127.3, 127.4, 127.6, 127.7, 127.8, 127.9, 128.0,
129.3, 128.6, 137.7, 137.9, 138.1, 138.5, 141.7, 142.3, 142.8 (C-Ar)
ppm. MS (MALDI, positive mode, matrix: DHB): m/z ϭ 639.0 [M
ϩ Na]ϩ. C40H40O6 (616.75): calcd. C 77.89, H 6.53; found C 78.21,
H 6.83.
Diphenylmethyl 2,3,4,6-Tetra-O-acetyl-α-D-glucopyranoside (11a):
White powder (0.26 g, 83%); Rf ϭ 0.45 (petroleum ether/ethyl acet-
ate, 2:1). [α]D ϭ ϩ107.6 (c ϭ 1.0, CH2Cl2); m.p. 127 °C. H NMR
(600 MHz, CDCl3): δ ϭ 2.00Ϫ2.10 (4 AcO), 3.90 (m, 1 H, 6-H),
3.97 (m, 1 H, 5-H), 4.15 (dd, J6,5 ϭ 3.9, Jgem ϭ 12.4 Hz, 1 H, 6Ј-
1
H), 4.89 (dd, J1,2 ϭ 3.7, J2,3 ϭ 9.9 Hz, 1 H, 2-H), 5.06 (dd, J4,3
ϭ
9.8, J4,5 ϭ 9.9 Hz, 1 H, 4-H), 5.15 (d, J1,2 ϭ 3.7 Hz, 1 H, 1-H),
5.60 (dd, J3,2 ϭ 9.9, J3,4 ϭ 9.8 Hz, 1 H, 3-H), 5.67 (s, 1 H, CH),
7.26Ϫ7.37 (m, 10 H, Ar-H) ppm. 13C NMR (150.8 MHz, CDCl3):
δ ϭ 20.5, 20.6 (4 AcO), 61.6 (C-6), 67.7 (C-5), 68.4 (C-4), 70.2 (C-
3), 70.6 (C-2), 81.0 (CH), 94.3 (C-1), 126.8, 127.1, 127.7, 128.0,
128.4, 128.5, 140.4, 141.4 (C-Ar), 169.5, 169.8, 170.1, 170.6 (4 CO)
ppm. MS (MALDI, positive mode, matrix: DHB): m/z ϭ 537.0 [M
ϩ Na]ϩ, 553.0 [M ϩ K]ϩ. C27H30O10 (514.53): calcd. C 63.02, H
5.87; found C 63.15, H 5.97.
3,4,6-Tri-O-benzyl-2-O-(9-fluorenyl)-α/β-
Wilkinson’s catalyst (342 mg, 0.36 mmol) was added to a solution
of 10b (1.21 g, 1.85 mmol) in toluene/EtOH/H2O mixture
D-glucopyranose
(15b):
a
(40:40:2 mL) and the reaction mixture was heated at reflux at 110
°C for 16 h. The reaction was processed as above and the product
was purified by column chromatography on silica gel with petro-
leum ether/ethyl acetate (8:1) as eluent to afford 15b (0.75 g, 67%)
as a colourless oil; Rf ϭ 0.36 (petroleum ether/ethyl acetate, 2:1).
1
[α]D ϭ 15.2 (c ϭ 1.0, CH2Cl2). H NMR (250 MHz, CDCl3): δ ϭ
9-Fluorenyl
2,3,4,6-Tetra-O-acetyl-α-
D-glucopyranoside
(11b):
2.02 (br. s, 1 H, OH), 3.55 (m, 2 H, 6-H, 5-H), 3.67 (m, 2 H, 6Ј-H,
4-H), 4.06 (m, 1 H, 3-H), 4.51 (dd, J2,1 ϭ 3.8, J2,3 ϭ 9.8 Hz, 1 H,
2-H), 4.62 (d, Jgem ϭ 11.6 Hz, 1 H, CHPh), 4.71 (d, Jgem ϭ 11.6 Hz,
Colourless foam (0.55 g, 76%); Rf ϭ 0.37 (petroleum ether/ethyl
acetate, 2:1). [α]D ϭ ϩ17.4 (c ϭ 1.0, CH2Cl2). 1H NMR (250 MHz,
CDCl3): δ ϭ 1.90Ϫ2.11 (4 AcO), 3.90 (dd, J5,4 ϭ 9.5, J5,6 ϭ 3.9 Hz,
1 H, CHPh), 4.80 (d, Jgem ϭ 9.5 Hz, 1 H, CHPh), 4.86 (d, Jgem
11.6 Hz, 1 H, CHPh), 4.88 (m, 1 H, CHPh), 4.95 (d, Jgem
ϭ
1 H, 5-H), 4.20 (m, 2 H, 6-H, 6Ј-H), 4.83 (dd, J2,1 ϭ 3.7, J2,3
ϭ
ϭ
9.9 Hz, 1 H, 2-H), 5.11 (dd, J4,3 ϭ 9.4, J4,5 ϭ 9.5 Hz, 1 H, 4-H),
5.30 (d, J1,2 ϭ 3.7 Hz, 1 H, 1-H), 5.51 (dd, J3,2 ϭ 9.9, J3,4 ϭ 9.4 Hz,
1 H, 3-H), 5.70 (s, 1 H, CH), 7.10Ϫ7.61 (m, 8 H, Ar-H) ppm. 13C
NMR (150.8 MHz, CDCl3): δ ϭ 20.5, 20.6, 20.7 (4 AcO), 61.7 (C-
6), 67.6 (C-5), 68.5 (C-4), 70.0 (C-3), 70.8 (C-2), 81.1 (CH), 95.0
11.6 Hz, 1 H, CHPh), 5.47 (d, J1,2 ϭ 3.8 Hz, 1 H, 1-H), 5.70 (s, 1
H, CH), 7.11Ϫ7.72 (m, 23 H, Ar-H) ppm. MS (MALDI, positive
mode, matrix: DHB): m/z ϭ 636.0 [M ϩ Na]ϩ, 652.0 [M ϩ K]ϩ.
C40H38O6 (614.74): calcd. C 78.15, H 6.23; found C 78.35, H 6.28.
(C-1), 120.1, 125.1, 125.8, 127.5, 127.6, 129.4, 129.6, 140.5, 141.1, O-(3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α-
D
-glucopyranosyl) Tri-
stirred solution of 15a (1.54 g,
2.5 mmol) in dry dichloromethane (40 mL) and trichloroaceto-
141.5, 142.5, 147.7 (C-Ar), 169.5, 170.0, 170.6 (CO) ppm. MS
chloroacetimidate (16a): A
(MALDI, positive mode, matrix: DHB): m/z ϭ 535.0 [M ϩ Na]ϩ,
4126
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 4121Ϫ4131

Protection of Hydroxy Groups with Diphenylmethyl and 9-Fluorenyl Trichloroacetimidates
nitrile (2.5 mL, 25 mmol) was treated at room temperature with 75.1 (C-5), 77.9 (C-4), 82.4 (CH), 83.2 (C-2), 84.5 (C-3), 105.2 (C-
FULL PAPER
DBU (35 µL) and the mixture was then left to stand for 1.5 h. The
solvent was evaporated and the product was purified by column
chromatography (3% triethylamine in toluene) to give 16a (1.86 g,
84%) as a yellow oil; Rf ϭ 0.65 (3% triethylamine in toluene).
[α]D ϭ 6.4 (c ϭ 1.0, CH2Cl2). H NMR (250 MHz, CDCl3): δ ϭ
3.56 (m, 3 H, 6-H, 6Ј-H, 4-H), 3.81 (dd, J1,2 ϭ 3.4, J2,3 ϭ 9.5 Hz,
1 H, 2-H), 4.02 (m, 1 H, 5-H), 4.20 (dd, J3,2 ϭ 9.3, J3,4 ϭ 9.5 Hz,
1), 119.7, 125.5, 127.3, 127.5, 127.7, 128.0, 128.4, 128.6, 138.1,
138.3, 140.0, 140.2, 144.3, 144.5 (C-Ar) ppm. MS (MALDI, posi-
tive mode, matrix: DHB): m/z ϭ 652.0 [M ϩ Na]ϩ. C41H40O6
(628.76): calcd. C 78.32, H 6.40; found C 78.64, H 6.42.
1
n-Octyl 3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-β-D-glucopyranoside
(18a): A solution of trichloroacetimidate 16a (0.46 g, 0.6 mmol)
and octanol (0.94 mL, 6.0 mmol) in dry dichloromethane (20 mL)
was treated with TMSOTf (13 µL, 0.06 mmol) and the mixture was
then stirred for 1 h at room temperature. The reaction mixture was
processed as above and the product was purified by column chro-
matography on silica gel with petroleum ether/ethyl acetate (20:1)
as eluent to afford 18a (0.37 g, 86%) as a colourless oil; Rf ϭ 0.82
(petroleum ether/ethyl acetate, 5:1). [α]D ϭ Ϫ27.6 (c ϭ 2.0,
1 H, 3-H), 4.48 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.55 (d, Jgem
ϭ
10.3 Hz, 1 H, CHPh), 4.62 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.91
(m, 2 H, 2 CHPh), 4.97 (d, Jgem ϭ 10.3 Hz, 1 H, CHPh), 5.76 (s,
1 H, CH), 6.28 (d, J1,2 ϭ 3.4 Hz, 1 H, 1-H), 7.01Ϫ7.53 (m, 25 H,
Ar-H), 8.62 (br. s, 1 H, NH) ppm.
O-[3,4,6-Tri-O-benzyl-2-O-(9-fluorenyl)-α-
chloroacetimidate (16b): stirred solution of 15b (1.54 g,
2.5 mmol) in dry dichloromethane (40 mL) and trichloroacetonitr-
ile (2.5 mL, 25 mmol) was treated at room temperature with DBU 8.7 Hz, 1 H, 2-H), 3.63 (m, 2 H, 6-H, 6Ј-H), 3.71 (m, 1 H, 3-H),
D-glucopyranosyl]
Tri-
A
CH2Cl2). 1H NMR (600 MHz, CDCl3):
[CH3(CH2)5], 3.46 (m, 2 H, CH2), 3.54 (dd, J2,1 ϭ 7.6, J2,3
δ
ϭ 0.87Ϫ1.55
ϭ
(35 µL) and the mixture was then left to stand for 2 h. The reaction
was processed as above and the product was purified by column
chromatography (3% triethylamine in toluene) to give 16b (1.46 g,
77%) as a yellow oil; Rf ϭ 0.65 (3% triethylamine in toluene).
[α]D ϭ Ϫ32.4 (c ϭ 2.0, CH2Cl2). 1H NMR (250 MHz, CDCl3): δ ϭ
3.87 (m, 2 H, CH2), 4.43 (d, J1,2 ϭ 7.6 Hz, 1 H, 1-H), 4.45 (d,
gem ϭ 10.6 Hz, 1 H, CHPh), 4.51 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh),
4.58 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh), 4.73 (d, Jgem ϭ 10.6 Hz, 1
H, CHPh), 4.80 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh), 4.95 (d, Jgem
10.6 Hz, 1 H, CHPh), 6.14 (s, 1 H, CH), 7.17Ϫ7.34 (m, 25 H, Ar-
J
ϭ
3.51 (m, 1 H, 6-H), 3.67 (m, 2 H, 2-H, 6Ј-H), 3.80 (m, 1 H, 3-H), H) ppm. 13C NMR (150.8 MHz, CDCl3): δ ϭ 14.1, 22.7, 26.2, 29.4,
4.05 (m, 1 H, 5-H), 4.20 (dd, J4,3 ϭ 9.2, J4,5 ϭ 9.3 Hz, 1 H, 4-H), 29.7, 31.8 [CH3(CH2)5], 68.9 (CH2), 70.0 (C-6), 73.4 (CH2), 74.8
4.44 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.50 (d, Jgem ϭ 10.7 Hz, 1 (C-5), 74.9, 75.7 (2 CH2), 77.9 (C-4), 78.2 (C-2), 82.8 (CH), 84.6
H, CHPh), 4.61 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.75 (d, Jgem
10.7 Hz, 1 H, CHPh), 4.83 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.95 128.1, 128.2, 128.3, 138.1, 138.7, 141.8 (C-Ar) ppm. MS (MALDI,
(d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 5.69 (s, 1 H, CH), 6.01 (d, J1,2
positive mode, matrix: DHB): m/z ϭ 751.0 [M ϩ Na]ϩ, 767.0 [M
3.4 Hz, 1 H, 1-H), 7.02Ϫ7.76 (m, 23 H, Ar-H), 8.50 (br. s, 1 H, ϩ K]ϩ. C48H56O6 (728.91): calcd. C 79.09, H 7.74; found C 79.32,
ϭ
(C-3), 104.1 (C-1), 126.6, 126.9, 127.4, 127.5, 127.6, 127.7, 127.9,
ϭ
NH) ppm.
H 7.85.
Methyl 3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-β-
D-glucopyranoside
n-Octyl 3,4,6-Tri-O-benzyl-2-O-(9-fluorenyl)-α/β-D-glucopyranoside
(17a): A solution of 16a (0.46 g, 0.6 mmol) and methanol (0.24 mL, (18b): Colourless oil (0.35 g, 80%); Rf ϭ 0.63 (petroleum ether/ethyl
1
6.0 mmol) in dry dichloromethane (20 mL) was treated with
acetate, 5:1). [α]D ϭ 23.5 (c ϭ 1.0, CH2Cl2). H NMR (600 MHz,
TMSOTf (13 µL, 0.06 mmol) and the mixture was then stirred for CDCl3): δ ϭ 0.87Ϫ1.71 [CH3(CH2)5], 3.49 (m, 2 H, α-2-H, α-4-H),
1.5 h at room temperature. The reaction mixture was quenched by
the addition of solid sodium hydrogencarbonate, filtered and con-
centrated. The crude residue was purified by column chromatogra-
phy on silica gel with petroleum ether/ethyl acetate (15:1) as eluent
3.55 (m, 2 H, 5-H, α-6-H), 3.64 (dd, J2,1 ϭ 8.7, J2,3 ϭ 9.0 Hz, 1 H,
β-3-H), 3.69 (m, 4 H, β-2-H, β-CH2, β-4-H), 3.95 (m, 1 H, α-3-H),
4.09 (m, 2 H, α-CH2), 4.27 (d, J1,2 ϭ 3.4 Hz, 1 H, α-1-H), 4.42 (d,
Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.47 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh),
to afford 17a (0.31 g, 81%) as a colourless oil; Rf ϭ 0.65 (petroleum 4.53 (m, 1 H, CHPh), 4.58 (d, J1,2 ϭ 8.1 Hz, 1 H, β-1-H), 4.60 (d,
ether/ethyl acetate, 5:1). [α]D ϭ Ϫ15.6 (c ϭ 2.0, CH2Cl2). 1H NMR
(600 MHz, CDCl3): δ ϭ 3.40 (s, 3 H, OCH3), 3.45 (m, 1 H, 5-H),
J
gem ϭ 10.6 Hz, 1 H, CHPh), 4.64 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh),
4.86 (d, Jgem ϭ 10.6 Hz, 1 H, CHPh), 5.77 (s, 1 H, α-CH), 6.1 (s,
3.53 (m, 2 H, 4-H, 2-H), 3.63 (dd, J6,5 ϭ 4.7, Jgem ϭ 10.7 Hz, 1 H, 1 H, β-CH), 6.93Ϫ7.38 (m, 23 H, Ar-H) ppm. 13C NMR
6-H), 3.71 (m, 2 H, 3-H, 6Ј-H), 4.32 (d, J1,2 ϭ 7.6 Hz, 1 H, 1-H),
4.45 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.52 (d, Jgem ϭ 12.2 Hz, 1
(150.8 MHz, CDCl3): δ ϭ 14.1, 22.6, 26.1, 16.3, 29.1, 29.2, 31.7
[CH3(CH2)5], 67.7 (CH2), 68.3 (C-6), 68.9, 69.4, 70.3 (3 CH2), 74.9
(C-5), 76.9 (α-2-C), 77.8 (C-4), 81.8 (CH), 82.7 (β-2-C), 84.6 (C-3),
H, CHPh), 4.59 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh), 4.74 (d, Jgem
ϭ
10.7 Hz, 1 H, CHPh), 4.78 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.93 97.4 (α-1-C), 104.2 (β-1-C), 119.7, 119.8, 125.5, 125.8, 127.3, 127.4,
(d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 6.03 (s, 1 H, CH), 7.10Ϫ7.34 (m, 127.6, 127.7, 127.9, 128.2, 128.3, 128.6, 128.8, 129.1, 138.2, 140.2
25 H, Ar-H) ppm. MS (MALDI, positive mode, matrix: DHB): (C-Ar) ppm. MS (MALDI, positive mode, matrix: DHB):
m/z ϭ 653.0 [M ϩ Na]ϩ, 669.0 [M ϩ K]ϩ. C41H42O6 (630.78): m/z ϭ 750.7 [M ϩ Na]ϩ.
calcd. C 78.06, H 6.71; found C 77.80, H 6.50.
Methyl O-(3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-β-D-glucopyrano-
Methyl
3,4,6-Tri-O-benzyl-2-O-(9-fluorenyl)-β-
D-glucopyranoside
syl)-(1؊6)-2,3,4-tri-O-benzyl-α-
D-glucopyranoside (19a): Colourless
(17b): Colourless oil (0.24 g, 64%); Rf ϭ 0.54 (petroleum ether/ethyl
acetate, 4:1). [α]D ϭ Ϫ5.7 (c ϭ 2.0, CH2Cl2). H NMR (600 MHz,
oil (0.43 g, 68%); Rf ϭ 0.47 (petroleum ether/ethyl acetate, 5:1).
[α]D ϭ 34.8 (c ϭ 1.0, CH2Cl2). H NMR (600 MHz, CDCl3): δ ϭ
1
1
CDCl3): δ ϭ 3.54 (m, 1 H, 5-H), 3.65 (dd, J3,2 ϭ 9.1, J3,4 ϭ 9.2 Hz, 3.27 (s, 3 H, OCH3), 3.35 (m, 1 H, 5-Hb), 3.39 (m, 1 H, 3-Hb), 3.43
1 H, 3-H), 3.71 (s, 3 H, OCH3), 3.73 (m, 2 H, 6-H, 4-H), 3.79 (m, (dd, J1,2 ϭ 3.4, J2,3 ϭ 9.7 Hz, 1 H, 2-Ha), 3.47 (dd, J2,1 ϭ 7.8,
1 H, 6Ј-H), 4.09 (dd, J2,1 ϭ 8.0, J2,3 ϭ 9.1 Hz, 1 H, 2-H), 4.49 (d, J2,3 ϭ 10.1 Hz, 1 H, 2-Hb), 3.51 (m, 2 H, 6-Hb, 4-Hb), 3.56 (dd,
J1,2 ϭ 8.0 Hz, 1 H, 1-H), 4.50 (d, Jgem ϭ 11.5 Hz, 1 H, CHPh), J6,5 ϭ 4.8, Jgem ϭ 10.2 Hz, 1 H, 6-Ha), 3.60 (m, 2 H, 6Ј-Ha, 4-Ha),
4.53 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.57 (d, Jgem ϭ 11.5 Hz, 1
H, CHPh), 4.59 (d, Jgem ϭ 11.5 Hz, 1 H, CHPh), 4.61 (d, Jgem
10.7 Hz, 1 H, CHPh), 4.88 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 5.96 (s,
1 H, CH), 6.98Ϫ7.63 (m, 23 H, Ar-H) ppm. 13C NMR (150.8 MHz, 4.43 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.47 (d, Jgem ϭ 12.2 Hz, 1
CDCl3): δ ϭ 57.2 (OCH3), 68.8 (C-6), 73.5, 74.9, 76.0 (3 CH2), H, CHPh), 4.53 (d, J1,2 ϭ 3.3 Hz, 1 H, 1-Ha), 4.56 (d, Jgem
3.74 (m, 1 H, 5-Ha), 3.92 (dd, J3,2 ϭ 9.2, J3,4 ϭ 9.7 Hz, 1 H, 3-Ha),
ϭ
4.04 (m, 1 H, 6Ј-Hb), 4.31 (d, J1,2 ϭ 7.8 Hz, 1 H, 1-Hb), 4.37 (d,
Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.41 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh),
ϭ
Eur. J. Org. Chem. 2003, 4121Ϫ4131
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4127

I. A. I. Ali, E. S. H. El Ashry, R. R. Schmidt
FULL PAPER
10.7 Hz, 1 H, CHPh), 4.60 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh), 4.64 0.14 mmol) and the mixture was then stirred for 1.5 h. The reaction
(d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.70 (d, Jgem ϭ 10.7 Hz, 1 H, mixture was quenched by the addition of solid sodium hydrogen-
CHPh), 4.74 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh), 4.75 (d, Jgem
10.7 Hz, 1 H, CHPh), 4.90 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.93 fied by column chromatography on silica gel, with petroleum ether/
(d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 6.12 (s, 1 H, CH), 7.03Ϫ7.26 (m, ethyl acetate (10:1) as eluent, to afford 23 (0.90 g, 89%) as a colour-
ϭ
carbonate, filtered and concentrated. The crude residue was puri-
40 H, Ar-H), 13C NMR (150.8 MHz, CDCl3): δ ϭ 55.0 (OCH3), less oil; Rf ϭ 0.37 (petroleum ether/ethyl acetate, 5:1). [α]D ϭ 32.0
68.2 (Cb-6), 68.9 (Ca-6), 69.0 (Cb-4), 69.6 (Ca-5), 73.2, 73.4, 73.7 (3 (c ϭ 2.0, CH2Cl2). 1H NMR (600 MHz, CDCl3): δ ϭ 3.76 (s, 3 H,
CH2), 74.9 (Cb-5), 75.1, 75.5, 75.6 (3 CH2), 77.1 (Cb-2), 77.9 (Cb- OCH3), 3.77 (m, 1 H, 6-H), 3.86 (dd, J6,5 ϭ 4.4, Jgem ϭ 10.0 Hz,
3), 79.6 (Ca-2), 81.7 (Ca-3), 82.3 (CH), 84.7 (Ca-4), 97.9 (Ca-1), 1 H, 6Ј-H), 3.94 (m, 1 H, 5-H), 4.09 (m, 1 H, 2-H), 4.13 (dd, J3,2 ϭ
104.1 (Cb-1), 126.6, 127.3, 127.5, 127.6, 127.7, 127.8, 127.9, 128.0, 2.7, J3,4 ϭ 9.5 Hz, 1 H, 3-H), 4.29 (dd, J4,3 ϭ 9.5, J4,5 ϭ 9.6 Hz, 1
128.1, 128.2, 128.3, 128.4, 128.5, 138.0, 138.1, 138.3, 138.6, 138.9,
141.6, 142.9 (C-Ar) ppm. MS (MALDI, positive mode, matrix:
H, 4-H), 4.50 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.59 (d, Jgem
ϭ
11.0 Hz, 1 H, CHPh), 4.63 (d, Jgem ϭ 11.9 Hz, 1 H, CHPh), 4.66
DHB): m/z ϭ 1085.9 [M ϩ Na]ϩ, 1101.1 [M ϩ K]ϩ. C68H70O11 (d, Jgem ϭ 11.9 Hz, 1 H, CHPh), 4.71 (d, Jgem ϭ 11.9 Hz, 1 H,
(1063.3): calcd. C 76.81, H 6.63; found C 76.90, H 7.01.
CHPh), 4.94 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 5.49 (d, J1,2 ϭ
1.1 Hz, 1 H, 1-H), 5.82 (s, 1 H, CH), 6.78 (d, J ϭ 9.0 Hz, 2 H,
phenol), 6.94 (d, J ϭ 9.0 Hz, 2 H, phenyl), 7.23Ϫ7.37 (m, 25 H,
Ar-H) ppm. 13C NMR (150.8 MHz, CDCl3): δ ϭ 55.6 (OCH3),
67.1 (CH2), 69.1 (C-6), 72.2 (CH2), 72.4 (C-5), 72.7 (C-2), 73.2
(CH2), 74.7 (C-4), 80.1 (C-3), 82.6 (CH), 97.2 (C-1), 114.5, 117.7,
127.3, 127.4, 127.5, 127.9, 128.2, 128.3, 128.4, 128.5, 138.4, 138.5,
142.0, 142.1, 150.1, 154.8 (C-Ar) ppm. MS (MALDI, positive
mode, matrix: DHB): m/z ϭ 745.0 [M ϩ Na]ϩ, 761.0 [M ϩ K]ϩ.
C47H46O7 (722.86): calcd. C 78.09, H 6.41; found C 78.21, H 6.50.
Methyl O-[3,4,6-Tri-O-benzyl-2-O-(9-fluorenyl)-α/β- -glucopyrano-
D
syl]-(1؊6)-2,3,4-tri-O-benzyl-α- -glucopyranoside (19b): Colourless
D
oil (0.38 g, 61%); Rf ϭ 0.43 (petroleum ether/ethyl acetate, 5:1).
1
[α]D ϭ 24.6 (c ϭ 2.0, CH2Cl2). H NMR (600 MHz, CDCl3): δ ϭ
3.37 (m, 1 H, β-2-Ha), 3.42 (s, 3 H, OCH3), 3.45 (m, 3 H, 5-Hb, α-
4-Ha, β-4-Ha), 3.54 (m, 2 H, α-3-Hb, α-2-Hb), 3.58 (m, 2 H, 6-Ha,
α-2-Ha), 3.70 (m, 3 H, α-4-Hb, β-3-Hb, 6-Hb), 3.88 (m, 3 H, 5-Ha,
β-3-Ha, α-3-Ha), 4.01 (m, 2 H, β-2-Hb, 6Ј-Ha), 4.29 (d, Jgem
ϭ
12.1 Hz, 1 H, CHPh), 4.35 (d, Jgem ϭ 10.8 Hz, 1 H, CHPh), 4.43
(m, 2 H, 1-Ha, β-1-Hb), 4.47 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.58
(d, Jgem ϭ 10.8 Hz, 1 H, CHPh), 4.63 (d, J1,2 ϭ 3.6 Hz, 1 H, α-1-
Hb), 4.65 (m, 3 H, 3 CHPh), 4.76 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh),
4.81 (d, Jgem ϭ 10.8 Hz, 1 H, CHPh), 4.94 (d, Jgem ϭ 10.8 Hz, 1
3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α-D-mannopyranose (24). (a)
From 22: Wilkinson’s catalyst (684 mg, 0.72 mmol) was added to a
solution of 22 (2.4 g, 3.7 mmol) in a toluene/EtOH/H2O mixture
(80:80:5 mL) and the reaction mixture was heated at reflux at 110
°C. After 8 h, the solvent was evaporated in vacuo and the residue
was purified by flash chromatography (petroleum ether/ethyl acet-
ate, 10:1) to give an α/β mixture of 24 (1.53 g, 68%) as a colourless
oil; Rf ϭ 0.45 (petroleum ether/ethyl acetate, 3:1). [α]D ϭ 17.8 (c ϭ
1.0, CH2Cl2). (b) From 23: A solution of 23 (2.4 g, 3.3 mmol) was
dissolved in an acetonitrile/water mixture (60 mL, 4:1). Ammonium
cerium() nitrate (4.96 g, 9 mmol) was added at 0 °C; after 30 min,
the mixture was diluted with dichloromethane (50 mL) and satu-
rated NaHCO3 solution. The aqueous layer was extracted twice
with dichloromethane. The organic layer was dried with MgSO4
and the solvents were removed in vacuo. The residue was purified
by flash chromatography (petroleum ether/ethyl acetate, 10:1) to
give an α product of 24 (1.3 g, 63%). 1H NMR (250 MHz, CDCl3):
δ ϭ 1.96 (br. s, 1 H, OH), 3.76 (m, 2 H, 6-H, 6Ј-H), 4.04 (m, 1 H,
5-H), 4.07 (m, 1 H, 2-H), 4.12 (m, 2 H, 4-H, 3-H), 462 (m, 3 H, 3
H, CHPh), 4.98 (d, Jgem ϭ 10.8 Hz, 1 H, CHPh), 5.29 (d, Jgem
ϭ
10.8 Hz,, 1 H, CHPh), 5.72 (s, 1 H, CH), 7.03Ϫ7.36 (m, 38 H, Ar-
H) ppm. 13C NMR (150.8 MHz, CDCl3): δ ϭ 55.1 (OCH3), 66.2
(Cb-6), 68.1 (Cb-5), 69.2 (Cb-4), 69.6 (Ca-6), 69.7 (Ca-5), 73.3, 73.4,
73.5, 73.8 (4 CH2), 75.0 (β-4-Cb), 75.7, 75.8 (2 CH2), 77.5 (α-2-Ca),
77.7 (α-4-Ca), 78.0 (α-3-Cb), 78.2 (β-4-Cb), 79.4 (β-2-Cb), 81.3 (β-
2-Cb), 81.7 (α-3-Ca), 81.9 (β-3-Ca), 85.3 (β-3-Cb), 97.5 (Ca-1), 97.9
(α-1-Cb), 103.9 (β-1-Cb), 119.7, 119.8, 126.1, 127.3, 127.5, 127.6,
127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 138.5, 140.2,
143.9 (C-Ar) ppm. MS (MALDI, positive mode, matrix: DHB):
m/z ϭ 1083 [M ϩ Na]ϩ. C68H68O11 (1061.28): calcd. C 76.95, H
6.65; found C 77.27, H 6.70.
Allyl 3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α-D-mannopyranoside
(22): A solution of 2a (0.46 g, 1.4 mmol) and 20[40] (0.69 g,
1.4 mmol) in dry dichloromethane (30 mL) was treated with
TMSOTf (26 µL, 0.14 mmol) and the mixture was then stirred for
30 min. The reaction mixture was quenched by the addition of solid
sodium hydrogencarbonate, filtered and concentrated. The crude
residue was purified by column chromatography on silica gel with
petroleum ether/ethyl acetate (15:1) as eluent, to afford 22 (0.81 g,
88%) as colourless oil; Rf ϭ 0.48 (petroleum ether/ethyl acetate,
5:1). [α]D ϭ Ϫ12.0 (c ϭ 1.0, CH2Cl2). 1H NMR (250 MHz,
CDCl3): δ ϭ 3.72 (m, 3 H, 6-H, 6Ј-H, 5-H), 3.91 (m, 1 H, 2-H),
4.15 (m, 2 H, 4-H, 3-H), 4.51 (m, 4 H, CH2ϪCHϭCH2, 2 CHPh),
4.53 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.57 (d, Jgem ϭ 11.1 Hz, 1
CHPh), 4.65 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.69 (d, Jgem
ϭ
10.9 Hz, 1 H, CHPh), 4.98 (d, Jgem ϭ 10.9 Hz, CHPh), 5.31 (d,
J1,2 ϭ 1.5 Hz, 1 H, 1-H), 5.77 (s, 1 H, CH), 7.22Ϫ7.46 (m, 25 H,
Ar-H) ppm. MS (MALDI, positive mode, matrix: DHB): m/z ϭ
639.0 [M ϩ Na]ϩ, 655.0 [M ϩ K]ϩ. C40H40O6·H2O (643.75): calcd.
C 74.63, H 6.70; found C 74.62, H 6.44.
3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α-
D-mannopyranosyl
Tri-
chloroacetimidate (25a): A stirred solution of 24 (3.1 g, 5 mmol)
in dry dichloromethane (40 mL) and trichloroacetonitrile (2.5 mL,
25 mmol) was treated at room temperature with DBU (70 µL) and
the mixture was then left to stand for 2 h. The solvent was evapo-
rated and the product was purified by column chromatography (3%
triethylamine in toluene) to give 25a (3.1 g, 82%) as a yellow oil;
Rf ϭ 0.72 (3% triethylamine in toluene). [α]D ϭ Ϫ9.5 (c ϭ 2.0,
CH2Cl2). 1H NMR (250 MHz, CDCl3): δ ϭ 3.73 (m, 1 H, 6-H),
3.79 (m, 1 H, 6Ј-H), 3.91 (m, 1 H, 5-H), 3.95 (m, 1 H, 2-H), 4.01
(m, 1 H, 3-H), 4.25 (dd, J4,3 ϭ 9.6, J4,5 ϭ 9.7 Hz, 1 H, 4-H), 4.46
(m, 2 H, 2 CHPh), 4.52 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.55 (d,
H, CHPh), 4.73 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.90 (d, Jgem
ϭ
11.0 Hz, 1 H, CHPh), 4.92 (d, J1,2 ϭ 1.5 Hz, 1 H, 1-H), 5.09 (m, 2
H, CHϭCH2), 5.71 (s, 1 H, CH), 5.80 (m, 1 H, CHϭCH2),
7.08Ϫ7.85 (m, 25 H, Ar-H) ppm. MS (MALDI, positive mode,
matrix: DHB): m/z ϭ 679.7 [M ϩ Na]ϩ, 695.7 [M ϩ K]ϩ. C43H44O6
(656.81): calcd. C 78.63, H 6.75; found C 78.51, H 6.68.
4-Methoxyphenyl 3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α-D-man-
nopyranoside (23): A solution of diphenylmethyl trichloroacetimid-
ate (2a, 0.46 g, 1.4 mmol) and 21[41] (0.78 g, 1.4 mmol) in dry di-
Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.61 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh),
chloromethane (30 mL) was treated with TMSOTf (26 µL, 4.93 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 5.72 (s, 1 H, CH), 6.36 (d,
4128  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2003, 4121Ϫ4131

Protection of Hydroxy Groups with Diphenylmethyl and 9-Fluorenyl Trichloroacetimidates
J1,2 ϭ 1.9 Hz, 1-H), 7.11Ϫ7.46 (m, 25 H, Ar-H), 8.51 (s, 1 H, (dd, J6Ј,5 ϭ 4.1, Jgem ϭ 11.5 Hz, 1 H, 6Ј-Ha), 3.90 (m, 2 H, 2-Hb,
FULL PAPER
NH) ppm.
3-Hb), 3.97 (dd, J3,2 ϭ 9.6, J3,4 ϭ 9.3 Hz, 1 H, 3-Ha), 4.19 (dd,
4,3 ϭ 9.2, J4,5 ϭ 9.3 Hz, 1 H, 4-Hb), 4.47 (d, Jgem ϭ 12.0 Hz, 1 H,
J
Octyl 3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α/β-D-mannopyrano-
CHPh), 4.51 (d, Jgem ϭ 11.2 Hz, 1 H, CHPh), 4.54 (m, 3 H, 3
CHPh), 4.58 (d, J1,2 ϭ 3.5 Hz, 1 H, 1-Ha), 4.66 (d, Jgem ϭ 12.0 Hz,
1 H, CHPh), 4.70 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.79 (d, Jgem ϭ
12.0 Hz, 1 H, CHPh), 4.83 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.87
(d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.90 (d, Jgem ϭ 11.0 Hz, 1 H,
side (26a): A solution of 25a (0.46 g, 0.6 mmol) and octanol
(0.94 mL, 6.0 mmol) in dry dichloromethane (20 mL) was treated
with TMSOTf (13 µL, 0.06 mmol) and the mixture was then stirred
for 10 min. The reaction mixture was quenched by the addition
of solid sodium hydrogencarbonate, filtered and concentrated. The
crude residue was purified by column chromatography on silica gel,
with petroleum ether/ethyl acetate (30:1) as eluent, to afford 26a
(0.37 g, 86%) as a colourless oil; Rf ϭ 0.42 (petroleum ether/ethyl
acetate, 10:1). [α]D ϭ 15.5 (c ϭ 1.0, CH2Cl2). 26aα: (0.12 g, 28.5%).
1H NMR (600 MHz, CDCl3): δ ϭ 0.87Ϫ1.50 [CH3(CH2)5], 3.36
(m, 2 H, CH2), 3.79 (m, 2 H, 6-H, 5-H), 3.87 (dd, J6Ј,5 ϭ 4.8,
Jgem ϭ 10.8 Hz, 1 H, 6Ј-H), 3.90 (d, J2,1 ϭ 3.6, J2,3 ϭ 9.3 Hz, 1 H,
2-H), 3.95 (dd, J3,2 ϭ 9.3, J3,4 ϭ 9.4 Hz, 1 H, 3-H), 4.18 (dd, J4,3 ϭ
9.4, J4,5 ϭ 9.7 Hz, 1 H, 4-H), 4.54 (d, Jgem ϭ 11.6 Hz, 1 H, CHPh),
4.58 (m, 3 H, 3 CHPh), 4.73 (d, Jgem ϭ 12.1 Hz, 1 H, CHPh), 4.89
(d, J1,2 ϭ 3.6 Hz, 1 H, 1-H), 4.90 (d, Jgem ϭ 11.6 Hz, CHPh), 5.75
(s, 1 H, CH), 7.25Ϫ7.36 (m, 25 H, Ar-H) ppm. 13C NMR
(150.8 MHz, CDCl3): δ ϭ 14.1, 22.6, 26.1, 29.2, 29.3, 29.4, 31.8
[CH3(CH2)6], 67.6 (CH2), 69.4 (C-6), 71.9 (CH2), 72.0 (C-5), 73.3
(C-2), 74.9 (CH2), 75.1 (C-4), 80.5 (C-3), 82.4 (CH2), 98.0 (C-1),
82.5 (CH), 127.2, 127.3, 127.4, 127.5, 127.6, 128.0, 128.1, 128.2,
128.3, 138.1, 138.5, 138.6, 142.2, 142.3 (C-Ar) ppm. MS (MALDI,
positive mode, matrix: DHB): m/z ϭ 751.0 [M ϩ Na]ϩ, 767.0 [M
ϩ K]ϩ. C48H56O6 (728.91): calcd. C 79.09, H 7.74; found C 78.72,
H 7.71. 26aβ: (0.25 g, 57%). Colourless oil; Rf ϭ 0.38 (petroleum
ether/ethyl acetate, 10:1). [α]D ϭ Ϫ27.0 (c ϭ 2.0, CH2Cl2). 1H
NMR (600 MHz, CDCl3): δ ϭ 0.92Ϫ1.68 [CH3(CH2)5], 3.41 (m, 2
H, CH2), 3.51 (m, 2 H, 3-H, 5-H), 3.85 (m, 2 H, 6-H, 6Ј-H), 4.04
CHPh), 4.99 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 5.02 (d, J1,2
ϭ
4.8 Hz, 1 H, 1-Hb), 5.74 (s, 1 H, CH), 7.25Ϫ7.41 (m, 40 H, Ar-H)
ppm. 13C NMR (150.8 MHz, CDCl3): δ ϭ 55.0 (OCH3), 65.5 (Ca-
6), 68.9 (CH2), 69.1 (Cb-6), 69.7 (Ca-5), 71.8 (CH2), 71.9 (Cb-5),
72.5 (CH2), 72.7 (Cb-2), 73.1, 74.4, 74.7, (3 CH2), 74.9 (Cb-4), 75.0,
75.7 (2 CH2), 77.5 (Ca-4), 79.7 (Cb-3), 80.0 (Ca-2), 82.0 (Ca-3), 83.3
(CH), 97.7 (Ca-1); 98.3 (Cb-1), 112.2, 114.6, 116.0, 127.3, 127.4,
127.5, 127.6, 127.8, 127.9, 128.1, 128.2, 128.3, 128.4, 138.0, 138.1,
138.3, 138.5, 142.1, 142.2 (C-Ar) ppm. MS (MALDI, positive
mode, matrix: DHB): m/z ϭ 1085.2 [M ϩ Na]ϩ, 1102.1 [M ϩ K]ϩ.
C68H70O11 (1063.30): calcd. C 76.81, H 6.63; found C 76.39, H
6.58. 27aβ: (0.36 g, 57%). Rf ϭ 0.38 (petroleum ether/ethyl acetate,
1
5:1). [α]D ϭ 2.3 (c ϭ 1.0, CH2Cl2). H NMR (600 MHz, CDCl3):
δ ϭ 3.18 (s, 3 H, OCH3), 3.29 (m, 2 H, 4-Ha, 6-Ha), 3.37 (m, 1 H,
6-Hb), 3.38 (m, 2 H, 6Ј-Ha, 6Ј-Hb), 3.64 (m, 2 H, 5-Ha, 5-Hb), 3.73
(m, 1 H, 2-Ha), 3.92 (m, 2 H, 3-Ha, 3-Hb), 4.01 (m, 2 H, 4-Hb, 2-
Hb), 4.26 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.29 (d, Jgem ϭ 11.0 Hz,
1 H, CHPh), 4.44 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.45 (d, J1,2
ϭ
3.4 Hz, 1 H, 1-Hb), 4.49 (m, 2 H, 2 CHPh), 4.53 (d, Jgem ϭ 12.0 Hz,
1 H, CHPh), 4.58 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.68 (d, Jgem ϭ
12.0 Hz, 1 H, CHPh), 4.70 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.76
(d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.82 (d, Jgem ϭ 11.0 Hz, 1 H,
CHPh), 4.89 (d, J1,2 ϭ 3.3 Hz, 1 H, 1-Ha), 4.95 (d, Jgem ϭ 11.0 Hz,
1 H, CHPh), 6.06 (s, 1 H, CH), 7.09Ϫ7.23 (m, 40 H, Ar-H) ppm.
MS (MALDI, positive mode, matrix: DHB): m/z ϭ 1085.2 [M ϩ
Na]ϩ, 1102.1 [M ϩ K]ϩ. C68H70O11 (1063.30): calcd. C 76.81, H
6.63; found C 76.59, H 6.96.
(dd, J2,1 ϭ 2.0, J2,3 ϭ 9.6 Hz, 1 H, 2-H), 4.19 (dd, J3,4 ϭ J4,5
ϭ
7.5 Hz, 1 H, 4-H), 4.34 (d, Jgem ϭ 11.9 Hz, 1 H, CHPh), 4.41 (d,
J1,2 ϭ 3.0 Hz, 1 H, 1-H), 4.43 (d, Jgem ϭ 11.9 Hz, 1 H, CHPh),
4.62 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.66 (d, Jgem ϭ 11.9 Hz, 1
H, CHPh), 4.72 (d, Jgem ϭ 11.9 Hz, 1 H, CHPh), 4.96 (d, Jgem
ϭ
Methyl
(2,3,4,6-Tetra-O-benzyl-α/β-
D-mannopyranosyl)-(1؊6)-
11.9 Hz, 1 H, CHPh), 6.28 (s, 1 H, CH), 7.27Ϫ7.48 (m, 25 H, Ar-
H) ppm. 13C NMR (150.8 MHz, CDCl3): δ ϭ 14.1, 22.7, 26.2, 29.3,
29.4, 29.7, 31.8 [CH3(CH2)5], 69.5 (C-6), 69.9 (CH2), 71.1 (CH2),
71.4 (C-2), 73.3 (CH2), 74.7 (C-4), 75.1 (CH2), 76.0 (C-5), 82.2
(CH), 82.5 (C-3), 102.0 (C-1), 126.7, 127.3, 127.4, 127.5, 127.6,
127.7, 128.0, 128.2, 128.6, 138.3, 138.4, 138.6, 142.1, 142.9 (C-Ar)
ppm. MS (MALDI, positive mode, matrix: DHB): m/z ϭ 751.0 [M
ϩ Na]ϩ, 767.0 [M ϩ K]ϩ. C48H56O6 (728.91): calcd. C 79.09, H
7.74; found C 78.60, H 7.84.
2,3,4-tri-O-benzyl-α-
D
-glucopyranoside (27b): A solution of trichlo-
roacetimidate 25b (0.41 g, 0.6 mmol) and glucose derivative 7
(0.28 mL, 0.6 mmol) in dry dichloromethane (20 mL) was treated
with TMSOTf (13 µL, 0.06 mmol) and the mixture was then stirred
for 30 min. The reaction mixture was processed as above and the
product was purified by column chromatography on silica gel, with
petroleum ether/ethyl acetate (10:1) as eluent, to afford 27b (0.48 g,
81%) as a colourless oil; Rf ϭ 0.37 (petroleum ether/ethyl acetate
5:1). [α]D ϭ 18.5 (c ϭ 1.0, CH2Cl2).
n-Octyl 2,3,4,6-Tetra-O-benzyl-α/β-D-mannopyranoside (26b): A
4-Methoxyphenyl 3-O-Allyl-2,4-di-O-benzyl-α-D-mannopyranoside
solution of the trichloroacetimidate 25b (0.41 g, 0.6 mmol) and n-
octanol (0.14 mL, 0.9 mmol) in dry dichloromethane (20 mL) was
treated with TMSOTf (13 µL, 0.06 mmol) and the mixture was then
stirred for 45 min. The reaction mixture was processed as above
and the product was purified by column chromatography on silica
gel, with petroleum ether/ethyl acetate (15:1) as eluent, to afford
26b (0.29 g, 75%) as a colourless oil; Rf ϭ 0.63 (petroleum ether/
ethyl acetate, 5:1). [α]D ϭ 35.7 (c ϭ 1.0, CH2Cl2).
(28): LiAlH4 (0.5 g, 13.1 mmol) was added in three portions with
stirring to a solution of methoxyphenyl 3-O-allyl-2-O-benzyl-4,6-
O-benzylidene-α--mannopyranoside[39] (1.63 g, 3.2 mmol) in di-
ethyl ether/dichloromethane (1:1, 50 mL), and the mixture was
slowly heated to its boiling point. AlCl3 (1.5 g) in diethyl ether
(20 mL) was added to the hot solution over 30 min. The mixture
was heated at reflux for 2 h and cooled, the excess of LiAlH4 was
decomposed with ethyl acetate (8 mL) and addition of water
(15 mL). After dilution with diethyl ether (50 mL), the organic
layer was washed with water (3 ϫ 30 mL), dried and concentrated
under vacuum. The crude material was purified by flash chroma-
tography (petroleum ether/ethyl acetate, 3:1) to obtain 28 (1.42 g,
Methyl O-(3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α/β-
D-mannopyr-
anosyl)-(1؊6)-2,3,4-tri-O-benzyl-α- -glucopyranoside (27a): Treat-
D
ment of 25a and 7 as described for 26a gave 27a as a colourless oil
(0.48 g, 76%). 27aα: (0.12 g, 19%). Rf ϭ 0.41 (petroleum ether/ethyl
1
acetate, 5:1). [α]D ϭ 21.5 (c ϭ 2.0, CH2Cl2). H NMR (600 MHz, 87%) as a colourless oil; Rf ϭ 0.34 (petroleum ether/ethyl acetate,
CDCl3): δ ϭ 3.31 (s, 3 H, OCH3), 3.39 (dd, J4,5 ϭ 9.5, J4,3
ϭ
5:1). [α]D ϭ 17.6 (c ϭ 0.5, CH2Cl2). 1H NMR (250 MHz, CDCl3):
δ ϭ 2.30 (br. s 1 H, OH), 3.69 (s, 3 H, OCH3), 4.02 (m, 2 H, 6-H,
5-H), 4.13 (m, 1 H, 6Ј-H), 4.18 (m, 3 H, 3-H, OCH2), 4.21 (m, 1
9.6 Hz, 1 H, 4-Ha), 3.44 (dd, J2,1 ϭ 3.4, J2,3 ϭ 9.6 Hz, 1 H, 2-Ha),
3.64 (m, 3 H, 5-Ha, 6-Ha, 6-Hb), 3.73 (m, 2 H, 5-Hb, 6Ј-Hb), 3.83
Eur. J. Org. Chem. 2003, 4121Ϫ4131
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4129

I. A. I. Ali, E. S. H. El Ashry, R. R. Schmidt
H, 2-H), 4.72 (m, 1 H, 4-H), 4.86 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh), 1143.3 [M ϩ K]ϩ. C70H72O12 (1105.34): calcd. C 76.06, H 6.55;
FULL PAPER
4.91 (d, Jgem ϭ 12.2 Hz, 1 H, CHPh), 4.97 (d, Jgem ϭ 10.5 Hz, 1
H, CHPh), 5.23 (d, Jgem ϭ 10.5 Hz, 1 H, CHPh), 5.36 (m, 2 H,
CHϭCH2), 5.44 (d, J1,2 ϭ 1.5 Hz, 1 H, 1-H), 6.00 (m, 1 H, CHϭ
CH2), 6.75 (m, 4 H, Ar-H), 7.31 (m, 10 H, Ar-H) ppm. MS
(MALDI, positive mode, matrix: DHB): m/z ϭ 528.5 [M ϩ Na]ϩ,
5.45 [M ϩ K]ϩ. C30H34O7 (506.59): calcd. C 71.13, H 6.76; found
C 71.45, H 6.86.
found C 76.27, H 6.57.
4-Methoxyphenyl O-(2,3,4,6-Tetra-O-benzyl-α/β-D-mannopyrano-
syl)-(1؊6)-3-O-allyl-2,4-di-O-benzyl-α-D-mannopyranoside (28b): A
solution of trichloroacetimidate 25b (0.41 g, 0.6 mmol) and 28
(0.30 mL, 0.6 mmol) in dry dichloromethane (20 mL) was treated
with TMSOTf (13 µL, 0.06 mmol) and the mixture was then stirred
for 75 min. The reaction mixture was processed as above and the
product was purified by column chromatography on silica gel, with
petroleum ether/ethyl acetate (15:1) as eluent, to afford 28b (0.47 g,
76%, α:β ഠ 1:1) as a colourless oil; Rf ϭ 0.42 (petroleum ether/
ethyl acetate, 5:1). [α]D ϭ 23.3 (c ϭ 2.0, CH2Cl2). 1H NMR
(600 MHz, CDCl3): δ ϭ 3.35 (m, 2 H, 3-Hb, 5-Hb), 3.57 (s, 3 H,
4-Methoxyphenyl O-(3,4-6-Tri-O-benzyl-2-O-diphenylmethyl-α/β-
D-
mannopyranosyl)-(1؊6)-3-O-allyl-2,4-di-O-benzyl-α- -mannopyra-
D
noside (28a): A solution of 25a (0.46 g, 0.6 mmol) and 28 (0.30 mL,
0.6 mmol) in dry dichloromethane (20 mL) was treated with
TMSOTf (13 µL, 0.06 mmol) and the mixture was then stirred for
30 min. The reaction mixture was processed as above and the prod-
uct was purified by column chromatography on silica gel, with
petroleum ether/ethyl acetate (15:1) as eluent, to afford 28a (0.47 g,
69%) as a colourless oil; Rf ϭ 0.34 (petroleum ether/ethyl acetate,
OCH3), 3.61 (m, 2 H, 2-Hb, 6-Ha), 3.71 (dd, J6,5 ϭ 5.6, Jgem
ϭ
10.6 Hz, 1 H, 6-Hb), 3.74 (m, 2 H, 4-Hb, 6Ј-Hb), 3.90 (m, 3 H, 4-
Ha, 5-Ha, 2-Ha), 4.00 (m, 1 H, 3-Ha), 4.16 (m, 3 H, 6Ј-Ha, OCH2),
4.19 (d, J1,2 ϭ 2.8 Hz, 1 H, β-1-Hb), 4.37 (d, Jgem ϭ 11.0 Hz, 1 H,
CHPh), 4.41 (d, Jgem ϭ 11.0 Hz, 1 H, CHPh), 4.49 (d, Jgem
11.0 Hz, 1 H, CHPh), 4.51 (m, 3 H, 3 CHPh), 4.66 (d, Jgem
12.0 Hz, 1 H, CHPh), 4.76 (d, Jgem ϭ 10.0 Hz, 1 H, CHPh), 4.80
(d, Jgem ϭ 10.0 Hz, 1 H, CHPh), 4.83 (d, Jgem ϭ 12.0 Hz, 1 H,
CHPh), 4.86 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.90 (d, Jgem
10.0 Hz, 1 H, CHPh), 5.25 (d, J1,2 ϭ 1.1 Hz, 1 H, α-1-Hb), 5.41 (d,
J1,2 ϭ 1.1 Hz, 1 H, 1-Ha), 5.43 (m, 2 H, CHϭCH2), 6.01 (m, 1 H,
CHϭCH2), 6.67 (d, J ϭ 9.0 Hz, 2 H, Ar-H), 6.90 (d, J ϭ 9.0 Hz,
2 H, Ar-H), 7.17Ϫ7.38 (m, 30 H, Ar-H) ppm. 13C NMR
(150.8 MHz, CDCl3): δ ϭ 55.4 (OCH3), 68.5 (Ca-6), 69.7 (Cb-6),
71.1 (OCH2), 71.2, 71.4 (2 CH2), 72.5 (Ca-5), 72.6, 72.8 (2 CH2),
73.3 (Cb-2), 73.6 (CH2), 74.4 (Ca-2), 74.8 (CH2), 74.5 (Ca-4), 74.9
(Cb-4), 75.8 (Cb-5), 79.7 (Ca-3), 82.2 (Cb-3), 92.1 (CHϭCH2), 94.8
(α-Cb-1), 96.9 (Ca-1), 101.9 (β-Cb-1), 117.8 (CHϭCH2), 127.2,
127.3, 127.4, 127.6, 127.7, 127.8, 127.9, 128.0, 128.2, 128.3, 128.4,
128.5, 134.9, 138.4, 138.8 (C-Ar) ppm. MS (MALDI, positive
mode, matrix: DHB): m/z ϭ 1052.4 [M ϩ Na]ϩ, 1068.8 [M ϩ K]ϩ.
1
ϭ
5:1). [α]D ϭ 30.0 (c ϭ 1.0, CH2Cl2). 28aα: (0.11 g, 17%). H NMR
ϭ
(600 MHz, CDCl3): δ ϭ 3.56 (s, 3 H, OCH3), 3.61 (m, 1 H, 6-Ha),
3.71 (m, 1 H, 6-Hb), 3.80 (m, 2 H, 5-Ha, 6Ј-Hb), 3.87 (m, 3 H, 3-
Hb, 4-Ha, 5-Hb), 3.90 (m, 1 H, 6Ј-Ha), 3.93 (m, 2 H, 2-Ha, 2-Hb),
3.96 (dd, J3,2 ϭ 2.9, J3,4 ϭ 10.7 Hz, 1 H, 3-Ha), 4.13 (m, 2 H,
CH2ϪCHϭCH2), 4.19 (dd, J4,3 ϭ 9.5, J4,5 ϭ 9.7 Hz, 1 H, 4-Hb),
4.30 (m, 2 H, 2 CHPh), 4.48 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.52
(d, Jgem ϭ 11.1 Hz, 1 H, CHPh), 4.57 (d, Jgem ϭ 11.1 Hz, 1 H,
ϭ
CHPh), 4.69 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.71 (d, Jgem
ϭ
12.0 Hz, 1 H, CHPh), 4.74 (d, Jgem ϭ 11.1 Hz, 1 H, CHPh), 4.89
(d, Jgem ϭ 11.1 Hz, 1 H, CHPh), 4.94 (d, Jgem ϭ 11.1 Hz, 1 H,
CHPh), 4.99 (d, J1,2 ϭ 1.1 Hz, 1 H, 1-Hb), 5.20 (m, 2 H, CHϭ
CH2), 5.36 (d, J1,2 ϭ 1.4 Hz, 1 H, 1-Ha), 5.67 (s, 1 H, CH), 6.05
(m, 1 H, CHϭCH2), 6.75 (d, J ϭ 9.0 Hz, 2 H, phenyl), 6.93 (d,
J ϭ 9.0 Hz, 2 H, phenyl), 7.21Ϫ7.39 (m, 35 H, Ar-H) ppm. 13C
NMR (150.8 MHz, CDCl3): δ ϭ 55.4 (OCH3), 66.1 (Ca-6), 67.1
(CH2), 69.2 (Cb-6), 71.1 (CH2ϪCH), 71.5 (Ca-5), 71.9 (Cb-5), 72.7
(CH2), 72.9 (Cb-2), 73.2, 73.3, 74.4 (3 CH2), 74.5 (Ca-4), 74.6
(CH2), 74.7 (Cb-4), 79.8 (Cb-3), 82.2 (CH), 85.0 (CHϭCH2), 96.9
(Ca-1), 98.0 (Cb-1), 114.6 (CH2ϭCH), 127.2, 127.4, 127.5, 127.6,
127.8, 127.9, 128.1, 128.2, 128.3, 128.4, 134.8, 138.6, 142.3, 142.5,
150.3, 154.8 (C-Ar) ppm. MS (MALDI, positive mode, matrix:
DHB): m/z ϭ 1128.0 [M ϩ Na]ϩ, 1144.0 [M ϩ K]ϩ. C70H72O12
(1105.34): calcd. C 76.06, H 6.55; found C 76.48, H 6.62. 28aβ:
(0.36 g, 52%). Rf ϭ 0.31 (petroleum ether/ethyl acetate, 5:1). [α]D ϭ
7.9 (c ϭ 2.0, CH2Cl2). 1H NMR (600 MHz, CDCl3): δ ϭ 3.34 (dd,
J6,5 ϭ 2.5, Jgem ϭ 9.4 Hz, 1 H, 6-Hb), 3.41 (m, 1 H, 5-Hb), 3.63 (s,
3 H, OCH3), 3.64 (dd, J6,5 ϭ 5.3, Jgem ϭ 9.8 Hz, 1 H, 6-Ha), 3.72
(m, 3 H, 3-Hb, 4-Ha, 6Ј-Ha), 3.79 (m, 2 H, 2-Hb, 6-Hb), 3.94 (m, 1
H, 5-Ha), 4.03 (m, 2 H, 3-Ha, 4-Hb), 4.15 (m, 1 H, 2-Ha), 4.17 (m,
2 H, CH2ϪCHϭCH2), 4.18 (d, J1,2 ϭ 3.6 Hz, 1 H, 1-Hb), 4.20 (d,
Methyl O-(3,4,6-Tri-O-benzyl-2-O-diphenylmethyl-α-
anosyl)-(1؊4)-2,3,6-tri-O-benzyl-α- -glucopyranoside (29a): Treat-
ment of 25a and 8 as described for 28a gave 29a as a colourless oil
(0.42 g, 67%). 29aα: Rf ϭ 0.41 (petroleum ether/ethyl acetate, 5:1).
[α]D ϭ 36.5 (c ϭ 2.0, CH2Cl2). H NMR (600 MHz, CDCl3): δ ϭ
3.37 (s, 3 H, OCH3), 3.49 (dd, J2,1 ϭ 3.4, J2,3 ϭ 9.6 Hz, 1 H, 2-
Ha), 3.62 (m, 1 H, 5-Hb), 3.69 (m, 1 H, 6-Ha), 3.72 (m, 2 H, 6Ј-Ha,
6-Hb), 3.75 (m, 1 H, 6Ј-Hb), 3.81 (m, 2 H, 3-Ha, 5-Ha), 3.83 (dd,
D-mannopyr-
D
1
J
3,2 ϭ 2.8, J3,4 ϭ 9.4 Hz, 1 H, 3-Hb), 3.90 (m, 1 H, 2-Hb), 4.10 (dd,
J4,3 ϭ 9.4, J4,5 ϭ 9.5 Hz, 1 H, 4-Hb), 4.15 (m, 1 H, 4-Ha), 4.30 (d,
gem ϭ 12.0 Hz, 1 H, CHPh), 4.39 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh),
J
4.45 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh), 4.49 (m, 2 H, 2 CHPh), 4.52
(m, 2 H, 2 CHPh), 4.55 (d, Jgem ϭ 10.8 Hz, 1 H, CHPh), 4.58 (d,
J1,2 ϭ 3.4 Hz, 1 H, 1-Ha), 4.66 (d, Jgem ϭ 12.0 Hz, 1 H, CHPh),
4.87 (d, Jgem ϭ 10.8 Hz, 1 H, CHPh), 4.96 (d, Jgem ϭ 12.0 Hz, 1
H, CHPh), 5.40 (s, 1 H, CH), 5.41 (d, J1,2 ϭ 1.0 Hz, 1 H, 1-Hb),
7.12Ϫ7.31 (m, 40 H, Ar-H) ppm. 13C NMR (150.8 MHz, CDCl3):
δ ϭ 55.2 (OCH3), 69.3 (Ca-6), 69.4 (Cb-6), 69.8 (Cb-5), 71.6, 72.2,
72.6 (3 CH2), 73.0 (Ca-5), 73.2, 73.3 (2 CH2), 73.8 (Cb-2), 74.5
(CH2), 74.7 (Ca-4), 79.6 (Cb-3), 79.8 (Ca-2), 81.0 (Cb-4), 81.4 (Ca-
3), 81.5 (CH), 97.7 (Ca-1), 99.6 (Cb-1), 126.4, 126.9, 127.2, 127.3,
127.4, 127.5, 127.6, 127.8, 127.9, 128.0, 128.1, 128.2, 128.3, 137.8,
138.2, 138.6, 138.9, 142.0, 142.4 (C-Ar) ppm. MS (MALDI, posi-
tive mode, matrix: DHB): m/z ϭ 1086.0 [M ϩ Na]ϩ, 1102.0 [M ϩ
K]ϩ. C68H70O11 (1063.30): calcd. C 76.81, H 6.63; found C 76.27,
H 6.60.
Jgem ϭ 11.8 Hz, 1 H, CHPh), 4.27 (d, Jgem ϭ 11.8 Hz, 1 H, CHPh),
4.49 (m, 3 H, 3 CHPh), 4.58 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.65
(d, Jgem ϭ 11.8 Hz, 1 H, CHPh), 4.75 (d, Jgem ϭ 11.8 Hz, 1 H,
CHPh), 4.90 (d, Jgem ϭ 10.7 Hz, 1 H, CHPh), 4.93 (d, Jgem
10.7 Hz, 1 H, CHPh), 5.26 (m, 2 H, CHϭCH2), 5.38 (d, J1,2
ϭ
ϭ
2.8 Hz, 1 H, 1-Ha), 6.15 (m, 1 H, CHϭCH2), 6.24 (s, 1 H, CH),
6.65 (d, J ϭ 9.0 Hz, 2 H, phenyl), 6.90 (d, J ϭ 9.0 Hz, 2 H, phenyl),
7.22Ϫ7.34 (m, 35 H, Ar-H) ppm. 13C NMR (150.8 MHz, CDCl3):
δ ϭ 55.4 (OCH3), 67.1, 68.0, 69.3, 70.1, 71.0 (5 CH2), 74.4 (Cb-2),
76.4 (Cb-6), 76.5 (Ca-6), 78.0 (CH2), 78.1 (Ca-4), 79.6 (Ca-5), 81.3
(Ca-3), 81.4 (Cb-4), 81.5 (Ca-2), 83.0 (Cb-5), 89.0 (Cb-3), 89.6 (CH),
97.4 (Ca-1), 109.1 (Cb-1), 114.5, 116.6, 117.1, 117.9, 118.1, 126.6,
127.1, 127.3, 127.4, 127.6, 127.7, 127.8, 128.0, 128.1, 128.3, 128.8,
134.6, 134.9, 138.1, 138.4, 138.6, 142.0, 143.2 (C-Ar) ppm. MS
Methyl
(2,3,4,6-Tetra-O-benzyl-α/β-D-mannopyranosyl)-(1؊4)-
(MALDI, positive mode, matrix: DHB): m/z ϭ 1127.3 [M ϩ Na]ϩ, 2,3,6-tri-O-benzyl-α-
D-glucopyranoside (29b): A solution of trichlo-
4130  2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2003, 4121Ϫ4131

Protection of Hydroxy Groups with Diphenylmethyl and 9-Fluorenyl Trichloroacetimidates
FULL PAPER
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Received May 27, 2003
Eur. J. Org. Chem. 2003, 4121Ϫ4131
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4131