Reactions of N-, S- and O-nucleophiles with 3,4,6-tri-O-benzyl-D-glucal mediated by triphenylphosphane hydrobromide versus those with HY zeolite

Article abstract of DOI:10.1002/ejoc.200500916

Direct C-N bond formation has been accomplished by reaction of 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-D-arabinohex-1-enitol (3,4,6-tri-O-benzyl-D-glucal) with N-nucleophiles, using triphenylphosphane hydrobromide as catalyst in dichloromethane or THF. 2-D

Full text of DOI:10.1002/ejoc.200500916

FULL PAPER
DOI: 10.1002/ejoc.200500916
Reactions of N-, S- and O-Nucleophiles with 3,4,6-Tri-O-benzyl- -glucal
D
Mediated by Triphenylphosphane Hydrobromide versus Those with HY Zeolite
Amélia P. Rauter,*[a] Tânia Almeida,[a] Ana I. Vicente,[a] Verónica Ribeiro,[a]
João C. Bordado,[b] João P. Marques,[b] Fernando Ramôa Ribeiro,[b] Maria J. Ferreira,[c]
Conceição Oliveira,[c] and Michel Guisnet[d]
Dedicated to Professor András Lipták on the occasion of his 70th birthday
Keywords: Glycosides / Glycosylation / Nucleosides / Rearrangement / Zeolites
Direct C–N bond formation has been accomplished by reac-
tion of 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy- -arabino-
hex-1-enitol (3,4,6-tri-O-benzyl- -glucal) with N-nucleo-
vity. This procedure has led to an easy and straightforward
synthesis of a variety of biomolecules, in moderate to high
yield, with the first use of triphenylphosphane hydrobromide
for N- and S-glycosylation. An alternative method for C–O
and C–S bond formation uses HY zeolite to promote the
Ferrier rearrangement of 3,4,6-tri-O-benzyl-D-glucal to give
exclusively the corresponding 2,3-unsaturated α-O- and α-S-
glycosides in moderate yields.
D
D
philes, using triphenylphosphane hydrobromide as catalyst
in dichloromethane or THF. 2-Deoxy-S- and -O-glycosides
have also been prepared with thiols, sterols, flavonoids,
alcohols and sugars as nucleophiles, with α-stereoselectivity.
Sterically demanding reagents such as sterols, flavonoids,
sugars and an indole give only the α-anomer in dichloro-
methane, while the purine nucleosides in THF were obtained
as anomeric mixtures whilst maintaining the α-stereoselecti-
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2006)
sulfonic acid resin,[16] p-toluenesulfonic acid[17] and cam-
phorsulfonic acid[18] has also been reported for the prepara-
tion of 2-deoxy glycosides. Falck et al.[19] have introduced
an O-glycosylation reaction that uses triphenylphosphane
hydrobromide (TPHB) as catalyst, in dichloromethane at
room temperature, which appears to be unique in its capa-
bility to exclusively promote direct addition of oxygen nu-
cleophiles to glucals with α-selectivity using a wide variety
of acceptors.[19–23] The dominant anomeric effect contrib-
utes to the α-stereoselectivity observed in these reactions.
Recently, a polymer-bound diphenylphosphane hydrobro-
mide[24] has been described to promote the synthesis of 2-
deoxy glycosides with α-selectivity in high yield. However,
allylically rearranged 2,3-unsaturated glycosides were found
to be minor products (ca. 10%) in the reaction of 3,4-di-O-
acetyl-1,5-anhydro-2,6-dideoxy--arabino-hex-1-enitol, with
octanol and dodecanol catalysed by TPHB in dichloro-
Introduction
Glycosylation of glycals has been widely used for the syn-
thesis of biologically interesting oligosaccharides and glyco-
conjugates[1–5] and for the preparation of 2-deoxy glyco-
sides,[6] which are common structural units in many biolo-
gically active natural products such as antibiotics[7–10] or
cardiac glycosides,[8–11] as well as versatile synthetic inter-
mediates.[12] The synthesis of C-glycosides by palladium-
mediated coupling of glycals with suitable aromatic or het-
erocyclic aglycons has also been reported.[13] Boron trichlo-
ride and boron tribromide have been used as catalysts to
synthesise silylated 2-deoxy-α--O-glycosides in good
yields,[14] and the formation of 2-deoxy glycosides catalysed
by boron trifluoride etherate depends upon the glycal start-
ing material and the nucleophile.[15] The use of anhydrous
[a] Departamento de Química e Bioquímica/Centro de Química e
Bioquímica, Faculdade de Ciências da Universidade de Lisboa, methane under reflux.[20] Glycosides of this type are also
Ed. C8, 5o Piso, 1749-016 Lisboa, Portugal
valuable synthetic intermediates for the preparation of de-
Fax: +351-21-7500088
oxy glycosides and constitute the structural units of several
antibiotics.[2] A simple route for their synthesis consists of
the acid-catalysed reaction of alcohols with glycals, which
undergo a Ferrier rearrangement due to the formation of
an allyloxycarbenium ion.[25] A diversity of catalysts have
been employed in this reaction, including BF3·Et2O,[26]
SnCl4,[27] InCl3,[28] InBr3,[29] Yb(OTf)3,[30] ZnCl2,[31]
E-mail: aprauter@fc.ul.pt
[b] Centro de Engenharia Biológica e Química, Instituto Superior
Técnico,
Av. Rovisco Pais, 1049-001 Lisboa, Portugal
[c] Centro de Química Estrutural, Instituto Superior Técnico,
Av. Rovisco Pais, 1049-001 Lisboa, Portugal
[d] Laboratoire de Catalyse en Chimie Organique, CNRS UMR
6503, Université de Poitiers,
40 Avenue du Recteur Pineau, 86022 Poitiers, France
Eur. J. Org. Chem. 2006, 2429–2439
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A. P. Rauter et al.
FULL PAPER
LiBF4,[32,33] Sc(OTf)3,[34] BiCl3
and montmorillonite and β-glycosides with different α/β ratios. The α- and β-
[35]
K-10.[36] Most of the reported Lewis acid catalysed allylic anomers of the octyl and dodecyl glycosides were isolated
rearrangements have been successful with 3-O-acyl pro- in 71% (2a), 71% (3a), 15% (2b) and 16% (3b) yields (en-
tected glycals.[25] Glycal rearrangement of other 3-O-pro- tries 1 and 2, Table 1). Thioglycosidation with allyl mercap-
tected glycals, however, has only seldom been described, al- tan and propane-2-thiol, under reflux, gave an inseparable
though the rearrangement of 3-O-methyl--glucal[37] and 3- mixture of diastereoisomers 11a and 11b (42%) with an α/
O-benzyl--glucal[38], promoted by BF3·Et2O, has been re- β ratio of 1:1 and 12a and 12b (65%) with an α/β ratio of
ported. Ceric ammonium nitrate[39] also mediates the 2:1; the latter were also formed at 0 °C but in a lower yield
Ferrier rearrangement of 3-O-benzyl glycals with ethane- (entries 13–15, Table 1). When cholesterol, lanosterol, the
thiol, although the 2,3-unsaturated products were formed racemic flavonoids 6-hydroxyflavanone, 7-hydroxyflavanone
only as minor compounds. Again, the dominant anomeric and 4-hydroxyflavanone, methyl 2-O-benzoyl-4,6-di-O-ben-
effect contributes to the α-stereoselectivity observed. How- zylidene-α--glucopyranoside and methyl 2,6-di-O-piva-
ever, stereoselective palladium-catalysed O-glycosylation loyl-α--ribo-hexopyranosid-3-ulose were used as nucleo-
using glycals has also been reported to give Ferrier prod- philes, with dichloromethane as solvent, this method was
ucts[40] in which the anomeric configuration is controlled by stereoselective and gave only the corresponding α-anomer
the reagent rather than by the anomeric or neighbouring- (entries 3–5, 8, 9, 11, 12, Table 1). Hence, the anomeric ste-
group effects. Synthesis of 2,3-unsaturated C-glycosides reochemistry, which is due to stereoelectronic effects, may
was recently described by reaction of glycals with either arise from the kinetic anomeric effect expected for trapping
organozinc reagents[41] or catalysed by HClO4/SiO2.[42]
the intermediate oxonium ion, and the α/β ratios obtained
Acid zeolites, which are widely used as catalysts, are may be due to differing magnitudes of this effect inherent
microporous crystalline materials that allow environmen- in the developing C-1-nucleophile bonding.[21] When the re-
tally acceptable procedures for the synthesis of fine chemi- action of 6-hydroxyflavanone was run in THF at room tem-
cals.[43–46] Among them, the HY zeolites have been em- perature, only the α-anomer was obtained. However, when
ployed in carbohydrate chemistry to promote isomerisation running the reaction in THF under reflux the yield and the
and hydrolysis of disaccharides[47,48] and hydrolysis of α-stereoselectivity decreased for the flavanon-6-yl glycoside,
methyl glucosides[49] and sucrose.[50] The synthesis of butyl and the corresponding β-anomer was detected in low yield
glucopyranosides[51] and glucosylation of alcohols with 1,2- (entries 6 and 7, Table 1). The same occurred when 4-hy-
anhydro-α--glucopyranose derivatives, catalysed by HY droxyflavanone was used under the same conditions (en-
zeolites, have also been reported.[52] The acetonation of try 10, Table 1). These results contradict those expected
various monosaccharides promoted by this solid catalyst fa- when considering the high donor number (DN
=
vours the formation of the thermodynamically less stable 20.0 kcalmol–1)[55] and the low polarity[55] of THF. These
isomers (the furanose derivatives) when -galactose and - parameters are both in favour of an increase of the α-selec-
arabinose are used as starting materials.[53] The reaction tivity of the reaction, as reported for glycosylation reactions
with -sorbose afforded the first synthesis of 1,2-O-isopro- with trichloroacetimidate donors run at low to room tem-
pylidene-α--sorbopyranose.[53] These results encouraged perature in THF and in dichloromethane.[56] The α-direc-
the further exploitation of the use of zeolites as promoters tional effect of ethers as solvents is well known and may be
of other reactions, namely the reaction of alcohols, flavon- due to the interaction of the ether oxygen atom with the
oids and thiols with -glucal. Furthermore, changing over sugar oxonium ion intermediate. Their low polarity also
to zeolites instead of using environmentally hazardous cata- contributes to the anomeric outcome, since the anomeric
lysts is an additional benefit.
effect is stronger in solvents of low polarity, as confirmed
We report herein the first C–N and C–S bond formation also by the results reported on the glycosylation with thio-
using TPHB as catalyst, by reaction of 1,5-anhydro-3,4,6- glycosides as donors at room temperature using dichloro-
tri-O-benzyl-2-deoxy--arabino-hex-1-enitol (1; 3,4,6-tri-O- methane and/or ethers as solvents.[57] The explanation for
benzyl--glucal) with an indole, purine or thiol to afford the results obtained may be related to the stability of the
the corresponding 2-deoxy nucleosides and 2-deoxy-S-gly- oxycarbenium–solvent intermediate, which probably de-
cosides. This reaction was extended to a variety of O-nu- creases with increasing temperature.
cleophiles such as aliphatic alcohols, sterols, sugars and fla-
The anomeric configuration of the glycosides was as-
vonoids. We also undertook the first approach towards the signed from the NMR spectroscopic data given in the Ex-
Ferrier rearrangement of 1 mediated by an HY zeolite perimental Section. The HMBC correlations detected for
(FAU topology),[54] which gives exclusively the α-anomer of the cholesteryl and lanosteryl glycosides 4 and 5, respec-
the 2,3-unsaturated 2,3-dideoxy-O- and -S-glycosides; N- tively, were determinant for their assignment (Table 2), par-
nucleophiles are unreactive with this promoter.
ticularly those for carbons C-10Ј and C-13Ј of compound 4
and C-4Ј, C-8Ј, C-9Ј, C-10Ј, C-13Ј and C-14Ј of compound
5. Due to their stereogenic centre at position 2, the 2Ј-H
resonances of the flavanone glycosides appear as a complex
signal, which is consistent with the presence of inseparable
Results and Discussion
Reaction of 1 with octanol, dodecanol and both the thi- α--diastereoisomers in dichloromethane for 6a–8a and
ols in the presence of TPHB afforded the corresponding α- α,β--diastereoisomers in THF under reflux (entries 5–10,
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Reactions of N-, S- and O-Nucleophiles with 3,4,6-Tri-O-benzyl--glucal
FULL PAPER
Table 1). Assignment of the quaternary carbon atoms of the atom in the flavonoid glycosides 6a and 7a due to the sub-
flavonoid A ring of compound 7a was accomplished by stitution at position 4ЈЈ.
considering the HMBC correlations of C-4Јa at δ =
Condensation of 1 with 5,6-dimethoxyindole, catalysed
162.4 ppm with the multiplet at δ = 6.75–6.70 ppm, which by TPHB, was investigated in the presence of solvents with
contains the resonances of 6Ј-H, 8Ј-H, while C-7Ј and C-8aЈ different boiling points and with increasing polarity,[55] such
were assigned at δ = 163.3 and 163.0 ppm, both of which as toluene, THF and dichloromethane, either at room tem-
have correlations with 5Ј-H at δ = 7.86 ppm. This proton perature or under reflux (entries 16–19, Table 1). The α--
also exhibits an HMBC correlation with C-4Ј (carbonyl car- nucleoside 13 was isolated in low yield (12–20%) under
bon atom), as expected. For compound 8a, the C-1ЈЈ signal these reaction conditions, while the β-anomer was not de-
at δ = 132.0 ppm was confirmed by its HMBC correlation tected by TLC in the reaction mixture. Reaction at C-3 of
with 3ЈЈ-H and 5ЈЈ-H at δ = 7.17 ppm, which appears at the indole ring was ruled out by examination of the NMR
lower chemical shift than those detected for this carbon spectra of compound 13, which presents the resonances of
Table 1. O-, S-, and N-Glycosylation mediated by TPHB.
Eur. J. Org. Chem. 2006, 2429–2439
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A. P. Rauter et al.
FULL PAPER
Table 1. (continued).
[a] Conditions: 3,4,6-tri-O-Benzyl--glucal 1 (1 mmol), nucleophile (2 mmol), TPHB (0.079 mmol). [b] Recovered starting material (%).
2-H and 3-H at δ = 6.77 and 6.33 ppm, respectively, each 1Ј-H with C-8 and C-4, of 8-H with C-4 and C-5 and of 2-
as a doublet, and of CH-2 and CH-3 at δ = 123.5 and H with C-4 and C-6 observed for compounds 14a and 15a.
102.4 ppm, respectively. The low solubility of 6-chloropu-
When the reaction was carried out in the presence of the
rine and 6-bromopurine in dichloromethane hampers their acid zeolite HY, with octanol, 6-hydroxyflavanone and
reactivity, therefore THF was used instead. The 2-deoxynu- propane-2-thiol as nucleophiles in dichloroethane, the 2,3-
cleosides 14a,b and 15a,b were obtained in 39% and 48% unsaturated α--glycosides 16, 17 and 18 were obtained in
isolated yield, respectively, as anomeric mixtures with an α/ moderate yields (55–47%; Scheme 1, route b), while in
β ratio of 2:1 and 3:1 (entries 20 and 21, Table 1), the start- dichloromethane, which has a lower boiling point, the
ing material being recovered in 26% and 23% yield, respec- yields were lower (entries 1–4, 9 and 10, Table 3). No reac-
tively. The reaction is regioselective, and the presence of the tion was detected when methyl 2-O-benzoyl-4,6-di-O-ben-
N9-isomers was confirmed by the HMBC correlations of zylidene-α--glucopyranoside, methyl 2,6-di-O-pivaloyl-α-
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Reactions of N-, S- and O-Nucleophiles with 3,4,6-Tri-O-benzyl--glucal
FULL PAPER
Table 2. Relevant HMBC correlations for assignment of NMR data glycoside. This result can be explained on the basis of the
of compounds 4 and 5.
HSAB concept. Protonation of the hard C-3 oxygen centre
13C
HMBC
by the zeolite leads to formation of the Ferrier product,
while TPHB protonates the softer C-2 enolic centre, as sug-
gested by Falck et al.[19] Treatment of octyl 3,4,6-tri-O-
benzyl-2-deoxy-α--arabino-hexopyranoside (2a) with the
acid zeolite under the same reaction conditions but in the
absence of octanol did not lead to any reaction products,
thus confirming that debenzoxylation only takes place if an
allyloxycarbenium ion can be formed, as expected. The
shape-selectivity of the zeolite may also influence the selec-
tivity in obtaining exclusively 2,3-unsaturated glycosides
over the corresponding 2-deoxy glycosides, due to the pos-
sible hindrance of the diffusion of the reagents and the reac-
tion products, or to steric limitations in the formation of
the transition state. The mono-esterification of polyols me-
diated by HY is an example of a shape-selective reaction
inside the pores, whose rate and yield depend on the Si/Al
ratio.[59]
Carbon atom
4
1Ј
3Ј
4Ј
6Ј
8Ј
9Ј
10Ј
12Ј
13Ј
14Ј
16Ј
17Ј
22Ј
23Ј
24Ј
25Ј
37.1
m (H-2eq, H-4Јax, H-4Јeq), Me-19Ј
m (H-2eq, H-4Јax, H-4Јeq)
Me-19Ј
m (H-2eq, H-4Јax, H-4Јeq)
H-6Ј, Me-19Ј
Me-19Ј
Me-19Ј
Me-18Ј
Me-18Ј
Me-18Ј
Me-18Ј
Me-18Ј, Me-21Ј
Me-21Ј
Me-26Ј, Me-27Ј
Me-26Ј, Me-27Ј
Me-26Ј, Me-27Ј
75.9
40.0
121.6
31.9
50.1
36.7
39.8
42.3
56.7
28.2
56.1
36.2
23.8
39.5
28.0
5
In the present work, the acid zeolite HY promotes
stereoselective O- and S-glycosidation to give exclusively the
α-anomer of the Ferrier product. Since most of the available
catalysts are successful only with 3-O-acyl-protected glycals,
the methodology developed should prove to be synthetically
useful for the preparation of 2,3-unsaturated glycosides pro-
tected with benzyl groups, which are stable in a wide variety
of reaction conditions, and may be used for further syn-
thetic approaches that avoid protection/deprotection steps,
which diminish the overall reaction yield.
4Ј
5Ј
8Ј
9Ј
10Ј
12Ј
13Ј
14Ј
17Ј
23Ј
28Ј
29Ј
37.4
51.1
134.8
134.9
38.9
31.5
50.2
44.9
50.8
36.8
1 6.8
29.1
Me-19Ј
Me-28Ј, Me-29Ј
Me-30Ј
Me-19Ј
Me-28Ј, Me-29Ј, H-3Ј
Me-18Ј, Me-30Ј
Me-18Ј, Me-30Ј, Me-21Ј
Me-18Ј, Me-30Ј
Me-18Ј, Me-30Ј
H-21Ј, Me-26Ј, Me-27Ј
H-3Ј
H-3Ј
Conclusions
-ribo-hexopyranosid-3-ulose and 5,6-dimethoxyindole
were the nucleophiles used (entries 5–8, 11 and 12, Table 3).
The 2,3-unsaturation was confirmed by the signals of C-2,
The results obtained for the reaction of 1,5-an-
hydro-3,4,6-tri-O-benzyl-2-deoxy--arabino-hex-1-enitol (1)
with N-, S- and O-nucleophiles, in the presence of TPHB
or HY zeolite enable the following considerations:
(i) TPHB-catalysed glycosylation is an efficient and
straightforward method to link not only a variety of O-
nucleophiles to glycals, but also S- and N-nucleophiles, thus
affording the corresponding 2-deoxy-O-, -S-glycosides and
2-deoxynucleosides;
(ii) The reaction with aliphatic alcohols, propane-2-thiol
and purines is α-stereoselective, giving α/β ratios that de-
pend upon the nucleophile used, while sterically demanding
nucleophiles such as sterols, flavonoids and sugars lead ex-
clusively to the corresponding α-glycoside;
3
C-3 and 2-H, 3-H. The J1,2 coupling constant is in agree-
ment with the presence of 1-H equatorially attached to 2,3-
unsaturated pyranoid structures,[58] thus indicating that the
obtained compounds are α-anomers. The α-configured
Ferrier product 17 is an inseparable mixture of 2ЈR and 2ЈS
diastereoisomers, as confirmed by the resonances of 2Ј-H,
3Јax-H, 3Јeq-H and 5Ј-H, which appear as complex signals
instead of exhibiting the expected coupling patterns.
(iii) When the reaction with O- and S-nucleophiles is medi-
ated by HY zeolite, only the α-anomer of the Ferrier prod-
uct is obtained. This new method constitutes a simple ex-
perimental procedure that provides a cleaner technology in
which the zeolite is easily separated from the reaction media
and can therefore be regenerated;
Scheme 1.
(iv) This approach leads to an easy entry to 2,3-unsaturated
The Ferrier reaction promoted by the acid zeolite occurs O- and S-glycosides and provides a method to transform 3-
by debenzoxylation at position 3, leading to a highly stabi- O-benzyl glycals into Ferrier products in moderate yield
lised allyloxycarbenium ion, which undergoes nucleophilic and expands the synthetic use of the Ferrier rearrangement
attack at the anomeric position to afford the α-configured to benzyl-protected compounds.
Eur. J. Org. Chem. 2006, 2429–2439
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A. P. Rauter et al.
FULL PAPER
Table 3. Ferrier Rearrangement promoted by HY zeolite.
[a] Conditions: 3,4,6-tri-O-Benzyl--glucal 1 (1 mmol), nucleophile (2.5 mmol), HY zeolite, 150 min. [b] Recovered starting material (%).
termined by the t-plot procedure). The global composition was ob-
tained from the elemental chemical analysis, and their framework
Experimental Section
composition was determined by 29Si and 27Al magic angle spinning
nuclear magnetic resonance (MAS NMR); HY presented a frame-
work with a Si/Al ratio of 4.5 and a global Si/Al ratio of 2.7, with
a residual sodium content of 2% of the total cationic positions.
Zeolite Preparation and Characterisation: The acid form of the zeo-
lite, HY, was prepared by calcination of the corresponding ammo-
nium form, NH4Y (LZY-82 from Union Carbide), at 500 °C (under
dry air flow, 60 mLmin–1 g–1). The sample was characterised by X-
ray powder diffraction and showed a good level of crystallinity.
Scanning electron microscopy (SEM) was used to evaluate crystal
sizes and morphology; HY presented spherical particles with a dia-
meter of about 1 µm. The surface area and pore size distribution
was evaluated by nitrogen adsorption at 77 K; HY presented a BET
apparent surface area of 731 m2 g–1, and a micropore volume and
external surface area of 0.30 cm3 g–1 and 15m2 g–1, respectively (de-
The acidity of the HY sample was evaluated by temperature-pro-
grammed desorption (TPD) of ammonia. Details of the procedure
and the corresponding thermograms can be found in a previous
reference.[60]
General: All reactions were monitored by TLC (silica gel 60 F254
,
Merck) with detection by UV light and/or by vanillin in sulfuric
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Reactions of N-, S- and O-Nucleophiles with 3,4,6-Tri-O-benzyl--glucal
4-H, 5-H, 1ЈB-H), 2.36 (ddd, 3J1,2eq = 1.5, J2eq,2ax = 12.6, J2eq,3
FULL PAPER
2
3
acid solution (2.5%) spray, followed by heating at 120 °C. Solutions
were concentrated on a rotary evaporator under reduced pressure
below 40 °C. Column chromatography (CC) was performed on sil-
ica gel 60 G (0.040–0.063 mm, E. Merck) and elution under low
pressure. Melting points were determined with an Electrothermal
9100 instrument and are uncorrected. 1H and 13C NMR spectra,
DEPT, COSY, NOESY, HMQC and HMBC experiments were re-
corded using the following spectrometers: a BRUKER CPX 300
operating at 300.14 MHz for 1H and 75.43 MHz for 13C, a
BRUKER Avance 400 operating at 400.13 MHz for 1H and
100.62 MHz for 13C, and a BRUKER DRX500 operating at
500.13 MHz for 1H and 125.77 MHz for 13C, equipped with a BBI-
XYZ probe head (5 mm diameter). All the spectrometers were op-
erating at a constant temperature of 298 K. The solvent used was
CDCl3 (1% v/v Me4Si or 0.03% v/v Me4Si, Aldrich). IR spectra
were recorded with a Hitachi 270-50 spectrometer and UV spectra
on a Shimadzu UV-1603 using dichloromethane as solvent. Optical
rotations were recorded with a Perkin–Elmer 343 polarimeter. Ele-
mental analyses were performed at the Microanalyses Service of
the Instituto Superior Técnico, Universidade Técnica de Lisboa.
High resolution mass spectra were obtained with a Finnigan FT/
MS 2001 DT, FT-ICR/MS mass spectrometer equipped with a
Nd:YAg laser operating at its fundamental wavelength (1064 nm).
=
4.8 Hz, 1 H, 2eq-H), 1.75–1.62 (m, 3 H, 2ax-H, 2Ј-H), 1.32 (br. s,
3
8 H, 3Ј-H–7Ј-H), 0.93 (t, J7Ј,8Ј = 6.9 Hz, 3 H, 8Ј-H) ppm. 13C
NMR (75.43 MHz, CDCl3, 25 °C): δ = 138.3 (Cq, Ph), 128.4, 128.3,
128.0, 127.7, 127.6, 127.5 (CH, Ph), 99.8 (C-1), 79.5 (C-3), 78.2
(C-4), 75.2 (C-5), 74.9, 73.4, 71.4 (OCH2Ph), 69.5, 69.4 (C-6, C-1Ј),
36.7 (C-2), 31.8, 29.6, 29.4, 29.2, 26.1, 22.6 (C-2Ј–C-7Ј), 14.1 (C-8Ј)
ppm. HRMS: calcd. for C35H46O5 546.334922; found 546.334525.
Dodecyl
3,4,6-Tri-O-benzyl-2-deoxy-α-
D-arabino-hexopyranoside
(3a) and Dodecyl 3,4,6-Tri-O-benzyl-2-deoxy-β-D-arabino-hexopyr-
anoside (3b): Reaction of 1 with dodecanol (381 mg, 2 mmol) for
50 min gave 3a as a syrup (431 mg, 71%) and 3b also as a syrup
(99.2 mg, 16%).
3a: Rf = 0.63 (EtOAc/n-hexane, 1:2). [α]2D0 = +52 (c = 1, CH2Cl2).
IR (neat): ν = 1600 cm–1 (C=C, Ph). UV: λmax (ε) = 253 nm (9966),
˜
1
234 (1026). H NMR (300.14 MHz, CDCl3, 25 °C): δ = 7.39–7.19
3
(m, 15 H, Ph), 4.97 (d, J1,2ax = 2.7 Hz, 1 H, 1-H), 4.94, 4.90 (part
2
A of AB system, JAB = 12.0 Hz, 1 H, OCH2Ph), 4.70–4.66 (m, 3
3
H, OCH2Ph), 4.56–4.52 (m, 2 H, OCH2Ph), 3.80 (ddd, J2eq,3
=
3
3
5.4, J2ax,3 = 11.4, J3,4 = 8.9 Hz, 1 H, 3-H), 3.83–3.78 (m, 2 H, 5-
3
H, 6A-H), 3.71–3.62 (m, 3 H, 4-H, 6B-H, 1ЈA-H), 3.35 (dt, J1ЈA,1ЈB
3
2
= 9.6, J1ЈB,2Ј = 6.6 Hz, 1 H, 1ЈB-H), 2.28 (dd, J2ax,2eq = 12.9,
3J2eq,3 =5.4 Hz, 1 H, 2eq-H), 1.74 (ddd, J1,2ax = 2.7, J2ax,2eq
=
3
2
Typical Experimental Procedure for the Preparation of 2-Deoxy
Glycosides Mediated by TPHB: A solution of the nucleophile
(2 mmol) in dry dichloromethane (or THF or toluene when indi-
cated; the lowest volume necessary to dissolve the nucleophile) was
added to a solution of 1 (417 mg, 1 mmol) in dichloromethane (or
THF or toluene when indicated; 5 mL) and TPHB (27 mg,
0.079 mmol). The mixture was stirred under reflux for 150 min (or
as otherwise indicated). After cooling to room temp., CH2Cl2
(30 mL) was added to the reaction mixture and the solution washed
with a saturated solution of NaHCO3 (20 mL). Evaporation and
column chromatography with EtOAc/n-hexane or EtOAc/toluene
afforded the corresponding 2-deoxy glycosides.
12.9, 3J2ax,3 = 11.4 Hz, 1 H, 2ax-H), 1.59–1.55 (m, 2 H, 2Ј-H), 1.29
3
(br. s, 18 H, 3Ј-H–11Ј-H), 0.91 (t, J11Ј,12Ј = 6.6 Hz, 3 H, 12Ј-H)
ppm. 13C NMR (75.43 MHz, CDCl3, 25 °C): δ = 138.7, 138.5,
138.1 (Cq, Ph), 129.7, 128.9, 128.3, 127.9, 127.8, 127.5, 127.4 (CH,
Ph), 97.3 (C-1), 78.3 (C-4), 77.7 (C-3), 74.9, 73.4, 71.7 (OCH2Ph),
70.6 (C-5), 68.9 (C-6), 67.4 (C-1Ј), 35.5 (C-2), 31.9, 29.6, 29.5, 29.4,
29.3, 26.2, 22.6 (C-2Ј–C-11Ј), 14.1 (C-12Ј) ppm. HRMS: calcd. for
C39H54O5 602.397590; found 602.397125.
3b: Rf = 0.73 (EtOAc/n-hexane, 1:2). [α]2D0 = –3 (c = 1, CH2Cl2).
IR (neat): ν = 1600 cm–1 (C=C, Ph). UV: λmax (ε) = 235 nm (1768).
˜
1H NMR (300.14 MHz, CDCl3, 25 °C): δ = 7.35–7.19 (m, 15 H,
2
Ph), 4.92, 4.88 (part A of AB system, JAB = 12.0 Hz, OCH2Ph),
Octyl 3,4,6-Tri-O-benzyl-2-deoxy-α-D-arabino-hexopyranoside (2a)
3
3
4.70–4.53 (m, 5 H, OCH2Ph), 4.43 (dd, J1,2ax = 9.6, J1,2eq
=
and Octyl 3,4,6-Tri-O-benzyl-2-deoxy-β-D-arabino-hexopyranoside
2
3
1.8 Hz, 1 H, 1-H), 3.89 (dt, J1ЈA,1ЈB = 9.9, J1ЈA,2Ј = 6.9 Hz, 1 H,
1ЈA-H), 3.75–3.67 (m, 3 H, 3-H, 6A-H, 6B-H), 3.49–3.41 (m, 3 H,
(2b): Reaction of 1 with octanol (261 mg, 2 mmol) for 50 min gave
2a as a syrup (388 mg, 71%) and 2b also as a syrup (83 mg, 15%).
4-H, 5-H, 1ЈB-H), 2.36 (ddd, 3J1,2eq = 1.8, J2eq,2ax = 12.3, J2eq,3
=
2
3
2a: Rf = 0.49 (EtOAc/n-hexane, 1:6). [α]2D0 = +23 (c = 1, CH2Cl2).
5.1 Hz, 1 H, 2eq-H), 1.70–1.57 (m, 3 H, 2ax-H, 2Ј-H), 1.25 (br. s,
IR (neat): ν = 1600 cm–1 (C=C, Ph). UV: λmax (ε) = 231 nm (1877).
18 H, 3Ј-H–11Ј-H), 0.88 (t, 3J11Ј,12Ј = 6.0 Hz, 3 H, 12Ј-H) ppm. 13
C
˜
1H NMR (300.14 MHz, CDCl3, 25 °C): δ = 7.56–7.20 (m, 15 H,
Ph), 4.99–4.91 (m, 2 H, 1-H, part A of AB system, OCH2Ph), 4.70–
NMR (75.43 MHz, CDCl3, 25 °C): δ = 138.3 (Cq, Ph), 128.3, 127.9,
127.6, 127.4 (CH, Ph), 99.7 (C-1), 79.4 (C-3), 78.1 (C-4), 75.2 (C-5),
74.9, 73.4, 71.3 (OCH2Ph), 69.4 (C-6, C-1Ј), 36.7 (C-2), 31.8, 29.6,
3
3
4.53 (m, 5 H, OCH2Ph), 3.81 (ddd, 3J3,4 = 9.0, J2eq,3 = 5.1, J2ax,3
= 11.1 Hz, 1 H, 3-H), 3.73–3.64 (m, 5 H, 4-H, 5-H, 6A-H, 6B-H, 29.4, 29.3, 26.0, 22.6 (C-2Ј–C-11Ј), 14.0 (C-12Ј) ppm. HRMS:
3
3
1ЈA-H), 3.38 (dt, J1ЈA,1ЈB = 9.5, J1ЈB,2Ј = 6.6 Hz, 1 H, 1ЈB-H), 2.31
calcd. for C39H54O5 602.397292; found 602.397125.
2
3
(dd, J2ax,2eq = 12.9, J2eq,3 = 5.1 Hz, 1 H, 2eq-H), 1.76 (ddd,
Cholesteryl 3,4,6-Tri-O-benzyl-2-deoxy-α- -arabino-hexopyranoside
D
3
3
2J2ax,2eq = 12.9, J2ax,3 = 11.1, J1,2ax = 2.8 Hz, 1 H, 2ax-H), 1.61–
(4): Reaction of 1 with cholesterol (774 mg, 2 mmol) for 75 min
gave 4 as a white solid (540 mg, 67%); m.p. 122–124 °C; Rf = 0.53
3
1.56 (m, 12 H, 2Ј-H – 7Ј-H), 0.93 (t, J7Ј,8Ј = 6.6 Hz, 3 H, 8Ј-H)
ppm. 13C NMR (75.43 MHz, CDCl3, 25 °C): δ = 138.7, 138.5,
138.2 (Cq, Ph), 128.3, 127.8, 127.5 (CH, Ph), 97.3 (C-1), 78.3 (C-4),
77.7 (C-3), 74.9, 73.4, 71.7 (OCH2Ph), 70.6 (C-5), 68.9 (C-6), 67.3
(C-1Ј), 35.5 (C-2), 31.8, 29.3, 26.2, 22.6 (C-2Ј–C-7Ј), 14.0 (C-8Ј)
ppm. C35H46O5 (546.74): calcd. C 76.89, H 8.48; found C 76.74, H
8.65.
(EtOAc/n-hexane, 1:5). [α]2D0 = +47 (c = 1.1, CH Cl ). IR (KBr): ν
˜
2
2
= 1625 cm–1 (C=C), 1590 cm–1 (C=C, Ph). UV: λmax (ε) = 259 nm
(1843), 230 (1968). 1H NMR (500.13 MHz, CDCl3, 25 °C): δ =
7.45–7.29 (m, 15 H, Ph), 5.41 (br. s, 1 H, 6Ј-H), 5.26 (br. s, 1 H, 1-
3
H), 5.03, 4.99 (part A of AB system, JAB = 10.8 Hz, 1 H,
3
OCH2Ph), 4.78–4.59 (m, 5 H, OCH2Ph), 4.15 (ddd, J2ax,3 = 10.8,
2b: Rf = 0.54 (EtOAc/n-hexane, 1:6). [α]2D0 = +5 (c = 1, CH2Cl2).
3J2eq,3 = 4.0, 3J3,4 = 8.0 Hz, 1 H, 3-H), 4.01–3.91 (m, 2 H, 5-H, 6A-
H), 3.82–3.71 (m, 2 H, 4-H, 6B-H), 3.60–3.57 (m, 1 H, 3Ј-H), 2.43–
2.35 (m, 3 H, 2eq-H, 4Јax-H, 4Јeq-H), 1.11 (s, 3 H, 19Ј-Me), 1.04
IR (neat): ν = 1600 cm–1 (C=C, Ph). UV: λmax (ε) = 238 nm (3253).
˜
1H NMR (300.14 MHz, CDCl3, 25 °C): δ = 7.40–7.23 (m, 15 H,
3
3
Ph), 4.96, 4.92 (part A of AB system, OCH2Ph, JAB = 12.0 Hz),
4.75–4.58 (m, 5 H, OCH2Ph), 4.47 (dd, J1,2ax = 9.6, J1,2eq
1.5 Hz, 1 H, 1-H), 3.94 (dt, J1ЈA,1ЈB = 9.3, J1ЈA,2Ј = 6.6 Hz, 1 H,
1ЈA-H), 3.79–3.75 (m, 3 H, 3-H, 6A-H, 6B-H), 3.54–3.46 (m, 3 H,
(d, 3J20Ј,21Ј = 6.3 Hz, 3 H, 21Ј-Me), 0.99 (d, J25Ј,Me = 6.0 Hz, 6 H,
3
3
=
26Ј-Me, 27Ј-Me), 0.79 (s, 3
H, 18Ј-Me) ppm. 13C NMR
2
3
(125.77 MHz, CDCl3, 25 °C): δ = 140.8 (C-5Ј), 138.8, 138.5, 138.2
(Cq, Ph), 128.3, 127.9, 127.5 (CH, Ph), 121.6 (C-6Ј), 95.0 (C-1),
Eur. J. Org. Chem. 2006, 2429–2439
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2435

A. P. Rauter et al.
FULL PAPER
78.4 (C-4), 77.8 (C-3), 75.9 (C-3Ј), 75.0, 73.4, 71.7 (OCH2Ph), 70.7
(C-5), 69.0 (C-6), 56.7 (C-14Ј), 56.1 (C-17Ј), 50.1 (C-9Ј), 42.3
(C-13Ј), 40.0 (C-4Ј), 39.8 (C-12Ј), 39.5 (C-24Ј), 37.1 (C-1Ј), 36.7
(C-10Ј), 36.2 (C-22Ј), 36.0 (C-2), 35.8 (C-20Ј), 31.9 (C-8Ј), 28.2
(C-16Ј), 28.0 (C-25Ј), 27.7 (C-2Ј), 24.3 (C-15Ј), 23.8 (C-23Ј), 22.8
(C-27Ј), 22.6 (C-26Ј), 21.0 (C-19Ј), 19.3 (C-11Ј), 18.7 (C-21Ј), 11.9
(C-18Ј) ppm. HRMS: calcd. for C54H74O5 802.553732; found
802.553625.
44.6 (C-3Ј), 35.3 (C-2) ppm. HRMS: calcd. for C42H40O7
656.275482; found 656.277405.
(2ЈR)-/(2ЈS)-Flavanon-7-yl 3,4,6-Tri-O-benzyl-2-deoxy-α-
D-arabino-
hexopyranoside (7a): Reaction of with 7-hydroxyflavanone
1
(480 mg, 2 mmol) gave 7a as a syrup (459 mg, 70%), with the start-
ing material 1 being recovered in 14% yield (59 mg); Rf = 0.42
(EtOAc/n-hexane, 1:3). IR (neat): ν = 1689 cm–1 (C=O). UV: λmax
˜
1
(ε) = 345 nm (4341), 258 (8328). H NMR (400.13 MHz, CDCl3,
3
25 °C): δ = 7.86 (d, J5Ј,6Ј = 8.8 Hz, 1 H, 5Ј-H), 7.45–7.19 (m, 20
Lanosteryl 3,4,6-Tri-O-benzyl-2-deoxy-α-D-arabino-hexopyranoside
H, Ph), 6.75–6.70 (m, 2 H, 6Ј-H, 8Ј-H), 5.74 (br. s, 1 H, 1-H), 5.47–
(5): Reaction of 1 with lanosterol (853 mg, 2 mmol) for 60 min gave
5 as a syrup (346 mg, 43%); Rf = 0.53 (EtOAc/n-hexane, 1:2).
2
5.41 (m, 1 H, 2Ј-H), 4.92, 4.90 (part A of AB system, JAB
=
[α]2D0 = +66 (c = 1, CH Cl ). IR (neat): ν = 1600 cm–1 (C=C, Ph).
10.8 Hz, 1 H, OCH2Ph), 4.75–4.43 (m, 5 H, OCH2Ph), 4.15 (ddd,
˜
2
2
3J2ax,3 = 10.8, 3J2eq,3 = 4.8, 3J3,4 = 9.0 Hz, 1 H, 3-H), 3.82–3.48 (m,
UV: λmax (ε) = 247 nm (1843), 230 (1968). 1H NMR (500.13 MHz,
2
4 H, 4-H, 5-H, 6-H), 3.02 (dd, 3J2Ј,3Јax = 13.2, J3Јax,3Јeq = 16.8 Hz,
CDCl3, 25 °C): δ = 7.47–7.27 (m, 15 H, Ph), 5.26 (d, 3J1,2a = 3.0 Hz,
1 H, 1-H), 5.21 (br. t, J23Ј,24Ј = 6.0 Hz, 1 H, 24Ј-H), 5.01, 4.97
(part A of AB system, JAB = 10.8 Hz, 1 H, OCH2Ph), 4.76–4.57
(m, 5 H, OCH2Ph), 4.15 (ddd, J2ax,3 = 11.1, J2eq,3 = 4.8, J3,4
3
2
3
1 H, 3Јax-H), 2.84 (dd, J2Ј,3Јeq = 2.4, J3Јax,3Јeq = 16.8 Hz, 1 H,
2
3
2
3Јeq-H), 2.46 (dd, J2ax,2eq = 13.2, J2eq,3 = 4.8 Hz, 1 H, 2eq-H),
1.90 (ddd, 3J1,2ax = 2.2, 2J2ax,2eq = 13.2, 3J2ax,3 = 10.8 Hz, 1 H, 2ax-
H) ppm. 13C NMR (100.62 MHz, CDCl3, 25 °C): δ = 190.8 (C-4,
C=O), 163.3 163.0 (C-8Јa, C-7Ј), 162.8 (C-4Јa), 138.8, 138.5, 138.3,
137.9 (Cq, Ph), 128.5 (C-5Ј), 128.8, 128.4, 127.9, 127.7, 126.2, 126.1
(CH-Ph), 111.3, 103.9 (C-6Ј, C-8Ј) 95.9 (C-1), 79.8 (C-2Ј), 77.6
(C-4), 77.2 (C-3), 75.1, 73.4, 72.1 (OCH2), 72.0 (C-5), 68.4 (C-6),
44.5 (C-3Ј), 35.1 (C-2) ppm. HRMS: calcd. for C42H40O7
656.275482; found 656.277406.
3
3
3
=
=
3
3
3
9.0 Hz, 1 H, 3-H), 4.02 (ddd, J4,5 = 10.2, J5,6A = 3.6, J5,6B
1.8 Hz, 1 H, 5-H), 3.88 (dd, 3J5,6A = 3.6, 2J6A,6B = 10.5 Hz, 1 H, 6A-
H), 3.76–3.68 (m, 2 H, 4-H, 6B-H), 3.22 (dd, 3J2ЈA,3Ј = 3.3, 3J2ЈB,3Ј
=
2
3
11.1 Hz, 1 H, 3Ј-H), 2.27 (dd, J2ax,2eq = 12.3, J2eq,3 = 4.8 Hz, 1
H, 2eq-H), 1.68, 1.60 (each s, 3 H, 26Ј-H, 27Ј-H), 0.98 (s, 3 H, 19Ј-
H), 0.96, 0.80 (each s, 3 H, 28Ј-H, 29Ј-H), 0.92 (d, 3J20Ј,21Ј = 7.0 Hz,
3 H, 21Ј-H), 0.88 (s, 3 H, 30-H), 0.69 (s, 3 H, 18Ј-H) ppm. 13C
NMR (125.77 MHz, CDCl3, 25 °C): δ = 139.2, 139.0, 138.7 (Cq,
Ph), 134.9 (C-9Ј), 134.8 (C-8Ј), 131.3 (C-25Ј), 130.2, 128.8, 128.7,
128.5, 128.4, 128.3, 128.2, 128.0, 127.9 (CH, Ph), 125.7 (C-24Ј),
93.7 (C-1), 82.1 (C-3Ј), 79.0 (C-4), 78.1 (C-3), 75.4, 73.9, 72.2
(OCH2Ph), 71.8 (C-5), 69.4 (C-6), 51.1 (C-5Ј), 50.8 (C-17Ј), 50.2
(C-13Ј), 44.9 (C-14Ј), 38.9 (C-10Ј), 37.4 (C-4Ј), 36.8 (C-23Ј), 35.6
(C-1Ј), 31.5 (C-12Ј), 29.1 (C-29Ј), 26.2, 18.1 (C-26Ј, C-27Ј), 36.9,
36.6, 31.3, 30.2, 28.7, 26.9, 25.4, 24.7, 23.0, 18.7 (C-2Ј, C-2, C-6Ј,
C-7Ј, C-11Ј, C-15Ј, C-16Ј, C-20Ј, C-22Ј, C-30Ј), 19.7 (C-19Ј), 19.1
(C-21Ј), 16.8 (C-28Ј), 16.2 (C-18Ј) ppm. C57H78O5 (843.23): calcd.
C 81.19, H 9.32; found C 81.43, H 9.18.
(2ЈR)-/(2ЈS)-Flavanon-4Ј-yl 3,4,6-Tri-O-benzyl-2-deoxy-α/β-D-arab-
ino-hexopyranoside (8a,b): Reaction of 1 with 4Ј-hydroxyflavanone
(480 mg, 2 mmol) gave 8a as a syrup (376 mg, 57%, in dichloro-
methane), with the starting material 1 being recovered in 20% yield
(82 mg), or 8a,b as a syrup (257 mg, 39%, in THF under reflux, α/
β = 8.8/1, with the starting material 1 being recovered in 8%
(33 mg); Rf = 0.40 (EtOAc/n-hexane, 1:3).
8a: IR (neat): ν = 1698 cm–1 (C=O). UV: λmax (ε) = 325.5 nm
˜
(8000), 280.0 (2246), 256.5 (8000). 1H NMR (400.13 MHz, CDCl3,
3
4
25 °C): δ = 7.94 (dd, J5Ј,6Ј = 7.6, J5Ј,7Ј = 1.6 Hz, 1 H, 5Ј-H), 7.51
(td, 4J5Ј,7Ј = 1.6, 3J7Ј,8Ј = 3J6Ј,7Ј = 8.4 Hz, 1 H, 7Ј-H), 7.40–7.17 (m,
18 H, Ph), 7.11 (d, J2ЈЈ,3ЈЈ = J5ЈЈ,6ЈЈ = 8.0 Hz, 2 H, 3ЈЈ-H, 5ЈЈ-H),
7.08–6.98 (m, 2 H, 6Ј-H, 8Ј-H), 5.74 (d, J1,2ax = 2.4 Hz, 1 H, 1-
H), 5.44 (dd, J2Ј,3Јax = 13.6, J2Ј,3Јeq = 2.4 Hz, 1 H, 2Ј-H), 4.96,
3
3
(2ЈR)-/(2ЈS)-Flavanon-6-yl 3,4,6-Tri-O-benzyl-2-deoxy-α,β-D-arab-
3
ino-hexopyranoside (6a,b): Reaction of 1 with 6-hydroxyflavanone
(480 mg, 2 mmol) gave 6a as a syrup {358 mg (54%) in dichloro-
methane [167 mg (25%) in THF at room temp.], the starting mate-
rial 1 being recovered in 21% yield (88 mg) in dichloromethane
[32% (133 mg) in THF at room temp. for 180 min]} or 6a,b as a
syrup [405 mg (62%) in THF under reflux for 180 min, α/β = 4.6/
1, with 75 mg (18%) of the starting material 1 being recovered]; Rf
= 0.43 (EtOAc/n-hexane, 1:5).
3
3
2
4.92 (part A of AB system, JAB = 12.0 Hz, OCH2Ph), 4.79 – 4.45
(m, 5 H, OCH2Ph), 4.22 (td, 3J2eq,3 = 4.8, 3J2ax,3 = 3J3,4 = 10.5 Hz,
1 H, 3-H), 3.88–3.76 (m, 3 H, 4-H, 5-H, 6A-H), 3.62 (dd, 2J6A,6B
=
10.5, 3J5,6 = 5.1 Hz, 1 H, 6B-H), 3.10 (dd, 2J3Јax,3Јeq = 16.8, J2Ј,3Јax
3
3
2
= 13.5 Hz, 1 H, 3Јax-H), 2.89 (dd, J2Ј,3Јeq = 2.4, J3Јax,3Јeq
16.8 Hz, 1 H, 3Јeq-H), 2.51 (dd, J2ax,2eq = 12.8, J2eq,3 = 4.8 Hz,
1 H, 2eq-H), 1.93 (ddd, J1,2ax = 2.4, J2ax,2eq = 12.8, J2ax,3
=
2
3
3
2
3
=
6a: IR (neat): ν = 1698 cm–1 (C=O). UV: λmax (ε) = 345 nm (4341),
˜
10.5 Hz, 1 H, 2ax-H) ppm. 13C NMR (100.62 MHz, CDCl3,
25 °C): δ = 192.2 (C-4Ј, C=O), 161.6 (C-8Јa), 156.9 (C-4ЈЈ), 138.5,
138.4, 138.0 (Cq, Ph), 136.2 (C-7Ј), 132.0 (C-1ЈЈ), 128.5, 128.4,
128.1, 127.9, 127.7 (CH-Ph), 127.1 (C-5Ј), 121.6 (C-6Ј), 120.9
(C-4Јa), 118.1 (C-8Ј), 116.6 (C-3ЈЈ, C-5ЈЈ), 95.9 (C-1), 79.4 (C-2Ј),
75.2, 73.4, 72.0 (OCH2), 71.3 (C-4), 68.6 (C-5), 68.5 (C-6), 44.5
(C-3Ј), 35.4 (C-2) ppm. HRMS: calcd. for C42H40O7 656.27759;
found 656.277405.
258 (8328). 1H NMR (400.13 MHz, CDCl3, 25 °C): δ = 7.61 (d,
4J5Ј,7Ј = 2.0 Hz, 1 H, 5Ј-H), 7.45–7.18 (m, 21 H, 4 Ph, 7-ЈH), 6.97
(d, 3J7Ј,8Ј = 8.8 Hz, 1 H, 8Ј-H), 5.67 (br. s, 1 H, 1-H), 5.43–5.37 (m,
2
1 H, 2Ј-H), 4.94, 4.91 (part A of AB system, JAB = 12.0 Hz, 1 H,
2
OCH2Ph), 4.76, 4.73, 4.72, 4.69 (AB system, JAB = 11.6 Hz, 2 H,
2
OCH2Ph), 4.63, 4.60, 4.56, 4.53 (AB system, JAB = 12.0 Hz, 2 H,
2
OCH2Ph), 4.47, 4.44 (part B of AB system, JAB = 12.0 Hz, 1 H,
3
3
3
OCH2Ph), 4.17 (td, J3,4 = J2ax,3 = 9.0, J2eq,3 = 4.8 Hz, 1 H, 3-
H), 3.87–3.60 (m, 4 H, 4-H, 5-H, 6A-H, 6B-H), 3.07–2.98 (m, 1 H, Methyl
(3,4,6-Tri-O-benzyl-2-deoxy-α-
D-arabino-hexopyranosyl)-
2
3Јax-H), 2.88 (br. d, J3Јax,3Јeq = 16.8 Hz, 1 H, 3Јeq-H), 2.48 (dd, (1Ǟ3)-2-O-benzoyl-4,6-di-O-benzylidene-α-
D-glucopyranoside (9):
3
3
2J2ax,2eq = 12.8, J2eq,3 = 4.8 Hz, 1 H, 2eq-H), 1.95 (ddd, J1,2ax
=
Reaction of 1 with methyl 2-O-benzoyl-4,6-di-O-benzylidene-α--
glucopyranoside (787 mg, 2 mmol) gave 9 as a syrup (512 mg,
64%); Rf = 0.50 (EtOAc/n-hexane, 1:4). [α]2D0 = +88 (c = 1,
2.2, J2ax,2eq = 12.8, J2ax,3 = 9.0 Hz, 1 H, 2ax-H) ppm. 13C NMR
(100.62 MHz, CDCl3, 25 °C): δ = 191.8 (C-4Ј, C=O), 156.9, 150.93,
150.86 (C-4Ј, C-6Ј, C-8Ј), 138.9, 138.8, 138.6, 138.4, 138.1 (Cq-Ph),
2
3
CH Cl ). IR (neat): ν = 1731 cm–1 (C=O). UV: λmax (ε) = 253 nm
˜
2
2
128.9, 128.5, 128.4, 127.9, 127.8, 127.7, 126.2 (C-7Ј, CH-Ph), 119.2 (1476). 1H NMR (300.14 MHz, CDCl3, 25 °C): δ = 8.08 (d, J =
(C-8Ј), 112.9 (C-5Ј), 96.5 (C-1), 79.8, 79.7 (C-2Ј), 77.9 (C-4) 77.3 8.4 Hz, 2 H, Ph), 7.51–7.27 (m, 21 H, Ph), 7.00 (d, J = 8.4 Hz, 2
(C-3), 75.1, 73.4, 72.0 (OCH2Ph), 71.8 (C-5), 68.6 (C-6), 44.7 or
2436
H, Ph), 5.63 (s, 1 H, CH, benzylidene), 5.56 (br. s, 1 H, 1Ј-H) 5.20
www.eurjoc.org
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2429–2439

Reactions of N-, S- and O-Nucleophiles with 3,4,6-Tri-O-benzyl--glucal
FULL PAPER
3
3
3
2
(dd, J1,2 = 3.6, J2,3 = 9.6 Hz, 1 H, 2-H), 5.05 (d, J1,2 = 3.6 Hz,
5.02, 4.98 (1 H, part A of AB system, JAB = 11.1 Hz, OCH2Ph),
2
3
3
1 H, 1-H), 4.80, 4.76 (part A of AB system, JAB = 11.1 Hz,
4.79–4.54 (m, 5 H, OCH2Ph), 4.29 (ddd, J4,5 = 9.6, J5,6A = 1.8,
3
3
OCH2Ph), 4.65–4.35 (m, 7 H, 3-H, 6eq-H, OCH2Ph), 4.00–3.76 (m,
3J5,6B = 3.3 Hz, 1 H, 5-H), 3.90 (ddd, J2ax,3 = 11.7, J2eq,3 = 5.1,
5 H, 4-H, 5-H, 3Ј-H, 5Ј-H, 6ax-H), 3.64–3.58 (m, 2 H, 4Ј-H, 6ЈA- 3J3,4 = 9.6 Hz, 1 H, 3-H), 3.93–3.54 (m, 3 H, 4-H, 6A-H, 6B-H),
2
3
3
H), 3.48–3.43 (m, 4 H, 6ЈB-H, OCH3) 2.33 (dd, J2Јax,2Јeq = 12.9,
3.30 (dq, JCH,Me1 = 6.6, JCH,Me2 = 6.9 Hz, 1 H, SCH), 2.48–2.34
(m, 1 H, 2eq-H), 2.15 (td, 3J1,2ax = 5.4, 2J2ax,2eq = 3J2ax,3 = 12.6 Hz,
1-H, 2ax-H) ppm. 13C NMR (75.43 MHz, CDCl3, 25 °C) for 12a:
δ = 136.2, 136.0, 135.9, 135.8 (Cq, Ph), 125.9, 125.6, 125.4, 125.3
(CH, Ph), 77.3 (C-1), 75.8 (C-3), 78.4 (C-4), 72.6, 71.0, 69.1,
3
2
3J2Јeq,3Ј = 4.8 Hz, 1 H, 2Јe-H), 1.70 (td, J1Ј,2Јax = 3.0, J2Јax,2Јeq
=
12.9, 3J2Јax,3Ј = 12.6 Hz, 1 H, 2Јax-H) ppm. 13C NMR (75.43 MHz,
CDCl3, 25 °C): δ = 165.9 (C=O, Bz), 138.8, 138.1, 137.1 (Cq, Ph),
134.0, 130.7, 129.9, 129.1, 128.8, 128.7, 128.4, 128.2, 127.9, 126.8
(CH, Ph), 102.2 (CH, benzylidene), 98.8 (C-1), 98.7 (C-1Ј), 83.5 (OCH2Ph), 68.6 (C-5), 67.3 (C-6), 33.7 (C-2), 32.7 (SCH), 21.5,
(C-4), 78.7 (C-4Ј), 77.9 (C-3Ј) 75.1, 74.3, 72.6 (OCH2Ph), 72.8 21.3 (Me) ppm. C30H36O4S (492.67): calcd. C 73.14, H 7.37, S 6.51;
(C-2), 72.5 (C-3), 71.7 (C-5Ј), 69.8 (C-6), 69.2 (C-6Ј), 62.8 (C-5), found C 73.07, H 7.41, S 6.55.
56.2 (OCH3), 36.3 (C-2Ј) ppm. C48H50O11 (802.90): calcd. C 71.80,
1-(3,4,6-Tri-O-benzyl-2-deoxy-α-D-arabino-hexopyranosyl)-5,6-di-
H 6.28; found C 71.93, H 6.00.
methoxyindole (13): Reaction of 1 with 5,6-dimethoxyindole
(355 mg, 2 mmol) gave 13 as a white solid [69 mg (12%) in dichlo-
romethane under reflux; 117 mg (20%) in dichloromethane at room
temp., 24 h; 118 mg (20%) in THF under reflux, 180 min; 115 mg
(19%) in toluene under reflux], with the starting material 1 being
recovered in: 77% yield (320 mg) in dichloromethane under reflux;
36% (150 mg) in dichloromethane at room temp.; 22% (92 mg) in
Methyl
(1Ǟ4)-2,6-di-O-pivaloyl-α-
(3,4,6-Tri-O-benzyl-2-deoxy-α-
D
-arabino-hexopyranosyl)-
D-ribo-hexopyranosid-3-ulose (10): Reac-
tion of 1 with methyl 2,6-di-O-pivaloyl-α--ribo-hexopiranosid-3-
ulose (720 mg, 2 mmol) gave 10 as a syrup (310 mg, 40%); Rf =
0.58 (EtOAc/toluene 1:3). [α]2D0 = +8.1 (c = 0.4, CH2Cl2). IR (neat):
ν = 1743 cm–1 (C=O). UV: λmax (ε) = 245 nm (1077). 1H NMR
˜
(300.14 MHz, CDCl3, 25 °C): δ = 7.35–7.17 (m, 15 H, Ph), 5.22– THF; 19 % (79 mg) in toluene; m.p. 101.4–102.0 °C; Rf = 0.50
3
5.20 (m, 2 H, 1Ј-H, 2-H), 5.10 (d, J1,2 = 4.2 Hz, 1 H, 1-H), 4.90,
(EtOAc/toluene, 1:5). [α]2D0 = +105 (c = 1, CH Cl ). IR (KBr): ν =
˜
2 2
2
4.86 (part A of AB system, JAB = 10.8 Hz, OCH2Ph), 4.67–4.47
(m, 6 H, 6A-H, OCH2Ph), 4.36 (d, J4,5 = 9.0 Hz, 1 H, 4-H) 4.25
1648 cm–1 (C=C). UV: λmax (ε) = 261 nm (732). 1H NMR
(300.14 MHz, CDCl3, 25 °C): δ = 7.42–7.18 (m, 16 H, Ph, 7-H),
3
3
2
3
3
3
(dd, J5,6B = 6.2, J6A,6B = 11.4 Hz, 1 H, 6B-H) 4.04 (td, J4,5
=
7.01 (s, 1 H, 4-H), 6.77 (d, J2,3 = 3.3 Hz, 2-H), 6.32 (d, J2,3 =
3
3
3
3J5,6A = 9.0, J5,6B = 6.2 Hz, 1 H, 5-H), 3.93 (td, J2Јax,3Ј = 10.2,
3.3 Hz, 1 H, 3-H), 6.01 (br. d, J1Ј,2Јax = 3.6 Hz, 1 H, 1Ј-H), 4.90–
4.47 (m, 6 H, OCH2Ph), 4.14 (ddd, J2Јax,3Ј = 9.6, J2Јeq,3Ј = 4.5,
3
2
3
3
3J2Јeq,3Ј = 6.0, J3Ј,4Ј = 10.5 Hz, 1 H, 3Ј-H), 3.78 (dd, J6ЈA,6ЈB
=
10.2, J5Ј,6ЈA = 2.4 Hz, 1 H, 6ЈA-H) 3.67–3.61 (m, 3 H, 4Ј-H, 5Ј-H, 3J3Ј,4Ј = 8.1 Hz, 1 H, H-3Ј), 3.91 (s, 3 H, OMe), 3.87–3.79 (m, 4 H,
3
2
3
3
2
6ЈB-H), 3.43 (s, 3 H, OCH3) 2.60 (dd, J2Јax,2Јeq = 12.0, J2Јeq,3Ј
=
OMe, 4Ј-H), 3.71 (dd, J5Ј,6ЈA = 3.6, J6ЈA,6ЈB = 10.5 Hz, 1 H, 6ЈA-
3
2
3
2
6.0 Hz, 1 H, 2Јeq-H), 1.77 (ddd, J1Ј,2Јax = 3.9, J2Јax,2Јeq = 12.0, H), 3.54 (dd, J5Ј,6ЈB = 2.4, J6ЈA,6ЈB = 10.5 Hz, 1 H, 6ЈB-H), 3.32
3
3
3
3J2Јax,3Ј = 10.2 Hz, 1 H, 2Јax-H) ppm. 13C NMR (75.43 MHz,
CDCl3, 25 °C): δ = 197.6 (C-3), 176.5, 175.6 (C=O, Piv), 138.7,
138.1, 137.9, (Cq, Ph), 128.4, 128.1, 127.9, 127.6 (CH, Ph), 99.8
(C-1), 97.6 (C-1Ј), 77.7 (C-4Ј), 77.0 (C-3Ј), 75.8 (C-4), 75.1, 73.5,
71.6 (OCH2Ph), 74.6 (C-2), 72.3 (C-5Ј), 70.8 (C-5), 68.4 (C-6Ј), 62.6
(C-6), 55.5 (OCH3), 38.9 (Cq, Piv), 34.8 (C-2Ј), 27.2, 27.1 (CH3,
Piv) ppm. C44H56O12 (776.91): calcd. C 67.94; H 7.39; found C
67.79; H 7.54.
(ddd, J4Ј,5Ј = 9.6, J5Ј,6ЈA = 3.6, J5Ј,6ЈB = 2.4 Hz, 1 H, 5Ј-H), 2.72
3
2
3
(ddd, J1Ј,2Јeq = 1.8, J2Јeq,2Јax = 14.1, J2Јeq,3Ј = 4.5 Hz, 1 H, 2Јeq-
3
2
3
H), 2.23 (ddd, J2Јeq,3’ = 4.5, J2Јeq,2Јax = 14.1, J2Јax,3Ј = 9.6 Hz, 1
H, 2Јax-H) ppm. 13C NMR (75.43 MHz, CDCl3, 25 °C): δ = 146.9,
145.4 (C-5, C-6), 138.3, 138.2, 137.8 (Cq, Ph), 130.9, 121.6 (C-3a,
C-7a), 128.6, 128.5, 128.3, 128.1, 127.9, 127.8, 127.7 (CH, Ph),
123.5 (C-2), 102.4 (C-3), 102.1 (C-4), 95.4 (C-7), 80.4 (C-1Ј), 77.6
(C-4Ј), 76.6 (C-3Ј), 74.8, 73.4, 72.4 (OCH2), 71.4 (C-5Ј), 68.4 (C-6Ј),
56.2, 56.1 (OMe), 29.7 (C-2Ј) ppm. HRMS: calcd. for C37H39NO6
593.27518; found 593.27739.
Prop-2-en-1-yl
3,4,6-Tri-O-benzyl-2-deoxy-1-thio-α,β-D-arabino-
hexopyranoside (11a,b): Reaction of 1 with prop-2-en-thiol (149 mg,
2 mmol) gave 11a,b as a syrup (205 mg, 42%, α/β = 1/1); Rf = 0.55
Typical Experimental Procedure for the Reaction of 1,5-
(EtOAc/n-hexane, 1:7). IR (neat): ν = 1600 cm–1 (C=C, Ph). UV: Anhydro-3,4,6-tri-O-benzyl-2-deoxy-
D-arabino-hex-1-enitol (1) with
˜
1
λmax (ε) = 256 nm (890.16), 229 (568.32). H NMR (300.14 MHz, Purines Mediated by TPHB: The purine (3 mmol) was dissolved in
CDCl3, 25 °C) for 11a: δ = 7.37–7.20 (m, 15 H, Ph), 5.87–5.76 (m,
dry THF (20 mL) and the mixture was stirred at 70 °C until total
dissolution of the nucleophile. A solution of 1 (625 mg, 1.5 mmol)
3
1 H, = CH), 5.38 (d, J1,2ax = 5.1 Hz, 1 H, 1-H), 5.19–5.10 (m, 2
2
H, = CH2), 4.92, 4.88 (part A of AB system OCH2, JAB = 11.1 Hz, in dry THF (10 mL) and TPHB (80 mg, 0.24 mmol) was added to
3
1 H), 4.72–4.45 (m, 5 H, OCH2Ph), 4.16 (ddd, 3J4,5 = 9.9, J5,6A
=
the solution of the nucleophile and the mixture was stirred at 70 °C
3
1.8, J5,6B = 3.6 Hz, 1 H, 5-H), 3.99–3.91 (m, 1 H, 3-H), 3.84–3.41 for 180 min. After cooling to room temp. CH2Cl2 (30 mL) was
(m, 3 H, 4-H, 6A-H, 6B-H), 3.25–3.08 (m, 2 H, SCH2), 2.32–2.24 added to the reaction mixture and the solution washed with a satu-
(m, 1 H, 2eq-H), 2.07 (td, 3J1,2ax = 5.1, 2J2ax,2eq = 3J2ax,3 = 11.7 Hz,
rated solution of NaHCO3 (20 mL). Evaporation and column
1 H, 2ax-H) ppm. 13C NMR (75.43 MHz, CDCl3, 25 °C) for 11a: chromatography with EtOAc/petroleum ether afforded the corre-
δ = 138.3 (Cq, Ph), 133.7 (CH=), 128.3, 127.9, 127.8, 127.6 (CH,
Ph), 117.4 (=CH2), 78.8 (C-1), 78.2 (C-3), 80.8 (C-4), 75.0, 73.4,
71.4 (OCH2Ph), 71.1 (C-5), 69.5 (C-6), 36.4 (C-2), 33.1 (SCH2)
ppm. HRMS: calcd. for C30H34O4S 490.219636; found 490.217231.
sponding nucleoside.
9-(3,4,6-Tri-O-benzyl-2-deoxy-α,β-D-arabino-hexopyranosyl)-6-chlo-
ropurine (14a,b): Reaction of 1 with 6-chloropurine (464 mg,
3 mmol) gave 14a,b as a syrup (330 mg, 39%, α/β = 2/1), with the
1-Methylethyl 3,4,6-Tri-O-benzyl-2-deoxy-1-thio-α,β-D-arabino- starting material 1 being recovered in 26% yield (162 mg); Rf =
hexopyranoside (12a,b): Reaction of 1 with prop-2-enthiol (153 mg,
2 mmol) gave 12a,b as a syrup (320 mg, 65%, α/β = 2/1; 241 mg,
49%, α/β = 2/1, at room temp. for 24 h); Rf = 0.57 (EtOAc/n-hex-
0.50 (EtOAc/petroleum ether, 1:1.5). IR (neat): ν = 1728, 1593,
˜
1
1500, 1458, 1266 cm–1. UV: λmax (ε) = 266.5 nm (5782). H NMR
(400.13 MHz, CDCl3, 25 °C) for 14a: δ = 8.69 (s, 1 H, 2-H), 8.30
3
ane, 1:7). IR (neat): ν = 1600 cm–1 (C=C, Ph). UV: λmax (ε) =
(s, 1 H, 8-H), 7.39–7.16 (m, 15 H, Ph), 6.22 (br. t, J1Ј,2Јax = 4.8,
˜
1
258.5 nm (568). H NMR (300.14 MHz, CDCl3, 25 °C) for 12a: δ
3J1Ј,2Јeq = 4.4 Hz, 1 H, 1Ј-H), 4.96, 4.94 (part A of AB system,
2JAB = 10.8 Hz, OCH2Ph), 4.78–4.48 (m, 5 H, OCH2Ph), 3.98 (ddd,
3
= 7.44–7.27 (m, 15 H, Ph), 5.61 (d, J1,2ax = 5.4 Hz, 1 H, 1-H),
Eur. J. Org. Chem. 2006, 2429–2439
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2437

A. P. Rauter et al.
FULL PAPER
3J2Јax,3Ј = 8.7, J2Јeq,3Ј = 4.4, J3Ј,4Ј = 7.5 Hz, 1 H, 3Ј-H), 3.81–3.67 anone (600 mg, 2.5 mmol) mediated by the zeolite gave 17 as a
3
3
2
(m, 4 H, 4Ј-H, 5Ј-H, 6ЈA-H, 6ЈB-H), 3.40 (dt, J2Јeq,2Јax = 14.0,
syrup [255 mg (46%) in dichloroethane; 236 mg (43%) in dichloro-
3J1Ј,2Јeq = 3J2Јeq,3Ј = 4.4 Hz, 1 H, 2Јeq-H), 2.29 (ddd, 3J1Ј,2Јax = 4.8, methane], with the starting material 1 being recovered in 7% yield
2J2Јeq,2Јax = 14.0, J2Јax,3Ј = 8.7 Hz, 1 H, 2Јax-H) ppm. 13C NMR (29 mg) in dichloroethane and 8% (33 mg) in dichloromethane; Rf
3
(100.62 MHz, CDCl3, 25 °C) for 14a: δ = 152.0 (C-2), 151.4 (C-4),
151.3 (C-6), 144.5 (C-8), 138.0, 137.8, (Cq, Ph), 132.1 (C-5), 128.6,
= 0.43 (EtOAc/n-hexane, 1:4). IR (neat): ν = 1698 cm–1 (C=O). UV:
˜
1
λmax (ε) = 230.0 nm (277). H NMR (300.14 MHz, CDCl3, 25 °C):
128.5, 127.9, 127.8 (CH, Ph), 80.5 (C-1Ј), 75.8 (C-4Ј), 75.5 (C-3Ј), δ = 7.66–7.65 (m, 1 H, 5Ј-H), 7.50–7.26 (m, 21 H, 4 Ph, 7Ј-H), 6.97
3
3
74.5 (C-5Ј), 74.0, 73.5, 71.6 (OCH2), 68.3 (C-6Ј), 31.6 (C-2Ј) ppm. (d, J7Ј,8Ј = 9.0 Hz, 1 H, 8Ј-H), 6.22 (d, J2,3 = 10.5 Hz, 1 H, 3-H),
HRMS: calcd. for C32H3135ClN4O4 570.203383; found 570.204511.
5.93 (ddd, J1,2 = 2.7, J2,4 = 2.1, J2,3 = 10.5 Hz, 1 H, 2-H), 5.64
(br. s, 1 H, 1-H), 5.45–5.38 (m, 1 H, 2Ј-H), 4.67–4.47 (m, 4 H,
3
4
3
9-(3,4,6-Tri-O-benzyl-2-deoxy-α,β- -arabino-hexopyranosyl)-6-bro-
D
3
3
OCH2Ph), 4.23 (br. d, J4,5 = 9.3, 1 H, 4-H), 4.11 (td, J4,5 = 9.3,
mopurine (15a,b): Reaction of 1 with 6-bromopurine (600 mg,
3 mmol) gave 15a,b as a white solid (414 mg, 48%, α/β = 3/1), with
the starting material 1 being recovered in 23% yield (143 mg); m.p.
113.2–114.6 °C; Rf = 0.61 (EtOAc/petroleum ether, 1:1). IR (neat):
3J5,6A = J5,6B = 3.0 Hz, 1 H, 5-H), 3.73–3.72 (m, 2 H, 6A-H, 6B-
3
H), 3.06–2.97 (m, 1 H, 3Јax-H), 2.89–2.81 (m, 2J3Јax,3Јeq = 16.8 Hz,
1 H, 3Јeq-H) ppm. 13C NMR (100.62 MHz, CDCl3, 25 °C): δ =
192.4 (C-4Ј, C=O), 155.1, 149.3 (C-4Јa, C-8Јa), 139.5 (Cq, Ph),
132.6 (C-3), 129.5, 129.0, 128.5, 128.2, 126.8 (C-7Ј, CH, Ph), 126.2
(C-2), 119.8 (C-8Ј), 114.6 (C-5Ј), 94.8 (C-1), 80.4 (C-2Ј), 74.0, 72.0
(OCH2), 71.1 (C-4), 70.8 (C-5), 69.4 (C-6), 45.3 (C-3Ј) ppm.
HRMS: calcd. for C35H32O6 548.218761; found 548.219890.
ν = 1722, 1590, 1500, 1458, 1263 cm–1. UV: λ
(ε) = 240.5 nm
˜
max
(2376.92). 1H NMR (400.13 MHz, CDCl3, 25 °C) for 15a: δ = 8.57
(s, 1 H, 2-H), 8.25 (s, 1 H, 8-H), 7.28–7.09 (m, 15 H, Ph), 6.14 (br.
t, 3J1Ј,2Јax = 4.8, J1Ј,2Јeq = 4.4 Hz, 1 H, H-1Ј), 4.84, 4.81 (part A of
AB system, JAB = 10.8 Hz, OCH2Ph), 4.70–4.42 (m, 5 H, OCH2),
3
2
3
3
3
3.89 (ddd, J3Ј,4Ј = 7.5, J2Јax,3Ј = 8.8, J2Јeq,3Ј = 4.4, 1 H, 3Ј-H),
Propan-2-yl 4,6-Di-O-benzyl-2,3-dideoxy-1-thio-α-D-erythro-hex-2-
3.73–3.60 (m, 4 H, 4Ј-H, 5Ј-H, 6ЈA-H, 6ЈB-H), 3.32 (dt, 2J2Јeq,2Јax
14.0, J1Ј,2Јeq = J2Јeq,3Ј = 4.4 Hz, 1 H, 2Јeq-H), 2.20 (ddd, J1Ј,2Јax
=
enopyranoside (18): Reaction of 1 with propane-2-thiol (191 mg,
2.5 mmol) mediated by the zeolite gave 18 as a syrup [211 mg (55%)
in dichloroethane; 176 mg (46 %) in dichloromethane], with the
starting material 1 being recovered in 2% yield (10 mg) in dichloro-
ethane and 4% (20 mg) in dichloromethane; Rf = 0.61 (EtOAc/n-
3
3
3
2
3
= 4.8, J2Јeq,2Јax = 14.0, J2Јax,3Ј = 8.8 Hz, 1 H, 2Јax-H) ppm. 13C
NMR (100.62 MHz, CDCl3, 25 °C) for 15a: δ = 150.8 (C-2), 149.1
(C-4), 143.4 (C-8), 142.4 (C-6), 136.9, 136.7 (Cq, Ph), 133.6 (C-5),
128.7, 128.0, 127.5, 127.4, 126.9, 126.8 (CH, Ph), 79.5 (C-1Ј), 74.7
(C-4Ј), 74.4 (C-3Ј), 73.5 (C-5Ј), 72.9, 72.5, 70.6 (OCH2), 67.2 (C-6Ј),
30.6 (C-2Ј) ppm. C32H31BrN4O4 (615.52): calcd. C 62.44, H 5.08,
N 9.10; found C 62.27, H 5.23, N 9.12.
hexane, 1:6). [α]2D0 = –14 (c = 1, CH Cl ). IR (neat): ν = 1620 cm–1
˜
2
2
1
(C=C). UV: λmax (ε) = 246.5 nm (12134). H NMR (400.13 MHz,
CDCl3, 25 °C): δ = 7.22–7.11 (m, 10 H, Ph), 5.82 (d, 3J2,3 = 9.9 Hz,
3
4
3
1 H, 3-H), 5.72 (ddd, J1,2 = 3.0, J2,4 = 1.5, J2,3 = 9.9 Hz, 1 H,
2-H), 5.53 (d, J1,2 = 3.0 Hz, 1 H, 1-H), 4.58–4.28 (m, 4 H,
OCH2Ph), 4.13–4.07 (m, 2 H, 4-H, 5-H), 3.67–3.55 (m, 2 H, 6-H),
3.10–2.99 (q, J1Ј,2ЈA = J1Ј,2ЈB = 6.9 Hz, 1 H, 1Ј-H), 1.20–1.18 (m,
6 H, CH3) ppm. 13C NMR (100.62 MHz, CDCl3, 25 °C): δ = 138.3,
138.2 (Cq, Ph), 128.1 (C-3), 128.0 (C-2), 128.5, 128.4, 128.3, 127.7,
127.8 (CH-Ph), 79.8 (C-1), 73.3, 71.1 (OCH2Ph) 70.3 (C-4), 69.02
(C-5), 68.99 (C-6), 36.4 (SCH), 24.0, 23.9 (CH3) ppm. HRMS:
calcd. for C23H28O3 384.1745635; found 384.175915.
3
Typical Experimental Procedure for the Reaction of 1 with Octanol,
6-Hydroxyflavanone and Propane-2-thiol Mediated by HY Zeolite:
1,5-Anhydro-3,4,6-tri-O-benzyl-2-deoxy--arabino-hex-1-enitol (1;
417 mg, 1 mmol) and HY zeolite (160 mg, previously activated at
140 °C) were added to a solution of the nucleophile (2.5 mmol) in
dry dichloroethane (or dichloromethane) (4 mL) and the mixture
was stirred under reflux for 150 min. Addition of further solvent
(20 mL) was followed by filtration and evaporation of the filtrate
under reduced pressure. The residue obtained was purified by col-
umn chromatography with EtOAc/n-hexane mixtures to afford the
corresponding 2,3-unsaturated glycosides.
3
3
Acknowledgments
Octyl 4,6-Di-O-benzyl-2,3-dideoxy-α-D-erythro-hex-2-enopyrano-
The authors thank the Fundação para a Ciência e Tecnologia for
side (16): Reaction of 1 with octanol (326 mg, 2.5 mmol) mediated
by the zeolite gave 16 as a syrup [239 mg (54%) in dichloroethane;
196 mg (47%) in dichloromethane], with the starting material 1 be-
ing recovered in 2% yield (8 mg) in dichloroethane and 3% (13 mg)
in dichloromethane; Rf = 0.54 (EtOAc/n-hexane, 1:6). [α]2D0 = +33
fellowships.
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3
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2438
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© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2006, 2429–2439

Reactions of N-, S- and O-Nucleophiles with 3,4,6-Tri-O-benzyl--glucal
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Received: November 23, 2005
Published Online: March 16, 2006
Eur. J. Org. Chem. 2006, 2429–2439
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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