Synthesis of methoxy-substituted exocyclic (E)- and (Z)-unsaturated methyl pyranosides and a study of their reactivity towards lewis acids

Article abstract of DOI:10.1002/ejoc.200300105

The first synthesis of methoxy-substituted exocyclic (E) - and (Z)-unsaturated methyl pyranosides is reported involving the syn elimination of a selenoxide derivative as a key step. The rearrangement of these exocyclic enol ethers in the presence of TIBAL and DIBAL-H is also described. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200300105

FULL PAPER
Synthesis of Methoxy-Substituted Exocyclic (E)- and (Z)-Unsaturated Methyl
Pyranosides and a Study of Their Reactivity towards Lewis Acids
[a]
[a]
[a]
[b]
´
´
´ ˆ
Aurelie Deleuze, Matthieu Sollogoub, Yves Bleriot, Jerome Marrot, and
[a]
¨
Pierre Sinay*
´
Dedicated to Gerard Descotes in appreciation of his remarkable contribution to the
organic chemistry of carbohydrates
Keywords: Carbohydrates / Aluminum / Lewis acids / Carbocycles
The first synthesis of methoxy-substituted exocyclic (E)- and
(Z)-unsaturated methyl pyranosides is reported involving the
syn elimination of a selenoxide derivative as a key step. The
rearrangement of these exocyclic enol ethers in the presence
of TIBAL and DIBAL-H is also described.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
many biological processes.[10] We thus logically decided to
investigate the possible mode of action of TIBAL on oxy-
substituted enol ethers. As may be anticipated, the acetate
1 is not compatible with TIBAL and the putative rearrange-
ment failed.[11]
Compound 2 should be more suitable for the TIBAL re-
arrangement. To the best of our knowledge, this kind of
methoxy-substituted exocyclic (E)- and (Z)-unsaturated
methyl pyranosides has not been reported in the literature
so far, and we have only found two examples, 3[12] and 4[13]
(Figure 1), of endocyclic unsaturated derivatives in carbo-
hydrate chemistry combining these features.
The conversion of carbohydrates into carbocycles is an
attractive route for the synthesis of polyfunctionalised
carbocyclic derivatives from readily available sugar precur-
sors.[1] We have recently developed triisobutylaluminium-
(TIBAL-)[2] and TiCl3OiPr[3]-mediated carbocyclisations
which, in contrast with the classical Ferrier-II reaction,[4]
retain the anomeric substituent. This methodology has been
successfully applied to the synthesis of carbasugar ana-
logues of -idose,[5] S-, Se-, and C-arylglycosides,[6] and
di-[7] and trisaccharides.[8] As depicted in Scheme 1, the
Ferrier-II reaction has previously been extended to the con-
version, in acceptable yield, of the easily preparable acetyl-
ated enol ether 1 into a fully oxygenated cyclohexane de-
rivative.[9] This is a useful transformation, inasmuch as in-
ositols constitute a family of natural products involved in
Figure 1. Structure of the alkoxy derivatives 2Ϫ4
The difficulty associated with the synthesis of such com-
pounds has already been underlined by Jones and Scott in
their synthesis of 3:[12] ‘‘The oxyglycal 3 ... represents a new
class of acetal-protected oxyglycals, which is unavailable by
classic methods.’’ In carbohydrate chemistry, mixed O,Se-
acetals have previously been utilized to synthesise endo-[14]
and exocyclic unsaturated derivatives[15] as well as oxy-sub-
stituted endocyclic unsaturated derivatives.[16] We therefore
explored this option to provide an entry, so far unknown,
to alkoxy-substituted exocyclic unsaturated derivatives.
Scheme 1. Access to inositols from an acetylated enol ether by a
Ferrier-II reaction
[a]
´
´
Ecole Normale Superieure, Departement de Chimie, UMR
8642,
24 rue Lhomond, 75231 Paris, Cedex 05, France
Fax: (internat.) ϩ 33-1/44323397
E-mail: Pierre.Sinay@chimie.ens.fr
[b]
´
Institut Lavoisier, Universite de Versailles-Saint-Quentin
45, avenue des Etats-Unis, 78035 Versailles Cedex, France
2678
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300105
Eur. J. Org. Chem. 2003, 2678Ϫ2683

Exocyclic (E)- and (Z)-Unsaturated Methyl Pyranosides
FULL PAPER
Results and Discussion
The known aldehyde 5[17] was first easily converted into
the dimethyl acetal 6 as shown in Scheme 2.
Scheme 2. Synthesis of mixed O,Se-acetals 8 and 9; reagents and
conditions: i) CSA, MeOH, 50 °C, 76%; ii) BF3·OEt2, PhSeH, Ϫ10
°C (7/8/9 ϭ 1:5:5, 96%)
Figure 2. X-ray crystallographic structure of mixed O,Se-acetal 8
highly detrimental, affording only unwanted asymmetric
O,O-acetals, resulting from a nucleophilic substitution of
Aluminium selenolates, such as iBu2AlSePh[18] or Et2Al- the selenoxide. Thus, the use of various standard oxidation
SePh,[19] have been shown to convert symmetric O,O-acetals conditions such as NaIO4 in methanol or mCPBA only af-
into monoselenoacetals in good yield. In our case, these forded the O,O-acetals 6 and 12 in moderate yields without
reagents led only to undesired reactions. Such a transform- traces of the expected exocyclic unsaturated derivatives
ation has also been reported through the use of seleno- (Scheme 3). Such a behaviour has previously been ob-
phenol in the presence of Lewis acids. While the use of served.[24]
[20]
SnCl4
as a Lewis acid gave only the bis(selenophenyl)
Davis’ reagent,[25] known to perform an oxidation with-
[21]
acetal derivative 7, BF3·OEt2
allowed access to the de- out the release of a nucleophile, was then used[26] in the
sired mixed O,Se-acetals 8 and 9 in a gratifying 86% yield, presence of vinyl acetate to trap the released PhSeOH,[15]
as a 1:1 easily separable diastereoisomeric mixture. It is thus affording the methoxy-substituted exocyclic derivatives
noteworthy that the Lewis acid had to be added first, fol- 10 and 11 in 30 and 50% yield, from the acetals 8 and 9,
lowed, after 10 min of stirring, by the selenophenol. The respectively (Scheme 4). Finally, the use of Ti(OiPr)4 and
stereochemistry of the new stereogenic centre was eluci- tBuOOH[24,27] in the presence of anhydrous triethylamine,
dated by solving the crystal structure[22] of the mixed acetal proved to be the best conditions and gave the methoxy-
8 (Figure 2).
substituted exocyclic derivatives 10 and 11 in 60 and 77%
The following key step consisted of the oxidation of the yield from 8 and 9, respectively (Scheme 4). The expected
selenium atom of the mixed O,Se-acetals to afford the se- syn elimination of the selenoxide was confirmed by determi-
lenoxide, which should easily eliminate to provide the corre- nation of the stereochemistry of the newly formed double
sponding enol ether. A similar strategy has been reported bond. Compound 11 showed an NOE between 1-H and Cϭ
to synthesise a fluoro-substituted exocyclic unsaturated fu- COCH3 and between 6-H and CH2Ph at the C-4 position,
ranose derivative.[23] Preliminary studies demonstrated that demonstrating a (Z) geometry for the double bond. Fur-
the presence of a nucleophile in the reaction mixture is thermore, the observation of an NOE between 6-H and the
Scheme 3. Compounds obtained from mixed O,Se-acetals 8 and 9 under various oxidation conditions
Eur. J. Org. Chem. 2003, 2678Ϫ2683
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A. Deleuze, M. Sollogoub, Y. Bleriot, J. Marrot, P. Sinay¨
FULL PAPER
conversion into a carbocycle. The reaction is stereospecific,
but the absolute configuration of the created stereogenic
centre was not determined in this work. This is an exocyclic
variation of the isomerisation of a benzylated glycal de-
scribed by Descotes and Martin.[28] The (Z) isomer 11 was
next treated with diisobutylaluminium hydride (DIBAL-H)
in toluene at 50 °C to give, after careful chromatography,
pure compounds 15[29] and 16 in low yields. We propose
that the (Z) isomer 11 is first converted into 14, as in the
case of TIBAL. This asymmetric acetal thus generated at
C-6 is then nonselectively reduced, via an alkoxycarbenium
ion, to afford a mixture of 6-O-benzyl and -methyl ethers.
Likewise, the conjugation of the ring oxygen lone pairs with
the endocyclic double bond allows another reduction at C-
3. Treatment of the exocyclic unsaturated derivative 11 with
other Lewis acids such as TiCl4, SnCl4, AlBr3, BF3.OEt2,
TMSOTf, Cu(SO3CF3)2 or Hg(OAc)2 only afforded re-
arranged compounds and complex mixtures of products.
Conclusion
Scheme 4. Compounds obtained from pure mixed O,Se-acetals 8
and 9 under various oxidation conditions
In this work, we have developed a synthetic strategy to
obtain a so-far unknown category of sugar derivatives, that
is to say methoxy-substituted exocyclic (E)- and (Z)-unsatu-
rated methyl pyranosides. This is a very rare assembly of
functions, whose chemistry can now be explored. For ex-
ample, we have shown that the presence of a methoxy group
on the exocyclic unsaturated derivative completely turns off
the carbohydrate-carbocycle conversion and drives an al-
lylic rearrangement.
anomeric OCH3 for compound 10 confirmed the (E) ge-
ometry for this compound (Figure 3).
Experimental Section
Figure 3. NOEs observed for enol ethers 10 and 11
In conclusion, we have developed in this work a selective
General Methods: Melting points were recorded with a Büchi model
entry into the methoxy-substituted exocyclic unsaturated 535 m.p. apparatus and are uncorrected. 1H NMR spectra (δH)
were recorded with a Bruker AC 250 (250 MHz) or a Bruker DRX
500 (500 MHz) spectrometer. 13C NMR spectra (δC) were recorded
with a Bruker AC 250 (62.9 MHz) or a Bruker DRX 500
(100.6 MHz) spectrometer and multiplicities were assigned using
the DEPT sequence. All chemical shifts are quoted on the δ scale.
Mass spectra were recorded with a JMS-700 spectrometer using
fast atom bombardment (FAB-MS) or chemical ionisation (CI,
derivatives 10 and 11 from the easily available aldehyde 5.
These compounds are now available for a study of reac-
tions, such as the Ferrier-II reaction, similar to the trans-
formation depicted in Scheme 1. At this stage, the TIBAL-
or DIBAL-H-mediated potential rearrangement was inves-
tigated (Scheme 5).
Treatment of oxyglycals 10 or 11 with TIBAL in toluene
at 50 °C afforded the derivatives 13 or 14 in 47 and 44%
yield, respectively. These compounds are formed by an al-
NH3) as stated. Optical rotations were measured with
a
PerkinϪElmer 241 polarimeter with a path length of 1 dm. Con-
centrations are given in g/100 mL. Microanalyses were performed
´
lylic rearrangement, which is thus favoured over the desired by the microanalysis service of the Universite Pierre et Marie Curie,
Scheme 5. Reactivity of enol ethers towards TIBAL and DIBAL-H; reagents and conditions: i) TIBAL, toluene, 50 °C; ii) DIBAL-H,
toluene, Ϫ78 °C, 20%
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Exocyclic (E)- and (Z)-Unsaturated Methyl Pyranosides
FULL PAPER
3
Paris. Thin layer chromatography (TLC) was carried out on alu-
minium sheets coated with 60F254 silica, and plates were developed
using a spray of 0.2% w/v cerium() sulfate and 5% ammonium
3J1,2 ϭ 3.6, J2,3 ϭ 9.3 Hz, 1 H, 2-H), 3.50 (s, 3 H, CH3O) ppm.
13C NMR (400 MHz, CDCl3): δ ϭ 138.55, 138.24, 138.05 (3 ϫ
C
ipso), 133.64, 133.27 (2 ϫ aromatic C), 131.82, 130.12 (2 ϫ aro-
molybdate in 2  sulfuric acid. Flash chromatography was carried matic C), 129.14Ϫ127.31 (aromatic C), 98.01 (C-1), 81.68 (C-3),
out using Merck silica gel 60 (230Ϫ400 mesh). Solvents and com-
mercially available reagents were dried and purified before use ac-
cording to standard procedures.
80.36 (C-4), 80.04 (C-2), 74.25 (C-5), 75.72, 75.00, 73.39 (3 ϫ
CH2Ph), 55.48 (CH3O) 46.47 (C-6) ppm. MS (CI; NH3): m/z ϭ
778 [M ϩ NH4]ϩ. C40H40O5Se2 (758.66): calcd. C 63.33, H 5.31;
found C 63.77, H 5.67.
Methyl 2,3,4-Tri-O-benzyl-α-D-gluco-hexodialdo-1,5-pyranoside Di-
Further elution afforded the mixed O,Se-acetal 8 (3.8 g, 6 mmol,
43% yield) as a solid. [α]2D0 ϭ Ϫ9 (c ϭ 1.0, CHCl3); m.p. 118Ϫ119
°C (cyclohexane). 1H NMR (400 MHz, CDCl3): δ ϭ 7.66Ϫ7.19 (m,
20 H, aromatic H), 5.35 (d, 3J5,6 ϭ 0.9 Hz, 1 H, 6-H), 5.08 (d, 3J ϭ
methyl Acetal (6): Aldehyde 5 (7 g, 15.2 mmol) was dissolved in dry
methanol (200 mL) and camphorsulfonic acid (3.86 g, 15.2 mmol)
was added. The reaction mixture was stirred at 50 °C under argon
overnight and TLC (cyclohexane/ethyl acetate, 1:1) showed the ab-
sence of starting material (Rf ϭ 0.38) and formation of a new prod-
uct (Rf ϭ 0.7). The reaction mixture was neutralised with aq.
Na2CO3 (100 mL), washed with water and the aqueous layer was
extracted with ethyl acetate. The organic extracts were combined,
dried with MgSO4 and concentrated to afford an oil which was
purified by flash chromatography (cyclohexane/ethyl acetate, 5:1
then 3:1 then 1:1) to afford acetal 6 (5.84 g, 11.5 mmol, 76% yield)
as a colourless oil. [α]2D0 ϭ ϩ17 (c ϭ 0.9, CHCl3). 1H NMR
(400 MHz, CDCl3): δ ϭ 7.39Ϫ7.30 (m, 15 H, aromatic H), 5.02 (d,
3J ϭ 11.0 Hz, 1 H, CHPh), 4.91 (d, 3J ϭ 11.0 Hz, 1 H, CHPh),
4.85 (d, 3J ϭ 11.0 Hz, 1 H, CHPh), 4.82 (d, 3J ϭ 12.1 Hz, 1 H,
3
10.8 Hz, 1 H, CHPh), 4.98 (d, J ϭ 11.0 Hz, 1 H, CHPh), 4.86 (d,
3J ϭ 12.4 Hz, 1 H, CHPh), 4.85 (d, 3J ϭ 10.4 Hz, 1 H, CHPh),
3
3
4.74 (d, J ϭ 11.1 Hz, 1 H, CHPh), 4.72 (d, J1,2 ϭ 3.5 Hz, 1 H,
1-H), 4.72 (d, 3J ϭ 11.0 Hz, 1 H, CHPh), 4.18 (dd, J4,5 ϭ 9.3,
3
3J5,6 ϭ 0.9 Hz, 1 H, 5-H), 4.15 (t, J2,3 ϭ J3,4 ϭ 9.1 Hz, 1 H, 3-
3
3
H), 3.92 (t, J3,4 ϭ 3J4,5 ϭ 9.1 Hz, 1 H, 4-H), 3.67 (dd, J1,2 ϭ 3.5,
3J2,3 ϭ 9.1 Hz, 1 H, 2-H), 3.48, 3.47 (2 ϫ s, 2 ϫ 3 H, 2 ϫ CH3O)
ppm. 13C NMR (400 MHz, CDCl3): δ ϭ 138.51, 138.15, 138.00 (3
ϫ Cipso), 134.17 (aromatic C), 134.12 (aromatic C), 130.95Ϫ127.35
(aromatic C), 97.97 (C-1), 92.23 (C-6), 81.91 (C-3), 80.07 (C-2),
79.09 (C-4), 75.69, 74.82, 73.37 (3 ϫ CH2Ph), 74.06 (C-5), 57.81,
55.34 (2 ϫ CH3O) ppm. MS (CI; NH3): m/z ϭ 652 [M ϩ NH4]ϩ.
C35H38O6Se (633.63): calcd. C 66.34, H 6.04; found C 66.14, H
6.20.
3
3
CHPh), 4.68 (d, 3J ϭ 12.1 Hz, 1 H, CHPh), 4.68 (d, 3J1,2 ϭ 3.5 Hz,
3
1 H, 1-H), 4.64 (d, 3J ϭ 11.0 Hz, 1 H, CHPh), 4.53 (d, J5,6
ϭ
3
3
1.7 Hz, 1 H, 6-H), 4.02 (t, J2,3 ϭ J3,4 ϭ 9.3 Hz, 1 H, 3-H), 3.82
(dd, J4,5 ϭ 10.0, J5,6 ϭ 1.7 Hz, 1 H, 5-H), 3.63 (dd, J3,4 ϭ 9.3,
Further elution afforded the mixed O,Se-acetal 9 (3.8 g, 6 mmol,
43% yield) as a solid. [α]2D0 ϭ Ϫ6 (c ϭ 1.2, CHCl3); m.p. 76Ϫ77 °C
(cyclohexane). 1H NMR (400 MHz, CDCl3): δ ϭ 7.64Ϫ7.26 (m,
20 H, aromatic H), 5.28 (d, 3J5,6 ϭ 1.8 Hz, 1 H, 6-H), 5.03 (d, 3J ϭ
3
3
3
3J4,5 ϭ 10.0 Hz, 1 H, 4-H), 3.59 (dd, J1,2 ϭ 3.5, J2,3 ϭ 9.3 Hz, 1
H, 2-H), 3.48, 3.44, 3.41 (3 ϫ s, 3 ϫ 3 H, 3 ϫ CH3O) ppm. 13C
NMR (400 MHz, CDCl3): δ ϭ 138.75, 138.25, 138.07 (3 ϫ Cipso),
127.57Ϫ128.44 (aromatic C), 102.56 (C-6), 98.20 (C-1), 82.10 (C-
3), 79.66 (C-2), 78.13 (C-4), 75.73, 74.91, 73.40 (3 ϫ CH2Ph), 70.16
(C-5), 56.12, 55.53, 55.29 (3 ϫ CH3O) ppm. MS (CI; NH3): m/z ϭ
526 [M ϩ NH4]ϩ. C30H36O7 (508.6): calcd. C 70.85, H 7.13; found
C 70.76, H 7.32.
3
3
3
10.9 Hz, 1 H, CHPh), 4.91 (d, J ϭ 11.3 Hz, 1 H, CHPh), 4.86 (d,
3J ϭ 10.9 Hz, 1 H, CHPh), 4.85 (d, 3J ϭ 12.2 Hz, 1 H, CHPh),
3
3
4.70 (d, J ϭ 12.2 Hz, 1 H, CHPh), 4.69 (d, J1,2 ϭ 3.7 Hz, 1 H,
1-H), 4.57 (d, 3J ϭ 11.3 Hz, 1 H, CHPh), 4.21 (dd, J4,5 ϭ 9.5,
3
3J5,6 ϭ 1.8 Hz, 1 H, 5-H), 4.04 (t, J2,3 ϭ J3,4 ϭ 9.3 Hz, 1 H, 3-
3
3
H), 3.77 (dd, 3J3,4 ϭ 9.3, 3J4,5 ϭ 9.5 Hz, 1 H, 4-H), 3.61 (dd, 3J1,2 ϭ
3
3.7, J2,3 ϭ 9.3 Hz, 1 H, 2-H), 3.56, 3.23 (2 ϫ s, 2 ϫ 3 H, 2 ϫ
CH3O) ppm. 13C NMR (400 MHz, CDCl3): δ ϭ 138.67, 138.24,
137.99 (3 ϫ Cipso), 134.68 (aromatic C), 134.20 (aromatic C),
130.94Ϫ127.44 (aromatic C), 98.50 (C-1), 89.84 (C-6), 81.92 (C-3),
79.53 (C-2), 78.20 (C-4), 75.26 (C-5), 75.81, 75.00, 73.45 (3 ϫ
CH2Ph), 57.84, 55.79 (2 ϫ CH3O) ppm. MS (CI; NH3): m/z ϭ 652
[M ϩ NH4]ϩ. C35H38O6Se (633.63): calcd. C 66.34, H 6.04; found
C 66.67, H 6.30.
Methyl
glucopyranoside (7), Methyl (6R)-2,3,4-Tri-O-benzyl-6-O-methyl-6-
C-phenylseleno-α- -glucopyranoside (8) and Methyl (6S)-2,3,4-Tri-
O-benzyl-6-O-methyl-6-C-phenylseleno-α- -glucopyranoside (9):
2,3,4-Tri-O-benzyl-6-deoxy-6,6-di-C-phenylseleno-α-D-
D
D
Acetal 6 (7.2 g, 14.17 mmol) was dissolved in CH2Cl2 (40 mL) un-
der argon and the reaction mixture was cooled to Ϫ20 °C.
BF3·Et2O (1.44 mL, 11.34 mmol) was then added and the reaction
mixture was stirred at Ϫ20 °C for 10 min. Selenophenol (1.65 mL,
15.59 mmol) was then added and the reaction mixture stirred for
Methyl
(5E)-2,3,4-Tri-O-benzyl-6-C-methoxy-α-D-xylo-hex-5-
15 min at Ϫ20 °C and then left to warm to room temperature and enopyranoside (10). Method 1: Acetal 8 (1.0 g, 1.58 mmol) was dis-
stirred overnight. TLC monitoring (cyclohexane/ethyl acetate, 2:1) solved in dry dichloromethane (20 mL) under argon, and pyridine
showed the absence of starting material (Rf ϭ 0.37) and three new (0.65 mL, 7.89 mmol) and vinyl acetate (15 mL, 167.4 mmol) were
spots (Rf ϭ 0.68, 0.71, 0.74). The reaction mixture was then diluted
with CH2Cl2 (60 mL), cooled to 0 °C, neutralised with aq.
NaHCO3 (100 mL), and washed with water (100 mL). The organic
layer was dried with MgSO4 and concentrated under reduced press-
ure. Purification by careful flash chromatography (cyclohexane/
added consecutively. The reaction mixture was cooled to 0 °C and
a solution of Davis’ reagent (580 mg, 1.89 mmol) in dry dichloro-
methane (5 mL) was added dropwise. The reaction mixture was
allowed to warm to room temperature, stirred for 2 h and concen-
trated under reduced pressure. Purification by flash chromatogra-
ethyl acetate, 20:1 then 3:1) afforded Se,Se-acetal 7 (1.25 g, phy (cyclohexane/ethyl acetate, 10:1) afforded enediol 10 (225 mg,
1.64 mmol) as a yellow solid. [α]2D0 ϭ Ϫ133 (c ϭ 1.0, CHCl3); m.p.
0.47 mmol, 30% yield) as an oil. Method 2: Acetal 8 (200 mg,
80Ϫ81 °C (cyclohexane). 1H NMR (400 MHz, CDCl3): δ ϭ 0.316 mmol) was dissolved in dry dichloromethane (2 mL) under
7.52Ϫ7.02 (m, 25 H, aromatic H), 5.02 (d, 3J ϭ 10.7 Hz, 1 H,
argon and the solution cooled to 0 °C. Anhydrous triethylamine (75
µL, 0.536 mmol) was then added, followed by dropwise addition of
3
CHPh), 4.93 (d, J ϭ 11.1 Hz, 1 H, CHPh), 4.87 (br. s, 1 H, 6-H),
4.86 (d, 3J ϭ 12.1 Hz, 1 H, CHPh), 4.80 (d, 3J ϭ 10.8 Hz, 1 H, tBuOOH (5.5  in decane, 132 µL, 0.726 mmol) and Ti(OiPr)4 (94
CHPh), 4.73 (d, 3J ϭ 12.1 Hz, 1 H, CHPh), 4.72 (d, 3J1,2 ϭ 3.6 Hz,
µL, 0.316 mmol). The reaction mixture was stirred at 0 °C for
45 min. TLC monitoring (cyclohexane/ethyl acetate, 2:1) showed a
3
1 H, 1-H), 4.41 (d, 3J ϭ 11.2 Hz, 1 H, CHPh), 4.11 (dd, J4,5
ϭ
3
3
3
9.3, J5,6 ϭ 0.9 Hz, 1 H, 5-H), 4.01 (t, J2,3 ϭ J3,4 ϭ 9.1 Hz, 1 H, new product (Rf ϭ 0.54) and some remaining starting material
3-H), 3.93 (dd, J3,4 ϭ 9.1, J4,5 ϭ 9.3 Hz, 1 H, 4-H), 3.63 (dd,
3
3
(Rf ϭ 0.64). The reaction mixture was allowed to warm to room
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A. Deleuze, M. Sollogoub, Y. Bleriot, J. Marrot, P. Sinay¨
FULL PAPER
temperature and was concentrated under reduced pressure. Purifi-
cation by flash chromatography (cyclohexane/ethyl acetate, 7:1) af-
raphy (cyclohexane/ethyl acetate, 5:1 then 2:1 then 1:1) afforded an
inseparable diastereoisomeric mixture of acetals 12 (30 mg,
0.047 mmol, 31% yield). 1H NMR (400 MHz, CDCl3): δ ϭ
forded enediol 10 (90 mg, 0.189 mmol, 60% yield) as an oil. [α]2D0
ϭ
ϩ5 (c ϭ 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ 7.42Ϫ7.30 8.12Ϫ8.10 (m, 6 H, PhCl), 7.58 (m, 2 H, PhCl), 7.43Ϫ7.30 (m, 30
4
3
(m, 15 H, aromatic H), 6.25 (d, J4,6 ϭ 1.4 Hz, 1 H, 6-H), 4.85 (d,
H, aromatic H), 6.34 (d, 3J5,6 ϭ 1.4 Hz, 1 H, 6-H), 4.59 (d, J5,6
ϭ
3J ϭ 10.9 Hz, 1 H, CHPh), 4.84 (d, 2 H, 2 ϫ CHPh), 4.76 (d, 3J ϭ
1.5 Hz, 1 H, 6-HЈ), 5.05 (d, J ϭ 10.9 Hz, 1 H, CHPhЈ), 5.00 (d,
3
3
3
11.1 Hz, 1 H, CHPh), 4.72 (d, J ϭ 12.3 Hz, 1 H, CHPh), 4.64 (d,
3J ϭ 10.7 Hz, 1 H, CHPh), 4.98 (d, J ϭ 11.3 Hz, 1 H, CHPhЈ),
3J1,2 ϭ 3.1 Hz, 1 H, 1-H), 4.55 (d, 3J ϭ 11.2 Hz, 1 H, CHPh), 4.27
4.91Ϫ4.85 (m, 5 H, 3 ϫ CHPh, 2 ϫ CHPhЈ), 4.75 (d, J1,2
ϭ
3
3
4
3
(dd, J3,4 ϭ 6.5, J4,6 ϭ 1.4 Hz, 1 H, 4-H), 4.06 (dd, J2,3 ϭ 8.4, 1.6 Hz, 1 H, 1-HЈ), 4.72 (d, 2 H, CHPh, CHPhЈ), 4.70 (d, 3J ϭ
3J3,4 ϭ 6.5 Hz, 1 H, 3-H), 3.57 (dd, J1,2 ϭ 3.1, J2,3 ϭ 8.4 Hz, 1 11.1 Hz, 1 H, CHPhЈ), 4.61 (d, 3J ϭ 10.3 Hz, 1 H, CHPh), 4.09 (t,
3
3
H, 2-H), 3.63, 3.47 (2 ϫ s, 2 ϫ 3 H, 2 ϫ CH3O) ppm. 13C NMR 3J2,3 ϭ J3,4 ϭ 9.3 Hz, 1 H, 3-HЈ), 4.06 (t, J2,3 ϭ J3,4 ϭ 9.5 Hz,
3
3
3
3
4
(400 MHz, CDCl3): δ ϭ 139.14 (C-6), 138.57, 138.53, 138.31 (3 ϫ
1 H, 3-H), 4.02 (dd, J4,5 ϭ 10.1, J5,6 ϭ 1.4 Hz, 1 H, 5-HЈ), 3.93
4
3
3
C
ipso), 131.83 (C-5), 128.43Ϫ127.43 (aromatic C), 99.72 (C-1), 79.91 (dd, 3J4,5 ϭ 10.0, J5,6 ϭ 1.5 Hz, 1 H, 5-H), 3.73 (t, J3,4 ϭ J4,5
ϭ
3
3
(C-3), 78.13 (C-2), 76.84 (C-4), 74.60, 73.40, 72.82 (3 ϫ CH2Ph),
9.5 Hz, 1 H, 4-H), 3.62 (dd, J1,2 ϭ 4.5, J2,3 ϭ 9.5 Hz, 1 H, 2-H),
3
3
3
60.59, 55.73 (2 ϫ CH3O) ppm. MS (CI; NH3): m/z ϭ 494 [M ϩ 3.62 (dd, J1,2 ϭ 1.5, J2,3 ϭ 9.3 Hz, 1 H, 2-HЈ), 3.55 (dd, J3,4
ϭ
NH4]ϩ. HRMS: C29H36O6N: calcd. 494.2543; found 494.2547.
9.2, J4,5 ϭ 10.1 Hz, 1 H, 4-HЈ), 3.59, 3.48 (2 ϫ s, 2 ϫ 3 H, 2 ϫ
3
CH3OЈ), 3.39, 3.36 (2 ϫ s, 2 ϫ 3 H, 2 ϫ CH3O) ppm. 13C NMR
(400 MHz, CDCl3): δ ϭ 165.10 (CϭO), 164.68 (CϭOЈ), 138.56,
138.40, 137.58, 137.52, 134.67, 134.62 (6 ϫ Cipso), 133.50Ϫ127.65
(aromatic C), 98.26 (C-1), 97.93 (C-1Ј), 97.26 (C-6Ј), 97.09 (C-6),
82.00 (C-3Ј), 81.99 (C-3), 79.87 (C-2Ј), 79.44 (C-2), 77.54 (C-4Ј),
77.51 (C-4), 75.90, 75.78, 75.04, 74.83, 73.50, 73.42 (6 ϫ CH2Ph),
70.52 (C-5Ј), 70.45 (C-5), 57.86, 55.24 (2 ϫ CH3OЈ), 55.66, 55.09
(2 ϫ CH3OЈ) ppm. MS (CI; NH3): m/z ϭ 650 [M ϩ NH4]ϩ.
C36H37O8Cl (633.13): calcd. C 68.29, H 5.89; found C 68.65, H
6.23.
Methyl (5Z)-2,3,4-Tri-O-benzyl-6-C-methoxy-α- -xylo-hex-5-
D
enopyranoside (11). Method 1: Acetal 9 (1.1 g, 1.735 mmol) was dis-
solved in dry dichloromethane (33 mL) under argon, and pyridine
(0.7 mL, 8.68 mmol) and vinyl acetate (8 mL, 86.75 mmol) were
then added consecutively. The reaction mixture was cooled to 0
°C and a solution of Davis’ reagent (700 mg, 2.29 mmol) in dry
dichloromethane (4 mL) was added dropwise. The reaction mixture
was allowed to warm to room temperature, stirred for 2 h and
concentrated under reduced pressure. Purification by flash chroma-
tography (cyclohexane/ethyl acetate, 10:1) afforded enediol 11
(406 mg, 0.85 mmol, 50% yield) as an oil. Method 2: Acetal 9
(500 mg, 0.789 mmol) was dissolved in dry dichloromethane (4 mL)
under argon and the solution cooled to 0 °C. Anhydrous triethyl-
Methyl (6R or 6S)-2,3-Di-O-benzyl-6-C-benzyloxy-4,5-didehydro-4-
deoxy-6-O-methyl-α-
D-glucopyranoside (13): TIBAL (1.3 mL,
1.26 mmol) was added to a solution of enediol 10 (86 mg,
amine (188 µL, 1.34 mmol) was added, followed by dropwise ad- 0.181 mmol), dissolved in dry toluene (1 mL) under argon. The re-
dition of tBuOOH (5.5  in decane, 330 µL, 1.81 mmol) and action mixture was heated up to 50 °C for 1 h. TLC monitoring
Ti(OiPr)4 (236 µL, 0.789 mmol). The reaction mixture was stirred (cyclohexane/ethyl acetate, 3:1) showed conversion of the starting
at 0 °C for 45 min. TLC monitoring (cyclohexane/ethyl acetate, 2:1)
showed a new product (Rf ϭ 0.72) and some remaining starting
material (Rf ϭ 0.82). The reaction mixture was allowed to warm
to room temperature and was concentrated under reduced pressure.
Purification by flash chromatography (cyclohexane/ethyl acetate,
7:1) afforded enediol 11 (289 mg, 0.607 mmol, 77% yield) as an oil.
material (Rf ϭ 0.4) into three new products (Rf ϭ 0.40, 0.50, 0.55).
The reaction mixture was then cooled and hydrolised with water
(20 mL). The aqueous layer was extracted with ethyl acetate and
the organic phase was washed with water, dried with MgSO4, fil-
tered and concentrated. Purification by flash chromatography
(cyclohexane/ethyl acetate, 10:1) afforded 13 (40 mg, 0.084 mmol,
47% yield) as an oil. [α]2D0 ϭ Ϫ12 (c ϭ 1.2, CHCl3). 1H NMR
(400 MHz, CDCl3): δ ϭ 7.40Ϫ7.30 (m, 15 H, aromatic H), 5.36
1
[α]2D0 ϭ Ϫ131 (c ϭ 1.0, CHCl3). H NMR (400 MHz, CDCl3): δ ϭ
4
7.41Ϫ7.30 (m, 15 H, aromatic H), 5.95 (d, J4,6 ϭ 1.8 Hz, 1 H, 6-
H), 4.95 (d, 3J ϭ 10.9 Hz, 1 H, CHPh), 4.87 (d, 3J ϭ 10.9 Hz, 1 H, (dd, J3,4 ϭ 2.8, J4,6 ϭ 0.6 Hz, 1 H, 4-H), 4.93 (d, J1,2 ϭ 2.5 Hz,
3
4
3
CHPh), 4.85 (d, 3J ϭ 12.1 Hz, 1 H, CHPh), 4.84 (d, 3J ϭ 11.4 Hz, 1 1 H, 1-H), 4.89 (d, 4J4,6 ϭ 0.6 Hz, 1 H, 6-H), 4.86 (d, 3J ϭ 12.2 Hz,
3
H, CHPh), 4.74 (d, 3J ϭ 11.4 Hz, 1 H, CHPh), 4.74 (d, J1,2
ϭ
1 H, CHPh), 4.79 (d, 3J ϭ 12.2 Hz, 1 H, CHPh), 4.73 (d, 3J ϭ
3.5 Hz, 1 H, 1-H), 4.72 (d, 3J ϭ 12.9 Hz, 1 H, CHPh), 4.00 (dd,
11.8 Hz, 1 H, CHPh), 4.69 (d, J ϭ 12.1 Hz, 1 H, CHPh), 4.68 (d,
3
3J3,4 ϭ 8.6, 4J4,6 ϭ 1.8 Hz, 1 H, 4-H), 3.96 (t, 3J2,3 ϭ 3J3,4 ϭ 8.6 Hz, 3J ϭ 12.0 Hz, 1 H, CHPh), 4.60 (d, 3J ϭ 11.9 Hz, 1 H, CHPh),
3
3
3
3
3
1 H, 3-H), 3.62 (dd, J1,2 ϭ 3.5, J2,3 ϭ 8.6 Hz, 1 H, 2-H), 3.65,
4.35 (dd, J2,3 ϭ 7.3, J3,4 ϭ 2.8 Hz, 1 H, 3-H), 3.84 (dd, J1,2 ϭ
3.51 (2 ϫ s, 2 ϫ 3 H, 2 ϫ CH3O) ppm. 13C NMR (400 MHz,
2.6, J2,3 ϭ 7.3 Hz, 1 H, 2-H), 3.52, 3.39 (2 ϫ s, 2 ϫ 3 H, 2 ϫ
3
CDCl3): δ ϭ 138.65, 138.07, 138.01 (3 ϫ Cipso), 134.65 (C-6), CH3O) ppm. 13C NMR (400 MHz, CDCl3): δ ϭ 146.60 (C-5),
128.67 (C-5), 128.42Ϫ127.60 (aromatic C), 99.20 (C-1), 81.81 (C-
138.39, 138.12, 137.61 (3 ϫ Cipso), 128.39Ϫ127.59 (aromatic C),
3), 79.47 (C-2), 78.21 (C-4), 75.58, 74.37, 73.53 (3 ϫ CH2Ph), 60.41, 100.58 (C-4), 99.65 (C-1), 98.50 (C-6), 76.40 (C-2), 73.28 (C-3),
56.03 (2 ϫ CH3O) ppm. MS (CI; NH3): m/z ϭ 494 [M ϩ NH4]ϩ. 73.12, 71.44, 67.44 (3 ϫ CH2Ph), 56.72, 52.93 (2 ϫ CH3O) ppm.
C29H32O6 (476.56): calcd. C 73.09, H 6.77; found C 73.16, H 6.95.
Methyl 2,3,4-Tri-O-benzyl-6-O-methyl-6-C-(4-chlorobenzoyl)-α-
MS (CI; NH3): m/z ϭ 494 [M ϩ NH4]ϩ. HRMS: C29H36O6N:
calcd. 494.2543; found 494.2539.
D-
glucopyranoside (12): A 1:1 mixture of acetals 8 and 9 (100 mg,
Methyl (6S or 6R)-2,3-Di-O-benzyl-6-C-benzyloxy-4,5-didehydro-4-
0.158 mmol), dissolved in dry dichloromethane (2 mL), was cooled
deoxy-6-O-methyl-α-D-glucopyranoside (14): TIBAL (1.9 mL,
to Ϫ60 °C and a solution of mCPBA (28 mg, 0.166 mmol) in dry 1.89 mmol) was added to a solution of enediol 11 (128 mg,
dichloromethane (2 mL) was added. After 1 h, TLC monitoring
(cyclohexane/ethyl acetate, 2:1) showed a new spot. The reaction
mixture was diluted with dichloromethane (10 mL), neutralised
with aq. NaHCO3 (10 mL), and then washed with aq. NaCl
(10 mL) and water (10 mL). The organic layer was dried with
MgSO4, filtered and concentrated. Purification by flash chromatog-
0.267 mmol), dissolved in dry toluene (1 mL) under argon. The re-
action mixture was heated up to 50 °C for 1 h. TLC monitoring
(cyclohexane/ethyl acetate, 3:1) showed conversion of the starting
material (Rf ϭ 0.4) into two new products (Rf ϭ 0.50, 0.55). The
reaction mixture was then cooled and hydrolysed with water
(20 mL). The aqueous layer was extracted with ethyl acetate and
2682
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 2678Ϫ2683

Exocyclic (E)- and (Z)-Unsaturated Methyl Pyranosides
FULL PAPER
the organic phase was washed with water, dried with MgSO4, fil-
CH3O), 29.60 (C-3) ppm. MS (CI; NH3): m/z ϭ 282 [M ϩ NH4]ϩ.
tered and concentrated. Purification by flash chromatography HRMS: C15H21O4: calcd. 265.1440; found 265.1429.
(cyclohexane/ethyl acetate, 10:1) afforded 14 (56 mg, 0.117 mmol,
44% yield) as an oil. [α]2D0 ϭ Ϫ150 (c ϭ 0.9, CHCl3). 1H NMR
[1] [1a]
[1b]
(400 MHz, CDCl3): δ ϭ 7.43Ϫ7.30 (m, 15 H, aromatic H), 5.37
R. J. Ferrier, Top. Curr. Chem. 2001, 215, 277.
P. I .
3
4
3
(dd, J3,4 ϭ 2.9, J4,6 Ͻ 0.5 Hz, 1 H, 4-H), 4.91 (d, J1,2 ϭ 2.5 Hz,
1 H, 1-H), 4.90 (d, 4J4,6 Ͻ 0.5 Hz, 1 H, 6-H), 4.86 (d, 3J ϭ 12.2 Hz,
1 H, CHPh), 4.80 (d, 3J ϭ 12.2 Hz, 1 H, CHPh), 4.70 (d, 3J ϭ
Dalko, P. Sinay¨, Angew. Chem. 1999, 111, 819; Angew. Chem.
Int. Ed. 1999, 38, 773.
[2]
[3]
S. K. Das, J.-M. Mallet, P. Sinay¨, Angew. Chem. 1997, 109, 513;
Angew. Chem. Int. Ed. Engl. 1997, 36, 493.
M. Sollogoub, J.-M. Mallet, P. Sinay¨, Tetrahedron Lett. 1998,
39, 4871.
3
12.8 Hz, 1 H, CHPh), 4.69 (d, J ϭ 11.8 Hz, 1 H, CHPh), 4.68 (d,
3J ϭ 12.0 Hz, 1 H, CHPh), 4.61 (d, 3J ϭ 12.0 Hz, 1 H, CHPh),
3
3
3
4.36 (dd, J2,3 ϭ 7.3, J3,4 ϭ 2.9 Hz, 1 H, 3-H), 3.83 (dd, J1,2
ϭ
[4]
[5]
R. J. Ferrier, J. Chem. Soc., Perkin Trans. 1 1979, 1455.
3
2.5, J2,3 ϭ 7.3 Hz, 1 H, 2-H), 3.54, 3.41 (2 ϫ s, 2 ϫ 3 H, 2 ϫ
CH3O) ppm. 13C NMR (400 MHz, CDCl3): δ ϭ 146.69 (C-5),
138.35, 138.09, 137.62 (3 ϫ Cipso), 128.36Ϫ127.56 (aromatic C),
100.00 (C-4), 99.58 (C-1), 98.37 (C-6), 76.28 (C-2), 73.17 (C-3),
73.07, 71.36, 67.34 (3 ϫ CH2Ph), 56.66, 52.89 (2 ϫ CH3O) ppm.
MS (CI; NH3): m/z ϭ 494 [M ϩ NH4]ϩ. HRMS: C29H36O6N:
calcd. 494.2543; found 494.2539.
´
M. Sollogoub, A. J. Pearce, A. Herault, P. Sinay¨, Tetrahedron:
Asymmetry 2000, 11, 283.
[6]
[7]
[8]
M. Sollogoub, J.-M. Mallet, P. Sinay¨, Angew. Chem. 2000, 112,
370; Angew. Chem. Int. Ed. 2000, 35, 362.
A. J. Pearce, M. Sollogoub, J.-M. Mallet, P. Sinay¨, Eur. J. Org.
Chem. 1999, 2103.
A. J. Pearce, R. Chevalier, J.-M. Mallet, P. Sinay¨, Eur. J. Org.
Chem. 2000, 2203.
S. L. Bender, R. J. Budhu, J. Am. Chem. Soc. 1991, 113, 9883.
B. V. L. Potter, D. Lampe, Angew. Chem. 1995, 107, 2085; An-
gew. Chem. Int. Ed. Engl. 1995, 34, 1933.
P. Jenkins, personal communication.
Methyl
pyranoside (15) and Methyl 2-O-Benzyl-4,5-didehydro-3,4-dideoxy-
6-O-methyl-α- -glucopyranoside (16): A solution of enediol 11
2,6-Di-O-benzyl-4,5-didehydro-3,4-dideoxy-α-D-gluco-
[9]
[10]
D
[11]
[12]
[13]
(160 mg, 0.336 mmol) in dry toluene (2 mL) under argon was co-
oled to Ϫ78 °C. DIBAL-H (1.57 mL, 2.35 mmol) was then added
and the reaction mixture was stirred at Ϫ78 °C for 3 h, by which
time TLC monitoring (cyclohexane/ethyl acetate, 2:1) showed con-
version of the starting material (Rf ϭ 0.5) into two new products
(Rf ϭ 0.30, 0.45). The reaction mixture was warmed to room tem-
perature and then hydrolysed with water (20 mL). The aqueous
layer was extracted with ethyl acetate, the organic extracts were
combined, dried with MgSO4, filtered and concentrated. Purifi-
cation by flash chromatography (cyclohexane/ethyl acetate, 10:1)
afforded compound 15 (17 mg, 15%) as an oil. [α]2D0 ϭ ϩ75 (c ϭ
G. S. Jones, W. J. Scott, J. Am. Chem. Soc. 1992, 114, 1491.
D. Craig, J. P. Tierney, C. Williamson, Tetrahedron Lett. 1997,
38, 4153.
[14] [14a]
D. J. Goldsmith, D. C. Liotta, M. Volmer, W. Hoekstra,
[14b]
L. Waykole, Tetrahedron 1985, 41, 4873.
Castillon, Tetrahedron Lett. 1994, 35, 5513.
J.-M. Lancelin, J.-R. Pougny, P. Sinay¨, Carbohydr. Res. 1985,
136, 369.
M. Kassou, S.
´
[15]
[16]
[17]
[18]
G. Jaurand, J.-M. Beau, P. Sinay¨, J. Chem. Soc., Chem. Com-
mun. 1982, 701.
H. Hashimoto, K. Asano, F. Fuji, J. Yoshimura, Carbohydr.
Res. 1982, 104, 87.
Y. Nishiyama, S. Nakata, S. Hamanaka, Chem. Lett. 1991,
1775.
R. Hoffmann, R. Brückner, Chem. Ber. 1992, 125, 1957.
B. Hermans, L. Hevesi, J. Org. Chem. 1995, 60, 6141.
A. Krief, M. Hobe, E. Badaoui, J. Bousbaa, W. Dumont, A.
Nazih, Synlett 1993, 707.
Selected crystal structure data for 8: crystal system orthorhom-
bic; space group P212121; Z ϭ 4; cell parameters a ϭ 5.6945(6),
1
0.1, CHCl3). H NMR (400 MHz, CDCl3): δ ϭ 7.40Ϫ7.31 (m, 10
H, aromatic H), 5.01 (d, 3J1,2 ϭ 2.5 Hz, 1 H, 1-H), 4.89 (dd, 3J3,4 ϭ
3
4
3
2.4, J3Ј,4 ϭ 5.3, J4,6 Ͻ 0.5 Hz, 1 H, 4-H), 4.72 (d, J ϭ 12.5 Hz,
1 H, CHPh), 4.64 (d, 3J ϭ 12.5 Hz, 1 H, CHPh), 4.60 (d, 3J ϭ
12.1 Hz, 1 H, CHPh), 4.54 (d, 3J ϭ 12.0 Hz, 1 H, CHPh), 3.87 (br.
[19]
[20]
[21]
3
3
3
s, 2 H, 6-H, 6-HЈ), 3.75 (ddd, J1,2 ϭ 2.5, J2,3 ϭ 10.1, J2,3Ј
ϭ
3
[22]
6.7 Hz, 1 H, 2-H), 3.54 (s, 3 H, CH3O), 2.28Ϫ2.23 (m, J2,3
ϭ
3
3
10.1, J2,3Ј ϭ 6.7, J3,4 ϭ 2.4 Hz, 2 H, 3-H, 3-HЈ) ppm. 13C NMR
(400 MHz, CDCl3): δ ϭ 146.10 (C-5), 138.02, 138.00 (2 ϫ Cipso),
128.44Ϫ127.58 (aromatic C), 99.09 (C-4), 97.34 (C-1), 72.11 (C-2),
72.10, 71.29(2 ϫ CH2Ph), 69.57 (C-6), 55.97 (CH3O), 29.69 (C-3)
ppm. MS (CI; NH3): m/z ϭ 358 [M ϩ NH4]ϩ. HRMS: C21H28O4N:
calcd. 358.2018; found 358.2016. Ref.[29] 1H NMR (270 MHz,
b ϭ 22.663(2), c ϭ 24.575(2); radiation (Mo-Kα) λ ϭ 0.71073
˚
A; 382 variables for 4573 reflections; final R ϭ 0.0723, Rw
ϭ
0.0683; CCDC-203167 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from
the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
3
3
CDCl3): δ ϭ 4.98 (d, J1,2 ϭ 2.2 Hz, 1 H, 1-H), 4.86 (dd, J3,4
ϭ
3
2.6, J3Ј,4 ϭ 5.1 Hz, 1 H, 4-H).
Further elution afforded compound 16 (5 mg, 5%) as an oil. [α]2D0
ϭ
[23]
[24]
M. J. Robins, S. F. Wnuk, K. B. Mullah, N. K. Dalley, J. Org.
Chem. 1994, 59, 544.
ϩ35 (c ϭ 0.1, CHCl3). 1H NMR (400 MHz, CDCl3): δ ϭ
3
`
A. P. Brunetiere, J. Y. Lallemand, Tetrahedron Lett. 1988, 29,
7.42Ϫ7.32 (m, 5 H, aromatic H), 5.00 (d, J1,2 ϭ 2.5 Hz, 1 H, 1-
3
3
4
2179.
H), 4.89 (ddd, J3,4 ϭ 2.4, J3Ј,4 ϭ 5.1, J4,6 Ͻ 0.5 Hz, 1 H, 4-H),
[25]
[26]
F. A. Davis, O. D. Stringer, J. Org. Chem. 1982, 47, 1774.
J. C. Anderson, S. V. Ley, D. Santafianos, R. N. Sheppard,
Tetrahedron. 1991, 47, 6813.
4.72 (d, 3J ϭ 12.4 Hz, 1 H, CHPh), 4.63 (d, 3J ϭ 12.4 Hz, 1 H,
3
3
CHPh), 3.83 (br. s, 2 H, 6-H, 6-HЈ), 3.75 (ddd, J1,2 ϭ 2.5, J2,3
10.5, J2,3Ј ϭ 6.8 Hz, 1 H, 2-H), 3.55, 3.38 (2 ϫ s, 2 ϫ 3 H, 2 ϫ
CH3O), 2.40Ϫ2.21 (m, J2,3 ϭ 10.5, J2,3Ј ϭ 6.8, J3,4 ϭ 2.5 Hz, 2
H, 3-H, 3-HЈ) ppm. 13C NMR (400 MHz, CDCl3): δ ϭ 145.95 (C-
5), 138.00 (Cipso), 128.49Ϫ127.55 (aromatic C), 99.21 (C-4), 99.37
(C-1), 72.14 (C-6), 72.10 (C-2), 71.29 (CH2Ph), 57.92, 55.95 (2 ϫ
ϭ
3
[27]
´
´
Y. D ı az, A. El-Laghdach, M. I. Matheu, S. Castillon, J. Org.
Chem. 1997, 62, 1501.
3
3
3
[28]
[29]
G. Descotes, J.-C. Martin, Carbohydr. Res. 1977, 56, 168.
Y. Shibata, Y. Kosuge, S. Ogawa, Carbohydr. Res. 1990, 199, 37.
Received February 18, 2003
Eur. J. Org. Chem. 2003, 2678Ϫ2683
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2683