Triisobutylaluminium (TIBAL) promoted rearrangement of C-glycosides

Article abstract of DOI:10.3390/10080843

Triisobutylaluminium-promoted rearrangement of unsaturated glycosides containing electron-donating aglycons, such as C-aryl glycosides, provides direct access to highly functionalised cyclohexane derivatives.

Full text of DOI:10.3390/10080843

Molecules 2005, 10, 843-858
molecules
ISSN 1420-3049
http://www.mdpi.org
Triisobutylaluminium (TIBAL) Promoted Rearrangement of
C-glycosides
Matthieu Sollogoub* and Pierre Sinaÿ
Ecole Normale Supérieure, Département de Chimie, UMR 8642 : CNRS-ENS-UPMC Paris 6, 24 rue
Lhomond, 75231 Paris Cedex 05, France; http://www.chimie.ens.fr/UMR8642/Glycoscience/index.html
* Author to whom correspondence may be addressed; e-mails: Matthieu.Sollogoub@ens.fr
Received: 8 October 2004; in revised form: 4 November 2004 / Accepted: 10 November 2004
Published: 31 August 2005
Abstract: Triisobutylaluminium-promoted rearrangement of unsaturated glycosides
containing electron-donating aglycons, such as C-aryl glycosides, provides direct access to
highly functionalised cyclohexane derivatives.
Keywords: Carbohydrates, C-glycosides, carbocycles, rearrangements
Introduction
The conversion of carbohydrates into carbocycles provides a powerful method for the preparation of
highly functionalised enantiomerically pure carbocycles. The pyranose-cyclohexane conversion has
received particular attention due to the myriad of bioactive substances such as aminocyclitols, inositols
and carbasugars, which are attainable. Among those a more complex one has attracted particular
attention: pancratistatine [1-3] (Figure 1). It is a polyfunctionalised cyclohexane directly connected to
an aromatic ring.
The classical Ferrier-II reaction [2] involving Hg(II) catalysed rearrangement of readily available
hex-5-enopyranosides into cyclohexanones has, thus far, been the most widely exploited. In 1997 we
reported that the same starting material used for the Ferrier-II reaction, carbohydrate based vinyl acetals
(hex-5-enopyranosides) such as 1, undergo smooth reductive rearrangement with triisobutylaluminium
(TIBAL) to afford highly functionalized cyclohexanes such as 2 (Scheme 1) [3].

Molecules 2005, 10
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Figure 1
HO
HO
OH
OH
O
O
NH
O
OH
(+)-pancratistatine
In sharp contrast with the Ferrier-II reaction, this rearrangement proceeds with retention of the
aglycon moiety, due to initial endo-glycosidic bond cleavage leading to a carbacationic intermediate A
stabilised by the methoxy group. On the other hand, the original anomeric configuration is preserved.
Scheme 1
AliBu3
O
O
TIBAL
BnO
BnO
BnO
BnO
BnO
BnO
OMe
BnO
OMe
1
A.L.
O
endo-cleavage
BnO
BnO
Cyclisation
reduction
BnO
OBn
OH
BnO
OMe
OMe
2
A
We next reasoned that it should be possible to replace the methoxy group by other electron-donating
groups (EDG) that would stabilise the analogous carbacationic intermediate B and therefore promote
endo cleavage. (Scheme 2) We would like to concentrate in this article on C-glycosides and provide a
full experimental account of our preliminary results [4].
Scheme 2
O
O
TIBAL
BnO
BnO
BnO
BnO
EDG
EDG
OBn
OBn
EDG : electron-donating group
B

Molecules 2005, 10
845
Results and Discussion
The C-aryl-glycosides are a family of C-glycosides possessing an electron-donating aglycon, and
their carbocyclisation could constitute a new entry into pancratistatine and similar structures. To test
this hypothesis we first synthesised the unsaturated C-phenyl glycoside 7. Starting from
acetobromoglucose 3 [5] we introduced the phenyl group using a Grignard reagent and then
reacetylated to obtain the C-glucoside 4 [6]. Selective iodination, elimination, and protecting group
exchange afforded the unsaturated C-phenyl glucoside 7 (Scheme 3).
Scheme 3.
OAc
OAc
I
O
i, ii
O
O
iii-v
AcO
AcO
AcO
AcO
AcO
AcO
OAc
OAc
OAc
Br
4, 62 %
5, 74 %
3
O
O
vii, viii
vi
AcO
AcO
BnO
BnO
OAc
6, 73 %
OBn
7, 68 %
Reagents and conditions: i) PhMgBr, Et2O, reflux, 1 hour; ii) Ac2O, Pyr., R.T., 12 hours; iii) MeONa,
MeOH, R.T., 5 hours; iv) I2, PPh3, DMF, R.T., 45 min.; v) Ac2O, Pyr., R.T., 4 hours; vi) DBU, THF, reflux,
3 hours; vii) MeONa, MeOH, 12 hours; viii) BnBr, NaH, DMF, R.T., 5 hours.
Compound 7 was then reacted with TIBAL and gave the desired carbocycle 8 (35 %) along with the
de-O-benzylated [7] open-chain product 9 (35 %).
Scheme 4.
HO
O
BnO
BnO
BnO
HO
BnO
BnO
i
OBn
OBn
9, 35%
Reagents and conditions: i) TIBAL (10 eq.), Toluene, 50 °C, 12 hours
OBn
OH
7
8, 35%
Product 9 is the result of an overall reductive cleavage of the endocyclic C5-O bond, a reaction
which has already been described in enol ethers [8,9]. A hydro-alumination-elimination mechanism, as
shown in Scheme 5, may explain this process.

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846
Scheme 5
O
BnO
HO
BnO
BnO
HO
Ph
Ph
OBn
OBn
7
9
hydroalumination
debenzylation
AliBu2
AliBu2
O
O
elimination
BnO
BnO
BnO
BnO
Ph
Ph
H
OBn
OBn
The reaction was here slower than usual, indicating that the phenyl might not be a strong enough
EDG. We therefore turned our attention to anisole as EDG and synthesised unsaturated compound 13 in
the same manner as 7 via the known 10 [10]. (Scheme 6)
Scheme 6.
OAc
OAc
I
OMe
OMe
i, ii
O
O
iii-v
O
AcO
AcO
AcO
AcO
AcO
AcO
OAc
OAc
OAc
Br
10, 52 %
11, 61 %
3
OMe
OMe
O
O
vii, viii
vi
AcO
AcO
BnO
BnO
OAc
12, 68 %
OBn
13, 62 %
Reagents and conditions: i) (MeO)PhMgBr, Et2O, reflux, 1 hour; ii) Ac2O, Pyr., R.T., 12 hours; iii) MeONa,
MeOH, R.T., 5 hours; iv) I2, PPh3, DMF, R.T., 45 min.; v) Ac2O, Pyr., R.T., 8 hours; vi) DBU, THF, reflux,
3 hours; vii) MeONa, MeOH, 12 hours; viii) BnBr, NaH, DMF, R.T., 5 hours.
Under the action of TIBAL compound 13 only gave 10 % of the open-chain product 16 and 86 % of
a mixture of expected carbocycles 14 and 15 in a 4/1 ratio. (Scheme 7)

Molecules 2005, 10
847
Scheme 7.
OMe
OMe
BnO
OMe
X
O
HO
i
BnO
BnO
BnO
BnO
OBn
BnO
OBn
OBn
Y
13
14, 68%, X=H, Y=OH
15, 18 %, X=OH, Y=H
16, 10%
Reagents and conditions: i) TIBAL (6 eq.), Toluene, 50 °C, 1 hour
To achieve the demonstration that a better EDG gives a better reaction we synthesised compound
20, using again the same methodology, except for the C-glycosylation of trimethoxybenzene to give
C-glucoside 17 [11]. (Scheme 8)
Scheme 8.
OAc
OAc
I
OMe
ii-iv
OMe
MeO
O
MeO
O
i
O
AcO
AcO
AcO
AcO
AcO
AcO
OAc
OAc
OAc
OMe
OMe
Br
3
17, 57 %
18, 65 %
MeO
O
OMe
vi, vii
OMe
MeO
O
v
AcO
AcO
BnO
BnO
OAc
OBn
OMe
OMe
19, 71 %
20, 88 %
Reagents and conditions: i) Ph(OMe)3, ZnO, M.S., ClCH2CH2Cl, reflux, 30 min.; ii) MeONa, MeOH, R.T.,
5 hours; iii) I2, PPh3, DMF, R.T., 45 min.; iv) Ac2O, Pyr., R.T., 4 hours; v) DBU, THF, reflux, 2 hours; vi)
MeONa, MeOH, 12 hours; vii) BnBr, NaH, DMF, R.T., 2 hours.
Indeed, when compound 20 is submitted to the action of TIBAL, carbocyclic products 21 and 22 are
the only ones obtained in a 3:2 molar ratio. (Scheme 9)
Scheme 9.
MeO
O
MeO
OMe
OMe
X
i
BnO
BnO
BnO
BnO
OBn
OBn
OMe
Y
OMe
20
21, 57%, X=H, Y=OH
22, 38 %, X=OH, Y=H
Reagents and conditions: i) TIBAL (5 eq.), Toluene, 50 °C, 30 min.

Molecules 2005, 10
848
To really complete the demonstration, we also need to show that a weak EDG only induces the ring
opening. To that end we selected the known C-butyl unsaturated derivative 27 [12]. Its synthesis, shown
in Scheme 10, is slightly different from the previous ones and starts from lactone 23 [13] (Scheme 10).
Scheme 10.
OBn
OBn
OH
i, ii
iii, iv
O
O
O
BnO
BnO
BnO
BnO
BnO
BnO
nBu
nBu
OBn
OBn
OBn
O
23
24, 88 %
25, 85 %
I
vi
O
v
O
BnO
BnO
BnO
BnO
nBu
nBu
OBn
27, 92 %
OBn
26, 94 %
Reagents and conditions: i) BuLi, Et2O, -78 °C, 30 min.; ii) Et3SiH, BF3.OEt2, CH2Cl2, -78 °C, 30 min.; iii)
TFA, Ac2O, R.T., 2 hours, iv) MeOH, MeONa, R.T., 10 min.; v) I2, PPh3, Imidazole, toluene, 70 °C, 30
min.; vi) DBU, THF, 70 °C, 1 hour.
Compound 27 reacts with TIBAL to give a single open-chain product 28 [14], hence achieving our
demonstration. (Scheme 11)
Scheme 11.
O
BnO
BnO
BnO
BnO
HO
i
nBu
nBu
OBn
OBn
27
28, 82%
Reagents and conditions: i)TIBAL (5 eq.), toluene, 50 °C, 2 hours 30 min.
Conclusions
We have demonstrated that unsaturated C-glycosides could be carbocyclised by the action of
TIBAL, provided that the aglycon is sufficiently electron-donating in nature. Among other applications,
this reaction opens a new access to compounds of the pancratistatine family.
Experimental Section
General
Melting points were recorded on a Büchi 510 apparatus and are uncorrected. Optical rotations were
measured on a Perkin Elmer 241 digital polarimeter with a path length of 1 dm. Mass spectra were
recorded on a Nermag R10-10 spectrometer, using chemical ionisation with ammonia. Elemental

Molecules 2005, 10
849
analyses were performed by the Service d'Analyse de l'Université Pierre et Marie Curie, 75252 Paris
Cedex 05, France. NMR spectra were recorded on a Brüker AM-400 (400 MHz and 100.6 MHz, for 1H
13
1
13
and C, respectively) or Brüker AC-250 (250 MHz and 63 MHz, for H and C, respectively) using
CDCl3 as solvent and TMS as internal standard. TLC was performed on silica gel 60 F254 (Merck) and
developed by charring with conc. H2SO4. Flash column chromatography was performed using silica gel
60 (230-400 mesh, Merck).
(2,3,4-Tri-O-acetyl-6-deoxy-6-iodo-β-D-glucopyranosyl) benzene (5)
I
O
AcO
AcO
OAc
A catalytic amount of sodium is added to a solution 4 (3.74 g, 6.7 mmol) in methanol (40 mL), and
the solution is stirred for 5 hours. It is then neutralised using IR 120 (H+) resin, filtered and evaporated
in vacuo. The residue is dissolved in anhydrous DMF (15 mL), then PPh3 (4.8 g, 13.4 mmol) is added
and the solution is cooled to 0 °C under argon. A solution of diiodine (4.6 g, 13.4 mmol) in anhydrous
DMF (5 mL) is then added dropwise and the solution stirred for 45 min at R.T, until the completion of
the reaction is detected by TLC (9:1 dichloromethane/MeOH). The solvent is evaporated and the
residue is next dissolved in pyridine (20 mL) and acetic anhydride (10 mL). The reaction, monitored by
TLC (7:3 cyclohexane/AcOEt), is complete in 4 hours at R.T. The solvent is then removed in vacuo and
the residue purified by silica gel flash column chromatography (1:4 AcOEt/cyclohexane) to afford
20
compound 5 (2.9 g, 74 %) as a white solid. [α] = + 6 (c = 1.25, CHCl3); m.p. = 162-163 °C
D
(AcOEt/cyclohexane); 1H-NMR (250 MHz): δ = 7.31-7.20 (5H, H arom.), 5.29 (t, 1H, J2,3 = 9.4 Hz, J3,4
= 9.4 Hz, H-3), 5.06 (dd, 1H, J4,5 = 9.4 Hz, H-4), 5.05 (dd, 1H, J1,2 = 9.7 Hz, H-2), 4.38 (d, 1H, H-1),
3.46 (ddd, 1H, J5,6a = 3.0 Hz, J6b,5 = 5.7 Hz, H-5), 3.34 (dd, 1H, J6b,6a = 11.1 Hz, H-6a), 3.16 (dd, 1H, H-
13
6b), 2.02, 1.94, 1.74 (3 x s, 3 x 3H, 3 x Ac); C-NMR (63 MHz): δ = 170.2, 169.2, 168.6 (3 x Ac),
136.1 (C arom. quat.), 128.7, 128.3, 126.9 (5 C arom.), 79.6 (C-1), 76.3 (C-5), 73.7 (C-3), 72.7 (C-2),
72.4 (C-4), 20.6, 20.5, 20.2 (3 x Ac), 3.9 (C-6); MS m/z 494 (M+NH4)+; Anal. calc. C, 45.39; H, 4.44;
found. C, 45.51; H, 4.51.
(2,3,4-Tri-O-acetyl-6-desoxy-β-D-xylo-hex-5-enopyranosyl) benzene (6)
O
AcO
AcO
OAc
Compound 5 (2.9 g, 6.7 mmol) is dissolved in dry THF (30 mL) and DBU (6.1 mL, 40.6 mmol) is
added. The mixture is heated at 70 °C until after 3 hours the end of the reaction is detected by TLC (7:3
cyclohexane/AcOEt). The solvent is then removed in vacuo and the residue purified by silica gel flash
column chromatography (1:5 AcOEt/cyclohexane) to afford compound 6 (1.7 g, 73 %) as a white solid.
20
[α] = -53 (c = 1.2, CHCl3); m.p. = 132 °C (AcOEt/cyclohexane); 1H-NMR (250 MHz): δ = 7.32-7.22
D

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(5H, H arom.), 5.59-5.51 (m, 1H, H-4), 5.29-5.12 (m, 2H, H-3, H-2), 4.79 (s, 1H, H-6a), 4.51 (s, 1H,
H-6b), 4.49-4.39 (m, 1H, H-1), 2.09, 1.96, 1.74 (3 x s, 3 x 3H, 3 x Ac); 13C-NMR (63 MHz): δ = 170.1,
169.3, 168.8 (3 x Ac), 153.8 (C-5), 135.9 (C arom. quat.), 129.1, 128.5, 127.1 (5 C arom.), 96.5 (C-6),
80.8 (C-1), 73.4 (C-3), 72.7 (C-2), 69.6 (C-4), 20.7, 20.6, 20.3 (3 x Ac); MS: m/z 366 (M+NH4)+; 349
(M+H)+; Anal. calc. C, 62.06; H, 5.79; found. C, 62.05; H, 5.88.
(2,3,4-Tri-O-benzyl-6-desoxy-β-D-xylo-hex-5-enopyranosyl) benzene (7)
O
BnO
BnO
OBn
A catalytic amount of sodium is added to a solution 6 (1.1 g, 3.2 mmol) in methanol (10 mL) and the
solution is stirred for 12 hours. The solvent is evaporated without neutralisation and the residue
dissolved in dry DMF (100 mL) to which benzyl bromide (4.4 mL, 32 mmol) and NaH (0.9 g, 60% in
suspension in oil, 19.2 mmol) are added. The mixture is stirred at R.T. until the end of the reaction is
detected after 5 hours by TLC (9:1 cyclohexane/AcOEt ). Excess NaH is quenched with methanol, and
the mixture is extracted with ether and washed with water. The organic layer is dried (MgSO ), filtered
4
and concentrated. The residue is purified by silica gel flash column chromatography (1:99
20
AcOEt/cyclohexane) to afford compound 7 (1.05 g, 68 %) as a white solid. [α] = -51 (c = 1.1,
D
CHCl3); m.p. = 71 °C (AcOEt/cyclohexane); 1H-NMR (250 MHz): δ = 7.31-6.92 (20H, H arom.), 4.70
(d, 1H, J = 11.3 Hz, -CHPh), 4.65 (d, 1H, J = 11.7 Hz, -CHPh), 4.63 (s, 1H, H-6a), 4.59 (d, 1H, J = 11.2
Hz, -CHPh), 4.53 (d, 1H, J = 11.5 Hz, -CHPh), 4.53 (s, 1H, H-6b), 4.37 (d, 1H, J1,2 = 9.7 Hz, H-1),
4.19 (d, 1H, J = 10.5 Hz, -CHPh), 3.91 (d, 1H, J4,3 = 7.4 Hz, H-4), 3.64 (d, 1H, J = 11.9 Hz, -CHPh),
3.62 (t, 1H, J2,3 = 7.7 Hz, H-3), 3.47 (dd, 1H, H-2); 13C-NMR (63 MHz): δ = 156.6 (C-5), 138.7, 138.5,
138.0, 137.7 (4 C arom. quat.), 128.6-127.7 (20 C arom.), 95.2 (C-6), 84.7 (C-3), 83.7 (C-2), 81.3 (C-1),
79.3 (C-4), 74.7, 74.6, 73.0 (3 CHPh); MS :m/z 510 (M+NH4)+; Anal. calc. C, 80.46; H, 6.64; found. C,
80.45; H, 6.59.
(1R,2S,3S,4R,5R)-2,3,4-Tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) benzene (8) and 2,4-di-O-benzyl-
5,6-dehydro-1-C(S)-phenyl-D-glucitol (9)
A solution of TIBAL (0.6 mL, 0.6 mmol, 1M in toluene) is added to a solution of 7 (55 mg, 0.11
mmol) in dry toluene (1 mL) at R.T. under argon. The mixture is stirred at 50 °C for 12 hours, until the
end of the reaction is detected by TLC (4:1 cyclohexane/AcOEt). The mixture is cooled to R.T. and
water (2 mL) is slowly added, and stirred for 15 min. After extraction with AcOEt (3 x 10 mL) and
washing with water (10 mL) the organic layer is dried (MgSO ), filtered and the solvent is evaporated.
4
The residue purified by silica gel flash column chromatography (1:9 AcOEt/cyclohexane) to afford two
major products 8 (18 mg, 35 %), as a white solid, and 9 (16 mg, 35 %) as an oil.

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(1R,2S,3S,4R,5R)-2,3,4-Tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) benzene (8)
BnO
BnO
OBn
OH
20
1
[α] = -24 (c = 0.6, CHCl3); m.p. = 96 °C (AcOEt/cyclohexane); H-NMR (250 MHz): δ = 7.42-6.90
D
(20H, arom. H), 4.85 (d, 1H, J = 10.8 Hz, -CHPh), 4.79 (d, 1H, J = 10.8 Hz, -CHPh), 4.72 (d, 1H, J =
11.5 Hz, -CHPh), 4.64 (d, 1H, J = 11.5 Hz, -CHPh), 4.41 (d, 1H, J = 10.2 Hz, -CHPh), 4.17-4.09 (m,
1H, H-5), 3.88 (t, 1H, J2,3 = 9.2 Hz, J3,4 = 9.2 Hz, H-3), 3.82 (d, 1H, J = 10.2 Hz, -CHPh), 3.53 (dd, 1H,
J4,5 = 3.0 Hz, H-4), 3.47 (dd, 1H, J1,2 = 9.1 Hz, H-2), 3.27 (ddd, 1H, J1,6a = 11.0 Hz, J1,6e = 3.7 Hz, H-1),
13
2.50 (br s, 1H, -OH), 2.04 (dt, 1H, J6e,6a = 14.5 Hz, J6e,5 = 3.7 Hz, H-6e), 1.65 (br t, 1H, H-6a); C-
NMR (63 MHz):δ = 142.4, 139.0, 138.3, 138.1 (4 C arom. quat.), 128.6-126.7 (20 C arom.), 86.0 (C-2),
83.4 (C-3), 83.3 (C-4), 76.0, 75.4, 72.8 (3 CHPh), 66.8 (C-5), 42.8 (C-1), 34.3 (C-6); MS: m/z 512
(M+NH4)+; Anal. calc. C, 80.13; H, 6.93; found. C, 79.95; H, 7.08.
2,4-Di-O-benzyl-5,6-dehydro-1-C(S)-phenyl-D-glucitol (9)
HO
BnO
HO
OBn
20
[α] = -2 (c = 0.3, CHCl3); 1H-NMR (400 MHz): δ = 7.39-7.29 (15H, arom. H), 5.54 (ddd, 1H, J5,6a
=
D
10.5 Hz, J5,6b = 17 Hz, J5,4 = 8 Hz, H-5), 5.33 (dd, 1H, J6a,6b = 1.5 Hz, H-6a), 5.23 (dd, 1H, H-6b), 5.20
(dd, 1H, J1,2 = 5.1 Hz, J1,OH = 6.7 Hz, H-1), 4.60 (d, 1H, J = 11.3 Hz, -CHPh), 4.58 (d, 1H, J = 11.2 Hz,
-CHPh), 4.46 (d, 1H, J = 11.3 Hz, -CHPh), 4.34 (d, 1H, J = 11.2 Hz, -CHPh), 4.06 (t, 1H, J4,3 = 8 Hz,
H-4), 3.94 (d, 1H, J = 6.7 Hz, 1-OH), 3.72 (ddd, J3,2 = 1.8 Hz, J3,OH = 3.2 Hz, H-3), 3.60 (dd, 1H, H-2),
3.12 (d, 1H, 3-OH); 13C-NMR (100 MHz): δ = 141.6, 137.7, 137.6 (3 C arom. quat.), 134.3 (C-5),
128.5-126.1 (15 C arom.), 120.9 (C-6), 81.3 (C-4), 79.4 (C-2), 73.0 (C-1), 72.9 (C-3), 71.7, 70.6 (2
CHPh); MS: m/z 422 (M+NH4)+; Anal. calc. C, 77.20; H, 6.98; found. C, 77.56; H, 7.09.
4-(2,3,4-Tetra-O-acetyl-6-desoxy-6-iodo-β-D-glucopyranosyl) anisole (11)
I
OMe
O
AcO
AcO
OAc
A catalytic amount of sodium is added to a solution 10 (3.7 g, 8.4 mmol) in methanol (50 mL), and
+
the solution is stirred for 12 hours. It is then neutralised using IR 120 (H ) resin, filtered and evaporated
in vacuo. The residue is dissolved in anhydrous DMF (20 mL), then PPh (4.7 g, 17.9 mmol) is added,
3
and the solution is cooled to 0 °C under argon. A solution of diiodine (4.5 g, 17.9 mmol) in anhydrous
DMF (5 mL) is then added dropwise and the solution stirred for 30 min at R.T., until the end of the

Molecules 2005, 10
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reaction is detected by TLC (9:1 dichloromethane/MeOH). The solvent is evaporated and the residue is
dissolved in pyridine (20 mL) and acetic anhydride (10 mL). The reaction is monitored by TLC (7:3
cyclohexane/AcOEt) for 4 hours at R.T. The solvent is then removed in vacuo and the residue purified
by silica gel flash column chromatography (1:4 AcOEt/cyclohexane) to afford compound 11 (2.6 g, 61
20
1
%) as a white solid. [α] = -8 (c = 1.8, CHCl3); m.p. = 99 °C (EtOH); H-NMR (250 MHz): δ = 7.21
D
(d, 2H, J = 8.8 Hz, 2 H arom.), 6.81 (d, 2H, J = 8.8 Hz, 2 H arom.), 5.29 (t, 1H, J2,3 = 9.4 Hz, J3,4 = 9.4
Hz, H-3), 5.12-4.98 (m, 2H, H-4 H-2), 4.33 (d, 1H, J1,2 = 9.7 Hz, H-1), 3.73 (s, 3H, OMe), 3.44 (ddd,
1H, J5,6a = 3.0, J6b,5 = 5.7 Hz, J5,4 = 9.3 Hz, H-5), 3.32 (dd, 1H, J6b,6a = 11.2 Hz, H-6a), 3.13 (dd, 1H, H-
13
6b), 2.03, 1.94, 1.75 (3 x s, 3 x 3H, 3 x Ac); C-NMR (63 MHz): δ = 170.3, 169.3, 168.8 (3 x Ac),
159.9 (C arom. quat.), 128.4, 113.8 (5 C arom.), 79.4 (C-1), 76.3 (C-5), 73.8 (C-3), 72.7 (C-2), 72.4 (C-
4), 55.2 (OMe), 20.7, 20.6, 20.4 (3 x Ac), 4.2 (C-6); MS: m/z 524 (M+NH4)+; Anal. calc. C, 45.07; H,
4.58; found. C, 44.98; H, 4.54.
(2,3,4-Tri-O-acetyl-6-desoxy-β-D-xylo-hex-5-enopyranosyl) anisole (12)
OMe
O
AcO
AcO
OAc
Compound 11 (1.6 g, 3.2 mmol) is dissolved in dry THF (15 mL) and DBU (2.9 mL, 19 mmol) is
added. The mixture is heated at 70 °C until the end of the reaction is detected by TLC (7:3
cyclohexane/AcOEt) after 3 hours. The solvent is then removed in vacuo and the residue purified by
silica gel flash column chromatography (1:5 AcOEt/cyclohexane) to afford 12 (812 mg, 68 %) as a
20
1
white solid. [α] = -51 (c = 1.0, CHCl3); m.p. = 94 °C (Et2O/pentane); H-NMR (250 MHz): δ = 7.14
D
(d, 2H, J = 8.8 Hz, 2 H arom.), 6.72 (d, 2H, J = 8.8 Hz, 2 H arom.), 5.47-5.39 (m, 1H, H-4), 5.17-5.04
(m, 2H, H-3, H-2), 4.69 (sl, 1H, H-6a), 4.43 (sl, 1H, H-6b), 4.35-4.22 (m, 1H, H-1), 3.64 (s, 3H, OMe),
1.99, 1.87, 1.65 (3 x s, 3 x 3H, 3 x Ac); 13C-NMR (63 MHz): δ = 169.9, 169.1, 168.6 (3 x Ac), 159.9 (C
arom. quat.), 153.6 (C-5), 128.3, 127.7, 113.7 (5 C arom.), 96.1 (C-6), 80.4 (C-1), 73.3 (C-3), 72.4 (C-
2), 69.4 (C-4), 55.0 (OMe), 20.5, 20.4, 20.2 (3 x Ac); MS: m/z 396 (M+NH4)+, 379 (M+H)+; Anal. calc.
C, 60.31; H, 5.86; found. C, 60.17; H, 5.98.
(2,3,4-Tri-O-benzyl-6-desoxy-β-D-xylo-hex-5-enopyranosyl) anisole (13)
OMe
O
BnO
BnO
OBn
A catalytic amount of sodium is added to a solution 12 (350 mg, 0.92 mmol) in methanol (3 mL),
and the solution is stirred for 12 hours. The solvent is evaporated without neutralisation and the residue
dissolved in dry DMF (30 mL) to which benzyl bromide (1.1 mL, 9.2 mmol) and (222 mg, 60% in
suspension in oil, 5.5 mmol) are added. The mixture is stirred at R.T. until the end of the reaction is
detected by TLC (9:1 cyclohexane/AcOEt) after 5 hours. Excess NaH is quenched with methanol, and

Molecules 2005, 10
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the mixture is extracted with ether and washed with water. Organic layer is dried (MgSO ), filtered and
4
concentrated. The residue purified by silica gel flash column chromatography (1:99
20
AcOEt/cyclohexane) to afford 13 (299 g, 62 %) as a white solid. [α] = -53 (c = 1.0, CHCl3); m.p. =
D
77-78 °C (Et2O/pentane); 1H-NMR (250 MHz): δ = 7.33-6.75 (19H, H arom.), 4.81 (d, 1H, J = 11.3 Hz,
-CHPh), 4.54 (d, 1H, J = 12.0 Hz, -CHPh), 4.72 (s, 1H, H-6a), 4.69 (d, 1H, J = 11.3 Hz, -CHPh), 4.64
(d, 1H, J = 11.5 Hz, -CHPh), 4.63 (s, 1H, H-6b), 4.42 (d, 1H, J1,2 = 9.7 Hz, H-1), 4.31 (d, 1H, J = 10.5
Hz, -CHPh), 4.00 (d, 1H, J4,3 = 7.4 Hz, H-4), 3.81 (d, 1H, J = 10.5 Hz, -CHPh), 3.76 (s, 3H, OMe), 3.71
(t, 1H, J2,3 = 7.7 Hz, H-3), 3.53 (dd, 1H, H-2); 13C-NMR (63 MHz): δ = 156.7 (C-5), 159.9, 138.5,
138.0, 137.7 (4 C arom. quat.), 130.9-113.9 (20 C arom.), 95.2 (C-6), 84.7 (C-3), 83.8 (C-2), 81.1 (C-1),
79.4 (C-4), 74.8, 74.6, 73.0 (3 CHPh), 55.5 (OMe); MS: m/z 540 (M+NH4)+; Anal. calc. C, 77.62; H,
6.71; found. C, 77.61; H, 6.67.
1R,2S,3S,4R,5S)-2,3,4-Tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) anisole (14), (1R,2S,3S,4R,5R)-
2,3,4-tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) anisole (15) and 2,3,4-tri-O-benzyl-5,6-dehydro-1-
C(S)-anisyl-D-glucitol (16)
A solution of TIBAL (1 mL, 1 mmol, 1M in toluene) is added to a solution of 13 (85 mg, 0.16
mmol) in dry toluene (1 mL) at R.T. under argon. The mixture is stirred at 50 °C for 1 hour, until the
end of the reaction is detected by TLC (7:3 cyclohexane/AcOEt). The mixture is cooled to R.T. and
water (2 mL) is slowly added, and stirred for 15 min. After extraction with AcOEt (3 x 10 mL) and
washing with water (10 mL) the organic layer is dried (MgSO4), filtered and the solvent is evaporated.
The residue purified by silica gel flash column chromatography (1/9 AcOEt/cyclohexane) to afford
three major products 14 (58 mg, 68 %) as a white solid, 15 (58 mg, 68 %) as a white solid and 16 (9 mg,
10 %) as an oil.
(1R,2S,3S,4R,5R)-2,3,4-Tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) anisole (14)
OMe
BnO
BnO
OBn
OH
20
[α] = -34 (c = 0.9, CHCl3); m.p. = 110-111 °C (AcOEt/cyclohexane); 1H-NMR (400 MHz): δ = 7.31-
D
6.69 (19H, arom. H), 4.97 (d, 1H, J = 10.8 Hz, -CHPh), 4.92 (d, 1H, J = 10.8 Hz, -CHPh), 4.83 (d, 1H, J
= 11.5 Hz, -CHPh), 4.79 (d, 1H, J = 11.5 Hz, -CHPh), 4.55 (d, 1H, J = 10.2 Hz, -CHPh), 4.27-4.21 (m,
1H, H-5), 4.00 (t, 1H, J2,3 = 10.3 Hz, J3,4 = 10.3 Hz, H-3), 3.98 (d, 1H, J = 10.3 Hz, -CHPh), 3.96 (s, 3H,
OMe), 3.64 (dd, 1H, J4,5 = 3.1 Hz, H-4), 3.54 (dd, 1H, J1,2 = 9.1 Hz, H-2), 3.27 (ddd, 1H, J1,6a = 11.0 Hz,
J1,6e = 3.7 Hz, H-1), 2.66 (br s, 1H, -OH), 2.13 (dt, 1H, J6e,6a = 14.5 Hz, J6e,5 = 3.7 Hz, H-6e), 1.73 (br t,
1H, H-6a); 13C-NMR (100 MHz): δ = 158.3, 138.9, 138.2, 138.0, 134.3 (5 C arom. quat.), 128.9-113.7 (
19 C arom.), 86.0 (C-2), 83.6 (C-3), 83.2 (C-4), 75.9, 75.3, 72.6 (3 CHPh), 66.6 (C-5), 55.2 (OMe), 41.8
(C-1), 34.3 (C-6); MS: m/z 542 (M+NH4)+; Anal. calc. C, 77.31; H, 7.08; found. C, 77.26; H, 7.16.

Molecules 2005, 10
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(1R,2S,3S,4R,5S)-2,3,4-Tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) anisole (15)
OMe
HO
BnO
BnO
OBn
20
1
[α] = -6 (c = 1.0, CHCl3); m.p. = 122 °C (AcOEt/cyclohexane); H-NMR (400 MHz): δ = 7.41-6.88
D
(19H, arom. H), 5.09 (d, 1H, J = 11.3 Hz, -CHPh), 5.00 (d, 1H, J = 10.8 Hz, -CHPh), 4.92 (d, 1H, J =
10.8 Hz, -CHPh), 4.77 (d, 1H, J = 11.3 Hz, -CHPh), 4.50 (d, 1H, J = 10.1 Hz, -CHPh), 3.91 (d, 1H, J =
10.1 Hz, -CHPh), 3.86 (s, 3H, OMe), 3.71 (dddd, 1H, J5,OH = 1.7 Hz, J5,4 = 9.1 Hz, J5,6e = 4.6 Hz, J5,6a
13.4 Hz, H-5), 3.67 (t, 1H, J3,2 = 9.1 Hz, J3,4 = 9.1 Hz, H-3), 3.58 (dd, 1H, J2,1 = 10.2 Hz, H-2), 3.48 (t,
1H, H-4), 2.75 (ddd, 1H, J1,6a = 13.0 Hz, J1,6e = 3.6 Hz, H-1), 2.40 (d, 1H, -OH), 2.11 (dt, 1H, J6e,6a
=
=
13.2 Hz, J6e,5 = 4.2 Hz, H-6e), 1.77 (td, 1H, H-6a); 13C-NMR (100 MHz): δ = 158.5, 138.6, 137.9,
138.0, 133.7 (5 C arom. quat.), 128.7-113.9 (19 C arom.), 86.4 (C-2), 86.3 (C-4), 86.0 (C-3), 75.7, 75.5,
75.4 (3 CHPh), 71.2 (C-5), 55.3 (OMe), 44.6 (C-1), 35.6 (C-6); MS: m/z 542 (M+NH4)+; Anal. calc. C,
77.31; H, 7.08; found. C, 77.19; H, 7.34.
2,3,4-Tri-O-benzyl-5,6-dehydro-1-C(S)-anisyl-D-glucitol (16)
OMe
HO
BnO
BnO
OBn
20
[α] = -10 (c = 0.2, CHCl3); 1H-NMR (400 MHz): δ = 7.39-6.88 (19H, arom. H), 5.78 (ddd, 1H, J5,6a
=
D
10.3 Hz, J5,6b = 17.4 Hz, J5,4 = 7.8 Hz, H-5), 5.31 (dd, 1H, J6a,6b = 1.4 Hz, H-6a), 5.24 (dd, 1H, H-6b),
4.91 (bt, 1H, J1,2 = 5.1 Hz, J1,OH = 5.1 Hz, H-1), 4.86 (d, 1H, J = 11.4 Hz, -CHPh), 4.66 (d, 1H, J = 11.4
Hz, -CHPh), 4.63 (d, 1H, J = 11.6 Hz, -CHPh), 4.40 (d, 1H, J = 11.6 Hz, -CHPh), 4.34 (d, 1H, J = 11.5
Hz, -CHPh), 4.29 (d, 1H, J = 11.5 Hz, -CHPh), 4.19 (dd, 1H, J = 7.6 Hz, J = 6.5 Hz, H-4), 3.85 (s, 3H,
13
OMe), 3.69-3.62 (m, 2H, H-3 H-2), 3.38 (d, 1H, -OH); C-NMR (100 MHz): δ = 158.9, 138.2, 138.1,
138.0, 133.9 (5 C arom. quat.), 135.3 (C-5), 128.5-113.6 (19 C arom.), 127.6 (C-6), 81.3 (C-4), 81.0,
80.7 (C-2 C-3), 72.6 (C-1), 74.3, 72.6, 70.6 (3 CHPh); HRMS: m/z calc. 542.2906 (M+NH4)+; found.
542.2905 (M+NH4)+.
1,3,5-Trimethoxy-2-(2,3,4-tri-O-acetyl-6-desoxy-6-iodo-β-D-glucopyranosyl) benzene (18)
I
OMe
MeO
O
AcO
AcO
OAc
OMe
A catalytic amount of sodium is added to a solution 17 (4.5 g, 9.0 mmol) in methanol (50 mL), and
the solution is stirred for 5 hours. It is then neutralised using IR 120 (H+) resin, filtered and evaporated
in vacuo. The residue is dissolved in anhydrous DMF (20 mL), then PPh3 (4.7 g, 18 mmol) is added,
and the solution is cooled to 0 °C under argon. A solution of diiodine (4.6 g, 18 mmol) in anhydrous

Molecules 2005, 10
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DMF (20 mL) is then added dropwise and the solution stirred for 45 min at R.T., until the end of the
reaction is detected by TLC (9:1 dichloromethane/MeOH). Solvent is evaporated. The residue is next
dissolved in pyridine (20 mL) and acetic anhydride (10 mL). The reaction is monitored by TLC (1:1
cyclohexane/AcOEt) for 3 hours at R.T. The solvent is then removed in vacuo and the residue purified
by silica gel flash column chromatography (1:4 AcOEt/cyclohexane) to give compound 18 (3.32 g, 65
20
%) as a white solid. [α] = -9 (c = 1.1, CHCl3); m.p. = 157 °C (iPrOH); 1H-NMR (250 MHz): δ = 6.05-
D
5.96 (m, 2H, 2 H arom.), 5.84 (t, 1H, J1,2 = 9.7 Hz, J2,3 = 9.7 Hz, H-2), 5.30 (t, 1H, J3,4 = 9.4 Hz, H-3),
5.04 (d, 1H, J4,5 = 9.4 Hz, H-4), 4.98 (d, 1H, H-1), 3.79 (s, 3H, OMe), 3.72 (s, 6H, 2 x OMe), 3.39-3.31
(m, 1H, H-5), 3.28 (dd, 1H, J5,6a = 3.2, J6b,6a = 10.8 Hz, H-6a), 3.13 (dd, J6b,5 = 4.8 Hz, 1H, H-6b), 2.02,
1.94, 1.67 (3 x s, 3 x 3H, 3 x Ac); 13C-NMR (63 MHz): δ = 170.4, 169.4, 169.1 (3 x Ac), 161.8, 161.1,
160.1 (4 x C arom. quat.), 91.4, 90.6 (2 C arom.), 76.1 (C-5), 74.8 (C-3), 73.0 (C-4), 71.6 (C-1), 69.8
(C-2), 56.2, 55.3 (3 x OMe), 20.9, 20.8, 20.6 (3 x Ac), 5.0 (C-6) ; MS: m/z 584 (M+NH4)+; Anal. calc.
C, 44.53; H, 4.80; found. C, 44.44; H, 4.76
1,3,5-Trimethoxy-2-(2,3,4-tri-O-acetyl-6-desoxy-β-D-xylo-hex-5-enopyranosyl) benzene (19)
MeO
O
OMe
AcO
AcO
OAc
OMe
Compound 18 (1.5 g, 2.6 mmol) is dissolved in dry THF (15 mL) and DBU (2.5 mL, 16 mmol) is
added. The mixture is heated at 70 °C until the end of the reaction is detected after 2 hours by TLC (7:3
cyclohexane/AcOEt). The solvent is then removed in vacuo and the residue purified by silica gel flash
column chromatography (1:5 AcOEt/cyclohexane) to compound 19 (826 mg, 71 %) as a white solid.
20
[α] = -43 (c = 1.2, CHCl3); m.p. = 142 °C (Et2O/pentane); 1H-NMR (250 MHz): δ = 6.03 (s, 2H, 2 H
D
arom.), 5.98 (dd, 1H, J1,2 = 10.2 Hz, J2,3 = 9.6 Hz, H-2), 5.54 (dl, 1H, J4,3 = 9.6 Hz, H-4), 5.17 (t, 1H, H-
3), 5.02 (d, 1H, H-1), 4.72 (sl, 1H, H-6a), 4.45 (sl, 1H, H-6b), 3.75, 3.73 (2 x s, 9H, 3 x OMe), 2.08,
1.97, 1.68 (3 x s, 3 x 3H, 3 x Ac); 13C-NMR (63 MHz): δ = 169.9, 169.2, 167.0 (3 x Ac), 161.9, 160.3,
154.1, 103.4, 90.7 (6 C arom. C-5), 95.0 (C-6), 73.9 (C-3), 72.7 (C-1), 69.5 (C-4), 69.3 (C-2), 55.8, 55.0
(3 x OMe), 20.6, 20.2 (3 x Ac); MS: m/z 456 (M+NH4)+; 439 (M+H)+; Anal. calc. C, 57.53; H, 5.98;
found. C, 57.55; H, 6.01.
1,3,5-Trimethoxy-2-(2,3,4-tri-O-benzyl-6-desoxy-β-D-xylo-hex-5-enopyranosyl) benzene (20)
MeO
O
OMe
BnO
BnO
OBn
OMe
A catalytic amount of sodium is added to a solution 19 (300 mg, 0.68 mmol) in methanol (3 mL),
and the solution is stirred for 12 hours. The solvent is evaporated without neutralisation and the residue
dissolved in dry DMF (30 mL) to which benzyl bromide (0.8 mL, 6.8 mmol) and NaH (165 mg, 60% in
suspension in oil, 4.1 mmol) are added. The mixture is stirred at R.T. until the end of the reaction is

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detected after 2 hours by TLC (9:1 cyclohexane/AcOEt). Excess NaH is quenched with methanol, and
the mixture is extracted with ether and washed with water. Organic layer is dried (MgSO ), filtered and
4
concentrated. The residue purified by silica gel flash column chromatography (1:99
20
1
AcOEt/cyclohexane) compound 20 (350 mg, 88 %) as an oil. [α] = -28 (c = 1.4, CHCl3); H-NMR
D
(250 MHz): δ = 7.42-6.04 (17H, H arom.), 5.05 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.86 (d, 1H, J = 10.7 Hz, -
CHPh), 4.77 (d, 1H, J = 10.3 Hz, -CHPh), 4.73 (d, 1H, J = 10.8 Hz, CHPh), 4.70 (sl, 1H, H-6a), 4.68
(sl, 1H, H-6b), 4.67 (d, 1H, J = 11.4 Hz, -CHPh), 4.45 (d, 1H, J = 10.8 Hz, -CHPh), 4.39 (dd, 1H, J2,3
=
9.9 Hz, H-2), 4.06 (d, 1H, J = 10.7 Hz, -CHPh), 4.02 (dl, 1H, J4,3 = 8.7 Hz, H-4), 3.76, 3.70 (2 s, 9H, 3 x
OMe), 3.64 (t, 1H, H-3); 13C-NMR (63 MHz): δ = 161.6, 160.4, 157.5, 138.6, 138.3, 138.2, 128.3-
127.3, 106.4, 91.0 (25 C arom. C-5), 94.2 (C-6), 85.6 (C-3), 79.8 (C-4), 79.2 (C-2), 73.5 (C-1), 75.2,
74.2, 73.4 (3 CHPh), 55.8, 55.2 (3 x OMe); MS: m/z 600 (M+NH4)+, 583 (M+H)+; Anal. calc. C, 74.20;
H, 6.57; found. C, 74.56; H, 6.86.
1,3,5-Trimethoxy-2-(1R,2S,3S,4R,5R)-2,3,4-tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) benzene (21)
and 1,3,5-trimethoxy-2-(1R,2S,3S,4R,5S)-2,3,4-tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) benzene
(22)
A solution of TIBAL (0.9 mL, 0.9 mmol, 1M in toluene) is added to a solution of 20 (100 mg, 0.17
mmol) in dry toluene (1 mL) at R.T. under argon. The mixture is stirred at 50 °C for 30 min, until the
end of the reaction is detected by TLC (7:3 cyclohexane/AcOEt). The mixture is cooled to R.T. and
water (2 mL) is slowly added, and stirred for 15 min. After extraction with AcOEt (3 x 10 mL) and
washing with water (10 mL) the organic layer is dried (MgSO4), filtered and the solvent is evaporated.
The residue purified by silica gel flash column chromatography (3:7 AcOEt/cyclohexane) to afford a
2/1 mixture of two major unseparable products 21 and 22 (95 mg, 95 %) as an oil.
1,3,5-Trimethoxy-2-((1R,2S,3S,4R,5R)-2,3,4-tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) benzene (21)
MeO
OMe
BnO
BnO
OBn
OH
OMe
(Extracted from the NMR of the mixture of isomers)
1H-NMR (400 MHz): δ = 7.45-6.92 (15H, arom. H), 6.25 (d, 1H, J = 2.3 Hz, arom. H), 6.12 (d, 1H, J =
2.3 Hz, arom. H), 5.16-4.78 (m, 4H, 4 -CHPh), 4.66 (d, 1H, J = 10.5 Hz, -CHPh), 4.27 (dd, 1H, J1,2
=
10.9 Hz, J2,3 = 9.1 Hz, H-2), 4.26-4.22 (m, 1H, H-5), 4.21 (d, 1H, J = 10.6 Hz, -CHPh), 4.04 (ddd, 1H,
J1,6a = 13.2 Hz, J1,6e = 3.9 Hz, H-1), 3.98 (t, 1H, J3,4 = 9.2 Hz, H-3), 3.87 (s, 3H, OMe), 3.84 (s, 3H,
OMe), 3.77 (s, 3H, OMe), 3.65 (dd, 1H, J4,5 = 3.3 Hz, H-4), 2.59 (br s, 1H, -OH), 2.36-2.24 (m, 1H, H-
13
6a), 1.87 (dt, 1H, J6e,6a = 14.0 Hz, J6e,5 = 3.6 Hz, H-6e); C-NMR (100 MHz): δ = 160.1-90.7 (24 C
arom.), 86.6 (C-4), 83.8 (C-3), 82.2 (C-2), 76.7-72.5 (3 CHPh), 67.0 (C-5), 56.2-54.9 (3 OMe), 31.7 (C-
1), 30.7 (C-6); MS: m/z 602 (M+NH4)+; Anal. for the mixture of isomers calc. C, 73.95; H, 6.89; found.
C, 73.89; H, 6.91.

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1,3,5-Trimethoxy-2-((1R,2S,3S,4R,5S)-2,3,4-tri-O-benzyl-2,3,4,5-tetrahydroxycyclohexyl) benzene (22)
MeO
OMe
HO
BnO
BnO
OBn
OMe
(Extracted from the NMR of the mixture of isomers)
1H-NMR (400 MHz): δ = 7.45-6.92 (15H, arom. H), 6.25 (d, 1H, J = 2.3 Hz, arom. H), 6.15 (d, 1H, J =
2.3 Hz, arom. H), 5.16-4.78 (m, 4H, 4 -CHPh), 4.65 (d, 1H, J = 10.4 Hz, -CHPh), 4.36 (dd, 1H, J1,2
=
10.8 Hz, J2,3 = 9.0 Hz, H-2), 4.19 (d, 1H, J = 10.6 Hz, -CHPh), 3.88 (s, 3H, OMe), 3.83 (s, 3H, OMe),
3.81 (s, 3H, OMe), 3.71 (ddd, 1H, J5,6a = 11.6 Hz, J5,6e = 5 Hz, J5,4 = 9.1 Hz, H-5), 3.66 (t, 1H, J3,4 = 9.2
Hz, H-3), 3.55 (ddd, 1H, J1,6a = 13.2 Hz, J1,6e = 3.9 Hz, H-1), 3.52 (t, 1H, H-4), 2.45 (br s, 1H, -OH),
2.36-2.24 (m, 1H, H-6a), 1.87 (dt, 1H, J6e,6a = 14.0 Hz, J6e,5 = 3.6 Hz, H-6e); 13C-NMR (100 MHz): δ =
160.1-90.7 (24 C arom.), 86.6 (C-4), 83.6 (C-3), 82.4 (C-2), 76.7-72.5 (3 CHPh), 71.6 (C-5), 56.2-54.9
(3 OMe), 34.3 (C-1), 32.2 (C-6); MS: m/z 602 (M+NH4)+; Anal. for the mixture of isomers calc. C,
73.95; H, 6.89; found. C, 73.89; H, 6.91.
2,3,4-Tri-O-benzyl-5,6-dehydro-1-C(S)-butyl-D-glucitol (28)[14].
BnO
BnO
HO
nBu
OBn
A solution of TIBAL (1.2 mL, 1.2 mmol, 1M in toluene) is added to a solution of 27 (110 mg, 0.23
mmol) in dry toluene (1 mL) at R.T. under argon. The mixture is stirred at 50 °C for 2 hours 30 min,
until the end of the reaction is detected by TLC (7:3 cyclohexane/AcOEt). The mixture is cooled to R.T.
and water (2 mL) is slowly added, and stirred for 15 min. After extraction with AcOEt (3 x 10 mL) and
washing with water (10 mL) the organic layer is dried (MgSO ), filtered and the solvent is evaporated.
4
The residue purified by silica gel flash column chromatography (3:7 AcOEt/cyclohexane) to afford a
20
20
major product 28 (90 mg, 82 %) as an oil. [α] = -17 (c = 1.8, CHCl3), lit.[14] [α] = -21 (c = 18.7,
D
D
CHCl3); 1H-NMR (250 MHz): δ = 7.51-7.12 (15H, arom. H), 5.85 (ddd, 1H, J5,6a = 11.5 Hz, J5,6b = 16.4
Hz, J5,4 = 7.6 Hz, H-5), 5.31 (dd, 1H, J6a,6b = 1.5 Hz, H-6a), 5.28 (dd, 1H, H-6b), 4.73 (d, 1H, J = 11.3
Hz, -CHPh), 4.65 (d, 1H, J = 11.2 Hz, -CHPh), 4.56 (d, 2H, J = 11.6 Hz, 2 -CHPh), 4.42 (d, 1H, J =
11.4 Hz, -CHPh), 4.31 (d, 1H, J = 11.5 Hz, -CHPh), 4.18 (dd, 1H, J4,3 = 5.7 Hz, H-4), 3.85-3.75 (m, 1H,
H-1), 3.74 (dd, J3,2 = 4.0 Hz, H-3), 3.47 (dd, J2,1 = 5.4 Hz, H-2), 2.86 (d, 1H, J = 6.1 Hz, -OH), 1.6-0.7
(m, 9H, butyl); MS :m/z 492 (M+NH4)+
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