Trimethylaluminium promoted rearrangements of unsaturated sugars into cyclohexanes

Article abstract of DOI:10.1016/j.tetasy.2003.11.029

Trimethylaluminium induces a stereoselective rearrangement of unsaturated glycosides into polyfunctionalised cyclohexanic rings containing a tertiary alcohol and retaining the anomeric group. In contrast with the previously used triisobutylaluminium, no de-O-benzylation reaction was observed.

Full text of DOI:10.1016/j.tetasy.2003.11.029

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 15 (2004) 699–703
Trimethylaluminium promoted rearrangements of unsaturated
sugars into cyclohexanes
a
a
a
b
Cai Jia,a,b Alan J. Pearce, Yves Bleriot, Yongmin Zhang, Li-He Zhang,
ꢀ
Matthieu Sollogouba, and Pierre Sinay
a,
*
*
€
aEcole Normale Supꢀerieure, Dꢀepartement de Chimie, UMR CNRS 8642, 24 rue Lhomond, 75231 Paris Cedex 05, France
bNational Research Laboratory of Natural and Biomimetic Drugs, Peking University, 38 Xueyuan Road, Beijing 100083, PR China
Received 7 November 2003; accepted 19 November 2003
Abstract—Trimethylaluminium induces a stereoselective rearrangement of unsaturated glycosides into polyfunctionalised cyclo-
hexanic rings containing a tertiary alcohol and retaining the anomeric group. In contrast with the previously used triisobutylalu-
minium, no de-O-benzylation reaction was observed.
ꢀ 2003 Elsevier Ltd. All rights reserved.
1. Introduction
extend this carbocyclisation to C-, S- or Se-glycosides6
and, more importantly, to disaccharides.7 During this
work, we established that Ti(IV) was not suitable for the
rearrangement of disaccharides, whereas AliBu3 pro-
moted the rearrangement of hexenopyranosides bearing
a sugar aglycon, thereby providing an attractive syn-
thesis of pseudo-disaccharides.8 As shown in Scheme 1,
AliBu3 mediated rearrangement of particular disaccha-
rides may be accompanied7 by a de-O-benzylation side
reaction,9 due to the reducing properties of the reagent.
The glycoside to carbocycle conversion provides an
attractive method for the synthesis of polyfunctionalised
enantiomerically pure carbocyclic derivatives from
readily available sugar precursors.1;2 In the classical
Ferrier-II reaction,3 the transformation relies on the
exo-cleavage of the glycosidic bond. In contrast, AliBu3
(TIBAL) or TiCl3OiPr5 assisted rearrangements pre-
serve the anomeric group. This feature allowed us to
4
HO
BnO
BnO
OBn
OBn
O
O
O
BnO
OBn
BnO
BnO
OBn
i Bu3Al(11 eq), PhMe
50 ˚C, 4 h
OMe
OBn
O
63%
O
HO
BnO
BnO
BnO
OBn
OMe
OBn
OBn
O
O
BnO
OH
OMe
26%
Scheme 1.
* Corresponding authors. Tel.: +33-1-4432-3390; fax: +33-1-4432-3397; e-mail addresses: matthieu.sollogoub@ens.fr; pierre.sinay@ens.fr
0957-4166/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.11.029

700
C. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 699–703
The secondary hydroxyl group, which is present in the
cyclohexane moiety (see Scheme 1) also originates from
a reduction of a transient ketone function.
We therefore synthesised the unsaturated sugar 4 start-
ing from the known iodide 3,13 and treated it with AlMe3.
This reaction gave three separable compounds: the ter-
tiary alcohol 5 (52%), the de-O-allylated product 6 (18%)
and the unexpected side product 7 (15%) (Scheme 3).
Within the framework of a general program on the
Al-mediated carbohydrate rearrangements, we report
herein on the use of AlMe3, an aluminium-based Lewis
acid devoid of reducing properties.
A plausible reaction mechanism leading to the cyclo-
hexanic compound 7 is proposed in Scheme 4. The ini-
tially generated ketone 8 undergoes an elimination to
afford the unsaturated ketone 9, which is finally trans-
formed into compound 7 through a Claisen rearrange-
ment. The hexenopyranoside 4 was transformed into the
ketone 8 in 73% yield by the action of 1 equiv of TiCl4 at
)78 ꢁC. Treatment of this ketone with AlMe3 gave a
mixture of the alcohol 5 (32%) and of the product 7
(18%), which indicates the probable intermediacy of the
ketone 8 in all those reactions.
2. Results and discussion
When hexenopyranoside 110 was treated with 15 equiv of
AlMe3 at 80 ꢁC, a single carbocyclic product 2 was
formed in 72% yield (Scheme 2). The introduction of the
methyl group is completely stereoselective and the R
configuration of carbon 1 was unambiguously assigned
from the X-ray crystallographic structure of compound
211 (Fig. 1).
We next treated the disaccharide 107 with AlMe3
(15 equiv) at 60 ꢁC for 2 h and observed the formation of
the rearranged product 11 in 75% yield, as a single iso-
mer (Scheme 5). No de-O-benzylation was observed in
this case (compare with Scheme 1).
2
6
1
O
BnO
BnO
BnO
AlMe3 (15 eq), PhMe
4
5
BnO
Indeed, as shown in Scheme 6, the selective de-O-benz-
ylation of the model perbenzylated glucose derivative
1214 is much slower with AlMe3 than with AliBu3,9 but
still allows the regioselective access to the free hydroxyl
in position 2 after a prolonged reaction time.
80 °C, 100 min.
3
OBn
OBn
OH
OMe
OMe
1
2, 72%
Scheme 2.
3. Conclusion
In summary, we have delineated a novel stereoselective
access to polyhydroxylated cyclohexanes containing a
tertiary alcohol promoted by AlMe3, starting from
6-deoxy-hex-5-eno-pyranosides. Compared to previous
syntheses of related compounds15–17 total stereoselection
both at C-1 and C-5 was observed, as well as retention
of the aglycon allowing transformations of a disacchar-
ide such as 10. Furthermore, in comparison with the
AliBu3-mediated rearrangement on disaccharides, this
version leads to tertiary alcohols without de-O-benzyl-
ation side reaction.
Figure 1.
We have previously shown that the allyl group was not
removed during the AliBu3-induced rearrangement.12
RO
BnO
OBn
OH
OMe
I
5, R=All, 52%
6, R= H, 18%
O
O
AllBr, NaH
AlMe3 (15 eq)
HO
BnO
AllO
BnO
6
HO
DMF, R.T., 2h30
PhMe, 80 °C, 90 min.
OBn
OBn
1
2
5
OMe
OBn
OMe
OMe
3
4
3
4, 72%
HO
7
8
9
7, 15%
Scheme 3.

C. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 699–703
701
O
O
O
AlMe3
AlMe3
O
AllO
BnO
AllO
BnO
or TiCl4 (73%)
OMe
OBn
OBn
OMe
OMe
OBn
9
4
8
AlMe3
AlMe3
HO
OMe
OBn
AllO
BnO
HO
OBn
HO
OMe
7, 18%
from 8
5, 32% from 8
Scheme 4.
O
1'
BnO
BnO
BnO
BnO
OBn
OBn
AlMe3 (15 eq)
OBn
OBn
O
OH
O
O
PhMe, 60 °C, 2h
O
BnO
1
BnO
OBn
OMe
OBn
OMe
10
11, 75 %
Scheme 5.
OBn
OBn
formed using silica gel 60 (230–400 mesh, Merck).
Trimethylaluminium was purchased from Aldrich as a
2 M solution in toluene.
O
O
AlMe3 (15 eq)
BnO
BnO
BnO
BnO
PhMe, 60 °C
OBn
OMe
OH
OMe
12
13
4.1. (1R,2S,3R,4S,5S)-2,3,4-Tribenzyloxy-5-methyloxy-
1-hydroxy-1-methyl cyclohexane 2
4h
0%
61%
4 days
Trimethylaluminium (17.8 mL, 35.6 mmol, 2 M in tolu-
ene) was added to a stirred solution of 110 (1.06 g,
2.23 mmol) in anhydrous toluene (10 mL) at room tem-
perature under argon. The mixture was heated at 80 ꢁC
for 100 min, when TLC (AcOEt/cyclohexane, 3:7) indi-
cated completion of the reaction. The mixture was
cooled to 0 ꢁC and toluene saturated with water (20 mL),
then water (20 mL) were added dropwise over 15 min.
AcOEt (50 mL) was added at room temperature and the
aqueous layer was extracted with AcOEt (2 · 100 mL).
Combined extracts were dried (MgSO4), filtered and the
solvent was removed in vacuo. The residue was purified
by flash chromatography (cyclohexane/AcOEt, 3:1) to
afford 2 (789 mg, 72%), as a colourless oil.
Scheme 6.
4. Experimental
General: Solvents were freshly distilled from Na/benzo-
phenone (THF, toluene), or P2O5 (CH2Cl2). Reactions
were carried under Ar, unless stated otherwise. Melting
€
points were recorded on a Buchi 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 ionisa-
tion with ammonia. Elemental analyses were performed
20
D
ꢀ
by the Service dÕAnalyse de lÕUniversite Pierre et Marie
Curie, 75252 Paris Cedex 05, France. NMR spectra were
2: ½aꢀ ¼ ꢁ0:7 (c 2.4, CHCl3); mp 48–52 ꢁC (hexane); dH
(400 MHz, CDCl3) 7.41–7.30 (m, 15H, H arom.), 5.03
(d, 1H, J ¼ 11:2 Hz, CHPh), 5.02 (d, 1H, J ¼ 10:5 Hz,
CHPh), 4.92 (d, 1H, J ¼ 10:5 Hz, CHPh), 4.84 (d, 1H,
J ¼ 11:9 Hz, CHPh), 4.76 (d, 1H, J ¼ 11:9 Hz, CHPh),
4.73 (d, 1H, J ¼ 11:2 Hz, CHPh), 4.16 (t, 1H,
J3;2 ¼ J3;4 ¼ 9:6 Hz, H-3), 4.12 (br s, 1H, OH), 3.72 (q,
1H, J ¼ 3 Hz, H-5), 3.54 (s, 3H, OMe), 3.49 (dd, 1H,
€
recorded on a Bruker AM-400 (400 and 100.6 MHz, for
13
1H and C, respectively) or Bruker AC-250 (250 and
€
63 MHz, for H and 13C, respectively) using TMS as
1
internal standard. TLC was performed on silica gel
60 F254 (Merck) and developed by charring with
concd H2SO4. Flash column chromatography was per-

702
C. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 699–703
H-4), 3.19 (d, 1H, H-2), 2.15 (dd, 1H, J6a;5 ¼ 3:5 Hz,
J6a;6b ¼ 15:2 Hz, H-6a), 1.32 (dd, 1H, J6b;5 ¼ 2:5 Hz,
H-6b), 1.17 (s, 3H, CH3); dC (100 MHz, CDCl3) 138.8,
138.4, 138.3 (3 C arom. quat.), 128.7–127.5 (15 C
arom.), 85.5 (C-2), 82.8 (C-4), 80.9 (C-3), 78.3 (C-5),
76.0, 75.9, 73.0 (3 · CHPh), 73.5 (C-1), 58.9 (OMe), 35.8
(C-6), 26.3 (C-7); m=z 480 (M+NH4)þ; Anal. Calcd
for C29H34O5: C, 75.28; H, 7.42; found. C, 75.29; H,
7.50.
ous layer was extracted with AcOEt (2 · 100 mL).
Combined extracts were dried (MgSO4), filtered and the
solvent was removed in vacuo. The residue was purified
by flash chromatography (graduent cyclohexane/AcOEt,
5:1 to 3:1) to afford 7 (79 mg, 15%), further elution
afforded 5 (351 mg, 52%) and then 6 (110 mg, 18%).
20
5: ½aꢀ ¼ þ7:5 (c 0.8, CHCl3); dH (400 MHz, CDCl3)
D
7.41–7.30 (m, 10H,
H
arom.), 6.04 (dddd, 1H,
0
JB;Ca ¼ 16 Hz, JB;Cb ¼ 10:3 Hz, JB;A ¼ 6:3 Hz, JB;A
¼
5:7 Hz, H–B), 5.29 (dq, 1H, JCa;Cb ¼ JCa;A ¼ 1:6 Hz, H–
Ca), 5.19 (dq, 1H, JCb;A ¼ 1:3 Hz, H–Cb), 4.95 (d, 1H,
J ¼ 10:5 Hz, CHPh), 4.91 (d, 1H, J ¼ 10:5 Hz, CHPh),
4.81 (d, 1H, J ¼ 11:9 Hz, CHPh), 4.75 (d, 1H,
4.2. Methyl 2,3-di-O-benzyl-4-O-allyl-6-deoxy-a-D-
xylo-hex-5-enopyranoside 4
0
Methyl 2,3-di-O-benzyl-6-deoxy-6-iodo-a-
D
-glucopyr-
J ¼ 11:9 Hz, CHPh), 4.49 (ddt, 1H, JA;A ¼ 12:2 Hz, H–
anoside13 3 (500 mg, 1.0 mmol) was dissolved in anhy-
drous DMF (4 mL), allyl bromide (0.18 mL, 2.0 mmol)
and sodium hydride (210 mg, 5.0 mmol, 60% in mineral
oil) were then added. After 2 h 30 min of stirring at room
temperature, TLC (toluene/AcOEt, 9:1) indicated com-
pletion of the reaction. Excess NaH was quenched by
MeOH (3 mL). The solvent was removed in vacuo and
the residue was partitioned between DCM (50 mL) and
water (50 mL). The aqueous layer was extracted with
DCM (2 · 50 mL) and the combined extracts were
washed with brine (50 mL), dried (MgSO4), filtered and
the solvent was removed in vacuo. The residue was
purified by flash chromatography (AcOEt/cyclohexane:
1/7) to afford 4 (296 mg, 72%), as a colourless oil.
A), 4.49 (ddt, 1H, H–A0), 4.14 (br s, 1H, OH), 4.07 (t,
1H, J3;2 ¼ J3;4 ¼ 9:7 Hz, H-3), 3.72 (q, 1H,
J5;4 ¼ J5;6 ¼ 3 Hz, H-5), 3.54 (s, 3H, OMe), 3.45 (dd, 1H,
H-4), 3.08 (d, 1H, H-2), 2.17 (dd, 1H, J6a;5 ¼ 3:4 Hz,
J6a;6b ¼ 15:2 Hz, H-6a), 1.34 (dd, 1H, J6b;5 ¼ 2:5 Hz, H-
6b), 1.27 (s, 3H, CH3); dC (100 MHz, CDCl3), 138.8,
138.3 (2 C arom. quat.), 135.4 (C–B), 128.4–127.6 (10 C
arom.), 117.0 (C–C), 85.5 (C-2), 82.7 (C-4), 80.8 (C-3),
78.4 (C-5), 76.0 (CHPh), 75.2 (C–A), 73.5 (C-1), 73.0
(CHPh), 58.9 (OMe), 35.7 (C-6), 26.3 (C-7); m=z 430
(M+NH4)þ; Anal. Calcd for C25H32O5: C, 72.75; H,
7.83; found. C, 72.68; H, 7.93.
20
D
6: ½aꢀ ¼ ꢁ6:4 (c 0.7, CHCl3); dH (400 MHz, CDCl3)
7.46–7.30 (m, 10H, H arom.), 4.97 (d, 1H, J ¼ 10:9 Hz,
CHPh), 4.91 (d, 1H, J ¼ 10:9 Hz, CHPh), 4.81 (d, 1H,
J ¼ 11:9 Hz, CHPh), 4.73 (d, 1H, J ¼ 11:9 Hz, CHPh),
4.08 (br s, 1H, OH-5), 3.83 (t, 1H, J3;2 ¼ J3;4 ¼ 9:2 Hz,
H-3), 3.74 (dt, 1H, J5;4 ¼ J5;6b ¼ 2:8 Hz, J5;6a ¼ 3:6 Hz,
H-5), 3.55 (s, 3H, OMe), 3.47 (dd, 1H, H-4), 3.33 (t,
1H,J ¼ 8:4 Hz, H-2), 2.61 (bd, 1H, 6.9 Hz, OH-2), 2.20
(dd, 1H, J6a;5 ¼ 3:9 Hz, J6a;6b ¼ 15:2 Hz, H-6a), 1.42 (dd,
1H, J6b;5 ¼ 2:2 Hz, H-6b), 1.28 (s, 3H, CH3); dC
(100 MHz, CDCl3), 138.8, 138.2 (2 C arom. quat.),
128.6–127.6 (10 C arom.), 82.0 (C-4), 81.3 (C-3), 78.5
(C-5), 78.4 (C-2), 75.8 (CHPh), 75.1 (C-1), 73.0 (CHPh),
59.0 (OMe), 35.7 (C-6), 25.8 (C-7); m=z 390 (M+NH4)þ;
Anal. Calcd for C22H28O5: C, 70.94; H, 7.58; found. C,
70.81; H, 7.75.
20
4: ½aꢀ ¼ ꢁ16 (c 1.0, CHCl3); dH (400 MHz, CDCl3)
D
7.42–7.30 (m, 10H,
H
arom.), 6.00 (ddt, 1H,
JB;Ca ¼ 17:3 Hz, JB;Cb ¼ 10:5 Hz, JB;A ¼ 5:7 Hz, H–B),
5.36 (ddt, 1H, JCa;Cb ¼ JCa;A ¼ 1:6 Hz, H–Ca), 5.24 (ddt,
1H, JCb;A ¼ 1:3 Hz, H–Cb), 4.91 (s, 2H, 2 CHPh), 4.87
(d, 1H, J ¼ 12:2 Hz, CHPh), 4.85 (br s, 1H, H-6a), 4.73
(br s, 1H, H-6b), 4.71 (d, 1H, J ¼ 12:2 Hz, CHPh), 4.65
(d, 1H, J1;2 ¼ 3:4 Hz, H-1), 4.29 (dt, 2H, J ¼ 12:7 Hz, 2
H–A), 3.95 (t, 1H, J3;2 ¼ J3;4 ¼ 9:3 Hz, H-3), 3.82 (dt,
1H, J4;6 ¼ 2:1 Hz, H-4), 3.61 (d, 1H, H-2), 3.46 (s, 3H,
OMe); dC (100 MHz, CDCl3) 153.8 (C-5), 138.6, 138.1 (2
C arom. quat.), 134.4 (C–B), 128.4–127.6 (10 C arom.),
117.3 (C–C), 99.0 (C-1), 96.6 (C-6), 81.1 (C-3), 79.1, 79.0
(C-2 and C-4), 75.8, 73.6 (2 CHPh), 73.3 (C–A), 55.4
(OMe); m=z 414 (M+NH4)þ, 397 (M+H)þ; Anal. Calcd
for C24H28O5: C, 72.70; H, 7.12; found. C, 72.72; H, 7.16.
7: dH (400 MHz, CDCl3) 7.40–7.35 (15H, H arom.), 6.00
(dddd, 1H, J8;9a ¼ 17:2 Hz, J8;9b ¼ 9:9 Hz, J8;7 ¼ 9:1 Hz,
J8;7 ¼ 5:6 Hz, H-8), 5.19 (bd, 1H, H-9a), 5.19 (bd, 1H,
H-9b), 4.72 (d, 1H, J ¼ 11:5 Hz, CHPh), 4.55 (d, 1H,
J ¼ 11:5 Hz, CHPh), 4.51 (br s, 1H, OH), 3.88 (q, 1H,
J1;2 ¼ J1;6 ¼ 3 Hz, H-1), 3.71 (dd, 1H, J2;3 ¼ 12:6 Hz,
H-2), 3.51 (s, 3H, OMe), 2.81–2.72 (m, 1H, H-7a), 2.46
(ddd, 1H, J7a;7b ¼ 14:8 Hz, J ¼ 11:1 Hz, J ¼ 3:5 Hz
H-7b), 2.34 (dt, 1H, J3;2 ¼ 11:6 Hz, J3;7a ¼ J3;7b ¼ 4:2 Hz,
H-3), 1.97 (dd, 1H, J6a;6b ¼ 14:9 Hz, J6a;1 ¼ 3:5 Hz,
H-6a), 2.17 (dd, 1H, J6a;1 ¼ 3:4 Hz, H-6b), 1.36 (s, 3H,
CH3), 1.17 (s, 3H, CH3); dC (100 MHz, CDCl3), 138.6
(C-8), 138.2 (C arom. quat.), 128.4, 127.9, 127.7 (5 C
arom.), 116.3 (C-9), 78.6, 74.3 (C-4, C-5), 77.5 (C-2),
76.9 (C-1), 71.4 (CHPh), 58.3 (OMe), 40.7 (C-3), 34.4
(C-6), 30.0 (C-7), 22.8, 21.6 (2 Me); m=z 338 (M+NH4)þ,
321 (M+H)þ; Exact Mass calcd. for C19H29O4: 321.2066
(M+H)þ; found. 321.206.
4.3. Rearrangement of hexenopyranoside 4 into
(1R,2S,3R,4S,5S)-2-allyloxy-3,4-dibenzyloxy-5-methyl-
oxy-1-hydroxy-1-methyl cyclohexane 5, (1R,2S,3R,4S,
5S)-3,4-dibenzyloxy-5-methyloxy-1,2-dihydroxy-
1-methyl cyclohexane 6 and cyclohexane 7
Trimethylaluminium (12.5 mL, 25 mmol, 2 M in toluene)
was added to a stirred solution of 4 (650 mg, 1.64 mmol)
in anhydrous toluene (7 mL) at room temperature under
argon. The mixture was heated at 80 ꢁC for 90 min,
when TLC (AcOEt/cyclohexane, 3:7) indicated comple-
tion of the reaction. The mixture was cooled to 0 ꢁC and
toluene saturated with water (20 mL), then water
(20 mL) were added dropwise over 15 min. AcOEt
(50 mL) was added at room temperature and the aque-

C. Jia et al. / Tetrahedron: Asymmetry 15 (2004) 699–703
703
4.4. (2S,3R,4S,5S)-2-Allyloxy-3,4-tribenzyloxy-5-meth-
yloxy cyclohexanone 8
J ¼ 11:2 Hz, CHPh), 4.22–4.18 (m, 1H, H-50), 4.01 (t,
1H, J4;3 ¼ J4;5 ¼ 9:6 Hz, H-4), 3.99 (bt, 1H,
J3 ;2 ¼ J3 ;4 ¼ 8:2 Hz, H-30), 3.87 (t, 1H, J3;2 ¼ 9:3 Hz,
H-3), 3.83–3.67 (m, 4H, H-5, H-6, OH), 3.55 (dd, 1H, H-
2), 3.41 (s, 3H, OMe), 3.11 (bd, 1H, H-40), 3.09 (d, 1H,
0
0
0
0
TiCl4 (34 lL, mmol) was added to a cooled ()78 ꢁC)
solution of 4 (73 mg, mmol) in dry dichloromethane
(1 mL), under argon. The reaction mixture was stirred at
)78 ꢁC for 2 h, and then poured into a stirred ice-cold
solution of NaHCO3. The aqueous layer was extracted
with DCM (2 · 10 mL). Combined extracts were dried
(MgSO4), filtered and the solvent was removed in vacuo.
The residue was purified by flash chromatography
(cyclohexane/AcOEt, 4:1) to afford 8 (53 mg, 73%), as a
white solid.
H-20), 1.90 (dd, 1H, J6 a;5 ¼ 5:0 Hz, J6 a;6 b ¼ 14:6 Hz, H-
60a), 1.23 (bd, 1H, H-60b), 1.13 (s, 3H, CH3); dC
(100 MHz, CDCl3), 139.1, 138.7, 138.6, 138.3, 138.0,
137.5 (6 C arom. quat.), 128.4–126.9 (30 C arom.), 97.9
(C-1), 84.8 (C-20), 82.4 (C-40), 81.1 (C-3), 79.8 (C-2), 79.7
(C-30), 76.1 (C-4), 75.9, 75.3 (2 CHPh), 74.8 (C-50), 74.3,
73.6, 73.4, 72.7 (4 CHPh), 70.1 (C-5), 68.7 (C-6), 55.2
(OMe), 37.9 (C-60), 26.4 (Me); m=z 912 (M+NH4)þ;
Anal. Calcd for C56H62O10: C, 75.14; H, 6.98; found. C,
75.12; H, 7.11.
0
0
0
0
20
8: ½aꢀ ¼ ꢁ41 (c 1.0, CHCl3); mp 61 ꢁC (cyclohexane/
D
ethyl acetate); dH (400 MHz, CDCl3) 7.42–7.30 (m, 10H,
H
arom.),
5.99
(dddd,
1H,
JB;Ca ¼ 16 Hz,
References and notes
JB;Cb ¼ 10:3 Hz, JB;Ab ¼ 6:3 Hz, JB;Aa ¼ 5:7 Hz, H–B),
5.35 (dq, 1H, JCa;Cb ¼ JCa;A ¼ 1:6 Hz, H–Ca), 5.23 (dq,
1H, JCb;A ¼ 1:3 Hz, H–Cb), 4.92 (d, 1H, J ¼ 10:5 Hz,
CHPh), 4.88 (d, 1H, J ¼ 10:5 Hz, CHPh), 4.87 (d, 1H,
J ¼ 12:1 Hz, CHPh), 4.79 (d, 1H, J ¼ 11:9 Hz, CHPh),
4.41 (ddt, 1H, JAa;Ab ¼ 12:2 Hz, H–Aa), 4.11 (ddt, 1H,
H–Ab), 4.10 (t, 1H, J3;2 ¼ J3;4 ¼ 8:8 Hz, H-3), 3.98 (d,
1H, H-2), 3.83–3.78 (m, 2H, H-4 H-5), 3.42 (s, 3H,
OMe), 2.79 (dd, 1H, J6a;5 ¼ 4:1 Hz, J6a;6b ¼ 14:5 Hz, H-
6a), 2.36 (dd, 1H, J6b;5 ¼ 1; 4 Hz, H-6b); dC (100 MHz,
CDCl3) 203.7 (C-1), 138.4, 138.1 (2 C arom. quat.),
134.3 (C–B), 128.4–127.7 (10 C arom.), 117.6 (C-C), 85.4
(C-2), 82.2 (C-3), 82.7, 75.3 (C-4 or C-5), 76.0 (CHPh),
73.0 (CHPh), 72.7 (C–A), 57.3 (OMe), 40.4 (C-6); m=z
414 (M+NH4)þ; Anal. Calcd for C24H28O5: C, 72.69; H,
7.13; found. C, 72.51; H, 7.16.
1. Ferrier, R. J. Top. Curr. Chem. 2001, 215, 277–291;
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2831.
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2. Dalko, P. I.; Sinay, P. Angew. Chem. 1999, 111, 819–823;
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Dalko, P. I.; Sinay, P. Angew. Chem., Int. Ed. 1999, 38,
773–776.
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1458.
4. Das, S. K.; Mallet, J.-M.; Sinay, P. Angew. Chem., Int. Ed.
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1997, 36, 493–496; Das, S. K.; Mallet, J.-M.; Sinay, P.
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Angew. Chem. 1997, 109, 513–516.
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1998, 39, 3471–3472.
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2000, 112, 370–372; Sollogoub, M.; Mallet, J.-M.; Sinay,
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P. Angew. Chem., Int. Ed. 2000, 35, 362–364.
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J. Org. Chem. 1999, 2103–2117.
8. Sollogoub, M.; Pearce, A. J.; Herault, A.; Sinay, P.
ꢀ
Tetrahedron: Asymmetry 2000, 11, 283–294.
€
4.5. Methyl 4-[(1R,2S,3R,4S,5S)-2,3,4-tribenzyloxy-1,5-
dihydroxy-5-methyl-cyclohexyl]-2,3,4-O-benzyl-a-D-
glucopyranoside 11
€
9. Sollogoub, M.; Das, S. K.; Mallet, J.-M.; Sinay, P. C. R.
ꢀ
Acad. Sci. Paris, t.2, Serie IIc 1999, 441–448.
10. Semeria, D.; Philippe, M.; Delaumeny, J.-M.; Sepulchre,
A.-M. Synthesis 1983, 710–713.
Trimethylaluminium (0.57 mL, 1.14 mmol, 2 M in tolu-
ene) was added to a stirred solution of 107 (100 g,
0.11 mmol) in anhydrous toluene (1 mL) at room tem-
perature under argon. The mixture was heated at 60 ꢁC
for 2 h, when TLC (AcOEt/cyclohexane, 3:7) indicated
completion of the reaction. The mixture was cooled to
0 ꢁC and toluene saturated with water (2 mL), then
water (5 mL) were added dropwise over 15 min. AcOEt
(5 mL) was added at room temperature and the aqueous
layer was extracted with AcOEt (2 · 10 mL). Combined
extracts were dried (MgSO4), filtered and the solvent
was removed in vacuo. The residue was purified by flash
chromatography (cyclohexane/AcOEt, 3:1) to afford 11
(76 mg, 75%), as a colourless oil.
11. Selected crystal structure data for 2; crystal system
orthorhombic; Space Group P 212121; Z ¼ 4; cell para-
meters: a ¼ 20:350ð7Þ, b ¼ 20:475ð7Þ, c ¼ 6:150ð3Þ, a ¼ 90,
ꢁ
b ¼ 90, c ¼ 90; radiation (Mo-Ka) k ¼ 0:710690 A; 183
variables for 2930 reflections; final R ¼ 0:0697,
RW ¼ 0:0762; Crystallographic data (excluding structure
factors) have been deposited at the Cambridge Crystallo-
graphic Data Centre as supplementary publication no.
CCDC 207537. Copies of the data can be obtained free of
charge on application to CCDC, 12 Union Road, Cam-
bridge CB2 1EZ, UK [Fax: (internat.) +44-1223/336-033;
E-mail: deposit@ccdc.cam.ac.uk].
ꢂ
12. Sollogoub, M. These de Doctorat, Universite Paris 6,
ꢀ
1999.
13. Kohn, A.; Schmidt, R. R. Liebigs Ann. Chem. 1987, 1045–
1054.
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93, 556–557.
15. Verduyn, R.; van Leeuwen, S. H.; van der Marel, G. A.;
van Boom, J. H. Recl. Trav. Chim. Pays-Bas 1996, 115,
67–71.
16. Klemer, A.; Kohla, M. Liebigs Ann. Chem. 1984, 1662–
1671.
20
D
11: ½aꢀ ¼ þ33:5 (c 0.8, CHCl3); dH (400 MHz, CDCl3)
7.39–7.09 (m, 30H, H arom.), 5.02 (d, 1H, J ¼ 11:6 Hz,
CHPh), 4.93 (d, 1H, J ¼ 11:6 Hz, CHPh), 4.88 (d, 1H,
J ¼ 11:2 Hz, CHPh), 4.72 (d, 1H, J ¼ 12:1 Hz, CHPh),
4.71 (d, 2H, J ¼ 12:0 Hz, 2 CHPh), 4.63 (d, 1H,
J ¼ 12:0 Hz, CHPh), 4.62 (d, 1H, J1;2 ¼ 3:6 Hz, H-1),
4.60 (d, 1H, J ¼ 11:2 Hz, CHPh), 4.59 (d, 1H,
J ¼ 12:1 Hz, CHPh), 4.49 (d, 1H, J ¼ 12:0 Hz, CHPh),
4.36 (d, 1H, J ¼ 11:2 Hz, CHPh), 4.27 (d, 1H,
17. Suami, T.; Ogawa, S.; Ishibashi, T.; Kasahara, I. Bull.
Chem. Soc. Jpn. 1976, 49, 1388–1390.