Preparation of 2-deoxy-2-C-p-tolylsulfonyl-β-D-glucopyranosyl p-tolyl sulfones having non-chair conformation and their elimination reactions

Article abstract of DOI:10.1039/b707802a

When the title sulfones, which have non-chair conformations, were stirred with silica gel, elimination of sulfinic acid occurred to give a 1-enitol derivative, if the hydroxyl group at C-6 was protected, whereas such an elimination did not proceed if the

Full text of DOI:10.1039/b707802a

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Preparation of 2-deoxy-2-C-p-tolylsulfonyl-b-D-glucopyranosyl p-tolyl
sulfones having non-chair conformation and their elimination reactions{
Tohru Sakakibara,* Tomomi Suganuma and Yasuhiro Kajihara
Received (in Bloomington, IN, USA) 23rd May 2007, Accepted 16th July 2007
First published as an Advance Article on the web 6th August 2007
DOI: 10.1039/b707802a
caused by steric hindrance due to the two vicinal equatorial tosyl
groups8 and a by strong bias for the hydroxymethyl group at C-5
to occupy the equatorial position.9 Acetylation of 5 with acetic
anhydride in the presence of catalytic amounts of boron trifluoride
etherate gave the tri-O-acetate 6.10 Conventional benzylidenation
of 5 gave the 4,6-O-benzylidene derivative 7 (Scheme 1). These
derivatives again occupy a non-chair conformation. During
column chromatography on silica gel (Merck silica gel 60, mesh),
elimination of sulfinic acid partially occurred from the benzylidene
derivative 7 to afford the 1-enitol derivative 8, the structure of
which was determined from 1H NMR (d, 7.87, d, J1,3 0.7 Hz, H-1),
13C NMR (d, 155.28, C-1; 119.53, C-2) and elemental analyses.
When a neutral silica gel (Kanto, silica gel 60N, 40–50 mm) was
When the title sulfones, which have non-chair conformations,
were stirred with silica gel, elimination of sulfinic acid occurred
to give a 1-enitol derivative, if the hydroxyl group at C-6 was
protected, whereas such an elimination did not proceed if the
hydroxy group was free.
Replacement reactions at an anomeric center (C-1) are important
in biological and chemical processes and hence they have been
investigated extensively.1 The theory of stereoelectronic effects
predicts that in a b-D-glucopyranoside departure of a leaving
group from C-1 should proceed through a non-chair conformation
such as a boat or sofa form in which a lone pair on the ring
oxygen atom can be antiperiplanar to the leaving group.2
However, direct experimental evidence seems not to be presented,
because
a b-D-glucopyranoside inevitably occupies a chair
conformation in solution. In fact, to our best knowledge, there is
no report that describes a b-D-glucopyranosyl derivative which
has a leaving group at C-1 taking up a non-chair conformation
in solution.3
A sulfonyl group at C-1 behaves as a leaving group;4 therefore,
we have synthesized 2-C-p-tolylsulfonyl-b-D-glucopyranosyl p-tolyl
sulfone, expecting that such a compound exceptionally occupies
a non-chair conformation, because we found that methyl 4,6-
O-benzylidene-2,3-dideoxy-2,3-C-di-p-tolylsulfonyl-b-D-glucopyra-
noside (1) adopts a non-chair conformation in solution.5
The intended ditosyl derivative 5 was prepared by addition of
p-tolylsulfenyl chloride to tri-O-acetyl-D-glucal (2),6 followed by
addition of sodium p-tolylthiolate in methanol, and then oxidation
with m-chloroperbenzoic acid (Scheme 1). Compound 5, as
expected, occupies a non-chair conformation as judged from the
coupling constants, J1,2 3.3, J2,3 5.4, J3,4 8.6, and J4,5 10.3 Hz. It is
noteworthy that compound 5 occupies the non-chair conformation
instead of a 1C4 conformation. The latter conformation is observed,
for example, in phenyl 1-seleno-2,3,4,6-tetrakis-O-triisopropylsilyl-
b-D-glucopyranoside.7 A non-chair conformation for 5 should be
Graduate School of Integrated Science, Yokohama City University,
22-2, Seto, Kanazawa-ku, Yokohama 236-0027, Japan.
E-mail: baratoru@yokohama-cu.ac.jp; Fax: +81-45-787-2413;
Tel: +81-45-787-2183
{ Electronic supplementary information (ESI) available: NMR data of
3–12 and NMR spectra of 6 and 7. See DOI: 10.1039/b707802a
Scheme 1 Reagents and conditions: (i) TolSCl, CH2Cl2, room temp., 59 h,
63%; (ii) NaSTol, MeOH, Ar atmosphere, room temp., 8 h, 72%; (iii)
mCPBA, CH2Cl2, Ar atmosphere, 1 h, 63%; (iv) Ac2O, BF3OEt2, room
temp., 20 h, 97%; (v) PhCH(OMe)2, CSA, MeCN, room temp., 1 h, 91%;
(vi) silica gel 60N, DMF, room temp., 24 h, 70% from 7 and 82% from 6.
3568 | Chem. Commun., 2007, 3568–3570
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used, the decomposition was suppressed to give the benzylidene
derivative 7 in 91% yield. When acetate 6 or benzylidene
derivative 7 in DMF was stirred with silica gel (Merck) at room
temperature for 24 h, elimination of sulfinic acid completely
occurred to give the 1-enitols 9 and 8, respectively, in high yields
(Scheme 1). Similar treatment of the nonprotected 5, however,
resulted in the recovery of 5. Thus, elimination of sulfinic acid
was affected by the hydroxyl group at C-6; that is, if the hydroxyl
group was free, the elimination reaction was suppressed, whereas
it occurred smoothly, if the hydroxyl group was protected.
Different from the 4,6-O-benzylidene derivative 8, tri-O-acetyl-
5
1-enitol 9 occupies a H4 conformation, as judged from small
coupling constants: J3,4 3.2 and J4,5 2.3 Hz. This is in good
agreement with the case of 3,4,6-tri-O-acetyl-2-deoxy-2-nitro-D-
glucal.11
To confirm the generality of the phenomenon, we have syn-
thesized the cyclohexane-1,2-diacetal 10 and its 6-O-acetate 11
4
(Scheme 2).12 These compounds again did not take up the C1
4
conformation, but a SO or 4,OB-like conformation: J1,2 4.5, J2,3
9.7, J3,4 10.7, J4,5 10.5 Hz for 10 and J1,2 3.7, J2,3 9.2, J3,4 11.0, J4,5
10.3 Hz for 11. The same treatment of the acetate 11 with silica gel
(Merck), as described above, gave the 1-enitol 12 in 80% yield
(Scheme 2), whereas even after 48 h the starting material was
recovered in the case of the 6-O free 10.
Fig. 1 Fully optimized structures of 13 (left) and 14 (right).
Notes and references
1 For example: Carbohydrate Chemistry, ed. G.-J. Boons, Blackie
Academic & Professional, London, 1998, ch. 4 and 5; A. F. Bochkov
and G. E. Zaikov, Chemistry of the O-glycosidic Bond, Pergamon Press,
Oxford, 1979.
2 D. G. Gorenstein, J. B. Findlay, B. A. Luxon and D. Kar, J. Am. Chem.
Soc., 1977, 99, 3473; A. J. Kirby, Acc. Chem. Res., 1984, 17, 305;
C. W. Andrews, J. P. Bowen and B. Fraser-Reid, J. Chem. Soc., Chem.
Commun., 1989, 1913; C. W. Andrews, B. Fraser-Reid and J. B. Bowen,
J. Am. Chem. Soc., 1991, 113, 8293; M. L. Sinnott, The Anomeric Effect
and Associated Stereoelectronic Effects, in ACS Symp. Ser. 539, ed.
G. R. J. Thatcher, ACS, Washington, DC, 1992, ch. 6, pp. 97–113;
P. Deslongchamps, Organic Chemistry Series, Vol. 1: Stereoelectronic
Effects in Organic Chemistry, Pergamon Press, Oxford, 1983.
3 The crystal structure of methyl 2-benzylamino-4,6-O-benzylidene-2,3-
dideoxy-3-C-phenylsulfonyl-b-D-glucopyranoside occupies a 1,4B con-
formation: C. G. Suresh, B. Ravindran, K. N. Rao and T. Pathak, Acta
Crystallogr., Sect. C: Cryst. Struct. Commun., 2000, C56, 1030. The
crystal structure of a puckered pyranoside (N-acetyl/muramic acid) at
an active site of the enzyme lysozyme has a sofa conformation:
R. Kuroki, L. H. Weaver and B. W. Matthews, Science, 1993, 262,
2030.
Scheme 2 Reagents and conditions: (i) 1,1,2,2-tetramethoxycyclohexane,
CH(OMe)3, CSA, MeOH, reflux for 18 h, 46%; (ii) Ac2O, BF3OEt2, room
temp., 99%; (iii) silica gel 60N in DMF, room temp., 24 h, 80%.
Although experimental evidence is not obtained at the present
stage, hydrogen bonding between the hydroxyl group at C-6 and
the ring oxygen atom (O-5) probably suppressed the elimination of
the anomeric sulfonyl group.
4 For example: D. S. Brown, S. V. Ley, S. Vile and M. Thompson,
Tetrahedron, 1991, 47, 1329.
Ab initio calculations (B3LYP/6-31+G*)13 of model 13 (Fig. 1)
for the benzylidene derivative 7 were in good agreement with
experimental results; the non-chair conformer (C-3 and C-4 are
slightly lower and upper, respectively, from the ideal B2,5
conformation) was more stable than the 4C1 conformer by
2.0 kcal mol21. STO-3G level calculations of model compound
14 (Fig. 1) for the cyclohexane-1,2-diacetal 10 indicated that a non-
chair conformer (the pyranose ring occupies a BO,3-like conforma-
tion, but its C-4 and C-5 take up fairly upper and slightly lower
positions, respectively) is more stable than a chair conformer by
2.3 kcal mol21. During optimization at the 6-31G* level calcula-
tion, however, the chair and non-chair conformers gave the
same non-chair conformer, which is in good agreement with
the coupling constants observed.
5 T. Sakakibara, K. Suzuki, A. Sakai, M. Shindo, C. Nagano, S. Narumi,
Y. Kajihara and K. Mochizuki, Tetrahedron Lett., 2003, 44, 5711.
6 The same reaction was performed to give a mixture which was used in
the next reaction without separation: I. P. Smoliakova, R. Caple and
D. Gregory, J. Org. Chem., 1995, 60, 1221.
7 H. Abe, M. Terauchi, A. Matsuda and S. Shuto, J. Org. Chem., 2003,
68, 7439 and references cited therein.
8 E. J. Corey, G. Sarakinos and A. Fischer, Tetrahedron Lett., 1999, 40,
7745.
9 S. J. Angyal, Angew. Chem., Int. Ed. Engl., 1969, 8, 157.
10 4, J1,2 10.5, J2,3 10.2, J3,4 8.7, J4,5 9.4; 6, J1,2 2.7, J2,3 2.9, J3,4 6.2, J4,5 9.7;
7, J1,2 1.6, J2,3 2.9, J3,4 8.3, J4,5 10.2, J5,6a 10.2, J5,6e 5.3; 8, J1,3 0.7, J3,4
7.3, J4,5 10.3, J5,6a 10.3, J5,6e 5.1; 12, J1,3 1.4, J3,4 9.2, J4,5 10.8 Hz. In
general, correlation between H-1 and H-5 is stronger than that of H-1
and H-3 or H-3 and H-5 because the distance between H-1 and H-5 is
shorter than that of H-1 and H-3 or H-3 and H-5. In NOESY spectra,
weak correlation between H-1 and H-5 was often observed in these non-
chair conformers, suggesting that a small amount of 1C4 conformer was
also present in an equilibrium.
This work is partially supported by a Grant-in-Aid for Scientific
Research (No. 63540407) from the Ministry of Education, Science
and Culture in Japan and The Grants in Support of the Promotion
of Research at Yokohama City University.
11 R. U. Lemieux, T. L. Nagabhushan and S. W. Gunner, Can. J. Chem.,
1968, 46, 405.
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S. V. Ley, H. W. M. Priepke and S. L. Warriner, Angew. Chem., Int. Ed.
Engl., 1994, 33, 2290.
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