The first ring inversion of pyranoses induced by bulky silyl protections at the 2- and 3-positions

Article abstract of DOI:10.1016/j.tetlet.2004.10.078

The pyranose rings of the 2,3-bis-O-tert-butyldiphenylsilyl-α- and β-d-glucopyranoses, and of the 2,3-bis-O-tert-butyldimethylsilyl-β-d- glucopyranose were in the ¹C₄ form. These findings indicate that the introduction of bulky silyl protecting groups at the 2- and 3-positions can flip a pyranose ring into the axial-rich chair form. Previous such ring inversions have been carried out by the silyl protections at the 3- and 4-positions.

Full text of DOI:10.1016/j.tetlet.2004.10.078

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9207–9209
The first ring inversion of pyranoses induced by bulky
silyl protections at the 2- and 3-positions
Hidetoshi Yamada,* Koki Tanigakiuchi, Kohei Nagao,
Kotaro Okajima and Tatsuya Mukae
School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda 669-1337, Japan
Received 6 September 2004; revised 14 October 2004; accepted 15 October 2004
Available online 2 November 2004
Abstract—The pyranose rings of the 2,3-bis-O-tert-butyldiphenylsilyl-a- and b-D-glucopyranoses, and of the 2,3-bis-O-tert-butyldi-
methylsilyl-b-D-glucopyranose were in the 1C4 form. These findings indicate that the introduction of bulky silyl protecting groups at
the 2- and 3-positions can flip a pyranose ring into the axial-rich chair form. Previous such ring inversions have been carried out by
the silyl protections at the 3- and 4-positions.
Ó 2004 Elsevier Ltd. All rights reserved.
A pair of adjacent bulky silyloxy groups on a pyranose
or a pyranoside ring sometimes keeps the ring in the
chair form with more axial substituents (the axial-rich
chair form). Despite the fact that dozens of such exam-
ples have been found so far, previous stable axial-rich
conformers always possess the bulky silyloxy groups at
least on the C-3 and C-4 positions;1,2 that is, it has not
been observed that a stable axial-rich chair form is in-
duced by the silyloxy groups only on the C-2 and C-3
positions (Fig. 1).3
As a part of our study regarding the ring conformations
of six-membered rings possessing bulky silyloxy
groups,1d,g,4,5 we investigated the ring conformation of
the silyl-protected D-glucopyranoses 1–4 (Scheme 1),
which have tert-butyldimethylsilyl (TBS) or tert-butyldi-
phenylsilyl (TBDPS) groups on the O-2 and O-3. In this
SPh
SPh
O
2
OH
OH
OSiR3
OSiR3
b
O
O
a
3
O
O
O
TBSO
MeO C
2
C6H4OCH3-p
C6H4OCH3-p
OTBS
OTIPS
SPh
O
Me
O
5
6: SiR3 = TBS
7: SiR3 = TBDPS
4
4
3
3
O
TBSO
TIPSO
HO
SPh
OSiR3
O
OH
O
OH
OSiR3
OSiR3
TBDPSO
O
c
O
O
O
TBSO
4
3
2
3
OSiR3
TBSO
TBDPSO
OH
OMe
OH OH
OH OH
Figure 1. Examples of the stable 1C4 conformers containing silyloxy
groups at the 3- and 4-positions,1a,g,2d and an example that the 2,3-bis-
O-silylated compounds retain the 4C1 form.3
8: SiR3 = TBS
9: SiR3 = TBDPS
1:α-OH, SiR3 = TBS
2: -OH, SiR = TBS
β
3
3: α-OH, SiR3 = TBDPS
4: -OH, SiR = TBDPS
β
3
Keywords: Ring conformation; 1C4; Pyranose ring; D-Glucose; Bulky
silyl protections.
Scheme 1. Reagents and conditions: (a) TBSOTf or TBDPSOTf,
DMF, 2,6-lutidine, 100°C; (b) p-TsOHÆH2O, THF/MeOH (1:1), rt,
70% for 8 (from 5 via 6), 50% for 9 (from 5 via 7); (c) NBS, THF/H2O
(1:1), rt, 74% for 1 and 2 (from 8), 83% for 3 and 4 (from 9).
*
Corresponding author. Tel.: +81 79 565 8342; fax: +81 79 565
9077; e-mail: hidetosh@kwansei.ac.jp
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.078

9208
H. Yamada et al. / Tetrahedron Letters 45 (2004) 9207–9209
Table 1. 1H NMR coupling constants and NOESY correlation of 1–4, 10, and 11
Compound Anomer Protecting group
at the 2,3-positions
3JHH (Hz)a
W-coupling (Hz) (position)
NOESY correlation
H-l–H-2 H-2–H-3 H-3–H-4 H-4–H-5
1b
a
b
a
b
a
b
TBS
TBS
TBDPS
TBDPS
—
3.3
1.9
1.0
2.9
3.8
8.0
8.9
2.1
2.9
2.1
9.9
9.2
8.5
1.6
1.5
1.0
9.6
9.1
9.9
2.9
0.0
3.2
9.6
9.8
—
—
—
2b
0.8 (H-1–H-3), 0.7 (H-2–H-4)
1.4 (H-2–H-4)
0.8 (H-1–H-3), 1.4 (H-2–H-4) C-1–OH–H-6
3b
4b
10c
11c
H-1–H-6
—
—
—
—
—
a At room temperature.
b In acetone-d6.
c In D2O.
communication, we describe that the introduction of
bulky silyl protecting groups to the 2- and 3-positions
can flip the ring conformation into the axial-rich chair
form.
chair form, and the minor was the b-isomer (2). The
large coupling constant between the H-1 and H-2 of
the b-glucose 11 was narrowed to 1.9Hz in 2, and the
other coupling constants were also small. Furthermore,
the w-couplings between H-1 and H-3 and between H-2
and H-4 were observed. Therefore, 2 was the b-isomer in
Compounds 1–4 were prepared as follows (Scheme 1).
The direct introduction of the two TBS or the two
TBDPS groups to the 2- and 3-hydroxy groups of
phenyl 4,6-O-p-methoxybenzylidene-1-thio-b-D-gluco-
pyranoside (5)6 was possible by using the corresponding
silyl triflates to provide the bis-silylated 6 and 7, fol-
lowed by removal of the p-methoxybenzylidene group
to afford diols 8 and 9, respectively.7,8 The hydrolysis
of the phenylthio group of 8 gave anomeric mixtures
of the 2,3-bis-O-TBS-glucopyranoses 1 and 2 (74:26).
Similarly, 9 afforded a mixture of 3 and 4 (63:37). Since
these anomeric mixtures cannot be separated, further
investigations into the ring conformation were per-
formed using these mixtures.
1
the C4 conformation (Table 2). In the mixture of the
bis(TBDPS)-protected 3 and 4, both the major and
minor isomers showed small vicinal coupling constants
and the w-couplings. Therefore, both the a- and b-iso-
mers were in the axial-rich chair form. Thus, the ano-
meric stereochemistries were determined by NOESY
spectra as the major one was the a-isomer (3) and the
minor was the b-one (4), because correlations between
H-1 and H-6 and between the hydrogen of the anomeric
hydroxy group and H-6 were observed in the major and
the minor isomers, respectively. The ring conformations
of these a-isomers, therefore, were in the equatorial-rich
chair form when the TBS groups were introduced into
O-2 and O-3, and in the axial-rich chair form when
the TBDPS groups were introduced. Ring conformation
of the corresponding b-isomers, 2 and 4, were both the
axial-rich chair forms.10
The anomeric stereochemistries and the ring conforma-
tions of 1–4 were determined based on the coupling con-
1
stants in the H NMR and NOESY spectra. Table 1
summarizes the vicinal (3JHH) and the w-shaped long-
range coupling constants (4JHH), and NOESY correla-
tions. Corresponding data of the a- and b-D-glucopyra-
noses (10 and 11) are also included for comparison.9 In
the anomeric mixture of the bis(TBS)-protected 1 and 2,
the coupling constants of the major isomer were sub-
stantially similar to the data of 10. Therefore, the major
isomer was the a-one (1) which is in the equatorial-rich
As is the case with the corresponding 3,4-derivatives,1g
the introduction of the TBDPS groups at the 2- and
3-positions also flipped the pyranose rings into the
axial-rich chair form (3 and 4). In contrast, the ring con-
formations of the corresponding bis(TBS)-protected
compounds were affected by the anomeric stereochemis-
try (1 and 2). It has been believed that a steric repulsion
Table 2. Ring conformations of the 2,3-bis-O-silylated glucopyranoses 1–4, 10, and 11
Anomer
Protecting group at the 2- and 3-positions
TBS
None
TBDPS
HO
TBDPSO
HO
HO
O
O
a
HO
HO
O
OH
HO
TBSO
3
2
2
3
HO
TBSO
OH
HO
OTBDPS
OH
3
10
1
HO
HO
OH
OH
HO
HO
HO
TBDPSO
TBSO
b
O
O
O
OH
HO
HO
OTBDPS
HO
OTBS
11
2
4

H. Yamada et al. / Tetrahedron Letters 45 (2004) 9207–9209
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ring inversion induced by the introduction of just two
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References and notes
10. The ring conformation of the phenylthio glucosides 8
and 9 were 4C1 and skew boat form, respectively.
Details of these conformations will be reported
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