3-O-Acyl triggered tandem Lewis acid catalyzed intramolecular cyclization of diacetone glucose derivatives to 5-O-acyl-3,6-anhydro-d-glucose

Article abstract of DOI:10.1016/j.tetlet.2011.07.034

BF₃ mediated one-pot conversion of 3-O-acyl-d-glucose-1,2:5,6- diacetonide derivatives to 5-O-acyl-3,6-anhydro-d-glucose is described through a tandem selective intramolecular cyclization sequence.

Full text of DOI:10.1016/j.tetlet.2011.07.034

Tetrahedron Letters 52 (2011) 4854–4856
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
3-O-Acyl triggered tandem Lewis acid catalyzed intramolecular cyclization
of diacetone glucose derivatives to 5-O-acyl-3,6-anhydro-D-glucose
⇑
Rajashaker Bantu , Hari Babu Mereyala , Lingaiah Nagarapu, Srinivas Kantevari
Organic Chemistry Division-II, Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
BF3 mediated one-pot conversion of 3-O-acyl-
D-glucose-1,2:5,6-diacetonide derivatives to 5-O-acyl-3,6-
Received 5 April 2011
Revised 5 July 2011
Accepted 9 July 2011
Available online 22 July 2011
anhydro-
D
-glucose is described through a tandem selective intramolecular cyclization sequence.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
BF
Tandem selective intramolecular cyclization
-O-acyl-3,6-anhydro- -glucose
3
mediated
5
D
Carbohydrate chirons are versatile compounds with proven end
1
O
uses in organic synthesis. Discovery of new reactions and elegant
preparation of chiral templates from abundantly available carbo-
hydrates continue to attract the attention of synthetic organic
chemists.
H
O
*
O
O
O
H
O
H
*
*
Lewis Acid
*
*
*
O
O
B
We report here a novel reaction (Scheme 1) that involves trans-
O
formation of chiral acyloxy tetrahydrofuranodioxalane
A to
A
acyloxy tetrahydrofuran derivative B with retention of sterochem-
istry at all the stereo centers. The reaction is triggered by activation
of the neighboring acyloxy group by a Lewis acid. The protocol
developed here is unique and new to carbohydrate chemistry.
The protocol has been adequately demonstrated on a wide array
of carbohydrate derivatives 1a–d, 2e–h, 3i,j to give their corre-
Scheme 1. General synthesis of acyl anhydro-D-glucose.
have been prepared from the corresponding hydroxy derivatives
1–3 by the literature described methods and were fully character-
5
ized by spectral methods. 3-O-Formyl-
a-
D-glucofuranose deriva-
sponding 3,6-anhydro-
D-glucose derivatives 4a–h. Such bicyclic
tives 1a, 2e, 3i, and j were obtained by reaction of the respective
3-hydroxy derivatives 1, 2, and 3 with triphosgene/DMF/NaH un-
der modified Vilsmeyer conditions; 3-O-methylthiothiocarbonyl
derivatives 1c and 2g by reaction of 1 and 2, respectively, by reac-
tion with carbondisulfide/methyl iodide/NaH in THF.
carbohydrate templates have been earlier evaluated for antiviral
activity as modified nucleosides2 and the bicylic chiral template
itself has been the key starting material for the synthesis of natural
products viz., furanodictine A and furanodictine B, possessing
neuronal differentiation activity.3 The rigid structural frame of
With the desired 3-O-acyl glucofuranose derivatives in hand, a
series of experiments were carried out to check the suitability of
the substrate and catalysts for the transformation (Scheme 1).
Initially, substrates 1a–d bearing 2,2-dimethyl-1,3-dioxalane on
the C-5,6-carbon were reacted with BF ÁEt O in CH Cl at room
3
,6-anhydro-D-glucose earlier has been used for designing new chi-
4
ral resolving agents.
As a starting point for this study, a wide range of carbohydrate
derivatives with variation of acyl substituents, such as formyl-
3
2
2
2
1
a,2e,3i,j, acetyl-1b,2f, benzoyl-2d,h and xanthyl-1c,2g on C-3-hy-
temperature for 3 h to observe the formation of the corresponding
droxy; and alkyl and phenyl substituents on 1,3-dioxalane ring
3,6-anhydro-D-glucose derivatives 4a–d, respectively, in 54.5–
8
8.0% yields (Scheme 2) (Table 1). The 3-O-formyl derivative 1a
was found to be superior among the acyl substituents tried for
the purpose in terms of yield.
It was then decided to study whether the bulk of substituents
on the neighboring 1,3-dioxalane ring has any decisive role in
the progress of the reaction. It was expected that the
⇑
Corresponding author. Tel.: +91 40 27191510; fax: + 91 40 27193382.
E-mail addresses: rajashekarbantu@yahoo.co.in (R. Bantu), mereyalahb@rediff-
mail.com (H.B. Mereyala).
Present address: Jupiter Bioscience Ltd, 10-2-71, Road No. 3, West Marredpally,
Secunderabad 500 026, India. Tel.: +91 40 44778080; fax: +91 40 27702515.
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.034

R. Bantu et al. / Tetrahedron Letters 52 (2011) 4854–4856
4855
R2
R2
O
R3
H
O
O
O
5
O
4
1
BF .Et O / CH Cl
3 2 2 2
1
2
O
R1
O
R1
5
4
6
X
H
2
3
rt
6
3
3
O
O
O
R O
R1
R1
H
1
-3
4
1
2
3
1
a) R = R = CH , R = HCO
1
3
1
2
3
3
1
2
3
5
)
)
)
R = R = :C(CH ) , R = H
4a) R = CH , R = H, X=O
3
3
2
1
2
3
1
2
3
1b) R = R = CH , R = COCH
3 3
1
3
R = R = :C(CH ) , R = H
4b) R = CH , R = CH , X=O
3 3
2
5
2
1
2
3
1
3
1c) R = R = CH , R = CSSCH
3 3
R = :C(CH ) , R = :C(CH ) , R = H
1
3
2
5
3 2
1
2
3
4c) R = CH3, R = SCH3, X=S
) R ,R3 = H
2
1d) R = R = CH3, R = COPh
1
3
1
2
3
3
4d) R = CH , R = Ph, X=O
2
2
2
2
3
3
e) R = R = (CH ) , R = HCO
2
5
1
2
3
1
3
4
e) R = (CH ) , R = H, X=O
f) R = R = (CH ) , R = COCH3
2 5
2
5
1
2
3
1
3
g) R = R = (CH ) , R =CSSCH3
4f) R = (CH2)5, R = CH3, X=O
2
5
1
2
3
1
3
h) R = R = (CH2)5, R = COPh
4g) R = (CH ) , R = SCH , X=S
2 5 3
1
2
3
i) R = CH , R = (CH ) , R = HCO
1
3
3
2 5
4h) R = (CH ) , R = Ph, X=O
2
5
1
2
3
j) R = (CH ) , R = CH , R = HCO
2
5
3
Scheme 2. Preparation of 5-O-acyl-3,6-anhydro-D-glucose derivatives.
Table 1
BF O catalyzed reaction of 1–3 to 4
ÁEt
3
2
Substrate 1
Product 2
3,6-Anhydro-5-O-formyl-1,2-O-isopropylidene-
5-O-Acetyl-3,6-anhydro-1,2-O-isopropylidene-
3,6-Anhydro-(5-O-methylthio thiocarbonyl)-1,2-O-isopropylidene-
-glucofuranose
3,6-Anhydro-5-O-benzoyl-1,2-O-isopropylidene-
3,6-Anhydro-1,2-O-cyclohexylidene-5-O-formyl-
3,6-Anhydro-5-O-acetyl-1,2-O-cyclohexylidene-
Yield (%)
3
3
1
-O-Formyl-1,2:5,6-di-O-isopropylidene-
-O-Acetyl-1,2:5,6-di-O-isopropylidene-
,2:5,6-Di-O-isopropylidene-3-O-methylthio thiocarbonyl-
-glucofuranose
-O-Benzoyl-1,2:5,6-di-O-isopropylidene-
,2:5,6-Di-O-cyclohexylidene-3-O-formyl-
-O-Acetyl-1,2:5,6-di-O-cyclohexylidene-
,2:5,6-Di-O-cyclohexylidene-3-O-methylthio thiocarbonyl-
-glucofuranose
-O-Benzoyl-1,2:5,6-di-O-cyclohexylidene-
-O-Formyl-5,6-cyclohexylidene-1,2-O-isopropylidene-
-glucofuranose
,2-Cyclohexylidene-3-O-formyl-5,6-isopropylidene-
-glucofuranose
a
-
D
D
-glucofuranose
1a
1b
1c
a
-
D
D
-glucofuranose
4a
4b
4c
88.0
75
67
a-
-glucofuranose
a-
-glucofuranose
a-
D
a-D
3
1
3
1
a
a
a
-
D
-glucofuranose
-glucofuranose
-glucofuranose
1d
2e
2f
a
a
-
-
D-glucofuranose
4d
4e
4f
54.5
78.4
65.1
63.6
-
D
D
D-glucofuranose
-
a-D-glucofuranose
2g
3,6-Anhydro-5-O-methylthio thiocarbonyl-1,2-O-cyclohexylidene-
-glucofuranose
3,6-Anhydro-5-O-benzoyl-1,2-O-cyclohexylidene-
3,6-Anhydro-5-O-formyl-1,2-O-isopropylidene-
4g
a-
D
a-D
3
3
a
-D
-glucofuranose
2h
3i
a
-
D-glucofuranose
4h
4a
52.3
89.9
a-D-glucofuranose
a-D
1
3j
3,6-Anhydro-1,2-O-cyclohexylidene-5-O-formyl-
a-
D-glucofuranose
4e
85.6
a-D
Table 2
Study of various catalysts for the transformation of 1a to 4a
Entry Catalyst
Time 4a
(h)
Product yield (%)
1,2:5,6-Di-O-iso-
propylidene-a-D-
(
100 mol %)
1
,2-O-
Isopropylidene
a-
D-
glucofuranose (5)
glucofuranose(1)
i
ii
TiCl
4
8
5
3
1
3
3
1
3
0
0
0
0
0
0
0
89.9
71
78
87
77
76
74
79
0
25
17
10
13
15
10
17
0
SnCl
p-TSA-pyridine
AlCl
Ce(NH
Bi(NO
4
iii
iv
v
vi
vii
viii
3
4
)
2
(NO
Á5H
COOH
ÁEt
3
)
O
6
3
)
3
2
CF
BF
3
3
2
O
intramolecular cyclization requires planarity to proceed smoothly
and the bulky groups would deter the reaction. Accordingly, sub-
strates 2e–h bearing bulky cyclohexylidene on the 1,3-dioxalane
3-O-formyl derivatives 3i and 3j were reacted under similar
conditions to obtain the corresponding 4a and 4e, respectively, in
89.9% and 85.6% yields (Table 1).
ring were reacted with BF
conditions to obtain the corresponding 3,6-anhydro-
derivatives 4e–h in 52.3–78.4% yield (Table 1), respectively.
Among these derivatives, once again the 3-O-formyl derivative 2e
was found to be superior and the presence of bulky substituents
on the 1,3-dioxalane have no effect. Finally, the other two possible
3
ÁEt
2
O in CH
2
Cl
2
under similar reaction
-glucose
In order to find a suitable catalyst that could improve the yield
and substrate selectivity; several catalysts were tried for the reac-
tion of 1a (Table 2). Most of the catalysts resulted in deprotection
of the neighboring 1,3-dioxalane ring and or the 3-O-acyl group
D
resulting in the formation of 1,2-O-isopropylidene-a-D-glucofura-
nose and 1,2:5,6-di-O-isopropylidene- -glucofuranose almost
a-D

4
856
R. Bantu et al. / Tetrahedron Letters 52 (2011) 4854–4856
H
H
O
O
6
5
4
1
O
R1
5
4
1
O
R1
6
O
3
2
O
3
2
BF .Et O
O
O
3
2
O
O
R2
R1
R2
O
R1
O
R2
R2
O
O
BF3
R
R
1
X
H
H
R
O
O
O
4
O
O
R1
1
R1
5
1
4
6
5
2
O
3
2
O
3
6
O
O
O
O
R2
R1
O
R1
H
R2
4
OBF3
R
Y
Scheme 3. Plausible mechanisam.
quantitatively. Among the catalysts tried for the purpose, BF3
etherate was found to be the most suitable for the transformation
of 1–3 to 4 in terms of yield and simplicty. The bulk on the dioxa-
lane ring did not play any decisive role on the progress of the
reaction.
Supplementary data
Supplementary data (experimental data) associated with this
article can be found, in the online version, at doi:10.1016/j.tetlet.
2011.07.034.
From the mechanism point of view, the cascade reaction is
triggered by Lewis acid activation of 3-O-acyl substituent of 1 to
form the acyl cation intermediate X. Stabilization of the acyl cation
by the electron rich neighboring oxygen atom of the dioxolane
leads to 3 ? 5 acyl migration and intramolecular cyclization via
References and notes
1
.
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A190; (d) Taylor, E. W.; Van Roey, P.; Schinazi, R. F.; Chu, C. K. Antiviral Chem.
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the transition state Y to give 3,6-anhydro-
Scheme 3).
In conclusion, a new reaction is described wherein the 3-O-for-
myl, acetyl, xanthyl, and benzoyl ester derivatives of isopropyli-
dene and cyclohexylidene- -glucofuranose derivatives, undergo
D-glucose derivative 4
(
2
D
tandem intramolecular cyclization reaction, on activation by Lewis
acid with concomitant migration of the acyl group to give the
3
4
5
.
.
.
corresponding 3,6-anhydro-
D-glucose derivatives. A new method
to synthesize 3,6-anhydro-
D-glucose has been achieved.
(a) Mereyala, H. B.; Pallavi, P. Tetrahedron: Asymmetry 2003, 14, 2683–2685; (b)
Mereyala, H. B.; Fatima, L.; Pallavi, P. Tetrahedron: Asymmetry 2004, 15, 585–
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The authors gratefully acknowledge Dr. J.S. Yadav, Director, IICT,
Hyd. and Dr. V.V.N. Reddy, Head, Organic Chemistry Division-II,
IICT for their constant encouragement and support.
1998, 63, 6273–6280.