Stereoselective synthesis of α-glucosides from 3-O-propargyl protected glucal exploiting the alkynophilicity of AuCl3

Article abstract of DOI:10.1016/j.tetlet.2006.01.048

The stereoselective synthesis of 2,3-unsaturated α-d-glucosides by the S_N2′ addition of diverse aglycones onto 4,6-di-O-benzyl-3-O-propargyl glucal was achieved using a catalytic quantity of AuCl₃. The Au catalyzed reaction was explo

Full text of DOI:10.1016/j.tetlet.2006.01.048

Tetrahedron Letters 47 (2006) 2021–2023
Stereoselective synthesis of a-glucosides from 3-O-propargyl
protected glucal exploiting the alkynophilicity of AuCl3
Sudhir Kashyap and Srinivas Hotha*
Division of Organic Chemistry: Synthesis, Combi Chem—Bio Resource Center, National Chemical Laboratory, Pune 411 008, India
Received 23 November 2005; revised 20 December 2005; accepted 12 January 2006
Available online 3 February 2006
0
Abstract—The stereoselective synthesis of 2,3-unsaturated a-D-glucosides by the S 2 addition of diverse aglycones onto 4,6-di-O-
N
3
benzyl-3-O-propargyl glucal was achieved using a catalytic quantity of AuCl . The Au catalyzed reaction was explored using various
aliphatic, aromatic, alicyclic and monosaccharide aglycones. The current protocol tolerates diverse functional groups and is highly
stereoselective, fast, catalytic and mild.
Ó 2006 Elsevier Ltd. All rights reserved.
Glycals are excellent templates for initiating diversity
oriented synthesis to achieve stereochemically pure
O
O
Nu
1
RO
Au3+
Nu
RO
compound libraries possessing unique structural archi-
2
tecture and complexity. One type of important chiral
O
O
intermediate that can be obtained from glycals is
1
2
3
2
,3-unsaturated glycosides. Various natural products,
4
2b
Figure 1. Au-mediated alkoxycyclization.
glycopeptides, natural product-like compounds,
modified carbohydrate derivatives, nucleosides and
oligosaccharides were synthesized involving 2,3-unsatu-
5
6
To begin our investigation, the easily accessible glucal 3
was converted to 4,6-di-O-benzyl glucal 4 which was
then transformed to the corresponding 3-O-propargyl
derivative 5 using NaH/propargyl bromide/n-Bu NI in
90% yield (Scheme 1). Subsequently, an acetonitrile
solution of 5 was treated with 3 mol % AuCl in aceto-
nitrile in the presence of methanol at 80 °C for 4 h.
rated glycosides as key intermediates. The 2,3-olefinic
group in the pyran rings can be diversified by a number
of complexity generating reactions such as asymmetric
dihydroxylation, amino hydroxylation, hydrogenation
1
2
4
7
and epoxidation in order to achieve structural diversity.
3
2
,3-Unsaturated glycosides are routinely synthesized via
0
S 2 addition of alcohols onto per-O-acetylated glycal
N
in the presence of a Lewis acid, a process known as
the Ferrier reaction.
8
Surprisingly, we found that the reaction did not result in
the formation of any alkoxycyclized product but instead
0
In our programme2
b,8c,9
the S
N
2 addition product 6a in 38% yield with 50%
directed towards the develop-
1
recovery of the starting material 5. In the H NMR spec-
trum of the product of the Au-mediated reaction, reso-
nances due to the olefin moiety were observed between
d 5.62 and 6.10 ppm and the methoxy group was identi-
fied at d 3.44 ppm as a sharp singlet. Furthermore, the
ment of diversity oriented synthesis of oxygen-rich
chemical scaffolds, we considered performing alkoxycyc-
1
0
lization on 3-O-propargyl bearing glucal 1 by chemo-
selective activation of the terminal alkyne exploiting
the alkynophilicity of Au to afford scaffold
(
2
1
3
Fig. 1).1 We disclose in this letter our observations
1
C NMR spectrum showed that the olefinic carbons
were at d 126.5 and 130.8 ppm and the anomeric carbon
was evident at d 95.7 ppm. However, the DEPT NMR
spectrum revealed that there was no methylene group
in the olefinic region which confirmed that the resultant
product was the 2,3-unsaturated methyl glucoside
which demonstrated that a Ferrier-like reaction takes
place even with a propargyl group in the C-3 position
of the glucal.
1
3,8c
3+
*
Corresponding author. Tel.: +91 20 2590 2401; fax: +91 20 2589
153; e-mail: s.hotha@ncl.res.in
6a.
Mechanistically, the alkynophilic Au activated
3
the triple bond to make the propargyl moiety a leaving
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.048

2022
S. Kashyap, S. Hotha / Tetrahedron Letters 47 (2006) 2021–2023
NaH, DMF
propargyl Br
O
AuCl3
ROH
O
O
BnO
BnO
HO
HO
BnO
BnO
O
OR
Ref. 12
BnO
o
acetonitrile
nBu
h, 90%
NI, 0 C-rt
4
o
0
C-rt
BnO
3
O
OH
OH
15 h, 67%
3
4
5
6a R = Me
N3
O
OMe
O
OMe
OBz
O
O
O
R =
BzO
O
O
O
O
O
OBz
6
b (65%)
6c (68%)
6d (63%)
6e (55%)
6f (58%)
6g (66%)
6h (60%)
Scheme 1. Synthesis of a range of 2,3-unsaturated a-D-glucosides from 4,6-di-O-benzyl-3-O-propargyl glucal.
OHR
a
Supplementary data
O
BnO
Au3+
b
Path a
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2
5
BnO
O
2
006.01.048.
Au
Path b
6
Figure 2. Mechanism.
References and notes
. (a) Schreiber, S. L. Science 2000, 287, 1964–1969; (b)
Spring, D. R. Org. Biomol. Chem. 2003, 1, 3867–3870; (c)
Shang, S.; Tan, D. S. Curr. Opin. Chem. Biol. 2005, 9, 1–
1
group thereby leading to a Ferrier-like reaction (Fig. 2,
path b) instead of trapping the Au–alkyne complex via
an alkoxycyclization (Fig. 2, path a).
1
1; (d) Arya, P.; Quevillon, S.; Joseph, R.; Wei, C.-Q.;
Gan, Z.; Parisien, M.; Sesmilo, B.; Reddy, P. T.; Chen,
Z.-X.; Durieux, P.; Laforce, D.; Campeau, L. C.; Khadem,
S.; Daroszewska, M.; Barnes, M. L. Pure Appl. Chem.
2005, 77, 163–178.
. (a) Kubota, H.; Lim, J.; Depew, K. M.; Schreiber, S. L.
Chem. Biol. 2002, 9, 265–276; (b) Hotha, S.; Tripathi, A.
J. Comb. Chem. 2005, 7, 968–976.
. (a) Domon, D.; Fujiwara, K.; Ohtaniuchi, Y.; Takezawa,
A.; Takeda, S.; Kawasaki, H.; Murai, A.; Kawai, H.;
Suzuki, T. Tetrahedron Lett. 2005, 46, 8279–8283; (b)
Reddy, B. G.; Vankar, Y. D. Tetrahedron Lett. 2003, 44,
The overall yield of the reaction was enhanced to 67%
when the reaction was carried out at 0 °C–rt for 15 h with
1
4
5
mol % of AuCl under an argon atmosphere. Having
3
2
identified that propargyl ethers can act as a leaving group
0
in the Au catalyzed S 2 reaction, we performed parallel
N
syntheses of 2,3-unsaturated a-glucosides using a diverse
range of aglycones. Thus compound 5 was treated with
various aglycones to afford aromatic 6b, aliphatic 6c, ali-
cyclic 6d and monosaccharidic (6e–h) 2,3-unsaturated a-
3
1
3,14
glucosides in good yields (Scheme 1).
It should be
4
765–4767; (c) Lewis, A.; Stefanuti, I.; Swain, S. A.;
noted that the current methodology tolerates various
functional groups such as olefin (6c,e), isopropylidene
Smith, S. A.; Taylor, R. J. K. Tetrahedron Lett. 2001, 42,
5549–5552; (d) Patterson, L.; Keown, L. E. Tetrahedron
Lett. 1997, 38, 5727–5730.
. (a) Chambers, D. J.; Evans, G. R.; Fairbanks, A. J.
Tetrahedron: Asymmetry 2005, 16, 45–55; (b) Dorgan, B.
J.; Jackson, R. F. W. Synlett 1996, 859–861.
. Schmidt, R. R.; Angerbauer, R. Angew. Chem., Int. Ed.
Engl. 1977, 16, 783–784.
. (a) Schmidt, R. R.; Angerbauer, R. Carbohydr. Res. 1979,
(
6e–g), azide 6g and esters 6h.
4
In summary, we have identified for the first time that the
alkynophilicity of Au(III) promotes a Ferrier-like reac-
tion when 3-O-propargyl bearing glucal was treated with
5
AuCl in the presence of aglycones. The utility of the
3
6
methodology was established using a diverse range of
aglycones and the synthesis of more compounds exploit-
ing pentenyl glucoside 6c for our diversity oriented syn-
thesis programme is currently underway. It is pertinent
7
2, 272–275; (b) Borrachero-Moya, P.; Cabrera-Escri-
bano, F.; G o´ mez-Guill e´ n, M.; Peredes-Le o´ n, M. R.
Carbohydr. Res. 1998, 308, 181–190; (c) Danishefsky,
S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed. 1996, 35,
1380–1419; (d) Bussolo, V. D.; Kim, Y.-J.; Gin, D. Y. J.
Am. Chem. Soc. 1998, 120, 13515–13516.
to mention that the AuCl mediated reaction is stereo-
3
selective, moisture tolerant and catalytic.
7
8
. Kim, H.; Men, H.; Lee, C. J. Am. Chem. Soc. 2004, 126,
1
336–1337.
. (a) Ferrier, R. J.; Prasad, N. J. Chem. Soc. (C) 1969, 570–
Acknowledgements
574; (b) Ferrier, R. J.; Prasad, N. J. Chem. Soc. (C) 1969,
581–586; (c) Hotha, S.; Tripathi, A. Tetrahedron Lett.
2005, 46, 4555–4558, and references cited therein.
S.H. thanks the DST, New Delhi (SR/S1/OC-06/2004),
for financial support. S.H. is grateful for the encourage-
ment of Dr. K. N. Ganesh. S.K. acknowledges a fellow-
ship from CSIR-New Delhi.
9
. (a) Hotha, S.; Kashyap, S. J. Org. Chem. 2006, 71, 364–
367; (b) Hotha, S.; Maurya, S. K.; Gurjar, M. K.
Tetrahedron Lett. 2005, 46, 5329–5332; (c) Hotha, S.;

S. Kashyap, S. Hotha / Tetrahedron Letters 47 (2006) 2021–2023
2023
Anegundi, R. I.; Natu, A. A. Tetrahedron Lett. 2005, 46,
585–4588.
0. Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2005, 127,
962–6963.
1. (a) Hashmi, A. S. K.; Frost, T. M.; Bats, J. W. J. Am.
Chem. Soc. 2000, 122, 11553–11554; (b) Hashmi, A. S. K.;
Ding, L.; Bats, J. W.; Fischer, P.; Frey, W. Chem. Eur. J.
12. Franck, R. W.; Marzabadi, C. H. J. Org. Chem. 1998, 63,
4
2197–2208.
1
13
1
1
13. All products gave satisfactory H, C, DEPT NMR (see
supporting information) and CHNS analysis.
6
14. General experimental procedure: To a solution of com-
pound 5 (1 mmol) in anhydrous acetonitrile (5 mL) was
added aglycone (2 mmol) and AuCl (5 mol % in aceto-
3
2
003, 9, 4339–4345; (c) Asao, N.; Aikawa, H.; Yamamoto,
nitrile) at 0 °C and the resulting mixture stirred at rt for
15 h. The reaction mixture was concentrated in vacuo,
the crude residue was redissolved in ethyl acetate and
washed with water. The organic layers were dried over
Y. J. Am. Chem. Soc. 2004, 126, 7458–7459; (d) Arcode, A.;
Bianchi, G.; Marinelli, F. Synthesis 2004, 610–618; (e) Yao,
T.; Zhang, X.; Larock, R. C. J. Am. Chem. Soc. 2004, 126,
1
1164–11165; (f) Hashmi, A. S. K.; Sinha, P. Adv. Synth.
2 4
anhydrous Na SO , concentrated in vacuo and the
Catal. 2004, 346, 432–438; (g) Zhang, L.; Kozmin, S. A. J.
Am. Chem. Soc. 2005, 127, 6962–6963; (h) Shi, Z.; He, C.
J. Am. Chem. Soc. 2004, 126, 5964–5965; (i) Shi, Z.; He, C.
J. Org. Chem. 2004, 69, 3669–3671.
resulting residue was purified by silica gel column
chromatography using light petroleum (60–80 °C) and
ethyl acetate to afford the 2,3-unsaturated a-glucosides in
good yields.