Gold mediated glycosylations: Selective activation of propargyl 1,2-orthoesters in the presence of aglycones containing a propargyl moiety

Article abstract of DOI:10.1039/b806707d

Selective activation of propargyl 1,2-orthoesters in the presence of propargyl glycosides and propargyl ethers was studied; a catalytic amount of AuBr₃ activated the propargyloxy group of the 1,2-orthoester thereby giving access to disaccharide

Full text of DOI:10.1039/b806707d

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
Gold mediated glycosylations: selective activation of propargyl
1,2-orthoesters in the presence of aglycones containing
a propargyl moietyw
Gopalsamy Sureshkumar and Srinivas Hotha*
Received (in Cambridge, UK) 21st April 2008, Accepted 27th May 2008
First published as an Advance Article on the web 21st July 2008
DOI: 10.1039/b806707d
Selective activation of propargyl 1,2-orthoesters in the presence
of propargyl glycosides and propargyl ethers was studied; a
catalytic amount of AuBr3 activated the propargyloxy group of
the 1,2-orthoester thereby giving access to disaccharides with the
propargyl group at the reducing end; furthermore, propargyl
ethers were unaffected under the reaction conditions.
Scheme 1
Synthesis of molecular scaffolds via alkyne activation exploit-
successful, we should be able to synthesize disaccharides with
ing alkynophilic gold catalysts has gained a lot of attention in
the recent times.1 Frequently, one of the intermediates (viny-
l–Au) in the catalytic cycle is trapped by the carbon electro-
philes,2 a proton,2 sulfonyl,3 benzyl4 and silyl groups5 giving
access to interesting chemical architectures.6 However, we
postulated that the expulsion of the vinyl–Au intermediate
(A) from the pyranosyl ring occurs when a propargyl gluco-
pyranoside (1) was treated with a gold(III) catalyst resulting in
the formation of an oxocarbenium ion (B) which when
attacked by an aglycone yielded a mixture of a,b-glucopyrano-
sides (Scheme 1).7
the propargyl group at the reducing end which in turn can be
exploited to synthesize glycoconjugates.9 Many benefits en-
visaged by orthogonal activation10 of n-pentenyl orthoesters in
the presence of n-pentenyl glycosides were recently illustrated
by Fraser-Reid et al.10a Thus we studied the effect of AuBr3 in
a reaction containing both propargyl 1,2-orthoester as well as
the propargyl glycoside. Accordingly, we designed an aglycone
6 in such a way that it possesses both propargyl glycoside and
hydroxyl functionality.
The glycosylation reaction between propargyl 1,2-orthoester
(4) and propargyl glucoside (6) at room temperature revealed
that AuBr3 activated the propargyloxy group of orthoester to
work as a glycosyl donor resulting in the formation of a
disaccharide 7 with the propargyl group at the reducing
end.11,12 In the 1H NMR spectrum of compound 7, the
presence of the propargyl moiety was evident since the reso-
nances due to the alkyne group were noticed at d 2.38 ppm
(1 H, t, J 2.3 Hz) and the 13C NMR spectrum showed
resonances due to two anomeric carbons at d 95.0 and
101.3 ppm indicating the presence of two sugar residues.11
Later on, propargyl 1,2-orthoesters were utilized for the
1,2-trans stereoselective synthesis of glycosides and disacchar-
ides upon treatment with AuBr3 in the presence of 4 A
molecular sieves powder at room temperature.8 In this com-
munication, we report our recent results which imply that
AuBr3 selectively activates the propargyloxy group of 1,2-
orthoesters in the presence of competing propargyl glycosides
or ethers.
To begin our investigation, propargyl 2,3,4,6-tetra-O-benzyl-
a-D-glucopyranoside (1) and aglycone 2 were treated with
10 mol% of AuBr3 in acetonitrile to obtain an a,b-mixture
of disaccharides 3 in 68% yield at 60 1C while no reaction
occurred at room temperature.7a The propargyl 1,2-orthoester
of glucose (4) reacted with the same aglycone 2 at room
temperature affording 1,2-trans disaccharide (5) in 65% yield
(Scheme 2). In this premise, we envisioned that the preferential
activation of propargyloxy group of the 1,2-orthoester can be
achieved in the presence of propargyl glycoside if the reaction
was performed at the room temperature in the presence of a
catalytic amount of AuBr3 and 4 A molecular sieves powder. If
Division of Organic Chemistry, Combi Chem—Bio Resource Center,
National Chemical Laboratory, Pune, 411 008, India. E-mail:
s.hotha@ncl.res.in; Fax: +91 20 2590 2624; Tel: + 91 20 2590 2401
w Electronic supplementary information (ESI) available: General
experimental procedures and 1H, 13C, DEPT NMR spectral charts.
See DOI: 10.1039/b806707d
Scheme 2 Synthesis of disaccharides by gold catalysis.
ꢀc
This journal is The Royal Society of Chemistry 2008
4282 | Chem. Commun., 2008, 4282–4284

View Article Online
Table 1 Synthesis of disaccharides as propargyl glycosides
Table 2 Synthesis of propargyl ether containing disaccharides
101.3 ppm. Also, we synthesized a disaccharide (23) from the
glucosyl donor 4 and the galactosyl aglycone (22) in 71% yield.11
In addition to this, we have also noticed that the aglycones 20
and 22 reacted well with propargyl 1,2-orthoesters of galactose
(16) and mannose (14) to give disaccharides (24–26) containing
the propargyl ether unaffected.11
This interesting observation was then investigated for the
generality by means of aglycones containing secondary alco-
hols (8 and 10) and a ribofuranoside (12). In all the cases the
reaction proceeded smoothly giving the respective disacchar-
ides (9, 11 and 13) in good yields (Table 1).11 In continuation,
the general applicability of the current study has been extended
to the propargyl 1,2-orthoesters of mannose (14) and galactose
(16).11 Gratifyingly, mannosyl orthoester 14 reacted with the
aglycone 6 affording disaccharide 15 in good yield and con-
currently galactosyl 1,2-orthoester 16 also reacted with agly-
cones 6, 8 and 12 resulting in the formation of disaccharides
17–19 with the propargyl group at the reducing end.11 It is
pertinent to mention that the formation of 10–15% of
propargyl 2,3,4,6-tetra-O-benzoyl-b-D-glycopyranoside was
observed along with the required disaccharides.
In summary, we have investigated the selective activation of
propargyl 1,2-orthoesters in the presence of propargyl glyco-
sides and ethers using a catalytic amount of AuBr3. It is
interesting to note that the AuBr3 activated the propargyloxy
group of 1,2-orthoesters though there is a competing propar-
gyl moiety present in the reaction system. The utility of these
propargylated disaccharides is currently underway to synthe-
size pseudo-oligosaccharides, neoglycoconjugates and higher
saccharides.13 Results from such studies will be reported in
future.
S. H. thanks DST, New Delhi for the financial assistance.
G. S. K. acknowledges the CSIR, New Delhi for financial
assistance.
Furthermore, the selectivity of AuBr3 towards the propargyl
1,2-orthoester in the presence of propargyl ether of monosac-
charides was also explored (Table 2). Accordingly, the propargyl
1,2-orthoester of glucose (4) was allowed to react with aglycone
having 4-O-propargyl ether (20) under AuBr3/CH2Cl2/4 A
molecular sieves powder conditions at room temperature to
obtain a disaccharide (21) with the 4-O-propargyl group intact.11
In the 1H NMR spectrum of compound 21 the alkyne –CH was
noticed at d 2.38 ppm (1 H, t, J 2.3 Hz) and the 13C NMR
spectrum confirmed the presence of two sugar residues by
showing resonances due to anomeric carbons at d 97.6 and
Notes and references
1 (a) A. S. K. Hashmi, Angew. Chem., Int. Ed., 2005, 44, 6990–6993;
(b) S. Ma, S. Yu and Z. Gu, Angew. Chem., Int. Ed., 2006, 45,
200–203; (c) R. A. Widenhoefer and S. Han, Eur. J. Org. Chem.,
2006, 4555–4563; (d) N. Asao, Synlett, 2006, 1645–1656;
(e) L. Zhang, J. Sun and S. A. Kozmin, Adv. Synth. Catal., 2006,
348, 2271–2296; (f) A. S. K. Hasmi and G. J. Hutchings, Angew.
Chem., Int. Ed., 2006, 45, 7896–7936; (g) D. J. Gorin and F. D.
Toste, Nature, 2007, 446, 395–403; (h) A. Furstner and P. W.
Davies, Angew. Chem., Int. Ed., 2007, 46, 3410–3449; (i) A. S. K.
Hashmi, Chem. Rev., 2007, 107, 3180–3211.
¨
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 4282–4284 | 4283

View Article Online
2 (a) L. Zhang, J. Am. Chem. Soc., 2005, 127, 16804–16805;
(b) I. Nakamura, T. Sato and Y. Yamamoto, Angew. Chem., Int.
Ed., 2006, 45, 4473–4475.
3 I. Nakamura, U. Yamagishi, D. Song, S. Knota and Y.
Yamamoto, Angew. Chem., Int. Ed., 2007, 46, 2284–2287.
4 P. Dube and F. D. Toste, J. Am. Chem. Soc., 2006, 128,
12062–12063.
and D. Y. Gin, J. Am. Chem. Soc., 2001, 123, 8766–8772; (f) O. J.
Plante, E. R. Palmacci and P. H. Seeberger, Adv. Carbohydr.
Chem. Biochem., 2003, 58, 35–54; (g) G. Ragupathi, F. Koide, P.
O. Livingston, Y. S. Cho, A. Endo, Q. Wan, M. K. Spassova,
S. J. Keding, J. Allen, O. Ouerfelli, R. M. Wilson and
S. J. Danishefsky, J. Am. Chem. Soc., 2006, 128, 2715–2725;
(h) D. P. Galonic and D. Y. Gin, Nature, 2007, 446, 1000–1007.
´
5 I. Nakamura, T. Sato, M. Terada and Y. Yamamoto, Org. Lett.,
2007, 9, 4081–4083.
10 (a) B. Fraser-Reid, J. Ku, K. N. Jayaprakash and J. C. Lopez,
Tetrahedron: Asymmetry, 2006, 17, 2449–2463; For orthogonal
activation studies see: ; (b) R. Geurtsen, D. S. Holmes and
G.-J. Boons, J. Org. Chem., 1997, 62, 8145–8154; (c) P.
Pornsuriyasak and A. V. Demchenko, Tetrahedron: Asymmetry,
2005, 16, 433–439; (d) P. Pornsuriyasak and A. V. Demchenko,
Chem. Eur. J., 2006, 12, 6630–6646; (e) A. V. Demchenko and C.
D. Meo, Tetrahedron Lett., 2002, 43, 8819–8822.
6 (a) A. Hoffmann-Roder and N. Krause, Org. Biol. Chem., 2005, 3,
¨
387–391; (b) A. S. K. Hashmi and G. J. Hutchings, Angew. Chem.,
Int. Ed., 2006, 45, 7896–7936; (c) A. S. K. Hashmi, Chem. Rev.,
2007, 107, 3180–3211; (d) R. Skouta and C.-J. Li, Tetrahedron,
2008, 64, 4917–4938; (e) J. Muzart, Tetrahedron, 2008, 64,
5815–5849.
7 (a) S. Hotha and S. Kashyap, J. Am. Chem. Soc., 2006, 128,
9620–9621; (b) S. Kashyap and S. Hotha, Tetrahedron Lett., 2006,
47, 2021–2023; (c) S. Kashyap, S. R. Vidadala and S. Hotha,
Tetrahedron Lett., 2007, 48, 8960–8962.
8 G. Sureshkumar and S. Hotha, Tetrahedron Lett., 2007, 48,
6564–6568.
9 (a) R. R. Schmidt, Angew. Chem., Int. Ed. Engl., 1986, 25, 212–235;
(b) K. Toshima and K. Tatsuta, Chem. Rev., 1993, 93, 1503–1531;
(c) R. R. Schmidt and W. Kinzy, Adv. Carbohydr. Chem. Biochem.,
1994, 50, 21–123; (d) K. M. Koeller and C.-H. Wong, Chem. Rev.,
2000, 100, 4465–4494; (e) H. M. Nguyen, Y. Chen, S. G. Duron
11 See ESIw.
12 General experimental procedure for AuBr3 mediated glycosylation:
To a solution of glycosyl donor (0.1 mmol), glycosyl acceptor
(0.11 mmol) and 4 A powdered molecular sieves in anhydrous
CH2Cl2 (5 mL) was added AuBr3 (10 mol%) under argon at room
temperature. The reaction mixture was stirred at room temperature
for the specified time and then filtered and the filtrate concentrated
in vacuo. The resulting residue was purified by silica gel column
chromatography using ethyl acetate–petroleum ether as the mobile
phase.
13 S. Hotha and S. Kashyap, J. Org. Chem., 2006, 71, 364–367.
ꢀc
This journal is The Royal Society of Chemistry 2008
4284 | Chem. Commun., 2008, 4282–4284