Gold- and Silver-Catalyzed Glycosylation with Pyranone Glycosyl Donors: An Efficient and Diastereoselective Synthesis of α-Anomers

Article abstract of DOI:10.1055/s-0034-1379929

A mild, efficient and diastereoselective gold- and silver-catalyzed O-glycosylation with pyranone glycosyl donors is described. The reactions led to the formation of α-anomers in up to 91% yield with good diastereoselectivities.

Full text of DOI:10.1055/s-0034-1379929

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 1683–1686
letter
1683
W. Liu et al.
Letter
Synlett
Gold- and Silver-Catalyzed Glycosylation with Pyranone Glycosyl
Donors: An Efficient and Diastereoselective Synthesis of α-Ano-
mers
Wenfeng Liua
Qian Chen*a
Jiashen Lianga
Zhiyun Dua
O
O
O
[Au] or [Ag]
ROH
O
Me
BocO
O
Me
RO
O
Me
Kun Zhanga
Xi Zhenga
George A. O’Dohertyb
X
CO2 + t-BuOH
α/β = 3:1
α-anomers
up to 91% yield
good diastereoselectivities
a School of Chemical Engineering and Light Industry,
Guangdong University of Technology, Guangzhou,
Guangdong 510006, P. R. of China
qianchen@gdut.edu.cn
b Department of Chemistry and Chemical Biology,
Northeastern University, Boston, MA 02115, USA
Received: 19.01.2015
Accepted after revision: 04.05.2015
Published online: 25.06.2015
D-/L-α-manno-oligosaccharides using pyranones with tert-
butoxycarboxy (Boc) leaving groups as glycosyl donors.4 In
addition, we have some success using this method for the
synthesis of naturally occurring rare sugar structural mo-
tifs.5 However, glycosyl donors with high optical purity
(e.g., α-L-3 or β-L-3, Scheme 1), which are separated by
chromatography from mixed-α/β-pyranones, are required
for the Pd(0)-catalyzed glycosylation. Thus, we have been
interested in studying the diastereoselective glycosylation
with mixed-α/β-pyranone glycosyl donors. Platinum-, gold-
and silver-catalyzed organic reactions have been success-
fully developed in recent years and showed powerful reac-
tivities for a variety of functional groups under mild condi-
tions.6,7 There is also a successful gylcosylation protocol
with glycosyl ortho-alkynylbenzoates as donors and a
gold(I) complex (e.g., [Ph3PAuOTf]) as the catalyst.3 With
the above background, we envisioned that our pyranone
glycosyl donor (L-3) might decompose into an onium inter-
mediate 4 with platinum, gold or silver salt, and the subse-
quent nucleophilic additions of alcohols to 4 might give α-
anomers 5 as major isomers (Scheme 2). Herein, we de-
scribe a mild, efficient and diastereoselective Au(III)- and
Ag(I)-catalyzed O-glycosylation with pyranone L-3 as the
glycosyl donor, and the reactions smoothly give α-anomers
in good yields with good diastereoselectivities under mild
conditions.
DOI: 10.1055/s-0034-1379929; Art ID: st-2015-w0036-l
Abstract A mild, efficient and diastereoselective gold- and silver-cata-
lyzed O-glycosylation with pyranone glycosyl donors is described. The
reactions led to the formation of α-anomers in up to 91% yield with
good diastereoselectivities.
Key words alcohols, carbohydrates, catalysis, diastereoselectivity,
glycosylation
The O-glycosylation method has been of particular in-
terest due to the rapid development of synthetic and bio-
logical studies of oligosaccharides and natural products
containing sugar motifs.1 A variety of glycosylation meth-
ods have been developed such as using glycosyl halides,
thioglycosides, 1-O-acyl sugars, orthoesters, 1-O- and S-car-
bonates, glycosyl imidates, 4-pentenyl glycosides, phos-
phate/phosphite derivatives, sulfoxides, 1-O-silylated gly-
cosides, 1,2-anhydrosugars, 1-hydroxyl sugars, glycals, and
glycosyl ortho-alkynylbenzoates as glycosyl donors.2,3 How-
ever, to our knowledge, most of glycosyl donors are unable
to be activated with a catalytic amount of promoters. De-
velopment of a novel O-glycosylation method, especially ac-
tivated with catalysts, is still in demand.
Recently, we have developed a Pd(0)-catalyzed O-glyco-
sylation reaction via Pd π-allyl intermediates and demon-
strated its use in the de novo synthesis of all-D-, all-L-, and
1) NBS, H2O
O
OH
Me
O
2) (Boc)2O
Noyori (S,S)
O
O
Me
96%
82%, 2 steps
BocO
O
Me
L-3 (α/β = 3:1)
(S)-2
1
Scheme 1 Preparation of pyranone glycosyl donor L-3
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1683–1686

1684
W. Liu et al.
Letter
Synlett
O
O
O
[M]
ROH
O
Me
BocO
O
Me
RO
O
Me
X
CO2 + t-BuOH
major isomer
α-anomer 5
L-3
4
[M] = [Pt], [Au] or [Ag]
Scheme 2 Hypothesis of Pt-, Au- or Ag-catalyzed glycosylation
To test the hypothesis, pyranone L-3 (α/β = 3:1) was pre-
pared according to our previous protocol4c,d (Scheme 1), and
dihydrocholesterol was chosen as the glycosyl acceptor for
the attempt of Pt-, Au-, or Ag-catalyzed glycosylation reac-
tions. The experimental results are summarized in Table 1.
We first examined the reaction of L-3 with dihydrocholes-
terol in the presence of 5 mol% of PtCl2 in toluene at 80 °C
for two hours (Table 1, entry 1). To our delight, the desired
glycoside L-5a was obtained in 75% yield, and the α/β ratio
was about 2.8:1. Using PtCl4 instead of PtCl2, the ratio was
increased to 4.0:1 when the reaction was carried out at
room temperature (Table 1, entry 2). We then turned to
gold and silver catalysts. The reactions catalyzed by AuCl3,
AuCl, AgBF4, and AgSbF6 also afforded L-5a in good yields
with similar ratio (α/β = ca. 4.4:1) in CH2Cl2 at room tem-
perature (Table 1, entries 3–6). As a comparison, we then
tried Ag-catalyzed glycosylation with α-L-3 (Table 1, entry
7) or β-L-3 (Table 1, entry 8), and both glycosyl donors gave
Table 1 Glycosylation of Pyranone Glycosyl Donors with Dihydrocholesterola
[M]
(5 mol%)
H
L-3
+ dihydrocholesterol
O
solvent
H
H
O
O
H
L-5a
Entry
[M]
Solvent
Temp
Yield (%)b
Ratioc α/β
1
2
PtCl2
PtCl4
AuCl3
AuCl
toluene
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
toluene
Et2O
80 °C
r.t.
75
70
82
68
80
84
78
76
85
82
80
66
63
78
81
77
2.8:1
4.0:1
4.4:1
4.4:1
4.2:1
4.4:1
4.4:1
4.4:1
4.8:1
5.6:1
5.6:1
5.6:1
6.8:1
7.1:1
9.3:1
9.3:1
3
r.t.
4
r.t.
5
AgBF4
r.t.
6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AuCl3
r.t.
7d
8e
9
r.t.
r.t.
0 °C
10
11
12
13
14
15
16
–20 °C
–78 °C
–20 °C
–20 °C
–20 °C
–20 °C
–20 °C
DCE
THF
THF
a The reaction of 3 (0.40 mmol) and dihydrocholesterol (0.80 mmol) was carried out in the presence of 5 mol% of catalysts in anhyd solvents (2.0 mL) under N2
atmosphere.
b Isolated yield based on 3.
c Ratio was determined by 1H NMR.
d α-L-3 was used as the glycosyl donor
e β-L-3 was used as the glycosyl donor.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1683–1686

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Ag
O
[Pd]
X
O
O
O
Ag(I)
Pd(0)
BocO
O
Me
O
O
O
Me
O
Me
β-L-3
6
CO2
+
O
t-BuOH
O
O
O
Ag
Ag
ROH
O
O
CO2
O
Me
RO
O
Me
4
β-L-5 only
ROH
H
Ag(I)
H
O
t-BuOH
RO
O
Me
α-L-5
major isomer
Scheme 3 The comparison of the catalytic mechanism between Pd(0) and Ag(I)
the desired α-anomer as the major product. To improve the
α/β ratio, the reaction temperature was also screened, and
the ratio of L-5a was achieved in 5.6:1 at –20 °C (Table 1,
entry 10). Switching the solvent from CH2Cl2 to Et2O, DCE
and THF increased the ratio (Table 1, entries 12–15), and
the use of THF as the solvent led to 9.3:1 ratio (Table 1, en-
try 15). Using AuCl3 instead of AgSbF6, the reaction also
Table 2 Gold- and Silver-Catalyzed O-Glycosylation of L-3a
AuCl3 (5 mol%)
O
O
or AgSbF6 (5 mol%)
+
ROH
THF, –20 °C, 30 min
BocO
O
Me
RO
O
Me
L-3
L-5
Entry
ROH
Product
L-5a
Yield (%)b α/β Ratioc
gave the desired products in good yield with the same α/β
ratio (Table 1, entry 16).
1
2
77d
dihydrocholesterol
BnOH
9.3:1
81e
As a comparison with our previous Pd(0)-catalyzed gly-
cosylation (Scheme 3), for example, Boc-pyranone β-L-3 af-
forded glycoside β-L-5 via a Pd π-allyl intermediate 6.4,5 On
the contrary, Ag(I)-catalyzed glycosylation with β-L-3
mainly gave glycoside α-L-5 (entry 8, Table 1). It is probably
due to the diastereoselective additions of alcohols to the
onium intermediate 4, which demonstrates this glycosyla-
tion involved a Lewis acid catalysis. Moreover, we also tried
Lewis acid promoted glycosylation (e.g., BF3·Et2O) with L-3,
while the desired glycosides were not detected.
3
4
85d
15:1
83e
L-5b
L-5c
5
6
70d
11:1
75e
PhCH2CH2OH
CyOH
7
8
70d
L -5d
L-5e
16:1
>99:1
10:1
71e
9
10
88d
91e
menthol
11
12
65d
66e
adamantol
L-5f
We then set out to explore the generality of this glyco-
sylation catalyzed by Au(III) or Ag(I) catalyst,8 and the gly-
cosylation results of L-3 with a variety of alcohols are sum-
marized in Table 2. All glycosyl acceptors were well tolerat-
ed, leading to the corresponding α-anomers as the major
isomers in up to 91% yield with good diastereoselectivities
(α/β ratio ranged from 9.3:1 to >99:1). It is worth noting
that the mannose acceptor efficiently gave the desired gly-
coside in 85% yield with Ag(I) catalyst (Table 2, entry 14),
while poor yield was obtained when the reaction was cata-
lyzed by Au(III) catalyst (Table 2, entry 13).
OMe
43d
85e
O
13
14
HO
L-5g
>99:1
O
O
a The reaction of L-3 (0.40 mmol) and alcohols (0.80 mmol) was carried out
in the presence of 5 mol% of AuCl3 or AgSbF6 in anhyd THF (2.0 mL) at –20
°C under nitrogen atmosphere.
b Isolated yield based on L-3.
c Ratio was determined by 1H NMR.
d AuCl3 was used.
e AgSbF6 was used.
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W. Liu et al.
Letter
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In conclusion, a gold- and silver-catalyzed O-glycosyla-
tion with pyranone glycosyl donors has been developed.
This method has significant merits: (1) the yields are good;
(2) the diastereoselectivities are generally good; (3) the do-
nors are easily prepared from achiral starting materials; (4)
the promotion is catalytic; (5) the reaction conditions are
mild. This novel glycosylation should lead to new and use-
ful applications in organic synthesis. Further investigations
on the synthesis of oligosaccharides and natural products
using this protocol are ongoing and will be reported in due
course.
Chem. 2008, 73, 5211. (h) Iyer, A.; Zhou, M.; Azad, N.; Elbaz, H.;
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Acknowledgment
This project was supported by the National Natural Science Founda-
tion of China (21242002), the 100 Young Talents Programme of
Guangdong University of Technology (220413506), the Guangdong
Undergraduate Innovation Training Program (1184513178), and the
Open Funding of Hubei Novel Reactor & Green Chemical Technology
Key Laboratory (RGCT201302).
Supporting Information
(8) General Procedure for Gold- and Silver-Catalyzed Glycosyla-
tion: To a solution of glycosyl donor L-3 (0.40 mmol) and the
appropriate alcohol (0.80 mmol) in anhyd THF (2.0 mL) was
added AuCl3 or AgSbF6 (0.020 mmol) at –20 °C under nitrogen
atmosphere. The mixture was stirred at –20 °C for 30 min. After
removal of the solvent under reduced pressure, the residue was
then purified by flash column chromatography on silica gel
using an appropriate eluent to give the desired glycoside.
α-L-5a: colorless oil; [α]D21 +21.5 (c = 0.5, CH2Cl2). 1H NMR (400
MHz, CDCl3): δ = 6.80 (dd, J = 10.2, 3.5 Hz, 1 H), 6.05 (d, J = 10.2
Hz, 1 H), 5.33 (d, J = 3.5 Hz, 1 H), 4.59 (t, J = 6.8 Hz, 1 H), 3.64–
3.72 (m, 1 H), 1.95–1.98 (m, 1 H), 1.72–1.88 (m, 3 H), 1.46–1.68
(m, 7 H), 0.94–1.38 (m, 20 H), 1.37 (d, J = 6.8 Hz, 3 H), 0.89 (d, J =
6.4 Hz, 3 H), 0.87 (d, J = 1.6 Hz, 3 H), 0.85 (d, J = 1.6 Hz, 3 H), 0.80
(s, 3 H), 0.64 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 197.29,
144.17, 127.20, 91.36, 77.89, 70.28, 56.48, 56.31, 54.38, 44.84,
42.61, 40.04, 39.53, 37.11, 36.19, 35.79, 35.62, 35.50, 34.54,
32.08, 29.34, 28.85, 28.25, 28.01, 24.22, 23.84, 22.81, 22.56,
21.25, 18.68, 15.27, 12.25, 12.08. ESI-MS: m/z = 499.2 [M+ + H].
α-L-5g: white solid; mp 126–127 °C; [α]D21 +105.3 (c = 0.5, CH2-
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1379929.
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Cl2). H NMR (400 MHz, CDCl3): δ = 6.82 (dd, J = 10.2, 3.5 Hz, 1
H), 6.07 (d, J = 10.2 Hz, 1 H), 5.28 (d, J = 3.5 Hz, 1 H), 4.79–4.86
(m, 2 H), 4.08–4.12 (m, 2 H), 3.64–3.68 (m, 1 H), 3.52–3.55 (m, 1
H), 3.36 (s, 3 H), 1.57 (s, 3 H), 1.37 (d, J = 6.7 Hz, 3 H), 1.34 (s, 3
H), 1.30 (d, J = 6.3 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ =
197.62, 142.75, 127.51, 109.25, 98.04, 93.28, 80.21, 77.13,
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 1683–1686