Bronsted Acids of Anionic Chiral Cobalt(III) Complexes as Catalysts for the Iodoglycosylation or Iodocarboxylation of Glycals

Article abstract of DOI:10.1055/s-0037-1611810

Bronsted acids of anionic chiral Co(III) complexes were found to act as efficient phase-transfer catalysts for the diastereoselective iodoglycosylation or iodocarboxylation of glycals with a variety of alcohols or carboxylic acids, respectively, with N -iodosuccinimide as the iodo cation source. The corresponding 2-deoxy-2-iodoglycosides, including monosaccharides and disaccharides, and 2-deoxy-2-iodoglycosyl carboxylates, which are of high synthetic and biological importance, were obtained in high yields (up to 88%) with good diastereoselectivities (up to 9:1 dr).

Full text of DOI:10.1055/s-0037-1611810

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–H
letter
A
en
R. Wang et al.
Letter
Synlett
Brønsted Acids of Anionic Chiral Cobalt(III) Complexes as Catalysts
for the Iodoglycosylation or Iodocarboxylation of Glycals
Rui Wang ◊a
Wen-Qiang Wu ◊a
Na Li ◊a
Jia Shen ◊b
Kun Liua
R2OH (3)
t-Bu
I
O
Λ-(S,S)-1c
O
t-Bu
O
R1O
i-Pr
(10 mmol%)
NIS, 4 Å MS,
CH2Cl2, r.t.
I+
(NIS)
O
4α
OR2
N
i-Pr
H
Co
O
N
R1O
H+
H
[Co*]-
(Λ-(S,S)-1c)
O
O
31 examples
up to 84% yield,
9:1 dr (α/β)
2
O
Jie Yu*a
0
0
0
0-
0
0
0
2-9
9
6
8-1
4
2
9
I
O
R1O
t-Bu
Λ-(S,S)-1c
R2COOH (5)
a Department of Applied Chemistry, Anhui Agricultural University,
Hefei, 230036, P. R. of China
6α
OCOR2
t-Bu
jieyu@ahau.edu.cn
b Tobacco Research Institute, Anhui Academy of Agricultural
Sciences, Hefei, 230031, P. R. of China
◊ These authors contributed equally to this work.
Received: 08.02.2019
Accepted after revision: 03.04.2019
Published online: 23.04.2019
or TMSI(OAc)2 with an oxidant [for example, H2O2, CAN,
Cu(OAc)2, PhI(OAc)2,6 PPh3,6h or TfOH5d] have been reported,
the exploration of high-performance catalytic systems that
are, in principle, distinct from previous ones remains essen-
tial for the development of mild and efficient stereoselec-
tive glycosylation methods. Furthermore, there are few re-
ports on the catalytic stereocontrol of such reactions with
chiral catalysts, due to the difficulty of asymmetric inter-
molecular halogenation7,8 or glycosylation.4,9
The potential of the octahedral chiral-at-metal com-
plexes, in which the metal center does not serve as a cata-
lytic center to activate substrate by coordination but merely
provides a rigid framework and an environment of centro-
chirality, is less well recognized.10 We have recently devel-
oped Brønsted acids and sodium salts of anionic chiral
Co(III) complexes as efficient catalysts for the highly
enantioselective bromoaminocyclization of olefins and for
the Povarov reaction of enol ethers with 2-azadienes.11
More importantly, the chiral Co(III)-complex-templated
Brønsted acids have been proved to function as bifunctional
phase-transfer catalysts to shuttle N-bromosuccinimide
(NBS) to the reaction solution and to control stereoselectiv-
ity.11c,d We therefore speculated that such anionic chiral
Co(III) complexes might also serve as alternative chiral-an-
ion-mediated catalysts12 with an iodo-cation source for the
iodoglycosylation4,6a,13 of glycals 214 with alcohols 3 or car-
boxylic acids 5 (Scheme 1).
DOI: 10.1055/s-0037-1611810; Art ID: st-2019-r0074-l
Abstract Brønsted acids of anionic chiral Co(III) complexes were found
to act as efficient phase-transfer catalysts for the diastereoselective
iodoglycosylation or iodocarboxylation of glycals with a variety of alco-
hols or carboxylic acids, respectively, with N-iodosuccinimide as the
iodo cation source. The corresponding 2-deoxy-2-iodoglycosides, in-
cluding monosaccharides and disaccharides, and 2-deoxy-2-iodoglyco-
syl carboxylates, which are of high synthetic and biological importance,
were obtained in high yields (up to 88%) with good diastereoselectivi-
ties (up to 9:1 dr).
Key words Brønsted acids, phase-transfer catalysis, iodoglycosyla-
tion, iodocarboxylation, glycals
Mono- and oligosaccharides are prevalent motifs in bio-
logically active natural products such as glycopeptides, gly-
coproteins, proteoglycans, and glycolipids.1 Deoxy sugars
also constitute key intermediates with widespread applica-
tions in medicinal and pharmaceutical research.2 Therefore,
the development of efficient methods for the synthesis of
these glycomolecules in high stereoselectivity and with
broad structural diversity is undoubtedly appealing in
chemistry, biology, and related fields.2f,3 Remarkable prog-
ress has been made, especially in transition-metal-cata-
lyzed and organocatalyzed conventional glycosylations for
the preparation of complex carbohydrates.4 In this study,
we focused on the iodoglycosylation and iodocarboxylation
of glycals by using anionic chiral Co(III) complexes as
phase-transfer catalysts, affording the corresponding 2-de-
oxy-2-iodoglycosides and 2-deoxy-2-iodoglycosyl carbox-
ylates, which are of high synthetic and biological impor-
tance.5 Although iodoglycosylations and iodoacetoxylations
through stoichiometric glycosylations using glycals and al-
cohols or acetic acid in the presence of an electrophilic io-
dine reagent (NIS) or an iodate reagent such as NH4I, NaI, I2,
Here, we present our preliminary studies on catalytic
iodoglycosylation and iodocarboxylation reactions for the
preparation of 2-deoxy-2-iodoglycosides 4 and 2-deoxy-2-
iodoglycosyl carboxylates 6 by using anionic chiral Co(III)
complexes 1.
The diastereoselective iodoglycosylation of 3,4,6-tri-O-
benzyl-D-glucal (2a) and benzyl alcohol (3a) with NIS at
room temperature was initially tested, and the correspond-
ing 2-deoxy-2-iodoglycoside 4aa was obtained in 69% yield
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H

B
R. Wang et al.
Letter
Synlett
2.5:1 dr, even at a low temperature of –40 °C (entries 6 and
8).5d Several Brønsted acids, such as p-toluenesulfonic acid
and the chiral phosphoric acids PA1 and PA2, were also
tested, and the results suggested that the proton has no im-
pact on the diastereoselectivity (entries 10–12). When
DMAP and PPh3 were employed as the catalysts, the / ra-
tio of 4aa was only 3:1 (entries 13 and 14). A series of an-
ionic chiral Co(III) complexes, either as sodium salts or
Brønsted acids, were then screened (entries 15–21), Λ-
(S,S)-1c afforded the best diastereomeric ratio of 4:1 in the
highest yield of 86% (entry 18). The metal-centered chirali-
ty in the chiral Co(III)-complex-templated Brønsted acids
had little effect on the stereochemical outcome of the iodo-
glycosylation (entries 16, 19, and 20). Several iodinating re-
agents, such as 1,3-diiodo-5,5-dimethylhydantoin (DIH)
and N-iodosaccharine (NISC), were then tested, and NIS was
found to be the optimal iodine source for this protocol (en-
tries 18, 22, and 23). To our delight, changing the ratio of 2a,
3a, and NIS ratio slightly improved the diastereoselectivity
(entry 24). Moreover, a screening of the reaction parame-
ters, including the solvent, temperature, and additives, sug-
gested that the reaction in CH2Cl2 at room temperature gave
a higher / ratio of 5:1 with 4 Å MS (entries 24–34).
Our Strategy - Iodoglycosylation and Iodocarboxylation of Glycals with NIS
I
H
N
N
O
O
O
O
(NIS)
H+[Co*]-
I+[Co*]-
O
OOCR2
I
O
O
OR2
R1O
R1O
R2OH (3)
*
*
*
*
R1O
or
R1O
+
or
R1O
R1O
I
R2COOH (5)
R1O
R1O
6
2
R1O
O
4
t-Bu
t-Bu
t-Bu
O
O
t-Bu
t-Bu
t-Bu
R3
R3
H
H
O
O
O
O
O
O
R3
M
R3
H
R3
H
H
H
N
Co
N
N
N
Co
N
Co
N
M
M
R3
O
O
O
O
O
O
O
O
O
t-Bu
t-Bu
Λ-(S,S)-1
t-Bu
Δ-(S,S)-1
t-Bu
t-Bu
t-Bu
Δ-(R,R)-1
1a: R3 = t-Bu, M = H; 1b: R3 = t-Bu, M = Na; 1c: R3 = i-Pr, M = H; 1d: R3 = i-Pr, M = Na.
Scheme 1 Chiral Co(III)-complex-templated phase-transfer catalysis
with a 2:1 dr (/ ratio) without a catalyst (Table 1, entry
1). As expected, the reaction occurred smoothly in the pres-
ence of various Lewis acids (entries 2–9), delivering the
product in good yields (up to 86%), albeit with only up to
Table 1 Optimization of the Conditions for Iodoglycosylationa
O
OBn
I
BnO
BnO
Ar
cat. (10 mmol%)
+ source, 4 Å MS,
solvent, r.t.
O
BnO
BnO
I
O
O
O
BnO
+
+
I
BnOH
4aaα
P
OH
3a
BnO
2a
O
OBn
BnO
BnO
O
I
O
S
O
I+ source:
O
Ar
N
PA1: Ar = 4-O2NC6H4
PA2: Ar = 2,4,6-(i-Pr)3C6H2
I
N
N
O
I
N
I
O
BnO
4aaβ
Me
(NIS)
(NISC)
(DIH)
Me
O
Entry
Catalyst
Solvent
I+ source
Yieldb (%)
drc (/)
1
2d
–
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
69
76
86
85
78
55
59
45
50
69
61
51
54
2:1
ZnBr2
1.5:1
1:1
3d
Sc(OTf)3
Mg(OTf)2
TMSOTf
TMSOTf
TfOH
4d
1.6:1
1.5:1
2:1
5d
6d,e
7d
1.8:1
2.5:1
2.5:1
1.5:1
2:1
8d,e
9d
TfOH
AgOTf
TsOH·H2O
PA1
10d
11
12
13d
PA2
2:1
DMAP
3:1
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H

C
R. Wang et al.
Letter
Synlett
Table 1 (continued)
Entry
Catalyst
PPh3
Solvent
I+ source
Yieldb (%)
drc (/)
14d,e
15
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CCl4
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
DIH
NISC
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
85
82
85
56
86
78
50
79
40
12
82
74
85
79
76
51
74
60
80
79
64
3:1
Λ-(S,S)-1a
Δ-(R,R)-1a
Λ-(S,S)-1b
Λ-(S,S)-1c
Δ-(R,R)-1c
Δ-(S,S)-1c
Λ-(S,S)-1d
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
3:1
16
3.5:1
3.8:1
4:1
17
18
19
3.5:1
2:1
20
21
3:1
22
3:1
23
3:1
24f
25f
26f
27f
28f
29f,g
30f,h
31f,i
32f,j
33f,k
34f,l
5:1
3.5:1
3.8:1
4.5:1
3:1
CHCl3
DCE
toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
4:1
4.5:1
3:1
4:1
4:1
4:1
a Unless otherwise noted, the reaction was performed with glycal 2a (0.1 mmol), 3a (0.15 mmol), NIS (0.12 mmol), catalyst (0.01 mmol), 4 Å MS (100 mg) in the
solvent (1 mL) at r.t. under N2 in the absence of light for 24 h.
b Yield of isolated product 4aa.
c Determined by 1H NMR.
d Catalyst (20 mmol%) was used.
e The reaction was carried out at –40 °C.
f The 2a/3a/NIS ratio was 1:1.2:1.1.
g The reaction was carried out at 35 °C.
h The reaction was carried out at 0 °C.
i The reaction was carried out at –20 °C.
j 3 Å MS (100 mg) was used instead of 4 Å MS.
k 5 Å MS (100 mg) was used instead of 4 Å MS.
l No additive was used.
With the optimized reaction conditions in hand,15 we
next explored the scope of the iodoglycosylation with re-
spect to the alcohol 3. As shown in Table 2, various substit-
uents on the aryl moiety of the benzyl alcohols 3b–f were
tolerated, affording the corresponding 2-deoxy-2-iodogly-
cosides 4 in up to 73% yield with up to 4.5:1 dr (Table 2, en-
tries 1–5). The electronic nature of the substrates had no
evident influence on the reactivity. In addition, 1-naphthyl-
methanol was also well tolerated and provided the product
4ag with 4:1 dr (entry 6). Nonbenzylic aliphatic alcohols
3h–n were also suitable substrates, giving the desired gly-
cosides 4ah–an in high yields and up to 6.5:1 dr (entries 7–
13). Sterically hindered alcohols 3j and 3k readily partici-
pated in the reaction with up to 6.5:1 dr (entries 9 and 10).
The Z-alkene in 3n was also well tolerated (4:1 dr; entry
13). More importantly, the iodoglycosylation proceeded un-
der mild conditions with monosaccharides such as the pri-
mary alcohol 3o and the secondary alcohol 3p, giving the
corresponding disaccharides with up to 9:1 dr (entries 14
and 15).
The scope of the iodoglycosylation using Brønsted acid
of anionic chiral Co(III)-complexes 1 with regard to the gly-
cals 2 was also evaluated (Table 3). Glycals with other hy-
droxy-protecting groups, such as 2b and 2c, were good sub-
strates for the iodoglycosylation reaction, giving the corre-
sponding products in moderate to high yields and with up
to 8:1 dr (entries 1–8). Moreover, tri-O-benzyl-D-galactal
(2d), the C4-epimer of 2a, afforded the corresponding prod-
ucts in moderate yields with similar diastereoselectivities
(up to 6.5:1 dr; entries 9 and 10).16
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H

D
R. Wang et al.
Letter
Synlett
Table 2 Scope of the Alcohols 3 for the Iodoglycosylationa
O
OR
O
OR
Λ-(S,S)-1c (10 mmol%)
NIS, 4 Å MS, CH2Cl2, r.t.
O
BnO
BnO
BnO
BnO
BnO
+
+
ROH
I
BnO
I
BnO
4aα
BnO
4aβ
BnO
2a
3
Entry
1
Alcohol
Product
Yieldb (%)
72
drc (/)
drd (Lit.)
OH
4ab
4:1
–
–
–
–
O2N
(3b)
OH
2
3
4
4ac
4ad
4ae
62
73
56
4.5:1
4:1
MeO
(3c)
OH
tBu
(3d)
O2N
OH
OH
4:1
(3e)
MeO
5
4af
66
4.5:1
–
(3f)
6
7
CyOH (3g)
4ag
4ah
75
84
4:1
–
–
Ph(CH2)2OH (3h)
4.5:1
OH
8
4ai
78
4.5:1
4.8:16h
(3i)
9
10
11
i-PrOH (3j)
t-BuOH (3k)
Me(CH2)7OH (3l)
4aj
4ak
4al
73
72
78
5:1
2:16h
–
6.5:1
4:1
2.3:16h
Et
HO
12
13
4am
4an
78
76
4:1
4:1
–
–
Et
(3m)
CH3
HO
(3n)
HO
O
BnO
14e
4ao
4ap
88
53
6.5:1
9:1
2.5:16h
BnO
BnO
OMe
(3o)
O
O
O
OH
15e
–
O
O
(3p)
a Unless otherwise noted, the reaction was performed with glycal 2a (0.1 mmol), alcohol 3 (0.12 mmol), NIS (0.11 mmol), Λ-(S,S)-1c (0.01 mmol), and 4 Å MS
(100 mg) in CH2Cl2 (1 mL) at r.t., under N2 in the absence of light for 24 h.
b Yield of isolated product.
c Determined by 1H NMR.
d Anomer ratios reported in the literature.
e The reaction was carried out on a 0.1 mmol scale for 72 h with a 2a/3/NIS ratio of 2:1:2.4.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H

E
R. Wang et al.
Letter
Synlett
Table 3 The Scope of Glycals for the Iodoglycosylationa
Table 4 The scope of the Iodocarboxylationa
O
OCOR
I
Λ-(S,S)-1c (10 mmol%)
Λ-(S,S)-1c (10 mmol%)
NIS, 4 Å MS, CH2Cl2, r.t.
O
O
OR2
R1O
O
OR2
I
BnO
BnO
BnO
BnO
O
NIS, 4 Å MS, CH2Cl2, r.t.
R1O
RCOOM
+
R2OH
R1O
+
+
(M = H or Na)
I
3
4α
4β
BnO
6α
+
O
2
BnO
2a
5
Entry Glycal
Alcohol Product Yieldb
(%)
drc
(/)
drd
(Lit.)
OCOR
I
BnO
BnO
5:16d
O
1
3a
4ba
80
8:1
AcO
9:16e
–
BnO
6β
AcO
2
3
3c
3f
4bc
4bf
54
55
5:1
4:1
AcO 2b
Entry Acid or Na Salt
Product Catalyst
Yieldb (%) drc
6:16d
11:16e
1
2
3
4
5
6
7
8
9
BzONa (5a)
BzOH (5b)
AcONa (5c)
AcOH (5d)
BzONa (5a)
AcONa (5c)
BzOH (5b)
AcOH (5d)
6a
6a
6b
6b
6a
6b
6a
6b
–
–
–
–
14
82
29
70
28
28
74
65
67
3.5:1
4
5
6
7
8
3g
3h
3a
3c
3j
4bg
4bh
4ca
4cc
4cj
70
63
60
66
61
5:1
–
–
–
–
–
2:1
4.5:1
2.5:1
1.8:1
3.8:1
5.5:1
6.5:1
5.5:1d
6:1
4:1
5:1
5:1
O
BzO
BzO
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
Λ-(S,S)-1c
BzO
2c
9
3c
3k
4dc
4dk
47
52
4:1
–
–
O
BnO
BnO
10
6.5:1
4-F3CC6H4CO2H (5e) 6c
2d
BnO
COOH
a Unless otherwise noted, the reaction was performed with glycal 2 (0.1
mmol), alcohol 3 (0.2 mmol), NIS (0.15 mmol), Λ-(S,S)-1c (0.01 mmol), and
4 Å MS (100 mg) in CH2Cl2 (1 mL) at r.t. under N2 in the absence of light for
48 h.
10
11
6d
Λ-(S,S)-1c
Λ-(S,S)-1c
62
75
6:1
(5f)
b Yield of isolated product.
2,6-Cl2C6H4CO2H
(5g)
6e
7.5:1
c Determined by 1H NMR.
d Anomer ratios reported in the literature.
a Unless otherwise noted, the reaction was performed with glycal 2a (0.1
mmol), 5 (0.15 mmol), NIS (0.12 mmol), Λ-(S,S)-1c (0.01 mmol), and 4 Å
MS (100 mg) in CH2Cl2 (1 mL) at r.t. under N2 in the absence of light for 12 h.
b Yield of isolated product.
Encouraged by these results, we next studied the iodo-
carboxylation of glycal 2a with carboxylic acids and sodium
salts 5 to give the corresponding 2-deoxy-2-iodoglycosyl
carboxylates 6 (Table 4).17 The reaction of the sodium salts
5a and 5c and the acids 5b and 5d in the absence of the chi-
ral-Co(III)-complex-templated Brønsted acid were first test-
ed, and products 6a and 6b were obtained with low diaste-
reoselectivities (Table 4, entries 1-4). Interestingly, the
presence of the Brønsted acid of a chiral Co(III) complex Λ-
1c resulted in enhanced diastereoselectivity (up to 6.5:1 dr;
entries 5–8), but the sodium salts of the acids still gave low
yields (entries 5 and 6). It is suggested that the presence of
an acidic proton might promote the reaction and that the
bulky chiral Co(III) complexes influence the stereocontrol.
The protocol also tolerated other carboxylic acids, and the
corresponding glycosyl carboxylates 6c–e were obtained
with good diastereoselectivities (up to 7.5:1 dr; entries 9–11).
Next, we performed a 1H NMR spectral analysis of mix-
tures of NIS with Brønsted acid Λ-(S,S)-1c or benzoic acid
(5b) in CDCl3 at room temperature. The presence of succin-
imide in the former mixture clearly revealed that Λ-(S,S)-1c
reacted with NIS to produce a new complex,11c,d thereby
leading to the formation of succinimide, while no evidence
was found to show that there is an interaction between
benzoic acid (5b) and NIS in the latter mixture (Figure 1).
c Determined by 1H NMR.
d The reported anomer ratio of 5d was 4:1.6f
On the basis of the interesting experimental results and
our previous work,11c,d we propose a plausible mechanism
for these reaction of a chiral-Co(III)-templated Brønsted
acid in combination with NIS. As shown in Scheme 2, the
Brønsted acid 1 might undergo an exchange reaction with
NIS to generate a reactive chiral iodinating reagent 7, as
1
suggested by the H NMR spectral analysis. The chiral ion-
pair 7 might then undergo diastereoselective reaction with
the glycal 2 to afford the 2-deoxy-2-iodoglycoside 4 or a 2-
deoxy-2-iodoglycosyl carboxylate 6 through nucleophilic
addition of the alcohol 3 or carboxylic acid 5, respectively,
with regeneration of Brønsted acid 1. The stereochemical
outcomes were not good enough to have been caused by
the competition of the rapid noncatalytic reaction of NIS.
In summary, we have developed a diastereoselective
iodoglycosylation or iodocarboxylation of glycals with NIS
mediated by a chiral-Co(III)-complex-templated Brønsted
acid. The catalytic reaction proceeds under mild conditions,
providing convenient access to 2-deoxy-2-iodoglycosides or
2-deoxy-2-iodoglycosyl carboxylates in up to 88% yield and
with up to 9:1 dr. The anionic chiral Co(III) complexes also
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H

F
R. Wang et al.
Letter
Synlett
H
N
O
O
H
H
H
H
[Co*]-H+ (Λ-1c) + NIS
PhCOOH (5b) + NIS
I
N
O
O
H
H
H
H
Figure 1 1H NMR analysis of mixtures of NIS with Brønsted acid Λ-(S,S)-1c or benzoic acid (5b) in CDCl3.
Supporting Information
2 + 3 or 5
NIS
4 or 6
exchange
Supporting information for this article is available online at
noncatalytic
reaction
https://doi.org/10.1055/s-0037-1611810.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
H
N
References and Notes
O
O
[Co*]-I+ (7)
[Co*]-H+
1
soluble
(1) (a) Varki, A. Glycobiology 1993, 3, 97. (b) Carbohydrates in Chem-
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(ion-pair)
I
O
R1O
I
O
O
[Co*]-
R1O
R1O
OR2
4α or 6α
2
O
R2
H
3 or 5
Scheme 2 Proposed mechanism
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function as bifunctional phase-transfer catalysts to shuttle
the N-iodosuccinimide to the reaction solution. Further
studies will focus on the development of stereoselective ha-
logenations catalyzed by Brønsted acids of anionic chiral
Co(III) complexes.
Funding Information
We are grateful for financial support from NSFC (Grants 21672002),
Anhui Provincial Natural Science Foundation (1908085J07), Young
Talent Program in Anhui Provincal University (gxyqZD2017017),
Opening Project of State Key Laboratory of Tea Plant Biology and Utili-
zation (SKLTOF20150108) and the Key Project of Anhui Tabaco Com-
pany (20160551015).
N
ati
o
n
a
lNaturalS
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a
(2
1
6
7
2
0
0
2)
Acknowledgment
We sincerely thank Prof. Zheng-Zhu Zhang and Dr. Chuan-Zhi Yao
(AHAU) for their support.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H

G
R. Wang et al.
Letter
Synlett
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(15) 2-Deoxy-2-Iodoglycoside 4aa; Typical Procedure
A 10-mL oven-dried vial was charged with catalyst Λ-1c (7.2
mg, 0.01 mmol), NIS (24.8 mg, 0.11 mmol), activated 4 Å MS
(100 mg), glycal 2a (41.6 mg, 0.10 mmol), and distilled CH2Cl2 (1
mL) at r.t. in the absence of light. Alcohol 3a (0.12 mmol) was
added and the resulting solution was stirred vigorously under
N2 for 24 h. The reaction was then quenched with Et3N (140 L,
1.0 mmol) and sat. aq Na2S2O3 (0.2 mL). The mixture was puri-
fied by flash column chromatography to give the 2-deoxy-2-
iodoglycosides 4aa as an / mixture.
4aa
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H

H
R. Wang et al.
Letter
Synlett
Colorless oil; yield: 43.9 mg (67%); Rf = 0.43 (PE–EtOAc, 10:1);
[]D20 +3.45 (c 1.27, CHCl3). 1H NMR (600 MHz, CDCl3):  = 7.48–
7.35 (m, 4 H), 7.35–7.19 (m, 14 H), 7.16 (d, J = 6.2 Hz, 2 H), 5.30
(s, 1 H), 4.84 (d, J = 10.8 Hz, 1 H), 4.72–4.66 (m, 3 H), 4.52–4.46
(m, 5 H), 3.92–3.91 (m, 2 H), 3.80–3.75 (m, 1 H), 3.69 (d, J = 10.8
Hz, 1 H), 3.37–3.34 (m, 1 H). 13C NMR (151 MHz, CDCl3):
 = 138.46, 138.29, 137.80, 136.98, 128.51, 128.44, 128.35,
128.10, 128.08, 128.05, 127.82, 127.69, 127.52, 100.85, 100.80,
76.05, 75.31, 73.47, 72.51, 71.04, 69.54, 69.00, 33.58, 33.55.
HRMS (ESI): m/z [M + Na]+ calcd for C34H35NaIO5: 673.1427;
found: 673.1420.
mL) at r.t. in the absence of light. BzOH (5a; 0.15 mmol) was
added and the resulting solution was stirred vigorously under
N2 for 12 h. The reaction was then quenched with Et3N (140 L,
1.0 mmol) and sat. aq Na2S2O3 (0.2 mL). The mixture was puri-
fied by flash column chromatography to give the glycosyl car-
boxylate 6a as a / mixture.
6a
Colorless oil; yield: 42.7 mg (64%); Rf = 0.4 (PE–EtOAc, 8:1);
[]D20 +3.78 (c 0.82, CHCl3). 1H NMR (600 MHz, CDCl3):  = 7.93
(d, J = 7.0 Hz, 2 H), 7.59 (t, J = 7.4 Hz, 1 H), 7.43 (t, J = 7.8 Hz, 2 H),
7.41–7.35 (m, 4 H), 7.34–7.24 (m, 9 H), 7.22–7.16 (m, 2 H), 6.66
(s, 1 H), 4.90 (d, J = 10.5 Hz, 1 H), 4.76–4.72 (m, 2 H), 4.58–4.52
(m, 4 H), 4.13–4.09 (m, 1 H), 4.07–4.03 (m, 1 H), 3.83 (dd, J =
11.3, 4.0 Hz, 1 H), 3.71 (dd, J = 11.3, 1.6 Hz, 1 H), 3.33 (dd, J = 8.7,
4.1 Hz, 1 H). 13C NMR (151 MHz, CDCl3):  = 164.07, 138.37,
138.08, 137.26, 133.75, 129.92, 129.12, 128.62, 128.57, 128.49,
128.38, 128.34, 128.32, 128.11, 127.94, 127.81, 127.59, 96.17,
76.20, 75.63, 75.31, 73.67, 71.22, 68.65, 31.20. HRMS (ESI): m/z
[M+Na]+ calcd for C34H33INaO6: 687.1220; found: 687.1215.
6a
4aa
White solid; yield: 9.5 mg (15%); mp 101–103 °C; Rf = 0.38 (PE–
20
EtOAc, 10:1); []D +4.91 (c 0.55, CHCl3). 1H NMR (600 MHz,
CDCl3):  = 7.47–7.36 (m, 4 H), 7.36–7.26 (m, 14 H), 7.19 (d, J =
6.9 Hz, 2 H), 4.97 (d, J = 10.2 Hz, 1 H), 4.92 (d, J = 11.7 Hz, 1 H),
4.85 (d, J = 10.1 Hz, 1 H), 4.80 (d, J = 10.9 Hz, 1 H), 4.68 (d, J =
11.8 Hz, 1 H), 4.62 (t, J = 9.6 Hz, 2 H), 4.57 (t, J = 12.5 Hz, 2 H),
4.01–3.94 (m, 1 H), 3.77–3.70 (m, 3 H), 3.64 (t, J = 9.2 Hz, 1 H),
3.49 (d, J = 7.6 Hz, 1 H). 13C NMR (151 MHz, CDCl3):  = 138.17,
137.90, 137.85, 136.88, 128.55, 128.48, 128.42, 128.33, 128.18,
127.98, 127.89, 127.83, 127.76, 101.98, 86.01, 79.79, 75.62,
75.42, 75.03, 73.65, 71.39, 68.72, 32.68. HRMS (ESI): m/z [M +
Na]+ calcd for C34H35NaIO5: 673.1427; found: 673.1422. (see
Supporting Information for further information).
20
Colorless oil; yield: 6.5 mg (10%); Rf = 0.4 (PE–EtOAc, 8:1); []D
+65.61 (c 0.22, CHCl3). 1H NMR (600 MHz, CDCl3):  = 8.11 (d, J =
7.7 Hz, 2 H), 7.60 (t, J = 7.3 Hz, 1 H), 7.47 (t, J = 7.7 Hz, 2 H), 7.43
(d, J = 7.4 Hz, 2 H), 7.36 (t, J = 7.3 Hz, 2 H), 7.34–7.23 (m, 9 H),
7.17 (d, J = 7.4 Hz, 2 H), 6.05 (d, J = 9.5 Hz, 1 H), 5.00 (d, J = 10.2
Hz, 1 H), 4.91 (d, J = 10.2 Hz, 1 H), 4.82 (d, J = 10.8 Hz, 1 H), 4.60
(dd, J = 15.7, 11.5 Hz, 2 H), 4.48 (d, J = 12.1 Hz, 1 H), 4.19 (t, J =
9.8 Hz, 1 H), 3.87–3.69 (m, 5 H). 13C NMR (151 MHz, CDCl3):
 = 164.67, 137.76, 133.75, 130.34, 128.56, 128.51, 128.45,
128.16, 128.01, 127.98, 127.86, 127.80, 95.09, 85.65, 79.07,
76.17, 75.76, 75.10, 73.71, 68.02, 30.23. HRMS (ESI): m/z
[M+Na]+ calcd for C34H33INaO6: 687.1220; found: 687.1217. (See
Supporting Information for further information).
(16) Iodoglycosylations of either glucal (2b) or galactal (2d) with
alcohol 3c in the absence of the chiral-CoIII-complex-templated
Brønsted acid were also tested, affording the desired 2-deoxy-2-
iodoglycosides in yields of 52% and 24% with 2.5:1 and 1.8:1 dr,
respectively.
(17) 2-Deoxy-2-Iodoglycosyl Carboxylate 6a; Typical Procedure
A 10-mL oven-dried vial was charged with catalyst Λ-1c (7.2
mg, 0.01 mmol), NIS (27.0 mg, 0.12 mmol), activated 4 Å MS
(100 mg), glycal 2a (41.6 mg, 0.10 mmol), and distilled CH2Cl2 (1
© Georg Thieme Verlag Stuttgart · New York — Synlett 2019, 30, A–H