Sulfonium Salts of Iodine(I) Species as Efficient Reagents for the Regioselective Bisfunctionalisation of Glycals and Enol Ethers

Article abstract of DOI:10.1002/ejoc.201501183

A new sulfonium-salt-based iodine(I) reagent system for the vicinal functionalisation of glycals and enol ethers has been developed. The unprecedented iodine(I) complex, Me₃SI(OAc)₂, generated in situ from Me₃SI and PhI(OAc)₂, effectively promoted the one-pot iodocarboxylation using carboxylic acids, and iodoazidation using NaN₃ or TMSN₃ (trimethylsilyl azide). The scope and generality of the new reagent was probed for a wide range of substrates, including various substituted aromatic carboxylic acids, heterocyclic, alicyclic, and aliphatic carboxylic acids, and amino acids to obtain various functionalised glycoconjugates in high yields (99 %) and with diastereoselectivities up to 100 %. A new sulfonium-salt-based iodine(I) reagent system has been developed for the vicinal functionalisation of glycals and enol ethers. The unprecedented iodine(I) complex generated in situ from Me₃SI and PhI(OAc)₂ effectively promoted iodocarboxylation and iodoazidation reactions in excellent yields and with diastereoselectivities up to 100 %.

Full text of DOI:10.1002/ejoc.201501183

DOI: 10.1002/ejoc.201501183
Full Paper
Glycal Chemistry
Sulfonium Salts of Iodine(I) Species as Efficient Reagents for the
Regioselective Bisfunctionalisation of Glycals and Enol Ethers
Thurpu Raghavender Reddy,[a] Dodla Sivanageswara Rao,[a] Kalvacherla Babachary,[a] and
Sudhir Kashyap*[a,b]
Abstract: A new sulfonium-salt-based iodine(I) reagent system azide). The scope and generality of the new reagent was
for the vicinal functionalisation of glycals and enol ethers has probed for a wide range of substrates, including various substi-
been developed. The unprecedented iodine(I) complex, tuted aromatic carboxylic acids, heterocyclic, alicyclic, and ali-
Me3SI(OAc)2, generated in situ from Me3SI and PhI(OAc)2, effect- phatic carboxylic acids, and amino acids to obtain various func-
ively promoted the one-pot iodocarboxylation using carboxylic tionalised glycoconjugates in high yields (99 %) and with dia-
acids, and iodoazidation using NaN3 or TMSN3 (trimethylsilyl stereoselectivities up to 100 %.
Introduction
Hotha and coworkers investigated the regioselective functional-
isation of glycals using cetylammonium bromide (CTAB) under
critical micelle concentration conditions in combination with
trivalent iodine.[6a] In another report, a trivalent iodine com-
pound was used together with phosphinic acid for the iodo-
phosphoryloxylation of glycals.[6g] Reagents that have been
used for the iodoacetoxylation of alkenes and glycals include
CAN (ceric ammonium nitrate)/NaI/AcOH,[7a] IDCP (iodonium di-
collidine perchlorate),[7b] NIS (N-iodosuccinimide),[7c–7e] KIO3/
AcOH at 60 °C,[7f] NH4I/H2O2/Ac2O,[7g] and I2 in combination
with Cu(OAc)2[7h] or other heavy metal salts such as AgI, TlI, HgII,
or BiIII salts in glacial AcOH at high temperature. The use of
toxic heavy metal salts is restricted for the synthesis of active
pharmaceutical ingredients (APIs),[8] which encourages the de-
velopment of greener protocols for such transformations.
Considering the strongly electrophilic nature of the central
iodine atom in iodine(III) species such as PIDA [phenyliodine(III)
diacetate], and the inherent ability of these iodine atoms to
transfer weakly bound ligands, we hypothesised that a new
class of stable and effective organosulfur-based iodine(I) spe-
cies could be generated through the PhI(OAc)2-mediated oxid-
ation of trimethylsulfonium salts (Scheme 1). Sulfonium salts
such as trimethylsulf(ox)onium iodide have been in the Corey–
Chaykovsky reaction to generate sulfur ylides, such as dimethyl-
sulf(ox)onium methylide (Scheme 2, a).[9] Moreover, sulfonium
salts are important alkylating agents (Scheme 2, b).[10] For in-
stance, S-Adenosylmethionine (SAM) is a natural methylating
agent that is involved in the regulation of several cellular proc-
esses (Scheme 2, c).[10b–10d]
The rapid advancement of hypervalent iodine as an environ-
mentally benign and valuable oxidising agent has led to the
development of greener and more attractive alternatives to
toxic metal oxidants.[1] Over the decades, numerous hyperva-
lent iodine-based reagents have been developed, with particu-
lar focus on their applications in metal-catalyst-free reactions.
The vicinal bisfunctionalisation of olefins using hypervalent iod-
ine reagents is one important application for these reagents.[2]
Interest in the synthetic utility of iodine-based reagents in
stereo- and regioselective transformations has increased in re-
cent years. These low-toxic, highly efficient, and mild reagents[3]
have found promising and practical applicability in
carbohydrate chemistry.[4,5] The remarkable reactivity of iod-
ine(III) species towards the C-1–C-2 olefin moiety in glycals, an
electron-rich π-bond system, has been explored for a variety
of transformations.[4–6] In particular, the synthesis of 2-deoxy-2-
halo-glycopyranosyl acetates have attracted considerable atten-
tion, since these products can be used as glycosyl donors for
the assembly of biologically important 2-deoxy glycoconju-
gates.[6]
Kirschning and coworkers have explored the unique reactiv-
ity of hypervalent iodine, including polymer-supported iodate
reagents and their potential applications in the 1,2-cohalogena-
tion of C–C multiple bonds and glycal substrates.[5] Recently,
[a] Discovery Laboratory, Organic and Biomolecular Chemistry Division,
Indian Institute of Chemical Technology (CSIR),
Tarnaka, Uppal Road, Hyderabad 500007, India
E-mail: skashyap.iict@gov.in
Despite the remarkable synthetic applicability of sulfonium
salts in alkylation reactions and as the precursors to Corey's
sulfur ylides, iodine(I) surrogates of trimethylsulf(ox)onium salts
have no precedent in organic chemistry. We report in this
paper the preparation and application of new iodine(I)-based
sulfonium salts, and emphasise the metal-free 1,2-cohalogena-
tion process that is possible using these reagents. As part of
skashyap@iict.res.in
[b] Academy of Scientific and Innovative Research,
Indian Institute of Chemical Technology (CSIR),
Hyderabad 500007, India
http://www.iictindia.org
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501183.
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Table 1. Initial studies and optimisation of diacetoxyiodate(I) reagent.[a]
Scheme 1. Rational for 1,2-cohalogenation of olefin using sulfonium salts-
based iodate(I) reagent.
Entry Reagent (equiv.) Solvent
Time
Yield [%][b] α-manno/β-gluco[c]
1
2
3
4
5
6
7
3a (1.1)
–
–
–
CH2Cl2
CH3CN
toluene
EtOAc
THF
24 h
24 h
24 h
24 h
36 h
24 h
10 min
10 min
8 h
68
72
55
56
42
84
92
98
93
96
94
84
70:30
75:25
76:24
73:27
73:27
75:25
78:22
80:20
76:24
77:23
79:21
70:30
–
3a (2.2)
3a (1.1)
1a (1.1), 2 (1.1) AcOH
–
–
–
CH3CN
AcOH
8[d]
9[d]
10[d]
11[d]
CH2Cl2
CH3CN
toluene
8 h
12 h
30 min
12[d] 1b (1.1), 2 (1.1) AcOH
[a] Reaction conditions: 5a (50 mg, 0.18 mmol, 1.0 equiv.), solvent (1 mL),
25 °C. [b] Isolated yield after column chromatography. [c] Diastereomeric ra-
tios were determined by 1H NMR spectroscopy. [d] Reactions were carried
out in one pot.
To further improve the yield and selectivity of this reaction,
we tested different solvents. The solvent screening revealed
that acetonitrile was most effective solvent; it delivered the de-
sired product in acceptable yield (72 %) with a slightly in-
creased diastereoselectivity (Table 1, entry 2). In contrast, the
use of toluene, EtOAc, or THF resulted in poor yields (Table 1,
entries 3–5). Further increasing the amount of 3a (2.2 equiv.)
increased the reaction rate, and led to a slight improvement in
the yield (84 %) without changing the dr (Table 1, entry 6). A
remarkable improvement was achieved when the reaction was
run in acetic acid as the solvent for 10 min (Table 1, entry 7).
The use of a mixed solvent system or lowering the temperature
led to a decrease in the yield without enhancing the selectivity.
Next, we wondered whether the reaction could be carried
out in one pot by generating 3a in situ using 1a and 2 (Table 1,
entries 8–11). This reaction did proceed to give the desired
product (i.e., 6) in 98 % yield and with a better diastereoselect-
ivity (Table 1, entry 8). As shown in Table 1, in almost all the
solvents tested, the reaction proceeded smoothly and cleanly
to give 6 in high yield, with slight variations in the diastereo-
selectivity (Table 1, entries 9–11). Trimethylsulfoxonium iodide
(1b) efficiently promoted this transformation when used to-
gether with 2, albeit with a lower selectivity than that seen
when 1a was used together with 2 (Table 1, entry 12).
Scheme 2. Sulfonium salts in chemistry and biology.
our research directed towards the development of new glycos-
ylation protocols and syntheses of glycoconjugates,[11] we have
studied the efficiency of these reagents for the synthesis of 2-
deoxy-2-halosugars, exploiting the enol ether functionality of
glycals.
Results and Discussion
The sulfonium bis(acetoxy)iodate(I) complex Me3SI(OAc)2 (3a)
was conveniently prepared from trimethylsulfonium iodide (1a)
through oxidative transfer of acetyl groups using PhI(OAc)2 (2)
as a stoichiometric oxidant (Scheme 3).[12a] Iodobenzene (4) was
formed as a by-product.
Having developed these optimised reaction conditions, we
went on to investigate the scope of new reagent system. The
Scheme 3. Sulfonium bis(acetoxy)iodate(I) complex.
Initially, we attempted to seek an effective method for the results are presented in Table 2. Initially, we explored the iodo-
iodoacetoxylation of 3,4,6-tri-O-acetyl- -glucal (5a) with 3a, acetoxylation of various protected glucals 5b–5e. A variety of
D
and the results are summarised in Table 1. Accordingly, a pre- protecting groups, including benzoyl, methyl, benzyl, and silyl
formed solution of 5a in CH2Cl2 was treated with 3a (1.1 equiv.) groups, were tolerated by the new reagent system, and the
under an inert atmosphere at room temperature. The reaction corresponding glycosyl acetates were obtained (Table 2,
wasfinishedwithin24h,andgavethecorrespondingglycosylacet- entries 1–4). We also screened the reactivity of other glycals
ate (i.e., 6) as a mixture of 2-deoxy-2-iodo-α-mannopyranosyl under the same conditions. Of particular note, the reaction of
and 2-deoxy-2-iodo-β-glucopyranosyl acetates in 68 % yield
D
-galactal (5f) with the sulfonium-based iodine(I) reagent gave
(dr = 2.3:1) as the result of 1,2-anti addition. (Table 1, entry 1).
significantly better results than those obtained with the phos-
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phonium or ammonium analogues in terms of yield and dia-
Encouraged by these results, we next studied the feasibility
of using the new iodine(I) reagent with other carboxylic acids
to generate structurally diverse glycoconjugates (Table 3). As a
model reaction, the in-situ iodocarboxylation of the unfunction-
alised C-1=C-2 double bond in glycal 5a with benzoic acid
(2.2 equiv.) was carried out by using 1a and 2 in CH3CN as the
solvent. 2-Iodo-2-deoxyglycosyl benzoate 19 was obtained in
moderate yield (with a 1.6:1 diastereoisomeric ratio), along with
a significant amount of glycosyl acetate 6 (dr = 3:1). This side-
product was formed as a result of competitive nucleophilic at-
tack by acetate, liberated by the reaction of 3a with benzoic
acid. We then adopted a variant method to overcome this se-
lectivity issue. Treatment of 2 (1.1 equiv.) and benzoic acid
(2.2 equiv.) with 1a (1.1 equiv.) in CH3CN presumably provides
stereoselectivity[12b] (Table 2, entry 5).
Table 2. Scope of Me3SI(OAc)2 promoted one-pot iodoacetoxylation (TBS =
tert-butyldimethylsilyl).[a]
Table 3. One-pot iodocarboxylation of 5a with carboxylic (amino) acids.[a]
[a] Reaction conditions: Glycal (1.0 equiv.), 1a (1.1 equiv.), 2 (1.1 equiv.), acetic
acid (1 mL), 25 °C. [b] Isolated and unoptimised yield after purification by
column chromatography. [c] Ratios were determined by 1H NMR spectro-
scopy, based on relative integration of anomeric protons.
We also investigated whether the protocol could be used
with glycals derived from 6-deoxysugars. Thus, we carried out
[a] Reaction conditions: (i) 1a (1.1 equiv.), 2 (1.1 equiv.), carboxylic acid
(2.2 equiv.), CH3CN (10 mL), 25 °C, 1 h, azeotroping off the acetic acid;
(ii) CH3CN (2 mL), 5a (1.0 equiv.), 25 °C, 1 h. Diastereomeric ratios were deter-
mined by 1H NMR spectroscopic analysis of the isolated compounds, and are
given in parentheses. [b] Reaction was carried out without azeotroping off
the acetic acid. [c] Reaction was carried out at 80 °C for 1 h after removing
the solvent. [d] Reaction was conducted at 0 °C for 5 h after removing the
solvent. [e] Reactions was carried out in CH2Cl2 as the solvent, 25 °C, 8 h.
[f] (i) 2 (1.1 equiv.), carboxylic acid (2.2 equiv.), CH3CN (10 mL), 25 °C, 1 h,
azeotroping off the acetic acid; (ii) CH3CN (2 mL), 1a (1.1 equiv.), 5a
(1.0 equiv.), 25 °C, 1 h.
iodoacetoxylation reactions of
-xylal (5i), -arabinal (5j), and
D
-rhamnal (5g),
L
-rhamnal (5h),
D
D
L-arabinal (5k) using in-situ gen-
erated 3a, and the corresponding glycosyl acetates were ob-
tained (Table 2, entries 6–10).
The disaccharide-derived substrates
D
-lactal (5l) and D-maltal
(5m), containing 1,4-glycosidic linkages, participated smoothly
in this process to give the corresponding disaccharide acetates
in excellent yields (Table 2, entries 11–12).
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reactive iodine(I)-based sulfonium salt 3b, with molecular for- used as key precursors for the synthesis of 2-amino-2-deoxy-
mula Me3SI(OBz)2. Following azeotropic removal of acetic acid, glycosides.[14]
3b should be capable of promoting the chemoselective 1,2-
cohalogenation of the C=C bond.
As shown in Table 4, we first tested different azide sources
and reaction conditions. In an initial experiment, azidoiodin-
ation of 5a using 3a with TMSN3 (trimethylsilyl azide; 3 equiv.)
in CH2Cl2 as the solvent gave a mixture of glycosyl azides 46
(42 % yield) and glycosyl acetates 6 (36 % yield) after 24 h at
ambient temperature (Table 4, entry 1). Increasing the amount
of TMSN3 to 5 equiv. (Table 4, entry 2) and switching the solvent
to acetonitrile overcame the competition from acetate, and 46
was formed chemoselectively in an improved yield of 90 %
(Table 4, entry 3). When the azide source was changed to NaN3
(3.0 equiv.), the desired product was formed in an improved
yield of 96 % (Table 4, entry 4).
Subsequently, we investigated the effects of temperature
and solvent on the sterochemical outcome of this reaction (see
Table 3, footnotes [c–f]). When the iodocarboxylation reaction
was run at 80 °C, the desired product (i.e., 19) was formed in
excellent yield with a dr of 73:27. A similar diastereoselectivity
was obtained when the reaction was run at 0 °C, however this
required a prolonged reaction time. Changing the solvent sys-
tem or altering the sequence of addition of the reagents led to
slight improvements in the dr. However, the best results were
obtained when the reaction was carried out at room tempera-
ture using acetonitrile as the solvent. Thus, reagent 3b effi-
ciently promoted the iodobenzoyloxylation of glycal 5a to give
glycosyl benzoate 19 exclusively, in excellent yield, and with a
high dr of 91:9.[12c]
Table 4. Optimisation and substrate scope of azidoiodination.[a]
With this approach, the diastereoselectivity increased com-
pared with the I2/AgOBz reagent system,[12c] the reaction was
run at ambient temperature, and the amount of side-products
was diminished. We went on to study a wide range of sterically
diverse carboxylic acids, including aromatic, alicyclic, aliphatic,
and heterocyclic compounds. In general, the protocol tolerated
both electron-rich and electron-deficient carboxylic acids, and
the corresponding glycosyl carboxylates (i.e., 20–32) were
formed in excellent yields. It is noteworthy that 3,4,5-trimethox-
ybenzoic acid, a relatively highly substituted substrate, also
worked well in the one-pot process to give glycoside 33. In
addition, picolinic, nicotinic, and isonicotinic acids bearing het-
erocyclic groups reacted smoothly under the optimal condi-
tions to give pyridine derivatives 34–36. Furthermore, the alicy-
clic carboxylic acids cyclohexanecarboxylic acid, caprylic
acid,[13a,13b] and phenoxyacetic acid, which also contains a
phenyl ether linkage, were successfully coupled with sugar mol-
ecules to obtain the corresponding glycoconjugates (i.e., 37–
39). Significantly, derivatives of phenoxyacetic acid are used as
organic acid herbicides, and also in the investigation of clinical
pharmacokinetics of mammalian species.[13c]
Entry
Glycal
Azide
Time [h]
Product, yield[b]
dr[c]
1[d]
2[d,e]
3[e]
4
5
6
5a
5a
5a
5a
5d
5f
TMSN3
TMSN3
TMSN3
NaN3
NaN3
NaN3
24
16
12
8
10
12
12
12
46, 42 % (6, 36 %)
46, 84 %
71:29
71:29
75:25
77:23
100:0
84:16
55:45
65:35
46, 90 %
46, 96 %
47, 94 %
48, 89 %
49, 92 %
50, 95 %
7
8
5l
5m
NaN3
NaN3
[a] Reaction conditions: 3a (1.1 equiv.), azide (3.0 equiv.), CH3CN (2 mL), glycal
(1.0 equiv.), 0–25 °C. [b] Isolated yield. [c] Ratios were determined by 1H
NMR spectroscopy. [d] Reactions were carried out in CH2Cl2 as the solvent.
[e] 5.0 equiv. TMSN3 was used.
This protocol also worked well for the high-yielding azido-
iodination of other glycals (Table 4, entries 5–8). It is pertinent
to mention that benzylated glucal 5d reacted in a highly dia-
stereoselective manner to give the α-manno product exclusively
(Table 4, entry 5). In contrast, disaccharide glycals 5l and 5m
resulted in mixtures of α-manno/β-gluco products (Table 4, en-
tries 6 and 7).
The in situ generation of the complex trimethylsulfonium
bis(azido)iodate(I) (3c) from 3a using TMSN3 or NaN3 is an ad-
vantageous and promising alternative to the commonly used
halogen azide methods. Moreover, this process could signifi-
cantly overcome the “azidophobia”[15a] associated with the use
of highly explosive and toxic X–N3 or hydrazoic acid.[15b]
We further examined the reactivity of 3a in a metal-free
alkoxyiodination reaction. Thus, coupling of 5a with MeOH as
the nucleophile in the presence of 3a (1.1 equiv.) in CH3CN as
the solvent gave methyl 2-iodo-2-deoxyglycoside 51 in 94 %
yield as a diastereomeric mixture (dr = 84:16), with high select-
ivity in favour of the α-manno isomer along with β-gluco as the
minor isomer (Scheme 4).
Owing to the unique importance of amino acids and pept-
ides in biological systems, we next turned our attention to de-
rivatives of these compounds. Thus, different N-protected
[Fmoc (fluorenylmethoxycarbonyl), Cbz (benzyloxycarbonyl),
Bz] amino acids were successfully coupled with sugars to gener-
ate amino acid glycoconjugates (40–45).
When a combination of PIDA and trimethylsulfonium iodide
was used together with other carboxylic acids to generate re-
active sulfonium salts of iodine(I) dicarboxylates, the reactions
of these reagents with glycals always took place with anti regio-
selectivity. It is noteworthy that complete stereoselectivity was
observed for benzoic acids bearing chloro or bromo substitu-
ents, and also for 2-pyridinecarboxylic acid and 3-pyridine-
carboxylic acid.
We next demonstrated the versatility of the transition-metal-
free and operationally simple iodocarboxylation reaction by us-
Having established a robust method for iodocarboxylation,
we envisioned a straightforward approach to the haloazidation ing the sulfonium-based reagent system for the bisfunctionali-
of glycals. This would lead to 2-deoxyglycosyl azides, which are sation of a cyclic enol ether without substituents on the pyran
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Scheme 4. One-pot alkoxyiodination for the synthesis of 2-deoxy glycoside.
ring. Thus, treatment of 3,4-dihydro-2H-pyran (5n; DHP) with 3a isomer (Scheme 7). This finding suggests that the utility of the
(1.1 equiv.) in DCE (1,2-dichloroethane) resulted in an iodo- new organosulfur-based iodate(I) reagent in metal-free dia-
carboxylation reaction to give trans-3-iodo-2-acetoxypyran (52) stereoselective processes is not limited to compounds contain-
in 86 % yield (Scheme 5).
ing activated C=C double bonds.
Scheme 7. Preparation of a β-iodocarboxylate from an unactivated alkene
with 3a.
Conclusions
Scheme 5. Stereoselective synthesis of β-iodo-acetoxy(azido) derivatives of
5n.
In summary, we present a new sulfonium-salt-based iodine(I)
reagent for the vicinal functionalisation of glycals to access
glycoconjugates in a stereocontrolled manner. The new iod-
ine(I) reagent is conveniently generated in situ under metal-free
conditions. It can be used with a wide range of substrates in
environmentally benign and high-yielding transformations. The
transformation is run at ambient temperature under mild reac-
tion conditions, and using a single equivalent of PIDA. Compar-
ing this to other protocols that require a threefold excess of
oxidant further highlights the effectiveness of the new rea-
gents. Further investigations into the 1,2-cohalogenation of C–
C multiple bonds using the developed iodine(I) reagents are in
progress.[17] It is likely that these unprecedented results on the
use of iodine(I) reagents as a new alternative for the bisfunc-
tionalisation of unactivated alkenes will contribute significantly
to modern organic chemistry.
Importantly, the iodoacetoxylation of 5n proceeded in with
good regioselectivity to give the corresponding β-iodocarboxyl-
ate as a single diastereomer,[16] confirming the benefits of the
new method. Similarly, trans-iodo-azido derivative 53 was con-
veniently prepared from 5n in high yield with exclusive anti
diastereoselectivity using the optimised iodoazidation reaction
conditions given in Table 4.
In addition, an amino acid, Bz-Phe-OH, was successfully in-
corporated into DHP (5n) by using this system at ambient tem-
perature to generate the corresponding trans-iodocarboxylate
(i.e., 54) in 92 % yield as a diastereomeric mixture (dr = 1:1;
Scheme 6). The structure of 54 was established by spectro-
scopic analysis; the data was consistent with previously re-
ported data.[2f] Thus, also in this case, the iodocarboxylation of
the enol ether proceeded in an anti regioselective manner.
Experimental Section
General Methods: All reactions were carried out in flame-dried
round-bottomed flasks, fitted with rubber septa or glass gas adapt-
ers, under a positive pressure of nitrogen or argon. Analytical thin-
layer chromatography (TLC) was carried out using aluminum-
backed UV F254 precoated silica gel flexible plates. Removal of sol-
vent under reduced pressure refers to distillation with a rotary evap-
orator attached to a vacuum pump (ca. 3 Torr). Melting points were
obtained in open capillary tubes using a micro melting-point appa-
ratus. NMR spectra were recorded with 300, 400, or 500 MHz nuclear
1
magnetic resonance spectrometers. H NMR chemical shifts (δ) are
Scheme 6. Iodocarboxylation of DHP (5n) with amino acid.
reported in ppm relative to tetramethylsilane (δ = 0.0 ppm), using
the residual solvent signal as an internal standard (δ = 7.26, singlet,
for CDCl3), or using tetramethylsilane itself. The proton resonances
are annotated as: chemical shift, multiplicity (s, singlet; d, doublet;
t, triplet; q, quartet; m, multiplet; br., broad), coupling constant (J
[Hz]), and integration. 13C NMR chemical shifts are reported in ppm,
Following the success of the 1,2-cohalogenation of enol-
ether-derived substrates, we next investigated the reactivity of
an alkene with this reagent. Pleasingly, the reaction of cyclohex-
ene (5o) with 3a in DCE proceeded smoothly to give the corre-
sponding β-iodocarboxylate (i.e., 55) in 86 % yield as a single and spectra were calibrated using the central line of the triplet at
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+
δ = 77.0 ppm for CDCl3. High-resolution mass analysis was carried
out with a mass spectrometer using the ESI-TOF technique.
–4.6, –5.3, –5.4 ppm. HRMS (ESI): calcd. for C26H59INSi3O6 [M +
NH4]+ 692.27149; found 692.26894.
Preparation of Me3SI(OAc)2 (3a): An equimolar mixture of trimeth-
ylsulfonium iodide (1) (500 mg, 2.45 mmol, 1.0 equiv) and PIDA
Compound 14: Following the general procedure using 3,4-di-O-
acetyl-D-xylal, and purifying by silica gel column chromatography
(2) (790 mg, 2.45 mmol, 1.0 equiv) in CH2Cl2 was stirred at room gave 14 (91 mg, 95 %; dr = 40:60) as an oily liquid. 1H NMR
temperature. The resulting turbid dark yellow mixture turned into
a dark brown then a dark red homogeneous solution after 15 min.
The reaction mixture was cooled to 0 °C. Diethyl ether was added
to give a yellow precipitate. This material was collected by filtration,
washed with diethyl ether, and dried in vacuo to give analytically
(500 MHz, CDCl3): δ = 5.83 (d, J = 9.0 Hz, 1 H), 5.34 (dd, J = 10.6,
8.8 Hz, 1 H), 5.00 (m, 1 H), 4.17 (dd, J = 11.7, 5.3 Hz, 1 H), 3.95 (dd,
J = 10.6, 9.0 Hz, 1 H), 3.53 (dd, J = 11.7, 10.2 Hz, 1 H), 2.16 (s, 3 H),
2.12 (s, 3 H), 2.04 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.6,
169.2, 168.5, 94.5, 74.2, 68.9, 63.5, 25.3, 20.7, 20.6, 20.5 ppm. HRMS
(ESI): calcd. for C11H15INaO7+ [M + Na]+ 408.97547; found 408.97659.
1
pure 3a (750 mg, 95 %), m.p. 98 °C. H NMR (500 MHz, CDCl3): δ =
3.22 [s, 9 H, (CH3)3], 1.99 (s, 6 H, CH3CO2) ppm. 13C NMR (125 MHz,
CDCl3): δ = 176.4 (CH3CO2), 27.8 [(CH3)3], 21.6 (CH3CO2) ppm.
C7H15IO4S (322.2): calcd. C 26.10, H 4.69, S 9.95; found C 26.45; H,
4.73; S, 9.73.
Compound 15: Following the general procedure using 3,4-di-O-
acetyl-D-arabinal, and purifying by silica gel column chromatogra-
phy gave 15 (80 mg, 83 %; dr = 72:28) as an oily liquid. 1H NMR
(400 MHz, CDCl3): δ = 6.01 (d, J = 8.3 Hz, 1 H), 5.59 (t, J = 2.5 Hz, 1
H), 5.11 (ddd, J = 12.3, 5.2, 2.9 Hz, 1 H), 4.23 (dd, J = 8.3, 3.1 Hz, 1
H), 3.99–3.92 (m, 2 H), 2.21 (s, 3 H), 2.15 (s, 3 H), 2.03 (s, 3 H) ppm.
General Procedure for One-Pot Iodoacetoxylation: A preformed
solution of Me3SI (1a; 1.1 equiv.) and PhI(OAc)2 (2; 1.1 equiv.) in
solvent (1 mL) was treated with glycal (1.0 equiv.) at room tempera- 13C NMR (100 MHz, CDCl3): δ = 169.5, 169.4, 168.8, 92.8, 69.8, 66.0,
+
ture. The mixture was stirred until the complete consumption of
glycal was observed. The mixture was diluted with EtOAc (10 mL),
and washed with saturated aqueous NaHCO3 (5 mL), and saturated
aqueous sodium thiosulfate (2 mL). The aqueous phases were ex-
tracted with EtOAc (3 × 30 mL). The combined organic layers were
washed with brine, dried with anhydrous Na2SO4, and concentrated
in vacuo. The residue was purified by silica gel column chromatog-
raphy to give the desired glycosides (6–18). All products were fully
characterised by 1H and 13C NMR spectroscopy and mass spectrom-
etry. The data were consistent with literature data, and were in com-
plete agreement with the assigned structures (see Supporting Infor-
mation for NMR spectra). The spectroscopic data for major isomers
are outlined here.
62.7, 24.0, 20.7, 20.6, 20.5 ppm. HRMS (ESI): calcd. for C11H15INaO7
[M + Na]+ 408.97547; found 408.97664.
Compound 16: Following the general procedure using 3,4-di-O-
acetyl-L-arabinal, and purifying by silica gel column chromatogra-
phy gave 16 (83 mg, 86 %; dr = 67:33) as an oily liquid. 1H NMR
(500 MHz, CDCl3): δ = 6.01 (d, J = 8.3 Hz, 1 H), 5.58 (t, J = 2.5 Hz, 1
H), 5.11 (ddd, J = 9.4, 5.1, 2.9 Hz, 1 H), 4.23 (dd, J = 8.3, 3.0 Hz, 1
H), 4.01–3.98 (m, 1 H), 3.95 (dd, J = 11.4, 9.6 Hz, 1 H), 2.20 (s, 3 H),
2.15 (s, 3 H), 2.02 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.6,
169.5, 168.9, 92.8, 69.9, 66.1, 62.7, 24.0, 20.7, 20.6 ppm. HRMS (ESI):
calcd. for C11H15INaO7 [M + Na]+ 408.97547; found 408.97717.
+
Compound 18: Following the general procedure using per-O-acet-
yl-D-maltal, and purifying by silica gel column chromatography gave
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-iodo-β-
1,3,4,6-Tetra-O-acetyl-2-deoxy-2-iodo-α-
D
D
-glucopyranose and
-mannopyranose (6):
18 as a white solid(62 mg, 94 %; dr = 90:10) as a white solid, m.p.
1
122 °C. H NMR (500 MHz, CDCl3): δ = 6.35 (d, J = 1.7 Hz, 1 H), 5.56
Following the general procedure using 3,4,6-tri-O-acetyl-D-glucal
(d, J = 3.9 Hz, 1 H), 5.40 (t, J = 9.9 Hz, 1 H), 5.09 (t, J = 9.7 Hz, 1 H),
4.92 (dd, J = 10.5, 4.1 Hz, 1 H), 4.53 (dd, J = 4.23, 1.8 Hz, 1 H), 4.50
(dd, J = 8.2, 4.4 Hz, 1 H), 4.45 (dd, J = 12.3, 2.1 Hz, 1 H), 4.28 (dd,
J = 12.5, 3.6 Hz, 1 H), 4.23 (dd, J = 9.3, 8.3 Hz, 1 H), 4.21 (dd, J =
6.7, 4.2 Hz, 1 H), 4.14–4.10 (m, 1 H), 4.08 (dd, J = 10.0, 2.1 Hz, 3 H),
4.01 (dt, J = 10.0, 2.4 Hz, 1 H), 2.21 (s, 3 H), 2.15 (s, 3 H), 2.13 (s, 3
H), 2.11 (s, 3 H), 2.04 (s, 3 H), 2.02 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 170.5, 170.1, 170.0, 169.8, 169.3, 168.3, 95.9, 94.2, 71.8,
71.3, 70.1, 69.4, 68.5, 67.8, 63.6, 63.6, 62.5, 61.3, 26.9, 21.1, 20.9, 20.7,
(50 mg, 0.18 mmol, 1.0 equiv), and puriyfiyng by silica gel column
chromatography afforded the pure products β-gluco (17 mg) and
α-manno (68 mg) in 98% overall yields.
Data for the β-gluco diastereomer: 1H NMR (500 MHz, CDCl3): δ =
5.88 (d, J = 9.4 Hz, 1 H), 5.35 (dd, J = 11.1, 9.1 Hz, 1 H), 5.02 (dd,
J = 10.0, 9.3 Hz, 1 H), 4.33 (dd, J = 12.5, 4.4 Hz, 1 H), 4.10 (dd, J =
12.5, 2.1 Hz, 1 H), 3.99 (dd, J = 11.1, 9.6 Hz, 1 H), 3.88 (ddd, J = 10.0,
4.4, 2.1 Hz, 1 H), 2.18 (s, 3 H), 2.10 (s, 3 H), 2.08 (s, 3 H), 2.03 (s, 3 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 170.5, 169.5, 169.5, 168.5, 93.9,
71.2, 73.0, 68.4, 61.4, 25.7, 20.7, 20.5 ppm. HRMS (ESI): calcd. for
+
20.6, 20.6, 20.5, 20.4 ppm. HRMS (ESI): calcd. for C26H39INO17 [M +
NH4]+ 764.12572; found 764.12857.
C14H23INO9 [M + NH4]+ 476.04120; found 476.04132.
+
General Procedure for Iodocarboxylation: An equimolar mixture
of Me3SI (1a; 1.1 equiv.) and PhI(OAc)2 (2; 1.1 equiv.) in CH3CN
(10 mL) was treated with carboxylic acid (2.2 equiv.) at room tem-
perature. The reaction mixture was stirred at room temperature for
1 h. The solvent was then evaporated, and the residue was dried
under vacuum to ensure the complete removal of acetic acid.
1
Data for the α-manno diastereomer: H NMR (300 MHz, CDCl3): δ =
6.40 (br. s, 1 H), 5.46 (t, J = 9.6 Hz, 1 H), 4.59 (dd, J = 9.4, 4.3 Hz, 1
H), 4.54 (dd, J = 4.3, 1.3 Hz, 1 H), 4.23 (dd, J = 12.4, 4.5 Hz, 1 H),
4.16 (dd, J = 12.4, 2.2 Hz, 1 H), 4.15–4.09 (m, 1 H), 2.17 (s, 3 H), 2.12
(s, 3 H), 2.11 (s, 3 H), 2.07 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 170.5, 169.8, 169.2, 168.0, 94.5, 71.2, 68.4, 66.8, 61.6, 27.0, 20.8,
20.7, 20.6, 20.5 ppm. MS (ESI): m/z = 476 [M + NH4]+, 481 [M + Na]+.
The residue was then redissolved in CH3CN (2 mL), and 3,4,6-tri-O-
acetyl- -glucal (5a; 1.0 equiv.) was added. After TLC showed that
D
Compound 10: Following the general procedure using 3,4,6-tri-O-
tert-butyldimethylsilyl-D-glucal, and purifying by silica gel column
the reaction was complete, the mixture was diluted with EtOAc
(10 mL), and washed with saturated aqueous NaHCO3 (5 mL), and
saturated aqueous sodium thiosulfate (2 mL). The organic phases
were extracted with EtOAc (3 × 30 mL). The combined organic lay-
chromatography gave 10 (56 mg, 82 %; dr = 86:14) as a semi-solid.
1H NMR (500 MHz, CDCl3): δ = 6.25 (d, J = 4.5 Hz, 1 H), 4.39 (m, 1
H), 3.97 (t, J = 6.2 Hz, 1 H), 3.91–3.83 (m, 2 H), 3.80 (dd, J = 11.1, ers were washed with brine, dried with anhydrous Na2SO4, and con-
4.7 Hz, 1 H), 3.73 (m, 1 H), 2.11 (s, 3 H), 0.97 (s, 9 H), 0.91 (s, 9 H), centrated in vacuo. The residue was purified by silica gel column
0.90 (s, 9 H), 0.16 (s, 6 H), 0.13 (s, 3 H), 0.12 (s, 3 H), 0.08 (s, 3 H), chromatography to give the desired glycoconjugates (19–45) in
0.06 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 168.9, 93.6, 82.5,
good yields. The characterisation data for the major products are
79.0, 70.0, 61.5, 27.8, 26.3, 25.9, 25.8, 20.9, 18.3, 18.0, –3.3, –4.4, –4.7,
given below.
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Compound 19: Following the general procedure using benzoic
acid, and purifying by silica gel column chromatography gave 19
(89 mg, 95 %; dr = 91:09) as a white solid, m.p. 156 °C. 1H NMR
(500 MHz, CDCl3): δ = 8.07 (dd, J = 8.0, 1.3 Hz, 2 H), 7.66–7.62 (m,
1 H), 7.50 (t, J = 7.6 Hz, 2 H), 6.65 (d, J = 1.3 Hz, 1 H), 5.54 (t, J =
9.6 Hz, 1 H), 4.73 (dd, J = 9.3, 4.4 Hz, 1 H), 4.70 (dd, J = 4.2, 1.5 Hz,
1 H), 4.26 (dd, J = 11.9, 4.2 Hz, 1 H), 4.25–4.20 (m, 1 H), 4.18 (dd,
J = 11.9, 1.9 Hz, 1 H), 2.13 (s, 3 H), 2.11 (s, 3 H), 2.09 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.6, 169.9, 169.3, 163.6, 134.0,
129.9, 128.7, 95.2, 71.7, 68.8, 67.0, 61.7, 27.2, 20.9, 20.7, 20.6 ppm.
δ = 170.6, 169.8, 169.2, 162.2, 139.4, 134.9, 133.2, 131.3, 127.4, 95.9,
72.0, 68.7, 66.8, 61.7, 26.8, 20.8, 20.6, 20.5 ppm. HRMS (ESI): calcd.
for C19H19Cl2INaO9 [M + Na]+ 610.93430; found 610.93231.
+
Compound 25: Following the general procedure using 3-bromo-
benzoic acid, and purifying by silica gel column chromatography
gave 25 (103 mg, 96 %) as a white solid, m.p. 140 °C. 1H NMR
(400 MHz, CDCl3): δ = 8.17 (t, J = 1.7 Hz, 1 H), 7.99 (dt, J = 7.8,
1.2 Hz, 1 H), 7.77 (ddd, J = 8.0, 1.9, 0.9 Hz, 1 H), 7.39 (t, J = 7.9 Hz,
1 H), 6.63 (d, J = 1.1 Hz, 1 H), 5.54 (t, J = 9.3 Hz, 1 H), 4.71–4.66 (m,
2 H), 4.29–4.17 (m, 3 H), 2.13 (s, 3 H), 2.12 (s, 3 H), 2.10 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.6, 169.8, 169.2, 162.5, 136.9,
132.8, 130.3, 128.4, 122.8, 95.7, 71.8, 68.7, 66.9, 61.7, 26.9, 20.9, 20.7,
+
HRMS (ESI): calcd. for C19H21INaO9 [M + Na]+ 543.01225; found
543.00987.
+
20.6 ppm. HRMS (ESI): calcd. for C19H20BrINaO9 [M + Na]+
Compound 20: Following the general procedure using 2-fluoro-
620.92276; found 620.92090.
benzoic acid, and purifying by silica gel column chromatography
1
gave 20 (89 mg, 92 %, dr = 90:10) as a white solid, m.p. 132 °C. H
Compound 26: Following the general procedure using 4-nitro-
NMR (500 MHz, CDCl3): δ = 7.99 (td, J = 7.9, 1.8 Hz, 1 H), 7.60 (m, 1
H), 7.27 (td, J = 7.6, 1.1 Hz, 1 H), 7.19 (ddd, J = 10.9, 8.9, 0.9 Hz, 1
H), 6.67 (br. s, 1 H), 5.54 (t, J = 9.3 Hz, 1 H), 4.72–4.69 (m, 2 H), 4.27–
4.23 (m, 2 H), 4.18 (dd, J = 13.4, 3.8 Hz, 1 H), 2.12 (s, 3 H), 2.11 (s, 3
H), 2.09 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.6, 169.8,
169.3, 163.3, 161.7 (d), 160.7, 135.6 (d), 132.5, 124.3 (d), 117.2 (d),
95.2, 71.7, 68.7, 66.8, 61.7, 27.2, 20.8, 20.7, 20.6 ppm. HRMS (ESI):
benzoic acid, and purifying by silica gel column chromatography
gave 26 (86 mg, 85 %; dr = 80:20) as a white solid, m.p. 121 °C. H
1
NMR (400 MHz, CDCl3): δ = 8.35 (d, J = 9.0 Hz, 1 H), 8.24 (d, J =
9.0 Hz, 1 H), 6.67 (d, J = 1.2 Hz, 1 H), 5.54 (t, J = 9.3 Hz, 1 H), 4.72–
4.68 (m, 2 H), 4.29–4.19 (m, 3 H), 2.14 (s, 3 H), 2.12 (s, 3 H), 2.10 (s,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.5, 169.9, 169.2, 162.0,
151.0, 133.9, 130.0, 123.8, 96.0, 72.0, 68.6, 66.8, 61.6, 26.4, 20.8, 20.7,
calcd. for C19H20FINaO9 [M + Na]+ 561.00282; found 561.00142.
+
20.6 ppm. HRMS (ESI): calcd. for C19H20INNaO11 [M + Na]+
+
587.99732; found 587.99626.
Compound 21: Following the general procedure using 4-fluoro-
benzoic acid, and purifying by silica gel column chromatography
gave 21 (81 mg, 84 %; dr = 84:16) as a white solid, m.p. 145 °C. H
Compound 27: Following the general procedure using o-toluic
acid, and purifying by silica gel column chromatography gave 27
(91 mg, 95 %; dr = 91:09) as a pale yellow solid, m.p. 105 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.3 Hz, 1 H), 7.48 (td, J =
7.5, 1.3 Hz, 1 H), 7.31 (t, J = 7.5 Hz, 2 H), 6.63 (d, J = 1.1 Hz, 1 H),
5.53 (t, J = 9.1 Hz, 1 H), 4.71–4.66 (m, 2 H), 4.27–4.17 (m, 3 H), 2.64
(s, 3 H), 2.12 (s, 3 H), 2.11 (s, 3 H), 2.08 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 170.6, 169.9, 169.3, 164.3, 141.1, 133.0, 132.0,
130.8, 126.0, 95.0, 71.7, 68.9, 67.0, 61.8, 27.4, 21.9, 20.9, 20.7,
20.6 ppm. HRMS (ESI): calcd. for C20H23INaO9+ [M + Na]+ 557.02790;
found 557.02566.
1
NMR (400 MHz, CDCl3): δ = 8.09 (dd, J = 8.9, 5.3 Hz, 1 H), 7.17 (t,
J = 8.6 Hz, 1 H), 6.63 (d, J = 0.9 Hz, 1 H), 5.53 (t, J = 9.5 Hz, 1 H),
4.73–4.68 (m, 2 H), 4.28–4.20 (m, 2 H), 4.18 (dd, J = 11.7, 2.0 Hz, 1
H), 2.13 (s, 3 H), 2.11 (s, 3 H), 2.09 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.6, 169.9, 169.3, 165.0, 162.7, 132.6 (d), 124.8 (d),
116.1 (d), 95.3, 71.7, 68.7, 67.0, 61.7, 27.0, 20.9, 20.7, 20.6 ppm. HRMS
(ESI): calcd. for C19H20FINaO9 [M + Na]+ 561.00282; found 561.
+
00120.
Compound 22: Following the general procedure using 2-chloro-
benzoic acid, and purifying by silica gel column chromatography
gave 22 (90 mg, 90 %) as a white solid, m.p. 132 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.89 (d, J = 8.1 Hz, 1 H), 7.50 (dd, J = 4.5,
0.9 Hz, 2 H), 7.38 (m, 1 H), 6.67 (br. s, 1 H), 5.52 (t, J = 9.3 Hz, 1 H),
4.72–4.68 (m, 2 H), 4.27–4.17 (m, 3 H), 2.12 (s, 3 H), 2.11 (s, 3 H),
2.07 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 170.6, 169.8, 169.3,
163.1, 135.5, 132.1, 131.4, 126.9, 95.8, 72.0, 68.8, 66.0, 61.8, 27.1,
Compound 28: Following the general procedure using p-toluic
acid, and purifying by silica gel column chromatography gave 28
(89 mg, 93 %; dr = 98:02) as a white solid, m.p. 112 °C. 1H NMR
(500 MHz, CDCl3): δ = 7.95 (d, J = 8.2 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2
H), 6.63 (d, J = 1.4 Hz, 1 H), 5.53 (t, J = 9.6 Hz, 1 H), 4.72 (dd, J =
9.4, 4.4 Hz, 1 H), 4.69 (dd, J = 4.4, 1.6 Hz, 1 H), 4.25 (dd, J = 11.9,
4.2 Hz, 1 H), 4.23–4.19 (m, 1 H), 4.17 (dd, J = 11.9, 2.0 Hz, 1 H), 2.44
(s, 3 H), 2.12 (s, 3 H), 2.11 (s, 3 H), 2.09 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 170.7, 169.9, 169.3, 163.7, 145.0, 130.0, 129.4,
125.8, 95.1, 71.6, 68.8, 67.1, 61.8, 27.4, 21.8, 20.9, 20.7, 20.6 ppm.
+
20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for C19H20ClINaO9 [M +
Na]+ 576.97327; found 576.97120.
Compound 23: Following the general procedure using 4-chloro-
benzoic acid, and purifying by silica gel column chromatography
gave 23 (96 mg, 96 %) as a white solid, m.p. 118 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.99 (d, J = 8.7 Hz, 2 H), 7.48 (d, J = 8.7 Hz, 2
H), 6.63 (br. s, 1 H), 5.53 (t, J = 9.4 Hz, 1 H), 4.71–4.68 (m, 2 H), 4.29–
4.16 (m, 3 H), 2.13 (s, 3 H), 2.11 (s, 3 H), 2.09 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 170.6, 169.9, 169.3, 162.9, 140.6, 131.3, 129.1,
127.0, 95.5, 71.9, 68.8, 67.0, 61.8, 26.9, 20.9, 20.7, 20.6 ppm. HRMS
+
HRMS (ESI): calcd. for C20H23INaO9 [M + Na]+ 557.02790; found
557.02567.
Compound 29: Following the general procedure using 4-tert-butyl-
benzoic acid, and purifying by silica gel column chromatography
gave 29 (93 mg, 90 %; dr = 68:32) as a a pale yellow solid, m.p.
120 °C. 1H NMR (500 MHz, CDCl3): δ = 7.99 (d, J = 8.5 Hz, 2 H), 7.52
(d, J = 8.5 Hz, 2 H), 6.64 (d, J = 1.3 Hz, 1 H), 5.53 (t, J = 9.4 Hz, 1 H),
4.74 (dd, J = 9.4, 4.4 Hz, 1 H), 4.69 (dd, J = 4.4, 1.5 Hz, 1 H), 4.27–
4.17 (m, 3 H), 2.12 (s, 3 H), 2.11 (s, 3 H), 2.09 (s, 3 H), 1.35 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 170.7, 169.9, 169.5, 163.6,
157.9, 130.1, 129.9, 125.7, 125.3, 94.9, 71.6, 68.8, 67.1, 61.8, 31.0,
(ESI): calcd. for C19H20ClINaO9 [M + Na]+ 576.97327; found
+
576.97353.
Compound 24: Following the general procedure using 2,4-di-
chlorobenzoic acid, and purifying by silica gel column chromatogra-
phy gave 24 (99 mg, 94 %; dr = 95:05) as a white solid, m.p. 123 °C.
1H NMR (400 MHz, CDCl3): δ = 7.87 (d, J = 8.3 Hz, 1 H), 7.53 (d, J =
2.0 Hz, 1 H), 7.38 (dd, J = 8.5, 2.0 Hz, 1 H), 6.66 (d, J = 0.9 Hz, 1 H),
5.53 (t, J = 9.2 Hz, 1 H), 4.71–4.68 (m, 2 H), 4.26–4.20 (m, 3 H), 2.12
(s, 3 H), 2.12 (s, 3 H), 2.08 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3):
+
27.4, 20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for C23H29INaO9 [M +
Na]+ 599.07485; found 599.07292.
Compound 30: Following the general procedure using o-anisic
acid, and purifying by silica gel column chromatography gave 30
(90 mg, 91 %; dr = 91:09) as a white solid, m.p. 125 °C. 1H NMR
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(500 MHz, CDCl3): δ = 7.87 (dd, J = 7.6, 1.6 Hz, 1 H), 7.55 (m, 1 H),
7.03 (m, 2 H), 6.63 (d, J = 1.3 Hz, 1 H), 5.51 (t, J = 9.6 Hz, 1 H), 4.82
(dd, J = 9.4, 4.2 Hz, 1 H), 4.64 (dd, J = 4.4, 1.5 Hz, 1 H), 4.29 (m, 1
H), 4.25 (dd, J = 12.2, 4.4 Hz, 1 H), 4.17 (dd, J = 11.9, 1.8 Hz, 1 H),
3.96 (s, 3 H), 2.11 (s, 6 H), 2.08 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.6, 169.8, 169.3, 163.7, 159.5, 134.7, 132.4, 120.3,
8.32 (dt, J = 7.9, 1.8 Hz, 1 H), 7.47 (dd, J = 7.9, 4.8 Hz, 1 H), 6.68 (d,
J = 1.2 Hz, 1 H), 5.54 (t, J = 9.4 Hz, 1 H), 4.72 (dd, J = 4.2, 1.5 Hz, 1
H), 4.69 (dd, J = 9.4, 4.4 Hz, 1 H), 4.27 (dd, J = 11.6, 3.9 Hz, 1 H),
4.22 (ddd, J = 11.7, 5.9, 1.5 Hz, 1 H), 4.19 (dd, J = 11.6, 9.7 Hz, 1 H),
2.13 (s, 3 H), 2.12 (s, 3 H), 2.10 (s, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 170.7, 169.8, 169.3, 162.5, 154.3, 151.0, 137.4, 124.7,
118.1, 112.0, 94.7, 71.4, 68.6, 67.2, 61.8, 55.8, 27.6, 20.9, 20.7, 123.6, 95.6, 71.9, 68.7, 66.9, 61.7, 26.7, 20.9, 20.7, 20.6 ppm. HRMS
20.6 ppm. HRMS (ESI): calcd. for C20H23INaO10+ [M + Na]+ 573.02281;
found 573.02081.
(ESI): calcd. for C18H21INO9 [M + H]+ 522.02555; found 522.02452.
+
Compound 36: Following the general procedure using isonicotinic
acid, and purifying by silica gel column chromatography gave 36
(88 mg, 94 %; dr = 94:06) as a pale yellow solid, m.p. 116 °C. 1H
Compound 31: Following the general procedure using p-anisic
acid, and purifying by silica gel column chromatography gave 31
(91 mg, 92 %; dr = 76:24) as a pale yellow solid, m.p. 109 °C. 1H NMR (500 MHz, CDCl3): δ = 8.86 (d, J = 4.7 Hz, 1 H), 7.87 (d, J =
NMR (500 MHz, CDCl3): δ = 7.02 (d, J = 8.8 Hz, 2 H), 6.97 (d, J =
5.9 Hz, 1 H), 6.66 (br. s, 1 H), 5.54 (t, J = 9.3 Hz, 1 H), 4.71–4.68 (m,
8.8 Hz, 2 H), 6.62 (br. s, 1 H), 5.51 (t, J = 9.4 Hz, 1 H), 4.73 (dd, J = 2 H), 4.26 (dd, J = 12.0, 7.9 Hz, 1 H), 4.23–4.18 (m, 2 H), 2.13 (s, 3
9.4, 4.2 Hz, 1 H), 4.68 (dd, J = 4.2, 1.3 Hz, 1 H), 4.27 (m, 1 H), 4.25–
4.12 (m, 3 H), 3.89 (s, 3 H), 2.12 (s, 3 H), 2.11 (s, 3 H), 2.09 (s, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 170.6, 169.9, 169.3, 164.2,
163.3, 132.4, 132.1, 120.8, 114.0, 113.9, 94.9, 71.6, 68.8, 67.1, 61.8,
H), 2.12 (s, 3 H), 2.10 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
170.7, 170.0, 169.3, 162.4, 150.8, 135.9, 122.9, 95.9, 71.9, 68.6, 66.8,
+
61.6, 26.4, 20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for C18H21INO9
[M + H]+ 522.02555; found 522.02457.
+
55.5, 27.4, 20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for C20H23INaO10
Compound 37: Following the general procedure using cyclohex-
anecarboxylic acid, and purifying by silica gel column chromatogra-
[M + Na]+ 573.02281; found 573.02075.
Compound 32: Following the general procedure using 4-butoxy- phy gave 37 (84 mg, 89 %; dr = 80:20) as a white semi-solid. 1H
benzoic acid, and purifying by silica gel column chromatography
gave 32 (94 mg, 88 %; dr = 86:14) as a pale yellow solid, m.p. 88 °C.
1H NMR (500 MHz, CDCl3): δ = 8.05 (d, J = 8.8 Hz, 2 H), 6.93 (d, J =
8.8 Hz, 2 H), 6.62 (d, J = 1.0 Hz, 1 H), 5.53 (t, J = 9.6 Hz, 1 H), 4.74
(dd, J = 9.4, 4.4 Hz, 1 H), 4.68 (dd, J = 4.2, 1.3 Hz, 1 H), 4.26 (dd, J =
12.0, 4.2 Hz, 1 H), 4.21 (m, 1 H), 4.18 (dd, J = 12.0, 2.1 Hz, 1 H), 4.03
(t, J = 6.5 Hz, 3 H), 2.12 (s, 3 H), 2.11 (s, 3 H), 2.09 (s, 3 H), 1.80 (m,
2 H), 1.54–1.47 (m, 2 H), 0.99 (t, J = 7.4 Hz, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 170.7, 169.9, 169.3, 163.6, 163.4, 132.3, 132.1,
121.4, 114.4, 114.2, 94.9, 71.5, 68.9, 68.0, 67.9, 67.1, 61.8, 31.1, 27.5,
NMR (400 MHz, CDCl3): δ = 6.39 (br. s, 1 H), 5.46 (t, J = 9.6 Hz, 1 H),
4.59 (dd, J = 9.4, 4.2 Hz, 1 H), 4.53 (dd, J = 4.2, 1.4 Hz, 1 H), 4.22
(dd, J = 12.3, 4.6 Hz, 1 H), 4.16 (dd, J = 12.3, 9.9 Hz, 1 H), 4.11 (ddd,
J = 9.9, 4.5, 2.4 Hz, 1 H), 2.41–2.29 (m, 1 H), 2.12 (s, 3 H), 2.11 (s, 3
H), 2.08 (s, 3 H), 1.95–1.20 (m, 10 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 173.1, 170.7, 169.9, 169.3, 94.4, 71.5, 68.8, 67.0, 61.9, 42.8, 29.7,
28.7, 25.7, 25.3, 20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for
C19H31INO9 [M + NH4]+ 544.10380; found 544.10321.
+
Compound 38: Following the general procedure using octanoic
acid, and purifying by silica gel column chromatography gave 38
+
20.9, 20.7, 20.6, 19.2, 13.8 ppm. HRMS (ESI): calcd. for C23H29INaO10
1
(92 mg, 94 %; dr = 83:17) as a white semi-solid. H NMR (400 MHz,
[M + Na]+ 615.06976; found 615.06828.
CDCl3): δ = 6.40 (d, J = 1.3 Hz, 1 H), 5.45 (t, J = 9.6 Hz, 1 H), 4.59
(dd, J = 9.4, 4.4 Hz, 1 H), 4.53 (dd, J = 4.2, 1.5 Hz, 1 H), 4.22 (dd, J =
12.3, 4.6 Hz, 1 H), 4.16 (dd, J = 12.3, 2.4 Hz, 1 H), 4.11 (ddd, J = 9.9,
4.5, 2.4 Hz, 1 H), 2.40 (t, J = 7.5 Hz, 2 H), 2.12 (s, 3 H), 2.11 (s, 3 H),
2.07 (s, 3 H), 1.68–0.83 (m, 14 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 171.0, 170.7, 169.9, 169.3, 94.5, 71.4, 68.8, 67.0, 61.8, 34.0, 31.6,
29.7, 28.9, 28.8, 24.7, 22.6, 20.9, 20.7, 20.6, 14.0 ppm. HRMS (ESI):
Compound 33: Following the general procedure using 2,3,4-tri-
methoxybenzoic acid, and purifying by silica gel column chroma-
tography gave 33 (94 mg, 86 %; dr = 70:30) as a pale yellow solid,
1
m.p. 95 °C. H NMR (500 MHz, CDCl3): δ = 7.31 (s, 2 H), 6.58 (d, J =
1.3 Hz, 1 H), 5.53 (t, J = 9.6 Hz, 1 H), 4.78 (dd, J = 9.6, 4.2 Hz, 1 H),
4.68 (dd, J = 4.2, 1.6 Hz, 1 H), 4.28–4.24 (m, 1 H), 4.23–4.17 (m, 2 H),
3.94 (s, 6 H), 3.93 (s, 3 H), 2.13 (s, 3 H), 2.12 (s, 3 H), 2.09 (s, 3 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 170.6, 169.8, 169.3, 163.3,
153.1, 143.2, 123.4, 107.3, 95.2, 71.7, 68.5, 67.1, 61.7, 60.9, 56.3, 27.2,
20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for C22H27INaO12+ [M + Na]+
633.04394; found 633.04528.
calcd. for C20H31INaO9 [M + Na]+ 565.09050; found 565.08933.
+
Compound 39: Following the general procedure using phenoxy-
acetic acid, and purifying by silica gel column chromatography gave
1
39 (89 mg, 90 %; dr = 75:25) as a white solid, m.p. 124 °C. H NMR
(400 MHz, CDCl3): δ = 7.32 (td, J = 7.4, 1.2 Hz, 2 H), 7.02 (t, J =
7.4 Hz, 1 H), 6.94 (dt, J = 7.8, 0.9 Hz, 2 H), 6.48 (d, J = 1.2 Hz, 1 H),
5.40 (t, J = 9.9 Hz, 1 H), 4.76 (d, J = 1.9 Hz, 1 H), 4.55 (dd, J = 4.4,
1.5 Hz, 1 H), 4.44 (dd, J = 9.5, 4.4 Hz, 1 H), 4.11 (dd, J = 12.5, 8.3 Hz,
1 H), 4.03 (dd, J = 12.8, 2.4 Hz, 1 H), 3.73 (ddd, J = 10.0, 4.1, 2.4 Hz,
Compound 34: Following the general procedure using picolinic
acid, and purifying by silica gel column chromatography gave 34
(87 mg, 93 %) as a white solid, m.p. 145 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.80 (ddd, J = 4.7, 1.2, 0.8 Hz, 1 H), 8.14 (dt, J = 6.8,
0.9 Hz, 1 H), 8.14 (td, J = 7.8, 1.7 Hz, 1 H), 7.55 (ddd, J = 7.7, 4.7, 1 H), 2.10 (s, 6 H), 2.06 (s, 3 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
1.2 Hz, 1 H), 6.70 (d, J = 1.4 Hz, 1 H), 5.54 (t, J = 9.5 Hz, 1 H), 4.79
(dd, J = 9.2, 4.4 Hz, 1 H), 4.75 (dd, J = 4.4, 1.5 Hz, 1 H), 4.33 (ddd,
J = 10.0, 4.2, 2.5 Hz, 1 H), 4.27 (dd, J = 12.2, 7.9 Hz, 1 H), 4.16 (dd,
J = 12.2, 2.2 Hz, 1 H), 2.13 (s, 3 H), 2.12 (s, 3 H), 2.08 (s, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 170.7, 169.9, 169.3, 162.5, 150.2,
146.7, 137.1, 127.6, 125.6, 95.9, 71.7, 68.8, 67.0, 61.7, 27.1, 20.9, 20.7,
170.6, 169.8, 169.2, 166.4, 157.5, 129.8, 122.1, 114.6, 95.3, 71.6, 68.5,
66.6, 64.9, 61.5, 26.6, 20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for
C20H27INO10 [M + NH4]+ 568.06742; found 568.06711.
+
Compound 40: Following the general procedure using Fmoc-β-Ala-
OH, and purifying by silica gel column chromatography gave 40
(116 mg, 91 %) as a white solid, m.p. 92 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.77 (d, J = 7.5 Hz, 2 H), 7.59 (d, J = 7.4 Hz, 2 H), 7.40 (t,
J = 7.4 Hz, 2 H), 7.32 (t, J = 7.6 Hz, 2 H), 6.42 (br. s, 1 H), 5.47 (t, J =
20.6 ppm. HRMS (ESI): calcd. for C18H20INNaO9 [M + Na]+
+
544.00750; found 544.00567.
Compound 35: Following the general procedure using nicotinic 9.2 Hz, 1 H), 5.35 (t, J = 4.8 Hz, 1 H), 4.57–4.53 (m, 2 H), 4.40 (d, J =
acid, and purifying by silica gel column chromatography gave 35
(91 mg, 97 %) as a white solid, m.p. 127 °C. 1H NMR (500 MHz,
CDCl3): δ = 9.27 (d, J = 1.9 Hz, 1 H), 8.86 (dd, J = 4.7, 1.5 Hz, 1 H),
6.1 Hz, 2 H), 4.24–4.10 (m, 3 H), 3.52 (q, J = 5.8 Hz, 2 H), 2.68 (t, J =
5.2 Hz, 2 H), 2.11 (s, 3 H), 2.10 (s, 3 H), 2.04 (s, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 170.6, 169.9, 169.8, 169.3, 156.3, 143.8, 143.7,
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141.3, 127.7, 127.0, 125.0, 120.0, 95.0, 71.6, 68.6, 66.9, 66.8, 61.8,
47.2, 36.4, 34.4, 26.9, 20.9, 20.7, 20.6 ppm. HRMS (ESI): calcd. for
26.8, 26.6, 20.9, 20.8, 20.7, 20.6, 20.6 ppm. HRMS (ESI): calcd. for
C28H30INNaO10 [M + Na]+ 690.08066; found 690.07911.
+
C30H32INNaO11 [M + Na]+ 732.09122; found 732.08945.
+
Compound 45: Following the general procedure using Fmoc-Pro-
OH, and purifying by silica gel column chromatography gave 45
(118 mg, 89 %) as a white solid, m.p. 82 °C. 1H NMR (500 MHz,
CDCl3): δ = 7.77 (d, J = 7.4 Hz, 2 H), 7.62 (t, J = 6.5 Hz, 2 H), 7.40 (t,
J = 7.3 Hz, 2 H), 7.32 (t, J = 7.3 Hz, 2 H), 6.38 (br. s, 1 H), 5.45 (t, J =
9.3 Hz, 1 H), 4.59–4.56 (m, 2 H), 4.47–4.42 (m, 2 H), 4.35–4.26 (m, 2
H), 4.21–4.14 (m, 2 H), 3.71–3.53 (m, 3 H), 2.36–2.27 (m, 1 H), 2.11–
1.95 (m, 3 H), 2.10 (s, 3 H), 2.09 (s, 3 H), 1.97 (s, 3 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 170.6, 170.2, 169.7, 169.2, 154.9, 144.1, 143.9,
141.3, 127.7, 127.0, 125.1, 125.1, 124.8, 120.0, 95.7, 71.7, 68.8, 67.7,
67.0, 61.8, 59.1, 47.3, 46.5, 29.8, 27.0, 24.5, 22.6, 20.8, 20.6, 20.4 ppm.
Compound 41: Following the general procedure using Fmoc-Leu-
OH, and purifying by silica gel column chromatography gave 41
(127 mg, 90 %; dr = 84:16) as a pale yellow solid, m.p. 79 °C. 1H
NMR (500 MHz, CDCl3): δ = 7.77 (d, J = 7.6 Hz, 2 H), 7.60 (d, J =
7.3 Hz, 2 H), 7.41 (t, J = 7.4 Hz, 2 H), 7.32 (t, J = 7.4 Hz, 2 H), 6.41
(br. s, 1 H), 5.46 (t, J = 9.3 Hz, 1 H), 5.18 (d, J = 8.0 Hz, 1 H), 4.56–
4.52 (m, 2 H), 4.44–4.41 (m, 3 H), 4.24–4.10 (m, 3 H), 2.09 (s, 6 H),
2.01 (s, 3 H), 1.77–1.61 (m, 3 H), 1.01–0.99 (m, 6 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 170.7, 170.5, 169.6, 169.2, 155.9, 143.8, 143.7,
141.3, 127.7, 127.0, 125.0, 120.0, 95.6, 71.8, 68.7, 67.2, 66.9, 61.8,
52.5, 47.2, 41.2, 26.8, 24.9, 22.6, 21.9, 20.7, 20.6, 20.4 ppm. HRMS
+
HRMS (ESI): calcd. for C32H34INNaO11 [M + Na]+ 758.10688; found
+
(ESI): calcd. for C33H42IN2O11 [M + NH4]+ 769.18278; found
758.10519.
769.18269.
General Procedure for One-pot Iodoazidation: An equimolar
mixture of Me3SI (1a; 1.1 equiv.) and PhI(OAc)2 (2; 1.1 equiv.) in
solvent (1 mL) was treated with TMSN3 or NaN3 (5 equiv.) at 0 °C,
and the mixture was stirred at room temperature for 30 min. After
this time, glycal (1.0 equiv.) was added, and stirring was continued
until the reaction was complete. Usual work-up and purification by
silica gel column chromatography gave the glycosyl azides (46–50)
Compound 42: Following the general procedure using Fmoc-Phe-
OH, and purifying by silica gel column chromatography gave 42
(130 mg, 92 %; dr = 84:16) as a pale yellow solid, m.p. 88 °C. 1H
NMR (500 MHz, CDCl3): δ = 7.77 (d, J = 7.6 Hz, 2 H), 7.57–7.55 (m,
2 H), 7.41 (t, J = 7.4 Hz, 2 H), 7.35–7.25 (m, 5 H), 7.20 (d, J = 7.3 Hz,
2 H), 6.31 (br. s, 1 H), 5.41 (t, J = 9.7 Hz, 1 H), 5.28 (d, J = 7.9 Hz, 1
H), 4.70 (dd, J = 14.1, 6.7 Hz, 1 H), 4.45–4.42 (m, 2 H), 4.37 (dd, J =
10.3, 7.0 Hz, 1 H), 4.30 (d, J = 2.7 Hz, 1 H), 4.23–4.20 (m, 1 H), 4.16
(dd, J = 11.6, 2.9 Hz, 1 H), 4.09 (dd, J = 12.6, 1.8 Hz, 1 H), 3.98 (m,
1 H), 3.17 (dd, J = 13.5, 5.9 Hz, 1 H), 3.13 (dd, J = 13.8, 6.8 Hz, 1 H),
2.10 (s, 3 H), 2.09 (s, 3 H), 2.00 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.6, 169.6, 169.5, 169.2, 155.6, 143.8, 143.6, 141.3,
129.1, 128.9, 127.7, 127.3, 127.1, 125.0, 125.0, 120.0, 95.6, 71.5, 68.5,
67.2, 66.6, 61.5, 54.8, 47.0, 38.1, 26.6, 22.6, 20.8, 20.7, 20.5 ppm.
1
in good yields. All the glycosides were characterised by H and 13C
NMR spectroscopy and MS/HRMS analysis, and data were found to
be consistent with the reported data.[15c]
3,4,6-Tetra-O-acetyl-2-deoxy-2-iodo-α-
and 3,4,6-Tetra-O-acetyl-2-deoxy-2-iodo-β-
Azide (46): Following the general procedure using 3,4,6-tri-O-
acetyl- -glucal (50 mg, 0.18 mmol, 1.0 equiv), and puriyfiyng by
D
-mannopyranosyl Azide
D
-glucoopyranosyl
D
silica gel column chromatography afforded 46 (78 mg, 96 %; dr =
77:23) as an oily liquid.
HRMS (ESI): calcd. for C36H36INNaO11 [M + Na]+ 808.12252; found
808.12093.
+
Data for α-manno diastereomer: 1H NMR (500 MHz, CDCl3): δ = 5.72
(d, J = 1.0 Hz, 1 H), 5.36 (t, J = 9.1 Hz, 1 H), 4.52 (dd, J = 9.0, 4.2 Hz,
1 H), 4.49 (dd, J = 4.2, 2.5 Hz, 1 H), 4.26 (dd, J = 12.5, 5.1 Hz, 1 H),
4.22 (dd, J = 12.5, 2.2 Hz, 1 H), 4.18 (ddd, J = 9.4, 4.4, 2.1 Hz, 1 H),
2.13 (s, 3 H), 2.10 (s, 3 H), 2.07 (s, 3 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 170.6, 169.7, 169.3, 91.0, 71.3, 68.6, 67.0, 61.8, 27.9, 20.9,
20.7, 20.6 ppm. MS (ESI): m/z = 459 [M + NH4]+.
Compound 43: Following the general procedure using Cbz-Phe-
OH, and purifying by silica gel column chromatography gave 43
(118 mg, 94 %; dr = 80:20) as a white solid, m.p. 91 °C. 1H NMR
(500 MHz, CDCl3): δ = 7.38–7.24 (m, 8 H), 7.18 (d, J = 7.3 Hz, 2 H),
6.31 (br. s, 1 H), 5.41 (t, J = 9.7 Hz, 1 H), 5.23 (d, J = 7.9 Hz, 1 H),
5.11 (d, J = 5.6 Hz, 2 H), 4.70 (dd, J = 13.8, 6.7 Hz, 1 H), 4.44 (dd,
J = 9.1, 3.9 Hz, 1 H), 4.29 (d, J = 3.2 Hz, 1 H), 4.22–4.09 (m, 2 H),
3.97 (m, 1 H), 3.16 (dd, J = 14.0, 6.7 Hz, 1 H), 3.11 (dd, J = 13.7,
6.4 Hz, 1 H), 2.11 (s, 3 H), 2.10 (s, 3 H), 2.06 (s, 3 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.7, 169.6, 169.5, 169.3, 155.6, 135.1, 129.6,
129.1, 128.9, 128.5, 128.3, 128.1, 127.3, 95.5, 71.4, 68.4, 67.2, 66.6,
61.5, 54.8, 38.0, 26.7, 20.8, 20.7, 20.6 ppm. HRMS (ESI): calcd. for
Compound 50: Following the general procedure using per-O-acet-
yl-D-maltal, and purifying by silica gel column chromatography gave
50 (62 mg, 95 %; dr = 65:35) as an oily liquid. 1H NMR (400 MHz,
CDCl3): δ = 5.66 (d, J = 1.2 Hz, 1 H), 5.54 (d, J = 4.0 Hz, 1 H), 5.42–
34 (m, 2 H), 5.08 (t, J = 9.9 Hz, 1 H), 4.96–4.7 (m, 2 H), 4.54–4.45 (m,
3 H), 4.31–3.91 (m, 7 H), 2.16 (s, 3 H), 2.12 (s, 3 H), 2.11 (s, 3 H), 2.04
(s, 3 H), 2.04 (s, 3 H), 2.01 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 170.5, 170.5, 170.4, 170.1, 169.9, 169.7, 169.4, 95.8, 90.6, 71.9,
71.8, 71.3, 71.1, 69.4, 68.5, 67.9, 62.4, 61.4, 27.4, 21.1, 20.7, 20.6, 20.6,
C29H32INNaO11 [M + Na]+ 720. 09122; found 720.08929.
+
Compound 44: Following the general procedure using Bz-Phe-OH,
and purifying by silica gel column chromatography gave 44
(107 mg, 89 %; dr = 80:20) as a white solid, m.p. 83 °C. 1H NMR
(500 MHz, CDCl3): δ = 7.74–7.72 (m, 4 H), 7.54–7.51 (m, 2 H), 7.46–
7.42 (m, 4 H), 7.36–7.33 (m, 4 H), 7.29–7.25 (m, 4 H), 7.23–7.22 (m,
20.5, 20.5 ppm. HRMS (ESI): calcd. for C24H32IN3NaO15 [M + Na]+
+
752.07703; found 752.07555.
2 H), 6.54 (d, J = 7.3 Hz, 1 H), 6.45 (d, J = 1.3 Hz, 1 H), 6.34 (d, J = Methyl 3,4,6-Tetra-O-acetyl-2-deoxy-2-iodo-α-
D
-mannopyran-
oside and Methyl 3,4,6-Tetra-O-acetyl-2-deoxy-2-iodo-β-
glucoopyranoside (51): 3,4,6-Tri-O-acetyl- -glucal (5a; 50 mg,
1.3 Hz, 1 H), 5.42 (t, J = 9.7 Hz, 1 H), 5.41 (t, J = 9.7 Hz, 1 H), 5.15
(dd, J = 13.1, 7.1 Hz, 1 H), 5.09 (dd, J = 13.8, 6.8 Hz, 1 H), 4.52 (dd,
J = 4.4, 1.5 Hz, 1 H), 4.47 (dd, J = 9.6, 4.4 Hz, 1 H), 4.44 (dd, J = 9.4,
4.4 Hz, 1 H), 4.34 (dd, J = 5.9, 1.6 Hz, 1 H), 4.21 (dd, J = 12.5, 4.4 Hz,
1 H), 4.15 (dd, J = 12.5, 4.4 Hz, 1 H), 4.12 (dd, J = 12.6, 2.4 Hz, 1 H),
4.06 (dd, J = 12.2, 2.2 Hz, 1 H), 4.05 (ddd, J = 9.3, 4.1, 2.4 Hz, 1 H),
3.73 (ddd, J = 10.0, 3.9, 2.2 Hz, 1 H), 3.31–3.23 (m, 4 H), 2.12 (s, 3
H), 2.09 (s, 6 H), 2.09 (s, 3 H), 2.07 (s, 3 H), 2.05 (s, 3 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 170.6, 170.6, 169.6, 169.4, 169.3, 169.2,
D-
D
0.18 mmol, 1.0 equiv.) and MeOH (0.5 mL) were dissolved in CH3CN
(0.5 mL). Me3SI(OAc)2 (3a; 71 mg, 0.20 mmol, 1.1 equiv.) was then
added to this solution at room temperature. The reaction mixture
was stirred at room temperature for 20 min, after which time TLC
showed the consumption of 5a. Usual work-up and purification by
silica gel column chromatography gave methyl glycosides 51 (74
mg, 94 %; dr = 84:16). 1H NMR (400 MHz, CDCl3): δ = 5.37 (t, J =
167.1 133.4, 132.0, 129.2, 128.9, 128.9, 127.5, 127.4, 127.01, 95.7, 9.7 Hz, 1 H), 5.08 (br. s, 1 H), 4.63 (dd, J = 9.4, 4.4 Hz, 1 H), 4.54 (dd,
95.6, 71.5, 71.5, 68.6, 68.4, 66.7, 66.6, 61.6, 61.6, 53.6, 53.4, 38.0, 37.9,
J = 4.4, 0.9 Hz, 1 H), 4.24 (dd, J = 12.2, 4.8 Hz, 1 H), 4.16 (dd, J =
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12.2, 2.4 Hz, 1 H), 4.01 (ddd, J = 9.9, 7.3, 2.4 Hz, 1 H), 3.41 (s, 3 H),
2.12 (s, 3 H), 2.09 (s, 3 H), 2.06 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 170.7, 169.8, 169.5, 102.3, 69.0, 69.0, 67.5, 62.2, 55.4,
Acknowledgments
S. K. gratefully acknowledges the Department of Science and
Technology (DST), New Delhi for an INSPIRE faculty award
(GAP0397) and a start-up research grant for young scientists
(GAP0471). K. B. acknowledges the Council of Scientific and In-
dustrial Research (CSIR), New Delhi, for a research fellowship.
The authors are also grateful to the director of the CSIR-IICT for
providing the necessary infrastructure.
+
29.2, 20.9, 20.7, 20.7 ppm. HRMS (ESI): calcd. for C13H23INO8 [M +
NH4]+ 448.04629; found 448.04520.
Iodoacetoxylation of Dihydropyran: A preformed solution of
Me3SI (1a; 288 mg, 1.41 mmol,1.1 equiv.) and PhI(OAc)2 (2; 454 mg,
1.41 mmol,1.1 equiv.) in DCE (1 mL) was treated with dihydropyran
(108 mg, 1.28 mmol, 1.0 equiv.) at room temperature. The mixture
was stirred until TLC indicated the complete consumption of start-
ing material. The mixture was diluted with EtOAc (10 mL), and
washed with saturated aqueous NaHCO3 (5 mL), and saturated
aqueous sodium thiosulfate (2 mL). The aqueous phases were ex-
tracted with EtOAc (3 × 30 mL). The combined organic layers were
washed with brine, and dried with anhydrous Na2SO4. The solvent
was evaporated under reduced pressure, and the residue was dried
in vacuo to give analytically pure 52 (298 mg, 86 %) as a colourless
oil. 1H NMR (400 MHz, CDCl3): δ = 5.89 (d, J = 5.7 Hz, 1 H), 4.15–
4.11 (m, 1 H), 4.06–4.01 (m, 1 H), 3.73 (ddd, J = 11.3, 7.5, 3.4 Hz, 1
H), 2.43–2.35 (m, 1 H), 2.15–2.05 (m, 1 H), 2.13 (s, 3 H), 1.82 (ddq,
J = 10.5, 7.0, 3.7 Hz, 1 H), 1.69–1.60 (m, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 168.9, 95.3, 64.9, 32.4, 26.2, 25.2, 20.9 ppm.
Keywords: Electrophilic addition · Hypervalent compounds ·
Iodine · Carbohydrates · Enol ethers
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Iodoazidation of Dihydropyran: An equimolar mixture of Me3SI
(1a; 290 mg, 1.41 mmol,1.1 equiv.) and PhI(OAc)2 (2; 455 mg, 1.41
mmol, 1.1 equiv.) in CH3CN (1 mL) was treated with NaN3 (250 mg,
3.85 mmol 3 equiv.) at 0 °C. The mixture was stirred at room temper-
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mmol,1.0 equiv.) was added, and stirring was continued until the
reaction was complete. Usual work-up gave analytically pure 2-az-
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liquid.[15c] 1H NMR (500 MHz, CDCl3): δ = 4.95 (d, J = 7.1 Hz, 1 H),
4.15–4.10 (m, 1 H), 3.96–3.91 (m, 1 H), 3.72–3.67 (m, 1 H), 2.43–2.38
(m, 1 H), 2.14–2.04 (m, 1 H), 1.72–1.63 (m, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 92.2, 66.0, 33.8, 27.3, 26.2 ppm.
Iodocarboxylation of Dihydropyran with Bz-Phe-OH: Following
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the general procedure for iodocarboxylation of glucal, but using
dihydropyran instead of glucal, and using N-benzoyl-L-phenyl-
alanine, usual work-up gave analytically pure 2-benzoylamino-3-
phenylpropionic acid 3-iodotetrahydropyran-2-yl ester (54; 126 mg,
92 %)[2f] as a mixture of diastereomers (1:1) without purification by
silica gel column chromatography. 1H NMR (500 MHz, CDCl3): δ =
7.72–7.70 (m, 4 H), 7.53–7.49 (m, 2 H), 7.43 (m, 4 H), 7.34–7.20 (10
H), 6.54 (d, J = 7.4 Hz, 1 H), 6.51 (d, J = 7.1 Hz, 1 H), 6.07 (d, J =
4.2 Hz, 1 H), 5.98 (d, J = 4.4 Hz, 1 H), 5.13 (q, J = 5.9 Hz, 1 H), 5.12
(q, J = 5.9 Hz, 1 H), 4.21 (q, J = 4.2 Hz, 1 H), 4.01 (q, J = 4.2 Hz, 1
H), 3.95–3.90 (m, 2 H), 3.79–3.71 (m, 2 H), 3.34–3.24 (m, 4 H), 2.29–
2.23 (m, 1 H), 2.18–2.10 (m, 1 H), 2.07–1.84 (m, 6 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 170.1, 169.9, 166.9, 135.7, 135.4, 133.7, 131.8,
124.5, 129.4, 128.7, 128.6, 127.3, 127.0, 96.3, 96.2, 64.2, 64.2, 53.5,
53.3, 38.0, 37.7, 30.9, 30.6, 25.5, 25.5, 23.8, 23.7 ppm. MS (ESI): m/z =
480 [M + H]+, 502 [M + Na]+.
Iodoacetoxylation of Cyclohexene: Following the general proce-
dure described for the iodoacetoxylation of dihydropyran using cy-
clohexene, analytically pure 55 was isolated (330 mg, 82 %) as a
colourless oil. 1H NMR (500 MHz, CDCl3): δ = 4.90 (dt, J = 9.6, 5.3 Hz,
1 H), 4.06 (ddd, J = 13.8, 9.6, 4.2 Hz, 1 H), 2.44–2.42 (m, 1 H), 2.13–
1.99 (m, 2 H), 2.09 (s, 3 H), 1.85–1.79 (m, 1 H), 1.61–1.55 (m, 1 H),
1.51–1.26 (m, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 169.9, 76.7,
37.9, 31.8, 31.6, 27.1, 23.6, 21.2 ppm.
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1
article): Copies of H and 13C NMR spectra of all products.
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Full Paper
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[12] a) See the Exp. Sect. for detailed experimental description, and see Sup-
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D
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D
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(3.0 equiv.) and PhI(OAc)2 (3.0 equiv.) gave all four possible isomers in
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iodine and silver benzoate gave the corresponding glycosyl benzoate
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[17] D. S. Rao, T. R. Reddy, K. Babachary, S. Kashyap, manuscript in preparation.
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Received: September 11, 2015
Published Online: November 25, 2015
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