Iodine monochloride (ICl) as a highly efficient, green oxidant for the oxidation of alcohols to corresponding carbonyl compounds

Article abstract of DOI:10.1080/00397911.2015.1005630

Iodine monochloride (ICl) was discovered to be a highly efficient, green oxidant, which can oxidize aldose hemiacetals, diarylmethanols, arylalkylmethanols, anddialkylmethanols to the corresponding aldose lactones, diarylmethanones, arylalkylmethanones, and dialkylmethanones, respectively, in high yields. ICl as a green, metal-free oxidant is characterized by mild reaction condition, short reaction time, good yield, and broad scope.

Full text of DOI:10.1080/00397911.2015.1005630

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Iodine Monochloride (ICl) as a Highly Efficient, Green
Oxidant for the Oxidation of Alcohols to Corresponding
Carbonyl Compounds
Peng Weiab, Datong Zhanga, Zhigang Gaoab, Wenqing Caib, Weiren Xub, Lida Tangb & Guilong
Zhaoab
a School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan,
P. R. China
b Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of
Pharmaceutical Research, Tianjin, P. R. China
Accepted author version posted online: 05 Feb 2015.
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To cite this article: Peng Wei, Datong Zhang, Zhigang Gao, Wenqing Cai, Weiren Xu, Lida Tang & Guilong Zhao (2015):
Iodine Monochloride (ICl) as a Highly Efficient, Green Oxidant for the Oxidation of Alcohols to Corresponding Carbonyl
Compounds, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
DOI: 10.1080/00397911.2015.1005630
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Iodine Monochloride (ICl) as a Highly Efficient, Green Oxidant for the Oxidation of
Alcohols to Corresponding Carbonyl Compounds
Peng Wei1,2, Datong Zhang1, Zhigang Gao1,2, Wenqing Cai2, Weiren Xu2, Lida Tang2,
Guilong Zhao1,2
1School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology,
Jinan, P. R. China, 2Tianjin Key Laboratory of Molecular Design and Drug Discovery,
Tianjin Institute of Pharmaceutical Research, Tianjin, P. R. China
Address correspondence:
Guilong Zhao, Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin
Institute of Pharmaceutical Research, Tianjin 300193, P. R. China. E-mail:
zhao_guilong@126.com
Datong Zhang, School of Chemistry and Pharmaceutical Engineering, Qilu University of
Technology, Jinan 250353, P. R. China. E-mail: dtzhang@qlu.edu.cn
Abstract
Iodine monochloride (ICl) was discovered to be a highly efficient, green oxidant, which
can oxidize aldose hemiacetals, diarylmethanols, arylalkylmethanols and
dialkylmethanols to the corresponding aldose lactones, diarylmethanones,
arylalkylmethanones and dialkylmethanones, respectively, in high yields. ICl as a green
metal-free oxidant is characterized by mild reaction condition, short reaction time, high
yield and broad scope.
1

KEYWORDS: Green oxidant; iodine monochloride; aldose hemiacetal; lactonization;
synthesis
INTRODUCTION
The oxidation of alcohols to the corresponding carbonyl compounds, such as lactones,
ketones and aldehydes, is among the most fundamental, useful and widely investigated
organic reactions. During the study of aryl C-glycosides as SGLT2 inhibitors for the
treatment of type 2 diabetes in our laboratories,[1,2] a variety of glyconolactones as the
glycosyl donors were needed during the synthesis. Glyconolactones 1, in particular
gluconolactones, are often used as the glycosyl donors for the synthesis of biologically
active C-glycosides in carbohydrate chemistry and medicinal chemistry,[3–5] which are
usually synthesized by oxidation of the corresponding aldose hemiacetals 2 with a variety
of oxidants[6–18] (Scheme 1). During the synthesis of glyconolactones on pilot scales in
our laboratories, a green metal-free oxidant that is characterized by being cheap, mild
reaction condition, short reaction time and high yield was urgently needed. Survey of the
literature revealed that the oxidants that could be employed to achieve this transformation
included DMSO/Ac2O,[6] DMSO/(COCl)2,[7] pyridinium chlorochromate (PCC),[8]
dipyridinium dichromate (PDC),[9] Dess-Martin periodinane,[10] N-methylmorpholine
N-oxide (NMMO)/tetrapropylammonium perruthenate (TPAP),[11] N-iodosuccinimide
(NIS)/tetrabutylammonium iodide (TBAI),[12]
4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammoniumtetrafluoroborate,[13]
2,2,6,6-tetramethylpiperidine-1-oxyl, radical (TEMPO)/ion-supported
(diacetoxyiodo)benzenes (IS-DIBs),[14] Ag2CO3,[15] PhBr/K2CO3/PPh3/Pd(OAc)2,[16]
2

I2/K2CO3,[17] and Br2/H2O/Ba2CO3[18]. Intensive examination found that the oxidizing
species involved in these oxidants basically fall into two categories, hypervalent
nonmetals, such as S, Br and I, and hypervalent metals, such as Cr, Ru, Pd and Ag. These
oxidants suffer from many drawbacks, such as poor atom economy (Dess-Martin
periodinane and NIS) and being toxic (those involving hypervalent metals or toxic heavy
metals, in particular Cr and Ba), expensive (those involving Ru, Pd and Ag) and not
readily available (such as TEMPO/IS-DIBs). Only DMSO/Ac2O and I2/K2CO3 seemingly
meet our criteria described above. However, further examination and experimentations
revealed that DMSO/Ac2O is associated with a prolonged reaction time (usually
overnight), unpleasant odor (arising from the byproduct dimethyl sulfide) and
complicated workup usually involving repeated washing with water to remove excessive
DMSO and column chromatography to remove the residual DMSO before purification by
crystallization,[1] while I2/K2CO3 is related to much longer than acceptable reaction times
(16-24 h for aldose hemiacetals even with 3 eq of oxidant).[17]
However, among the oxidants currently used for the oxidation of aldose hemiacetals to
lactones aforementioned, I2/K2CO3 is still the most promising one because it is only
associated with prolonged reaction time and a large quantity of oxidant (3 eq) which are
unacceptable in large-scale synthesis,[17] but doesn’t suffer from other serious drawbacks
aforementioned for the other oxidants. This fact prompted us to study the mechanism of
this oxidant with anticipation that based on its mechanism we could find a new oxidant
that could meet our criteria. As shown in Scheme 2, the oxidation action of I2/K2CO3
relies on the disproportionation of I2 in the presence of a base to produce an iodonium
3

species, which is in turn bound to the O atom of OH in an alcohol to be oxidized,
followed by elimination of HI to complete the oxidation.[17,19] According to this
mechanism, we proposed ICl as the more powerful analogue of I2 for this purpose. ICl is
widely used in inorganic and organometallic chemistry[20,21] and sometimes as iodinating
reagent for aromatics[22,23] and alkynes[24] in synthetic organic chemistry, which, however,
has never been used for the oxidation of alcohols to corresponding carbonyl compounds
so far to the best of our knowledge. ICl should be capable of producing iodonium species
much more readily and faster than I2 due to the larger polarization of the I-Cl bond than
the I-I bond in I2 (Scheme 2). We herein report the systematic study of ICl as the oxidant
to oxidize alcohols to the corresponding carbonyl compounds, including the optimization
of the reaction condition and the exploration of the scope of alcohol substrates.
RESULTS AND DISCUSSION
Because ICl was proposed to replace I2 to achieve the oxidation with anticipation of
shorter reaction time and less quantity of oxidant, comparative experiments with both of
them were then conducted in the preliminary attempts (Table 1).
2,3,4,6-Tetra-O-benzyl-D-glucopyranose 3 was selected as the aldose hemiacetal
substrate in both the preliminary attempts and the optimization of reaction conditions
(Table 1 and Table 2) since it was readily available and crystalline and the corresponding
product 2,3,4,6-tetra-O-benzyl-D-gluconolactone 4 was commonly used in the synthesis
of C-glucosides[25-27] (Table 1).
4

After the proposal of ICl as an oxidant for the oxidation of aldose hemiacetals to lactones,
we designed a number of parallel experiments to preliminarily test the feasibility of this
oxidant under the reaction condition initially used for I2[17] because both of them were
believed to act through an almost identical mechanism. As shown in entries 1-3 in Table 1,
with 3.0 eq of K2CO3 as base, 2.0-3.0 eq of I2 were tested (added neat to the reaction
mixture in one portion), and it turned out that as the quantity of I2 decreased, the reaction
time increased dramatically and the isolated yields of 4 decreased significantly, indicating
that 3.0 eq of I2 was really necessary to ensure a short reaction time and a high yield.[17]
In contrast, as shown in entry 4 in Table 1, when 3.0 eq of ICl were used in place of I2
under the same reaction condition to that with I2, the reaction time needed was
significantly shorter than that with 3.0 eq of I2 (2.5 h vs 10 h), but the yield was much
lower (51% vs 93%). After careful examination of the operational details of this reaction,
we found that the one-portion addition of ICl in a neat form just like the addition of I2 as
described in entries 1-3 in Table 1 could induce a moderate exothermic process, which, if
left uncontrolled, would lead to a considerably accelerated reaction rate and a low yield.
The low yield was likely due to the decomposition of 3 and/or 4 because some impurities
could be observed in the reaction mixture in this case. So, we devised to attempt lower
reaction temperatures and add ICl in the form of a solution in CH2Cl2 in a dropwise
manner. Thus, as shown in entries 4-7 in Table 1, as the temperature for the dropwise
addition of a solution of ICl in CH2Cl2 decreased from room temperature to -10°C, the
reaction time needed became longer while the yield increased moderately. The optimal
temperature for the addition of ICl was established to be 0°C (entry 5, Table 1), because
-5°C (entry 6, Table 1) and -10°C (entry 7, Table 1) produced comparable yields to that at
5

0°C. However, even when the reaction was carried out at 0°C to room temperature (entry
5, Table 1), the yield was still much lower than that with I2 (65% vs 93%) although the
reaction time needed was much shorter (5.5 h vs 10 h), which indicated that the best
reaction condition we got so far (entry 5, Table) still needed further optimization. So, we
attempted to decrease the quantity of ICl employed starting from 3.0 eq. As shown in
entries 5 and 8-13 in Table 1, when the quantity of ICl decreased gradually from 3.0 eq to
1.0 eq, the reaction time increased gradually while the yield increased first and then
dropped, with the best quantity being 1.5 eq which corresponded to a reaction time of 7 h
and a yield of 92% (entry 9, Table 1). So far, the best reaction condition we found (entry
9, Table 1) could already produce slightly shorter reaction time and a comparable yield
compared to that with I2 (entry 1 vs entry 9, Table 1). We went ahead to optimize the
quantity of the base. As shown in entries 9 and 14-17 in Table 1, when the quantity of
K2CO3 was more than 3.0 eq (entries 14 and 15, Table 1), the reaction time and yield
remained basically unchanged; however, when the quantity decreased starting from 3.0
eq (entries 16 and 17, Table 1), the reaction time increased dramatically and the yield
decreased moderately, indicating 3.0 eq of K2CO3 was optimal. It should be noted that
another two reagents capable of producing iodonium ion or I(III) species, IBr and ICl3,
were also tested in these preliminary experiments. IBr gave a similar result to that with
ICl (entry 18 vs entry 9); however, IBr is much more expensive than ICl, which led us to
abandon it. When ICl3 was used as the oxidant, much shorter reaction times were needed
compared to those with I2 and ICl, but the yields were unacceptably low (0% for 1.5 eq,
entry 19 in Table 1, and 25% for 0.6 eq, entry 20 in Table 1), strongly indicating that ICl3
is much more powerful than needed for this purpose. The results summarized in Table 1
6

demonstrated that ICl was a feasible and promising oxidant to replace I2 for oxidation of
aldose hemiacetals to corresponding lactones.
With in hand the preliminary results in Table 1, we moved on to optimize the other two
important parameters of reaction condition, the base and the solvent (Table 2). With
Na2CO3 and NaHCO3 as base (entries 1 and 2, Table 2), the reaction time increased
dramatically compared to that with K2CO3 and the yield were rather low. The poor yield
in this case presumably resulted from the decomposition of 3 and/or 4 by ICl which was
not consumed at a reasonable rate and was therefore cumulated in the reaction mixture.
With KHCO3, the reaction time remained unchanged (7 h) but the yield decreased
dramatically (entry 3, Table 2). The biggest surprise came with Cs2CO3 (entry 4), an
alkali metal carbonate often used in organic synthesis, with which the reaction time was
further shortened on the base of K2CO3 (3 h vs 7 h) while the yield was increased slightly
(97% vs 93%). However, another two alkali earth metal carbonates, CaCO3 and SrCO3,
gave rather poor yields although the reaction time was shortened as well (entries 6 and 7,
Table 2). The reaction time was uniformly shortened while the yield was uniformly
decreased when alkali metal or alkali earth metal hydroxides were employed as base
(entries 7-12, Table 2). It should be noted that among these hydroxides, Ca(OH)2 could
produce quite satisfactory result (entry 11, Table 2) compared to K2CO3 (entry 9, Table 1)
although its yield was interior to that with Cs2CO3 (entry 4, Table 2). Two typical alkali
earth metal oxides, MgO and CaO, produced notably poor yields (entries 13 and 14,
Table 2). Even poorer yields were observed with two commonly encountered organic
bases, Et3N and pyridine (entries 15 and 16, Table 2). So far, Cs2CO3 has been
7

established to be the optimal base. Since alcohols were also reported to be a class of good
solvent for the I2/K2CO3 system,[17,28-30] we also attempted some alcohols as solvent.
Unfortunately, typical alcohols, such as MeOH, EtOH and t-BuOH, led to rather poor
yields (entries 17-20, Table 2) although they behaved quite well in I2/K2CO3
system.[17,28-30] Noteworthy is that in cases where the poor yields were produced, a lot of
byproducts were observed presumably due to the decomposition induced by bases and/or
cumulated ICl in the reaction mixture that were not consumed at reasonable rates. The
optimal reaction condition was finally established to be, i) oxidant: 1.5 eq of ICl that
should be added dropwise in form of solution in CH2Cl2; ii) base: 3 eq of Cs2CO3; iii)
solvent: CH2Cl2; and iv) reaction temperature: 0°C-room temperature.
With in hand the optimized reaction condition for the new oxidant ICl, we moved on
to explore the scope of the alcohol substrates. As shown in entries 1-6 in Table 3, a
variety of glycopyranose (5, 7, 9, 11 and 13) and glycofuranose (15) hemiacetals could be
successfully oxidized to lactones thereof (6, 8, 10, 12, 14 and 16) quickly in excellent
yields. However, this oxidant is not applicable to allyl-protected aldose hemiacetal as
exemplified by 17 (entry 7, Table 3), because no desired product 18 was observed after
the reaction, which is presumably due to the electrophilic addition of ICl to the olefin
functionality. I2 was reported to be applicable to olefin-bearing substrate;[17] however,
oxidation of 17 with I2/K2CO3 following the reported procedure[17] also failed. In order to
extend the substrate scope, we studied another two classes of alcohols, diarylmethanols
and arylalkylmethanols. Diarylmethanols 19, 21 and 23 were successfully oxidized to
corresponding diarylmethanones 20, 22 and 24, respectively, in excellent yields (entries
8

8-10, Table 3). Except the conversion of 21 to 22 that needed 20 h to complete, another
two oxidations finished within 5 h. Arylalkylmethanols 25, 27, 29, 31 and 33 were also
successfully oxidized to corresponding arylalkylmethanones 26, 28, 30, 32 and 34,
respectively, quickly in excellent yields (entries 11-15, Table 3). To further extend the
scope of the substrate, two secondary alcohols, 35 and 37, were subjected to the oxidation
with ICl under the optimized reaction condition. Thus, 35 and 37 were rapidly oxidized to
corresponding ketones 36 and 38, respectively, in excellent yields (entries 16 and 17,
Table 3). Encouraged by the successful results aforementioned, extension of the scope
further to the synthesis of aldehydes was attempted (entries 18-20, Table 3). However,
attempts to oxidize benzyl alcohols 39 and 41 to corresponding benzaldehydes 40 and 42,
respectively, failed because both reactions produced a lot of byproducts along with the
desired products and the isolated yields were rather poor (entries 18 and 19, Table 3).
Treatment of 2-phenylethanol 43 with ICl under optimized reaction condition gave no
desired product 2-phenylacetaldehyde 44 at all (entry 20, Table 3), presumably due to the
instability of the product, an aliphatic aldehyde, in the oxidizing reaction medium.
In conclusion, we have discovered a highly efficient, green oxidant, iodine monochloride
(ICl), and optimized the reaction condition, including the equivalent of ICl, the base and
its equivalent, reaction temperature and solvent. Compared to the I2/K2CO3 system, the
ICl/Cs2CO3 system is characterized by less quantity of oxidant (1.5 eq of ICl vs 3 eq of
I2), shorter reaction time and higher yield. The substrate scope of the oxidant has been
intensively studied, and it is applicable to a variety of alcohol substrates with short
reaction times and high yields, such as aldose hemicacetals, diarylmethanols,
9

arylalkylmethanols and dialkylmethanols. However, it is not applicable to olefin-bearing
and primary alcohols.
EXPERIMENTAL
Melting points were determined with an X-4 microscopic melting point apparatus and are
uncorrected. IR spectrum was recorded on a Bruker Vector 22 FT-IR spectrometer as thin
films. 1H NMR and 13C NMR spectra were taken on a Bruker AV400 nuclear magnetic
resonance spectrometer, using DMSO-d6 or CDCl3 as solvent and TMS as internal
standard. High-resolution mass spectra (HR-MS) were obtained with an Agilent Q-TOF
6510 mass spectrometer with electro-spray ionization (ESI) technique and direct injection
method.
Starting aldose hemiacetals 3, 5, 7, 9, 11, 13, 15 and 17 were prepared according to
known procedures,[1,31-34] and other starting alcohols 19, 21, 23, 25, 27, 29, 31, 33, 35, 37,
39, 41 and 43 were commercially available.
General Procedure For The Oxidation Of 3 To 4 In Preliminary Experiments (Table
1)
Hemiacetal 3 (1.00 g, 1.85 mmol) was dissolved in 10 mL of dried CH2Cl2, and the
resulting mixture was stirred at temperatures specified in Table 1, followed by addition of
specified equivalents of K2CO3 in Table 1. The suspension was stirred at temperatures
specified in Table 1, and specified equivalents of oxidant dissolved in 2 mL of CH2Cl2
was added dropwise except entries 1-4 in Table 1 where the oxidant was added neat in
10

one portion. After addition, the reaction mixture was stirred at room temperature until the
reaction completed as indicated by TLC analysis which was conducted at 0.5-h intervals.
The reaction mixture was poured into 50 mL of ice-water while stirring, and the resulting
mixture was extracted with three 50-mL portions of CH2Cl2. The combined extracts were
washed successively with aqueous Na2S2O3 and brine, dried over Na2SO4 and evaporated
on a rotary evaporator to afford crude 4 as a residue, which was purified by column
chromatography to yield the pure 4 as a colorless oil. 1H NMR (400 MHz, DMSO-d6) δ:
7.27-7.36 (m, 18H), 7.21-7.23 (m, 2H), 4.85 (d, 1H, J = 11.6 Hz), 4.58-4.70 (m, 5H),
4.46-4.55 (m, 3H), 4.35 (d, 1H, J = 6.8 Hz), 4.01 (t, 1H, J = 6.0 Hz), 3.87 (dd, 1H, J = 5.6
Hz and 8.0 Hz), 3.66-3.73 (m, 2H). The 1H NMR data are in good agreement with those
reported.[35]
General Procedure For The Oxidation Of 3 To 4 For The Optimization Of Base And
Solvent (Table 2)
Hemiacetal 3 (1.00 g, 1.85 mmol, 1.0 eq) was dissolved in 10 mL of dried solvent
specified in Table 2, and the resulting mixture was stirred in an ice-water bath, followed
by addition of 3.0 equivalents of base specified in Table 2. The suspension was stirred at
this temperature, and ICl (0.45 g, 2.78 mmol, 1.5 eq) dissolved in 2 mL of CH2Cl2 was
added dropwise. After addition, the reaction mixture was stirred at room temperature until
the reaction completed as indicated by TLC analysis which was conducted at 0.5-h
intervals.
11

The reaction mixture was subjected to aqueous workup described above to yield the pure
4 as a colorless oil.
General Procedure For The Study Of The Substrate Scope Of Icl As Oxidant (Table
3)
Starting alcohols (1.00 g, 1.0 eq) specified in Table 3 was dissolved in 10 mL of dried
CH2Cl2 (for substrates in entries 8-20 in Table 3, 30 mL of dried CH2Cl2 was used), and
the resulting mixture was stirred in an ice-water bath, followed by addition of Cs2CO3
(3.0 eq). The suspension was stirred at this temperature, and ICl (1.5 eq) dissolved in 2
mL of CH2Cl2 was added dropwise. After addition, the reaction mixture was stirred at
room temperature until the reaction completed as indicated by TLC analysis which was
conducted at 0.5-h intervals.
The reaction mixture was subjected to aqueous workup described above to yield the pure
carbonyl compounds specified in Table 3.
2,3,4-Tri-O-benzyl-6-O-methyl-D-gluconolactone (8)
Colorless oil, 0.956 g, yield 96%. 1H NMR (CDCl3, 400 MHz) δ: 7.24-7.39 (m, 15H),
4.97 (d, 1H, J = 11.6 Hz), 4.69-4.73 (m, 2H), 4.65 (d, 1H, J = 11.2 Hz), 4.55-4.60 (m,
2H), 4.42-4.43 (m, 1H), 4.10-4.11 (m, 1H), 3.87-3.92 (m, 2H), 3.55-3.63 (m, 2H), 3.32 (s,
3H); 13C NMR (CDCl3, 100 MHz) δ: 168.82, 137.24, 137.23, 136.60, 128.15, 128.12,
128.08, 127.98, 127.80, 127.70, 127.67, 127.61, 80.66, 77.65, 77.00, 75.61, 73.55, 73.30,
12

73.26, 70.30, 58.94; IR (thin film) ν: 3063 (m), 3032 (m), 1756 (s), 1496 (m), 1457 (s);
HR-MS, calcd. for C28H34NO6 ([M+NH4]+) 480.2386, found 480.2388.
ACKNOWLEDGMENT
The authors are very grateful to the following foundations for financial support, the
Key Projects of Tianjin Science and Technology Support Plan (10ZCKFSH01300),
National Natural Science Foundation of China (21302141) and two Tianjin Municipal
Natural Science Foundations (14JCQNJC12900 and 14JCZDJC33500).
SUPPORTING INFORMATION
Supplemental data for this article can be accessed on the publisher’s website.
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18

Table 1. Results for preliminary tests for ICl to be an oxidant for the conversion of lactol
3 to lactone 4a
Reaction time Yield
Entry
Oxidant
Base
Temperature (°C)b
(h)c
(%)d
K2CO3 (3.0
eq)
1
2
3
4
5
6
I2 (3.0 eq)
I2 (2.5 eq)
I2 (2.0 eq)
ICl (3.0 eq)
ICl (3.0 eq)
ICl (3.0 eq)
ICl (3.0 eq)
rt
10
93
K2CO3 (3.0
eq)
rt
16
90
82
51
65
65
K2CO3 (3.0
eq)
rt
24
K2CO3 (3.0
eq)
rt
2.5
5.5
5.5
K2CO3 (3.0
eq)
0°C-rt
-5°C-rt
K2CO3 (3.0
eq)
K2CO3 (3.0
eq)
7
8
-10°C-rt
0°C-rt
5.5
6.5
66
78
ICl (2.0 eq) K2CO3 (3.0
19

eq)
K2CO3 (3.0
eq)
9
ICl (1.5 eq)
ICl (1.3 eq)
ICl (1.2 eq)
ICl (1.1 eq)
ICl (1.0 eq)
ICl (1.5 eq)
ICl (1.5 eq)
ICl (1.5 eq)
ICl (1.5 eq)
IBr (1.5 eq)
0°C-rt
0°C-rt
0°C-rt
0°C-rt
0°C-rt
0°C-rt
0°C-rt
0°C-rt
0°C-rt
0°C-rt
0°C-rt
20
7
92
85
80
75
72
92
91
89
71
93
0
K2CO3 (3.0
eq)
10
11
12
13
14
15
16
17
18
19
9
K2CO3 (3.0
eq)
13
20
>24
7
K2CO3 (3.0
eq)
K2CO3 (3.0
eq)
K2CO3 (4.0
eq)
K2CO3 (3.5
eq)
7
K2CO3 (2.5
eq)
9
K2CO3 (2.0
eq)
14
7
K2CO3 (3.0
eq)
ICl3 (1.5
eq)
K2CO3 (3.0
eq)
3

ICl3 (0.6
eq)
K2CO3 (3.0
eq)
20
0°C-rt
5
25
aReaction conditions: 1.00 g of 3 was dissolved in 10 mL of dried CH2Cl2 and then stirred
at temperatures specified in the table, followed by addition of specified equivalents of
K2CO3. The suspension was stirred at temperatures specified in the table, and specified
equivalents of oxidant dissolved in 2 mL of CH2Cl2 was added dropwise except for entry
1-4 where oxidants were added neat in one portion. After addition, the reaction mixture
was then stirred at room temperature until the reaction completed.
brt, room temperature.
cThe reaction course was monitored by TLC at 0.5-h intervals.
dIsolated yield.
21

Table 2. Results for the optimization of base and solvent for ICl to be an oxidant for the
conversion of lactol 3 to lactone 4a
Reaction time
Yield
(%)c
25
30
33
97
16
17
27
22
55
2
Entry
Base
Solvent
(h)b
20
20
7
1
Na2CO3
NaHCO3
KHCO3
Cs2CO3
CaCO3
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
2
3
4
3
5
4
6
SrCO3
4
7
NaOH
4
8
KOH
4
9
CsOH·H2O
Mg(OH)2
Ca(OH)2
Sr(OH)2·8H2O
MgO
6
10
11
12
13
14
15
6
3
79
65
4
6
6
CaO
4
22
0
Et3N
3
22

16
17
18
19
20
pyridine
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
CH2Cl2
1
3
3
3
3
2
MeOH
16
23
35
22
CH2Cl2/MeOH(1/1)
EtOH
t-BuOH
aReaction conditions: 1.00 g of 3 was dissolved in 10 mL of dried solvent specified in the
table and then stirred at 0°C, followed by addition of 3 eq of base specified in the table.
The suspension was stirred at 0°C, and 1.5 eq of ICl dissolved in 2 mL of CH2Cl2 was
added dropwise. After addition, the reaction mixture was then stirred at room temperature
until the reaction completed.
bThe reaction course was monitored by TLC at 0.5-h intervals.
cIsolated yield.
23

Table 3. Results for the study of the scope of alcohol substrates with ICl as oxidanta
Yield
Entry
Substrate
Product
Reaction time (h)b
(%)c
1
5
94
2
3
2
4
96
83
4
5
6
5
95
91
24

6
7
2
3
96
0
8
9
5
94
83
20
10
11
12
5
4
4
90
96
91
25

13
14
15
4
3
3
82
82
98
16
17
3
8
91
88
18
19
20
5
24
6
32
49
0
aReaction conditions: 1.00 g of substrate was dissolved in 10 mL of dried CH2Cl2 (for
substrates in entries 8-20, 30 mL of dried CH2Cl2 was used) and then stirred at 0°C,
26

followed by addition of 3 eq of Cs2CO3. The suspension was stirred at 0°C, and 1.5 eq of
ICl dissolved in 2 mL of CH2Cl2 was added dropwise. After addition, the reaction
mixture was then stirred at room temperature until the reaction completed.
bThe reaction course was monitored by TLC at 0.5-h intervals.
cIsolated yield.
27

Scheme 1. Synthesis of glyconolactones 1 by oxidation of the corresponding aldose
hemiacetals 2.
28