A Catalytic Deprotection of S,S-, S,O- and O,O-Acetals Using Bi(NO3)3·5 H2O under Air

Article abstract of DOI:10.1002/1615-4169(200107)343:5<473::AID-ADSC473>3.0.CO;2-O

S,S-Acetals are smoothly deprotected with air in the presence of a catalytic amount of Bi(NO₃)₃·5 H₂O (1-50 mol %) under ambient conditions to regenerate the original carbonyl compounds in good to excellent yield. This mild, simple, and environmentally benign system is successfully applied to the deprotection of S,O- and O,O-acetals and is compatible with various functional groups. From the mechanistic study of the reaction, the catalytic cycle is considered to be composed of the following four steps: (1) the nitrososulfonium ion of the S,S-acetal is formed by attack of nitrosonium ion (NO⁺) generated from Bi(NO₃)₃·5 H₂O through the equilibrium wth NO₂, (2) the nitrososulfonium ion is hydrolyzed to afford the hemithioacetal and thionitrite, (3) the hemithioacetal collapses to the original carbonyl compound and thiol, which is oxidized by NO⁺ to give disulfide and NO via thionitrite, and (4) the NO captures molecular oxygen from air to regenerate NO₂.

Full text of DOI:10.1002/1615-4169(200107)343:5<473::AID-ADSC473>3.0.CO;2-O

FULL PAPER
A Catalytic Deprotection of S,S-, S,O- and O,O-Acetals
Using Bi(NO3)3´5 H2O under Air
Naoki Komatsu,a,* Azusa Taniguchi,a Shinobu Wada,b Hitomi Suzukib
a Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606
-
8502, Japan
Fax: +81-75-753-4000, e-mail: komatsu@kuchem.kyoto-u.ac.jp
b Department of Chemistry, School of Science, Kwansei Gakuin University, Uegahara, Nishinomiya 662
-
0891, Japan
Received May 17, 2001; Accepted June 6, 2001
Abstract: S,S-Acetals are smoothly deprotected with generated from Bi(NO3)3´5 H2O through the equili-
air in the presence of a catalytic amount of brium with NO2, (2) the nitrososulfonium ion is hy-
Bi(NO3)3´5 H2O (1-50 mol %) under ambient condi- drolyzed to afford the hemithioacetal and thionitrite,
tions to regenerate the original carbonyl compounds (3) the hemithioacetal collapses to the original car-
in good to excellent yield. This mild, simple, and en- bonyl compound and thiol, which is oxidized by
vironmentally benign system is successfully applied NO+ to give disulfide and NO via thionitrite, and (4)
to the deprotection of S,O- and O,O-acetals and is the NO captures molecular oxygen from air to re-
compatible with various functional groups. From generate NO2.
the mechanistic study of the reaction, the catalytic
cycle is considered to be composed of the following
four steps: (1) the nitrososulfonium ion of the S,S- Keywords: acetals; bismuth nitrate; deprotection;
acetal is formed by attack of nitrosonium ion (NO+) oxidation; protecting groups; reaction mechanisms
tions,[7] we have reported preliminary results on the
deprotection of simple S,S-acetals with air and a cata-
Introduction
lytic amount of Bi(NO3)3´5 H2O under ambient condi-
The S,S-acetal function finds wide use in organic
tions.[8] This paper gives a full account of the depro-
synthesis as a carbonyl protecting group due to its
easy access[1] as well as high stability under both
tection, including (1) its compatibility with various
functional groups on the S,S-acetals, (2) an extension
acidic and basic conditions. In addition, this function
is often employed as the acyl anion equivalent.[2] In
to the deprotection of S,O- and O,O-acetals, and (3)
the reaction mechanism. To our knowledge, the lit-
particular, 2-lithio-1,3-dithiane derivatives have been
erature to date contains no precedent for such an eco-
widely used for the key reactions to combine the
nomical, mild and environmentally benign[9] dethio-
acetalization.
building blocks in natural product syntheses.[3] In
spite of these synthetic utilities, the use of S,S-acetals
is occasionally hampered by the lack of an efficient
procedure for regenerating the original carbonyl
functionality, although various methods have been
developed. The methods reported so far may be clas-
sified into three categories; chemical, photochemical,
and electrochemical.[4] The latter two need expensive
equipment and are not amenable to scaling-up of the
reaction. In addition, known chemical methods re-
quire the use of a stoichiometric or an excess amount
of the demasking reagent,[2b,5,6] which usually in-
cludes heavy metal salts such as mercury(II), sil-
ver(I), and copper(II) salts as well as oxidizing agents
such as molecular halogens, N-halosuccinimides,
and MCPBA.
Results and Discussion
Deprotection of S,S-Acetals
The S,S-acetals derived from aldehydes and ketones
were smoothly deprotected in the presence of 1
-
50 mol % of Bi(NO3)3´5 H2O and 2 equivalents of
water under air to regenerate the parent carbonyl
As part of our ongoing program on the use of the
bismuth salts as catalyst for organic transforma-
Scheme 1.
Adv. Synth. Catal. 2001, 343, No. 5
Ó WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2001
1615-4150/01/34305-473±480 $ 17.50-.50/0
473

asc.wiley-vch.de
Table 1. Deprotection of S,S-acetals in benzene using a catalytic amount of Bi(NO3)3´5 H2O (Scheme 1).
Run
R1
R2
R3
Bi(NO3)3 (mol %) additive (mol %) Reaction time (h)
Yield (%)[a]
1
2
3
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
Ph
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)2
(CH2)3
Et
1
2
5
-
-
-
-
10
5
3
1
2
91
94
86
75
89
89
4[b]
5[c]
6[d]
7[d]
8
5
10
20
20
-
BiCl3 (5)
-
NaN3 (10)
NO2 (20)
-
-
-
-
-
-
-
-
-
-
-
-
2
5
Trace[e]
86
0.5
4.5
10
12
24
6
6
4
9
4
4
2
5
5
5
10
5
24
4
2
4
6
2
6
10
2
3
4
10
3
9
2
91
91
10
11
12[b],[g]
13
14[i]
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
10
10
5
2
2
2
5
5
5
5
5
5
5
10
5
40
40
30
20
20
20
20
10
10
10
20
50
10
50
10
20
Ph
Ph
98[f]
99[f]
72[h]
8[e],[h]
91[h]
81
(CH2)2
(CH2)2
(CH2)3
(CH2)2
(CH2)3
(CH2)2
(CH2)3
(CH2)2
(CH2)3
(CH2)2
(CH2)2
(CH2)3
(CH2)2
(CH2)2
(CH2)3
(CH2)2
(CH2)3
(CH2)3
Et
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)2
(CH2)3
(CH2)2
(CH2)3
(CH2)3
Ph
Ph
p-ClC6H4
p-ClC6H4
p-AcOC6H4
p-AcOC6H4
3,4-(MeO)2C6H3
3,4-(MeO)2C6H3
p-O2NC6H4
2-Thienyl
2-Thienyl
trans-PhCH=CH
trans-PhCH=CH
trans-PhCH=CH
Me(CH2)6
Me(CH2)6
Me(CH2)6
Me(CH2)6
Ph
Ph
Ph
Ph
Me(CH2)5
Me(CH2)5
Me(CH2)4
Me(CH2)4
80
98
92
92
-
-
-
-
93
68[h]
74[h]
76[h]
Trace[e]
90
-
BiCl3 (10)
-
-
-
BiCl3 (5)
-
-
70
98[h]
75[h]
81[h]
96[h]
76[h]
76[h]
76[h]
72[j]
93[h]
92[h]
94[h]
98[h]
98[h]
Me
Me
Me
Me
Me
Me
Et
Et
BiCl3 (5)
Bi2(SO4)3 (5)
-
-
-
-
-
-
24
5
5
-
(CH2)5
-
[a] Isolated yield unless otherwise noted.
[b] Under oxygen.
[c] In CH2Cl2 containing 1.4 equivalents of water.
[d] In MeCN containing 1.4 equivalents of water.
[e] Most of the substrate remained intact.
[f] In runs 9 and 10, diphenyl disulfide was obtained in 83% and 99% yields, respectively.
[g] Consumption of oxygen was measured volumetrically (see text).[10]
[h] GC yield.
[i] Under argon.
[j] a-Nitroacetophenone was obtained in 11 % yield, along with acetophenone (Equation 3).
compounds in good to excellent yield as shown in Ta-
In order to find a suitable solvent system for this
ble 1. Under an argon atmosphere, the reaction scar- dethioacetalization, several solvents were exam-
cely proceeded (run 14), while the reaction was com- ined under the same conditions (Equation 1). The
plete within an hour under oxygen (run 4). These results are summarized in Table 2. Benzene was
results suggest that oxidation by molecular oxygen is found to be the best solvent to proceed the fastest re-
involved as a key step of the deprotection. This view is action rate (run 1). Toluene, dichloromethane, ace-
supported by the fact that an equimolar amount of tonitrile, 1,4-dioxane, and ethyl acetate can be used
molecular oxygen was consumed during the depro- as alternative solvents, although longer reaction
tection to produce diphenyl disulfide and p-anisalde- times were needed than for benzene to complete
hyde quantitatively (run 12).[10] Actually, Bi(NO3)3´5 the deprotection of S,S-acetal (runs 2
-6). A similar
H2O has been utilized as an oxidation catalyst for trend is observed in the amount of catalyst required;
sulfide to sulfoxide[11] and thiol to disulfide[12] trans- less than 5 mol % of Bi(NO3)3´5 H2O is sufficient for
formations under similar conditions.
the dethioacetalization in benzene (runs 1-3 in Ta-
474
Adv. Synth. Catal. 2001, 343, 473±480

FULL PAPERS
ble 1), while 10 and 20 mol % are necessary in di- with 5-10 and 30-40 mol % of the catalyst (runs 23-
chloromethane and acetonitrile, respectively (runs 5 24 and 25
and 6 in Table 1). In THF, DMF, hexane, CCl4, and
methanol, the reaction hardly proceeded.
-
27), respectively.
ꢀ1†
ꢀ2†
Table 2. Solvent effects in the deprotection of S,S-acetals
(Equation 1).
The dithioacetals from ketones and aliphatic alde-
hydes needed a larger amount of the catalyst (10 50
mol %) (runs 25 40) than those from aromatic alde-
Run
Solvent
Reaction time (h) Yield (%)[a]
-
-
1
2
3
4
5
6
7
8
benzene
toluene
CH2Cl2
MeCN
1,4-dioxane
AcOEt
2
3
5
100
100
94
hydes. When the reaction was sluggish, it was consid-
erably facilitated by the additional presence of a sec-
ond bismuth salt, i.e., BiCl3 and Bi2(SO4)3, as an
auxiliary additive (runs 26, 30, 33 and 34). Without
Bi(NO3)3´5 H2O, S,S-acetals remained intact even in
the presence of the second bismuth salt.
6
93
83
93
39
10
24
24
24
CHCl3
THF
10
A variety of S,S-acetals 1
successfully deprotected with the present system as
shown in Table 3. The alcohols 1 3 derived from 2-
-
5[5c,13] (Figure 1) was
[a] GC yield.
-
lithio-2-methyldithiane and the corresponding meth-
As for the catalysts, other bismuth salts such as
BiF3, BiCl3, BiOCl, BiBr3, BiI3, Bi(OAc)3, and
Bi2(SO4)3, and other metal nitrates such as
Zn(NO3)2´6 H2O, Pb(NO3)2, and La(NO3)3´6 H2O
showed little or no catalytic activity under the condi-
tions used for runs 2 and 6 in Table 1. As for the added
water, 2 equivalents gave the best result; larger and
smaller amounts of water (1 and 3 equivalents) re-
tarded the reaction considerably.
yl ketones[13c] were deprotected to give a-hydroxy ke-
Figure 1. Structures of compounds 1 ± 5.
Under the optimized conditions, the cyclic dithioa-
cetals derived from aromatic aldehydes were de-
masked using less than 5 mol % of the catalyst (runs
Table 3. Deprotection of various functionalized S,S-acetals
in benzene using a catalytic amount of Bi(NO3)3´5 H2O.
1
-
4 and 13
tional groups on the aromatic ring such as
Cl, OAc, and
NO2, and the thioacetal moieties (R3)
-
22 in Table 1) regardless of the func-
Yield (%)[a]
-
OMe,
-
Run
S,S-acetal Bi(NO3)3
BiCl3
(mol %)
Reaction
time (h)
(mol %)
-
-
such as dithiane, dithiolane and acyclic acetals. Hy-
droxy and dimethylamino functions at para-positions
made the catalytic reactions sluggish; an equimolar
amount of Bi(NO3)3´5 H2O was needed to make these
reactions proceed, affording a large amount of ni-
trated products along with the desired aldehydes
(Equation 2). In these reactions, the yields of the prod-
ucts were not reproducible probably because a con-
siderable amount of nitrogen oxides was generated
by the decomposition of Bi(NO3)3´5 H2O, which will
be discussed below, and nitrated the substrates and
the products indiscriminately. S,S-Acetals with a thio-
phene ring and conjugated double bond were depro-
tected to give the desired aldehydes in good yields
1
2
3
4
5
6
7
8
9
1
2
3
4
4
4
4
5
5
10
10
20
20
50
50
50
20
20
-
-
-
5
50
30
10
-
2
5
5
24
7
7
7
24
4
77
75
60
NR[b]
43[c],[d]
39[c],[d]
22[c],[e]
92[f]
10
95[f]
[a] Isolated yield unless otherwise noted.
[b] No reaction.
[c] GC yield.
[d] Trace amount of substrate was recovered after work-up.
[e] Substrate (27 %) was recovered after work-up.
[f] Yield of a crude product, which was found almost pure on
13C NMR spectra.
Adv. Synth. Catal. 2001, 343, 473±480
475

asc.wiley-vch.de
tones in good yields with 10-20 mol % of the catalyst from aldehydes and ketones were deprotected with
(runs 1
-
3). Although the deprotection of the ketone
5-20 mol % of Bi(NO3)3´5 H2O in wet benzene and/
4[5c,13b,13d] to the 1,2-diketone required 50 mol % of or acetonitrile/water to regenerate the carbonyl com-
Bi(NO3)3´5 H2O together with bismuth(III) chloride pounds in good to excellent yields. As for the depro-
(10-50 mol %) (runs 4-6), the S,S-acetal derived tection of O,O-acetals (dioxolanes), 0.1 mol % of Bi(-
from d-glucose 5[13a] was deprotected almost quanti- NO3)3´5 H2O is sufficient to regenerate the parent
tatively in the presence of 20 mol % of the catalyst carbonyl compounds quantitatively in acetonitrile/
(run 8). The copresence of 10 mol % BiCl3 remark- water (runs 13 and 15), while much larger amounts
ably accelerated the deprotection of 5 (run 9).
of the catalyst resulted in a poor yield in wet benzene
(run 14).
Such a remarkable difference depending on the
solvent system may imply the operation of a different
Deprotection of S,O- and O,O-Acetals
reaction mechanism. In acetonitrile/water, C-O
The present method is found to be effective for the de-
protection of S,O- and O,O-acetals (Scheme 2). S,O-
Acetals have also been known to require harsh condi-
tions and/or the use of a stoichiometric or an excess
amount of reagent for their deprotection in spite of
their synthetic importance similar to that of S,S-acet-
als.[5a,14] On the other hand, a simple chemoselective
method for the deprotection of O,O-acetals has been
developed using Bi(NO3)3´5 H2O as a catalyst quite re-
cently.[15]
The results of the deprotection of S,O- and O,O-
acetals are summarized in Table 4. Acetonitrile/water
(4/1 v/v) was found to be a complementary solvent to
the wet benzene used for the deprotection of S,S-acet-
als; much better yields were obtained in acetonitrile/
water (runs 8, 12 and 13) than in wet benzene (runs 7,
11 and 14), while the opposite trends were observed
bond fission is considered to occur preferentially via
hydrolysis under the catalysis of nitric acid generated
by hydrolysis of Bi(NO3)3´ 5 H2O,[15] while the C
-S
bond may be cleaved in wet benzene via oxidation
under the catalysis of NO+ generated by decomposi-
tion of Bi(NO3)3´5 H2O, which will be discussed be-
low. The recent report on a similar deprotection of
O,O-acetals describes that a suspension of Bi(-
NO3)3´5 H2O in water is acidic and that the resulting
nitric acid promotes the deprotection.[15] An addi-
tional point to note in the report is that no reaction is
observed with dioxolanes in dichloromethane even in
the presence of 25 mol % of Bi(NO3)3´5 H2O, which is
in marked contrast to our results (runs 13 and 15 in
Table 4).
in runs 3-4 and 9-10. All the oxathiolanes derived
Reaction Mechanism
From the above discussion, it has been established
that S,S-acetals were cleaved oxidatively by molecu-
lar oxygen. This poses the question: what is the oxi-
dant? A hint towards the answer was obtained from
Scheme 2.
Table 4. Deprotection of S,O- and O,O-acetals using a catalytic amount of Bi(NO3)3´5 H2O (Scheme 2).
Run
R1
R2
X
Solvent
Bi(NO3)3 (mol %) Reaction time (h)
Yield (%)[a]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
p-MeOC6H4
p-MeOC6H4
Ph
H
H
H
H
H
H
Me
Me
Me
Me
Me
Me
H
S
S
S
S
S
S
S
S
S
S
S
S
O
O
O
benzene[b]
5
9
10
5
10
5
5
24
24
19
24
32
6
64
68
MeCN/H2O (4/1)
benzene[b]
79
Ph
MeCN/H2O (4/1)
benzene[b]
NR[c]
70
p-NO2C6H4
Me(CH2)6
Ph
benzene[b]
81
benzene[b]
6
6[d],[e]
93[d]
74
Ph
MeCN/H2O (4/1) 10
24
20
36
6
24
3
p-BrC6H4
p-BrC6H4
Me(CH2)5
Me(CH2)5
Ph
Ph
Me(CH2)5
benzene[b]
20
5
5
MeCN/H2O (4/1)
24
benzene[b]
3[d],[e]
98[d]
95[d]
16[d],[e]
100[d]
MeCN/H2O (4/1) 10
MeCN/H2O (4/1)
0.1
5
0.1
H
Me
benzene[b]
4
3
MeCN/H2O (4/1)
[a] Isolated yield unless otherwise noted.
[b] Added 2 equivalents of H2O.
[c] No reaction.
[d] GC yield.
[e] Most of substrate remained intact.
476
Adv. Synth. Catal. 2001, 343, 473±480

FULL PAPERS
the by-products from the reactions. As we mentioned
above, various nitrated products were obtained in the
stoichiometric deprotection of 2-(4-hydroxyphenyl)-
1,3-dithiolane (Equation 2) as well as in the catalytic
deprotection
of
2-methyl-2-phenyl-1,3-dithiane
(Equation 3), implying the existence of nitrogen oxi-
des generated in situ.
ꢀ3†
The following experimental observations support
that this process involved NO2 as a key compound.
Light brown fumes were evolved when the S,S-acetal
was mixed with Bi(NO3)3´5 H2O without a solvent in
an open flask. The color was bleached immediately
when the flask was capped. These observations may
indicate the equilibrium between NO2 and N2O4.[11]
In addition, a catalytic amount of NO2 completed the
deprotection as with Bi(NO3)3´5 H2O (run 8 in Ta-
ble 1). In the literature, Bi(NO3)3´5 H2O is reported to
evolve nitrogen oxides (NO and NO2) during its ther-
mal decomposition[16] and has been employed for the
nitration of aromatic compounds[17] and for the oxi-
dation of sulfides,[11,18] alcohols,[17b,19] and dihydro-
pyridine.[17c] NO2 and nitrosonium salt are also used
for the oxidative deprotection of S,S-acetals.[6b,20]
These experimental observations, coupled with the
reported evidence, lead to the inescapable conclu-
sion that the in situ generated NO2 from
Bi(NO3)3´5 H2O works as the oxidant for the present
dethioacetalization. More precisely, NO+ is a most
likely oxidizing agent, because it is a strong oxidizing
agent produced via ionic dissociation of N2O4.[21] Ac-
tually, a catalytic amount of NaN3, a known NO+
quencher,[22] prevented the deprotection in the pre-
sence of a catalytic amount of Bi(NO3)3´5 H2O (run 7
in Table 1). In the nitration of phenols and oxidation
of benzyl alcohol with supported metal nitrate, NO+
generated from metal nitrate is accepted as the com-
mon active intermediate.[16]
Figure 2. A plausible catalytic cycle for the deprotection of
S,S-acetals using air and a catalytic amount of Bi(NO3)3´
5H2O.
fonium ion by capture of nitrate ion (NO3 ) as
reported.[21a,23]
In the second stage, the nitrososulfonium ion is hy-
drolyzed to afford the thionitrite (R3SNO) and the
hemithioacetal. Since thionitrites, except for tertiary
ones, are known to be red in solution,[24] the genera-
tion of thionitrite in our process is supported by the
fact that the mixture colored red during the reaction
in most cases. In the deprotection of S,S-acetals by di-
rect use of NO2, a pink-colored mixture is reported to
be discharged on completion of the reaction,[20b]
which also implies the formation of thionitrite as a
transient intermediate. A similar process from S,S-
acetal to thionitrite through hydrolysis of nitrososul-
fonium ion has been proposed by Jùrgensen[20d] and
Olah.[20c] Another role of bismuth salts may be as a
soft Lewis acid to facilitate the nucleophilic attack of
H2O via coordination with the sulfur atom during hy-
drolysis.
In the third stage, the parent carbonyl compound
and thiol are produced by the decomposition of the
hemithioacetal. The thiol is readily oxidized by NO+
to afford the corresponding disulfide and NO via thio-
nitrite.[24]
In the final stage, NO2 is regenerated via molecu-
lar oxygenation of NO in solution, completing the
catalytic cycle. Under an argon atmosphere, how-
ever, NO2 could not be regenerated, resulting in the
low conversion as mentioned above (run 14 in Ta-
ble 1). The same process from NO to NO2 is pro-
posed in the catalytic oxidation of sulfides with NO2
and O2.[23]
A plausible catalytic cycle in the deprotection of
S,S-acetals is illustrated in Figure 2. Similar mechan-
isms have been proposed by Jùrgensen in the depro-
tection of S,S-acetals using NaNO2,[20d] and by Olah in
the desulfurative fluorination using NO+BF4 .[20c]
The catalytic cycle is initiated by the formation of
the nitrososulfonium ion of the S,S-acetal by the at-
tack of NO+ generated from Bi(NO3)3´5 H2O. The bis-
muth salt may shift the equilibrium to the nitrososul-
The stoichiometry in the catalytic cycle unequivo-
cally agreed with that of the experimental result (run
Adv. Synth. Catal. 2001, 343, 473±480
477

asc.wiley-vch.de
was prepared according to the literature;[13a] yield: 98%;
mp 142 143 °C.
12 in Table 1), where an equimolar amount of dioxy-
gen was consumed to afford equimolar amounts of p-
anisaldehyde and diphenyl disulfide.
-
Benzylation of the d-glucose propane-1,3-diyl dithioacetal
was carried out as follows: to NaH (60% dispersion in oil,
2.5 g, 60 mmol) washed with dry hexane, d-glucose pro-
pane-1,3-diyl dithioacetal (1.35 g, 5.0 mmol) in 20 mL DMF
was added over 0.5 h under an argon atmosphere. After stir-
ring for 1 h at 25 °C, the mixture was cooled down to 10 °C,
and benzyl bromide (6.0 g, 35 mmol) was added dropwise
over 0.5 h. The resulting mixture was stirred at 10 °C for
12 h. After quenching the reaction by the addition of MeOH
(10 mL) followed by H2O (10 mL), the mixture was extracted
with AcOEt three times. The combined extracts were
washed with water three times and brine once, dried over
Na2SO4, and concentrated. The residue was flash chromato-
graphed on silica gel to give 2,3,4,5,6-penta-O-benzyl-d-glu-
cose propane-1,3-diyl dithioacetal; yield: 2.56 g (71%); col-
Conclusion
The present method for the deprotection of S,S-acet-
als features the combined use of a catalytic amount of
bismuth nitrate pentahydrate and molecular oxygen
from air; the major advantages are simple manipula-
tion, mild conditions, no use of toxic reagents, and
economy. This method is successfully applied to the
deprotection of a variety of functionalized S,S-acetals
as well as S,O- and O,O-acetals. From the mechanistic
point of view, NO+ generated from Bi(NO3)3´5 H2O is
considered to play a crucial role for this oxidative
cleavage as a real catalyst. The catalytic cycle of NO+
is composed of the following four steps as shown in
Figure 2: (1) the nitrososulfonium ion of the S,S-ace-
tal is formed by the attack of NO+ generated from
Bi(NO3)3´5 H2O through the equilibrium with NO2,
(2) the nitrososulfonium ion is hydrolyzed to afford
the hemithioacetal and thionitrite, (3) the hemithio-
acetal collapses to the original carbonyl compound
and thiol, which is oxidized by NO+ to give disulfide
and NO via thionitrite, and (4) the NO captures mole-
cular oxygen from air to regenerate NO2.
orless syrup; 1H NMR: d = 7.32
-7.25 (m, 25H, ArH), 4.91-
3.70 (m, 17H, CH2, CH), 2.89
-
2.53 (m, 6H, CH2); 13C NMR: d
= 138.42, 138.27, 138.05. 138.05, 137.96, 128.00, 127.88,
127.83, 127.41, 127.31, 127.10, 81.11, 79.75, 79.26, 78.29,
75.06, 73.84, 73.46, 72.94, 71.67, 69.34, 48.85, 29.56, 29.09,
25.69; anal. calcd. for C44H48O5S2: C, 73.30; H, 6.71%; found:
C, 73.17; H, 6.71%.
Preparation of S,O-Acetals
All S,O-acetals were prepared according to the recent re-
port.[25]
General Procedure for the Deprotection of S,S-
Acetals in Benzene
Experimental Section
General Procedures
To a solution of S,S-acetal (0.5 mmol) in dry benzene (10
1H (200 MHz) and 13C (50 MHz) NMR spectra were obtained
with a Varian Gemini-200 for solutions in CDCl3 with Me4Si
as an internal standard. Chemical shifts were reported in d,
and the coupling constants (J) are in Hz. IR spectra were re-
corded on a Shimadzu FTIR 8100S infrared spectrophoto-
meter. Mass spectra were recorded on a Shimadzu GCMS
QP5000 spectrometer. Melting points were determined with
a Yanaco MP-J3 apparatus and are uncorrected. Flash chro-
matography was performed with Wakogel C-300. Solvents
and reagents were used as commercially received unless
otherwise noted.
mL) were added finely powdered Bi(NO3)3´5 H2O (1-50
mol %) followed by two equivalents of water (1 mmol).
When needed, BiCl3 was also added. The mixture was mag-
netically stirred in a stoppered flask for an appropriate time
at ambient temperature, while the progress of the reaction
was intermittently monitored by GLC. Since there was an in-
duction period, the reaction time was sometimes not repro-
ducible. The stopper was loosened at intervals in order to
admit a fresh air into the reaction vessel. The reaction was
quenched by the addition of water and the products were ex-
tracted with AcOEt three times. The yield of carbonyl com-
pound was determined by isolation with flash column chro-
matography or GLC.
Preparation of S,S-Acetals
All S,S-acetals except for 1-
5[5c, 13] were prepared according
to our method.[1]
Typical Procedure for the Deprotection of 2-(p-
Methoxyphenyl)-1,3-dithiolane in Dichloro-
methane (Run 5 in Table 1)
2-(1-Hydroxy-1-methyl-3-phenylpropyl)-2-methyl-1,3-
dithiane (2)[13c]: Colorless oil; 1H NMR: d = 7.32
7.15 (m,
5H, ArH), 3.04 2.64 (m, 6H, CH2), 2.38 (s, 1H, OH), 2.29
-
-
-
1.76 (m, 4H, CH2), 1.81 (s, 3H, CH3), 1.47 (s, 3H, CH3); IR
(neat). m = 3490, 2980, 1497, 1455, 1277, 700 cm±1; MS (CI,
isobutane): m/z = 283 (M++1); anal. calcd. for C15H22OS2: C,
63.78; H, 7.85%; found: C, 63.82; H, 7.93%.
To
a
solution of 2-(p-methoxyphenyl)-1,3-dithiolane
(106.1 mg, 0.50 mmol) in dry dichloromethane (10 mL)
were added finely powdered Bi(NO3)3´5 H2O (25.8 mg,
0.053 mmol) and BiCl3 (8.0 mg, 0.025 mmol) followed by
water (13 lL, 0.72 mmol). The mixture was magnetically
stirred for 3.5 h at room temperature. The stopper was loo-
2,3,4,5,6-Penta-O-benzyl-d-glucose
propane-1,3-diyl
dithioacetal (5): d-Glucose propane-1,3-diyl dithioacetal
478
Adv. Synth. Catal. 2001, 343, 473±480

FULL PAPERS
sened at intervals in order to admit a fresh air into the reac-
tion vessel. The reaction was quenched by the addition of
water and the products were extracted with AcOEt three
times. After being dried with anhydrous MgSO4, the com-
bined extracts were concentrated and the residue was chro-
matographed on silica gel to give p-anisaldehyde; yield:
88%.
Chemie (Houben-Weyl), 4th Edn., Georg Thieme Ver-
lag, Stuttgart, 1992, pp. 481
-
482; (c) E. J. Corey, B. W.
3560.
Erickson, J. Org. Chem. 1971, 36, 3553
-
[6] To the best of our knowledge, two examples of cataly-
tic deprotection have been reported previously: (a) T.
Ravindranathan, S. P. Chavan, R. B. Tejwani, J. P.
Varghese, J. Chem. Soc., Chem. Commun. 1991, 1750
1751; (b) G. A. Olah, S. C. Narang, G. F. Salem, B. G. B.
Gupta, Synthesis 1979, 273 274.
-
-
Typical Procedure for the Deprotection of 2-(p-
Methoxyphenyl)-1,3-oxathiolane in Acetonitrile/
Water (Run 2 in Table 4)
[7] N. Komatsu in Organobismuth Chemistry (Eds.: H. Su-
zuki, Y. Matano), Elsevier, Amsterdam, 2001, Chap. 5
and references cited therein.
[8] N. Komatsu, A. Taniguchi, M. Uda, H. Suzuki, Chem.
To
a solution of 2-(p-methoxyphenyl)-1,3-oxathiolane
Commun. 1996, 1847-1848.
(48.8 mg, 0.25 mmol) in acetonitrile/water (4 mL/1 mL)
was added finely powdered Bi(NO3)3´5 H2O (10.9 mg,
0.022 mmol). The mixture was magnetically stirred for 24 h
at room temperature. The stopper was loosened at intervals
in order to admit fresh air into the reaction vessel. The
work-up procedure was similar to that of the deprotection
of 2-(p-methoxyphenyl)-1,3-dithiolane. p-Anisaldehyde was
obtained in 68% yield after flash column chromatography on
silica gel.
[9] Bismuth salts are of low toxicity, see: H. Suzuki in Or-
ganobismuth Chemistry (Eds.: H. Suzuki, Y. Matano),
Elsevier, Amsterdam, 2001, Chap. 1 and references ci-
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[10] Uptake of a half equivalent of molecular oxygen re-
ported in the previous communication[8] is corrected
to an equimolar amount in this paper.
[11] N. Komatsu, M. Uda, H. Suzuki, Chem. Lett. 1997,
1229-1230.
[12] N. Komatsu, M. Uda, H. Suzuki, unpublished result.
[13] (a) O. KoÈlln, H. Redlich, H. Frank, Synthesis 1995,
1383
H. Veschambre, Tetrahedron Lett. 1990, 31, 2599
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N.K. thanks Professor Keiji Maruoka of Kyoto University for
his encouragement.
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[14] A few examples of catalytic deprotection have been
reported to date: (a) M. Kirihara, Y. Ochiai, N. Arai, S.
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