Reaction of acetals with various carbon nucleophiles under non-acidic conditions: C-C bond formation via a pyridinium-type salt

Article abstract of DOI:10.1002/asia.201100812

Mild substitution reactions of acetals with carbon nucleophiles via the pyridinium-type salts generated by the treatment of acetals with TESOTf-2,4,6-collidine or 2,2′-bipyridyl have been developed. Various carbon nucleophiles, such as organocuprates, sil

Full text of DOI:10.1002/asia.201100812

DOI: 10.1002/asia.201100812
Reaction of Acetals with Various Carbon Nucleophiles under Non-Acidic
À
Conditions: C C Bond Formation via a Pyridinium-Type Salt
Hiromichi Fujioka,* Kenzo Yahata, Tomohito Hamada, Ozora Kubo, Takashi Okitsu,
Yoshinari Sawama, Takuya Ohnaka, Tomohiro Maegawa, and Yasuyuki Kita[a]
Abstract: Mild substitution reactions of
acetals with carbon nucleophiles via
the pyridinium-type salts generated by
the treatment of acetals with TESOTf-
2,4,6-collidine or 2,2’-bipyridyl have
been developed. Various carbon nucle-
ophiles, such as organocuprates, silyl
enol ethers, enamines, etc., reacted
with the pyridinium-type salts to give
the corresponding substituted products
in good yields. The reactions proceeded
under very mild conditions (non-acidic
conditions) and thus acid-sensitive
functional groups can be tolerated
during the reaction. In addition, only
an acetal can form the pyridinium-type
salt and react with nucleophiles in the
presence of a ketal. This unusual selec-
tivity is in contrast to general methods
conducted under acidic conditions.
Keywords: acetals · carbon nucleo-
À
philes · cations · C C bond forma-
tion · pyridinium-type salts
Introduction
etc. On the other hand, the use of organometallic reagents
as nucleophiles is not very common. Some acetals, such as
a,b-unsaturated acetals, can react with these reagents to
give substituted products[2–5] or the Lewis-acid-activated or-
ganocuprates can react with the acetals.[6] Therefore, nucleo-
À
The carbon carbon bond formation is a fundamental pro-
cess in organic synthesis and numerous methods have been
developed for achieving it. One of the most powerful meth-
ods is the reaction of the carbonyl groups with a variety of
carbon nucleophiles. Acetals are a typical carbonyl protect-
ing group as well as a synthetic equivalent of the carbonyl
group. In general, acetals are stable under strongly basic to
neutral conditions and do not react with nucleophilic re-
agents, for example, organolithium reagents and Grignard
reagents, under these conditions. However, acetals act as
strong electrophiles toward various nucleophiles under
acidic conditions owing to the generation of an oxonium ion
intermediate. Since Mukaiyama and Murakami reported the
first aldol-type reaction of acetals with silyl enol ethers
using a stoichiometric amount of TiCl4, a number of acid-
À
philes for C C bond formations are rather limited. In addi-
tion, these reactions have to be conducted under acidic con-
ditions.
We recently reported the deprotection of acetals in the
presence of ketals using a combination of triethylsilyl tri-
fluoromethanesulfonate (TESOTf) and 2,4,6-collidine
(Scheme 1).[7] The key to the reaction is the formation of
the corresponding collidinium salts, which are rather stable
even at 08C, in contrast to the oxonium ion intermediates.
À
mediated C C bond-forming reactions of acetals have been
reported.[1] To generate oxonium ions from acetals, strong
Lewis acids, such as trimethylsilyl trifluoromethanesulfonate
(TMSOTf), TiCl4, SnCl4, and BF3·Et2O, are usually used.
Typically, these reactions should be conducted at À788C[1a,c]
because the oxonium ion intermediates generated under
acidic conditions are unstable. A variety of carbon nucleo-
philes can react with the oxonium ion intermediates, such as
silyl enol ethers, enamines, cyanides, allyl trimethylsilane,
Scheme 1. The unprecedented acetal-selective deprotection in the pres-
ence of ketals via the formation of collidinium salts in combination with
TESOTf-2,4,6-collidine.
[a] Prof. Dr. H. Fujioka, K. Yahata, T. Hamada, O. Kubo, T. Okitsu,
Y. Sawama, T. Ohnaka, Dr. T. Maegawa, Prof. Dr. Y. Kita
Graduate School of Pharmaceutical Sciences
Osaka University
However, these salts are reactive toward nucleophiles. For
instance, hydrolysis of the collidinium salts proceeds readily
to give aldehydes via hemiacetal intermediates. The collidi-
nium salts are reactive towards not only water, but also
other heteroatom nucleophiles, oxygen-, sulfur-, and nitro-
gen nucleophiles (i.e., alcohols, thiols, azides, etc.) and the
corresponding mixed O,O-acetals, O,S-acetals, and N,O-ace-
tals were obtained in good-to-high yields (Scheme 2).[8] In
1-6 Yamada-oka Suita
Osaka 565-0871 (Japan)
Fax : (+81)6-6879-8229
E-mail: fujioka@phs.osaka-u.ac.jp
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201100812.
Chem. Asian J. 2012, 7, 367 – 373
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367

FULL PAPERS
2,4-dichlorophenol are reactive toward the Grignard re-
agents because 2,4-dichlorophenol acts as a good leaving
group.[3] We have previously reported the reaction of me-
thoxyethoxy acetals with Grignard reagents, and a substitu-
tion reaction occurred by chelation of the magnesium ion
with the methoxyethoxy group.[4] a,b-Unsaturated acetals
could react with Grignard reagents alone or in the presence
of a Lewis acid.[5] Organocuprates activated by BF3·Et2O
could also react with acetals[6] via oxonium ion intermedia-
tes.[6g] Therefore, these reactions were usually conducted at
low temperature. Accordingly, the mild substitution reaction
of an acetal with organometallic reagents is difficult but in-
teresting, especially under non-acidic conditions.
In our method, the electrophilic collidinium salts could be
generated under mild reaction conditions. We then applied
this method to the substitution reactions with organometal-
lic reagents. The reactions of the collidinium salt, generated
from acetal 1a under TESOTf-2,4,6-collidine conditions,
with various organometallic reagents were examined
(Table 1). Although phenyllithium did not give any desired
Scheme 2. The substitution reactions of acetals with various heteroatom
nucleophiles via the generation of collidinium salts from acetals in combi-
nation with TESOTf-2,4,6-collidine.
addition, acid-sensitive functional groups are tolerable with-
out any loss of them because our reactions proceeded under
weakly basic conditions (a slight excess of 2,4,6-collidine
over TESOTf was used). It is very significant that the selec-
tive formation of the collidinium salts from acetals led to
the chemoselective deprotection of the acetals, even in the
presence of ketals by distinguishing their steric environ-
ments.
We have also studied the reaction of the collidinium-salt
intermediates with Gilman reagents as carbon nucleo-
philes.[9] Herein, we report the scope of the reactivity of the
collidinium-salt intermediates to various carbon nucleo-
philes, including not only Gilman reagents, but also silyl
enol ethers, enamines, isocyanides, and cyanides (Scheme 3).
Table 1. Reaction of organometallic reagents and acetal 1a under
TESOTf-2,4,6-collidine conditions.
À
Ph M
Entry
Yield [%]
1
2
PhLi
PhMgBr
trace
33
Scheme 3. Carbon nucleophiles used in this work.
3
PhMgBr+CuI
Ph2Cu(CN)Li2
Ph2CuLi (3a)
90
65
93
4
5[a]
Results and Discussion
[a] When 2,6-lutidine was used instead of 2,4,6-collidine, 2a was obtained
in 72% yield.
Reactions with Organocuprates
To reveal the reactivity and usefulness of the collidinium
salts generated from acetals and 2,4,6-collidine, we investi-
gated several organometallic reagents (Grignard reagents,
organocuprates, and organolithium reagents). Acetals are
known to be intrinsically inert to organometallic reagents.
Only a limited number of examples of reactions with
product, phenylmagnesium bromide afforded the product 2a
in 33% yield (Table 1, entries 1 and 2). The combination of
CuI and phenylmagnesium bromide successfully reacted
with the salt to give compound 2a in 90% yield at 08C
(Table 1, entry 3). The use of a higher-order cuprate resulted
in a decreased yield (65%) (Table 1, entry 4), but the
Gilman reagent 3a afforded the best result (93%) among
the organometallic reagents (Table 1, entry 5).
Gilman reagents (3) bearing diverse alkyl groups reacted
with 1a via the collidinium salt; mostly afforded the substi-
tuted products (2) in good yields (Table 2). All the reactions
were completed within 0.5 hours. Only tBu2CuLi did not
afford the corresponding product (Table 2, entry 4).
organoACHTUNGTRENNUNGmetallic reagents have been reported and substitution
of one of the alkoxy groups proceeded to give the corre-
sponding products.[2] The reactions with Grignard reagents
required either the use of a special acetal moiety or activa-
tion by Lewis acids. For example, mixed acetals consisting of
Abstract in Japanese:
A variety of acetals are applicable for this reaction. Dieth-
yl acetal 1b, cyclic acetal 1c, and substituted dimethyl acetal
1d were converted into their corresponding collidinium salts
and treated with Ph2CuLi (3a) to give the substituted prod-
ucts 2i–k in good yields (Table 3, entries 1–3). It should be
noted that other functional groups, including acid-sensitive
tert-butyldimethylsilyl (TBS) and trityl (Tr) groups can be
368
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Chem. Asian J. 2012, 7, 367 – 373

À
C C Bond Formation via a Pyridinium-Type Salt
Table 2. Reaction with acetal 1a with various Gilman reagents under
TESOTf-2,4,6-collidine conditions.
The reactions of n-dodecanal dimethylacetal 1i with silyl
enol ether 4a (3 equiv) and silyl ketene acetals 4b and 4c (3
and 5 equiv, respectively) at room temperature proceeded
successfully under our reaction conditions. After the forma-
tion of the collidinium salt from 1i, the addition of 4a, 4b,
and 4c gave the corresponding ketone 5a and esters 5b and
5c in good yields, respectively (Table 4, entries 1–3). In
these reactions, the silyl ketene acetals afforded higher
yields than the silyl enol ether. We then chose silyl ketene
acetal 4c and investigated the scope of the acetal substrate.
The reaction of the aromatic acetal 1j and 4c afforded the
corresponding ester 5d in moderate yield (Table 4, entry 4).
Acetals 1g, 1h, and 1k–n, which contain other functional
groups including alcohol-protecting groups, underwent the
substitution reaction to afford the corresponding products
5e–j in good to high yields (Table 4, entries 5–10). Acid-
labile groups, which cannot tolerate the Lewis-acid-mediat-
ed substitution reaction conditions, were successfully incor-
porated into the substitution products (Table 4, entries 5 and
6). The free hydroxy group did not affect the reaction and
the silylated product 5i was obtained in good yield (Table 4,
entry 9).
Entry
R
Product
Yield [%]
1
2
3
4
5
6
Me (3b)
nBu (3c)
sBu (3d)
tBu (3e)
TMSCH2 (3 f)
2b
2c
2d
2e
2 f
2g
91
90
73
0[a]
96
87
PhACHTUNGTRENNUNG(CH2)2 (3g)
7
2h
86
ACHTUNGTRENNUNG(3 f)
[a] Unknown products were obtained.
Table 3. Reaction of acetals 1 with Ph2CuLi 3a under TESOTf-2,4,6-col-
lidine conditions.
Entry
1
Substrate
Product
t [h]
Yield [%]
80
Table 4. Reaction of acetals (1) with silyl enol ether and silyl ketene ace-
tals (4) under TESOTf-2,4,6-collidine conditions.
1.0
1b
2i
Entry
1[a]
Substrate
Silicon nucle-
ophile
Product
t
Yield
[%]
2
3
1.0
1.3
86
90
[h]
1c
1d
2j
2
2
77
96
1i
1i
4a
4b
5a
5b
2k
2
4
5
6
7
R=Me (1e)
R=Ac (1 f)
R=TBS (1g)
R=Tr (1h)
2l
2m
2n
2o
0.5
0.5
0.5
0.5
84
69
73
76
3[a]
1i
1j
2
89
68
4c
4c
5c
5d
4[a]
3.5
tolerated under the stated conditions, thereby indicating
that the reaction conditions are non-acidic in contrast to
other previously reported methods; the desired products 2l–
o were obtained in moderate to good yields (Table 3, en-
tries 4–7).
5
R=OTBS
(1g)
R=OTr
(1h)
R=OBn
(1k)
R=OBz
(1l)
4c
4c
4c
4c
4c
4c
5e
2
3
2
2
1
1
92
75
80
85
87
94
6
5 f
Reactions with Silyl Enol Ethers and Silyl Ketene Acetals
7
5g
Next, we examined the reactions of the collidinium salts
with a silyl enol ether and silyl ketene acetals. A number of
aldol-type reactions of acetals with silyl enol ethers and silyl
ketene acetals under acidic conditions have been reported.[1]
However, those reactions were limited to simple substrates
owing to the acidic conditions being necessary for the gener-
ation of the oxonium ion intermediates.
8
5h
R=OTES (5i)
5j
9[b]
R=OH
(1m)
R=Br (1n)
10
[a] 3 equiv nucleophile was used. [b] 3 equiv TESOTf and 4 equiv 2,4,6-
collidine were used.
Chem. Asian J. 2012, 7, 367 – 373
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369

H. Fujioka et al.
FULL PAPERS
via oxonium ion intermediates, and the isocyanide adducts
underwent further transformation leading to final products
such as cyanides, amides, etc.[11] We chose isocyanoacetoa-
mide 8a as a carbon nucleophile because the isocyano
moiety is known to react with aldehydes and subsequent re-
actions with the carbonyl groups on the amide afford oxa-
zoles in one-pot.[12] We used isocyanoacetoamide 8a as a nu-
cleophile and conducted the reaction under TESOTf-2,4,6-
collidine conditions (Table 6). After formation of the collidi-
nium salts from acetals 1g–n, the addition of 1.5 equivalents
of 8a gave the desired oxazoles 9a–h in high yields and all
reactions were completed within 0.5 hours (Table 6, en-
tries 1–8). This result is the first example of the reaction of
acetals and isocyanoacetoamide. No significant effects on
the co-existing functional groups were observed, even the
acid-sensitive ones (Table 6, entries 3–8). The simple isocya-
nide 8b also reacted effectively in this system and the isocy-
anide adducts were reduced in situ with LiBH4 to afford the
corresponding amines 10a–c in moderate yields (Table 6, en-
tries 9–11).
Reactions with Enamines
Enamines 6 also worked as good carbon nucleophiles for
the substitution reactions of acetals in our system (Table 5).
The reactions of enamines derived from morpholines 6a and
6b with the collidinium salt, generated from acetal 1i, pro-
ceeded to give the substituted products 7a and 7b in good
yields (Table 5, entries 1 and 2). Enamine 6c, prepared from
Table 5. Reaction of acetals (1) with enamines (6) under TESOTf-2,4,6-
collidine conditions.
Entry
1
Substrate
Enamine
Product
t
Yield
[%][a]
[h]
3
84
1i
1i
6a
6b
7a
Reactions with TMSCN
2
3
4
5.5
5
80
89
99
Finally, we examined the substitution reaction of acetals
with cyanide. The introduction of cyanide under acidic con-
ditions in the presence of a catalytic amount of Lewis acid
has been reported previously.[13] When the reaction was per-
formed under our reaction conditions using acetal 1i and
TMSCN, the yield of the product 11a was moderate (71%;
Table 7, entry 1). The decrease in the yield seemed to be
due to the lack of the leaving ability of 2,4,6-collidine. We
have already revealed that the structure of the pyridines is
very important and affects the reactivity of the pyridinium-
type salts in our reaction system.[7b] We have also reported
the mild deprotection of the acetal-type protecting groups
of alcohols (methoxymethyl-, b-methoxyethoxymethyl-, ben-
zyloxymethyl, and 2-[(trimethylsilyl)ethoxy]methyl ethers
and methylene acetal) using our reaction system. In their
cases, the use of 2,2’-bipyridyl was effective for the hydroly-
sis of the corresponding pyridinium-type salts whereas the
hydrolysis of the collidinium salts did not proceed at all.[14]
We then employed 2,2’-bipyridyl in the place of 2,4,6-colli-
dine for this cyanation reaction. As expected, the substitu-
tion occurred successfully during the reaction of the 2,2’-bi-
pyridylium salt formed from 1i and TMSCN to give cyanide
11a in good yield (83%; Table 7, entry 2). The optimized
conditions were applicable to the cyanation of other sub-
strates without affecting the acid-labile functional groups
(Table 7, entries 3–9).
7b
7b
1i
1j
6c
6c
9.5
7c
5
R=OTBS
(1g)
6c
6c
6c
6c
6c
6c
7d
7e
7 f
7g
4
88
78
95
78
74
89
6
R=OTr
(1h)
3.5
2
7
R=OBn
(1k)
8
R=OBz
(1l)
R=OH
(1m)
5.5
3.5
4
9[b]
R=OTES
(7h)
10
R=Br (1n)
7i
[a] All products were obtained as a threo/erythro mixture. [b] 3 equiv
TESOTf and 4 equiv 2,4,6-collidine were used.
pyrrolidine, could be used to afford the corresponding car-
bonyl compound 7b in good yield (Table 5, entry 3), where-
as it was not effective in the acid-catalyzed substitution reac-
tion.[10] The presence of other functional groups was also tol-
erated under the stated conditions (Table 5, entries 5–10).
Chemoselective Transformations of Acetals with Carbon
Nucleophiles in the Presence of Ketals
Ketals are known to undergo deprotection more-readily
than acetals under acidic conditions because the oxonium
ion intermediates from ketals are more stable than those
from acetals. On the other hand, preferential acetal depro-
Reactions with Isocyanides
We next focused on isocyanides (8) as carbon nucleophiles.
Isocyanides can react with acetals under acidic conditions
370
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Chem. Asian J. 2012, 7, 367 – 373

À
C C Bond Formation via a Pyridinium-Type Salt
Table 6. Reaction of acetals (1) with isocyanides (8) under TESOTf-2,4,6-
Table 7. Reaction of acetals (1) with cyanide under TESOTf-2,2’-bipyrid-
collidine conditions.
yl conditions.
Entry
1[a]
Substrate
Product
t [h]
Yield [%]
71
Entry
Substrate
Isocyanide
Product
Yield
[%]
3
1i
1i
11a
11a
2
3
3
5
83
98
1
93
84
1i
1j
8a
8a
9a
9b
1j
11b
2
4
5
6
7
R=OTBS (1g)
R=OTr (1h)
R=OBn (1k)
R=OBz (1l)
R=OH (1m)
R=Br (1n)
11c
11d
11e
11 f
4
3
3
4
4
4.5
87
82
86
85
80
93
8[b]
9
R=OTMS (11g)
11h
3
R=OTBS
(1g)
R=OTr
(1h)
R=OBn
(1k)
R=OBz
(1l)
8a
8a
8a
8a
8a
8a
9c
81
82
89
86
82
92
[a] 2,4,6-Collidine was used instead of 2,2’-bipyridyl; [b] 3 equiv TMSOTf
and 4 equiv 2,2’-bipyridyl were used.
4
9d
5
9e
6
9 f
R=OTES (9g)
9h
the presence of a ketal (Table 8). The chemoselective substi-
tution of 12 with Gilman reagent 3b proceeded to give com-
pound 13a and no ketal-substituted product was obtained
(Table 8, entry 1).[9] Silyl ketene acetal 4c also reacted with
12, affording only the acetal-substituted product 13b in
72% yield (Table 8, entry 2). Interestingly, the acid-cata-
lyzed substitution reaction (TESOTf and 4c in CH2Cl2 at
À788C) afforded only the ketal-deprotected product (14) as
the sole product,[15] which indicated that the formation of a
collidinium-salt intermediate is essential for this type of sub-
stitution reaction and the reaction conditions are not acidic.
The reaction using other carbon nucleophiles, 6c and 8a,
also afforded the corresponding acetal-substituted products
13c and 13d, respectively, in good yields under our reaction
conditions (Table 8, entries 3 and 4), whereas the reaction
with TMSCN resulted in a low yield (Table 8, entry 5).
7[a]
8
R=OH
(1m)
R=Br (1n)
9[b]
1i
1j
1g
67
72
61
8b
8b
10a
10b
10c
10[b]
11[b]
8b
[a] 3 equiv TESOTf and 4 equiv 2,4,6-collidine were used. [b] 1.5 equiv 8b
was used for this reaction. Isocyanide adduct was converted into amine 10 by
reduction with LiBH4.
Conclusions
À
In summary, we have developed a new C C bond-forming
reaction of acetals with a variety of carbon nucleophiles
under non-acidic conditions (Scheme 4).
tection in the presence of ketals has been achieved using
our method.[7] This is because TESOTf can distinguish be-
tween the steric environments of acetals and ketals and se-
lectively coordinate to the acetal oxygen. Successive attack
of the pyridines then leads to the chemoselective formation
of pyridinium-type salts from acetals. We have also accom-
plished the chemoselective substitution reactions of acetals
with heteroatom nucleophiles in the presence of ketals.[8a]
We presumed that the chemoselective substitution of acetals
with carbon nucleophiles would be feasible and then studied
the reaction of an acetal with diverse carbon nucleophiles in
Thus, the reactions of the collidinium salts with cuprates
(3) gave substituted products 2, and their reaction with silyl
enol ether or silyl ketene acetals (4) or enamines (6) afford-
ed the carbonyl compounds 5 or 7. Their reactions with iso-
cyanoamide 8a initially formed substituted products and
successive intramolecular cyclization of the amide carbonyl
group led to oxazoles (9) in one pot. Simple isocyanide 8b
reacted with the salts to give the substituted products, which
were then converted into their corresponding amines (10)
Chem. Asian J. 2012, 7, 367 – 373
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H. Fujioka et al.
FULL PAPERS
Table 8. Chemoselective substitution with various carbon nucleophiles
using TESOTf-2,4,6-collidine conditions.
Experimental Section
General Procedure for the Reaction of Acetal 1 with Carbon
Nucleophiles via a Pyridinium-Type Salt
TESOTf (2.0 equiv) was added dropwise at 08C under a N2
atmosphere to a solution of acetal 1 (1.0 equiv) and 2,4,6-col-
lidine (3.0 equiv) in CH2Cl2 (0.2m) and the reaction mixture
was stirred for 30 min at 08C. After the complete consump-
tion of 1 as confirmed by TLC (high polar component was
appeared on TLC), a nucleophile (5.0 equiv) was added to
the reaction mixture and the solution was warmed to RT. After the high-
polarity spot had disappeared, sat. NaHCO3 (aq.) was added to the reac-
tion mixture and the solution was extracted with CH2Cl2. The combined
organic layer was dried with Na2SO4 and evaporated in vacuo. The resi-
due was purified by column chromatography on silica gel to give the sub-
stituted product. (For the reaction with TMSCN, 2,2’-bipyridyl was used
in place of 2,4,6-collidine.)
Entry
1
C-nucleophile
R (product)
t [h]
Yield [%]
70
Me2CuLi (3b)
Me (13a)
4.5
2
2.5
8
72
4c
6c
13b
13c
3
74
4
3
3
76
31
Acknowledgements
8a
TMSCN
13d
CN (13e)
This work was supported financially by a Grant-in-Aid for Scientific Re-
search (B) and the Program for Disseminate Tenure Track System for
Promoting Science and Technology from the Ministry of Education, Cul-
ture, Science and Technology, the Japanese Government. Fellowships for
K.Y., O.K., and Y.S. from the Japan Society for the Promotion of Science
(JSPS), and financial support from The Uehara Memorial Foundation
and the Hoansha Foundation are also gratefully acknowledged.
5[a]
[a] 2,2’-Bipyridyl was used instead of 2,4,6-collidine.
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Scheme 4. The substitution reactions of acetals with various carbon nucle-
ophiles via the pyridinium-type salts generated from acetals under mild
conditions.
by subsequent reduction with LiBH4. Substitution of the col-
lidinium salts with TMSCN was less efficient. The use of
2,2ꢁ-bipyridyl in place of 2,4,6-collidine then improved the
reactivity and afforded 11 in good to high yields. A wide
range of functional groups were tolerable, under the
TESOTf-2,4,6-collidine conditions, including acid-sensitive
groups. The reactions can be conducted at 08C to room tem-
perature whereas the previous methods were usually per-
formed at À788C, because the reactions proceeded via
stable cationic pyridinium-type salt intermediates, rather
than via the unstable oxonium ion intermediates. The unpre-
À
cedented chemoselective C C bond formation of an acetal
with various carbon nucleophiles in the presence of a ketal
has also been achieved.
372
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À
C C Bond Formation via a Pyridinium-Type Salt
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ing intact.
.
Received: September 28, 2011
Published online: December 12, 2011
Chem. Asian J. 2012, 7, 367 – 373
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
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