A simple method for the removal of organotin residues from acetates and a homoallylic alcohol prepared from organostannane reagents: Column chromatography using 10%-moist SiO2

Article abstract of DOI:10.1246/cl.160736

Simple column chromatography using 10%-moist silica gel enabled efficient removal of organotin residues from geranyl acetate, which was prepared by the acetylation of geraniol with vinyl acetate in the presence of a catalytic amount of a 1,3-dichloro-substituted tetrabutyldistannoxane. The desired acetate contained only 2.4 ppm of organotin residues. In sharp contrast to this, a similar purification method using dry silica as the stationary phase provided acetate containing ca. 5000 ppm of organotin residues.

Full text of DOI:10.1246/cl.160736

Advance Publication Cover Page
A Simple Method for the Removal of Organotin Residues from Acetates and a
Homoallylic Alcohol Prepared from Organostannane Reagents:
Column Chromatography Using 10%-Moist SiO
2
Takanori Nishida, Daiki Matsuda, Issei Kasuga, Akihiro Orita,* and Junzo Otera*
Advance Publication on the web September 7, 2016
doi:10.1246/cl.160736
©
2016 The Chemical Society of Japan
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1
A Simple Method for the Removal of Organotin Residues from Acetates and a Homoallylic
Alcohol Prepared from Organostannane Reagents:
Column Chromatography Using 10%-Moist SiO
2
Takanori Nishida, Daiki Matsuda, Issei Kasuga, Akihiro Orita,* and Junzo Otera*
Department of Applied Chemistry and Biotechnology, Okayama University of Science,
1
-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan
E-mail: orita@dac.ous.ac.jp)
Simple column chromatography using 10%-moist silica
(
repeatedly with nitric acid in the presence of a small amount
of sulfuric acid in a Kjeldahl flask until powdery inorganic tin
components were obtained. After the powder had been
dissolved in hydrochloric acid, the concentration of Sn in
the solution was determined using inductively coupled plasma
atomic emission spectroscopy (ICP-AES). The results using
four types of silica gel (containing 0%, 5%, 10%, and 20%
moisture) are summarized in Table 1. Interestingly, the Rf
value of 3 (0.31, AcOEt/Hex (5:95)) was consistent regardless
of the amount of moisture present in the silica gel.
gel enabled efficient removal of organotin residues from
geranyl acetate, which was prepared by the acetylation of
geraniol with vinyl acetate in the presence of a catalytic
amount of a 1,3-dichloro-substituted tetrabutyldistannoxane.
The desired acetate contained only 2.4 ppm of organotin
residues. In sharp contrast to this, a similar purification
method using dry silica as the stationary phase provided
acetate containing ca. 5,000 ppm of organotin residues.
2
+
Organostannanes play pivotal roles in organic
1
syntheses. For instance, allylstannanes have been used in the
2
allylation of electrophiles such as aldehydes and ketones, and
2
C(sp ) or C(sp) components of organostannanes have been
utilized in Migita–Kosugi–Stille coupling reactions with aryl
3
halides. Halogen-substituted organostannanes (R
n
SnX
4
−
n
)
are known as mild Lewis acids, and 1,3-dichloro-1,1,3,3-
tetrabutyldistannoxane (1) catalyzes the acylation of alcohols
4
by transesterification without any loss of functional groups.
Despite the versatile applications described above,
organostannanes suffer from inevitable drawbacks, including
the difficulty involved in the complete removal of
organostannane residues from the desired products during
purification, which occurs as a result of the high miscibility of
organostannanes. Reducing the amount of organostannane
residues remaining in a product is desirable because the
toxicity of alkylstannanes, particularly trialkylstannanes, has
Entry
1
2
3
4
5
6
7
kept
in
b
c
d
e
f
g
Moisture
content of
dry
5%
10%
20%
10%
10%
a
h
silica gel
air
Sn content 4960 10.0
2.4
15.7
2.8
2.3
305
in 3 [ppm]
5
a
been reported. In order to remove/recycle organotin
The weight of silica gel was 50 times that of the crude product and
6
b
components, a number of technologies have been developed.
1
850 times that of the used tin catalyst. Dried at 120 °C for 24 h.
c
Practical methods to remove organostannane residues from
reaction products were reported by Harrowven and Curran. In
Dipped in water for 24 h, filtered, and dried at 75 °C for 20 h.
d
e
Water (2.5 g) was added to 5%-wet silica gel (50 g). Water (7.5 g)
f
these procedures, simple column chromatography on KF- or
was added to 5%-wet silica gel (50 g). Column chromatography
7
g
K
2
CO
3
-mixed silica gel reduced the organostannane
was repeated three times. The crude product was stirred with
components in the products to <30 and 13 ppm, respectively;
1
0%-moist silica gel (50 times the product weight) in 5%
8
,9
h
this technology has been widely used. In the course of our
study on organotin-catalyzed reactions, we found that column
chromatography using properly moist silica gel enabled an
efficient removal of organostannane residues from the desired
AcOEt/Hex overnight, and filtered. Silica gel kept in air for two
weeks was used. The amount of moisture was not determined.
product. Herein, we report the results of
investigation of the amount of organostannane residues
present in acetates and allylated products synthesized in
organotin-catalyzed reactions and the suitability of moist SiO
for removal of such organostannane residues.
First, geraniol 2 was acetylated with vinyl acetate in the
presence of a catalytic amount of 1. The crude geranyl acetate
a thorough
Acetylation of 2 with vinyl acetate proceeded smoothly
in the presence of 0.01 equivalents of 1 (0.04 equivalents of
Sn), and 2 was consumed completely at 30 °C in 24 h. The
reaction mixture was evaporated, and the crude product was
subjected to column chromatography on silica gel. When dry
silica gel was used, ICP-MS analysis indicated that 3
contained 4960 ppm of organostannane residues (Entry 1).
Purification of 3 by column chromatography using 5%- and
2
3
was subjected to column chromatography on silica gel (50
times weight of the crude product) that contained various
amounts of moisture (0%, 5%, 10%, and 20%) using 5%
AcOEt/hex as eluent. The isolated acetate 3 was boiled
1
0%-moist silica gel reduced the organostannane content in 3
to 10.0 and 2.4 ppm, respectively (Entries 2 and 3), whereas
0%-moist silica gel gave a contamination level of 15.7 ppm
2

2
(
Entry 4). Repeating the column chromatography or stirring 3
(60:40)), which was synthesized by 1-catalyzed acetylation of
7 with vinyl acetate (Scheme 1). When the crude acetylation
product 6 was subjected to column chromatography on moist
silica gel, spectroscopically pure acetate 6 was obtained in
89% yield; however, ICP analyses demonstrated that the
acetates 6 that were purified by column chromatography on
10%- and 5%-moist silica gels contained 107 and 69 ppm of
overnight in the presence of silica did not result in any further
removal of organostannane (Entries 5 and 6). When silica that
had been kept in air for two weeks was used (the moisture
content was not determined), acetate 3 containing 305 ppm of
Sn residues was obtained (Entry 7). With these results, the
amount of organostannane residue was investigated for the
geranyl 3 and octyl 4 acetates, which were prepared by
1
0
organostannane residues, respectively.
tetrabutyldistannoxane 1- or Bu
with vinyl acetate or Ac
chromatography purification using 10%-moist or dry silica gel
Table 2).
2
SnO 5-catalyzed acetylation
2
O, followed by column
(
Scheme 1. Acetylation of 7.
Silica gel for
column
Reaction conditions
It was observed that moist silica gel could efficiently
remove organostannane catalysts such as 1 and 5 from the
acetates; therefore, the suitability of 10%-moist silica gel in
the purification of homoallyl alcohol 8 was investigated.
Compound 8 was synthesized by allylation of benzaldehyde
Entry Acetate
Acetylating
Catalyst
10%-
dry
reagent
moist
1
2
3
3
3
3
AcOCH=CH
AcOCH=CH
2
2
1
5
1
2.4
4,960
17.2
4.2
with
tetraallylstannane/HCl
(Scheme
2)
or
Ac
2
O
6.9
7,147
a
allyltributylstannane/BF (Scheme 3). When the allylation of
3
(
1,099)
benzaldehyde was performed with tetraallylstannane in the
4
3
Ac
2
O
5
6.5
8,348
a
presence of
chromatography using 10%-moist silica gel furnished 8 in
7% yield (Scheme 2). The ICP-MS analysis of the alcohol 8
a
catalytic amount of HCl, column
(
988)
4.0
5.2
4.3
6.4
5
6
7
8
4
4
4
4
AcOCH=CH
AcOCH=CH
2
2
1
5
1
5
3,425
45.1
8
demonstrated an organostannane contamination level of 7.6
ppm. In contrast to this, the purification of 8 with dry silica
gel resulted in a Sn contamination level of 58.9 ppm, even
though the alcohol 8 was washed three times with an aqueous
solution of tetra-n-butylammonium fluoride (TBAF) prior to
the column chromatography.
Ac
Ac
2
O
O
2,959
10,146
2
a
5
%-moist silica gel was used.
Although 3 that was prepared from vinyl acetate/1
contained 2.4 ppm of organostannane residues (Entry 1, the
same as Entry 3 in Table 1), acetylation of 2 with vinyl
acetate/5 provided acetate
organostannane residues (Entry 2). When the acetylation of 2
with Ac O was performed in the presence of 1 or 5, 6.9 and
.5 ppm, respectively, of organostannanes were detected in
3
containing 4.2 ppm
2
6
the product (Entries 3 and 4). It is noteworthy that column
chromatography using 10%-moist silica gel was crucial to
remove organostannane residues from acetate 3 when it was
prepared from acetic anhydride because purification using
5
%-moist silica resulted in contamination by ca. 1,000 ppm of
organostannane (Entries 3 and 4). In the purification process
of octyl acetate 4, 10%-moist silica gel served well to remove
the organostannanes, leading to an acetate product containing
less than 6.4 ppm of organostannane residues (Entries 5–8). In
Scheme 2. Allylation of benzaldehyde with
tetraallylstannane.
2
the Bu SnO 5-catalyzed acetylation of 2 and octanol with
vinyl acetate (Entries 2 and 6), dry silica gel was slightly
useful to remove the organostannane residues (17.2 and 45.1
ppm, respectively).
Although the “moist” silica gel method served well in
the purification of the acetates 3 and 4, this protocol was not
so efficient for the highly polar acetate 6 (Rf 0.28, AcOEt/hex
Allylation
of
benzaldehyde
with
allyltributylstannane/BF3 proceeded smoothly; the crude
product was obtained in more than 300% yield after workup
because the product contained an equimolar amount of
Bu SnX. Washing the crude product with 10 mL of aqueous
TBAF (1.2 equivalents) enabled the efficient removal of the
3

3
Sn contaminants from the crude product; thus, the yield was
reduced from 300% to 170%. Subsequent column
chromatography of the crude product using 10%-moist silica
gel provided the desired homoallyl alcohol 8 containing 274
ppm of organostannane residues in 88% yield (Scheme 3).
During the purification of the homoallyl alcohol 8 derived
from allyltributylstannane, washing of the crude product with
aqueous TBAF solution was crucial; five washings and
subsequent column chromatography enabled reduction of the
Sn contamination to 146 ppm.
2
3
a) J. A. Marshal, Chem. Rev. 1996, 96, 31. b) Y. Nishigaichi, A.
Takuwa, Y. Naruta, K. Maruyama, Tetrahedron 1993, 49, 7395. c)
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4
5
6
See Chapter 23 of ref 1a for details.
E. Le Grognec, J-M. Chrétien, F. Zammattio, J-P. Quintard, Chem.
Rev. 2015, 115, 10207.
7
For KF-silica, a) D. C. Harrowven, I. L. Guy, Chem. Commun.
2
2 3
004, 1968. For K CO -silica, b) D. C. Harrowven, D. P. Curran, S.
L. Kostiuk, I. L. Wallis-Guy, S. Whiting, K. J. Stenning, B. Tang,
E. Packard, L. Nanson, Chem. Commun. 2010, 46, 6335.
8
a) T. O. Ronson, J. R. Carney, A. C. Whitwood, R. J. K. Taylor, I. J.
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Scheme
allyltributylstannane.
3.
Allylation
of
benzaldehyde
benzaldehyde
with
In
the
allylation
of
using
allyltributylstannane,
a
large amount of organostannane
residues with low polarity remained in 8 because an
equimolar amount of the highly miscible trialkylstannane
Bu
3
SnX was produced from allyltributylstannane as a
6
258.
byproduct. In contrast, the use of tetraallylstannane gave 0.25
equivalents of the inorganic salt SnX
removal of the organostannane residues.
9
1
A decomposition protocol for Bu SnX with H O /KHCO was also
3
2
2
3
and enabled facile
reported: a) T. Yamakawa, H. Kinoshita, K. Miura, J. Organomet.
Chem. 2013, 724, 129. b) K. Tamao, N. Ishida, J. Organomet.
Chem. 1984, 269, C37.
Supporting Information is also available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
4
Herein, we demonstrated a new methodology for the
removal of organostannane residues from acetates and
homoallyl alcohols by taking advantage of column
chromatography using moist silica gel. This method served
well in the acetylation reactions catalyzed by organostannanes
and allylation reactions using tetraallylstannane, and the
organostannane residues in the products were reduced to less
than 10 ppm. In acetylation reactions of highly polar alcohols
and allylation reactions using allyltributylstannane, however,
ICP analyses indicated that the products contained
considerable amounts of organostannane residues. Although
the mechanism for the efficient removal of organostannane
residues and the effect of moisture on silica gel are yet
unknown, further improvements in moist silica technology
and its application for the purification of functionalized
acetates and alcohols are in progress.
0
This work was supported by JSPS KAKENHI Grant
Numbers JP16H01164 in Middle Molecular Strategy and
JP15K05440, the Okayama Prefecture Industrial Promotion
Foundation and Grant for Promotion of OUS Research
Projects. The authors appreciate Mr. Kento Onari, Mr.
Takahiro Sakamoto, Ms. Saori Wada, Mr. Yuki Motoi, and
Mr. Mikiya Fujii for supplying the starting compounds.
References and Notes
1
a) Organotin Chemistry, Second Edition, ed. by A. G. Davies,
Wiley-VCH, Weinheim, 2004. b) Organotin Chemistry, ed. by A.
G. Davies, VCH, Weinheim, 1997. c) Tin in Organic Synthesis, ed.
by M. Pereyre, J.-P. Quintard, A. Rahm, Butterworths, London,
1
987.