Selective protonation/iodination of unsymmetrical zirconacyclopentadienes

Article abstract of DOI:10.1246/cl.2010.350

Selective monohalogenation reaction of unsymmetrical zirconacyclopentadienes was developed by selective protonation and iodination reactions. Among the examined acids, acetic acid and acetylacetone showed the best yield and selectivity to afford the corre

Full text of DOI:10.1246/cl.2010.350

doi:10.1246/cl.2010.350
350
Published on the web March 6, 2010
Selective Protonation/Iodination of Unsymmetrical Zirconacyclopentadienes
Eri Igarashi, Shenyong Ren, Ken-ichiro Kanno, and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Life Science, Hokkaido University,
Kita 21, Nishi 10, Kita-ku, Sapporo 001-0021
(Received December 28, 2009; CL-091149; E-mail: tamotsu@cat.hokudai.ac.jp)
Selective monohalogenation reaction of unsymmetrical
Table 1. Formation of monoiododienes 2a and 3a by selective
protonation/iodination of zirconacyclopentadiene 1a
zirconacyclopentadienes was developed by selective protonation
and iodination reactions. Among the examined acids, acetic acid
and acetylacetone showed the best yield and selectivity to afford
the corresponding monoiododienes. For the zirconacyclopenta-
diene prepared from 3-hexyne and diphenylacetylene, the Et-
bearing carbon-zirconium bond was selectively protonated with
more than 90% selectivity.
Et
Et
Et
1) H+ source (1.0 equiv)
Et
Et
Et
THF, -20 °C, 1 h
I
H
I
+
Cp2Zr
H
2) CuCl (2.0 equiv)
I2 (2.0 equiv), rt, 3 h
Ph
Ph
Ph
Ph
Ph
Ph
1a
2a
3a
Entry
Proton source
Yield of 2a + 3a/%
Ratio of 2a:3a
1
2
3
4
5
t-BuOH
H2O
17
37
53
57
74
35:65
16:84
19:81
11:89
8:92
Development of selective reaction of unsymmetrical metal-
lacycles which have two different metal-carbon bonds is
attractive and important.1 In particular, selective cleavage of
one of the two metal-carbon bonds is very attractive for organic
synthesis. Previously we have developed selective monohaloge-
nation reaction by NCS or NBS of unsymmetrical zircona-
cyclopentadienes2 which were conveniently prepared from two
different alkynes; one is alkyl-substituted alkyne and the other is
aryl-substituted alkyne as shown in eq 1.3 This selective reaction
could be applied for linear triene or tetraene formation from
three or four different alkynes.4 However, by this method
opposite monohalogenation product 3 could not be prepared. In
this paper we would like to report a novel procedure to provide
the opposite monohalogenation product 3 from the unsym-
metrical zirconacyclopentadienes.
MeOH
PhOH
O
O
6
7
8
PPTS
AcOH
55
80
52
10:90
9:91
PhCO2H
12:88
NO2
OH
9
34
0
13:87
O2N
10
CSA
−
7%-d
Et
Et
R
Et
AcOH
(1.0 equiv)
Et
Et
Et
D2SO4
R
monohalogenation
H
H
D
X
H
ð2Þ
Cp2Zr
previous work
Cp2Zr
AcO
THF
-20 °C, 1 h
rt
Ph
Ph
Ph
Ar
R
Ph
87%-d
Ph
4a
Ph
5a
77%
Ar
R
1a
2 (X = Cl, Br)
Cp2Zr
ð1Þ
Ar
R
In order to make this selective protonation useful, we
converted 4 into monoiodinated diene derivatives 3.5,6 Our
previous selective chlorination and bromination with NCS or
NBS of 1 afforded monohalogenation product 2 after hydrol-
ysis.3 Therefore, this selective protonation/halogenation pro-
vides 3 as products which are the isomers of 2.
Ar
R
1. monoprotonation
2. halogenation
1
H
this work
X
Ar
Ar
3 (X = I)
We found that when zirconacyclopentadiene 1a was treated
with 1 equiv of CH3CO2H, selective cleavage proceeded to give
4a as shown in eq 2. Its H NMR spectrum clearly showed a
Monoiodination was carried out by the selective protonation
with various proton sources followed by iodination with CuCl
giving 2a and 3a. The results are shown in Table 1.
1
triplet signal at 5.5 ppm assignable to the diene proton and a
singlet at 6.1 ppm assigned to Cp protons. Deuterolysis of 4a
with D2SO4 afforded monodeuterated product 5a in 77% NMR
yield, predominantly. Deuterium incorporations were 87% for
the phenyl-bearing carbon, and 7% for the ethyl-substituted one.
This selective protonation can be rationalized by the
different basicity of the two carbons attached to zirconium
atom, one with an alkyl group and the other with an aryl group.
The carbon attached to the alkyl group is more basic and
protonation occurs at the more basic carbon predominantly.
Reactions with 1 equiv of alcohols or water afforded the
products in relatively low yields. This is due to weak acidity of
alcohols. High yields and high selectivity were achieved by
using acetic acid and acetylacetone. The yield of 2a was 74%
when 1a was treated with acetylacetone followed by iodination
in the presence of CuCl. High selectivity (8:92) was achieved in
this case. The reaction of 1a with acetic acid gave 3a in 80%
combined yield with the selectivity of 2a:3a = 9:91.
Table 2 summarized the results of the protonation/iodina-
tion sequence with acetylacetone or acetic acid at various
Chem. Lett. 2010, 39, 350-351
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

351
Table 2. Temperature effects on the selective protonation/
iodination of zirconacyclopentadiene 1a
Table 4. Formation of monoiododienes with various substitu-
ents
Yield of
2 + 3/%a
Ratio of
Yield of
2a + 3a/%a
Ratio of
2a:3a
H+ source
Entry
R
Ar
Entry
Temp/°C
Time/h
2:3
1
2
3
4
5
6
Bu
Bn
Et
Et
Et
Et
Ph
74
81
87
78
76
75
9:91
8:92
6:94
9:91
4:96
31:69
1
2
3
4
5
6
0
50
12
12
12
1
65
96
71
96
68
33
8:92
5:95
7:93
7:93
13:87
9:91
O
O
Ph
p-Tol
AcOH
AcOH
AcOH
AcOH
0
p-MeOC6H4
p-FC6H4
3-thienyl
−20
−40
−78
3
3
aNMR yield.
aNMR yield.
Table 3. Reactions with various carboxylic acids
was observed under air after 1 d. After several trials, we found that
the use of an eluent containing triethylamine was effective for
avoiding the isomerization during the column separation.
In summary, we realized another selective synthesis of mono-
iodobutadienes in contrast to our previous report.3 The key step
was establishment of highly selective monoprotonation of un-
symmetrical zirconacyclopentadienes. Further functionalization
and conversion of thus obtained iododienes are now in progress.
Yield of
Ratio of
2a:3a
H+ source
Entry
2a + 3a/%a
HCO2H
1
2
3
4
93
92
94
93
9:91
11:89
9:91
CH3CH2CO2H
PhCOCH2CH2CO2H
11:89
H2N
CO2H
CO2H
References and Notes
1
For unsymmetrical metallacyclopentadienes, see: a) J. R.
Strickler, P. A. Wexler, D. E. Wigley, Organometallics 1988,
7, 2067. b) J. R. Strickler, P. A. Wexler, D. E. Wigley,
Organometallics 1991, 10, 118. c) B. C. V. Wagenen, T.
Livinghouse, Tetrahedron Lett. 1989, 30, 3495. d) S. L.
Buchwald, B. T. Watson, J. C. Huffman, J. Am. Chem. Soc.
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Balaich, P. E. Fanwich, I. P. Rothwell, Organometallics 1993,
12, 2911.
5
92
4:96
Br
C6F5CO2H
CF3CO2H
6
7
70
78
74
70
84
6:94
13:87
11:89
7:93
CCl3CO2H
HO2CCO2Hb
8
9
10
HO2C
CO2Hb
8:92
b
aNMR yield. 0.5 equiv.
2
Unsymmetrical zirconacyclopentadienes were prepared accord-
ing to the literature. a) T. Takahashi, F.-Y. Tsai, Y. Li, K.
Nakajima, M. Kotora, J. Am. Chem. Soc. 1999, 121, 11093. b) T.
Takahashi, Z. Xi, A. Yamazaki, Y. Liu, K. Nakajima, M. Kotora,
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temperatures. Among them, the reaction with acetylacetone at
50 °C provided the highest yield and selectivity. The yield was
96% and the ratio of 2a and 3a was 5:95. In contrast, protonation
with acetic acid at ¹20 °C for 1 h gave the best result.
Table 3 shows the results of the protonation/iodination
of 1a with various carboxylic acids. The ratio of 2a and 3a
was around 10:90. When relatively stronger acids such as
C6F5COOH, CF3COOH, CCl3COOH, and HOOCCOOH
(Entries 6-9) were used, the yields were not high.
Zirconacyclopentadienes with other substituents were also
examined for the monoiodination.7 The results are shown in
Table 4. A series of monoiododienes having Bu and Bn groups
for alkyl groups (Entries 1 and 2), electron-donating or
-withdrawing aryl groups (Entries 3-5) and heterocycle
(Entry 6) were obtained in high yields with high selectivity.
When the monoiododiene 3 formed, the stereochemistry of
the C=C bonds was kept. However, column separation with silica
gel led to isomerization of stereochemistry of 3. Even though the
crude NMR spectra showed one set of peaks for 3, after
purification another set of peaks was also observed. Previously
we met the similar C=C isomerization of arylated iodobuta-
dienes.8 In that case, the isomerization occurred during the
iodination reaction of a Zr-C bond. In the present case, however,
it occurred during silica gel column purification. Actually, stirring
of monoiododiene 3 with silica gel in hexane under nitrogen did
not afford the isomerized product, while 10% of isomerization
3
4
H. Ubayama, Z. Xi, T. Takahashi, Chem. Lett. 1998, 517.
K. Kanno, E. Igarashi, L. Zhou, K. Nakajima, T. Takahashi,
J. Am. Chem. Soc. 2008, 130, 5624.
5
For the iodination of zirconacyclopentadienes, see: a) C. Xi, S.
Huo, T. H. Afifi, R. Hara, T. Takahashi, Tetrahedron Lett. 1997,
38, 4099. b) E. Negishi, S. J. Holmes, J. M. Tour, J. A. Miller,
F. E. Cederbaum, D. R. Swanson, T. Takahashi, J. Am. Chem.
Soc. 1989, 111, 3336. c) H.-J. Zhang, Z. Song, C. Wang, C.
Bruneau, Z. Xi, Tetrahedron Lett. 2008, 49, 624. d) ref. 1e.
For the preparation of halo-dienes, see: a) E. Negishi, F. E.
Cederbaum, T. Takahashi, Tetrahedron Lett. 1986, 27, 2829. b)
S. Yamaguchi, R. Jin, K. Tamao, F. Sato, J. Org. Chem. 1998, 63,
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ref. 1e, 1h, and 5b.
6
7
8
Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.
html.
T. Takahashi, D. Y. Kondakov, Z. Xi, N. Suzuki, J. Am. Chem.
Soc. 1995, 117, 5871.
Chem. Lett. 2010, 39, 350-351
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/