Reaction of zirconacyclopentadienes with electrophiles such as benzaldehyde, methyl methacrylate and 1-bromo-2-butyne after treatment with RLi

Article abstract of DOI:10.1016/j.tetlet.2004.10.030

Zirconacyclopentadienes reacted with electrophiles after treatment with alkyllithium. For example, the reaction with benzaldehyde after treatment with methyllithium to give a nucleophilic addition product of a dienyl moiety to aldehyde, dienylcarbinol, in a moderate yield. Similar reaction of a zirconacyclopentadiene using butyllithium with methyl methacrylate afforded a Michael addition product in a good yield. Treatment of zirconacyclopentadienes with n-BuLi followed by 1-bromo-2-butyne gave a mono-propargylated diene derivative in 95% yield after hydrolysis. When propargyl chloride was treated with n-BuLi first and then added to zirconacyclopentadienes, penta-substituted benzene derivatives were formed in high yields.

Full text of DOI:10.1016/j.tetlet.2004.10.030

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9041–9043
Reaction of zirconacyclopentadienes with electrophiles such as
benzaldehyde, methyl methacrylate and 1-bromo-2-butyne
after treatment with RLi
Takashi Seki, Yoshinori Noguchi, Duan Zheng, Wen-Hua Sun and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University, Japan
SORST, Japan Science and Technology Agency (JST), Kita-Ku, Sapporo 001-0021, Japan
Received 28 August 2004; revised 6 October 2004; accepted 7 October 2004
Available online 22 October 2004
Abstract—Zirconacyclopentadienes reacted with electrophiles after treatment with alkyllithium. For example, the reaction with
benzaldehyde after treatment with methyllithium to give a nucleophilic addition product of a dienyl moiety to aldehyde, dienylcarb-
inol, in a moderate yield. Similar reaction of a zirconacyclopentadiene using butyllithium with methyl methacrylate afforded a
Michael addition product in a good yield. Treatment of zirconacyclopentadienes with n-BuLi followed by 1-bromo-2-butyne gave
a mono-propargylated diene derivative in 95% yield after hydrolysis. When propargyl chloride was treated with n-BuLi first and
then added to zirconacyclopentadienes, penta-substituted benzene derivatives were formed in high yields.
Ó 2004 Published by Elsevier Ltd.
Recently we have reported that reaction of zirconacyclo-
1
conacyclopentadienes with electrophiles such as benzal-
dehyde, methyl methacrylate and 1-bromo-2-butyne
after treatment with RLi.
pentadienes 1 with CO proceeded in the presence of n-
2
BuLi. In this reaction, we proposed the formation of a
dienyllithium derivative 2 as an intermediate, which in
turn reacts with CO to give a cyclopentadienyloxyzirc-
onocene anion derivative 3 (Scheme 1). The cyclopenta-
dienyloxyzirconocene 3 could be clearly observed by
NMR study. However, unfortunately, the formation of
a dienyllithium derivative 2 was not observed by NMR.
It is well known that zirconacyclopentadienes react with
,4
3
aldehydes in the presence of AlCl3.
Without any
additives they are not nucleophilic enough to react with
an aldehyde directly. However, when zirconacyclopenta-
diene 1a was treated with MeLi at ꢀ78°C followed by
the reaction with benzaldehyde at ꢀ40°C for 1h, com-
pound 4 was obtained in 40% yield after hydrolysis
(Eq. 2). This reaction did not proceed at ꢀ78°C and
the yield was low at 0°C. This result clearly shows that
the dienyl moiety of zirconacyclopentadiene became
nucleophilic and reactive towards aldehyde when it
In this letter we would like to report an evidence for the
formation of nucleophilic species in the reaction of zir-
5
was treated with MeLi.
n-BuLi
Li
Cp Zr
CO
Li+
Cp Zr
O
2
Cp Zr
2
2
Bu
Bu
1
3
R
R
R
2
R
R
R
R
1) R'Li
2) EX
3) H+
E
Cp Zr
2
Scheme 1.
R
ð1Þ
Keywords: Alkyllithium; Dienyllithium; Zirconate; Addition reaction;
Nucleophilic addition; Zirconacyclopentadiene.
4-6
1
*
Corresponding author. Tel.: +81 11 706 9149; fax: +81 11 706
150; e-mail: tamotsu@cat.hokudai.ac.jp
EX = PhCHO, CH=CH(Me)COOMe, Me
9
Br
0
040-4039/$ - see front matter Ó 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.10.030

9
042
T. Seki et al. / Tetrahedron Letters 45 (2004) 9041–9043
Et
Et
Et
cates that in the final stage a zirconium-containing four-
Ph
Et
Et
Et
membered ring is formed. The results are summarized
in Table 1.
1
) MeLi, -78 C
Cp Zr
2
OH
Et
4: 40%
ð2Þ
2) PhCHO, -40 C
) H+
Et
3
We have found that the reaction of zirconacyclopenta-
dienes with alkynyl lithium which afforded penta-substi-
1a
9
tuted benzene derivatives as shown in Eq. 6. Dumond
1
and Negishi also reported similar results.
0
Similar nucleophilic addition reaction could be observed
when 1a was treated with n-BuLi at ꢀ78°C and with
methyl methacrylate at ꢀ40°C. As shown in Eq. 3, the
tetraethyldiene moiety was added to the double bond
of methyl methacrylate to give 5 in 64% yield after
hydrolysis.
R
R
R
R
H+
R
R
Li
R'
Cp Zr
2
r.t., 1 - 3 h
ð6Þ
R'
R
1
R
10
The formation of the penta-substituted benzene shown
1
1–14
in Eq. 5 is related to the similar examples
utilizing
1
0
an alkynyl lithium in terms of their reaction mecha-
nisms. A possible mechanism is shown in Scheme 2.
The lithiated propargyl chloride coordinates to zirco-
nium of a zirconacyclopentadiene to give a zirconium
ð3Þ
1
5
ate complex 11. The ring opening of the zirconacyclo-
pentadiene occurs and a dienyllithium 12 is formed. The
intramolecular addition of the dienyllithium moiety of
12 to the carbon–carbon triple bond of the alkynyl
moiety gives a zirconacyclopentadiene 13. The reduc-
tive elimination of 13 and the following reaction of
Similarly, the reaction of zirconacyclopentadiene with n-
BuLi followed by 1-bromo-2-butyne afforded mono-
propargylated diene derivative in 95% yield after
hydrolysis.
ÔCp ZrÕ with an aryllithium afford a zirconium ate
2
complex 14. The nucleophilic attack of 14 to benzyl
chloride gives product 15. Further investigation is in
progress.
ð4Þ
Table 1. Formulation of penta-substituted benzene derivatives by the
reaction of zirconancylopentadienes with 3-chloro-1-lithioprop-1-yne
We have reported that zirconacyclopentadienes reacted
with propargyl halides in the presence of CuCl to
afford benzene derivatives. In this case with CuCl, the
Zirconacyclopentadiene
Product
Yield (%)
6
Et
carbon–carbon bond formation proceeded at the car-
bon–carbon triple bond of propargyl chlorides. There
was no propargylation product. The reaction with n-
BuLi reported here is in sharp contrast to the reaction
with CuCl. The carbon–carbon bond formation
occurred at the propargylic carbon and the mono-prop-
argylated diene derivatives were obtained after hydro-
lysis. This clearly shows that a hard nucleophile was
formed when zirconacyclopentadienes were treated with
RLi.
Et
Et
Et
Et
+
+
+
+
Cp
Cp
Cp
2
Zr
2
Zr
2
Zr
1a
1b
H
H
H
D
7a
7b
91
Et
Me
Me
Me
Et
Pr
Et
Pr
Pr
Pr
Pr
Pr
82
81
Pr
Et
Pr
Et
1c
7c
Et
Et
Cl
r.t., 1 - 3 h
Et
Et
H+
Et
Et
Li
Et
Et
Cp Zr
2
ð5Þ
Et
Et
CH
3
Et
Et
Et
1
D
Et
1
a
8a 96
a
7
a: 91%
DH C
2
Surprisingly, pretreated propargyl chloride with n-BuLi
Me
Me
Me
Me
Me
Me
Me
3
substituted benzene formation as shown in Eq. 5.
-chloro-1-lithioprop-1-yne led to the excellent penta-
7
I
,8
2
Cp Zr
1d
l
2
9d 62
2
IH C
Deuterolysis and iodinolysis instead of hydrolysis gave
a and 9d in 96% and 62% yield, respectively. This indi-
Me
8

T. Seki et al. / Tetrahedron Letters 45 (2004) 9041–9043
9043
Supplementary data
R
R
R
R
R
R
R
R
R
Cp Zr
2
Cl
R
R
Cp Zr
Li
Li
2
Supplementary data associated with this article can
be found, on the online version, at doi:10.1016/j.tetlet.
Cp Zr
2
R
2004.10.030.
Li
11
Cl
Cl
1
1
2
R
R
R
R
References and notes
Cp Zr
R
2
Cp Zr
2
Li
R
Cl
1. For a recent review, see Takahashi, T.; Li, Y. In Titanium
and Zirconium in Organic Synthesis; Marek, I., Ed.; Wiley-
VCH: Weinheim, 2002; p 50, and references therein.
2. Takahashi, T.; Huo, S.; Hara, R.; Noguchi, Y.; Nakajima,
K.; Sun, W.-H. J. Am. Chem. Soc. 1999, 121, 1094.
Li
CH2
R
R
CH Cl
2
13
14
3
4
. Xi, Z.; Li, P. Angew. Chem., Int. Ed. 2000, 39, 2950.
. Zhao, C.; Li, P.; Cao, X.; Xi, Z. Chem. Eur. J. 2002, 8,
4
R
R
R
H+
R
R
R
R
292.
. Fang, H.; Song, Q.; Wang, Z.; Xi, Z. Tetrahedron Lett.
004, 45, 5159.
. Kotora, M.; Noguchi, Y.; Takahashi, T. Collect. Czech.
Chem. Commun. 1999, 64, 1119.
7. Luker, T.; Whitby, R. J. Tetrahedron Lett. 1994, 35, 785.
Cp Zr
2
5
6
H C
3
2
R
7
1
5
D+
I2
8
9
. Gordon, G. J.; Whitby, R. J. Chem. Commun. 1997, 1321.
. This reaction was orally reported, see Takahashi, T.;
Noguchi, Y.; Sun, W.-H.; Regional Meeting in Hokkaido
Area of Chemical Society of Japan, Kushiro 1998, B08.
Et
Me
D
DH C
Et
Et
I
Me
Me
2
IH C
2
10. Dumond, Y. R.; Negishi, E. Tetrahedron 2004, 60, 1345.
Et
Me
1
1
1
1
1
1. Xi, Z.; Huo, S.-Q.; Noguchi, Y.; Takahashi, T. Chem.
Lett. 2000, 218.
2. Takahashi, T.; Kotora, M.; Xi, Z. J. Chem. Soc., Chem.
Commun. 1995, 361.
3. Takahashi, T.; Xi, Z.; Yamazaki, A.; Liu, Y.; Nakajima,
K.; Kotora, M. J. Am. Chem. Soc. 1998, 120, 1672.
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K. J. Am. Chem. Soc. 1999, 121, 11093.
5. Dixon, S.; Whitby, R. J. In Titanium and Zirconium in
Organic Synthesis; Marek, I., Ed.; Wiley-VCH: Weinheim,
2002; p 86.
8a
9d
Scheme 2.
Although we must await further investigation for the
structure of the zirconium species, it is clear that the
treatment of a zirconacyclopentadiene with alkyllithium
afforded a nucleophilic dienyl species, which provides
novel type of reactions of zirconacyclopentadienes.