Selective synthesis of α-methylenyl zirconacyclopentene via cross-coupling of alkyne and allene

Article abstract of DOI:10.1016/j.tetlet.2010.06.134

α-Methylenyl zirconacyclopentenes are synthesized regio- and stereoselectively via reductive intermolecular cross-coupling of alkynes and allenes promoted by zirconocene species 'Cp₂Zr'. An interesting reductive intramolecular coupling of the α

Full text of DOI:10.1016/j.tetlet.2010.06.134

Tetrahedron Letters 51 (2010) 4702–4704
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Selective synthesis of
of alkyne and allene
a-methylenyl zirconacyclopentene via cross-coupling
*
Weixin Zheng , Yangfeng Wu, Fenfen Zheng, Linfeng Hu, Ya Hong
College of Material Chemistry and Chemical Engineering, Hangzhou Normal University, 16 Xuelin Road, Xiasha, Hangzhou 310036, China
a r t i c l e i n f o
a b s t r a c t
Article history:
a
-Methylenyl zirconacyclopentenes are synthesized regio- and stereoselectively via reductive intermo-
lecular cross-coupling of alkynes and allenes promoted by zirconocene species ‘Cp2Zr’. An interesting
reductive intramolecular coupling of the -methylenyl zirconacyclopentene has been observed in the
Received 4 April 2010
Revised 13 June 2010
Accepted 30 June 2010
Available online 23 July 2010
a
presence of DMAD/CuCl, resulting in the generation of cyclobutene with an exocyclic double bond. Poly-
substituted 1,4-dienes can be given with high selectivity and good yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
a-Methylenyl zirconacyclopentene
Cross-coupling
1,4-Diene
Intramolecular coupling
Cyclobutene
Zirconacycle has emerged as a highly effective reagent in various
organic synthetic protocols and its chemistry has been extensively
explored.1 Besides the common zirconacyclopentane, ziconacycl-
opentene and zirconacyclopentadiene, some functionalized zirc-
onacycles have become more attractive in the last few decades. Xi
and co-workers synthesized a series of zirconacyclo-silacyclo
fused-ring intermediates which showed efficient activity in the for-
mation of some ring skeletons.2 Xie and co-workers developed the
zirconacycles incorporating a carboranyl unit for the preparation
of a range of functionalized carborane derivatives due to the rich
chemistry of the zirconacycles.3 Liu and co-workers Please check
the edit of the word ‘conversion’ in the sentence ‘Liu and...forma-
should be a significant strategy. In this case, allene, which has at-
tached much attention as a three-carbon unit and shown unique
reactivity in numerous protocols,2,5 has acted as an effective sub-
strate to result in the generation of the exocylic double bond. Urabe
and co-workers reported on the titanium alkoxide-mediated inter-
molecular coupling of functionalized allenes and alkynes affording
1,4-enynes.9 Micalizio and co-workers investigated the titanium-
mediated cross-coupling of allenic alcohols with alkynes which
underwentdivergent pathways to provide 1,4-dienes or cross conju-
gated trienes depending on the substitution of allenes.10 However,
although the structures of some zirconacyles involving allene had
been studied, their synthetic applications are rare owing to the poor
selectivity in the cyclization.11 Herein, we would like to exhibit the
tion’. and correct if necessary. reported on the preparation of
a-alky-
nylzirconacyclopentenes4a and -alkenyl zirconacyclopentenes4b
a
selective formation of a-methylenyl zirconacyclopentenes via the
giving the selectively chemical conversion to carbon–carbon bond
formation. The functionalized zirconacycle exhibited various
reactivities.
cross-coupling of the alkyne12 and allene mediated by the zircono-
cene (II) species. (Scheme 1).
A typical procedure is as follows. To a THF solution of zircona-
cyclopentene 1, prepared in situ from Takahashi reagent and
On the other hand, the exocylic carbon–carbon double bond is an
important building block in synthetic chemistry,6 which could be gi-
ven by the transition metal-promoted cross-coupling of allene and
R
R
Cp2ZrEt2
R
another p
-system.7 Compared with acyclic polysubstituted alkenes,
the regio- and stereochemistry of exocyclic double bonds are more
controllable owing to the efficient contribution of the cyclic skele-
ton.6a,8 Therefore, the synthesis of methylenyl substituted metalla-
cycle with full control of both the regio- and stereochemistry
Ph
R'
R
R
R
2
Cp2Zr
Cp2Zr
50 ºC,1h
R'
Ph
1
3
* Corresponding author. Tel.: +86 571 2886 2867; fax: +86 571 2886 7899.
E-mail addresses: zhengweixinzwx@yahoo.com.cn, wxzheng@hznu.edu.cn (W.
Zheng).
Scheme 1. Synthesis of a-methylenyl zirconacyclopentene 3.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.134

W. Zheng et al. / Tetrahedron Letters 51 (2010) 4702–4704
4703
Ph
H
Ph
Et
Et
2.63 (br)
Et
180.3
Cp2Zr
Et
H
138.7
H2C
Cp
2Zr
5.92 (br)
6.10 (br)
35.8
CH3
183.9
111.1
112.7
Ph
4d
147.0
Me Ph
Me Ph
3a
Figure 2. NOE of 4d.
Figure 1. In situ NMR data of 3a.
tios of the stereoisomers of 4a–d is above 99% based on the 1H
NMR of the mixture of the reaction.
alkyne,1c–e was added 1 equiv of allene 2 at 0 °C. The reaction mix-
ture was then stirred for further 1 h at 50 °C to afford the -meth-
a
Interestingly, when the in situ prepared a-methylenyl zircona-
ylenyl zirconacyclopentene 3 which was verified by in situ NMR of
the reaction mixture of 3a (R = Et, R0 = Me, 79% NMR yield using
dibromomethane as the internal standard). In the case of 13C
NMR (Fig. 1), there was a singlet at 111.12 and 112.73 ppm assign-
able to the two Cp rings. The two sp2 carbon attached zirconium
atom appeared characteristically at 180.32 and 183.87, respec-
tively. The sp2 carbon attached to the methyl group appeared at
147.02 ppm owing to the deshielding effect of the phenyl group
as well as the coordination of the external carbon–carbon double
bond to the zirconium center. The broad band of 2.63 in 1H NMR
assigned a CH2 involved in a metallacycle.
cyclopentene 3 was treated with 1.5 equiv of DMAD in the
presence of 2 equiv of CuCl at 0 °C in THF, 3-methylenylcyclobu-
ta-1-ene derivatives 7 were afforded during which the copper mir-
ror could be observed (Table 2).13 No NOE was observed between
the methyl and CH2 in the cyclobuta-1-ene 7a, which indicated
the E-configuration of the exocylic double bond (entry 1). Polymer-
ization during the reaction and purification by column chromatog-
raphy resulted in lower isolated yields (entries 1 and 5, Table 2).
Transmetallation of Zr–C to Cu–C bond has been proven to be
effective for activating the Zr–C bond.14 The dicopper-transmetal-
lation product 8 of the zirconacycle 3 is reasonably stable and
can not undergo the common intramolecular coupling even when
heated at 50 °C in THF for 3 h (Scheme 3). The addition of the
DMAD resulted in the formation of the cyclobutene species 7 and
the DMAD skeleton was not detected in any of the cases, which
indicated that the DMAD acted as an oxidant in this conversion.15
Therefore the cooperation of the DMAD and CuCl worked in this
reaction.
Hydrolysis of the reaction mixture with aqueous 3 N HCl affor-
ded 4a–h in excellent yield (Scheme 2, Table 1).
The stereochemical assignment of 3 is based on the NOESY
spectrum of 4d (entry 4). The NOE of 1H-CH2 and 4H-CH3 points
to a 1Z,4Z framework characteristic, respectively (Fig. 2), which
indicate the E-configuration of the exocyclic double bond in the
intermediate 3d. Besides the configuration of the double bond in-
side it zirconacyclopentene 3 has been restricted by the ring skel-
eton, the exocyclic double bonds of 3a–d have been generated
highly stereoselectively in this reductive cross-coupling. All the ra-
It was reported that the zirconacyclopentadiene, containing tow
conjugative Csp2-Zr bonds, underwent a cycloaddition with DMAD
in the presence of CuCl to produce benzene derivatives.16 In the
case of a-methylenyl zirconacyclopentene 3, the exocyclic double
bond leads to an unconjugative zirconacyclopentene, based on
which the chemistry of 3 absolutely differ from that of the
zirconacyclopentadiene.
R
R
R
H
R
3N HCl
H
Cp2Zr
In conclusion, we have demonstrated the efficient generation of
R'
a
-methylenyl zirconacyclopentene species via an intermolecular
R'
Ph
Ph
3
4a-h
reductive cross-coupling regio- and stereoselectively, which can
readily give the polysubstituted 1,4-diene derivatives in high yield.
Also, the methylenyl cyclobutene can be obtained from the intra-
molecular reductive cyclization of the active zirconocene species.
In addition, the internal and external carbon–carbon double bond
NBS
Ph
Br
DCl/D2O
Ph
Pr
D
Pr
Br
D
CH3
in the
a-methylenyl zirconacyclopentene will provide the poten-
Ph
Ph
Ph
6
5
Table 2
Scheme 2. Reaction of 3 with electrophiles.
Formation of methylenyl cyclobutene 7
R
R
R
R
2 CuCl/ 1.5 DMAD
r.t.
Table 1
Quenching of
Cp2Zr
a
-methylenyl zirconacyclopentene 3 with electrophiles
R'
Entry
3
El
Yield of 4–6a (%)
Ph
7a-e
R'
Ph
R
R0
3
1
2
3
4
5
6
7
8
9
10
Et
CH3 (3a)
CH3 (3b)
CH3 (3c)
CH3 (3d)
Ph (3e)
Ph (3f)
Ph (3g)
Ph (3h)
Ph (3f)
H+
H+
H+
H+
H+
H+
H+
H+
D+
Br+
90 (44) (4a)
92 (85) (4b)
77 (69) (4c)
84b (45) (4d)
96 (95) (4e)
95 (92) (4f)
74 (64) (4g)
91b (83) (4h)
87 (71) (5)
Entry
3
Product 7
Yielda (%)
n-Pr
n-Bu
Ph
R
R0
Et
1
2
3
4
5
Ph
Et
n-Pr
n-Bu
Ph
CH3 (3d)
Ph (3e)
Ph (3f)
Ph (3g)
Ph (3h)
7ab
7b
7c
7d
7e
71c (43)
91 (63)
89 (64)
80 (73)
69c (45)
n-Pr
n-Bu
Ph
n-Pr
Ph
CH3 (3d)
70 (65) (6)
a
b
c
GC yields. Isolated yields are given in the parentheses.
Ratio of E/Z of exocyclic double bond is 95:5.
NMR yields using dibromomethane as internal standard.
a
GC yields. Isolated yields are given in the parentheses.
NMR yields using dibromomethane as internal standard.
b

4704
W. Zheng et al. / Tetrahedron Letters 51 (2010) 4702–4704
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R
R
R
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2 CuCl
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Cu
Cu
Cp2Zr
Ph
R'
Ph
R'
8
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Ph
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Scheme 3. Formation of methylenylcyclobutene 7.
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reactivity of -methylenyl zirconacyclopentene is in progress.
a
Acknowledgments
This work was supported by the National Natural Science Foun-
dation of China (20972037, 20702010) and the Natural Science
Foundation of Zhejiang Province (Y406341). The authors are partic-
ularly grateful to Professor Tamotsu Takahashi at Hokkaido Univer-
sity, Japan for his great assistance.
Supplementary data
12. (a) Buchwald, S. L.; Watsonm, B. T.; Hoffmanm, J. C. J. Am. Chem. Soc. 1986, 108,
7411; (b) Buchwald, S. L.; Lum, R. T.; Dewan, J. C. J. Am. Chem. Soc. 1986, 108,
7441; (c) Takahashi, T.; Xi, C.; Xi, Z. J. Org. Chem. 1998, 63, 6802.
13. A typical procedure for the formation of 3-methylenecyclobuta-1-ene 7: To the
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.06.134.
prepared
a-methylenyl zirconacyclopentene 3a (1 mmol) in THF, DMAD
(1.5 mmol, 213 mg) was added in the presence of CuCl (2 mmol, 198 mg) at
0 °C. The reaction mixture was stirred at room temperature for further 6 h and
then quenched with water. The inorganic layer was extracted with diethyl
ether. The combined extract was washed with brine and dried over MgSO4.
After rotary evaporation, the residue was purified by column chromatography
to afford 7a in the GC yield of 71%.
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