CuCl-catalyzed reaction of zirconacyclopentenes with oxalyl chloride: a new pathway for the preparation of cyclopentenones

Article abstract of DOI:10.1016/j.tetlet.2009.07.065

Zirconacyclopentenes, which are easily prepared from alkynes and EtMgBr (or ethylene) and Cp₂ZrCl₂, reacted with oxalyl chloride in the presence of catalytic amount of CuCl to give cyclopentenones in high yields. The reaction was per

Full text of DOI:10.1016/j.tetlet.2009.07.065

Tetrahedron Letters 50 (2009) 5434–5436
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CuCl-catalyzed reaction of zirconacyclopentenes with oxalyl chloride: a new
pathway for the preparation of cyclopentenones
*
Chao Chen, Yundong Liu, Chanjuan Xi
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Zirconacyclopentenes, which are easily prepared from alkynes and EtMgBr (or ethylene) and Cp2ZrCl2,
reacted with oxalyl chloride in the presence of catalytic amount of CuCl to give cyclopentenones in high
yields. The reaction was performed conveniently in one pot from alkynes, EtMgBr, oxalyl chloride, and
Cp2ZrCl2.
Received 13 June 2009
Revised 12 July 2009
Accepted 14 July 2009
Available online 17 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Dedicated to Professor John M. Birmingham
on the occasion of his 80th birthday
Keywords:
Zirconacyclopentenes
Oxalyl chloride
Cuprous chloride
Cyclopentenones
Cyclopentenones are particularly useful precursors for the syn-
thesis of various cyclopentyl compounds due to their versatility.
Many methods are available for their synthesis.1–5 Among them,
coupling of an alkyne, an alkene, and CO using transition-metal
complexes is most attractive for the direct synthesis of a wide vari-
ety of cyclopentenones.3 However, the use of gaseous and highly
poisonous carbon monoxide represents a drawback of this proce-
dure. The application of this reaction in most cases is also re-
stricted by the demand for highly toxic carbonyl complexes (e.g.,
Co2(CO)8 and Mo(CO)6) and/or nobel metal as the catalysts (e.g.,
Ru or Rh). A carbonylation reaction in a mild and convenient con-
dition without carbon monoxide would make the reaction more
desirable.6
Oxalyl chloride, as carbonylated reagent, had been reported
previously to undergo condensation reactions with 2 equiv of
mono-functional organometallic compounds, such as Grignard re-
agents, organolithium, organocopper, and organotin compounds,
to form 1,2-diones.7 Recently we found that oxalyl chloride reacted
with zirconacyclopentadienes to afford cyclopentadienones, in
which the carbon-carbon bond of 1,2-dicarbonyl was cleaved and
oxalyl chloride finally served as a source of CO.8 More recently,
Müller et al reported one consecutive three-component synthesis
of alkynones by coupling of heterocycles and oxalyl chloride as a
source of the CO building block followed by Sonogashira reaction.9
Prompted by these results, we envisioned that the reaction of oxa-
lyl chloride with zirconacyclopentenes could afford cyclopente-
nones (Scheme 1), although a convenient procedure for the
preparation of cyclopentenones via the reaction of zirconacyclo-
pentenes with CO gas has been reported.3e,5a,h,i
Initial experiment showed that the reaction of zirconacyclopen-
tene 1a, generated by the reaction of 3-hexyne and Cp2ZrEt2 in
THF10 with oxalyl chloride in the presence of 2 equiv of CuCl led
to the formation of a complex, inseparable mixture. This result
was surprising, since such an amount of CuCl was the choice in
the reaction of zirconacyclopentadienes with oxalyl chloride to
give high yields of cyclopentadienones.8 Without CuCl, the reaction
did not proceed. Surprisingly, when catalytic amount of CuCl
(10 mol %) was added, the reaction proceeded smoothly and the
cyclopentenone 2a was obtained in 85% isolated yield. Meanwhile,
the generated gas was collected and detected by GC. Only CO gas
was observed11 (Scheme 2).
To extend the reaction, we tried out various substituted mono-
cyclic as well as bicyclic zirconacyclopentenes12 bearing alkyl, aryl,
and TMS groups. In all cases, the corresponding products were
formed in high yields. When terminal alkyne was used, the corre-
R1
R1
R2
+
R2
O
Cl
Cp2Zr
O
Cl
O
* Corresponding author. Tel.: +86 10 62782695.
E-mail address: cjxi@tsinghua.edu.cn (C. Xi).
Scheme 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.065

C. Chen et al. / Tetrahedron Letters 50 (2009) 5434–5436
5435
Without CuCl
rt
O
Cl
O
No reaction
Cl
Et
O
CuCl
Cu
M
Et
+
Cu
M
Cl
O
Cl
O
2 mol CuCl
O
Cp2Zr
Messy
Et
Cp2Zr
Cl
0ºC
Cl
1
4
3
Et
+ CO
1a
10 mol% CuCl
( )
O
O
O
Cl
0ºC
O
Cl
Cl
CuCl
Cl
2a: 85%
O
M
O
M
Cu
O
Scheme 2.
M
7
MCl
5
6
sponding products were obtained in moderate yields (entry 5). It is
noteworthy that when unsymmetrical alkynes were used two
regioisomers were observed (entries 3–5). The ratio of the two iso-
mers depended on the selectivity of the formation of zirconacyclo-
pentenes.10 The representative results are summarized in Table 1.
According to these results and the literature report,8,9,13 we pro-
pose a possible mechanism for this reaction (Scheme 3). Firstly, the
M=Cu or Cp2ZrCl
O
+ CO ( )
2
Scheme 3.
zirconacyclopentene 1 undergoes transmetallation with CuCl to
form the intermediate 3.14 Secondly, the coordination of one of
the two carbonyl groups to copper metals or copper and zircono-
cene moieties of the intermediate 3 affords seven-membered ring
4.8,13 The alkenylcopper moiety reacts with the chelated carbonyl
group to form 5.7 Then the elimination of CuCl recovers coordi-
nated C@O bond to form 6, which then undergoes an intramolecu-
lar nucleophilic attack by the remaining alkylcopper or
alkylzirconium moiety to give five-membered carbocycle 7. Finally
elimination of the MCl (M = Cu or Cp2ZrCl) accompanying decarb-
onylation gives product 2. This result is in sharp contrast to the
case of other dianionic reagent reactions with oxalyl chloride,
which usually gives complex and inseparable products.15 The che-
lating effect of the copper moieties and/or zirconocene moiety and
the formation of cyclopentenone derivatives and CO gas were as-
sumed to be the driving force in this reaction.
Table 1
Reaction of zirconacyclopentene with oxalyl chloride
Entry
Zirconacyclopetene
Cyclopentenone
Yielda (%)
Et
Et
Et
Et
1
85
Cp2Zr
O
2a
2b
2c
2d
2e
1a
Ph
Ph
Ph
Ph
2
3
4
5
6
7
82
Cp2Zr
O
1b
SiMe3
Me
Me3Si
Me
69b
93c
50d
88
Cp2Zr
We conclude that the reaction of zirconacyclopentenes with
oxalyl chloride in the presence of catalytic amount of CuCl gives
cyclopentenones. This reaction represents a new and convenient
pathway to substituted cyclopentenones using oxalyl chloride as
the carbon monoxide source without the need of CO.
O
1c
Ph
Ph
Me
Me
Cp2Zr
1d
O
Acknowledgment
Ph
Ph
O
This work was supported by the National Natural Science Foun-
dation of China (20172032) and (20872076).
Cp2Zr
1e
Supplementary data
Pr
Pr
Pr
Pr
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.07.065.
Cp2Zr
O
2f
1f
References and notes
Bu
Bu
Bu
Bu
83
1. (a) Wenkert, E.; Greenberg, R. S.; Raju, M. S. J. Org. Chem. 1985, 50, 4681; (b)
Pecunioso, A.; Menicagli, R. J. Org. Chem. 1988, 53, 2614; (c) Santelli-Rouvier, C.;
Santelli, M. Synthesis 1983, 429; (d) Denmark, S. E.. In Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, p
752; (e) Chenard, B. L.; Van Zyl, C. M.; Sanderson, D. R. Tetrahedron Lett. 1986,
27, 2801; (f) Hiyama, T.; Shinoda, M.; Tsukanaka, M.; Nozaki, H. Bull. Chem. Soc.
Jpn. 1980, 53, 1010; (g) Jacobson, R. M.; Lahm, G. P.; Clader, J. W. J. Org. Chem.
1980, 45, 395; (h) Yan, B.; Spilling, C. D. J. Org. Chem. 2008, 73, 5385.
2. (a) Trost, B. M.; Xie, J.; Maulide, N. J. Am. Chem. Soc. 2008, 130, 17258; (b) Oh, C.
H.; Karmakar, S. J. Org. Chem. 2009, 74, 370.
3. (a) Pauson, P. L. Tetrahedron 1985, 41, 5855; (b) Schore, N. E.. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991;
Vol. 5, p 1037; (c) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 7026;
(d) Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 1999, 64, 5547; (e) Negishi, E.. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press:
Cp2Zr
2g
O
1g
Ph
Ph
O
8
71
Cp2Zr
2h
1h
a
Isolated yields.
b
A mixture of two isomers in a ratio of 25:1, the ratio of two isomers was
detected by GC.
c
A mixture of two isomers in a ratio of 20:1.
A mixture of two isomers in a ratio of 2:1.
d

5436
C. Chen et al. / Tetrahedron Letters 50 (2009) 5434–5436
Oxford, 1991; p 1163. Chapter 9.5; (f) Huang, Q. F.; Hua, R. M. Chem. Eur. J.
10. (a) Takahashi, T.; Kageyama, M.; Denisov, V.; Hara, R.; Negishi, E. Tetrahedron
Lett. 1993, 34, 687; (b) Xi, Z.; Hara, R.; Takahashi, T. J. Org. Chem. 1995, 60, 4444;
(c) Takahashi, T.; Xi, C.; Xi, Z.; Kageyama, M.; Fischer, R.; Nakajima, K.; Negishi,
E. J. Org. Chem. 1998, 63, 6802.
2009, 15, 3817; (g) Moradov, D.; Quntar, A. A. A. A.; Youssef, M.; Smoum, R.;
Rubinstein, A.; Srebnik, M. J. Org. Chem. 2009, 74, 1029; (h) Paolillo, R.; Gallo, V.;
Mastrorilli, P.; Nobile, C. F.; Rosé, J.; Braunstein, P. Organometallics 2008, 27,
741.
11. Typical experimental procedure: Reactions were carried out as follows: A 25-mL
Schelenk tube under dried nitrogen was charged with Cp2ZrCl2 (0.350 g,
1.2 mmol) and THF (5 mL). To this solution was added ethylmagnesium
bromide (1.0 M, THF solution 2.4 mL, 2.4 mmol) at À78 °C. After stirring for 1 h,
4. (a) Büchi, G.; Egger, B. J. Org. Chem. 1971, 36, 2021; (b) Hayakawa, Y.;
Yokoyama, K.; Noyori, R. J. Am. Chem. Soc. 1978, 100, 1799; (c) Trost, B. M.
Angew. Chem., Int. Ed. 1986, 25, 1; (d) Barluenga, J.; Barrio, P.; Riesgo, L.; López,
L. A.; Tomás, M. J. Am. Chem. Soc. 2007, 129, 14422; (e) Li, Z.; Moser, W. H.;
Deng, R.; Sun, L. J. Org. Chem. 2007, 72, 10254.
3-hexyne (113lL, 1 mmol) was added and the reaction mixture was stirred at
0 °C for 3 h. To this solution were added 10 mol % of CuCl (10 mg) and oxalyl
chloride (85
5. (a) Negishi, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A. J. Am. Chem. Soc. 1985, 107,
2568; (b) Wender, P. A.; McDonald, F. E. Tetrahedron Lett. 1990, 31, 1369; (c)
Agnel, G.; Negishi, E. J. Am. Chem. Soc. 1991, 113, 7424; (d) Angel, G.;
Owczarczyk, Z.; Negishi, E. Tetrahedron Lett. 1992, 33, 1543; (e) Mori, M.;
Uesaka, N.; Shibasaki, M. J. Org. Chem. 1992, 57, 3519; (f) Saitoh, F.; Mori, M.;
Okamura, K.; Date, T. Tetrahedron 1995, 51, 4439; (g) Takahashi, T.; Kasai, K.; Xi,
Z.; Denisov, V. Chem. Lett. 1995, 347; (h) Takahashi, T.; Xi, Z.; Nishihara, Y.; Huo,
S.; Kasai, K.; Aoyagi, K.; Denisov, V.; Negishi, E. Tetrahedron 1997, 53, 9123; (i)
Takahashi, T.; Huo, S.; Hara, R.; Noguchi, Y.; Nakajima, K.; Sun, W.-H. J. Am.
Chem. Soc. 1999, 121, 1094; (j) Song, Q.; Chen, J.; Jin, X.; Xi, Z. J. Am. Chem. Soc.
2001, 123, 10419; (k) Song, Q.; Li, Z.; Chen, J.; Wang, C.; Xi, Z. Org. Lett. 2002, 4,
627; (l) Luo, Q.; Wang, C.; Zhangg, W.-X.; Xi, Z. Chem. Commun. 2008, 1593.
6. (a) Morimoto, T.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K. J. Am. Chem. Soc.
2002, 124, 3806; (b) Shibata, T.; Toshida, N.; Takagi, K. Org. Lett. 2002,
4, 1619.
7. (a) Larock, R. C. Comprehensive Organic Transformations; VCH: New York, 1989;
(b) O’Niel, B. T.. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Eds.; Pergamon Press: New York, 1991; Vol. 1, p 397; (c) Shirley, D. A. Org.
React. 1954, 8, 28; (d) Jorgenson, M. J. Org. React. 1970, 18, 1; (e) Faust, R.;
Weber, C.; Fiandanese, V.; Marchese, G.; Punzi, A. Tetrahedron 1997, 53, 14655;
(f) Faust, R.; Weber, C. J. Org. Chem. 1999, 64, 2571; (g) Rocha, D. R. Synlett 2007,
1172; (h) Kashiwabara, T.; Tanaka, M. J. Org. Chem. 2009, 74, 3958.
8. Chen, C.; Xi, C.; Jiang, Y.; Hong, X. J. Am. Chem. Soc. 2005, 127, 8024.
9. Merkul, E.; Oeser, T.; Müller, T. J. J. Chem. Eur. J. 2009, 15, 5006.
lL, 1.0 mmol) at À30 °C in turn. The reaction mixture was stirred
at 0 °C for 1 h. The mixture was quenched with 3 N HCl and extracted with
20 mL of ether thrice. The extract was washed with NaHCO3 and brine, and
dried over MgSO4. The solution was filtered and the solvent was evaporated in
vacuo. The residue was purified by column chromatography on silica gel
(petroleum ether/CH2Cl2 = 4:1 as eluent) to afford 2,3-diethylcyclopentene-1-
one 2a as light yellow oil (115 mg, 85% isolated yield).
12. Negishi, E.; Cederbaum, F. E.; Takhashi, T. Tetrahedron Lett. 1986, 25, 2829.
13. (a) Xi, Z.; Song, Q. J. Org. Chem. 2000, 65, 9157; (b) Xi, Z.; Song, Q.; Chen, J.;
Guan, H.; Li, P. Angew. Chem., Int. Ed. 2001, 40, 1913; (c) Chen, J.; Song, Q.; Li, P.;
Guan, H.; Jing, X.; Xi, Z. Org. Lett. 2002, 4, 2269; (d) Xi, Z. Eur. J. Org. Chem. 2004,
2773; (e) Fan, H.; Li, G.; Mao, G.; Xi, Z. Chem. Eur. J. 2004, 10, 3444.
14. For Cu(I)-catalyzed or -mediated reactions of organozirconium compounds
see: (a) Venanzi, L. M.; Lehman, R.; Keil, R.; Lipshutz, B. H. Tetrahedron Lett.
1992, 33, 5857; (b) Takahashi, T.; Kotora, M.; Kasai, K.; Suzuki, N. Tetrahedron
Lett. 1994, 35, 5685; (c) Honda, T.; Mori, M. Organometallics 1994, 13, 5464; (d)
Kasai, K.; Kotora, M.; Suzuki, N.; Takahashi, T. J. Chem. Soc., Chem. Commun.
1995, 109; (e) Lipshutz, B. H.; Segi, M. Tetrahedron 1995, 51, 4407; (f)
Takahashi, T.; Hara, R.; Nishihara, Y.; Kotora, M. J. Am. Chem. Soc. 1996, 118,
5154; (g) Dekura, F.; Honda, T.; Mori, M. Chem. Lett. 1997, 825; (h) Takahashi,
T.; Sun, W.-H.; Liu, Y.; Nakajima, K.; Kotora, M. Organometallics 1998, 17, 3841;
(i) Zhao, C.; Lu, J.; Yan, J.; Xi, Z. Tetrahedron Lett. 2003, 44, 6895; (j) Zhao, C.; Lu,
J.; Li, Z.; Xi, Z. Tetrahedron 2004, 60, 1417.
15. Langer, P.; Stoll, M. Angew. Chem., Int. Ed. 1999, 38, 1803.