Palladium-catalyzed ring enlargement of aryl-substituted methylenecyclopropanes to cyclobutenes

Article abstract of DOI:10.1021/ja061749y

Methylenecyclopropanes 1 could be converted to the corresponding cyclobutenes 2 under the catalysis of palladium acetate in the presence of metal bromide in 1,2-dichloroethane under mild conditions. A plausible reaction mechanism has been proposed on the

Full text of DOI:10.1021/ja061749y

Published on Web 05/20/2006
Palladium-Catalyzed Ring Enlargement of Aryl-Substituted
Methylenecyclopropanes to Cyclobutenes
Min Shi,*,† Le-Ping Liu,‡ and Jie Tang‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, China, and Department of Chemistry, East China Normal UniVersity,
3663 Zhongshanbei Lu, Shanghai 200062, China
Received March 14, 2006; E-mail: mshi@pub.sioc.ac.cn
Table 1. Optimization of Reaction Conditionsa
Methylenecyclopropanes (MCPs) 1 are highly strained but readily
accessible molecules that have served as useful building blocks in
organic synthesis.1,2 MCPs undergo a variety of ring-opening
reactions in the presence of transition metal and Lewis acid catalysts
because the relief of ring strain provides a potent thermodynamic
driving force.3,4 Several pathways for the cleavage of both proximal
and distal bonds of MCPs catalyzed by transition metals have been
reported.2a,5 Herein, we report a new such reaction in which
palladium-catalyzed ring enlargement of aryl-substituted MCPs 1
to the corresponding cyclobutenes 2 occurs in the presence of metal
bromides in 1,2-dichloroethane (DCE) under mild conditions.
Cyclobutenes are mainly used in cycloaddition and photochemi-
cal reactions,6 and a few strategies have been reported for their
synthesis. One of the most common routes to cyclobutenes is the
photochemical or thermal [2 + 2] cycloaddition reaction of an
alkyne and an alkene.7 In our ongoing investigation of the trans-
formation of MCPs, we envisioned that, if a metal carbene inter-
mediate was generated at the C1 position of MCPs, a ring enlarge-
ment would take place to give the corresponding cyclobutene pro-
duct.8 In this paper, we disclose a new Pd-catalyzed method for
the synthesis of 1-aryl cyclobutenes.
Using(2-benzyloxy)phenylmethylenecyclopropane(1a)as the sub-
strate, we investigated the feasibility of the proposed reaction and
found the optimal reaction conditions for the formation of the cor-
respondingcyclobutene,2a.The results are summarized in Table 1.
Palladium chloride and palladium bromide catalyzed the reaction
to afford 2a in 62 and 84% yields, respectively, within 24 h at
a Reaction conditions: 1a (0.3 mmol), palladium catalyst (3 mol %), bromide
room temperature in DCE (entries 1 and 2). Palladium acetate and
bis(triphenylphosphine)palladium chloride did not catalyze this
(10 mol %), solvent (2.0 mL). b Isolated yields. c Starting material consumed
after column chromatography.
reaction under the same conditions (entries 3 and 4). Bis(nitrile)-
h at room temperature to give the corresponding cyclobutenes 2 in
palladium halides, the more soluble Pd(II) catalysts, did not give
good yields and conversions (Table 2, entries 2-4, 7, 9, and 11-
better results than palladium halides (entries 5-7). However, in
15). On the other hand, having either an electron-withdrawing group
the presence of metal bromides such as copper bromide,9 zinc
or no substituent on the aromatic ring retarded the reaction (entries
bromide, and magnesium bromide, 2a was produced in excellent
1, 5, 6, and 10). For MCP 1i, higher temperature (80 °C) and longer
conversions and high yields under Pd(OAc)2 catalysis (entries
reaction time were required to give the corresponding cyclobutenes
8-12). Chloride and iodide salts are less effective than the bromide
2i in high yield and conversion (entry 8). It should be noted that,
salts (entries 13-15). Next, we examined the effect of solvent
if R is an alkyl group, no reaction occurred even at high temperature
choice on this reaction (entries 16-22). The reaction proceeded
(80 °C).
smoothly in THF, toluene, dichloromethane, chloroform, and
A plausible mechanism for this unusual ring enlargement of 1
dioxane, but the yields of 2a were not as high as those within DCE
to 2 is presented in Scheme 1. Regioselective bromopalladation of
(entries 16-20). In both acetonitrile and diethyl ether, only a trace
MCPs 15a,12 with PdBr2, which might be produced in situ from Pd-
of 2a was formed (entries 21 and 22). Other metal catalysts, such
(OAc)2 and MBrn (M ) Cu, Zn, Mg, Li), affords intermediate A.13
as RhCl(PPh3)3, RuCl3, PtCl2, and Au(PPh3)Cl, did not catalyze
Intermediate A undergoes â-hydrogen elimination to form inter-
this reaction under identical conditions.
mediate B, which subsequently generates palladium carbenoid C
Using the optimal reaction conditions, we carried out the
via hydropalladation with a reversed regioselectivity. Via an R-
palladium-catalyzed ring enlargement of a variety of MCPs 1 and
bromo migration,14 C is transformed to a palladium carbene D,15
found that the corresponding cyclobutenes 2 were obtained in
which yields the product 28 and regenerates the palladium bromide
moderate to high yields (Table 2). The product structures were
catalyst. To test the plausibility of this proposed mechanism, we
1
determined by H and 13C NMR spectroscopic data, HRMS, and
designed a deuterium labeling experiment. When deuterated sub-
microanalysis. Furthermore, the X-ray crystal structure of 2l10 was
strate 1a-d was subjected to the standard reaction conditions, cy-
determined and is presented in the Supporting Information.11
clobutene 2a-d (>99% D incorporation)16 with the deuterium at
An electron-donating group on the aromatic ring of 1 significantly
the 2-position was obtained in 83% yield (Scheme 2). This result
promoted the reaction, and these reactions were complete within 3
is consistent with the mechanism proposed in Scheme 1.
In conclusion, we have found a versatile palladium-catalyzed
ring enlargement reaction where methylenecyclopropanes are con-
† Chinese Academy of Sciences.
‡ East China Normal University.
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J. AM. CHEM. SOC. 2006, 128, 7430-7431
10.1021/ja061749y CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Ring Enlargement of MCPs 1 to Cyclobutenesa
(KGCX2-210-01), and the National Natural Science Foundation of China
for financial support (20025206, 203900502, and 20272069).
Supporting Information Available: 1H and 13C NMR, MS, HRMS,
and analytic data of the compounds shown in Tables 1 and 2 and Schemes
1 and 2, X-ray crystal structure of 2k, and a detailed description of
experimental procedures. This material is available free of charge via the
Internet at http://pubs.acs.org.
References
(1) Synthesis of MCPs: Brandi, A.; Goti, A. Chem. ReV. 1998, 98, 589.
(2) For recent reviews, see: (a) Nakamura, I.; Yamamoto, Y. AdV. Synth.
Catal. 2002, 344, 111. (b) Brandi, A.; Cicchi, S.; Cordero, F. M.; Goti,
A. Chem. ReV. 2003, 103, 1213. (c) Nakamura, E.; Yamago, S. Acc. Chem.
Res. 2002, 35, 867.
(3) Selected recent articles about transition metal catalyzed reactions of
MCPs: (a) Nakamura, I.; Oh, B. H.; Saito, S.; Yamamoto, Y. Angew.
Chem., Int. Ed. 2001, 40, 1298. (b) Camacho, D. H.; Nakamura, I.; Saito,
S.; Yamamoto, Y. J. Org. Chem. 2001, 66, 270. (c) Lautens, M.; Meyer,
C.; Lorenz, A. J. Am. Chem. Soc. 1996, 118, 10676. (d) Saito, S.; Masuda,
M.; Komagawa, S. J. Am. Chem. Soc. 2004, 126, 10540. (e) Brase, S.; de
Meijere, A. Angew. Chem., Int. Ed. Engl. 1995, 34, 2545. (f) Shi, M.;
Wang, B.-Y.; Huang, J.-W. J. Org. Chem. 2005, 70, 5606.
(4) Selected recent articles about Lewis acid mediated reactions of MCPs:
(a) Huang, J.-W.; Shi, M. Synlett 2004, 2343. (b) Shi, M.; Xu, B.; Huang,
J.-W. Org. Lett. 2004, 6, 1175. (c) Xu, B.; Shi, M. Org. Lett. 2003, 5,
1415. (d) Shi, M.; Shao, L.-X.; Xu, B. Org. Lett. 2003, 5, 579. (e) Patient,
L.; Berry, M. B.; Kilburn, J. D. Tetrahedron Lett. 2003, 44, 1015 and
references cited therein.
(5) (a) Ma, S.; Lu, L.; Zhang, J. J. Am. Chem. Soc. 2004, 126, 9645. (b)
Siriwardana, A. I.; Kamada, M.; Nakamura, I.; Yamamoto, Y. J. Org.
Chem. 2005, 70, 5932.
(6) Selected recent articles about cyclobutenes: (a) Feng, J.; Szeimies, G.
Eur. J. Org. Chem. 2002, 2942. (b) Kniep, C. S.; Padias, A. B.; Hall, H.
K., Jr. Tetrahedron 2000, 56, 4279. (c) Mislin, G. L.; Miesch, M. J. Org.
Chem. 2003, 68, 433. (d) Delas, C.; Urabe, H.; Sato, F. J. Am. Chem.
Soc. 2001, 123, 7937. (e) Tantillo, D. J.; Hoffmann, R. J. Am. Chem.
Soc. 2001, 123, 9855. (f) Murakami, M.; Hasegawa, M. Angew. Chem.,
Int. Ed. 2004, 43, 4874. (g) Liu, Y.; Liu, M.; Song, Z. J. Am. Chem. Soc.
2005, 127, 3662.
(7) For the synthesis of cyclobutenes, see: (a) Carbocyclic Four-member Ring
Compounds, Houben-Weyl, Methods of Organic Chemistry; de Meijere,
A., Ed.; Thieme: Stuttgart, 1997; Vol. 17f, E 17e-f. (b) Hall, H. K., Jr.;
Padias, A. B. J. Polym. Sci, Part A: Polym. Chem. 2003, 41, 625. (c)
Leigh, W. J.; Postigo, J. A. Can. J. Chem. 1995, 73, 191. (d) Barbero,
A.; Cuadrado, P.; Garcia, C.; Rincon, J. A.; Pulido, F. J. J. Org. Chem.
1998, 63, 7531. (e) Juteau, H.; Gareau, Y. Synth. Commun. 1998, 28,
3795. (f) Huang, D.-J.; Rayabarapu. D. K.; Li, L.-P.; Sambaiah, T.; Cheng,
C.-H. Chem.sEur. J. 2000, 6, 3706. (g) Takahashi, T.; Shen, B.; Nakajima,
K.; Xi, Z. J. Org. Chem. 1999, 64, 8706. (h) Villeneuve, K.; Tam, W.
Angew. Chem., Int. Ed. 2004, 43, 610. (i) Winkler, J. D.; Melaughlin, E.
C. Org. Lett. 2005, 7, 227.
(8) For the cycloisomerization of R-cyclopropanyl metal carbene to cy-
clobutene, see: (a) Furstner, A.; Davies, P. D.; Gress, T. J. Am. Chem.
Soc. 2005, 127, 8244. (b) Nieto-Oberhuber, C.; Lo´pez, S.; Mun˜oz, M. P.;
Cardenas, D. J.; Bun˜uel, E.; Nevado, C.; Echavarren, A. M. Angew. Chem.,
Int. Ed. 2005, 44, 6146. (c) Trost, B. M.; Tanoury, G. J. J. Am. Chem.
Soc. 1988, 110, 1636. (d) Trost, B. M.; Trost, M. K. Tetrahedron Lett.
1991, 32, 3647. (e) Nieto-Oberhuber, C.; Lo´pez, S.; Echavarren, A. M. J.
Am. Chem. Soc. 2005, 127, 6178.
a Reactions were carried out by use of MCP 1 (0.3 mmol) in 1,2-dichloroethane
(DCE) (2.0 mL) with palladium acetate (2.0 mg, 3 mol %) and copper(II) bromide
(7.0 mg, 10 mol %). b Isolated yields. c Starting material consumed after column
chromatography.
Scheme 1. Proposed Mechanism for the Pd-Catalyzed Ring
Enlargement of MCPs to Cyclobutenes
(9) For CuBr2 (2.0 equiv) mediated ring-opening reaction of MCPs giving
dibrominated compounds, see: Zhou, H.-W.; Huang, X.; Chen, W.-L.
Synlett 2003, 2080.
(10) The crystal data of 2k have been deposited in CCDC with number 289394.
(11) The 1H and 13C NMR spectroscopic data of compounds 2b, 2c, and 2d
(see the Supporting Information) are similar to those reported in previous
publications. See refs 7c, 7d, and (a) Wilt, J. W.; Kosturik, J. M.; Orlowski,
R. C. J. Org. Chem. 1965, 30, 1052. (b) Hill, E. A.; Engel, M. R. J. Org.
Chem. 1971, 36, 1536. (c) Kirmse, W.; Krzossa, B.; Steenken, S. J. Am.
Chem. Soc. 1996, 118, 7473.
(12) For recent articles on halopalladation to multi carbon-carbon bonds,
see: (a) Ma, S.; Lu, X. Chem. Commun. 1990, 733. (b) Ma, S.; Lu, X. J.
Org. Chem. 1991, 56, 5120. (c) Ma, S.; Zhu, G.; Lu, X. J. Org. Chem.
1993, 58, 3692. (d) Zhu, Z.; Zhang, Z. J. Org. Chem. 2005, 70, 3339.
(13) Another route for the formation of intermediate A and the corresponding
mechanism was presented in Supporting Information as Scheme SI-2.
(14) For the migration of R-halo to a metal center, see: (a) McCrindle, R.;
Arsenault, G. J.; Gupta, A.; Hampden-Smith, M. J.; Rice, R. E.; McAlees,
A. J. J. Chem. Soc., Dalton Trans. 1991, 949. (b) McCrindle, R.; Ferguson,
G.; McAlees, A. J.; Arsenault, G. J.; Gupta, A.; Jennings, M. C.
Organometallics 1995, 14, 2741. (c) Bernardi, F.; Bottoni, A.; Miscione,
G. P. Organometallics 2001, 20, 2751.
Scheme 2. Deuterium Labeling Experiment of the Ring Enlargement
Reaction
verted into the corresponding cyclobutene compounds. This rep-
resents a new ring-opening isomerization reaction pathway of meth-
ylenecyclopropane and a novel approach for the synthesis of 1-aryl-
substituted cyclobutenes. In this manner, a series of cyclobutenes
was obtained under mild conditions in moderate to good yields.
Acknowledgment. We thank the State Key Project of Basic Re-
search (Project 973) (No. G2000048007), Shanghai Municipal Committee
of Science and Technology (04JC14083), Chinese Academy of Sciences
(15) For an article on palladium carbene, see: (a) Fillion, E.; Taylor, J. J. Am.
Chem. Soc. 2003, 125, 12700 and references therein. (b) Nakamura, I.;
Bajracharya, G. B.; Mizushima, Y.; Yamamoto, Y. Angew. Chem., Int.
Ed. 2002, 41, 4328. (c) Yamamoto, Y.; Kuwabara, S.; Ando, Y.; Nagata,
H.; Nishiyama, H.; Itoh, K. J. Org. Chem. 2004, 69, 6697 and references
cited therein.
1
(16) Determined by H and 13C NMR spectroscopic data (see the Supporting
Information).
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