Palladium-catalyzed regioselective cyclopropanating allenylation of (2,3-butadienyl)malonates with propargylic carbonates and their application to synthesize cyclopentenones

Article abstract of DOI:10.1021/ol802465k

An efficient and highly regioselective route to synthesize polysubstituted 1,3,4-alkatrien-2-yl cyclopropane derivatives via Pd(0)-catalyzed highly regioselective coupling cyclization of (2,3-butadienyl)malonate or bis(phenylsulfonyl)methane with propargy

Full text of DOI:10.1021/ol802465k

ORGANIC
LETTERS
2009
Vol. 11, No. 1
117-120
Palladium-Catalyzed Regioselective
Cyclopropanating Allenylation of
(2,3-Butadienyl)malonates with
Propargylic Carbonates and Their
Application to Synthesize
Cyclopentenones
Wei Shu,† Guochen Jia,‡ and Shengming Ma*,†
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, P. R.
China, and Department of Chemistry, The Hong Kong UniVersity of Science and
Technology, Clear Water Bay, Kowloon, Hong Kong, P. R. China
masm@mail.sioc.ac.cn
Received October 25, 2008
ABSTRACT
An efficient and highly regioselective route to synthesize polysubstituted 1,3,4-alkatrien-2-yl cyclopropane derivatives via Pd(0)-catalyzed
highly regioselective coupling cyclization of (2,3-butadienyl)malonate or bis(phenylsulfonyl)methane with propargylic carbonates was reported.
The reaction proceeded smoothly under neutral conditions to afford the products in 73-96% yields. The products may be efficiently converted
to cyclopentenone derivatives via a catalytic Pauson-Khand reaction under ambient conditions.
During the last 10-15 years, allenes have been demonstrated
as a class of very powerful starting materials in organic
synthesis.1,2 In the next stage, the development of efficient
methods for the synthesis of allenes with a unique structural
feature from readily available starting materials will dictate
the future of allene chemistry.3,4 In this area, as is known,
the Pd(0)-catalyzed reactions of alkynes with an appropriate
leaving group5 at the propargylic position usually afforded
† Shanghai Institute of Organic Chemistry.
‡ The Hong Kong University of Science and Technology.
(2) (a) Landor, S. R., Ed. The Chemistry of the Allenes; Academic Press:
London, 1982; Vol. 1. (b) Krause, N.; Hashmi, A. S. K., Eds. Modern Allene
Chemistry; Wiley-VCH: Weinheim, Germany, 2004; Vols. 1 and 2. (c) Ma,
S. Pd-Catalyzed two- or three- component cyclization of functionalized
allenes. Topics in Organometallic Chemistry; Tsuji, J., Ed.; Springer-Verlag:
Heidelberg, 2005; pp 183-210.
(1) For reviews, see: (a) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan,
F. A. Chem. ReV. 2000, 100, 3067. (b) Marshall, J. A. Chem. ReV. 2000,
100, 3163. (c) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590.
(d) Wang, L. K.; Xiong, H.; Xu, Z. Acc. Chem. Res. 2001, 34, 535. (e) Lu,
X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535. (f) Bates, R.;
Satchareon, V. Chem. Soc. ReV. 2002, 31, 12. (g) Reissig, H. U.; Schade,
W.; Okala Amombo, M.; Pulz, R.; Hausherr, A. Pure Appl. Chem. 2002,
74, 175. (h) Sydnes, L. Chem. ReV. 2003, 103, 1133. (i) Ma, S. Acc. Chem.
Res. 2003, 36, 701. (j) Brandsma, L.; Nedolya, N. A. Synthesis 2004, 735.
(k) Tius, M. Acc. Chem. Res. 2003, 36, 773. (l) Hoffmann-Ro¨der, A.; Krause,
N. Angew. Chem., Int. Ed. 2004, 43, 1196. (m) Ma, S. Chem. ReV. 2005,
(3) Brummond, K. M.; DeForrest, J. E. Synthesis 2007, 795
.
(4) For most recent examples, see: (a) Lee, K.; Lee, P. H. Org. Lett.
2008, 10, 2441. (b) Campbell, M. J.; Pohlhaus, P. D.; Min, G.; Ohmatsu,
K.; Johnson, J. S. J. Am. Chem. Soc. 2008, 130, 9180. (c) Miura, T.;
Shimada, M.; Ku, S. Y.; Tamai, T.; Murakami, M. Angew. Chem., Int. Ed.
2007, 46, 7101. (d) Pu, X.; Ready, J. M. J. Am. Chem. Soc. 2008, 130,
105, 2829. (n) Ma, S. Aldrichim. Acta 2007, 40, 91
.
10874.
10.1021/ol802465k CCC: $40.75
Published on Web 12/03/2008
2009 American Chemical Society

Scheme 1
.
Optimization of the Reaction Temperature
Table 1. Solvent and PTC Effects on Pd(0)-Catalyzed Coupling
Cyclization of 1a in the Presence of Pentyn-3-yl Carbonate 2aa
yield of
entry
solvent
PTC
time (h)
3aab (%)
1
2
3
4
5
CH3CN
DMF
toluene
DCE
10 mol % TBAB
10 mol % TBAB
10 mol % TBAB
10 mol % TBAB
10 mol % TBAB
10 mol % TBAB
no PTC
30 mol % TBAB
10 mol % TBAI
10 mol % TBAC
1
1
1
1
1
1
48
1
1
1
94
65
91
87
92
88
THF
allenylic/propargylic palladium intermediates, which may
further react with alkenes, terminal or internal alkynes, and
CO to afford 1,2,4-trienes,6,7 4,5-allenyl aldehydes/ketones,7
2,3-allenoic acids,8 esters,8a,9 and amides,10 respectively. To
the best of our knowledge, the insertion of the above
σ-allenylpalladium species into an allene has not yet been
explored.11 As part of our program investigating the transi-
tion-metal-catalyzed coupling cyclization of functionalized
allenes12 we report here an efficient and exclusive route to
synthesize cyclopropylvinyl allene via the Pd(0)-catalyzed
regioselective coupling cyclization of (2,3-butadienyl)ma-
lonates or bis(phenylsulfonyl)methane with propargylic car-
bonates.
6
CH3NO2
CH3CN
CH3CN
CH3CN
CH3CN
7c
8
39d
(80)e
96
9
10
54
a The reaction was carried out using 0.2 mmol of 1a, 0.3 mmol of
2a, 5 mol % Pd(PPh3)4, and 10 mol % TBAB in 2 mL of solvent at 80 °C
in a Schlenk tube. TBAB ) tetrabutylammonium bromide. TBAI )
tetrabutylammonium iodide. TBAC ) tetrabutylammonium chloride.
b Isolated yield; the yield in parentheses is the NMR yield using mesitylene
as the interal standard. c The reaction was conducted at 40 °C. d 15% of
the starting material was recovered. e 8% of the starting material was
recovered.
Our initial investigation was based on the reaction of
dimethyl (2,3-butadienyl)malonate 1a with pentyn-3-yl car-
bonate 2a in the presence of 5 mol % of Pd(PPh3)4 and 10
mol % of TBAB in CH3CN at 40 °C. Interestingly, we
observed the exclusive formation of 1,3,4-alkatrien-2-yl
cyclopropane derivative 3aa as the only product in 65%
yield. The formation of the 5-membered product 4aa was
not observed. After some screening, best results were
obtained when the reaction was conducted at 80 °C, affording
3aa in 94% yield (Scheme 1).
Next, the solvent effect on the reaction was examined
(entries 1-6, Table 1). To our delight, this reaction was very
general for the solvents tested except for DMF (entry 2, Table
1). Among the solvents tested, CH3CN afforded the product
3aa in the highest yield (entry 1, Table 1). A survey of phase-
transfer catalysts (PTC) indicated that the presence of a
phase-transfer catalyst is essential to the reaction (entries
7-10, Table 1): the reaction is very sluggish in the absence
of PTC (entry 7, Table 1). However, increasing the amount
of TBAB did not favor the reaction (entry 8, Table 1). In
the presence of 10 mol % of TBAI, the yield of the desired
1,3,4-alkatrien-2-yl cyclopropane derivative 3aa can be
further improved to 96% (entry 9, Table 1). TBAC is also
effective, albeit with a much lower yield of 3aa (entry 10,
Table 1).
(5) For reviews, see: (a) Tsuji, J. Angew. Chem., Int. Ed. 1995, 34, 2589.
(b) Tsuji, J.; Mandai, T. Metal-Catalyzed Cross-Coupling Reactions;
Diederich, F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998; p 455.
(6) (a) Monteiro, N.; Arnold, A.; Balme, G. Synlett 1998, 1111. (b)
Cacchi, S.; Fabrizi, G.; Moro, L. Tetrahedron Lett. 1998, 39, 5101. (c)
Ishikura, M.; Matsuzaki, Y.; Katagiri, N. Tetrahedron 1998, 54, 13929
(7) Tadakatsu, M.; Masakazu, O.; Hiromasa, Y.; Tatsuya, N.; Hiroshi,
M. Tetrahedron Lett. 1991, 32, 3397
.
.
(8) (a) Marshall, J. A.; Wolf, M. A.; Wallace, E. M. J. Org. Chem.
1997, 62, 367. (b) Bartley, G. S.; Wallace, E. M. J. Org. Chem. 1996, 61,
5729. (c) Bartley, G. S.; Wallace, E. M. J. Org. Chem. 1995, 60, 796. (d)
Marshall, J. A.; Van Devender, E. A. J. Org. Chem. 2001, 66, 8037.
(9) (a) Tsuji, J.; Sugiura, T.; Minami, I. Tetrahedron Lett. 1986, 27,
731. (b) Mandai, T.; Tsujiguchi, Y.; Matsuoka, S.; Tsuji, J.; Saito, S.
Tetrahedron Lett. 1994, 35, 5697. (c) Li, Y.; Zou, H.; Gong, J.; Xiang, J.;
Luo, T.; Quan, J.; Wang, G.; Yang, Z. Org. Lett. 2007, 9, 4057
(10) Imada, Y.; Alper, H. J. Org. Chem. 1996, 61, 6766.
(11) Ma, S.; Gu, Z.; Deng, Y. Chem. Commun. 2006, 94.
.
To demonstrate the efficiency and scope of the present
method, we applied the above optimized reaction conditions
to a variety of (2,3-butadienyl)malonates 1 and propargylic
carbonates 2. The results are summarized in Table 2. To our
delight, besides the simple methyl (2,3-butadienyl)malonate,
ethyl- and benzyl-substituted methyl (2,3-butadienyl)ma-
lonates at the 2′ position afforded the corresponding 1,3,4-
alkatrien-2-ylcyclopropane derivatives with a quaternary
carbon center in good yields (entries 1-4, Table 2). It is
noted that the formation of all-carbon quaternary centers is
not easy since the process requires the creation of a new
(12) For some selected recent examples of cyclization of allenes, see:
(a) Kumareswaran, R.; Gallucci, J.; RajanBabu, T. V. J. Org. Chem. 2004,
69, 9151. (b) Dondas, H. A.; Fishwick, C. W. G.; Gai, X.; Grigg, R.; Kilner,
C.; Dumrongchai, N.; Kongkathip, B.; Kongkathip, N.; Polysuk, C.;
Sridharan, V. Angew. Chem., Int. Ed. 2005, 44, 7570. (c) Ma, S.; Gu, Z.
J. Am. Chem. Soc. 2005, 127, 6182. (d) Trillo, B.; Gulías, M.; López, F.;
Castedo, L.; Mascaren˜as, J. L. AdV. Synth. Catal. 2006, 348, 2381. (e) Gu,
Z.; Wang, X.; Shu, W.; Ma, S. J. Am. Chem. Soc. 2007, 129, 10948. (f)
Banaag, A. R.; Tius, M. S. J. Am. Chem. Soc. 2007, 129, 5328. (g)
Tsukamoto, H.; Matsumoto, T.; Kondo, Y. J. Am. Chem. Soc. 2007, 130,
388. (h) Piera, J.; Krumlinde, P.; Stru¨bing, D.; Ba¨ckvall, J. E. J. Am. Chem.
Soc. 2007, 129, 14120. (i) Hamaguchi, H.; Kosaka, S.; Ohno, H.; Fujii, N.;
Tanaka, T. Chem.sEur. J. 2007, 13, 1692. (j) Tsukamoto, H.; Kondo, Y.
Org. Lett. 2008, 10, 2633. (k) Trillo, B.; López, F.; Gulías, M.; Castedo,
L.; Mascaren˜as, J. L. Angew. Chem., Int. Ed. 2008, 47, 951.
118
Org. Lett., Vol. 11, No. 1, 2009

Table 2. Pd(0)-Catalyzed Coupling Cyclization of 1 with Propargylic Carbonates 2a
1
2
entry
R1
H
E
R2
Et
Et
-(CH2)5-
Et
R3
isolated yield of 3 (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
CO2Me (1a)
CO2Me (1b)
CO2Me (1b)
CO2Me (1c)
SO2Ph (1d)
CO2Me (1a)
CO2Me (1a)
CO2Me (1a)
CO2Me (1a)
CO2Me (1a)
CO2Me (1a)
CO2Me (1a)
CO2Me (1a)
H (2a)
H (2a)
H (2b)
H (2a)
H (2a)
H (2b)
H (2c)
H (2d)
96 (3aa)
78 (3ba)
92 (3bb)
92 (3ca)
92 (3da)
73 (3ab)
75 (3ac)
85 (3ad)
89 (3af)
79 (3ag)
91 (3ah)
96 (3ai)
90 (3aj)
Bn
Bn
Et
H
H
H
H
H
H
H
H
H
Et
-(CH2)5-
-(CH2)4-
Me
Me
Me
Me
Me
Me
Ph (2f)
n-Bu (2g)
c-C3H5 (2h)
CO2Me (2i)
CH2OMe (2j)
a The reaction was carried out using 0.1-0.2 mmol of 1, 1.5 equiv of 2, 5 mol % Pd(PPh3)4, and 10 mol % TBAI in 2 mL of CH3CN at 80 °C in
a Schlenk tube.
C-C bond at a sterically hindered carbon center.13 Moreover,
at room temperature),15 various polysubstituted cyclopen-
tenone derivatives 5 were obtained in good yields (Table
3). Cyclopentenones are core structural units extensively
existing in natural products and bioactive molecules.16
(2,3-butadienyl)bis(phenylsulfonyl)methane may also be used
in this reaction, affording the product in 92% yield (entry 5,
Table 2). As to the propargylic carbonates, not only terminal
propargylic carbonates are suitable substrates (entries 1-8,
Table 2) but also internal propargylic carbonates with phenyl,
alkyl, cycloalkyl, methoxycarbonyl, and methoxymethyl
substitution on the C-C triple bond have been successfully
employed in this reaction (entries 9-13, Table 2). Propar-
gylic carbonates possessing alkyl and cycloalkyl groups at
the propargylic position worked equally well under the
present conditions (Table 2).
Scheme 2. Plausible Mechanism of the Reaction
A rationale of this reaction is shown in Scheme 2.
Oxidative addition of 2 with Pd(0) would afford allenyl
palladium intermediate M1, which underwent intermolecular
carbopalladation with the allene moiety of 1 to generate
π-allyl palladium intermediate syn-M2. The malonate moiety
in syn-M2 was deprotonated by the methoxy anion, which
was followed by regioselective intramolecular attacking at
the π-allyl palladium moiety to afford the final product 3.
Disubstituted propargylic carbonates at the R-position may
stablize the allenyl palladium species M1.
In summary, we have demonstrated a new method for the
synthesis of allenes with a cyclopropylvinyl substituent. This
reaction proceeded smoothly under neutral conditions, and
the regioselectivity is exclusive for the formation of 1,3,4-
alkatrien-2-yl cyclopropane derivatives. These compounds
When these 2-cyclopropyl-1,3,4-trienes 3 were exposed
to the catalytic [4 + 1] cycloaddition reaction conditions14
(catalyzed by [RhCl(CO)2]2 (2.5 mol %) under 1 atm of CO
(13) For selected recent reviews, see: (a) Quaternary Stereocenters:
Challenges and Solutions for Organic Synthesis; Christoffers, J., Baro, A.,
Eds.; Wiley-VCH: Weinheim, 2005. (b) Trost, B. M.; Jiang, C. H. Synthesis
2006, 369.
(15) Wender, P. A.; Croatt, M. P.; Deschamps, N. M. Angew. Chem.,
Int. Ed. 2006, 45, 2459.
(14) For reports on Pauson-Khand reaction of vinyl allenes, see: (a)
Murakami, M.; Itami, K.; Ito, Y. Angew. Chem., Int. Ed. Engl. 1995, 34,
2691. (b) Murakami, M.; Itami, K.; Ito, Y. Organometallics 1999, 18, 1326.
(c) Murakami, M.; Itami, K.; Ito, Y. J. Am. Chem. Soc. 1999, 121, 4130.
(16) (a) Bickley, J. F.; Roberts, S. M.; Santor, M. G.; Snape, T. J.
Tetrahedron 2004, 60, 2569. (b) Chomcheon, P.; Sriubolmas, N.; Wiyak-
rutta, S.; Ngamrojanavanich, N.; Chaichit, N.; Mahidol, C.; Ruchirawat,
S.; Kittakoop, P. J. Nat. Prod. 2006, 69, 1351.
Org. Lett., Vol. 11, No. 1, 2009
119

of allenes and cyclopropanes,17,18 this method will be of
interest to synthetic organic chemists. Further studies on the
scope of the reaction and synthetic applications of the
products are being pursued in our laboratory.
Table 3. [4 + 1] Cycloaddition Reaction of 3 with COa
Acknowledgment. Financial support from National Natu-
ral Science Foundation of China (20429201 and 20732005),
State Basic and Research Development Program (Grant No.
2006CB806105), and Chinese Academy of Sciences is
greatly appreciated. We also thank Mr. Tao Bai in our group
for reproducing the results presented in entries 1, 4, and 9
of Table 2 and entry 5 of Table 3.
entry R1
R2
R3
time (h) yield of 5b (%)
1
2
3
4
5
6
H
H
Et
Me
H (3aa)
H (3ad)
H (3ca)
Ph (3af)
7
7
72(5a)
80(5b)
86(5c)
89(5d)
82(5e)
69 (5f)
Et Et
12
36
3
Supporting Information Available: Experimental pro-
cedures and analytical data of all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
H
H
H
Me
-(CH2)4- H (3ac)
Me n-Bu (3ag)
60
a The reaction was carried out using 0.1-0.2 mmol of 3 in 2 mL of
DCE. b Isolated yields.
OL802465K
may be successfully applied to the synthesis of polysubsti-
tuted cyclopentenones via a catalytic [4 + 1] cycloaddition
reaction under ambient conditions. Due to diverse reactivity
Afonso, M. M.; Palenzuela, J. A. Synthesis 2004, 757. (f) Murakami, M.;
Itami, K.; Ito, Y. Synlett 1999, 951. (g) Rega´s, D.; Ruiz, J. M.; Afonso,
M. M.; Galindo, A.; Palenzuela, J. A. Tetrahedron Lett. 2003, 44, 8471.
(18) For some selected transfomations of cycloprane derivatives, see:
(a) Sumida, Y.; Yorimitsu, H.; Oshima, K. Org. Lett. 2008, 10, 4677. (b)
Sethofer, S. G.; Staben, S. T.; Hung, O. Y.; Toste, F. D. Org. Lett. 2008,
10, 4315. (c) Pohlhaus, P. D.; Sanders, S. D.; Parsons, A. T.; Li, W.;
Johnson, J. S. J. Am. Chem. Soc. 2008, 130, 8642. (d) Lifchits, O.; Charette,
A. B. Org. Lett. 2008, 10, 2809. (e) Perreault, C.; Goudreau, S. R.; Zimmer,
L. E.; Charette, A. B. Org. Lett. 2008, 10, 689.
(17) For some selected transformations of vinyl allenes, see: (a)
Murakami, M.; Ashida, S.; Matsuda, S. J. Am. Chem. Soc. 2004, 126, 10838.
(b) López, S.; Rodr´ıguez, J.; Rey, J. G.; Lera, A. R. J. Am. Chem. Soc.
1996, 18, 1881. (c) Rega´s, D.; Afonso, M. M.; Rodr´ıguez, M. L.; Palenzuela,
J. A. J. Org. Chem. 2003, 68, 7845. (d) Souto, J. A.; López, C. S.; Faza,
O. N.; Alvarez, R.; de Lera, A. R. Org. Lett. 2005, 7, 1565. (e) Rega´s, D.;
120
Org. Lett., Vol. 11, No. 1, 2009