Rhodium(I)-catalyzed intramolecular ene reaction of vinylidenecyclopropanes and alkenes for the formation of bicyclo[5.1.0]octylenes

Article abstract of DOI:10.1021/ol902505p

"Chemical Equation Presented" An efficient catalytic system for the intramolecular ene reaction of allene and alkene of diarylvinylidenecyclopropanes has been established. The reaction was achieved by using [RhCl(CO)₂]₂ as the cataly

Full text of DOI:10.1021/ol902505p

ORGANIC
LETTERS
2010
Vol. 12, No. 1
64-67
Rhodium(I)-Catalyzed Intramolecular Ene
Reaction of Vinylidenecyclopropanes
and Alkenes for the Formation of
Bicyclo[5.1.0]octylenes
Wei Li,† Wei Yuan,† Min Shi,*,† Erik Hernandez,‡ and Guigen Li*,‡
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 and Biochemistry, Texas Tech UniVersity,
Lubbock, Texas 79409-1061
mshi@mail.sioc.ac.cn; guigen.li@ttu.edu
Received October 29, 2009
ABSTRACT
An efficient catalytic system for the intramolecular ene reaction of allene and alkene of diarylvinylidenecyclopropanes has been established.
The reaction was achieved by using [RhCl(CO)2]2 as the catalyst in co-solvents of toluene and acetonitrile. MeCN was found to play a crucial
role in controlling the reaction toward formation of bicyclo[5.1.0]octylene derivatives. An alternative system consisting of [RhCl(CO)2]2 and
toluene in the absence of MeCN was found to give [2 + 2] cycloaddition adducts. The structures have been unambiguously determined by
X-ray structural analysis. Deuterium labeling experiments were conducted to confirm the mechanism hypothesis.
Transition-metal-catalyzed stereoselective creation of func-
tionalized seven-membered rings has been challenging in
modern organic chemistry because these rings belong to the
carbocyclic cores of some of the most important and largest
families of natural products such as frondosin A-E, gua-
ianes, tiglianes, etc.1,2 The most successful strategy to build
these cores is to take advantage of the Rh-catalyzed and Ru-
catalyzed [5 + 2] cycloadditions of cyclopropane-anchored
olefins that were established by Wender2,3 and Trost,1,4
respectively.
In the past several years, we and others have been engaging
in the study of a series of reactions involving vinylidenecy-
clopropanes (VDCPs) as the susbtrates in which allene
moieties are connected onto the cyclopropane ring.5,6 During
continuing study of these reactions, we found that diarylvi-
nylidenecyclopropanes can be readily converted into novel
† Chinese Academy of Sciences.
‡ Texas Tech University.
(1) (a) Trost, B. M.; Hu, Y.; Horne, D. B. J. Am. Chem. Soc. 2007,
129, 11781. (b) Transition Metals in the Synthesis of Complex Organic
Compounds, 2nd ed.; Hegedus, L. S., Ed.; University Science Books:
Sausalito, CA, 1998. (c) Principles and Applications of Organotransition
Metal Chemistry, 2nd ed.; Collman, J. P., Hegedus, L. S., Norton, J. R.,
(3) (a) Wender, P. A.; Haustedt, L. O.; Lim, J.; Love, J. A.; Williams,
T. J.; Yoon, J.-Y. J. Am. Chem. Soc. 2006, 128, 6302. (b) Wender, P. A.;
Dyckman, A. J.; Husfeld, C. O.; Kadereit, D.; Love, J. A.; Rieck, H. J. Am.
Chem. Soc. 1999, 121, 10442. (c) Wender, P. A.; Takahashi, H.; Witulski,
B. J. Am. Chem. Soc. 1995, 112, 4720.
Finke, R. G., Eds.; University Science Books: Sausalito, CA, 1987
.
(2) (a) Wender, P. A.; Dyckman, A. J.; Husfeld, C. O.; Kadereit, D.;
Love, J. A.; Rieck, H. J. Am. Chem. Soc. 1999, 121, 5348. (b) Wender,
P. A.; Deschamps, N. M.; Gamber, G. G. Angew. Chem., Int. Ed. 2003, 42,
(4) Trost, B. M.; Shen, H. C.; Horne, D. B.; Toste, F. D.; Steinmetz,
B. G.; Koradin, C. Chem.sEur. J. 2005, 11, 2577. (b) Trost, B. M.; Shen,
H. C. Angew. Chem., Int. Ed. 2001, 40, 2313. (c) Trost, B. M.; Toste, F. D.;
Shen, H. J. Am. Chem. Soc. 2000, 122, 2379.
2146
.
10.1021/ol902505p  2010 American Chemical Society
Published on Web 12/01/2009

Table 1. Optimization of Conditions for Intramolecular Ene Reaction of Diphenylvinylidenecyclopropane 1a in the Presence of
[RhCl(CO)2]2
yield (%)b
entrya
solvent
DCE
DCE
DCE
DCE
DCE
DCE
DMF
x
additive
temp (°C)
time
2a
3
4
1
2
3
4
1
30
1
30
1
1
1
1
1
20
20
20
20
20
80
100
80
24 h
6 d
7 d
7 d
7 d
24 h
2.5 h
3 h
trace
trace
2.0 equiv DMB
2.0 equiv DMB
2.0 equiv COD
2.0 equiv DMB
23
43
trace
trace
complex
trace
trace
trace
5
6
7c
8
43
89
90
MeCN
toluene/MeCN
9d
100
1 h
a VDCP 1a (0.2 mmol) and [RhCl(CO)2]2 (4 mol %) were dissoved in 3 mL of solvent under 1 atm CO and stirred for several hours at different
temperatures. b Isolated yields. c 43% of the starting materials was recovered. d Toluene (2 mL) and MeCN (1 mL).
bicyclo[5.1.0]octylene core structures in toluene and MeCN
as co-solvents at enhanced temperature in the presence of
[RhCl(CO)2]2 as the catalyst. In addition, this catalytic system
without using MeCN was found to result in intramolecular
[2 + 2] cycloaddition adducts. In this paper, we would like
to disclose the preliminary results of this study as represented
by Schemes 1 and 4, with results summarized in Table 1
and 2.
remained even at higher temperatures. We then turned
attention to the use of [RhCl(CO)2]2, which has become a
powerful transitional metal catalyst for similar cycloaddition
reactions.2,3 We found that bicyclic[5.1.0]octylene derivative
2a was formed as a single diastereomer in a chemical yield
of 43% when the reaction was performed in DMF at 100 °C
in the presence of [RhCl(CO)2]2 (10 mol %) as the catalyst
(entry 7 in Table 1 and Table SI in Supporting Information).7
Inspired by this initial result, we continued optimizing
conditions using [RhCl(CO)2]2 as the catalyst. As revealed
in Table 1, when the reaction was performed at room
temperature (20 °C) under 1.0 or 30 atm of CO atmosphere
(Table 1, entries 1 and 2), trace amounts of Pauson-Khand
products 3 and 4 were detected without observing the
intramolecular ene reaction products. However, when 2,3-
dimethylbuta-1,3-diene (DMB, 2.0 equiv) was added into
the catalytic system as an additive, Pauson-Khand
products 3 and 4 were obtained in chemical yields of 23%
and 43%, respectively (Table 1, entry 3).7 Attempts to
increasing the formation of these two products were
unsuccessful under various catalytic conditions by using
other additives even at enhanced temperature (Table 1,
entries 4-6).
Scheme 1
Diphenylvinylidenecyclopropane 1a was utilized as the
model substrate for screening conditions under carbon
monoxide atmosphere in the presence of transition metal
catalysts such as PtCl2, PdCl2, Ru3(CO)12, RhCl(CO)(PPh3)2,
and Rh6(CO)16 that were then available to us in common
solvents of N,N-dimethylformamide (DMF) and dichloroet-
hane (DCE). Unfortunately, all of the above catalysts did
not result in anticipated products, and most starting materials
Pleasingly, we found that the combination of [RhCl(CO)2]2
and MeCN (as the catalyst and solvent, respectively) resulted
in the intramolecular ene reaction product 2a in 89% yield.
This result was achieved by performing the reaction at 80
°C for 3 h (Table 1, entry 7). We also found the reaction
occurred at a faster rate when a mixture of toluene and MeCN
(2:1) was employed instead of acetonitrile itself. The reaction
can be finished within 1 h leading to 2a in 90% yield under
this co-solvent system at slightly enhanced temperature
(5) (a) Li, W.; Shi, M. J. Org. Chem. 2008, 73, 6698, and references
therein. (b) Li, W.; Shi, M. J. Org. Chem. 2009, 74, 856. (c) Yao, L.-F.;
Shi, M. Chem.sEur. J. 2009, 15, 3875. (d) Shi, M.; Wu, L.; Lu, J.-M. J.
Org. Chem. 2008, 73, 8344. (e) Li, Q.; Shi, M.; Timmons, C.; Li, G. Org.
Lett. 2006, 8, 625.
(6) (a) Sugita, H.; Mizuno, K.; Saito, T.; Isagawa, K.; Otsuji, Y.
Tetrahedron Lett. 1992, 33, 2539. (b) Mizuno, K.; Sugita, H.; Kamada, T.;
Otsuji, Y. Chem. Lett. 1994, 449, and references therein. (c) Mizuno, K.;
Maeda, H.; Sugita, H.; Nishioka, S.; Hirai, T.; Sugimoto, A. Org. Lett.
2001, 3, 581.
(7) See Supporting Information for the X-ray crystal data of products
2g, 3, and 5f and the catalyst screening results.
Org. Lett., Vol. 12, No. 1, 2010
65

(Table 1, entry 8). Under CO atmosphere, the [RhCl(CO)2]2
catalyst can be better stabilized, and the reaction rate be
accelerated.
Scheme 2
.
Mechanism of [RhCl(CO)2]2-Catalyzed
Intramolecular Ene Reaction
Under the optimal condition, we next examined the scope
of generality of this reaction by using a variety of diarylvi-
nylidenecyclopropanes 1 as the substrates that were synthe-
sized using known procedures;5 the results are summarized
in Table 2. As revealed in Table 2, the corresponding ene
Table 2. [RhCl(CO)2]2-Catalyzed Intramolecular Ene Reaction
of Diarylvinylidenecyclopropane 1 under Optimal Condition
species C through an intramolecular cycloaddition to allene
moiety. A reductive elimination affords the product 2 along
with Rh(I) catalyst regeneration.
entrya
R1/R2/R3
time (h) 2, yield (%)b
1
C6H5/C6H5/p-CH3C6H4, 1b
C6H5/C6H5/p-CH3OC6H4, 1c
C6H5/C6H5/p-FC6H4, 1d
1
2b, 74
2c, 74
2d, 91
2e, 87
2f, 68
2g, 73
2h, 84
2i, 72
2j, 75
2k, 70
2l, 88c
2
6
3
0.5
0.5
1
Scheme 3. Deuterium Labeling Study of Mechanism
4
C6H5/C6H5/p-ClC6H4, 1e
C6H5/C6H5/p-BrC6H4, 1f
C6H5/C6H5/m-BrC6H4, 1g
p-CH3C6H4/p-CH3C6H4/C6H5, 1h
p-CH3OC6H4/p-CH3OC6H4/C6H5, 1i
p-ClC6H4/p-ClC6H4/C6H5, 1j
C6H5/C6H5/CH3, 1k
5
6
0.3
2
7
8
2
9
2
10
11
3
p-ClC6H4/C6H5/C6H5, 1l
1
a Reaction conditions: VDCP 1 (0.2 mmol) and [RhCl(CO)2]2 (4 mg, 4
mol %) were dissolved in toluene (2 mL) and MeCN (1 mL), and then the
mixtures were stirred for different times at 100 °C under 1 atm CO. b Isolated
yield. c Ratio of E- and Z-isomers is 1:1, which was determined by 1H NMR
spectroscopic data.
To obtain the evidence to support this mechanism, we
conducted deuterium labeling experiments (Scheme 3). The
labeling experiments were performed by subjecting deuter-
ated substrate 1f-d (75% D at the allylic C5 position) to the
standard catalytic system. After the reaction was finished,
the resulting deuterated product 2f-d was determined to be
in 79% yield along with 75% D contents at both C1 and C5
positions; this observation unambiguously confirms that the
complete deuterium transferring in 1f-d into bicyclo[5.1.0]-
octylene, 2f-d, via the Rh(I) complex catalyzed C-H
activation does occur under the present catalytic condition.
product, bicyclo[5.1.0]octylene 2,7 was obtained as a single
diastereomer for each case in good to high yields (68 - 91%)
that are not influenced by electron-donating or electron-
withdrawing substituents on the aromatic rings (Table 2,
entries 1-9). Even for the case of 1k in which R3 was an
aliphatic methyl group, the ene product (2k) can be obtained
in 70% yield (Table 2, entry 10). In the case of unsym-
metrical diarylvinylidenecyclopropane 1l, the bicyclo[5.1.0]
octylene (2l) was generated as E- and Z-isomeric mixtures
in a combined yield of 88% (Table 2, entry 11).
A plausible mechanism for this intramolecular ene reaction
is outlined in Scheme 2. As in a similar mechanism proposed
by Bergman,8 acetonitrile and the tethered terminal alkene
can be coordinated onto Rh(I) metal center to generate
intermediate A in situ. Subsequently, the oxidative addition
of rhodium(I) complex into the neighboring allylic C-H
bond gives a π-allyl rhodium-hydrogen species B,9 which
leads to a seven-membered carbocyclic rhodium-hydrogen
Scheme 4
.
[RhCl(CO)2]2-Catalyzed Reaction Performed in
Toluene
(8) (a) Taw, F. L.; White, P. S.; Bergman, R. G.; Brookhart, M. J. Am.
Chem. Soc. 2002, 124, 4192. (b) Prater, M. E.; Pence, L. E.; Cle´rac, R.;
Finniss, G. M.; Campana, C.; Auban-Senzier, P.; Je´rome, D.; Canadell, E.;
Dunbar, K. R. J. Am. Chem. Soc. 1999, 121, 8005.
To further confirm that MeCN acts as the ligand to Rh(I)
metal center and plays a crucial role for the present
[RhCl(CO)2]2-catalyzed intramolecular ene reaction, we next
performed the reactions of diphenylvinylidenecyclopropane
1a and 1f under the standard conditions solely in toluene
without the use of acetonitrile. Surprisingly, the reaction
(9) (a) Wegner, H. A.; De Meijere, A.; Wender, P. A. J. Am. Chem.
Soc. 2005, 127, 6530. (b) Brummond, K. M.; Chen, H.; Mitasev, B.; Casarez,
A. D. Org. Lett. 2004, 6, 2161. (c) Yu, Z.-X.; Cheong, P. H.-Y.; Liu, P.;
Legault, C. Y.; Wender, P. A.; Houk, K. N. J. Am. Chem. Soc. 2008, 130,
2378.
66
Org. Lett., Vol. 12, No. 1, 2010

proceeded along another direction (Scheme 4), i.e., the
corresponding bicyclo[5.1.0]octylene derivatives 2a and 2f
were not observed. Instead, the intramolecular [2 + 2]
cycloaddition reaction10 took place and gave adducts 5a and
5f in chemical yields of 29% and 24%, respectively.
details of this reaction are currently ongoing in our labora-
tories. Meanwhile, the intramolecular [2 + 2] cycloaddition
and Pauson-Khand reaction of diarylvinylidenecyclopro-
panes under similar conditions will also be systematically
investigated in the near future.
In conclusion, we have established a new efficient catalytic
system for an intramolecular ene reaction of allene and alkene
of diarylvinylidenecyclopropanes. In this new system con-
sisting of [RhCl(CO)2]2, toluene, and acetonitrile, MeCN was
found to play a crucial role in controlling the reaction toward
formation of bicyclo[5.1.0]octylene derivatives (2b-2l). An
alternative system consisting of [RhCl(CO)2]2 and toluene
in the absence of MeCN leads to [2 + 2] cycloaddition
adducts (5a and 5f). The structures have been unambiguously
determined by X-ray structural analysis. Deuterium labeling
experiments were conducted to confirm the mechanism
hypothesis. Further efforts on the scope and mechanistic
Acknowledgment. We thank the Shanghai Municipal
Committee of Science and Technology (08dj1400100-2),
National Basic Research Program of China (973)-
2009CB825300, and the National Natural Science Founda-
tion of China (20928001, 20472096, 20872162, 20672127,
20821002, 20732008), NIH (R03DA026960), and Robert A.
Welch Foundation (D-1361) for their generous support. We
thank Mr. Jie Sun for performing X-ray structural analysis.
1
Supporting Information Available: 13C and H NMR
spectroscopic and analytic data for 1a-1l, 2a-2l, 3, 4, 5a,
and 5f, as well as the X-ray crystal data of 2g, 3, and 5f.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(10) (a) Mukai, C.; Inagaki, F.; Yoshida, T.; Yoshitani, K.; Hara, Y.;
Kitagaki, S. J. Org. Chem. 2005, 70, 7159. (b) Saito, T.; Sugizaki, K.; Otani,
T.; Suyama, T. Org. Lett. 2007, 9, 1239. (c) Wang, H.; Sawyer, J. R.; Evans,
P. A.; Baik, M.-H. Angew. Chem., Int. Ed. 2008, 47, 342.
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