Rh(I)-catalyzed carbonylative carbocyclization of tethered ene- and yne-cyclopropenes

Article abstract of DOI:10.1021/ol101091r

Rh(I)-catalyzed carbonylative carbocyclization of ene- and yne-cyclopropene systems provides cyclohexenones and phenols with high efficiency, respectively.

Full text of DOI:10.1021/ol101091r

ORGANIC
LETTERS
2010
Vol. 12, No. 13
3082-3085
Rh(I)-Catalyzed Carbonylative
Carbocyclization of Tethered Ene- and
Yne-cyclopropenes
Changkun Li,† Hang Zhang,† Jiajie Feng,† Yan Zhang,† and Jianbo Wang*,†,‡
Beijing National Laboratory of Molecular Sciences (BNLMS) and Key Laboratory of
Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of
Chemistry, Peking UniVersity, Beijing 100871, China, and State Key Laboratory of
Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
wangjb@pku.edu.cn
Received May 12, 2010
ABSTRACT
Rh(I)-catalyzed carbonylative carbocyclization of ene- and yne-cyclopropene systems provides cyclohexenones and phenols with high efficiency,
respectively.
Transition-metal-catalyzed carbocyclization of the polyun-
saturated system has attracted significant attention.1 In
particular, carbonylative carbocyclization is a powerful
tool to construct ring systems possessing carbonyl func-
tional groups, as represented by carbonylative alkyne-
alkene [2 + 2 + 1] carbocyclization (Pauson-Khand
reaction), which has been widely used in the synthesis of
cyclopentenones.2 Pioneering work by Narasaka and Jeong
demonstrated that rhodium complexes were efficient
catalysts in the Pauson-Khand reaction.3,4 Wender and
co-workers have expanded metal-catalyzed [2 + 2 + 1]
carbocyclization into diene-yne, diene-ene, and diene-
allene systems and observed a remarkable rate-accelerating
effect of the diene moiety.5 Furthermore, Wender and co-
workers in 2002 reported the first Rh(I)-catalyzed intermo-
lecular [5 + 2 + 1] carbocyclization, in which vinylcyclo-
propene provides the five-carbon component.6 Intramolecular
Rh(I)-catalyzed [5 + 2 + 1] cycloaddition of the ene-vinylcy-
clopropane system has been developed recently by Yu and
co-workers, which is an efficient method to construct
bicyclooctenones.7
In contrast to these remarkable developments, the
formation of a six-membered ring through [3 + 2 + 1]
carbonylative carbocyclization has been much less devel-
oped, presumably due to the difficulty of introducing the
required three-carbon component. An obvious source of
a three-carbon component would be cyclopropane. Al-
though cyclopropane has been utilized in metal-catalyzed
carbocyclization reactions, the presence of a neighboring
† Peking University.
‡ Chinese Academy of Sciences.
(1) Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed.;
Wiley-VCH: Weinheim, 2005; Chapter 11, p 215. (Jeong N., Ed.); Chapter
12, p 241 (Robinson J. E., Ed.); Chapter 13, p 263 (Wender, P. A.; Gamber,
G. G.; Williams, T. J., Ed.).
(5) Croatt, M. P.; Wender, P. A. Eur. J. Org. Chem. 2010, 19, and
references cited therein.
(2) For a recent review on the Pauson-Khand reaction, see: Lee, H.-
(6) Wender, P. A.; Gamber, G. G.; Hubbard, R. D.; Zhang, L. J. Am.
Chem. Soc. 2002, 124, 2876.
W.; Kwong, F.-Y. Eur. J. Org. Chem. 2010, 789.
(3) Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998, 249
.
(7) Wang, Y.; Wang, J.; Su, J.; Huang, F.; Jiao, L.; Liang, Y.; Yang,
D.; Zhang, S.; Wender, P. A.; Yu, Z.-X. J. Am. Chem. Soc. 2007, 129,
10060.
(4) (a) Jeong, N. Organometallics 1998, 17, 3642. (b) Jeong, N.; Sung,
B. K.; Choi, Y. K. J. Am. Chem. Soc. 2000, 122, 6771
.
10.1021/ol101091r  2010 American Chemical Society
Published on Web 06/10/2010

double bond is necessary for metal coordination, which
results in the participation of five-carbon component in
the reaction in most cases.1,6-8 Koga and Narasaka have
examined the Rh-catalyzed carbonylative carbocyclization
of the tethered yne-cyclopropane system, in which the
cyclopropane moiety does not bear a neighboring double
bond.9 The cyclopropane did participate in the reaction as a
three-carbon component, giving [3 + 2 + 1] carbocyclization
products. However, the catalytic efficiency is not high,
apparently due to the difficulty of ring-opening of an isolated
cyclopropane moiety under the reaction conditions of Rh(I)
catalysis.
At the outset, nitrogen-tethered ene-cyclopropene
substrate 1a was used to examine the Rh(I)-catalyzed
cycloaddition with CO (Table 1). The Wilkinson catalyst
Table 1. Optimization for Rh(I)-Catalyzed Carbonylative
Cycloadditiona
entry
catalyst (5 mol %)
solvent temp (°C) yieldb (%)
We envisage that cyclopropene, which has a double bond
in the three-membered ring for metal coordination and
has much higher strain energy than cyclopropane or
methylenecyclopropane, will show high reactivity in the
carbocyclization reaction (eq 1).10-12 Indeed, it has been
well documented that ring-opening and/or metallocy-
clobutene formation occurs easily when cyclopropene reacts
with transition metals.13-16 In particular, Pd(II)- or Rh(I)-
catalyzed intermolecular [3 + 2] carbocyclization reactions
of cyclopropenone acetal or cyclopropenone with alkyne have
been reported.16 We communicate herein the Rh(I)-catalyzed
[3 + 2 + 1] carbonylative carbocyclization of ene- and
yne-cyclopropene systems, which provides bicyclohex-
enones and phenols, respectively.
1
2
3
4
5
6
7
8
Rh(PPh3)3Cl
Rh(PPh3)3Cl+AgSbF6
[Rh(COD)Cl]2
[Rh(COD)Cl]2+AgSbF6 DCE
[Rh(CO)2Cl]2 DCE
[Rh(CO)2Cl]2+AgSbF6 DCE
DCE
DCE
DCE
80
80
80
80
80
80
100
130
<5c
<5c
74
42
89
57
58
71
[Rh(CO)2Cl]2
[Rh(CO)2Cl]2
toluene
p-xylene
a Reaction conditions: 1a (50 mg, 0.12 mmol) in 5 mL of solvent.
b Isolated yield. c 1a was recovered.
alone or its combination with AgSbF6 at 80 °C in DCE
afforded only a trace amount of the desired bicyclohex-
enone 2a, with most of the starting material recovered
(entries 1 and 2). To our delight, [Rh(COD)Cl]2 under
the same conditions gave much higher yield (entry 3).
Compound 2a was obtained in 89% yield with
[Rh(CO)2Cl]2 (entry 5). Addition of Ag(I) salt had negative
effects (entries 4 and 6), presumably due to the side
reaction catalyzed by AgSbF6. Reaction in toluene and
p-xylene at high temperature with [Rh(CO)2Cl]2 gave only
moderate yields with recovery of starting materials (entries
7 and 8). The structure of 2a was confirmed by X-ray
crystallographic analysis (Figure 1). It is noteworthy that
2a has a trans configuration for the fused rings.
(8) For selected examples of vinylcyclopropane in metal-catalyzed
carbocyclization, see: (a) Wender, P. A.; Gamber, G. G.; Hubbard, R. D.;
Pham, S. M.; Zhang, L. J. Am. Chem. Soc. 2005, 127, 2836. (b) Wegner,
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L.; Yu, Z.-X. Org. Lett. 2010, 12, 1332. (k) Jiao, L.; Lin, M.; Yu, Z.-X.
Chem. Commun. 2010, 46, 1059. For selected examples of alkylidency-
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T. J.; Loza, R. J. Am. Chem. Soc. 1981, 103, 2404. (i) Padwa, A.; Blacklock,
T. J.; Loza, R. J. Org. Chem. 1982, 47, 3712. Mo-catalyzed reaction: (j)
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Org. Lett., Vol. 12, No. 13, 2010
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in 68% yield. The structure of 2i was confirmed by X-ray
crystallographic analysis (Figure 2).
Figure 1. X-ray structure of 2a.
The generality of this reaction was then examined under
the optimized conditions. As summarized in Scheme 1, the
Figure 2. X-ray structure of 2i.
Scheme 1. Rh(I)-Catalyzed Carbonylative Cycloaddition of 1a-i
Next, we examined the reactions of tethered yne-cyclo-
propene systems under the same reaction conditions. As
shown in Scheme 2, the reaction provides bicyclic phenols
Scheme 2. Rh(I)-Catalyzed Carbonylative Cycloaddition of 3a-g
reaction with a series of ene-cyclopropene substrates 1b-i
provided the expected bicyclohexenone derivatives as
single diastereomers in all cases. The reaction works well
with the oxygen- (1b-d,f) and carbon-tethered substrates
(1h). The substituent on the alkene moiety has an effect
on the yield (1c,d). In the case of 1c, the significant drop
of yield may be attributed to the methyl substituent in
the double bond, impeding the step of alkene insertion in
the reaction mechanism. The stereochemistry of 2c is
confirmed by NOESY experiments, which demonstrates
that the fused two rings also have a trans configuration.
When the two substituents on cyclopropene were alkyl
groups, the reaction was found to proceed much faster as
compared to their phenyl-substituted counterparts (1e-g).
In the case of 1g (cyclopropene is unsymmetrically
substituted), the Rh selectively inserts into the less
substituted C-C bond of cyclopropene, affording 2g as
the only carbocyclization product. When the substrate
bearing a cyclohexenyl moiety was subjected to the
reaction, tricyclic cyclohexenone product 2i was obtained
in moderate to good yields. The reaction gave slightly higher
yield when there was a substituent in the terminal carbon of
alkyne (3b,d,f,g), while a substituent in the propargylic
position (R2) did not significantly affect the yields (3c,d).
Similar to the reaction of ene-cyclopropenes, the reaction
of the substrate 3g, which bears an alkyl-substituted cyclo-
propenyl moiety, proceeded faster compared with its phenyl-
substituted counterpart.
To further expand the scope of this reaction, we investi-
gated the reaction of a tethered allene-cyclopropene system
(eq 2). The allene moiety did participate in the reaction, and
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Org. Lett., Vol. 12, No. 13, 2010

the expected [3 + 2 + 1] carbocyclization product was
obtained in 26% yield, with most of the starting material
recovered.
Scheme 3. Proposed Reaction Mechanism
To gain insight into the mechanism, the Rh(I)-catalyzed
reaction of 1a was carried out in the absence of CO. The
[3 + 2] carbocyclization product 7 was isolated in 28% yield,
together with 8 in 58% yield (eq 3). The structure of bicyclic
product 7 was confirmed by X-ray crystallographic analysis
(Figure 3). Interestingly, the fused bicyclic structure in
product 7 has a cis configuration.
or E′. In the absence of CO as shown in eq 3, G and H are
obtained from F′ through reductive elimination or ꢀ-hydride
elimination/reductive elimination. Since the possible cis-fused
cycloadduct E′ was not observed in the carbonylative reaction
and the reaction in the absence of CO only afforded cis-
fused cycloadduct G, it can be deduced that the carbonylative
carbocyclization follows path a rather than path b. However,
more rigorous study is needed to confirm the mechanism.
In conclusion, we have developed the first Rh(I)-catalyzed
[3 + 2 + 1] carbonylative carbocyclization reactions of ene-
and yne-cyclopropene systems. The results demonstrate that
the highly strained cyclopropene structure can be used as
an excellent three-carbon component in a transition-metal-
catalyzed carbocyclization reaction of polyunsaturated sys-
tems.
Figure 3. X-ray structure of 7.
A mechanistic rationale is proposed in Scheme 3.17
Complexation of the dissociated Rh(I) catalyst with substrate
forms intermediate A. Direct oxidative addition of the Rh(I)
to the σ-bond of the cyclopropene moiety generates rhoda-
cyclobutene intermediate B.13 From intermediate B, there
are two possible pathways: path a and path b. In path a, CO
insertion occurs first to give C, from which insertion of
alkene leads to intermediate D, which undergoes reductive
elimination to provide the final product E. In path b, alkene
insertion occurs first to generate F or F′, followed by CO
insertion and reductive elimination to give final product E
Acknowledgment. The project is supported by the NSFC
(Grant No. 20902005, 20832002, 20772003, 20821062) and
the 973 Program (No. 2009CB825300).
Supporting Information Available: Experimental pro-
cedures, characterization data, 1H and 13C NMR spectra for
all new compounds, and X-ray crystallography data (CIF)
for 2a, 2i, and 7. This material is available free of charge
via the Internet at http://pubs.acs.org.
(17) For mechanistic studies on Rh(I)-catalyzed carbonylative carbocy-
clization, see: (a) 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. (b) Wang,
H.; Sawyer, J. R.; Evans, P. A.; Baik, M.-H. Angew. Chem., Int. Ed. 2008,
47, 342.
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