Gold(I)-catalyzed intramolecular rearrangement of vinylidenecyclopropanes

Article abstract of DOI:10.1021/jo801579b

(Chemical Equation Presented) Vinylidenecyclopropanes 1 can undergo intramolecular rearrangement to give the corresponding functionalized 1,2-dihydronaphthalenes in the presence of gold catalyst under mild conditions. A plausible rearrangement mechanism h

Full text of DOI:10.1021/jo801579b

Gold(I)-Catalyzed Intramolecular Rearrangement of
Vinylidenecyclopropanes
Min Shi,* Lei Wu, and Jian-Mei Lu
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
mshi@mail.sioc.ac.cn
ReceiVed July 17, 2008
Vinylidenecyclopropanes 1 can undergo intramolecular rearrangement to give the corresponding
functionalized 1,2-dihydronaphthalenes in the presence of gold catalyst under mild conditions. A plausible
rearrangement mechanism has been proposed on the basis of control experiments.
Introduction
of vinylidenecyclopropane 1a to give an unexpected naphthalene
derivative 2a via an intramolecular Friedel-Crafts reaction in
the presence of hard Lewis or Brønsted acids, such as Sn(OTf)2
or HOTf, along with the release of a propene molecule.3b We
envisaged that if using gold(I), a most powerful soft Lewis acid,4
as a catalyst, the expected intramolecular rearrangement product
2-isopropylidene-1,1-dimethyl-1,2-dihydronaphthalene 3a might
be obtained under mild conditions. Herein, we wish to report
an interesting Au(I)-catalyzed tandem intramolecular rearrange-
ment of VDCPs 1 in nitromethane or a mixed solvent of
nitromethane and dichloromethane (1:1) that effectively pro-
duces 2-isopropylidene-1,1-dimethyl-1,2-dihydronaphthalene de-
rivatives 3 in good to high yields under mild conditions,
substantially enriching gold chemistry.
Skeleton rearrangements of highly strained small rings with
multiple bonds and functional groups have attracted much
attention from both synthetic and mechanistic viewpoints.
Among these interesting substances, vinylidenecyclopropanes
(VDCPs) are highly strained but readily accessible and stable
molecules that serve as useful building blocks in organic
synthesis.1 Thus far, it has been known that VDCPs can undergo
a variety of ring-opening/cycloaddition reactions upon heating
or photoirradiation as well as in the presence of Lewis acids
because the relief of ring strain can provide a powerful
thermodynamic driving force.2,3 As an interesting example,
recently we have found a novel intramolecular rearrangement
(1) For a recent review on the chemistry of vinylidenecyclopropanes, see:
(a) Maeda, H.; Mizuno, K. J. Synth. Org. Chem. Jpn. 2004, 62, 1014–1025. (b)
Isagawa, K.; Mizuno, K.; Sugita, H.; Otsuji, Y. J. Chem. Soc., Perkin Trans. 1
1991, 2283–2285, and references therein. (c) Al-Dulayymi, J. R.; Baird, M. S.
J. Chem. Soc., Perkin Trans. 1 1994, 1547–1548.
(2) (a) Maeda, H.; Hirai, T.; Sugimoto, A.; Mizuno, K. J. Org. Chem. 2003,
68, 7700–7706. (b) Pasto, D. J.; Brophy, J. E. J. Org. Chem. 1991, 56, 4554–
4556. (c) Sugita, H.; Mizuno, K.; Saito, T.; Isagawa, K.; Otsuji, Y. Tetrahedron
Lett. 1992, 33, 2539–2542. (d) Mizuno, K.; Sugita, H.; Kamada, T.; Otsuji, Y.
Chem. Lett. 1994, 449–452, and references therein. (e) Stepakov, A. V.; Larina,
A. G.; Molchanov, A. P.; Stepakova, L. V.; Starova, G. L.; Kostikov, R. R.
Russ. J. Org. Chem. 2007, 43, 41–49. (f) Poutsma, M. L.; Ibarbia, P. A. J. Am.
Chem. Soc. 1971, 93, 440–450. (g) Hendrick, M. E.; Hardie, J. A.; Jones, M. J.
Org. Chem. 1971, 36, 3061–3062.
(3) (a) Xu, G.-C.; Liu, L.-P.; Lu, J.-M.; Shi, M. J. Am. Chem. Soc. 2005,
127, 14552–14553. (b) Xu, G.-C.; Ma, M.; Liu, L.-P.; Shi, M. Synlett 2005,
1869–1872. (c) Zhang, Y.-P.; Lu, J.-M.; Xu, G.-C.; Shi, M. J. Org. Chem. 2007,
72, 509–516. (d) Lu, J.-M.; Shi, M. Org. Lett. 2007, 9, 1805–1808. (e) Lu, J.-
M.; Shi, M. Org. Lett. 2006, 8, 5317–5320. (f) Lu, J.-M.; Shi, M. Tetrahedron
2007, 63, 7545–7549. (g) Fitjer, L. Angew. Chem., Int. Ed. Engl. 1975, 14, 360–
361.
Results and Discussion
Initial examinations using diphenylvinylidenecyclopropane
(1a, 0.2 mmol) having four methyl groups at the 1- and
2-position of the cyclopropane as the substrate in the presence
of Ph3PAuCl (0.01-0.02 mmol, 0.05-0.10 equiv) and AgOTf
(0.01-0.02 mmol, 0.05-0.10 equiv) in dichloromethane (DCM,
2.0 mL) were aimed at determining the best conditions for this
(4) (a) Hashmi, A. S. K. Chem. ReV. 2007, 107, 3183. (b) Jime´mez-Nu´n˜ez,
E.; Echavarren, A. M. Chem. Commun. 2007, 333. (c) Fu¨rster, A.; Davies, P. W.
Angew. Chem., Int. Ed. 2007, 46, 3410. (d) Gorin, D. J.; Toste, F. D. Nature
2007, 446, 395. (e) Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46,
2750. (f) Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200. (g)
Hoffmann-Ro¨der, A.; Krause, N. Org. Biomol. Chem. 2005, 3, 387. (h) Arcadi,
A.; Di Giuseppe, S. Curr. Org. Chem. 2004, 8, 795. (i) Echavarren, A. M.;
Nevado, C. Chem. Soc. ReV. 2004, 33, 431.
8344 J. Org. Chem. 2008, 73, 8344–8347
10.1021/jo801579b CCC: $40.75 2008 American Chemical Society
Published on Web 10/09/2008

Gold(I)-Catalyzed Rearrangement of Vinylidenecyclopropanes
TABLE 1. Optimization of the Reaction Conditions
TABLE 2. Optimization of the Reaction Conditions with Different
Silver Salts and Phosphine Ligands
Au cat
(mol %)
AgX
(mol %)
temp
(°C)
yield
(%)b
entrya
solvent
MeNO2
1
2
3
4
5
6
7
8
9
Ph3PAuCl (10) AgOTf (10) rt
81
91
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
MeNO2
Ph3PAuCl (2)
Ph3PAuCl (5)
Ph3PAuCl (5)
Ph3PAuCl (5)
Ph3PAuCl (5)
Ph3PAuCl (5)
AgOTf (2)
AgOAc (5) rt
AgSbF6 (5) rt
AgBF4 (5)
AgOTf (5)
AgOTf (5)
rt
no reaction
87
Ph3PAuCl
(mol %)
AgOTf
(mol %)
temp
(°C)
yield
(%)b
entrya
solvent
CH2Cl2
CH2Cl2
CH2Cl2
C6H5Me
MeNO2
MeCN
THF
DMSO
DMF
ClCH2CH2Cl
Cl2CHCHCl2
MeOH
rt
complexd
10 77
-5 87
rt
rt
1
2
3
4
5
6
7
8
10
5
5
5
5
5
5
5
5
5
5
5
10
5
5
5
5
5
5
5
5
5
5
5
-15
-15
rt
rt
rt
rt
rt
rt
rt
62
64
80
Me3PAuCl (5) AgOTf (5)
89
78
(dppb)Au2Cl2
AgOTf (5)
complex
92
(2.5)c
10 MeNO2
11 MeNO2
12 MeNO2/
(2-furyl)3PAuCl AgOTf (5)
rt
rt
rt
85
trace
82
no reaction
trace
trace
trace
69
none
AgOTf (5)
AgOTf (5)
Ph3PAuCl (5)
CH2Cl2 (1/1)
13 MeNO2/
CH2Cl2 (3/1)
9
Ph3PAuCl (5)
AgOTf (5)
rt
79
10
11
12
rt
rt
rt
63
NRc
a 1a (0.2 mmol) in 2.0 mL of solvent. b Isolated yield. c dppb )
1,4-bis(diphenylphosphino)butane. d Many unidentified products were
formed.
a The reactions were conducted with 1a (0.2 mmol) in 2.0 mL of
solvent. b Isolated yield. c No reaction.
or in the presence of AgOTf, traces of 3a were formed (Table
2, entry 11). It should be noted that a mixed solvent of
nitromethane and dichloromethane (1:1) is also suitable for this
transformation (Table 2, entries 12 and 13). Therefore, the best
reaction conditions are to carry out the reaction in nitromethane
or a mixed solvent of nitromethane and dichloromethane (1:1)
at room temperature using Au(I) (5 mol %) generated from
Ph3PAuCl (5 mol %) and AgOTf (5 mol %) as a catalyst.
Although the yield of 3a showed a little difference with 5 or 2
mol % of Au(I) catalyst, the reaction proceeded more smoothly
and cleanly if using 5 mol % of Au(I) complex as the catalyst
on the basis of the analysis with TLC plates.
With these optimal reaction conditions identified, we next
carried out this interesting 1,2-dihydronaphthalene-forming
reaction using a variety of starting materials 1. The results of
these experiments are summarized in Table 3. As can be seen
from Table 3, the corresponding 1,2-dihydronaphthalene deriva-
tives 3 were obtained in 80-99% yields in a mixed solvent of
nitromethane and dichloromethane (1:1) or nitromethane (Table
3, entries 1-8 and entries 9-11). In some cases, for example,
VDCPs 1b and 1e, 1,2-dihydronaphthalene derivatives 3 were
obtained in slightly higher yields in nitromethane (Table 3,
entries 1 and 9, 4 and 11). Substituents on the aromatic rings
of 1 have significant influence on the yields of 3 as well as the
product distribution for unsymmetrical diarylvinylidenecyclo-
propanes 1. As for VDCPs 1d, and 1f-h bearing electron-
donating groups on the aromatic ring, the corresponding 1,2-
dihydronaphthalene derivatives 3 were obtained in lower yields
(Table 3, entries 3, 5-7, and 10). It should be noted that, in
the case of 1h, compound 3h′ was obtained as the major product
(3h/3h′ ) 1:6; Table 3, entry 7). In addition, using unsym-
metrical diarylvinylidenecyclopropane 1e bearing a moderately
electron-withdrawing group (Cl atom) on the benzene ring as
the substrate, two isomers 3e and 3e′ were obtained in 90 and
91% yields in nitromethane or nitromethane and dichlo-
intramolecular tandem Friedel-Crafts reaction, and the results
of these experiments are summarized in Table 1. We found that,
using Ph3PAuCl (10 mol %) and AgOTf (10 mol %) as the
catalysts, 2-isopropylidene-1,1-dimethyl-1,2-dihydronaphthalene
3a was formed in 62% yield at -15 °C rather than 2a (Table
1, entry 1). In the presence of Ph3PAuCl (5 mol %) and AgOTf
(5 mol %) at room temperature (20 °C) or at -15 °C, 3a was
obtained in 80 and 64% yields, respectively (Table 1, entries 2
and 3). In toluene, complex product mixtures were formed under
identical conditions (Table 1, entry 4 as complex). In ni-
tromethane, 3a was obtained in 92% yield (Table 1, entry 5).
Using acetonitrile (CH3CN), tetrahydrofuran (THF), DMSO, or
DMF as the solvent, either traces of 3a were formed or no
reactions occurred under the standard conditions (Table 1, entries
6-9). Using other halogenated solvents such as 1,2-dichloro-
ethane (DCE) and 1,1,2,2-tetrachloroethane afforded 3a in 69
and 63% yields, respectively (Table 1, entries 10 and 11). It
should be noted that no reaction occurred if using methanol as
a solvent, presumably due to the fact that the coordination of
the oxygen atom in CH3OH with a Au atom makes the Au
complex lose catalytic ability in this reaction (Table 1, entry
12).
Next, we further optimized the reaction conditions in ni-
tromethane with different silver salts and phosphine ligands,
and the results of these experiments are summarized in Table
2. As can be seen, increasing and decreasing the employed
amount of Ph3PAuCl and AgOTf did not improve the yields of
3a (Table 2, entries 1 and 2). Using AgOAc or AgBF4 to replace
AgOTf, either no reaction occurred or complex product mixtures
were obtained under identical conditions (Table 2, entries 3 and
5). With AgSbF6 instead of AgOTf, 3a was obtained in 87%
yield under the standard conditions (Table 2, entry 4). Changing
the reaction temperature and the phosphine ligands did not
significantly improve the yields of 3a (Table 2, entries 6-10).
The control experiment indicated that, without Au(I) catalyst
J. Org. Chem. Vol. 73, No. 21, 2008 8345

Shi et al.
SCHEME 1. Au(I)-Catalyzed Rearrangement of 1 under
TABLE 3. Au(I)-Catalyzed Rearrangement of 1 under These
Optimized Reaction Conditions
These Optimized Reaction Conditions
yield (%)b
3+3′+3′′
entrya R1
R2
R3
H
solvent
1b MeNO2/
CH2Cl2 (1/1)
1
F
F
3b, 91
2
3
4
5
6
Cl
Cl
H
H
H
H
1c
1d
1e
1f
3c, 99
3d, 80
Me Me
H
H
H
Cl
Me
Me
3e+3e′, 90 (2:1)c
3f+3f′, 80 (1:1)c
3g+3g′+3g′′,
85 (1.4:1.4:1)d
3h+3h′, 86 (1:6)c
3i+3i′+3i′′,
93 (6.5:2:1)d
3b, 94
Me 1g
SCHEME 2. Au(I)-Catalyzed Rearrangement of 1 under
These Optimized Reaction Conditions
7
8
H
H
OMe
F
H
F
1h
1i
9
10
11
F
F
H
H
H
1b MeNO2
1d
1e
Me Me
Cl
3d, 86
H
3e+3e′, 91 (2:1)c
a The reactions were conducted with 1 (0.2 mmol) in 2.0 mL of
mixed solvent of nitromethane/CH2Cl2 (1/1) or nitromethane in the
presence of Ph3PAuCl (5 mol %) and AgOTf (5 mol %). b Isolated
yield. c On the basis of 1H NMR spectroscopic data. d Determined
tentatively on the basis of GLC analysis.
romethane (1:1) with 3e as the major isomers, respectively,
suggesting that the intramolecular Friedel-Crafts reaction
preferentially takes place on the electron-rich aromatic ring
(Table 3, entries 4 and 11).5 As for unsymmetrical diarylvi-
nylidenecyclopropane 1g bearing two moderately electron-
donating groups (methyl group) on one benzene ring as the
substrate, three isomers 3g, 3g′, and 3g′′ were obtained in 85%
total yield (Table 3, entry 6). Similarly, in the case of
diarylvinylidenecyclopropane 1i having two electron-withdraw-
ing groups (F atom) on one benzene ring as the substrate, three
isomers 3i, 3i′, and 3i′′ were obtained in 93% total yield (Table
3, entry 8).
Moreover, as for monoaromatic group substituted VDCPs 1j,
1k, and 1l, the corresponding 1,2-dihydronaphthalene derivatives
3j, 3k, and 3l were obtained in 60, 67, and 80% yields,
indicating that the Au(I)-catalyzed rearrangement is also suitable
for vinylidenecyclopropanene having one aromatic group (Scheme
1). As for VDCP 1m having a strongly electron-donating
methoxy group at the meta-position of the benzene ring, the
corresponding products 3m′ and 3m′′ were obtained in 62 and
7% yield, respectively, suggesting that the substituents on the
benzene ring act in an inductive way to stabilize the intermedi-
ates (Scheme 1).
The control experiment shown in Scheme 2 indicated that,
in the presence of Na2CO3 (20 mol %), 3a was also formed in
44% yield along with 70% conversion under otherwise identical
conditions. In addition, adding 20 mol % of 2,4,6-tri-tert-
butylpyridine (TTBP) into the reaction afforded 3a in 15% yield
with 30% conversion. Moreover, using the Brønsted acid HOTf
as a catalyst, complex product mixtures were obtained (Scheme
2). These results suggest that Au(I) itself catalyzes this reaction
rather than the Brønsted acid HOTf.
On the basis of the above results, a plausible reaction
mechanism for the formation of 3 is outlined in Scheme 3 using
1a as a model. The corresponding cyclopropyl ring-opened
zwitterionic intermediate B or the resonance-stabilized zwitte-
rionic intermediate C is formed from the initial zwitterionic
intermediate A. Intramolecular Friedel-Crafts reaction with the
adjacent aromatic group takes place to produce zwitterionic
intermediate D, which affords the corresponding intermediate
E via deprotonation. Subsequent protonation of intermediate E
produces the corresponding 1,2-dihydronaphthalene derivative
3a along with the release of Au(I) catalyst to initiate the next
catalytic cycle. When VDCPs 1 bear electron-donating groups
on the aromatic ring, the key intermediate D is quite stable,
which can provide some other byproducts through further
(5) (a) Fleming, I. Chemtracts: Org. Chem. 2001, 14, 405–406. (b)
Kozikowski, A. P.; Ames, A. J. Am. Chem. Soc. 1980, 102, 860. (c) Hoffmann,
H. M. R.; Tsushima, T. J. Am. Chem. Soc. 1977, 99, 6008. (d) Snider, B.; Jackson,
A. J. Org. Chem. 1982, 47, 5393.
8346 J. Org. Chem. Vol. 73, No. 21, 2008

Gold(I)-Catalyzed Rearrangement of Vinylidenecyclopropanes
SCHEME 3. Plausible Mechanism for the Formation of 3
and 2-position of the cyclopropane undergo an interesting
intramolecular rearrangement to provide functionalized 1,2-
dihydronaphthalene derivatives in the presence of gold(I)
catalyst through intramolecular Friedel-Crafts reaction under
mild conditions. A plausible reaction mechanism has been
proposed that is based on the control experiments. Further
studies regarding the mechanistic details and scope of this
process are in progress.
Experimental Section
1
General Remarks. H NMR spectra were recorded on a 300
MHz spectrometer in CDCl3 using tetramethylsilane as the internal
standard. Infrared spectra were measured on a spectrometer. Mass
spectra were recorded by EI method, and HRMS was measured on
Kratos Analytical Concept mass spectrometer (EI or MALDI).
Satisfactory CHN microanalyses were obtained with an analyzer.
Melting points are uncorrected. All reactions were monitored by
TLC with silica gel coated plates. Flash column chromatography
was carried out using 300-400 mesh silica gel at increased pressure.
SCHEME 4. Au(I)-Catalyzed Rearrangement of 4a, 6a, and
6b under the Optimized Reaction Conditions
General Reaction Procedure for the Rearrangement of
Diarylvinylidenecyclopropanes. To a solution of diarylvinylidenecy-
clopropane 1 (0.2 mmol) and Ph3PAuCl (5 mg, 0.01 mmol) in a
mixed solvent of dichloromethane and nitromethane (2.0 mL, 1:1)
was added AgOTf (8 mg, 0.01 mmol), and the reaction mixture
was stirred for 10 min at room temperature (monitored by TLC).
After the starting materials (diarylvinylidenecyclopropanes 1) were
consumed, the solvent was removed under reduced pressure and
the residue was subjected to a flash column chromatography to give
the desired product 3 as a colorless liquid.
Compound 3a: A colorless liquid; IR (CH2Cl2) ν 3059, 2961,
2924, 2860, 1600, 1493, 1469, 1443, 1378, 1355, 779, 755, 699,
1
682, 594, 570, 451 cm-1; H NMR (300 MHz, CDCl3, TMS) δ
1.06 (3H, s, CH3), 1.30 (6H, s, 2CH3), 1.72 (3H, s, CH3), 5.82
(1H, s, CH), 7.18-7.28 (3H, m, Ar), 7.34-7.44 (6H, m, Ar); 13C
NMR (75 MHz, CDCl3, TMS) δ 20.0, 24.3, 25.9, 50.4, 116.8, 119.8,
121.4, 124.7, 126.35, 126.44, 128.2, 129.0, 136.0, 136.6, 137.8,
143.0, 151.1, 153.4; MS (EI) m/z (%) 274 (M+, 96), 259 (100),
244 (27), 229 (37), 215 (19), 202 (12); HRMS (EI) calcd for
C21H22O 274.1722, found 274.1721.
transformation, such as inter- or intramolecular Friedel-Crafts-
type reaction. Therefore, the corresponding functionalized 1,2-
dihydronaphthalenes 3 were formed in lower yields.
It should be noted that when using VDCPs 4a, 6a, and 6b as
the substrates under these optimized conditions, the correspond-
ing naphthalene derivative 5a and indene derivatives 7a and
7b were obtained in moderate to good yields, which are the
same as those of the reaction products catalyzed by hard Lewis
or Brønsted acid such as Sn(OTf)2, Ln(OTf)n (n ) 2 or 3), or
HOTf from intermediate C (Scheme 4).3a-c This is because that,
in the cases of VDCPs 4a, 6a, and 6b, they are impossible to
release a propene molecule as that of VDCP 1a even in the
presence of hard Lewis or Brønsted acid,3b and the reactions
proceed through the same pathway as that catalyzed by Au(I)
to provide the same reaction products.
Acknowledgment. We thank the Shanghai Municipal Com-
mittee of Science and Technology (04JC14083, 06XD14005),
National Basic Research Program of China (973)-2009CB825300,
and the National Natural Science Foundation of China for
financial support (20472096, 203900502, 20672127, and
20732008).
Supporting Information Available: Spectroscopic data of
all new compounds and the detailed descriptions of experimental
procedures. This material is available free of charge via the
Internet at http://pubs.acs.org.
In conclusion, we have found an interesting procedure where
vinylidenecyclopropanes having four methyl groups at the 1-
JO801579B
J. Org. Chem. Vol. 73, No. 21, 2008 8347