Oxidative isomerization of vinylidenecyclopropanes to dimethylenecyclopropanes and Bronsted acid-catalyzed further transformation

Article abstract of DOI:10.1002/ejoc.201001484

Oxidative isomerization of vinylidenecyclopropanes 1 produces dimethylenecyclopropane aldehydes 2 in moderate to good yields using tetrapropylammonium perruthenate (TPAP)/4-methylmorpholine N-oxide (NMO) as a catalytic system and the obtained dimethylenecyclopropanes 3 can be transformed to indene derivatives smoothly in the presence of Bronsted acid (HOTf). The scope and limitations as well as the plausible mechanisms have been discussed. Oxidative isomerization of vinylidenecyclopropanes to dimethylenecyclopropanesusing TPAP/NMO as a catalytic systemand the further transformation to indene derivatives in the presence of Bronsted acid. Copyright

Full text of DOI:10.1002/ejoc.201001484

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201001484
Oxidative Isomerization of Vinylidenecyclopropanes to
Dimethylenecyclopropanes and Brønsted Acid-Catalyzed Further
Transformation
Bei-Li Lu[a] and Min Shi*[a]
Keywords: Small ring systems / Ring expansion / Isomerization / Rearrangement / Oxidation
Oxidative isomerization of vinylidenecyclopropanes 1 pro-
duces dimethylenecyclopropane aldehydes 2 in moderate to
good yields using tetrapropylammonium perruthenate
(TPAP)/4-methylmorpholine N-oxide (NMO) as a catalytic
system and the obtained dimethylenecyclopropanes 3 can be
transformed to indene derivatives smoothly in the presence
of Brønsted acid (HOTf). The scope and limitations as well
as the plausible mechanisms have been discussed.
Oxidation reactions belong to the most important syn- cyclopropyl alcohol A[11] with two geminal methyl groups
thetic tools in organic chemistry and have achieved great (or other alkyl groups) on the cyclopropane could be
progress since the last century.[1] Numerous new oxidative smoothly oxidized to the corresponding vinylidenecyclopro-
reagents, such as activated dimethyl sulfoxide reagents,[2] pyl aldehyde B; see Equation (1). However, to our surprise,
hypervalent iodine compounds[3] and state-of-art transition using VDCP 1a having two geminal aromatic groups on the
metal oxidants,[4] have been created for oxidation. tetrapro- cyclopropane resulted in the formation of dimethylene-
pylammonium perruthenate (TPAP)/4-methylmorpholine cyclopropane aldehyde 2a under identical conditions as
N-oxide (NMO) reagent has been widely used in oxidation shown in Equation (2).
as a readily soluble, air stable and efficient oxidant since its
first report in 1987.[5] Vinylidenecyclopropanes (VDCPs)
are highly strained substances that serve as extremely versa-
tile building blocks in many organic reactions. Due to the
unique structural and electronic properties of VDCPs, a
wide variety of transformations have been disclosed.[6] For
example, the catalytic ring-opening/cycloaddition of
(1)
VDCPs for the formation of carbocyclic or heterocyclic
compounds[7] and intramolecular rearrangement reactions
of VDCPs[8] have been successfully developed. However, the
reports of isomerization of VDCPs to dimethylenecyclo-
propanes under mild conditions are rare. Most of them took
place upon heating at high temperature (130–360 °C)[9a–9f]
and only one procedure using ZnI2 as the catalyst has been
published.[9g] Herein, we describe the first example of an
oxidative isomerization of VDCPs to dimethylenecyclo-
(2)
propanes using tetrapropylammonium perruthenate
Our initial attempts to oxidize 1a failed to give any clean
(TPAP)/4-methylmorpholine N-oxide (NMO) as an efficient
products with various oxidants (Table 1, entries 1–5). Treat-
catalytic system under mild conditions.
ment of 1a with Dess–Martin periodinane afforded dimeth-
During our ongoing investigation on the intramolecular
ylenecyclopropane aldehyde 2a in 37% yield along with a
rearrangement of VDCPs in the catalysis of gold(I) com-
1:1 geometrical isomeric ratio (entry 6). A further improve-
plex and Brønsted acid,[10] we found that vinylidene-
ment was observed by using TPAP/NMO as oxidants, fur-
nishing 2a in 56% yield along with a 3:1 geometrical iso-
[a] State Key Laboratory of Organometallic Chemistry, Shanghai
meric ratio from –78 °C to room temperature (20 °C) (entry
Institute of Organic Chemistry, Chinese Academy of Sciences,
7). The examination of solvent effects revealed that chloro-
form (CHCl3) is the best solvent in this oxidative isomeriza-
tion reaction, affording 2a in 70% yield along with a 5:1 Z/
E ratio (entries 8–11).
354 Fenglin Road, Shanghai 200032 China
Fax: +86-21-64166128
E-mail: Mshi@mail.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001484.
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B.-L. Lu, M. Shi
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Table 1. Optimization of the reaction conditions for the oxidative isomerization of VDCP 1a.
[a] All reactions were carried out with 1a (0.1 mmol) in various oxidants and solvents (1.0 mL) at –78 °C to room temp./room temp. [b]
Isolated yields. [c] 50 mg) was added.
Further investigation revealed that this oxidative isomeri- high Z/E ratios in a mixed solvent [CHCl3 to CH2Cl2 (4:1)]
zation is general for a variety of VDCPs 1 as described in whatever R1 is a cyclic or non-cyclic substituents (Table 2,
Table 2. As for VDCPs 1b–1g or 1j in which R2 = H or Me, entries 1–6 and 9). Using VDCPs 1h and 1i having electron-
the reactions could not complete within 24 h and no further poor aromatic groups as the substrates, the reactions pro-
improvement was realized even increasing the reaction tem- ceeded smoothly to give the desired products 2h and 2i in
perature or prolonging the reaction time if using CHCl3 72% yield and 69% yield, respectively, as Z- and E-isomeric
as the solvent. Upon further optimization of the reaction mixtures in CHCl3 (entries 7 and 8). We also examined the
conditions, we found that for these substrates, the corre- substrate in which R2 = MeO, but it was found that the
sponding oxidative isomerization products 2b–2g or 2j corresponding product is too liable to be isolated as a pure
could be obtained in moderate to good yields along with form. As for the vinylidenecyclopropane in which R2
=
Table 2. Oxidative isomerization of VDCPs 1 under the optimal conditions.
[a] All reactions were carried out with 1 (0.2 mmol), TPAP (10 mol-%), Mol. sieves (4 Å, 100 mg) and NMO (1.5 equiv.) in different
solvents (2.0 mL) at –78 °C to room temp. [b] Isolated yields.
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Oxidative Isomerization of Vinylidenecyclopropanes
NO2 and the vinylidenecyclopropane in which R1 = Ph, R3 are aromatic or heteroaromatic groups (entries 1–16 and
these compounds are difficult to be prepared using our 19). It should be noted that this reaction was also suitable
present synthetic method shown in the Supporting Infor- for the substrates 3r and 3s containing aliphatic substitu-
mation.
ents, producing the corresponding indene derivatives 4r and
The respective dimethylenecyclopropane aldehydes 2 can 4s in 76% and 73% yields, respectively (entries 17 and 18).
be used to react with a wide range of Grignard reagents, The reason for the lower chemical yields of substrates 3r–
providing dimethylenecyclopropanes 3 in moderate to good 3t may be attributed to the aliphatic groups and the elec-
yields along with 2:1 to 26:1 Z/E ratios (Scheme 1, for the tron-rich thiophene group of R3 in their structures. Using
details please see the Supporting Information). The major substrates 3r and 3s in which R3 are aliphatic groups, the
isomers of 3 have been determined as Z-configurations by release of one water molecule to give a cationic intermediate
X-ray diffraction analysis of 3a (Figure 1).[12]
would be more difficult than these substrates in which R3
are aromatic groups. When R3 is an electron-rich thiophene
group, there might be some side reactions to take place un-
der acidic conditions, affording some unidentified byprod-
ucts.
Scheme 1. Synthesis of dimethylenecyclopropanes 3.
Figure 2. ORTEP drawing of 4a.
Table 3. Optimization of the reaction conditions for the Brønsted
acid-catalyzed intramolecular rearrangement of dimethylenecyclo-
propane 3a.
Figure 1. ORTEP drawing of 3a.
Dimethylenecyclopropane 3a could undergo an interest-
ing intramolecular rearrangement in the presence of tri-
fluoromethanesulfonic acid (TfOH) (10 mol-%) at room
temperature (20 °C) to afford indene derivative 4a in good
yield as a single stereoisomer. The E-configuration of 4a
was unambiguously determined by X-ray diffraction analy-
sis (Figure 2).[13] Solvent screening indicated that toluene is
the optimal media for this reaction, giving 4a in 88% yield
(Table 3, entries 1–5). We next examined the substrate scope
of this intramolecular rearrangement reaction using a vari-
ety of dimethylenecyclopropanes 3. The results are summa-
rized in Table 4. As can be seen from Table 4, the corre-
[a] All reactions were carried out with 3a (0.1 mmol) in the presence
of HOTf (10 mol-%) in various solvents (1.0 mL) at room temp.
sponding products 4 were obtained in good yields whether for 6 h. [b] Isolated yields.
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B.-L. Lu, M. Shi
SHORT COMMUNICATION
Table 4. Brønsted acid-catalyzed intramolecular rearrangement of
dimethylenecyclopropanes 3 under the optimal conditions.
Plausible mechanisms for the formation of dimethyl-
enecyclopropane aldehydes 2 and indene derivatives 4 are
outlined in Scheme 2. In the oxidative isomerization pro-
cess, primary alcohol 1 reacts very rapidly with the tetra-
hedral perruthenate ion [RuVIIO4]–[14] to give an alkoxyper-
ruthenate ion A. After a quick hydrogen migration, the
cyclopropane ring opening of intermediate B takes place,
leading to the formation of intermediate C (C1 and C2),
which undergoes recyclization to afford dimethylenecyclo-
propane aldehyde 2 along with regeneration of ruthenate(V)
species. It is plausible that the C4–C5 double bond in inter-
mediate C1 interacts with the sterically large R1 group, so
the intermediate C2 is more stable than intermediate C1.
Therefore, intermediate C1 is assumed to be transformed
into C2 during the reaction, leading to the formation of the
major isomer Z-2. The electronic effect of the substitutes
on the aromatic groups may also have an influence on the
Z/E geometric selectivity. In the catalysis of Brønsted acid
HOTf, dimethylenecyclopropanes 3 is first protonated at
the hydroxy group along with the release of one molecule
of water to give a cationic intermediate I and a resonance-
stabilized intermediate II. Subsequent ring-opening of
cyclopropane forms intermediate III, which undergoes in-
tramolecular Friedel–Crafts reaction with the adjacent aro-
matic ring accompanied with a deprotonation to give in-
dene derivative 4.
In conclusion, we have developed a novel oxidative isom-
erization of vinylidenecyclopropanes 1 to dimethylenecyclo-
propane aldehydes 2 using TPAP/NMO as a catalytic sys-
tem. The further transformation of these interesting di-
[a] All reactions were carried out with 3 (0.1 mmol) in the presence
of HOTf (10 mol-%) in toluene (1.0 mL) at room temp. for 6 h. [b]
Isolated yields.
Scheme 2. Plausible reaction mechanisms.
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Oxidative Isomerization of Vinylidenecyclopropanes
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[2]
[3]
Experimental Section
General Procedure for the Oxidative Isomerization of VDCPs 1a:
Under an argon atmosphere, vinylidenecyclopropane 1a (0.2 mmol)
in CHCl3 (2.0 mL) was added into a Schlenk tube containing NMO
(0.3 mmol) and powered 4-Å molecular sieves (100 mg). The mix-
ture was stirred at room temp. for 10 min then cooled to –78 °C.
Solid TPAP (0.01 mmol) was added in one portion to the stirred
mixture then warmed up to room temp. slowly. On completion the
reaction mixture was filtered through a short pad of silica, eluting
with CH2Cl2. The solvent was removed under reduced pressure and
the residue was purified by a flash column chromatography (the
silica gel was impregnated with triethylamine before use, eluent:
EtOAc/PE = 1:30). Compound 2a was isolated as a yellow oil in
70% yield along with a 5:1 E/Z ratio.
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General Procedure for the Preparation of 3a: Under an argon atmo-
sphere, the aldehyde 2a (0.1 mmol) was dissolved in THF (2.0 mL)
and added into a Schlenk tube. A solution of PhMgBr in THF
(0.12 mL, 9.0 m in THF, 0.15 mmol) was added dropwise to the
above Schlenk tube at 0 °C then warmed up to room temp. After
being stirred for 2.0 h at room temp. the reaction was over as moni-
tored by TLC, the mixture was quenched with a saturated ammo-
nium chloride solution and extracted with diethyl ether
(10.0 mLϫ3). The combined organic layer was dried with anhy-
drous Na2SO4. The solvent was removed under reduced pressure
and the residue was purified by a flash column chromatography
(silica gel, eluent: EtOAc/PE = 1:10). Compound 3a was isolated
as a yellow oil in 87% yield.
General Procedure for the Brønsted Acid-Catalyzed Rearrangement
Reaction of Dimethylenecyclopropane 3a: Under an argon atmo-
sphere, product 3a (0.1 mmol), HOTf (0.01 mmol) and toluene
(1.0 mL) were added into a Schlenk tube. The reaction mixture was
stirred at room temp. until the reaction completed. Then, the sol-
vent was removed under reduced pressure and the residue was puri-
fied by a flash column chromatography (silica gel, eluent: EtOAc/
PE = 1:50). Compound 4a was isolated as a yellow oil in 88% yield.
[7]
[8]
Supporting Information (see also the footnote on the first page of
this article): Experimental procedures, compound characterization
data and X-ray crystal data.
Acknowledgments
We thank the Shanghai Municipal Committee of Science and Tech-
nology (08dj1400100-2), National Basic Research Program of
China (973)-2009CB825300, and the National Natural Science
Foundation of China for financial support (20902019, 20872162,
20672127, 20821002, 20732008, 20772030 and 20702059).
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B.-L. Lu, M. Shi
SHORT COMMUNICATION
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graphic data for this paper. These data can be obtained free of
Published Online: December 10, 2010
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