Diels-Alder reactions for the construction of cyclopropylarenes

Article abstract of DOI:10.1002/ejoc.201200105

The straightforward synthesis of new bicyclopropyl-substituted alkynes and 1,3-dienes and their application in cobalt-catalyzed Diels-Alder reactions are described. The cycloaddition processes generated the desired bicyclopropyl-substituted arene derivatives in moderate to good yields, depending on the steric congestion of the reaction partners. The regioselectivity of the cycloaddition was controlled by the ligand coordinated to the cobalt center. The cyclopropyl moiety remained unchanged over the course of the Diels-Alder reaction, indicating that no radical type intermediates were formed. Only in a single case did the DDQ oxidation of the primarily formed dihydroaromatic product lead to ring opening of a cyclopropyl subunit. In all of the other cases, cyclopropyl-modified arenes with various functionalities were obtained. Copyright

Full text of DOI:10.1002/ejoc.201200105

Job/Unit: O20105
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FULL PAPER
DOI: 10.1002/ejoc.201200105
Diels–Alder Reactions for the Construction of Cyclopropylarenes[‡]
Marion Arndt,[a] Gerhard Hilt,*[a] Alexander F. Khlebnikov,[b] Sergei I. Kozhushkov,[c] and
Armin de Meijere*[c]
Keywords: Cycloaddition / Arenes / Small ring systems / Cobalt / Dehydrogenation
The straightforward synthesis of new bicyclopropyl-substi-
tuted alkynes and 1,3-dienes and their application in cobalt-
catalyzed Diels–Alder reactions are described. The cycload-
dition processes generated the desired bicyclopropyl-substi-
tuted arene derivatives in moderate to good yields, de-
pending on the steric congestion of the reaction partners. The
regioselectivity of the cycloaddition was controlled by the li-
gand coordinated to the cobalt center. The cyclopropyl moi-
ety remained unchanged over the course of the Diels–Alder
reaction, indicating that no radical type intermediates were
formed. Only in a single case did the DDQ oxidation of the
primarily formed dihydroaromatic product lead to ring open-
ing of a cyclopropyl subunit. In all of the other cases, cy-
clopropyl-modified arenes with various functionalities were
obtained.
dienes with subsequent dehydrogenation. In addition, the
incorporation of cyclopropyl-substituted starting materials
was conceived as a good test to exclude radical-type inter-
mediates in the mechanism for the cobalt-catalyzed Diels–
Alder reaction. Accordingly, we were highly interested to
see if the cyclopropyl moiety would stay intact over the
course of the cobalt-catalyzed cycloaddition and subse-
quent oxidation of the dihydroaromatic intermediates by
DDQ (2,3-dichloro-5,6-dicyano-1,4-quinone). An electron
transfer from the low-valent cobalt catalyst center to the
starting materials coordinated to the cobalt could result in
a radical opening the cyclopropyl group. Our first results
along these lines are reported herein.
Introduction
In their ongoing search for biologically active com-
pounds, research laboratories in the pharmaceutical as well
as the agrochemical industry always consider the cy-
clopropyl substituent which, because of its peculiar steric
and electronic properties,[1] frequently enhances desired fea-
tures.[2] In a considerable number of such compounds, the
cyclopropyl group is attached to an arene moiety, and in
recent years, even cyclopropyl-substituted cyclopropyl
groups, that is, 1- and 2-substituted bicyclopropyl substitu-
ents attached to arenes, have come into the focus of the
search for active compounds.[3] In view of the joint expertise
of our two research groups in the areas of catalyzed Diels–
Alder reactions[4] and the syntheses of simple cyclopropyl-
group containing building blocks for organic synthesis,[5] we
set out to test the possibilities of preparing cyclopropyl-
and bicyclopropyl-substituted arenes by [4+2] cycload-
ditions of appropriately substituted alkynes and buta-1,3-
Results and Discussion
Synthesis of New Alkynes and Buta-1,3-dienes
In the construction of cyclohexa-1,4-dienes through a
[4+2] cycloaddition, the desired cyclopropyl and bicy-
clopropyl substituents can be introduced with either the
correspondingly substituted alkyne or substituted buta-1,3-
diene. As both of these possibilities ought to be tested, all
of the correspondingly substituted building blocks 1–9 were
initially considered (Figure 1).
[‡] For one of us (A. de M.), this is considered to be Cyclopropyl
Building Blocks for Organic Synthesis, 162. Part 161: A. F.
Khlebnikov, S. I. Kozhushkov, D. S. Yufit, H. Schill, M. Regge-
lin, V. Spohr, A. de Meijere, Eur. J. Org. Chem. 2012, 1530–
1545. Part 160: V. A. Rassadin, V. V. Sokolov, A. F. Khlebnikov,
N. V. Ulin, S. I. Kozhushkov, A. de Meijere, Synthesis 2012,
372–376.
[a] Fachbereich Chemie, Philipps-Universität Marburg,
Hans-Meerwein-Str., 35043 Marburg, Germany
Fax: +49-6421-2825677
Cyclopropylacetylene (1)[6] is now commercially available
in bulk quantities,[7] and (1-cyclopropylcyclopropyl)acetyl-
ene (2) as well as (2-cyclopropylcyclopropyl)acetylene (3)
were easily prepared from the corresponding aldehydes 11[8]
and 14, respectively. Aldehydes 11 and 14 were obtained
from bromides 10[8] and 13,[9] respectively, by using a bro-
mine–lithium exchange with tert-butyllithium and then
trapping the corresponding cyclopropyllithium species with
dimethylformamide (Scheme 1). The treatment of aldehydes
E-mail: hilt@chemie.uni-marburg.de
[b] Department of Chemistry, Saint Petersburg State University,
Universitetskii Prosp. 26, 198504 St. Petersburg, Russia
[c] Institut für Organische und Biomolekulare Chemie der Georg-
August-Universität Göttingen,
Tammannstrasse 2, 37077 Göttingen, Germany
Fax: +49-551-399475
E-mail: ameijer1@uni-goettingen.de
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200105.
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M. Arndt, G. Hilt, A. F. Khlebnikov, S. I. Kozhushkov, A. de Meijere
FULL PAPER
11 and 14, which had already been used as precursors to
acetylenes 2 and 3. Indeed, adopting a known procedure for
the Horner–Wadsworth–Emmons olefination of aldehydes
with diethyl allylphosphonate,[15] we subjected 11 and 14 to
the established reaction conditions to give 1,3-butadienes 6
and 7 in 61 and 35% yield, respectively, the latter as a 1:1
mixture of cis and trans diastereomers (Scheme 2).
Figure 1. Cyclopropyl-substituted building blocks 1–9.
Cobalt-Catalyzed Diels–Alder Reactions of Cyclopropyl-
Substituted Alkynes
11 and 14 with carbon tetrabromide and triphenylphos-
phane (Ramirez–Corey–Fuchs alkenation[10]) gave the di-
bromovinyl derivatives 12 and 15, respectively.
The cobalt-catalyzed Diels–Alder reaction was envisaged
to convert the cyclopropyl-substituted 1,3-dienes and
acetylenes with nonactivated starting materials under mild
conditions.[4] For this purpose, alkyne 1 was treated with
different 1,3-dienes in dichloromethane at room tempera-
ture utilizing a cobalt catalyst consisting of [1,2-bis(diphen-
ylphosphanyl)ethane]cobalt dibromide [CoBr2(dppe)], zinc
powder, and zinc iodide. The cycloaddition process could
lead to the two regioisomers 17 and 18, but by utilizing the
cobalt(dppe) dibromide catalyst precursor, regioisomer 17
was formed predominantly (Scheme 3). On the other hand,
using catalyst precursor cobalt[2,4,6-trimethylphenyl-N-
(pyridin-2-ylmethylene)amine] dibromide led to the forma-
tion of 18 as the major regioisomer.[4] Thereby, both re-
gioisomers can be obtained from the same starting materi-
als. The results of the reaction of 1 with different 1,3-dienes
are summarized in Table 1.
Scheme 1. Synthesis of (1-cyclopropylcyclopropyl)acetylene (2) and
(2-cyclopropylcyclopropyl)acetylene (3).
The overall yields in the first two steps of these sequences
were 73 and 47%, respectively. The conversion of di-
bromovinyl derivative 12 to alkyne 2 employing the Fritsch–
Buttenberg–Wiechell rearrangement[11] was accomplished
with a satisfactory yield of 77%.[10b,12]
Scheme 3. Cobalt-catalyzed Diels–Alder reaction of 1 (for details
see Table 1).
One of the most important observations in terms of the
mechanistic interpretation of the cobalt-catalyzed Diels–
Alder reaction is that neither the transition-metal-catalyzed
cycloaddition process nor the DDQ oxidation led to any
significant amount of ring-opened products (Ͻ1%), and in
all cases, the cyclopropyl subunit remained intact. Accord-
ingly, the low-valent cobalt catalyst did not undergo an elec-
tron transfer from the metal to the ligand/substrate, other-
wise a radical-type ring opening would have been observed.
Also, all types of the 1,3-dienes appeared to be compatible
with the catalyst system. Electron-rich 1,3-butadienes such
as the 2-methoxy-1,3-butadiene (Table 1, Entry 5) and more
electron-neutral 1,3-dienes such as isoprene, 2,3-dimethyl-
1,3-butadiene (DMB), and myrcene were applied (Table 1,
Entries 1–4). Also, the electron-deficient 1,3-butadiene with
a methyl carboxylate group (Table 1, Entry 7) was con-
verted into the desired product 18f in good yield. In ad-
dition, the application of the pyridine-imine-type-derived
catalyst system generated meta-substituted product 18a in
an excellent yield. However, as it was previously found that
the steric bulk of the substituents was very important for
Although 1-cyclopropylbuta-1,3-diene (4)[13] and 2-
cyclopropylbuta-1,3-diene (5)[14] are known compounds, yet
inconveniently prepared, we concentrated on the previously
unknown compounds 1-(1Ј-cyclopropylcyclopropyl)buta-
1,3-diene (6) and 1-(2Ј-cyclopropylcyclopropyl)buta-1,3-
diene (7), as they should be easily accessible from aldehydes
Scheme 2. Preparation of (E)-1-(1Ј-cyclopropylcyclopropyl)buta-
1,3-diene (6) and (E)-1-(2Ј-cyclopropylcyclopropyl)buta-1,3-diene
(7).
2
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Diels–Alder Reactions for the Construction of Cyclopropylarenes
Table 1. Reaction of cyclopropylacetylene (1) with substituted 1,3- and 17%, respectively, however, the reactions with DMB
butadienes (see Scheme 3).
and 1,3-nonadiene led to the desired products 19 and 20 in
good to excellent yields (Scheme 4).
The higher steric encumbrance of 2 apparently reduces
its reactivity in the cobalt-catalyzed cycloaddition, so that
only a limited number of dienes gave acceptable results.
Nevertheless, the cyclopropyl subunits remained intact and
no ring-opened side products were observed.
The sterically less encumbered cyclopropyl-substituted
alkyne 3 was also applied in the cobalt-catalyzed Diels–
Alder reactions with 1,3-dienes (Scheme 5 and Table 2).
Scheme 5. Cobalt-catalyzed Diels–Alder reactions of 3 with 1,3-
butadienes (for details see Table 2).
Table 2. Reaction of (2-cyclopropylcyclopropyl)acetylene (3) with
1,3-butadienes (see Scheme 5).
[a] The catalyst system cobalt[2,4,6-trimethylphenyl-N-(pyridin-2-
ylmethylene)amine] dibromide, Zn, ZnI2, Fe was used. [b] In these
cases, the isomeric ratio meta/ortho is reported.
the regioselectivity,[16] the cyclopropyl substituent, appar-
ently, is only a moderately directing group in this respect.[17]
Only for the methoxy-substituted butadiene and the higher
substituted butadiene derivative (2-methylbuta-1,3-dienyl)-
benzene (Table 1, Entries 5 and 6), excellent levels of re-
gioselectivity were observed.
These results encouraged us to investigate the application
of more complex cyclopropyl-substituted alkynes such as 2
with a selected number of 1,3-dienes. The reactions with
myrcene and (2-methylbuta-1,3-dienyl)benzene gave the
[4+2] cycloadducts, but in rather disappointing yields of 14
Scheme 4. Application of 2 in cobalt-catalyzed Diels–Alder reac-
tions.
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FULL PAPER
As described above, alkyne 3 was synthesized as nearly a Table 3. Reaction of (E)-1-(1Ј-cyclopropylcyclopropyl)buta-1,3-
diene [(E)-6] with alkynes (see Scheme 6).
1:1 mixture of cis and trans isomers. Accordingly, the as-
signments of the NMR signals were less obvious, and in
some cases specific assignments were only tentative, as the
separation of the four possible regioisomers and dia-
stereomers could not be accomplished by column
chromatography on silica gel.
The application of alkyne 3 in the cobalt-catalyzed
Diels–Alder reaction gave the desired products mostly in
good yields, and generally, the para-substituted products 21
(Table 2, Entries 1, 3, and 4) were formed as the main re-
gioisomers. Also, it is noteworthy that in all cases the bi-
cyclopropyl groups stayed intact. These encouraging results
showed that alkynes 1 and 3 are well accepted in the cobalt-
catalyzed cycloaddition process, whereas the sterically more
bulky alkyne 2 led to good results with only a small number
of 1,3-dienes.
Cobalt-Catalyzed Diels–Alder Reactions of Cyclopropyl-
Substituted 1,3-Dienes
The second phase of our investigation of the cobalt-cata-
lyzed Diels–Alder reactions was performed with bicyclo-
propyl-modified butadiene derivatives 6 and 7. For these
transformations, one would expect that the conversions
with the sterically more congested diene (E)-6 would be as
(≈10%) of an unidentified side product, exhibiting olefinic signals
[a] The regioselectivity was estimated by integration of the peaks in
the GC–MS recording. The product also contains a small amount
in the 1H NMR spectrum. [b] CoBr2(dppe) (20 mol-%), Zn
(40 mol-%), and ZnI2 (40 mol-%) were used. The reaction tempera-
ture was 40 °C.
difficult as with alkyne 2. The reactions of (E)-6 with dif-
ferent alkynes utilizing the CoBr2(dppe) catalyst precursor
gave mainly the desired meta-substituted products 23,
whereas the more congested ortho-substituted regioisomer
24 was formed in only minor amounts (Scheme 6 and
Table 3).
be rationalized in terms of the steric bulk of the TIPS (tri-
isopropylsilyl) group which prohibits the DDQ from com-
ing into close contact with the dihydroaromatic intermedi-
ate and thus would be responsible for the reduced rate of
the electron-transfer reaction. In particular, the rate of the
second electron transfer from radical intermediate 27 to
DDQ (or its radical anion) appears to be reduced. Thereby,
the lifetime of radical intermediate 27 is increased so that
the ring opening to the proposed intermediate 28 can occur.
The second oxidation and a proton shift then led to 25, as
the only isolated product, in 53% yield.
Scheme 6. Cobalt-catalyzed Diels–Alder reactions of (E)-6 with
alkynes (for details see Table 3).
As expected, the reactions with terminal alkynes gave the
desired products 23 in moderate to good yields. However,
the incorporation of the internal alkyne unit as in 1,4-di-
methoxy-but-2-yne (Table 3, Entry 4) gave the desired prod-
uct 23c in only 19% yield, which indicates that the steric
bulk of the alkyne should be minimized to obtain good re-
sults.
In this investigation, the reaction of (triisopropylsilyl)eth-
yne with (E)-6 is the only case in which a ring-opened prod-
uct, such as 25 (Table 3, Entry 3), was obtained, and it is
derived most likely from radical-type intermediates. The
ring opening of the cyclopropyl substituent, next to the ar-
ene moiety, did not take place over the course of the cobalt-
catalyzed cycloaddition, as proven by NMR analysis of the
crude reaction mixture. Instead, the DDQ oxidation caused
Scheme 7. Ring opening of triisopropylsilyl-substituted intermedi-
the cyclopropyl substituent to open (Scheme 7). This can ate 26.
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Diels–Alder Reactions for the Construction of Cyclopropylarenes
In the case of phenyl-substituted derivative 23a, the GC– borane derivative (Table 4, Entry 3) was applied, and 29c
MS analysis showed the presence of a small amount of an- was isolated as a single regioisomer. In all of the cases inves-
1
other product. The H NMR spectrum showed signals of tigated, both diastereomers were converted into the desired
olefinic protons which in this case suggest that a small frac- products, meaning that the cobalt catalyst did not differen-
tion of the dihydroaromatic intermediate also underwent a tiate between the two diastereomeric starting materials of
ring-opening reaction upon DDQ oxidation. Unfortunately, (E)-7.
this side product could not be separated from the main
product 23a by column chromatography.
The application of diene (E)-7 in the cobalt-catalyzed
Diels–Alder reactions gave the regioisomers 29 as the main
Conclusions
products (Scheme 8 and Table 4).
In conclusion, the straightforward syntheses of alkynes
2 and 3 and butadiene derivatives 6 and 7 and their first
applications in cobalt-catalyzed Diels–Alder reactions have
been achieved. The use of these cyclopropyl-substituted al-
kynes and 1,3-dienes reveals they are an appropriate tool
for the syntheses of bicyclopropyl-substituted arenes. The
mild reaction conditions allowed the generation of various
functionalized dihydroaromatic intermediates without the
ring opening of the cyclopropyl moieties. In only one case,
the cyclopropyl ring opening was observed, when DDQ was
used for the oxidation step to generate arene derivative 25.
Accordingly, long-lived radical-type intermediates can be
excluded as participants in cobalt catalysis.
Scheme 8. Cobalt-catalyzed Diels–Alder reactions of (E)-7 with
alkynes (for details see Table 4).
Table 4. Reaction of (E)-1-(2Ј-cyclopropylcyclopropyl)buta-1,3-
diene [(E)-7] with alkynes (see Scheme 8).
Experimental Section
General Remarks: All reagents were used as purchased from com-
mercial suppliers without further purification. All reactions in non-
aqueous solvents were carried out using standard Schlenk tech-
niques under dry nitrogen or argon. The solvents were purified and
1
dried according to conventional methods prior to use. H and 13C
NMR spectroscopic data were recorded with a Varian Unity-300
1
(300 MHz for H NMR and 75.5 MHz for 13C NMR), an Avance
300 (300 MHz for 1H NMR and 75.5 MHz for 13C NMR), a DRX
1
400 (400 MHz for H NMR and 100 MHz for 13C NMR), an Av-
ance 500 (500 MHz for 1H NMR and 125 MHz for 13C NMR), or
an Inova-500 (125.7 MHz for 13C NMR) instrument. Chemical
shifts (δ) are given in ppm relative to the residual resonances of the
solvents (1H NMR, δ = 7.26 ppm for CHCl3; 13C NMR, δ =
77.0 ppm for CDCl3) or tetramethylsilane (1H NMR, δ = 0.00 ppm;
13C NMR, δ = 0.0 ppm), and coupling constants (J) are presented
as absolute values in Hz. The multiplicities of 13C NMR signals
were determined by using DEPT techniques. IR spectroscopy was
performed with a Bruker IFS 66 (FTIR) spectrometer, a Bruker
IFS 200 (FTIR), or a Nicolet Magna IR 750, and the samples were
prepared as KBr pellets or oils between KBr plates. EI-MS was
performed with a Finnigan MAT 95S (70 eV). High-resolution
mass spectrometry (HRMS) was performed with a Finnigan MAT
95S instrument. GC analysis was recorded with a GC-2010 Plus
Gas Chromatograph, Shimadzu. GC–MS was accomplished with
an Agilent 6890 gas chromatograph with a Hewlett Packard 5973
mass detector. For chromatography, the separations were carried
out on Merck Silica 60 (0.063–0.200 mm, 70–230 mesh ASTM) or
on Macherey–Nagel Silica 60 (0.040–0.063 mm, 230–400 mesh
ASTM). For TLC, Macherey–Nagel TLC plates Alugram® Sil G/
UV 254 or Merck TLC plates (Silica 60, F254) were used. Detec-
tion of the compounds under UV light was achieved at 254 nm,
and the plates were developed with MOPS reagent (10% molybdo-
phosphoric acid, solution in ethanol). The melting points were
[a] B(Pin) = 4,4,5,5-tetramethyl-1,3,2-dioxaborolane.
This less sterically encumbered diene (E)-7, compared to
(E)-6, led to the formation of the desired products in con-
siderably higher yields, even when an internal alkyne was
applied (Table 4, Entry 3).
Diene (E)-7 reacted well in the cobalt-catalyzed Diels–
Alder reaction with phenylacetylene (Table 4, Entry 1) as
well as with the terminal enyne (Table 4, Entry 2), and the
desired meta-substituted products 29a and 29b were formed
with excellent regioselectivities. Additionally, the pinacol- measured with a Büchi 540 capillary melting point apparatus, and
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the elemental analyses were performed with an HP185B CHN ana-
lyzer.
cis/trans-1,1-Dibromo-2-(2Ј-cyclopropylcyclopropyl)ethane (15): A
three-necked flask, equipped with a magnetic stir bar, a rubber sep-
tum, an addition funnel fitted with a rubber septum, and a nitrogen
inlet, was charged with carbon tetrabromide (49.8 g, 150 mmol),
and anhydrous dichloromethane (250 mL) was added with a sy-
ringe. The solution was cooled in an ice-water bath, and a solution
of triphenylphosphane (78.7 g, 300 mmol) in anhydrous dichloro-
methane (250 mL) was then added dropwise from the addition fun-
nel over 30 min. The reaction mixture was stirred at 0 °C for
10 min, and then a solution of 2-cyclopropylcyclopropanecarbal-
dehyde (8.26 g, 75.0 mmol, cis/trans, approximately 1:1.4) in anhy-
drous dichloromethane (20 mL) was added over 10 min with a sy-
ringe. The solution was stirred at 0 °C for 5 h and at room tempera-
ture for 10 h, and then water (500 mL) was added. The resulting
mixture was transferred to a separatory funnel, and the aqueous
layer was separated and then extracted with dichloromethane
(3ϫ200 mL). The combined organic layers were washed with brine
(200 mL), dried with Na2SO4, filtered, and concentrated under re-
duced pressure using a rotary evaporator. To the residue was added
diethyl ether (200 mL), and the resulting suspension was filtered to
remove triphenylphosphane oxide. The collected solid was washed
with diethyl ether (3ϫ100 mL), and the combined ethereal extracts
were concentrated under reduced pressure using a rotary evapora-
tor. The residue (oil, 11.56 g) was purified by column chromatog-
raphy (250 mL of silica gel, pentane) to give 15 (9.38 g, 47%,
cis/trans, approximately 1:1.4) as a yellowish oil which was used in
the next step without further purification. 1H NMR (300 MHz,
CDCl3): δ = 6.19 (d, J = 9.2 Hz, 0.4 H), 5.78 (d, J = 9.2 Hz, 0.6
H), 1.73–1.62 (m, 0.4 H), 1.43–1.34 (m, 0.6 H), 1.18–0.99 (m, 1.0
H), 0.96–0.81 (m, 1.2 H), 0.73–0.51 (m, 2.4 H), 0.49–0.33 (m, 1.6
H), 0.29–0.04 (m, 1.8 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
141.6, 139.1, 86.0, 84.9, 22.7, 21.8, 21.3, 21.1, 11.9, 11.4, 9.6, 4.5,
4.2, 3.4, 2.7 ppm. MS (EI): m/z = 264 [M]+, 224, 212, 146, 133,
121, 105, 93, 77, 67, 51.
1,1-Dibromo-2-(1-cyclopropylcyclopropyl)ethene (12):
A
three-
necked flask, equipped with a magnetic stir bar, a rubber septum,
and a nitrogen inlet, was charged with zinc (9.46 g, 144.6 mmol),
triphenylphosphane (39.4 g, 150.2 mmol), carbon tetrabromide
(49.8 g, 150.2 mmol), and anhydrous CH2Cl2 (300 mL) at 0 °C. The
mixture was then stirred for 30 h at room temperature. 1-Cy-
clopropylcyclopropanecarbaldehyde[8] (8.07 g, 73 mmol) was
added, and the reaction mixture was stirred for an additional 72 h.
The reaction mixture was then poured into pentane (400 mL), and
the insoluble materials were removed by filtration. The insoluble
fraction was taken through two additional cycles of dichlorometh-
ane extraction and pentane precipitation to remove all of the ole-
finic product. Evaporation of the solvent under reduced pressure
and distillation (54–56 °C, 0.01 Torr) gave pure 1,1-dibromo-2-(1-
cyclopropylcyclopropyl)ethene (15.3 g, 79%). 1H NMR (300 MHz,
CDCl3): δ = 6.63 (s, 1 H), 1.20–1.11 (m, 1 H), 0.66–0.62 (m, 2 H),
0.52–0.48 (m, 2 H), 0.39–0.32 (m, 2 H), 0.12–0.07 (m, 2 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 142.8, 141.2, 137.4, 91.7, 24.0,
14.6, 11.2, 2.3 ppm.
(1-Cyclopropylcyclopropyl)ethyne (2): Under nitrogen, a solution
of
1,1-dibromo-2-(1-cyclopropylcyclopropyl)ethene
(15.0 g,
56.4 mmol) in tetrahydrofuran (200 mL) at –78 °C was treated with
nBuLi (2.5 m in hexane, 48.2 mL, 120.5 mmol). After stirring at
–78 °C for 1 h, the reaction mixture was warmed to 25 °C and
maintained at this temperature for 1 h. Water was added, and the
resulting mixture was extracted with pentane. Fractional distil-
lation (113–114 °C, 760 Torr) afforded 2 (3.00 g, 50%) as a color-
1
less oil. H NMR (300 MHz, CDCl3): δ = 1.84 (s, 1 H), 0.93–0.89
(m, 1 H), 0.87–0.84 (m, 2 H), 0.62–0.58 (m, 2 H), 0.45–0.39 (m, 2
H), 0.30–0.25 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 88.8,
64.1, 15.6, 14.0, 12.6, 2.7 ppm. C8H10O (122.17): calcd. C 90.5, H
9.5; found C 90.6, H 9.3. The fraction with b.p. 105–112 °C (3.89 g)
contained two compounds that according to 1H NMR spectro-
scopic data were 1-chlorobutane (2.28 g) and (1-cyclopropylcy-
clopropyl)ethyne (1.61 g), that is, the total yield of 2 was 77 %.
cis/trans-(2-Cyclopropylcyclopropyl)ethyne (3): A solution of 1,1-di-
bromo-2-(2-cyclopropylcyclopropyl)ethene (9.34 g, 35.3 mmol,
cis/trans, approximately 1:1.4) in tetrahydrofuran (250 mL) at
–78 °C under nitrogen was treated with nBuLi (2.5 m in hexane,
41 mL, 102.8 mmol) for 50 min. After stirring at –78 °C for 1 h,
the reaction mixture was warmed to 25 °C and maintained at this
temperature for 1 h. Water (250 mL) was added, and the resulting
mixture was extracted with pentane (4ϫ50 mL). Column
chromatography (100 mL of silica gel, pentane), and distillation
(118–120 °C, 760 mm) afforded of 3 (2.18 g, 58%, cis/trans, approx-
2-Cyclopropylcyclopropanecarbaldehyde (14): tert-Butyllithium
(1.5 m in pentane, 42 mL, 63.1 mmol) was added dropwise (60 min)
to
a solution of 1-cyclopropylcyclopropyl bromide (9.96 g,
60 mmol) in diethyl ether (140 mL) at –78 °C. After 50 min at
–78 °C, dimethylformamide (4.82 g, 5.11 mL, 66 mmol) was added
with a syringe (10 min), and the mixture was allowed to slowly
warm to room temperature over 1.3 h. The reaction was quenched
with diluted HCl [H2O (250 mL) + conc. HCl (12 mL)], the water
layer was separated and extracted with diethyl ether (3ϫ100 mL)
and pentane (2ϫ50 mL). The combined organic phases were
washed with aqueous Na2HCO3 and brine and then dried with
Na2SO4. The solution was concentrated on a rotary evaporator at
0 °C (52 mbar) to give 14 (6.59 g, 100%) which was contaminated
with some impurities originating from the starting bromide. The
purification of the crude product by flash chromatography (silica
gel, pentane/diethyl ether, 1:2) was accompanied by partial decom-
1
imately 1:1.4) as a colorless oil. H NMR (600 MHz, CDCl3): δ =
1.81 (d, J = 2.2 Hz, 0.4 H), 1.73 (d, J = 2.2 Hz, 0.6 H), 1.38–1.34
(m, 0.4 H), 1.24–1.20 (m, 0.6 H), 1.19–1.15 (m, 0.6 H), 0.99–0.95
(m, 0.4 H), 0.82–0.70 (m, 2.2 H), 0.58–0.42 (m, 1.4 H), 0.40–0.36
(m, 0.6 H), 0.34–0.29 (m, 0.6 H), 0.26–0.19 (m, 1 H), 0.11–0.07 (m,
0.6 H), 0.04–0.00 (m, 0.6 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 87.3, 85.3, 65.7, 63.5, 24.1, 21.8, 13.0, 12.9, 11.6, 10.0, 5.5, 5.1,
4.2, 3.6, 3.3, 2.3 ppm. MS (EI): m/z = 106 [M]+, 105, 91, 78, 65,
54. C8H10O (122.17): calcd. C 90.5, H 9.5; found C 90.2, H 9.8. IR
(film): ν = 3310, 3081, 2117 cm–1.
˜
position to give 14 (4.23 g, 64%) as an approximate 1:1 mixture of
cis and trans isomers. H NMR (300 MHz, CDCl3): δ = 9.31 (d, J (2.5 m in hexane, 23.7 mL, 59.2 mmol) was added dropwise at
(E)-1-(1Ј-Cyclopropylcyclopropyl)buta-1,3-diene (6): n-Butyllithium
1
= 5.6 Hz, 0.5 H), 9.02 (d, J = 5.6 Hz, 0.5 H), 1.85–1.42 (m, 1 H),
–78 °C to a solution of diethyl allylphosphonate (10.6 g, 10.3 mL,
1.15–1.05 (m, 2 H), 0.95–0.80 (m, 2 H), 0.60–0.05 (m, 4 H) ppm. 59.2 mmol) in anhydrous tetrahydrofuran (120 mL). After stirring
13C NMR (75 MHz, CDCl3): δ = 201.9, 200.9, 29.4, 29.2, 26.7, for 15 min, a solution of 1-cyclopropylcyclopropanecarbaldehyde
25.0, 13.3, 13.0, 11.3, 9.1, 5.5, 5.2, 3.8, 2.7 ppm. MS (EI): m/z =
110 [M]+, 109, 95, 81, 79, 77, 69, 68, 67, 54, 53. A different prepara-
tion for aldehyde 14 has been published in patents, yet without
spectroscopic characterization.[3e,3f]
(5.43 g, 49.3 mmol) in hexamethylphosphoric triamide (HMPA,
20.1 g, 20.7 mL, 118 mmol) was added dropwise with a syringe.
The resulting solution was stirred at –78 °C for 2 h and then
warmed to room temperature. The stirring was continued for an
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20105
/KAP1
Date: 17-04-12 15:23:53
Pages: 11
Diels–Alder Reactions for the Construction of Cyclopropylarenes
1
additional 12 h, and then the reaction was quenched with a satu-
rated aqueous NH4Cl solution. The mixture was extracted with
diethyl ether (3ϫ100 mL). The combined organic phases were
washed with brine (100 mL), dried with NaSO4, and concentrated
to afford the crude product. Purification by flash chromatography
(silica gel, pentane) gave the desired diene 6 (4.03 g, 61%) as a
colorless oil. 1H NMR (300 MHz, CDCl3): δ = 6.40–6.26 (m, 2 H),
5.48–5.39 (m, 1 H), 5.18–5.07 (m, 1 H), 4.95–4.90 (m, 1 H), 1.24–
1.14 (m, 1 H), 0.53–0.50 (m, 2 H), 0.48–0.45 (m, 2 H), 0.45–0.42
(m, 2 H), 0.04–0.01 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 142.8, 137.4, 127.2, 113.9, 22.7, 13.3, 12.0, 2.2 ppm. MS (EI):
m/z = 134 [M]+, 133, 119, 105, 103, 93, 91, 79, 77, 67. C10H14O
(150.22): calcd. C 89.5, H 10.5; found C 89.7, H 10.2.
listed. H NMR (300 MHz, CDCl3, 18a): δ = 7.15 (t, J = 7.6 Hz,
1 H), 6.92–6.85 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3, 18a):
δ = 126.1 ppm. MS (EI): m/z = 132 [M]+, 129, 117, 115, 105, 91, 77,
65. The analytical data are consistent with those in the literature.[18]
1-Cyclopropyl-3-methylbenzene (18a): For the meta-selective Diels–
Alder reaction, the catalyst precursor cobalt[2,4,6-trimethylphenyl-
N-(pyridin-2-ylmethylene)amine] dibromide was used, and iron
powder (10 mol-%) was added to the catalyst system. After purifi-
cation by column chromatography (pentane), the product (18a/17a,
76:24, 129 mg, 97%) was obtained as a colorless oil. 1H NMR
(300 MHz, CDCl3, 18a): δ = 7.19 (t, J = 7.5 Hz, 1 H), 7.04–6.97
(m, 1 H), 6.96–6.88 (m, 2 H), 2.36 (s, 3 H), 1.90 (tt, J = 8.4, 5.1 Hz,
1 H), 1.02–0.89 (m, 2 H), 0.77–0.66 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3, 18a): δ = 143.9, 137.8, 128.2, 126.5, 126.1, 122.6,
(E)-1-(cis/trans-2Ј-Cyclopropylcyclopropyl)buta-1,3-diene (7): n-But-
yllithium (2.5 m in hexane, 15.8 mL, 39.9 mmol) was added drop-
wise at –78 °C to a solution of diethyl allylphosphonate (8.11 g,
7.88 mL, 45.2 mmol) in anhydrous tetrahydrofuran (95 mL). After
stirring for 15 min, a solution of 2-cyclopropylcyclopropanecarbal-
dehyde (4.15 g, 37.7 mmol, cis/trans, ≈1:1) in hexamethylphos-
phoric triamide (15.3 g, 15.8 mL, 90.5 mmol) was added dropwise
with a syringe. The resulting solution was stirred at –78 °C for 2 h
and then warmed to room temperature. The stirring was continued
for an additional 12 h, and then the reaction was quenched with a
saturated aqueous NH4Cl solution. The mixture was extracted with
diethyl ether (3ϫ100 mL). The combined organic phases were
washed with brine (100 mL), dried with Na2SO4, and concentrated
to afford the crude product. Purification by flash chromatography
(silica gel, pentane) gave the desired diene 7 (1.77 g, 35%, cis/trans,
≈1:1) as a colorless oil. 1H NMR (300 MHz, CDCl3): δ = 6.40–
6.05 (m, 2 H), 5.60–5.52 (m, 0.5 H), 5.30–5.22 (m, 0.5 H), 5.10–
5.08 (m, 0.5 H), 5.04–5.02 (m, 0.5 H), 4.92–4.90 (m, 0.5 H), 4.89–
4.87 (m, 0.5 H), 1.58–1.47 (m, 0.5 H), 1.26–1.15 (m, 0.5 H), 1.01–
0.76 (m, 2 H), 0.72–0.63 (m, 0.5 H), 0.58–0.28 (m, 3.5 H), 0.20–0.15
(m, 1 H), 0.12–0.01 (m, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 138.6, 137.2, 137.0, 136.0, 130.3, 128.2, 113.7, 113.5, 23.4, 22.3,
20.3, 20.2, 12.3, 12.1, 11.0, 9.4, 4.6, 4.4, 3.3, 2.4 ppm. MS (EI): m/z
= 134 [M]+, 119, 105, 93, 91, 79, 77, 67, 65. C10H14O (150.22):
calcd. C 89.5, H 10.5; found C 89.8, H 10.4.
1
21.4, 15.3, 9.0 ppm. Only the resolved signals of 17a are listed. H
NMR (300 MHz, CDCl3, 17a): δ = 7.11 (d, J = 8.0 Hz, 2 H), 7.04–
6.98 (m, 2 H), 2.35 (s, 3 H), 1.95–1.84 (m, 1 H) ppm. 13C NMR
(75 MHz, CDCl3, 17a): δ = 140.8, 134.8, 128.9, 125.6, 20.9, 15.0,
8.8 ppm. MS (EI): m/z = 132 [M]+, 129, 117, 115, 105, 91, 77, 65.
The analytical data are consistent with those in the literature.[18a]
4-Cyclopropyl-1,2-dimethylbenzene (17b): After purification by col-
umn chromatography (pentane), the product (73 mg, 99%) was ob-
tained as a yellow oil. H NMR (300 MHz, CDCl3): δ = 7.03 (d, J
= 7.7 Hz, 1 H), 6.88 (s, 1 H), 6.83 (d, J = 7.7 Hz, 1 H), 2.24 (s, 3
H), 2.23 (s, 3 H), 1.85 (ddd, J = 13.4, 8.6, 5.1 Hz, 1 H), 0.97–0.86
(m, 2 H), 0.70–0.61 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 141.3, 136.3, 133.5, 129.5, 127.2, 123.0, 19.7, 19.2, 14.9, 8.8 ppm.
MS (EI): m/z = 146 [M]+, 131, 127, 119, 115, 105, 91, 77, 65.
HRMS (EI): calcd. for C11H14 146.1096; found 146.1098. IR (film):
1
ν = 3081, 3007, 2967, 2921, 1615, 1507, 1462, 1045, 1018, 995,
˜
813 cm–1.
1-Cyclopropyl-4-(4-methylpent-3-enyl)benzene (17c): After purifica-
tion by column chromatography (pentane), the product (17c/18c,
86:14, 63 mg, 62%) was obtained as a colorless oil. 1H NMR
(300 MHz, CDCl3): δ = 7.12–7.04 (m, 2 H), 7.03–6.94 (m, 2 H),
5.22–5.13 (m, 1 H), 2.64–2.53 (m, 2 H), 2.27 (dt, J = 7.9, 7.4 Hz,
2 H), 1.87 (tt, J = 8.4, 5.0 Hz, 1 H), 1.69 (s, 3 H), 1.58 (s, 3 H),
0.97–0.86 (m, 2 H), 0.72–0.60 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 141.2, 139.5, 132.0, 128.3, 125.6, 123.9, 35.7, 30.1,
25.7, 17.7, 15.0, 8.9 ppm. MS (EI): m/z = 200 [M]+, 165, 141, 131,
115, 91, 77. HRMS (EI): calcd. for C15H20 200.1565; found
General Procedure for the Cobalt-Catalyzed Diels–Alder Reaction:
Anhydrous zinc iodide (10–20 mol-%), zinc powder (10–20 mol-%),
and [1,2-bis(diphenylphosphanyl)ethane]cobalt dibromide (5–
10 mol-%) were suspended in dichloromethane (1.0 mL) under an
argon atmosphere. Then, the 1,3-butadiene (0.5–0.6 mmol) and the
alkyne (0.5 mmol) were added, and the mixture was stirred at room
temperature or at 40 °C until the complete conversion of the start-
ing materials was observed as monitored by GC–MS (14–30 h).
The mixture was filtered through a small pad of silica gel (diethyl
ether), and the solvent was removed under reduced pressure. The
residual dihydroaromatic intermediate was oxidized with DDQ
(1.1 equiv.) in benzene (5 mL). After 1 h at room temperature, the
mixture was filtered through a short pad of deactivated silica gel
(diethyl ether), and the solvent was removed under reduced pres-
sure. The residue was purified by flash column chromatography on
silica gel. The ratios of regioisomers were determined by integration
200.1570. IR (film): ν = 3081, 3008, 2968, 2922, 2856, 1516, 1452,
˜
1378, 1019, 816 cm–1.
1-Cyclopropyl-4-methoxybenzene (17d): After purification by col-
umn chromatography (pentane/methyl tert-butyl ether, 50:1), the
product (17d/18d, Ͼ95:5, 62 mg, 83%) was obtained as a light yel-
low oil. 1H NMR (300 MHz, CDCl3): δ = 7.06–6.99 (m, 2 H), 6.85–
6.79 (m, 2 H), 3.79 (s, 3 H), 1.86 (tt, J = 8.4, 5.1 Hz, 1 H), 0.91
(ddd, J = 8.4, 6.3, 4.4 Hz, 2 H), 0.66–0.59 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 157.6, 135.8, 126.8, 113.8, 55.3, 14.6,
8.4 ppm. The analytical data are consistent with those in the litera-
ture.[19]
5-Cyclopropyl-2-methylbiphenyl (18e): After purification by column
chromatography (pentane Ǟ pentane/diethyl ether, 50:1), the prod-
uct (18e/17e, Ͼ95:5, 92 mg, 88%) was obtained as a yellow oil. H
1
of the GC and H NMR signals.
1
1-Cyclopropyl-4-methylbenzene (17a): After purification by column
chromatography (pentane), the product (17a/18a, 87:13, 111 mg,
NMR (300 MHz, CDCl3): δ = 7.47–7.39 (m, 2 H), 7.39–7.31 (m, 3
H), 7.18 (d, J = 7.6 Hz, 1 H), 7.04–6.96 (m, 2 H), 2.25 (s, 3 H),
1.92 (tt, J = 8.4, 5.1 Hz, 1 H), 1.01–0.92 (m, 2 H), 0.75–0.68 (m, 2
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 142.2, 141.8, 141.3,
1
84%) was obtained as a colorless oil. H NMR (300 MHz, CDCl3,
17a): δ = 7.11–7.04 (m, 2 H), 7.02–6.94 (m, 2 H), 2.31 (s, 3 H), 1.87
(tt, J = 8.5, 5.1 Hz, 1 H), 0.98–0.85 (m, 2 H), 0.72–0.61 (m, 2
H) ppm. 13C NMR (75 MHz, CDCl3, 17a): δ = 140.8, 134.8, 128.9, 132.3, 130.2, 129.2, 128.0, 127.2, 126.7, 124.5, 19.9, 15.0, 9.0 ppm.
125.6, 20.9, 15.0, 8.8 ppm. Only the resolved signals of 18a are
MS (EI): m/z = 208 [M]+, 193, 178, 165, 152, 139, 128, 115, 89, 77.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20105
/KAP1
Date: 17-04-12 15:23:53
Pages: 11
M. Arndt, G. Hilt, A. F. Khlebnikov, S. I. Kozhushkov, A. de Meijere
FULL PAPER
HRMS (EI): calcd. for C16H16 208.1252; found 208.1261. IR (film):
˜
was obtained in a diastereomeric ratio of 47:53 as a colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.08–6.99 (m, 4 H), 6.84–6.82
(m, 1 H), 6.78 (dd, J = 7.7, 1.7 Hz, 1 H), 2.25 (s, 3 H), 2.24 (s, 3
H), 2.23 (s, 3 H), 2.22 (s, 3 H), 2.05 (dt, J = 8.8, 6.1 Hz, 1 H), 1.61
(dt, J = 9.0, 5.0 Hz, 1 H), 1.13–1.05 (m, 1 H), 0.97–0.89 (m, 2 H),
0.82–0.74 (m, 2 H), 0.74–0.67 (m, 2 H), 0.46–0.34 (m, 2 H), 0.33–
0.27 (m, 1 H), 0.27–0.10 (m, 4 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 141.1, 137.4, 136.3, 135.8, 133.5, 133.3, 130.7, 129.5,
129.1, 127.1, 126.5, 122.9, 25.0, 22.5, 21.2, 21.0, 19.8, 19.7, 19.3,
19.2, 13.5, 12.4, 9.8, 9.6, 4.8, 4.6, 3.3, 2.6 ppm. MS (EI): m/z = 186
[M]+, 171, 157, 143, 132, 127, 119, 105, 91, 77. HRMS (EI): calcd.
ν = 3079, 2922, 1601, 1489, 1443, 1020, 909, 816, 770, 703 cm–1.
Methyl 3-Cyclopropylbenzoate (18f) and Methyl 2-Cyclopropyl-
benzoate (17f): After purification by column chromatography
(pentane/methyl tert-butyl ether, 50:1), the product (18f/17f, 63:38,
55 mg, 63%) was obtained as a light yellow oil. 1H NMR
(400 MHz, CDCl3): δ = 7.84–7.71 (m, 3 H), 7.39 (t, J = 7.6 Hz, 1
H), 7.35–7.25 (m, 2 H), 7.19 (t, J = 7.5 Hz, 1 H), 7.01 (d, J =
7.9 Hz, 1 H), 3.92 (s, 3 H), 3.91 (s, 3 H), 2.65 (tt, J = 8.6, 5.4 Hz,
1 H), 1.94 (tt, J = 8.5, 5.1 Hz, 1 H), 1.05–0.96 (m, 4 H), 0.77–0.72
(m, 2 H), 0.71–0.66 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 168.6, 167.3, 144.6, 144.4, 131.7, 131.2, 130.5, 130.1, 130.0,
128.2, 126.7, 126.6, 125.6, 125.2, 52.03, 51.95, 15.3, 13.4, 9.3,
8.7 ppm. MS (EI): m/z = 176 [M]+, 161, 148, 144, 133, 115, 105,
91, 77. HRMS (EI): calcd. for C11H12O2 176.0837; found 176.0828.
for C14H18 186.1409; found 186.1427. IR (film): ν = 3076, 3001,
˜
2968, 2921, 1614, 1507, 1452, 1017, 815 cm–1. The analytical data
of the trans isomer are consistent with those in the literature.[21]
1-(Bicycloprop-2-yl)-4-methoxybenzene (21c): After purification by
column chromatography (pentane/methyl tert-butyl ether, 50:1), the
product (21c/22c, Ͼ95:5, 58 mg, 60%) was obtained in a dia-
IR (film): ν = 3083, 3004, 2951, 1723, 1491, 1434, 1281, 1262, 1218,
˜
1128, 1076, 754 cm–1. The analytical data for methyl 3-cycloprop-
1
ylbenzoate (18f) are consistent with those in the literature.[20]
stereomeric ratio of 37:63 as a colorless oil. H NMR (300 MHz,
CDCl3): δ = 7.05 (d, J = 8.8 Hz, 2 H), 6.85–6.78 (m, 2 H), 6.70–
6.60 (m, 4 H), 3.64 (s, 3 H), 3.62 (s, 3 H), 1.89 (dt, J = 8.6, 6.2 Hz,
1 H), 1.46 (dt, J = 8.5, 5.1 Hz, 1 H), 0.96–0.86 (m, 1 H), 0.84–0.71
(m, 2 H), 0.67–0.44 (m, 4 H), 0.16–0.10 (m, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 157.6, 157.5, 135.7, 132.1, 130.2, 126.7,
113.7, 113.3, 55.3, 55.2, 24.7, 22.1, 20.9, 20.5, 13.2, 12.4, 9.8, 9.6,
4.7, 4.5, 3.3, 2.6 ppm. MS (EI): m/z = 188 [M]+, 173, 159, 144, 134,
128, 121, 115, 103, 91, 77. HRMS (EI): calcd. for C13H16O
4-(Bicyclopropyl)-1,2-dimethylbenzene (19): After purification by
column chromatography (pentane), the product (92 mg, 99%) was
obtained as a colorless oil. 1H NMR (300 MHz, CDCl3): δ = 7.16–
7.04 (m, 3 H), 2.27 (s, 3 H), 2.24 (s, 3 H), 1.27 (tt, J = 8.2, 5.2 Hz,
1 H), 0.73–0.64 (m, 2 H), 0.64–0.56 (m, 2 H), 0.46–0.37 (m, 2 H),
0.17–0.08 (m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 144.3,
136.1, 133.9, 129.4, 129.2, 125.3, 24.8, 19.9, 19.3, 17.4, 11.2,
2.7 ppm. MS (EI): m/z = 186 [M]+, 171, 156, 143, 128, 115, 105,
91, 77. HRMS (EI): calcd. for C14H18 186.1409; found 186.1398.
188.1201; found 188.1186. IR (film): ν = 3075, 3000, 2954, 2834,
˜
1613, 1515, 1463, 1291, 1247, 1178, 1038, 825 cm–1. The analytical
data of the trans isomer are consistent with those in the litera-
ture.[21]
IR (film): ν = 3078, 3003, 2967, 2921, 1505, 1453, 1017, 996,
˜
817 cm–1.
1-(Bicyclopropyl)-3-pentylbenzene (20): After purification by col-
umn chromatography (pentane), the product [20/1-(bicyclopropyl)-
2-pentylbenzene, Ͼ95:5, 59 mg, 51%] was obtained as a colorless
oil. 1H NMR (300 MHz, CDCl3): δ = 7.24–7.14 (m, 3 H), 7.00 (dt,
J = 6.7, 1.8 Hz, 1 H), 2.62–2.54 (m, 2 H), 1.68–1.55 (m, 5 H), 0.90
(t, J = 6.8 Hz, 3 H), 0.74–0.66 (m, 2 H), 0.66–0.58 (m, 2 H), 0.46–
0.38 (m, 2 H), 0.16–0.08 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 146.6, 142.7, 127.9, 127.8, 125.8, 125.0, 36.0, 31.6,
31.2, 25.0, 22.5, 17.2, 14.0, 11.6, 2.7 ppm. MS (EI): m/z = 228
[M]+, 213, 200, 171, 157, 143, 129, 115, 91, 77. HRMS (EI): calcd.
1-(Bicycloprop-2-yl)-4-(4-methylpent-3-enyl)benzene (21d): After
purification by column chromatography (pentane), the product
(21d/22d, 92:8, 53 mg, 44%) was obtained in a diastereomeric ratio
1
of 40:60 as a colorless oil. H NMR (300 MHz, CDCl3): δ = 7.20
(d, J = 7.9 Hz, 2 H), 7.14–7.05 (m, 4 H), 6.97 (d, J = 7.9 Hz, 2 H),
5.24–5.13 (m, 2 H), 2.62 (t, J = 7.1 Hz, 2 H), 2.59 (t, J = 7.8 Hz,
2 H), 2.35–2.22 (m, 4 H), 2.09 (dt, J = 8.6, 6.0 Hz, 1 H), 1.70 (s, 6
H), 1.68–1.61 (m, 1 H), 1.59 (s, 3 H), 1.57 (s, 3 H), 1.19–1.08 (m,
1 H), 1.01–0.89 (m, 2 H), 0.87–0.67 (m, 4 H), 0.50–0.08 (m, 9
H) ppm. 13C NMR (75 MHz, CDCl3): δ = 141.0, 139.5, 139.3,
137.3, 132.0, 129.0, 128.3, 127.9, 125.5, 123.9, 35.74, 35.66, 30.12,
30.10, 25.7, 25.1, 22.4, 21.4, 21.1, 17.7, 17.6, 13.6, 12.4, 9.7, 9.6,
4.8, 4.6, 3.3, 2.6 ppm. MS (EI): m/z = 240 [M]+, 207, 186, 171,
155, 141, 129, 117, 105, 91, 77, 69. HRMS (EI): calcd. for C18H24
for C17H24 228.1878; found 228.1864. IR (film): ν = 3078, 3004,
˜
2957, 2928, 2857, 1605, 1487, 1459, 1383, 1017, 784, 705 cm–1.
Note on Characterizations of 21a–21e: As described above, alkyne
3 was synthesized as nearly a 1:1 mixture of cis and trans isomers.
Accordingly, the assignments of the NMR signals of products 21a–
21e were less obvious, and in some cases specific assignments are
only tentative, as a separation of the four possible regioisomers and
diastereomers could not be accomplished by column chromatog-
raphy on silica gel.
240.1878; found 240.1861. IR (film): ν = 3076, 3001, 2968, 2924,
˜
2856, 1516, 1451, 1376, 1107, 1033, 1017, 887, 820 cm–1.
5-(Bicycloprop-2-yl)-2-methylbiphenyl (21e): After purification by
column chromatography (pentane), the product (21e/22e, Ͼ95:5,
39 mg, 32%) was obtained in a diastereomeric ratio of 40:60 as a
colorless oil. 1H NMR (300 MHz, CDCl3): δ = 7.49–7.29 (m, 10
H), 7.23–7.14 (m, 4 H), 7.00–6.90 (m, 2 H), 2.27 (s, 3 H), 2.23 (s,
3 H), 2.19–2.04 (m, 1 H), 1.74–1.63 (m, 1 H), 1.23–1.10 (m, 1 H),
1.03–0.90 (m, 2 H), 0.89–0.69 (m, 4 H), 0.52–0.07 (m, 9 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 142.3, 142.1, 141.7, 141.3, 141.1,
137.5, 132.3, 132.1, 130.7, 130.2, 129.8, 129.22, 129.15, 128.1,
128.00, 127.98, 127.2, 126.7, 126.6, 124.5, 25.2, 22.5, 21.3, 21.1,
20.0, 19.9, 13.6, 12.4, 9.8, 9.7, 4.8, 4.7, 3.3, 2.6 ppm. MS (EI): m/z
= 248 [M]+, 233, 219, 205, 194, 181, 165, 152, 141, 128, 115, 91,
77. HRMS (EI): calcd. for C19H20 248.1565; found 248.1549. IR
1-(Bicycloprop-2-yl)-4-methylbenzene (21a): After purification by
column chromatography (pentane), the product (21a/22a, 92:8,
46 mg, 53%) was obtained in a diastereomeric ratio of 41:59 as a
colorless oil. 1H NMR (300 MHz, CDCl3): δ = 7.22–7.16 (m, 2 H),
7.14–7.04 (m, 4 H), 6.98–6.92 (m, 2 H), 2.34 (s, 3 H), 2.32 (s, 3 H),
2.09 (dt, J = 8.7, 6.2 Hz, 1 H), 1.64 (dt, J = 8.9, 5.0 Hz, 1 H), 1.17–
1.07 (m, 1 H), 1.01–0.67 (m, 7 H), 0.50–0.08 (m, 10 H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 140.6, 137.0, 134.9, 134.7, 129.1,
128.9, 128.5, 125.6, 25.8, 25.1, 21.3, 21.1, 21.0, 20.9, 13.5, 12.4, 9.8,
9.6, 4.7, 4.5, 3.3, 2.6 ppm. MS (EI): m/z = 172 [M]+, 157, 143, 129,
118, 105, 91, 77, 65. The analytical data of the trans isomer are
consistent with those in the literature.[21]
(film): ν = 3075, 3000, 2923, 1601, 1574, 1504, 1489, 1443, 1139,
˜
1073, 1017, 896, 818, 771, 703 cm–1.
4-(Bicycloprop-2-yl)-1,2-dimethylbenzene (21b): After purification
3-(Bicyclopropyl)biphenyl (23a) and 2-(Bicyclopropyl)biphenyl (24a):
by column chromatography (pentane), the product (69 mg, 75%)
After purification by column chromatography (pentane/dichloro-
8
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Diels–Alder Reactions for the Construction of Cyclopropylarenes
methane, 10:1), the product (71 mg, 61%) was obtained as a mix-
ture of regioisomers and an unidentified side product (approxi-
mately 10%) as a colorless oil. H NMR (300 MHz, CDCl3): δ =
124.4, 124.2, 25.5, 22.6, 21.8, 21.6, 13.9, 12.4, 9.82, 9.78, 4.8, 4.6,
3.4, 2.6 ppm. MS (EI): m/z = 234 [M]+, 219, 205, 191, 180, 165,
152, 139, 128, 115, 102, 91, 77. HRMS (EI): calcd. for C18H18
1
7.67–7.57 (m, 3 H), 7.51–7.33 (m, 6 H), 1.43–1.30 (m, 1 H), 0.84–
0.77 (m, 2 H), 0.73–0.66 (m, 2 H), 0.52–0.43 (m, 2 H), 0.24–0.14
(m, 2 H) ppm. All of the signals could not be assigned in the 13C
NMR spectrum. The resolved signals are listed. 13C NMR
(75 MHz, CDCl3): δ = 147.3, 141.6, 141.1, 128.7, 128.5, 127.2,
127.1, 126.7, 124.6, 25.2, 24.9, 18.9, 17.2, 12.1, 11.7, 3.5, 2.8 ppm.
MS (EI): m/z = 234 [M]+, 219, 205, 191, 178, 165, 152, 141, 128,
115, 101, 91, 77. HRMS (EI): calcd. for C18H18 234.1409; found:
234.1408.
234.1409; found 234.1416. IR (film): ν = 3063, 2999, 1600, 1481,
˜
1449, 1420, 1075, 1017, 894, 758, 699 cm–1.
1-(Bicycloprop-2-yl)-3-cyclohexenylbenzene (29b): After purification
by column chromatography (pentane), the product (29b/30b,
Ͼ95:5, 78 mg, 71%) was obtained in a diastereomeric ratio of 50:50
as a yellow oil. 1H NMR (500 MHz, CDCl3): δ = 7.31 (s, 1 H),
7.23–7.10 (m, 5 H), 7.06 (s, 1 H), 6.88 (d, J = 7.3 Hz, 1 H), 6.14–
6.10 (m, 1 H), 6.10–6.06 (m, 1 H), 2.46–2.37 (m, 4 H), 2.25–2.17
(m, 4 H), 2.11 (dt, J = 8.6, 6.3 Hz, 1 H), 1.83–1.74 (m, 4 H), 1.70–
1.62 (m, 5 H), 1.19–1.12 (m, 1 H), 0.98–0.91 (m, 2 H), 0.87–0.78
(m, 2 H), 0.77–0.71 (m, 2 H), 0.47–0.33 (m, 3 H), 0.33–0.27 (m, 1
H), 0.27–0.10 (m, 5 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
143.5, 142.8, 142.1, 139.9, 136.81, 136.77, 128.0, 127.8, 127.5,
125.9, 124.6, 124.4, 123.7, 122.5, 122.2, 122.1, 27.52, 27.47, 25.89,
25.85, 25.2, 23.11, 23.08, 22.5, 22.21, 22.18, 21.8, 21.6, 13.7, 12.4,
9.8, 9.7, 4.8, 4.6, 3.3, 2.6 ppm. MS (EI): m/z = 238 [M]+, 223, 209,
184, 171, 165, 155, 141, 129, 105, 91, 81. HRMS (EI): calcd. for
[3-(Bicyclopropyl)phenyl]trimethylsilane (23b): After purification by
column chromatography (pentane), the product (23b/24b, Ͼ95:5,
1
51 mg, 44%) was obtained as a colorless oil. H NMR (300 MHz,
CDCl3): δ = 7.56–7.52 (m, 1 H), 7.41–7.27 (m, 3 H), 1.31 (tt, J =
8.1, 5.3 Hz, 1 H), 0.74–0.71 (m, 2 H), 0.71–0.63 (m, 2 H), 0.51–
0.40 (m, 2 H), 0.29 (s, 9 H), 0.19–0.12 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 145.8, 140.1, 132.6, 130.7, 128.5, 127.5, 25.2,
17.3, 11.4, 2.8, –1.1 ppm. MS (EI): m/z = 230 [M]+, 215, 202, 187,
171, 156, 141, 128, 115, 105, 91, 73, 59. HRMS (EI): calcd. for
C18H22 238.1722; found 238.1723. IR (film): ν = 3072, 3000, 2929,
˜
2858, 2834, 1601, 1486, 1435, 1345, 1017, 891, 787, 699 cm–1.
C H Si 230.1491; found 230.1494. IR (film): ν = 3078, 3004,
˜
15 22
2955, 2896, 1589, 1393, 1249, 1128, 1017, 859, 837, 753, 706 cm–1.
2-{2-[Bicycloprop-2-yl]-6-cyclohexenylphenyl}-4,4,5,5-tetramethyl-
1,3,2-dioxaborolane (29c): After purification by column chromatog-
raphy (pentane/methyl tert-butyl ether, 100:1), the product (29c/30c,
Ͼ99:1, 129 mg, 70%) was obtained in a diastereomeric ratio of
(Z)-[3-(1-Cyclopropylprop-1-enyl)phenyl]triisopropylsilane (25): Af-
ter purification by column chromatography (pentane) and bulb-to-
bulb distillation (0.1 mbar, 70 °C), the product {25/(Z)-[2-(1-cy-
clopropylprop-1-enyl)phenyl]triisopropylsilane, Ͼ99:1, 83 mg,
1
50:50 as a yellow oil. H NMR (500 MHz, CDCl3): δ = 7.17 (d, J
1
= 7.6 Hz, 1 H), 7.14 (d, J = 7.6 Hz, 1 H), 7.02 (d, J = 7.7 Hz, 1
H), 6.96 (d, J = 7.6 Hz, 1 H), 6.92 (dd, J = 7.6, 0.8 Hz, 1 H), 6.63
(d, J = 7.7 Hz, 1 H), 5.66–5.60 (m, 2 H), 2.38–2.32 (m, 4 H), 2.29
(dt, J = 8.7, 6.2 Hz, 1 H), 2.17–2.10 (m, 4 H), 1.85 (dt, J = 8.9,
5.1 Hz, 1 H), 1.80–1.72 (m, 4 H), 1.69–1.62 (m, 4 H), 1.36 (s, 12
H), 1.35 (s, 12 H), 1.30–1.21 (m, 1 H), 1.06–0.98 (m, 1 H), 0.95–
0.83 (m, 2 H), 0.81–0.76 (m, 2 H), 0.66 (dt, J = 8.8, 5.3 Hz, 1 H),
0.46–0.29 (m, 4 H), 0.20–0.09 (m, 4 H), 0.06 to –0.01 (m, 1 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 148.8, 148.7, 146.6, 142.9, 141.5,
141.4, 128.5, 127.7, 125.4, 125.31, 125.28, 123.9, 123.6, 120.4, 83.5,
83.3, 30.3, 30.2, 25.5, 25.4, 25.34, 25.28, 25.26, 24.9, 23.1, 23.0,
22.6, 22.02, 22.00, 21.9, 21.6, 13.5, 12.3, 9.3, 9.1, 4.5, 4.1, 3.4,
2.1 ppm. MS (EI): m/z = 364 [M]+, 335, 310, 295, 280, 264, 249,
235, 223, 210, 193, 181, 167, 153, 141, 128, 115, 101, 83. HRMS
53%} was obtained as a yellow oil. H NMR (300 MHz, CDCl3):
δ = 7.35–7.26 (m, 2 H), 6.90 (d, J = 7.8 Hz, 1 H), 6.73 (dd, J =
11.4, 1.3 Hz, 1 H), 5.86 (dq, J = 11.6, 6.9 Hz, 1 H), 1.93 (tt, J =
8.6, 5.3 Hz, 1 H), 1.78 (dd, J = 7.0, 1.7 Hz, 3 H), 1.38 (sept, J =
7.6 Hz, 3 H), 1.08 (d, J = 7.4 Hz, 18 H), 0.93 (ddd, J = 8.4, 6.2,
4.3 Hz, 2 H), 0.74–0.65 (m, 2 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 141.7, 136.2, 136.0, 133.9, 130.5, 129.5, 126.4, 123.2,
18.6, 14.5, 12.9, 10.8, 8.0 ppm. MS (EI): m/z = 314 [M]+, 271, 243,
229, 215, 201, 187, 169, 155, 141, 128, 115, 93, 73. HRMS (EI):
calcd. for C H Si 314.2430; found 314.2412. IR (film): ν = 3082,
˜
21 34
3011, 2943, 2865, 1592, 1463, 1383, 1366, 1094, 1044, 1016, 995,
883, 677, 666, 651 cm–1.
1-Bicyclopropyl-2,3-bis(methoxymethyl)benzene (23c): After purifi-
cation by column chromatography (pentane/methyl tert-butyl ether,
(EI): calcd. for C H BO 364.2574; found 364.2554. IR (film): ν
˜
24 33
2
1
20:1), the product (23 mg, 19%) was obtained as a yellow oil. H
= 3070, 2991, 2929, 2858, 2835, 1587, 1566, 1442, 1371, 1323, 1303,
NMR (300 MHz, CDCl3): δ = 7.32 (dd, J = 6.9, 2.2 Hz, 1 H), 7.25–
7.17 (m, 2 H), 4.76 (s, 2 H), 4.58 (s, 2 H), 3.47 (s, 3 H), 3.44 (s, 3
H), 1.08 (tt, J = 8.2, 5.3 Hz, 1 H), 0.78–0.72 (m, 2 H), 0.70–0.64
(m, 2 H), 0.35–0.27 (m, 2 H), 0.09–0.02 (m, 2 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 144.9, 138.4, 135.2, 130.9, 128.0, 127.1, 72.2,
68.4, 58.7, 58.5, 24.8, 18.8, 11.0, 2.7 ppm. MS (EI): m/z = 246
[M]+, 231, 217, 201, 182, 167, 154, 141, 128, 115, 102, 91, 77.
HRMS (EI): calcd. for C16H22O2 246.1620; found 246.1618. IR
1145, 1111, 1053, 858, 750, 675 cm–1.
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H NMR and 13C NMR spectra of all key inter-
mediates and products.
Acknowledgments
(film): ν = 3074, 2994, 2924, 2881, 2816, 1686, 1458, 1378, 1190,
˜
This work was supported by the Land Niedersachsen, the Fonds
der Chemischen Industrie, and Chemetall GmbH (chemicals). We
thank the German Science Foundation for its financial support.
1097, 1022, 954, 914, 792, 754 cm–1.
3-(Bicycloprop-2-yl)biphenyl (29a): After purification by column
chromatography (pentane/diethyl ether, 100:1), the product (29a/
30a, Ͼ99:1, 89 mg, 76%) was obtained in a diastereomeric ratio of
[1] a) A. de Meijere, Angew. Chem. 1979, 91, 867–884; Angew.
Chem. Int. Ed. Engl. 1979, 18, 809–826; b) K. B. Wiberg in
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1
50:50 as a light yellow oil. H NMR (300 MHz, CDCl3): δ = 7.66–
7.55 (m, 4 H), 7.54 (s, 1 H), 7.50–7.40 (m, 5 H), 7.40–7.31 (m, 5
H), 7.31–7.25 (m, 2 H), 7.03 (dt, J = 6.8, 1.6 Hz, 1 H), 2.19 (dt, J
= 8.7, 6.4 Hz, 1 H), 1.75 (dt, J = 8.6, 5.0 Hz, 1 H), 1.30–1.17 (m,
1 H), 1.06–0.76 (m, 6 H), 0.52–0.11 (m, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 144.2, 141.53, 141.45, 141.3, 140.7, 140.6,
128.7, 128.6, 128.2, 128.1, 127.20, 127.16, 127.1, 124.7, 124.5,
Eur. J. Org. Chem. 0000, 0–0
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M. Arndt, G. Hilt, A. F. Khlebnikov, S. I. Kozhushkov, A. de Meijere
FULL PAPER
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Received: January 30, 2012
Published Online: ᭿
10
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Job/Unit: O20105
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Date: 17-04-12 15:23:53
Pages: 11
Diels–Alder Reactions for the Construction of Cyclopropylarenes
Homogeneous Catalysis
M. Arndt, G. Hilt,* A. F. Khlebnikov,
S. I. Kozhushkov, A. de Meijere* ..... 1–11
Diels–Alder Reactions for the Construc-
tion of Cyclopropylarenes
The application of cyclopropyl-substituted
alkynes and 1,3-dienes in cobalt-catalyzed
Diels–Alder reactions led to various cyclo-
propyl-substituted arenes. In only one case,
the ring-opened product was isolated. This
shows that the cyclopropyl subunits were
generally compatible with the conditions of
the cobalt catalysis and of the subsequent
DDQ oxidation of the dihydroaromatic in-
termediates.
Keywords: Cycloaddition / Arenes / Small
ring systems / Cobalt / Dehydrogenation
Eur. J. Org. Chem. 0000, 0–0
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