Ruthenium-catalyzed sequential enyne cross-metathesis/ATRA reactions

Article abstract of DOI:10.1002/ejoc.201101263

Sequential enyne cross-metathesis reactions of arylalkynes with ethylene followed by atom transfer radical addition (ATRA) with ethyl dichloroacetate or dichloroacetonitrile provide 1,5-dichloropent-2-ene derivatives. The second-generation Grubbs alkylide

Full text of DOI:10.1002/ejoc.201101263

FULL PAPER
DOI: 10.1002/ejoc.201101263
Ruthenium-Catalyzed Sequential Enyne Cross-Metathesis/ATRA Reactions
Gregor Kiefer,[a] Jesus Ruiz,[a] Euro Solari,[a] Gerhard Hilt,[b] and Kay Severin*[a]
Keywords: ATRA / Metathesis / Radical reactions / Ruthenium
Sequential enyne cross-metathesis reactions of arylalkynes
with ethylene followed by atom transfer radical addition
(ATRA) with ethyl dichloroacetate or dichloroacetonitrile
provide 1,5-dichloropent-2-ene derivatives. The second-gen-
eration Grubbs alkylidene complex [RuCl2(=CHPh)(PCy3)-
(NHC)] [NHC = 1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidi-
nylidene] is used as the catalyst precursor for both reactions.
Preliminary results show that the reaction products can be
converted into vinylcyclopropanes by dechlorination with
magnesium or manganese.
Introduction
In 1999, the groups of Snapper and Demonceau reported
that the first-generation Grubbs catalyst 1 can mediate
atom transfer radical addition (ATRA) reactions of haloge-
nated compounds to olefins.[1] Subsequent studies have
shown that several other (alkylidene)ruthenium complexes
are also able to promote ATRA reactions.[2,3] These find-
ings triggered attempts to perform metathesis and ATRA
reactions in a sequential fashion with the same ruthenium
catalyst, and the first examples were described in 2005.[4]
It was demonstrated that 1 is able to catalyze ring-closing
metathesis (RCM)/atom transfer radical cyclization
(ATRC) cascades to give bicyclic lactams (Scheme 1a).[4a]
Recent studies have shown that this tandem reaction can be
combined with palladium-mediated rearrangements,[5] and
that the dimetallic complex 3 is also a suitable catalyst pre-
cursor.[6] In a related fashion, bicyclic lactones can be ob-
tained from RCM/ATRC reactions (Scheme 1b).[4b] In this
case, utilization of the second-generation Grubbs metathesis
catalyst 2 was advantageous. Sequential metathesis/radical
additions are not restricted to intramolecular reactions. An
RCM followed by an intermolecular ATRA (Scheme 1c)[4a]
and an intermolecular cross-metathesis (CM) combined
with an ATRC reaction have been reported.[7] However, in
both cases the products were obtained in moderate yields.
Here, we describe a new reaction cascade and show that
it is possible to combine enyne cross-metathesis reactions
with ATRA reactions in one pot to give 1,5-dichloropent-
2-ene derivatives, which are interesting starting materials for
the synthesis of vinylcyclopropanes.
Scheme 1. Examples of sequential metathesis/ATRA reactions.
Results and Discussion
[a] Institut des Sciences et Ingénierie Chimiques,
École Polytechnique Fédérale de Lausanne (EPFL),
1015 Lausanne, Switzerland
Ruthenium-catalyzed enyne metathesis reactions have
emerged as versatile C–C coupling reactions in synthetic
chemistry.[8] The enyne cross-metathesis of alkynes with eth-
ylene gives buta-1,3-dienes.[9] This reaction is best per-
formed in the presence of the second-generation Grubbs
Fax: +41-21-693-9305
E-mail: kay.severin@epfl.ch
[b] Philipps-Universität Marburg,
Hans-Meerwein-Straße, 35043 Marburg, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101263.
Eur. J. Org. Chem. 2012, 93–98
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
93

G. Kiefer, J. Ruiz, E. Solari, G. Hilt, K. Severin
FULL PAPER
catalyst 2.[10] To examine the feasibility of sequential enyne Table 1. Ru-catalyzed ATRA reactions between ethyl dichloroacet-
ate and 2-phenylbuta-1,3-diene.[a] The yields were determined by
GC–MS with mesitylene as the internal standard.
cross-metathesis/ATRA reactions, we initially focused on
the second step as ATRA reactions of 1,3-dienes have
hardly been investigated.[11] As test reactions, we used the
ATRA of ethyl dichloroacetate to 2-phenylbuta-1,3-diene.
Ethyl dichloroacetate displays a low intrinsic activity com-
pared to commonly used ATRA substrates such as CCl4.
However, it is more interesting from a synthetic point of
view (see below).
Initially, reactions were performed with the half-sand-
wich complex [Cp*RuCl2(PPh3)] in conjunction with mag-
nesium. This combination is one of the best catalyst systems
Catalyst
Additive
Yield A [%]
Yield B [%]
[Cp*RuCl2(PPh3)]
Mg
Mg
none
Mg
68
65
42
44
2
5
3
4
2
2
[RuCl2L(NHC)][b]
[a] Reaction conditions: [2-phenylbuta-1,3-diene] = 100 mm, [ethyl
dichloroacetate] = 130 mm, [Ru] = 5 mm, 80 °C, 16 h, 20 equiv. Mg
with respect to the diene. [b] L = (o-isopropoxyphenyl)methylene.
for ATRA reactions known to date.[12] The role of magne- yield of 70% was obtained. However, the regioselectivity
sium is in the generation and regeneration of the catalyti- was slightly lower with an increased yield of 5% for B {2%
cally active RuII complex.[12,13] In ATRA reactions with ter- for reactions with [Cp*RuCl2(PPh3)]}. The conversion of 2-
minal olefins, the new C–C bond is generated with high phenylbuta-1,3-diene was complete at the end of the reac-
selectivity at the terminal carbon atom of the olefin.[3a] Still, tion, which is likely to be because of competing polymeriza-
there are several possible isomers for addition products of tion processes. When magnesium was omitted, the yield of
ethyl dichloroacetate and 2-phenylbuta-1,3-diene. If the ad- the ATRA dropped substantially. This result is in line with
dition proceeds in a 1,4 fashion, isomers A and B are previous reports about the beneficial effects of Mg for tran-
formed, which are each a mixture of two stereoisomers sition-metal-catalyzed ATRA reactions.[12,14] We also tested
(Scheme 2). 1,2-Addition, on the other hand, gives the iso- the ATRA activity of Hoveyda’s alkylidene complex
mer(s) C and/or D as a mixture of diastereoisomers.
[RuCl2L(NHC)] [L = (o-isopropoxyphenyl)methylene],[15]
which is a competent enyne cross-metathesis catalyst.[8a]
The complex was also able to catalyze the ATRA reaction,
but its activity was lower than that of 2.
Having established that 2 is able to catalyze an ATRA
reaction with the enyne metathesis product 2-phenylbuta-
1,3-diene, we explored the possibility of performing sequen-
tial enyne cross-metathesis/ATRA reactions in one pot with
different aromatic alkynes. As outlined above, 2 is a suitable
catalyst precursor for enyne cross-metathesis and ATRA re-
actions. However, these results do not imply that 2 is neces-
sarily a suitable catalyst precursor for sequential enyne
cross-metathesis/ATRA reactions. During the enyne cross-
metathesis reaction, the complex might be converted into a
species that is inactive (or less active) as a catalyst in ATRA
reactions. As halogenated substrates, we used dichloroace-
tonitrile and ethyl trichloroacetate in addition to ethyl
dichloroacetate. The results are summarized in Table 2.
The enyne cross-metathesis of different aromatic alkynes
with ethylene followed by an ATRA reaction with ethyl
dichloroacetate gave the corresponding 1,4-addition prod-
Scheme 2. Possible reaction products of the ATRA reaction of 2-
phenylbuta-1,3-diene and ethyl dichloroacetate.
The reaction of 2-phenylbuta-1,3-diene (100 mm) with ucts in isolated yields of 28–57%. Isomer A was the domi-
ethyl dichloroacetate (130 mm) was carried out in toluene nant product in all cases with a slight preference for the (Z)
at 80 °C by using 5 mol-% of the catalyst precursor configuration. Reactions with dichloroacetonitrile were less
[Cp*RuCl2(PPh3)] and magnesium powder as the additive. efficient and required the addition of more catalyst during
After 16 h, the ATRA adducts A and B were formed in the ATRA step (another 2 mol-%). Still, the yields were
68 and 2% yield, respectively (Table 1). The 1,2-addition lower than those obtained with ethyl dichloroacetate. Iso-
products C and D were not observed. This result demon- mer A was again the dominant product, but this time the
strated that an ATRA reaction of ethyl dichloroacetate with preferred configuration was (E). Not unexpectedly, a reac-
an enyne metathesis product is feasible if forcing conditions tion with ethyl trichloroacetate, which is a substrate of high
are employed (high catalyst loading and elevated tempera- intrinsic activity,[12a] gave a good yield of 74% (isolated
ture).
Next, we investigated whether 2, which is a good enyne
yield 58%).
We have previously shown that the ATRA products de-
cross-metathesis catalyst,[10] was also able to promote the rived from simple olefins can be dehalogenated with acti-
reaction between 2-phenylbuta-1,3-diene and ethyl dichlo- vated magnesium[16] or manganese[17] to give cyclopropanes
roacetate. Under similar conditions as before, the same total by an intramolecular C–C coupling reaction. These results
94
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Eur. J. Org. Chem. 2012, 93–98

Ruthenium-Catalyzed Sequential Enyne Cross-Metathesis/ATRA Reactions
Table 2. Sequential enyne cross-metathesis/ATRA reactions in the intramolecular nucleophilic attack of the olefin and libera-
presence of catalyst 2.[a]
tion of chloride (SN2Ј-type reaction), but further investi-
gations are needed to substantiate this hypothesis. Cyclo-
propane 4 has previously been prepared in moderate yield
(56%) by Rh-catalyzed cyclopropanation of 2-phenylbuta-
1,3-diene with ethyl diazoacetate[20] and by an Ru-catalyzed
enyne cross-metathesis/cyclopropanation reaction cascade
(30%).[21] To the best of our knowledge, the synthesis of
cyclopropane 5 has not been reported before.
A comparison of the two dechlorination procedures is
given in Table 3. For the reaction with ethyl 2,6-dichloro-4-
phenylhex-4-enoate, both procedures provided cyclopro-
pane 4, but the utilization of magnesium gave a lower yield
than that obtained with manganese (42 vs. 64%). For reac-
tions with 2,6-dichloro-4-phenylhex-4-enenitrile, only de-
halogenation with manganese was successful.
R
RЈ
Yield
A [%] B [%]
Yield Isolated yield (E)/(Z)
A + B [%]
A
H
H
CHClCO2Et
CHClCN
65
39
62
48
49
35
5
8
4
8
9
12
13
15[b]
–
3
56
38
52
40
57
45
47
40
28
58
42:58
81:19
37:63
69:31
33:67
73:27
43:57
80:20
40:60[d]
40:60
Me CHClCO2Et
Me
F
Table 3. Reductive dechlorination of 1,5-dichloropent-2-ene deriva-
tives.
CHClCN
CHClCO2Et
CHClCN
F
R
Conditions[a] Time Yield Isolated yield (E)/(Z)
CF3 CHClCO2Et
55
[min] [%][b]
[%]
CF3
Ph
H
CHClCN
CHClCO2Et
CCl2CO2Et
41[b]
[c]
[c]
45[c]
66
42
64
–
50:50
50:50
–
–
CO2Et
CO2Et
CN
A
B
A
B
20
180
10
71
0[c]
70
[a] Reaction conditions: Enyne metathesis: [alkyne] = 100 mm, [2]
= 5 mm, 1 atm ethylene, toluene, 30 °C, 90 min; ATRA: 1.3 equiv.
RЈCl and 20 equiv. Mg with respect to the alkyne, 80 °C, 16 h.
When RЈ = CN, an additional amount of 2 mol-% catalyst and
1.3 equiv. of chlorinated compound dissolved in a small amount of
dichloroethane was added after 16 h and the mixture stirred for
another 16 h. The crude yields of A and B and the (E)/(Z) ratio
of A were determined by GC–MS with mesitylene as the internal
standard. [b] Additional stirring time of 34 h. [c] The determination
of the yield by GC–MS was not possible because of decomposition
CN
90
37
45:55
[a] Reaction conditions: A: 10 equiv. Mg, [LiCl] = 100 mm, THF,
room temp.; B: 10 equiv. Mn, 1 equiv. trimethylsilyl chloride,
1
0.05 equiv. PbCl2, THF, 60 °C. [b] Determined by H NMR spec-
troscopy with 1,3,5-triisopropylbenzene as the internal standard.
[c] Longer reaction times did not improve the yield.
The isolation of 4 and 5 was difficult as they decompose
during column chromatography on silica gel, neutral alu-
mina, and deactivated silica gel (NEt3). In the case of 4,
the crude products were acceptably clean (Ͼ90%, NMR).
Cyclopropane 5 was purified by trap-to-trap distillation,
which resulted in a substantial loss of material.
1
in the instrument. [d] Determined by H NMR spectroscopy.
Conclusions
The second-generation Grubbs metathesis catalyst 2 was
used to perform enyne cross-metathesis/ATRA reactions in
a sequential fashion. The new procedure provides 1,5-
dichloropent-2-ene derivatives with good regioselectivity.
The products are potentially interesting intermediates for
subsequent transformations as demonstrated by the synthe-
sis of the vinylcyclopropanes 4 and 5 by dechlorination with
manganese.
Scheme 3. Reductive dechlorination of 1,5-dichloropent-2-ene de-
rivatives to vinylcyclopropane derivatives.
prompted us to investigate dechlorination reactions with
the 1,4-addition products described above. We examined the
reactivity of ethyl 2,6-dichloro-4-phenylhex-4-enoate and
2,6-dichloro-4-phenylhex-4-enenitrile. As a reducing agent,
we employed magnesium in the presence of LiCl[18] or man-
ganese, which was preactivated with PbCl2 and chlorotri-
methylsilane.[19] Analysis of the reaction mixtures showed
that a dechlorination reaction had taken place in both cases.
However, instead of cyclopentenes, we observed the forma-
tion of vinlycyclopropanes 4 and 5 as a mixture of isomers
(Scheme 3). To the best of our knowledge, the reductive
coupling of 1,5-dichloropent-2-enes to give vinylcyclopro-
panes has not been described before. The mechanism might
Experimental Section
General: [Cp*RuCl2(PPh3)] was prepared as described in the litera-
ture.[22] [RuCl2(=CHPh)(PCy3)(NHC)] (2) and [RuCl2L(NHC)]
were purchased from Sigma Aldrich. The substrates were all
commercially available. Mg powder (Ͼ99%) was purchased from
Sigma Aldrich. To activate its surface, it was stirred magnetically
under dry dinitrogen for 5 d before use. Mn powder
(–140+325 mesh, 99.6%) was purchased from AlfaAesar. 1H and
involve the formation of a Grignard reagent followed by an 13C NMR spectra were recorded with a Bruker Avance DPX 400
Eur. J. Org. Chem. 2012, 93–98
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95

G. Kiefer, J. Ruiz, E. Solari, G. Hilt, K. Severin
FULL PAPER
spectrometer with the residual solvents as internal standards. All
spectra were recorded at room temperature. The isolated yields re-
fer to isomer A plus isomer B (see Table 2), whereas the NMR data
are given for the main isomer A. Unless otherwise stated, all reac-
tions were performed under dry nitrogen. The solvents were ob-
tained from a solvent purification system from innovative technol-
ogies (IT).
7.2 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): (E) and (Z) ole-
fin: δ = 169.1, 140.5, 139.3, 138.2, 138.0, 133.8, 129.4, 128.1, 127.2,
126.8, 126.6, 62.2, 62.1, 54.9, 54.7, 44.2, 41.4, 40.5, 35.2, 21.2, 21.1,
14.0 ppm. HRMS (EI): calcd. for C15H18Cl2O2 [M]+ 300.0684;
found 300.0672.
2,6-Dichloro-4-(p-tolyl)hex-4-enenitrile: Table 2, Entry 4. Isolated
1
yield: 102 mg, 40%. H NMR (400 MHz, CDCl3): (E) olefin: δ =
General Procedure for the Sequential Enyne Cross-Metathesis/
7.24–7.19 (m, 4 H), 6.11 (t, J = 8.0 Hz, 1 H), 4.33–4.25 (m, 3 H),
3.37 (dd, J = 14.4, 7.2 Hz, 1 H), 3.28 (dd, J = 14.4, 8.0 Hz, 1 H),
2.37 (s, 3 H) ppm; (Z) olefin: δ = 7.22–7.20 (m, 2 H), 7.11–7.09 (m,
2 H), 5.93 (t, J = 7.8 Hz, 1 H), 4.18 (dd, J = 8.2, 7.4 Hz, 1 H), 3.99
(d, J = 7.8 Hz, 2 H), 3.28 (dd, J = 14.4, 6.9 Hz, 1 H), 3.05 (dd, J
= 14.4, 8.2 Hz, 1 H), 2.39 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): (E) and (Z) olefin: δ = 138.9, 138.7, 138.3, 137.6, 135.6,
132.5, 129.7, 129.4, 128.6, 128.0, 126.5, 116.47, 116.46, 45.6, 40.9,
40.44, 40.40, 29.9, 36.8, 21.2, 21.1 ppm. HRMS (EI): calcd. for
C13H13Cl2N [M]+ 253.0425; found 253.0435.
ATRA Reactions: The arylacetylene (1.0 mmol),
2 (42 mg,
50 μmol), and mesitylene (internal standard, 42 μL, 0.30 mmol)
were dissolved in toluene (10 mL). The solution was degassed un-
der vacuum, purged with ethylene gas (1 atm), and stirred at 30 °C.
After 90 min, ethylene was removed by cycling with vacuum/N2.
Ethyl dichloroacetate (160 μL, 1.3 mmol) and activated Mg
(486 mg, 20 mmol) were added, and the reaction mixture was
stirred vigorously at 80 °C for 16 h. The mixture was cooled to
room temperature, Mg was removed by filtration, and the solution
was concentrated under vacuum. The residue was purified by flash
chromatography on silica gel (cyclohexane/dichloromethane, 7:3 or
8:2; Table 2, Entry 10). The products were obtained as colorless or
pale yellow oils. The (E)/(Z) configuration was assigned by a
ROESY experiment. For ethyl 2,6-dichloro-4-phenylhex-4-enoate
(Table 2, Entry 1), the isomer for which NOE coupling of the ole-
finic proton with the phenyl protons was observed was assigned as
the (E) isomer. The stereochemistry of the other products was as-
signed by comparison of the GC and NMR spectroscopic data with
those of ethyl 2,6-dichloro-4-phenylhex-4-enoate.
Ethyl 2,6-Dichloro-4-(4-fluorophenyl)hex-4-enoate: Table 2, Entry 5.
Isolated yield: 174 mg, 57%. 1H NMR (400 MHz, CDCl3): (E) ole-
fin: δ = 7.32–7.27 (m, 2 H), 7.05–7.02 (m, 2 H), 5.96 (t, J = 8.0 Hz,
1 H), 4.28 (d, J = 8.0 Hz, 2 H), 4.22–4.10 (m, 3 H), 3.28 (dd, J =
14.8, 6.4 Hz, 1 H), 3.30 (dd, J = 14.8, 8.4 Hz, 1 H), 1.25 (t, J =
7.2 Hz, 3 H) ppm; (Z) olefin: δ = 7.12–7.06 (m, 2 H), 7.22–7.17 (m,
2 H), 5.85 (t, J = 8.0 Hz, 1 H), 4.22–4.10 (m, 2 H), 4.07 (dd, J =
8.4, 6.8 Hz, 1 H), 3.90 (m, 2 H), 3.13 (dd, J = 14.0, 6.8 Hz, 1 H),
2.94 (dd, J = 14.0, 8.4 Hz, 1 H), 1.25 (t, J = 7.2 Hz, 3 H) ppm. 13
C
NMR (100 MHz, CDCl3): (E) and (Z) olefin: δ = 168.96, 168.93,
162.7 (d, J = 246 Hz), 162.5 (d, J = 246 Hz), 139.5, 138.4, 135.8
(d, J = 3 Hz), 132.7 (d, J = 4 Hz), 130.0 (d, J = 8 Hz), 128.5 (d, J
= 8 Hz), 128.1, 127.5, 115.8 (d, J = 21 Hz), 115.6 (d, J = 22 Hz),
62.3, 62.2, 54.7, 54.5, 44.1, 41.0, 40.2, 35.3, 14.0, 13.9 ppm. HRMS
(EI): calcd. for C14H15Cl2FO2 [M]+ 304.0433; found 304.0449.
Ethyl 2,6-Dichloro-4-phenylhex-4-enoate: Table 2, Entry 1. Isolated
yield: 161 mg, 56%. H NMR (400 MHz, CDCl3): (E) olefin: δ =
1
7.42–7.30 (m, 4 H), 7.21–7.19 (m, 1 H), 6.00 (t, J = 8.0 Hz, 1 H),
4.30 (d, J = 8.0 Hz, 2 H), 4.22–4.11 (m, 3 H), 3.32 (dd, J = 14.4,
6.8 Hz, 1 H), 3.19 (dd, J = 14.8, 8.4 Hz, 1 H), 1.28 (t, J = 7.2 Hz,
3 H) ppm; (Z) olefin: δ = 7.42–7.30 (m, 4 H), 7.21–7.19 (m, 1 H),
5.84 (t, J = 8.0 Hz, 1 H), 4.22–4.11 (m, 2 H), 4.09 (dd, J = 8.4,
6.8 Hz, 1 H), 3.94 (d, J = 8.0 Hz, 2 H), 3.16 (dd, J = 14.4, 6.9 Hz,
1 H), 2.94 (dd, J = 14.4, 8.0 Hz, 1 H), 1.25 (t, J = 7.2 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): (E) and (Z) olefins (CAr): δ =
128.7. 128.3, 128.20, 128.17, 128.0 ppm; (E) olefin: δ = 160.1, 139.7,
139.3, 126.8, 62.2, 54.8, 40.4, 35.2, 14.0 ppm; (Z) olefin: δ = 169.0,
140.4, 136.8, 127.1, 62.1, 54.6, 44.1, 41.3, 13.9 ppm. HRMS (EI):
calcd. for C14H16Cl2O2 [M]+ 286.0527; found 286.0534.
2,6-Dichloro-4-(4-fluorophenyl)hex-4-enenitrile: Table 2, Entry 6.
Isolated yield: 116 mg, 45%. 1H NMR (400 MHz, CDCl3): (E) ole-
fin: δ = 7.36–7.31 (m, 2 H), 7.14–7.08 (m, 2 H), 6.11 (t, J = 8.0 Hz,
1 H), 4.30 (d, J = 8.0 Hz, 2 H), 4.30 (dd, J = 8.0, 7.4 Hz, 1 H),
3.37 (dd, J = 14.8, 7.6 Hz, 1 H), 3.30 (dd, J = 14.8, 8.0 Hz, 1 H)
ppm; (Z) olefin: δ = 7.25–7.18 (m, 2 H), 7.17–7.08 (m, 2 H), 6.00
(t, J = 8.0 Hz, 1 H), 4.21 (dd, J = 8.0, 7.2 Hz, 1 H), 3.97 (d, J =
8.0 Hz, 2 H), 3.18 (dd, J = 14.0, 7.2 Hz, 1 H), 3.08 (dd, J = 14.4,
8.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): (E) and (Z) ole-
fin: δ = 163.0 (d, J = 249 Hz), 137.4, 136.8, 134.7 (d, J = 8 Hz),
130.0 (d, J = 8 Hz), 129.6, 129.0, 128.5 (d, J = 8 Hz), 125.3, 116.1
(d, J = 21 Hz), 45.5, 40.5, 40.3, 39.6, 37.0 ppm. HRMS (EI): calcd.
for C12H10Cl2FN [M]+ 257.0174; found 257.0175.
2,6-Dichloro-4-phenylhex-4-enenitrile: Table 2, Entry 2. Isolated
yield: 91 mg, 38%. 1H NMR (400 MHz, CDCl3): (E) olefin: δ =
7.45–7.31 (m, 4 H), 7.22–7.20 (m, 1 H), 6.13 (t, J = 8.0 Hz, 1 H),
4.30 (d, J = 8.0 Hz, 2 H), 4.29 (dd, J = 8.0, 7.4 Hz, 1 H), 3.32 (dd,
J = 14.4, 7.4 Hz, 1 H), 3.19 (dd, J = 14.4, 8.0 Hz, 1 H) ppm; (Z)
olefin: δ = 7.45–7.31 (m, 4 H), 7.22–7.20 (m, 1 H), 5.96 (t, J =
8.0 Hz, 1 H), 4.18 (dd, J = 8.4, 7.2 Hz, 1 H), 3.98 (d, J = 8.0 Hz,
2 H), 3.17 (dd, J = 14.0, 7.2 Hz, 1 H), 3.08 (dd, J = 14.0, 8.4 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3): (E) and (Z) olefin: δ =
138.6, 137.7, 129.4, 129.0, 128.9, 128.1, 126.7, 116.4, 45.6, 40.4,
39.8, 36.9 ppm. HRMS (EI): calcd. for C12H11Cl2N [M]+ 239.0281;
found 239.0281.
Ethyl
2,6-Dichloro-4-[4-(trifluoromethyl)phenyl]hex-4-enoate:
Table 2, Entry 7. Isolated yield: 167 mg, 47%. 1H NMR (400 MHz,
CDCl3): (E) olefin: δ = 7.63 (dd, J = 8.8, 0.8 Hz, 2 H), 7.44 (dd, J
= 8.8, 0.8 Hz, 2 H), 6.05 (t, J = 8.0 Hz, 1 H), 4.29 (d, J = 8.0 Hz,
2 H), 4.20–4.04 (m, 3 H), 3.32 (dd, J = 14.8, 6.8 Hz, 1 H), 3.20
(dd, J = 14.8, 8.0 Hz, 1 H), 1.25 (t, J = 7.2 Hz, 3 H) ppm; (Z)
olefin: δ = 7.67 (dd, J = 8.4, 0.8 Hz, 2 H), 7.36 (dd, J = 8.4, 0.8 Hz,
2 H), 5.91 (t, J = 8.0 Hz, 1 H), 4.20–4.04 (m, 2 H), 4.09 (dd, J =
Ethyl 2,6-Dichloro-4-(p-tolyl)hex-4-enoate: Table 2, Entry 3. Iso-
lated yield: 157 mg, 52%. 1H NMR (400 MHz, CDCl3): (E) olefin: 8.4, 6.8 Hz, 1 H), 3.89–3.86 (m, 2 H), 3.17 (dd, J = 14.4, 6.4 Hz, 1
δ = 7.23–7.16 (m, 2 H), 7.11–7.08 (m, 2 H), 5.98 (t, J = 8.0 Hz, 1
H), 3.08 (dd, J = 14.4, 8.0 Hz, 1 H), 1.27 (t, J = 7.2 Hz, 3 H)
H), 4.29 (d, J = 8.0 Hz, 2 H), 4.21–4.12 (m, 3 H), 3.30 (dd, J = ppm. 13C NMR (100 MHz, CDCl3): (E) and (Z) olefin: δ = 168.77,
14.8, 6.8 Hz, 1 H), 3.19 (dd, J = 14.8, 8.0 Hz, 1 H), 2.36 (s, 1 H) 168.75, 143.4, 140.7, 139.2, 138.2, 130.4 (q, J = 32 Hz), 130.3 (q, J
1.26 (t, J = 7.2 Hz, 3 H) ppm; (Z) olefin: δ = 7.23–7.16 (m, 4 H), = 32 Hz), 129.8, 128.7, 128.2, 127.2, 125.71 (q, J = 4 Hz), 125.67
5.84 (t, J = 8.0 Hz, 1 H), 4.20–4.12 (m, 2 H), 4.08 (dd, J = 8.0,
6.8 Hz, 1 H), 3.95 (d, J = 8.0 Hz, 2 H), 3.16 (dd, J = 14.4, 6.8 Hz,
1 H), 2.91 (dd, J = 14.4, 8.0 Hz, 1 H), 2.37 (s, 3 H), 1.28 (t, J =
(q, J = 4 Hz), 123.93 (q, J = 270 Hz), 123.87 (q, J = 270 Hz), 62.4,
62.3, 54.6, 54.4, 43.8, 40.7, 39.9, 35.1, 14.0, 13.9 ppm. HRMS (EI):
calcd. for C15H15Cl2F3O2 [M]+ 354.0401; found 354.0388.
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Ruthenium-Catalyzed Sequential Enyne Cross-Metathesis/ATRA Reactions
2,6-Dichloro-4-[4-(trifluoromethyl)phenyl]hex-4-enenitrile: Table 2,
Entry 8. Isolated yield: 123 mg, 40%. 1H NMR (400 MHz, CDCl3):
(E) olefin: δ = 7.66 (dd, J = 8.8, 0.4 Hz, 2 H), 7.46 (dd, J = 8.8,
0.4 Hz, 2 H), 6.19 (t, J = 8.0 Hz, 1 H), 4.30 (d, J = 8.0 Hz, 2 H),
4.30 (dd, J = 8.0, 7.2 Hz, 1 H), 3.40 (dd, J = 14.4, 7.2 Hz, 1 H),
3.33 (dd, J = 14.4, 8.0 Hz, 1 H) ppm; (Z) olefin: δ = 7.71 (dd, J =
colorless oil in 64% yield (138 mg) as a mixture of two diastereoiso-
mers [(E)/(Z) = 50:50, determined by NMR spectroscopy]. The
NMR spectroscopic data of 4 are in agreement with that reported
previously, and the isomers were assigned accordingly.[21] 1H NMR
(400 MHz, CDCl3): (E) isomer: δ = 7.36–7.25 (m, 5 H), 6.10 (dd,
J = 17.2, 10.4 Hz, 1 H), 5.08 (dd, J = 10.4, 1.2 Hz, 1 H), 4.62 (dd,
8.6, 0.6 Hz, 2 H), 7.37 (dd, J = 8.6, 0.6 Hz, 2 H), 6.05 (t, J = J = 17.2, 1.2 Hz, 1 H), 4.25–4.16 (m, 2 H), 2.26 (dd, J = 8.0, 6.0 Hz,
8.0 Hz, 1 H), 4.19 (dd, J = 8.4, 7.2 Hz, 1 H), 3.92 (d, J = 8.0 Hz,
2 H), 3.20 (dd, J = 14.4, 7.2 Hz, 1 H), 3.08 (dd, J = 14.4, 8.4 Hz,
1 H) ppm. 13C NMR (100 MHz, CDCl3): (E) olefin only: δ = 142.4,
136.5, 131.3, 130.9 (q, J = 32 Hz), 127.1, 126.0 (q, J = 4 Hz), 122.4
(q, J = 270 Hz), 116.1, 40.1, 39.3, 36.7 ppm. HRMS (EI): calcd.
for C13H10Cl2F3N [M]+ 307.0142; found 307.0145.
1 H), 1.77 (dd, J = 6.0, 4.8 Hz, 1 H), 1.57 (dd, J = 8.2, 4.8 Hz, 1
H), 1.31 (t, J = 6.8 Hz, 3 H) ppm; (Z) isomer: δ = 7.36–7.25 (m, 5
H), 5.68 (dd, J = 17.2, 10.4 Hz, 1 H), 5.01 (dd, J = 10.4, 0.8 Hz, 1
H), 4.65 (dd, J = 17.2, 0.8 Hz, 1 H), 3.95–3.81 (m, 2 H), 2.17 (dd,
J = 8.0, 6.0 Hz, 1 H), 2.00 (dd, J = 6.0, 4.8 Hz, 1 H), 1.42 (dd, J
= 8.0, 4.8 Hz, 1 H), 0.99 (t, J = 6.8 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): (E) isomer: δ = 171.4, 141.7, 138.8, 130.0,
128.4, 127.1, 116.6, 60.7, 38.1, 28.7, 20.5, 14.4 ppm; (Z) isomer: δ
= 170.3, 143.6, 137.8, 130.3, 128.1, 127.1, 114.3, 60.3, 38.2, 29.2,
18.8, 14.0 ppm. The assignment of the signals in the 13C NMR
spectrum was possible due to separation of the diastereoisomers by
column chromatography (silica gel, dichloromethane; partial de-
composition). HRMS (EI): calcd. for C14H16O2 [M]+ 216.1150;
found 216.1157.
Ethyl 4-(1,1Ј-Biphenyl-4-yl)-2,6-dichlorohex-4-enoate: Table 2, En-
try 9. Isolated yield: 102 mg, 28%. 1H NMR (400 MHz, CDCl3):
(E) olefin: δ = 7.64–7.59 (m, 4 H), 7.49–7.35 (m, 4 H), 7.27 (d, J
= 10.4 Hz, 1 H), 6.08 (t, J = 8.0 Hz, 1 H), 4.33 (d, J = 8.0 Hz, 2
H), 4.23–4.13 (m, 3 H), 3.37 (dd, J = 14.8, 6.4 Hz, 1 H), 3.23 (dd,
J = 14.8, 8.4 Hz, 1 H), 1.27 (t, J = 7.2 Hz, 3 H) ppm; (Z) olefin: δ
= 7.64–7.59 (m, 4 H), 7.49–7.35 (m, 4 H), 7.27 (d, J = 10.4 Hz, 1
H), 5.88 (t, J = 8.0 Hz, 1 H), 4.23–4.13 (m, 3 H), 4.00 (d, J =
8.0 Hz, 2 H), 3.16 (dd, J = 14.4, 6.8 Hz, 1 H), 2.98 (dd, J = 14.4,
8.0 Hz, 1 H), 1.29 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): (E) and (Z) olefin: δ = 169.1, 169.0, 141.2, 141.1, 140.34,
140.31, 140.1, 138.9, 138.5, 135.7, 128.9, 128.8, 128.7, 127.9, 127.6,
127.5, 127.4, 127.3, 127.2, 127.02, 126.98, 62.3, 62.1, 54.9, 54.7,
44.1, 41.4, 40.5, 35.1, 14.01, 13.95 ppm. HRMS (EI): calcd. for
C20H20Cl2O2 [M]+ 362.0840; found 362.0847.
2-Phenyl-2-vinylcyclopropanenitrile (5). Method A: This method is
analogous to that described for 4; however, no product was formed
in this case. Method B: A mixture of Mn powder (495 mg,
9.00 mmol, 10.0 equiv.), PbCl2 (12.5 mg, 45 μmol, 0.05 equiv.), and
Me3SiCl (115 μL, 98 mg, 0.90 mmol, 1 equiv.) in THF (5 mL) was
stirred at room temperature for 2 min. A solution of 2,6-dichloro-
4-phenylhex-4-enenitrile (220 mg, 0.90 mmol) in THF (5 mL) was
added. The reaction mixture was stirred at 60 °C for 90 min (moni-
tored by GC–MS). After cooling to room temperature, the reaction
mixture was quenched with water (15 mL), and the Mn powder
was removed by filtration. Dichloromethane (20 mL) was added,
and the organic phase was washed with water and dried with mag-
nesium sulfate. Evaporation of the solvent followed by trap-to-trap
distillation under vacuum gave 5 as a colorless oil in 37% yield
(56 mg) as a mixture of two diastereoisomers [(E)/(Z) = 45:55]. The
assignment was made based on the 1H NMR data in analogy to
that reported for 4.[20] 1H NMR (400 MHz, CDCl3): (E) isomer: δ
= 7.46–7.31 (m, 5 H), 5.98 (dd, J = 16.8, 10.4 Hz, 1 H), 5.31 (d, J
= 10.4 Hz, 1 H), 4.88 (d, J = 16.8 Hz, 1 H), 1.97 (dd, J = 8.4,
6.0 Hz, 1 H), 1.72 (dd, J = 8.8, 5.2 Hz, 1 H), 1.66 (pt, J = JЈ =
5.2 Hz, 1 H) ppm; (Z) isomer: δ = 7.46–7.31 (m, 5 H), 5.66 (dd, J
= 16.8, 10.2 Hz, 1 H), 5.01 (d, J = 10.2 Hz, 1 H), 4.82 (d, J =
16.8 Hz, 1 H), 1.89 (dd, J = 8.4, 6.0 Hz, 1 H), 1.82 (pt, J = JЈ =
5.2 Hz, 1 H), 1.60 (dd, J = 8.4, 5.2 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): (E) and (Z) isomer: δ = 140.7, 139.0, 136.2,
130.1, 129.4, 128.6, 128.0, 127.7, 119.5, 119.0, 118.2, 116.0, 36.3,
35.7, 20.2, 19.8, 11.89, 11.89 (signals overlap) ppm. HRMS (EI):
calcd. for C12H11N [M]+ 169.0891; found 169.0883.
Ethyl 2,2,6-Trichloro-4-phenylhex-4-enoate: Table 2, Entry 10. Iso-
1
lated yield: 187 mg, 58%. H NMR (400 MHz, CDCl3): (E) olefin:
δ = 7.36–7.25 (m, 5 H), 5.99 (t, J = 8.0 Hz, 1 H), 4.34 (d, J =
8.0 Hz, 2 H), 3.77 (s, 2 H), 3.72 (q, J = 7.2 Hz, 2 H), 1.14 (t, J =
7.2 Hz, 3 H) ppm; (Z) olefin: δ = 7.36–7.25 (m, 5 H), 5.94 (t, J =
7.6 Hz, 1 H), 3.93 (d, J = 8.0 Hz, 2 H), 3.82 (q, J = 7.2 Hz, 2 H),
3.61 (s, 2 H), 1.16 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): (E) and (Z) olefin: δ = 165.2, 165.1, 140.8, 138.6, 137.5,
136.9, 131.8, 130.6, 128.7, 128.3, 128.2, 128.09, 128.05, 127.5, 83.5,
83.1, 63.9, 63.8, 53.6, 45.2, 41.1, 41.0, 13.63, 13.58 ppm. HRMS
(EI): calcd. for C14H15Cl3O2 [M]+ 320.0684; found 320.0672.
Ethyl 2-Phenyl-2-vinylcyclopropanecarboxylate (4). Method A: Acti-
vated Mg powder (487 mg, 20.0 mmol, 10 equiv.) was added to an
LiCl (100 mm) solution in tetrahydrofuran (THF, 20 mL). Ethyl
2,2-dichloro-4-phenylhex-4-enoate (574 mg, 2.00 mmol, 1 equiv.)
was added, and the suspension was stirred at room temperature for
30 min, Mg was removed by filtration, and the solvent was removed
under reduced pressure. Dichloromethane (20 mL) was added, and
the suspension was filtered again. The solution was washed with
water, and the organic phase was dried with magnesium sulfate.
Evaporation of the solvent gave the crude product as a pale yellow
oil in 42% yield (91 mg) as a mixture of two diastereoisomers [(E)/
(Z) = 50:50, determined by NMR spectroscopy]. Method B: A mix-
ture of Mn powder (549 mg, 10.0 mmol, 10 equiv.), PbCl2 (14 mg,
50 μmol, 0.05 equiv.), and Me3SiCl (127 μL, 109 mg, 1.00 mmol,
1 equiv.) in THF (5 mL) was stirred at room temperature for 2 min.
Supporting Information (see footnote on the first page of this arti-
cle): 1H and 13C NMR spectra, gas chromatograms, and mass spec-
tra for the main isomers.
A
solution of 2,6-dichloro-4-phenylhex-4-enenitrile (287 mg,
Acknowledgments
1.00 mmol) in THF (5 mL) was added. The reaction mixture was
stirred at 60 °C for 90 min, and the conversion was monitored by
GC–MS. After cooling to room temperature, the reaction mixture
was quenched with water (15 mL), and the Mn powder was re-
moved by filtration. Dichloromethane (20 mL) was added, and the
organic phase was washed with water and dried with magnesium
The work was supported by the Swiss National Science Founda-
tion, the Studienstiftung des Deutschen Volkes (G. K.), and the
École Polytechnique Fédérale de Lausanne (EPFL). We thank
Marion Arndt and the mass analysis service of the University of
sulfate. Evaporation of the solvent gave the crude product as a Marburg for carrying out the HRMS experiments.
Eur. J. Org. Chem. 2012, 93–98
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www.eurjoc.org
97

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Received: August 30, 2011
Published Online: November 9, 2011
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Eur. J. Org. Chem. 2012, 93–98