Synthesis of Diazanorcaradienes and 1,2-Diazepines via the Tandem [4+2]-Cycloaddition/Retro-[4+2]-Cycloaddition Reaction between Methoxycarbonylcyclopropenes and Dimethoxycarbonyltetrazine

Article abstract of DOI:10.1002/ejoc.201801861

The reaction of di(methoxycarbonyl)tetrazine with substituted cycloprop-2-ene-1-carboxylates gives a series of 3,4-diazanorcaradienes and 1,2-diazepines. The influence of the nature of cyclopropenes and the reaction conditions on its selectivity was inves

Full text of DOI:10.1002/ejoc.201801861

A Journal of
Accepted Article
Title: Synthesis of Diazanorcaradienes and 1,2-Diazepines via the
Tandem Cycloaddition/Retro-Cycloaddition Reaction between
Methoxycarbonylcyclopropenes and Dimethoxycarbonyltetrazine
Authors: Alexander Yu. Belyy, Anastasia A Levina, Dmitry N. Platonov,
Rinat F. Salikov, Michael G Medvedev, and Yury V. Tomilov
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801861
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801861
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
TOC Graphic
Methyl cyclopropenecarboxylates and dimethoxycarbonyltetrazine undergo cascade cycloaddition and
retro-cycloaddition reactions. Depending on substituents in cyclopropenes the reaction either leads to
diazanorcaradienes or is accompanied with an electrocyclic ring-opening and a proton migration or a
“walk” rearrangement.
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
Synthesis of Diazanorcaradienes and 1,2-Diazepines via the Tandem [4+2]-
Cycloaddition/Retro-[4+2]-Cycloaddition Reaction between Methoxycarbonyl-
cyclopropenes and Dimethoxycarbonyltetrazine
Alexander Yu. Belyy,a Anastasia A. Levina,a Dmitry N. Platonov,a Rinat F. Salikov,a Michael
G. Medvedev,a,b,c,d Yury V. Tomilova
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prospect,
119991 Moscow, Russian Federation, Tel./fax: +7-499-135-63-90; e-mail: tom@ioc.ac.ru
b
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 119991
Moscow, Russian Federation
c
National Research University Higher School of Economics (HSE), Myasnitskaya str. 20, Moscow,
101000, Russian Federation
d Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1/3, Moscow, 119991,
Russian Federation
Abstract. The reaction of di(methoxycarbonyl)tetrazine with substituted cycloprop-2-ene-1-
carboxylates gives a series of 3,4-diazanorcaradienes and 1,2-diazepines. The influence of the
nature of cyclopropenes and the reaction conditions on its selectivity was investigated. The
addition of nucleophiles to norcaradienes was studied and a rare example of the “walk”
rearrangement in this class of compounds was revealed.
Introduction
The derivatives of cycloheptatriene sometimes existing in an equilibrium with norcaradiene1,2
as well as other seven-membered polyene systems are attractive for their high reactivity in
pericyclic reactions. Therein diazepines and diazanorcaradienes have been paid essentially less
attention having shown a slight difference from the carbocyclic systems. Thus, 3,4-diazepines
are significantly less stable than their isomeric 1,2-diazanorcaradienes in most cases3 and are
often regarded as intermediates in the formation and interconversions of the latter.4 So far the
main method for the synthesis of diazanorcaradienes consists in the cycloaddition reaction of
cyclopropenes with tetrazines which is accompanied with the retro-[4+2]-cycloaddition to give
target products wherein cyclopropenecarboxylates containing alkyl and aryl substituents were
used as starting material.5–7 The diazanorcaradiene derivatives were demanded for the
investigation of the rearrangements in these cyclic systems, however the final scope was
restricted, no diazepines formed therein. Methods for the synthesis of condensed diazepines
which do not transform into norcaradienes due to the presence of an aromatic cycles annulated
are known.8–11 Additionally, a series of diazepines have demonstrated biological activity12–14 and
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
the reaction between cyclopropenes and tetrazines is of interest as a bioorthogonal copper – free
analog of the “click-reaction”.4
Results and discussion
Our previous investigations of polyunsaturated cyclic molecules abundant with electron-
withdrawing groups revealed their rich reactivity towards either nucleophilic or electrophilic
reagents as well as in the pericyclic reactions.15–22 One of the key synthons therein was
1,2,3,4,5,6,7-hepta(methoxycarbonyl)cycloheptatriene (HMCH),15,16 as well as its closely related
carbocyclic analogs, relatively high acidity of HMCH being one of the key properties
determining its high reactivity.14 Electron-deficient 1,2-diazepines are analogues of HMCH in
which the two C–CO2Me moieties are substituted with nitrogen atoms which similarly stabilize
the negative charge. It is noteworthy that HMCH itself was not observed to undergo
isomerization into corresponding norcaradiene, although within some of its transformations such
as the reaction of hepta(methoxycarbonyl)cycloheptatrienide potassium with tropylium
tetrafluoroborate this process takes place even at –30°С.20
Apparently, the most convenient method for the synthesis of diazanorcaradienes containing
three ester groups in a molecule is the reaction of dimethoxycarbonyltetrazine 123 with
substituted methyl cycloprop-2-ene-1-carboxylates 2, which were in turn obtained via catalytic
cyclopropenation of acetylenes with methyl diazoacetate. Thus, the reactions of tetrazine 1 with
cycloprop-2-ene-1-carboxylates containing either two phenyl groups (2a) or a phenyl and a
trimethylsilyl (2b) or only one butyl group (2с) proceed in mild conditions at room temperature
to form stable 3,4-diazanorcaradienes 3a–c (Scheme 1). The structures of products 3b and 3c
(indirectly via the adduct 4c) were established by single crystal X-ray diffraction analysis (XRD,
Figure 1). The ester group at the C(7) atom in 3a is anti-configured relative to the phenyl groups
and syn-configured towards the dihydropyridazine ring (the geometry of 3b was proved to be
similar to that of 3a on the basis of NOESY data), whereas in 3c (4c) it is otherwise anti-
configured towards the ring, which is more likely due to their thermodynamic stabilities rather
than the kinetic differences within the first cycloaddition stage. Dissolved in methanol both 3a
and 3b add one molecule of methanol to form adducts 4a,b. Conversely, diazanorcaradiene 3c
turned out highly hygroscopic and the formation of hydrate 4c was observed even at the presence
of trace water. Thus, it forms in deuterochloroform and on silica gel which makes purification of
3c hardly possible. The high hygroscopicity of similar compounds was observed previously.5
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
Scheme 1. Formation of substituted 3,4-diazanorcaradien-2,5,7-tricarboxylates 3a–c and their reactions
with methanol or water.
Figure 1. Single crystal X-ray structures of molecules 3a (left) and 4c (right). Atoms are represented as
thermal ellipsoids (р=50%).
Upon heating in either toluene or xylene the compound 3a rearranges into 1,2-diazepine 5a.
The latter can be obtained via direct reaction of tetrazine 1 with cyclopropane 2a upon heating in
xylene at reflux for 2h. According to XRD, the structure of 5a does not correspond to the
expected C(1)–C(6) bond cleavage in diazanorcaradiene 3a. Apparently, the product 5a is
formed via subsequent walk rearrangement2 of 3a into 3a´ and electrocyclic ring-expansion into
5a (Scheme 2, Figure 2), wherein the relative configuration of intermediate 3a´ was suggested
according to the previous calculations of [1,5]-shifts within norcaradiene systemes.2
Unfortunately, upon heating in xylene at reflux, diazanorcaradienes 3b and 3c gave
unidentifiable mixtures. It is worth mentioning that to the best of our knowledge the
transformation of 3a into 5a is the first example of a rearrangement of a norcaradiene into a
diazepine.3
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
Scheme 2. Isomerization of diazanorcaradiene 3a into 1,2-diazepine 5a via the walk rearrangement into
3a´.
Figure 2. Single crystal X-ray structure of molecule 5a. Atoms are represented as thermal ellipsoids
(р=50%).
Formation of diazanorcaradienes 3d,e in the reaction of tetrazine
1
with
cyclopropenecarboxylates 2d,e could not be observed even at low temperatures (–30°С). Herein
1,2-diazepines are formed and immediately isomerized into 4-methylene-4,5-dihydro-1H-1,2-
diazepine-3,5,7-tricarboxylates 6a,b containing exo-cyclic double bonds (Scheme 3). The
structure of 6b was established by means of XRD (Figure 3). As it was mentioned previously,
diazepines in most cases are not stable, however they are regarded as stable intermediates in
interconversions of diazanorcaradienes. Herein the driving force of the ring-expansion is likely
the formation of exo-double-bonded products 6a,b.
Scheme 3. Formation of substituted 4-methylene-4,5-dihydro-1H-1,2-diazepines 6a,b.
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
Figure 3. Single crystal X-ray structure of molecule 6b. Atoms are represented as thermal ellipsoids
(р=50%).
Analogously, formation of dihydrodiazepine fragment with an exo-alkylidene double bond is
observed in the reaction of tetrazine 1 with cyclopropene 2f (see SI). However, the reaction leads
to a mixture of isomeric products whose separation was accompanied with desilylation and
isomerization reaction and was unsuccessful. In this case the reaction requires heating in toluene
which is apparently due to the low reactivity at the first stages. It is worth noting, that 2-(tert-
butyl)-3-(trimethylsilyl)cycloprop-2-ene-1-carboxylate gives no reaction with 1.
Methyl 2-phenylcycloprop-2-ene-1-carboxylate 7 could not be used in the synthesis of the
corresponding diazanorcaradiene via the reaction with tetrazine 1 because it trimerizes into 8
upon formation (Scheme 4, Figure 4), the mechanism presumably including ene reaction.24,25
Scheme 4. Formation of trimer 8. The relative stereochemistry is shown for one of the diastereomers
formed which was established by means of XRD.
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
Figure 4. Single crystal X-ray structure of molecule 8. Atoms are represented as thermal ellipsoids
(р=50%).
The introduction of a trimethylsilyl substituent into cyclopropane could be an alternative
pathway to diazanorcaradienes with a hydrogen atom at one of the angular positions, however
the reaction of 3b with TBAF initiates the rearrangement into pyridazine 9 (Scheme 5).
Scheme 5. Cleavage of TMS-substituted diazanorcaradiene 3b into pyridazine 9.
Conclusion
Thus, the cycloaddition reaction between substituted methyl cycloprop-2-ene-1-carboxylates and
di(methoxycarbonyl)tetrazine was found to be an appropriate approach to the synthesis of
diazanorcaradienes and 1,2-diazepines. Diazanorcaradienes are formed from diaryl- and
aryltrimethylsilyl- and monoalkylated cyclopropenecarboxylates, while the presence of an alkyl
group in trisubstituted cyclopropenes brings to formation of diazepines containing an
exomethylene double bond.
Experimental Section
1
13
General: H and C NMR spectra were recorded on a 300 and 75.5 MHz NMR spectrometer for
solutions in CDCl3 containing 0.05% of Me4Si as an internal standard. High resolution mass
spectra were obtained using a BrukermicrOTOF II instrument (ESI, positive or negative ion
modes, capillary voltage 4500 V). All chemical reagents and solvents were purchased from
commercial sources and used without additional purification. Dimethoxycarbonyltetrazine 1,23
methyl
2-phenyl-3-(trimethylsilyl)cycloprop-2-ene-1-carboxylate
2b26,
methyl
2,3-
dimethylcycloprop-2-ene-1-carboxylate 2d,27 2-(tert-butyl)-3-(trimethylsilyl)cycloprop-2-ene-1-
carboxylate28 were synthesized according to the literature procedures.
X-ray diffraction data for 2a, 2c and 4a were collected on a SMART APEX II area-detector
diffractometer (graphite monochromator, ω-scan technique), using MoKα-radiation (0.71073 Å).
The intensity data were integrated by the SAINT program29 and were corrected for absorption
and decay using SADABS30. All structures were solved by direct methods using SHELXS31, and
were refined on F2 using SHELXL-2014/2017.32 All non-hydrogen atoms were refined with
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
anisotropic displacement parameters. All hydrogen atoms were placed in ideal calculated
positions and refined as riding atoms with relative isotropic displacement parameters taken as
Uiso(H)=1.5Ueq(C) for methyl groups and Uiso(H)=1.2Ueq(C) for the rest ones. Crystal data and
structure refinement parameters of compounds 3a, 4c, 5a, 6b and 8 can be retrieved free of
charge from www.ccdc.cam.ac.uk/conts/retrieving.html (CCDC 1886318–1886322).
Trimethyl 1,6-diphenyl-3,4-diazabicyclo[4.1.0]hepta-2,4-diene-2,5,7-tricarboxylate (3a): A
mixture of dimethoxycarbonyltetrazine 1 (0.20 g, 1.0 mmol), methyl 2,3-diphenylcycloprop-2-
ene-1-carboxylate 2a (0.28 g, 1.1 mmol) and CH2Cl2 (6 mL) stirred for 30 h, the solvent was
removed in vacuo. The residue was recrystallized from methyl-tert-butyl ether (MTBE) to give
1
the desired product (0.39 g, 91%). M.p. 129–132 °C. H NMR (300 MHz, CDCl3): δ = 7.17–6.96
(m, 10 H), 4.14 (s, 1 H), 3.74 (s, 3 H), 3.64 (s, 6 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 164.9,
163.6, 153.7, 133.7, 129.5, 128.7, 128.6, 52.9, 52.8, 42.6, 21.3 ppm. HRMS (ESI+): m/z calcd.
+
for C23H21N2O6 [M+H]+ 421.1394; found 421.1390.
Trimethyl
1-phenyl-6-(trimethylsilyl)-3,4-diazabicyclo[4.1.0]hepta-2,4-diene-2,5,7-
tricarboxylate (3b): A mixture of dimethoxycarbonyltetrazine 1 (0.20 g, 1.0 mmol), methyl 2-
phenyl-3-(trimethylsilyl)cycloprop-2-ene-1-carboxylate 2b (0.27 g, 1.1 mmol) and CH2Cl2 (6
mL) stirred for 7 days, the solvent was removed in vacuo. The residue was purified by column
chromatography on silica gel (EtOAc/CHCl3, 1:4), recrystallization from MTBE gave the desired
1
product (0.24 g, 56%). M.p. 122–124 °C. H NMR (300 MHz, CDCl3): δ = 7.41–7.22 (m, 5H),
3.93 (s, 3H), 3.71 (s, 3H), 3.56 (s, 3H), 3.24 (s, 1H), –0.21 (s, 9H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 165.8, 165.6, 163.8, 156.5, 153.2, 136.9, 130.8, 129.4, 128.8, 53.0, 52.6, 52.5, 39.7,
29.3, 19.3, –0.9 ppm. HRMS (ESI+): m/z calcd. for C20H25N2O6Si+ [M+H]+ 417.1476; found
417.1467.
Trimethyl
1-butyl-3,4-diazabicyclo[4.1.0]hepta-2,4-diene-2,5,7-tricarboxylate
(3c):
A
mixture of dimethoxycarbonyltetrazine 1 (0.20 g, 1.0 mmol), methyl 2-butylcycloprop-2-ene-1-
carboxylate 2c (0.17 g, 1.1 mmol) and THF (6 mL) stirred for 20 h under argon, the solvent was
removed in vacuo. The residue was recrystallized from MTBE to give the desired product (0.37
g, 86%); 1H NMR (300 MHz, CDCl3): δ = 4.00 (s, 3 H), 3.97 (s, 3 H), 3.81 (s, 3 H), 3.37 (d, J =
5.1 Hz, 1 H), 2.38–2.17 (m, 1 H), 1.62–1.47 (m, 1 H), 1.29 (d, J = 5.1 Hz, 1 H), 1.26–1.11 (m, 4
13
H), 0.94–0.76 (m, 3 H) ppm. C NMR (75 MHz, CDCl3): δ = 169.2, 163.7, 163.7, 158.8, 154.3,
53.6, 53.3, 53.1, 34.6, 30.5, 29.7, 26.8, 24.7, 22.2, 13.7 ppm. HRMS (ESI+): m/z calcd. for
+
C15H23N2O6 [M+H]+ 325.1394; found 325.1395.
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
Trimethyl
5-methoxy-1,6-diphenyl-3,4-diazabicyclo[4.1.0]hept-2-ene-2,5,7-tricarboxylate
(4a): Trimethyl 1,6-diphenyl-3,4-diazabicyclo[4.1.0]hepta-2,4-diene-2,5,7-tricarboxylate 3a (0.2
g, 0.48 mmol) was dissolved in MeOH (5.5 mL), stirred for 24 h, the solvent was removed in
1
vacuo to give the desired product (0.2 g, 94%). M.p. 136–138 °C. H NMR (300 MHz,
(CD3)2CO): δ = 8.43 (br.s, 1 H), 7.39–7.21 (m, 4 H), 7.07–6.88 (m, 6 H), 3.69 (s, 1 H), 3.67 (s, 3
13
H), 3.55 (s, 3 H), 3.42 (s, 3 H), 3.25 (s, 3 H) ppm. C NMR (75 MHz, (CD3)2CO): δ = 166.7,
166.4, 164.3, 142.6, 137.2, 136.3, 133.1, 127.6, 126.7, 126.5, 126.2, 82.4, 51.4, 51.1, 50.8, 50.3,
+
36.6, 32.7 ppm. HRMS (ESI+): m/z calcd. for C24H21N2O7 [M+H]+ 453.1656; found 453.1649.
Trimethyl 1-butyl-5-hydroxy-3,4-diazabicyclo[4.1.0]hept-2-ene-2,5,7-tricarboxylate (4c): A
mixture of dimethoxycarbonyltetrazine 1 (0.20 g, 1.0 mmol), methyl 2-butylcycloprop-2-ene-1-
carboxylate 2c (0.17 g, 1.1 mmol) and CH3CN (6 mL) stirred for 5 h, the solvent was removed in
vacuo. The residue was recrystallized from MTBE to give the desired product (0.34 g, 97%).
1
M.p. 148–151 °C. H NMR (300 MHz, CDCl3): δ = 6.62 (с, 1 H), 4.26 (s, 1 H), 3.90 (s, 3 H),
3.86 (s, 3 H), 3.72 (s, 3 H), 2.98 (d, J = 5.0 Hz, 1 H), 2.87 (d, J = 5.0 Hz, 1 H), 2.21–2.01 (m, 1
13
H), 1.63–1.47 (m, 1 H), 1.29–0.97 (m, 4 H), 0.83 (т, J = 7.0 Hz, 3 H) ppm. C NMR (75 MHz,
CDCl3): δ = 172.2, 170.4, 163.3, 140.3, 80.0, 53.9, 52.6, 52.2, 40.8, 28.6, 27.5, 25.5, 23.5, 22.8,
+
13.7 ppm. HRMS (ESI+): m/z calcd. for C15H23N2O7 [M+H]+ 343.1500; found 343.1499.
Trimethyl 5,6-diphenyl-4H-1,2-diazepine-3,4,7-tricarboxylate (5a): (a) A mixture of
dimethoxycarbonyltetrazine 1 (0.20 g, 1.0 mmol), methyl 2,3-diphenylcycloprop-2-ene-1-
carboxylate 2a (0.28 g, 1.1 mmol) and p-xylene (6 mL) was heated at reflux 1 h, the solvent was
removed in vacuo. The residue was recrystallized from MTBE to give the desired product (0.36
g, 84%); (b) Trimethyl 1,6-diphenyl-3,4-diazabicyclo[4.1.0]hepta-2,4-diene-2,5,7-tricarboxylate
3a (0.2 g, 0.48 mmol) and p-xylene (4.0 mL) was heated at reflux for 1 h, the solvent was
removed in vacuo. The residue was recrystallized from MTBE to give the desired product (0.19
1
g, 95%). M.p. 123–125 °C. H NMR (300 MHz, CDCl3): δ = 7.41–7.22 (m, 5 H), 3.93 (s, 3 H),
13
3.71 (s, 3 H), 3.56 (s, 3 H), 3.24 (s, 1 H), –0.21 (s, 9 H) ppm. C NMR (75 MHz, CDCl3): δ =
165.8, 165.6, 163.8, 156.5, 153.2, 136.9, 130.8, 129.4, 128.8, 53.0, 52.6, 52.5, 39.7, 29.3, 19.3, –
+
0.9 ppm. HRMS (ESI+): m/z calcd. for C23H21N2O6 [M+H]+ 421.1394; found 421.1390.
Trimethyl 6-methyl-4-methylene-4,5-dihydro-1H-1,2-diazepine-3,5,7-tricarboxylate (6a): A
mixture of dimethoxycarbonyltetrazine 1 (0.20 g, 1.0 mmol), methyl 2,3-dimethylcycloprop-2-
ene-1-carboxylate 2d (0.13 g, 1.1 mmol) and p-xylene (6 mL) was heated at reflux for 1 h, the
solvent was removed in vacuo. The residue was recrystallized from MTBE to give the desired
1
product (0.25 g, 85%) as yellow crystals. M.p. 114-115 °C. H NMR (300 MHz, CDCl3): δ =
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
8.64 (br. s, 1 H), 5.59 (s, 1 H), 5.18 (s, 1 H), 3.93 (s, 1 H), 3.87 (s, 3 H), 3.86 (s, 3 H), 3.68 (s, 3
13
H), 2.34 (s, 3 H) ppm. C NMR (75 MHz, CDCl3): δ = 169.0, 164.9, 163.8, 135.9, 134.6, 131.5,
+
127.8, 116.1, 61.6, 52.6, 52.6, 52.6, 21.5 ppm. HRMS (ESI+): m/z calcd. for C13H17N2O6
[M+H]+ 297.1081; found 297.1079.
Trimethyl 4-methylene-6-phenyl-4,5-dihydro-1H-1,2-diazepine-3,5,7-tricarboxylate (6b): A
mixture of dimethoxycarbonyltetrazine
1
(0.20 g, 1.0 mmol), methyl 2-methyl-3-
phenylcycloprop-2-ene-1-carboxylate 2e (0.21 g, 1.1 mmol) and CH2Cl2 (5 mL) stirred for 4
days, the solvent was removed in vacuo. The residue was purified by column chromatography on
on silica gel (EtOAc/CHCl3, 1:4), recrystallization from MTBE to give the desired product (0.24
1
g, 65%) as yellow crystals. M.p. 143-145 °C. H NMR (300 MHz, CDCl3): δ = 8.80 (br.s, 1 H),
7.43–7.31 (m, 3 H), 7.26–7.20 (m, 2 H), 5.57 (s, 1 H), 4.99 (s, 1 H), 4.40 (s, 1 H), 3.89 (s, 3 H),
3.76 (s, 3 H), 3.50 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 169.2, 164.9, 164.3, 140.5,
137.5, 133.0, 131.5, 128.3, 128.2, 128.0, 127.9, 117.5,69.8, 61.7, 52.9, 52.7, 52.5 ppm. HRMS
+
(ESI+): m/z calcd. for C18H19N2O6 [M+H]+ 359.1238; found 359.1232.
Dimethyl 4-(2-methoxy-2-oxoethyl)-5-phenylpyridazine-3,6-dicarboxylate (7): A mixture of
trimethyl
1-phenyl-6-(trimethylsilyl)-3,4-diazabicyclo[4.1.0]hepta-2,4-diene-2,5,7-tricarboxylate
3b (0.15 g, 0.36 mmol) Bu4NF×3H2O (0.114 g, 0.36 mmol) and CHCl3 (5 mL) stirred for 2 days,
washed with water (3×5mL), the solvent was removed in vacuo. The residue was purified by
column chromatography on silica gel (EtOAc/CH2Cl2, 1:1) to give the desired product (0.12 g,
1
45%) as light yellow oil. H NMR (300 MHz, CDCl3): δ = 7.53–7.42 (m, 3 H), 7.25–7.17 (m, 2
H), 4.06 (s, 3 H), 3.87 (s, 2 H), 3.72 (s, 3 H), 3.67 (s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
169.4, 165.1, 164.8, 154.4, 152.3, 140.8, 134.2, 132.2, 129.5, 128.8, 128.3, 53.4, 53.0, 52.5, 34.7
+
ppm. HRMS (ESI+): m/z calcd. for C17H17N2O6 [M+H]+ 345.1081; found 345.1079.
Trimer of methyl 2-phenylcycloprop-2-ene-1-carboxylate (8): To
a
mixture of
phenylacetylene (5.0 g, 49 mmol), Cu[CH3CN]4PF6 (0.22 g, 0.59 mmol) and CH2Cl2 (10 mL)
was added a solution of methyl diazoacetate (6.0 g, 60 mmol) in CH2Cl2 (10 mL) via a syringe
pump in 8 h. After addition the reaction mixture was stirred for 30 min, the reaction mixture
filtered through silica gel, the solvent was removed in vacuo. The residue was purified by
column chromatography on silica gel (EtOAc/Petroleum ether, 1:4) to give the desired product
1
(6.4 g, 75%) as colorless crystals. M.p. 146–147 °C. H NMR (300 MHz, CDCl3): δ = 7.51–7.38
(m, 6 H), 7.36–7.15 (m, 9 H), 3.73 (s, 3 H), 3.53 (s, 3 H), 3.46 (s, 3 H), 3.21 (dd, J = 6.4, 5.0 Hz,
1 H), 3.00 (m, 2 H), 2.60 (dd, J = 9.7, 5.0 Hz, 1 H), 2.31 (dd, J = 9.3, 7.5 Hz, 1 H), 2.03 (dd, J =
13
9.3, 5.2 Hz, 1 H) ppm. C NMR (75 MHz, CDCl3): δ = 174.8, 170.3, 169.2, 136.0, 134.4, 129.4,
129.2, 129.1, 128.9, 128.9, 128.3, 128.0, 127.4, 126.7, 126.0, 111.6, 108.0, 52.2, 51.9, 51.4,
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
+
33.3, 32.6, 31.1, 30.2, 28.5, 20.1 ppm. HRMS (ESI+): m/z calcd. for C33H34NO6 [M+NH4]+
540.2381; found 540.2380.
Methyl 2,3-diphenylcycloprop-2-enecarboxylate (2a): To a mixture of 1,2-diphenylacetylene
(3.0 g, 16.85 mmol), Cu[CH3CN]4PF6 (63 mg, 5.9 mmol) and CH2Cl2 (10 mL) was added a
solution of methyl diazoacetate (2.53 g, 25.3 mmol) in CH2Cl2 (10 mL) via a syringe pump in 8
h. After addition the reaction mixture was stirred for 30 min, the reaction mixture filtered
through silica gel, the solvent was removed in vacuo. The residue was purified by column
chromatography on silica gel (EtOAc/Petroleum ether, 1:9) to give the desired product (1.6 g,
1
39%) as colorless crystals. M.p. 83–84 °C. H NMR (300 MHz, CDCl3): δ =7.72 (d, J = 7.4 Hz,
13
4 H), 7.60–7.33 (m, J = 6 H), 3.73 (s, 3 H), 2.87 (s, 1 H) ppm. C NMR (75 MHz, CDCl3): δ =
175.3, 130.0, 129.3, 128.9, 127.1, 107.6, 51.7, 21.5 ppm. HRMS (ESI+): m/z calcd. for
C17H14O2Na+ [M+Na]+ 273.086; found 273.0884.
Methyl 2-methyl-3-phenylcycloprop-2-ene-1-carboxylate (2d): To a mixture of 1-methyl-2-
phenylacetylene (1.5 g, 12.9 mmol), Cu[CH3CN]4PF6 (70 mg, 0.18 mmol) and CH2Cl2 (5 mL)
was added a solution of methyl diazoacetate (1.93 g, 19 mmol) in CH2Cl2 (10 mL) via a syringe
pump in 10 h. After addition the reaction mixture was stirred for 30 min, the reaction mixture
filtered through silica gel, the solvent was removed in vacuo. The residue was purified by
column chromatography on silica gel (EtOAc/Petroleum ether, 1:4) to give the desired product
1
(1.72 g, 71%) as colorless oil; H NMR (300 MHz, CDCl3): δ= 7.60–7.23 (m, 1 H), 3.71 (d, J =
13
7.9 Hz, 1 H), 2.46 (d, J = 5.9 Hz, 1 H), 2.38–2.29 (m, 1 H) ppm. C NMR (75 MHz, CDCl3): δ
= 176.2, 129.23, 128.6, 127.8, 106.3, 105.3, 51.5, 22.4, 10.7 ppm. HRMS (ESI+): m/z calcd. for
C12H12O2Na+ [M+Na]+ 211.0736; found 211.0730.
Methyl 2-butylcycloprop-2-ene-1-carboxylate (2c): To a mixture of 1-hexyne (3.28 g, 40
mmol), Rh2(OAc)4 (44 mg, 0.01 mmol) and CH2Cl2 (10 mL) was added a solution of methyl
diazoacetate (2,0 g, 20 mmol) in CH2Cl2 (8 mL) via a syringe pump in 10 h. After addition the
reaction mixture was stirred for 30 min, the reaction mixture filtered through silica gel, the
solvent was removed in vacuo. The residue was purified by column chromatography on silica gel
1
(EtOAc–Petroleum ether, 1:4) to give the desired product (2.3 g, 75%) as colorless oil. H NMR
(300 MHz, CDCl3): δ = 6.34 (d, J = 1.3 Hz, 1 H), 3.70 (s, 3 H), 2.51 (t, J = 7.0 Hz, 2 H), 2.15 (d,
J = 1.3 Hz, 1 H), 1.57 (m, 2 H), 1.40 (m, 2 H), 0.93 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 177.0, 115.6, 93.89, 51.4, 28.7, 24.6, 22.2, 19.5, 13.7 ppm. HRMS (ESI+): m/z
+
calcd. for C9H15O2 [M+H]+ 155.1067; found 155.1064.
Methyl 2-butyl-3-(trimethylsilyl)cycloprop-2-enecarboxylate (2f): (a) Preparation of
LiHMDS solution: To a solution of bis(trimethylsilyl)amine (4.38g, 27 mmol) in THF (10 mL)
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10.1002/ejoc.201801861
European Journal of Organic Chemistry
was added a solution of n-butyllithium in hexane (11.8 mL, 27 mmol) dropwise under argon,
maintaining the temperature at –30ºC.
(b) To a mixture of methyl 2-butylcycloprop-2-ene-1-carboxylate (3.22 g, 21 mmol), TMSCl
(3.4 g, 31 mmol) and THF (50 mL) was added the solution of LiHMDS in 5 min, maintaining the
temperature –80ºC. Then 10 mL of a saturated NH4Cl solution was added at –80°C, organic
phase were separated and dried over Na2SO4. The solvent was removed in vacuo and the residue
was purified by flash column chromatography on silica gel (EtOAc/Petroleum ether, 1:25) to
1
give the desired product (4.05 g, 85%) as colorless oil. H NMR (300 MHz, CDCl3): δ = 3.63 (s,
3 H), 2.59–2.43 (m, 1 H), 2.00 (s, 1 H), 1.67–1.49 (m, 2 H), 1.39 (m, 2 H), 0.92 (t, J = 7.3 Hz, 3
H), 0.19 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 177.5, 126.6, 103.2, 51.1, 29.1, 26.1,
22.2, 20.6, 13.7, –1.6 ppm. HRMS (ESI+): m/z calcd. for C12H23O2Si+ [M+H]+ 227.1462; found
227.1465.
Acknowledgements
The contribution of Center for molecular composition studies of INEOS RAS is gratefully
acknowledged. We are grateful to Dr. Evgeny V. Shulishov for NMR spectra. High-resolution
mass spectra were recorded in the Department of Structural Studies at Zelinsky Institute of
Organic Chemistry, Moscow.
Keywords
Cycloadditions, Rearrangements, Nitrogen heterocycles, Pericyclic reaction, Ring contraction
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