Cyclization reactions of 1-amino-5-trifluoromethyl-5-thienyl-1-azapenta-1, 4-dien-3-ones under superelectrophilic conditions: Synthesis of novel benzothiophenols, cyclopentenols and dihydrodiazepinols

Article abstract of DOI:10.1002/ejoc.200801194

Trifluoromethyl-substituted 1-amino-5-thienyl-1-aza-1,4-dien-3-ones 5, which are accessible in good yields from keto esters 1 in a three-step procedure, undergo three different types of cyclization reactions upon treatment with a large excess of trifluoro

Full text of DOI:10.1002/ejoc.200801194

FULL PAPER
DOI: 10.1002/ejoc.200801194
Cyclization Reactions of 1-Amino-5-trifluoromethyl-5-thienyl-1-azapenta-1,4-
dien-3-ones under Superelectrophilic Conditions: Synthesis of Novel
Benzothiophenols, Cyclopentenols and Dihydrodiazepinols
Nugzar Ghavtadze,[a] Roland Fröhlich,[a] and Ernst-Ulrich Würthwein*[a]
Keywords: Aza compounds / Cyclization / Cations / Ab initio calculations / Heterocycles
Trifluoromethyl-substituted 1-amino-5-thienyl-1-aza-1,4-dien- tion reactions to form novel dihydrodiazepinones 8a,b after
3-ones 5, which are accessible in good yields from keto esters
1 in a three-step procedure, undergo three different types of
cyclization reactions upon treatment with a large excess of
trifluoromethanesulfonic acid, depending on the substitution
pattern. Thus, starting materials 5a–f without a halogen sub-
stituent at the 3-position of the thienyl subunit undergo 1,6-
cyclization reactions (hydroxyannulation) to give benzothio-
phenol derivatives 6. In contrast, 5-(3-bromothienyl)-substi-
tuted compounds 5g–j undergo Nazarov 1,5-cyclization reac-
tions to produce cyclopentenols 7a–d. Finally, 1-dimeth-
tautomerization. On the basis of quantum chemical calcula-
tions we interpret these different types of multistep reactions
to be cyclization reactions that proceed under super-
electrophilic conditions through both mono- and dicationic
intermediates. Electrophilic and pericyclic cyclization modes
are discussed on the basis of the results of NICS calculations.
Several of the compounds 6, 7 and 9 were characterized by
X-ray diffraction.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ylamino-substituted 1-azadienones 5k,l undergo 1,7-cycliza- Germany, 2009)
able to disclose novel cyclization pathways leading to ind-
Introduction
enol derivatives by 1,5-cyclization,[5] or dihydrospiroindene-
pyrazole and dihydroindenodiazepine derivatives by a cas-
cade of electrocyclization reactions.[6] All these transforma-
tions are believed to involve dicationic superelectrophilic
species as highly reactive intermediates.[7]
In recent years several publications have appeared re-
porting on the Nazarov cyclization reaction, which is by far
the most widely used and well-established method for the
synthesis of five-membered carbocycles[1] These reactions,
and also the related aza-Nazarov transformations, might in
a number of cases involve so-called superelectrophilic con-
ditions with dications as intermediates, affording carbo-
and heterocyclic five-membered ring systems.[2,3]
Recently we were able to identify the electronic and topo-
logical preconditions for the successful application of the
aza-Nazarov reaction in heterocyclic synthesis and demon-
strated that 1-aza-1,4-dien-3-ones can be successfully used
in the synthesis of substituted 1H- and 2H-pyrroles by the
aza-Nazarov route.[4]
Furthermore, acid treatment of 5,5-disubstituted 1-aza-
1,4-dien-3-ones 5, which bear an aryl ring and also a very
strong electron-withdrawing substituent such as a CF3
group at the 5-position, also open up other reaction chan-
nels. As this substitution pattern precludes the final aroma-
tization step of the aza-Nazarov ring-closure product by de-
protonation, other mechanistic possibilities come into play,
depending on the nature of the substituents. Hence, we were
Results and Discussion
To extend the scope of these reactions, we herein focus
on hydrazine-derived 5,5-disubstituted 1-azapenta-1,4-dien-
3-ones that bear a thiophene (benzothiophene) or 3Ј-halo-
thiophene moiety (in contrast to a phenyl or a substituted
phenyl group as earlier[6]) at the 5-position of the 1-aza-1,4-
dien-3-one. With these electron-rich heterocyclic moieties at
the 5-position of the reacting system we expected additional
synthetic options and unusual reaction channels.
Such precursor molecules are accessible from the con-
densation of keto esters 1 with hydrazines, which gives the
corresponding hydrazones 2, followed by their conversion
into the corresponding phosphonates 3[8] and subsequent
Horner–Wadsworth–Emmons reactions with 2-(trifluo-
roacetyl)thiophene derivatives 4 to give the 1-aza-1,4-dien-
3-ones 5 (Scheme 1).
[a] Westfälische Wilhelms-Universität Münster, Organisch-Che-
misches Institut,
The cyclization of these special systems 5 upon proton-
ation with an excess of trifluoromethanesulfonic acid led to
results that are quite different to those we had observed
Corrensstraße 40, 48149 Münster, Germany
Fax: +49-251-83-39772
E-mail: wurthwe@uni-muenster.de
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1,5- 1,6- or 1,7-Electrocyclization Reactions
Scheme 3.
Scheme 1.
before.[6] Unexpected transformations took place and, de-
pending on the nature of the substituents X and R3, 1,6-,
1,5- and 1,7-cyclization products 6, 7 and 8 were obtained
(Scheme 2).
Figure 1. Molecular structures of 6b and 6e in the solid state (X-
ray diffraction).[9]
Table 1. Substitution patterns in compounds 5 and 6 and yields of
compound 6.
R1,R2
R3
Thienyl group Product Yield [%]
5a
5b
5c
5d
Me,Me
Me,Me
Me,Me
Me,Me
Me
Me
Me
2-benzothienyl
2-thienyl
3-benzothienyl
6a
6b
6c
6d
6a
14
28
48
20
15
2-thienyl 2-benzothienyl
Me 2-benzothienyl
5e –(CH2)2–O–(CH2)2–
Scheme 2.
Scheme 4.
Similar to our previous work,[6] the cyclization reactions
of the 1-aza-1,4-dien-3-ones 5 were carried out in dichloro-
methane by treatment of 5 with an up to 10-fold excess of
triflic acid at –10 to 0 °C. Weaker acids like trifluoroacetic
acid or polyphosphoric acid, as well as smaller excesses of
triflic acid, did not lead to satisfactory results. Furthermore,
the addition of acetic anhydride is necessary for the isola-
tion of the stable final products.
In the case of X = H, annulation reactions took place
and benzo- and dibenzothiophenes were isolated
(Scheme 3, Figure 1). The results are summarized in
Table 1.
In the case of azadienone 5f, besides the monoacetoxy
product 6e, the 2,3-diacetoxy derivative 9 was also detected
(Scheme 4, Figure 2).
Figure 2. Molecular structure of 9 in the solid state (X-ray diffrac-
tion).[9]
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The hydroxyannulation reaction can be extended to ben-
zofuran derivatives as well. The introduction of the 2-ben-
zofuranyl group (10) instead of the 2-benzothienyl substitu-
ent gave a similar cyclization product 11 in 18% yield
(Scheme 5).
Scheme 7.
Note that in these cases the formation of polymeric resi-
dues lowers the yields of the cyclization reactions. Trifluoro-
methyl ketones are known to enhance polymerization reac-
tions under superelectrophilic conditions.[10]
For the three types of transformations presented above
we suggest the following reasonable mechanisms.
Scheme 5.
Preventing these 1,6-cyclization reactions by replacing
the hydrogen atom at the 3-position of the thienyl subunit
by a halogen atom and employing a methyl group as the R3
substituent in the starting azadienone 5 led to the isolation
The necessary reaction conditions, the large excess of a
very strong acid, and literature data,[2,7] as well as our own
experiences[5,6] suggest dicationic species as intermediates
under superelectrophilic solvation. Thus, it is suggested that
the 1,6-cyclization reaction (hydroxyannulation reaction)
starts with a two-fold protonation (at least in equilibrium)
of the carbonyl function and the imine nitrogen atom of 5
to form a dicationic species. This highly reactive intermedi-
ate adds as an electrophile to the 3-position of the five-
membered heterocycle to form a six-membered ring. After
elimination of a proton along with a diazenium cation, the
annulation reaction is complete with the formation of 6
(Scheme 8).
of cyclopentenol derivatives
7 after acid treatment
(Scheme 6). The necessary azadienones 5g–j can be pre-
pared from dimethylhydrazine or various cyclic hydrazines.
The results of these cyclization reactions are summarized in
Table 2.
Scheme 6.
Table 2. Substitution patterns in compounds 5 and 7 and yields of
compound 7.
R1,R2
Product
Yield [%]
5g
5h
5i
Me,Me
–(CH2)2–O–(CH2)2–
–(CH2)5–
7a
7b
7c
7d
36
61
26
22
5j
–(CH2)6–
Then 1-ethyl-1-methylhydrazine-, 1-isopropyl-1-methyl-
hydrazine- or 1-aminopyrrolidine-derived azadienones 5
were subjected to the same acid treatment; the formation of
products was observed in the NMR and mass spectra, but
as complex mixtures and in very low yields. We further
found that it was impossible to replace the 3-halothienyl
group by a 3-halobenzothienyl group, probably because of
the steric demand of this moiety during the cyclization reac-
tion.
Scheme 8.
The postulated dicationic reaction mechanism is well
supported by quantum chemical calculations[11] at the SCS-
Introducing a 2-thienyl group instead of a Me group at MP2/6-311G(d,p)//B3LYP/6-311G(d,p) level of theory.[12]
the 2-position of the 1-azadienone as the R3 substituent was The computational results of the 1,6-cyclization reaction
expected to block the second pathway as the hydrogen indicate that the ring-closing step of the annulation reaction
atoms of the Me group play an important role in the second is a thermoneutral process (–0.6 kcal/mol) with a moderate
transformation.
activation barrier (17.0 kcal/mol) (Scheme 9, lower line).
Indeed, the tendency of the azadienones 5k,l towards cy- The NICS value[13] for the corresponding transition state is
clization is so high that another cyclization reaction channel rather low (lowest value –1.2) and the charge separation
was opened, thus providing two highly substituted diazep- between the two bond-forming terminal atoms amounts to
inol derivatives in fair yields (Scheme 7).
0.46 electrons, which indicates an electrophilic rather than
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1,5- 1,6- or 1,7-Electrocyclization Reactions
a pericyclic mechanism. For comparison, we also studied
the monocationic route. The calculations indicate a quite
endothermic pathway with a huge activation barrier
(Scheme 9, upper line).
Scheme 9. Calculated relative energies and activation energies
(above arrow) for the cyclization of the moncationic (upper line)
and dicationic species (lower line) [SCS-MP2/6-311G(d,p)//B3LYP/
6-311G(d,p) including ZPE].
Scheme 10.
The Nazarov cyclization leading to protonated 7a was
calculated to be highly exothermic (–33.7 kcal/mol) with a
The formation of the diacetoxy derivative 9 can also be very low activation barrier (0.8 kcal/mol; Scheme 12).
reasonably explained only by the dicationic mechanism
(Scheme 10) and nucleophilic acetoxy attack.
An interesting feature detected in the NMR spectra of
the cyclopentenol derivatives 7 is a hindered rotation[15]
The formation of the cyclopentenol derivatives 7 follows about the N–N bond, which can be explained by a high
the route of the classic Nazarov cyclization. Again, the reac- contribution of the zwitterionic resonance structure
tions start with the protonation of the carbonyl function (Scheme 13). Therefore, the two N-methyl groups of com-
1
and the imine nitrogen atom. Tautomerization of the O- pound 7a show different chemical shifts in the H and 13C
protonated (monocationic) azadienone, probably via a di- NMR spectra.
cationic intermediate, affords the monocationic penta-1,4-
We were able to obtain some crystals of compound 7c.
dien-3-one precursor for cyclization, which easily gives the An X-ray diffraction study of one of the crystals indicated
final cyclopentenol derivative after 4π–1,5-electrocycliza- an isomeric structure 7cЈ to the one that was identified by
tion, like a classic Nazarov reaction (Scheme 11).[14]
spectroscopic methods after the reaction. It is clearly
Scheme 11.
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N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
FULL PAPER
Scheme 12. Calculated relative energies and activation energy
(above arrow) for the electrocyclization of the 3-hydroxypentadien-
ylium ion [B3LYP/6-311G(d,p)//B3LYP/6-311G(d,p) including
ZPE].
Figure 3. Molecular structure 7cЈ in the solid state (X-ray crystal
structure).
the azadienone, followed by tautomerism, now involving
the NMe2 group (probably via a dication as intermediate),
to give an iminium cation. Ring-closure of the monocation
and subsequent deprotonation affords the final product 8
(Scheme 15).
Quantum chemical calculations indicate that the forma-
tion of the diazepinol is an exothermic process (–13.4 kcal/
mol) with a moderate activation barrier (15.0 kcal/mol;
(Scheme 16).
Scheme 13.
formed by a 1,3-shift of the piperidine moiety from the α-
nitrogen atom of the hydrazone group to the carbon atom
at the 3-position of the cyclopentenol ring. Presumably 7cЈ
was formed as a byproduct in a low yield, but was not de-
tected in the NMR spectra (Scheme 14, Figure 3).
Scheme 16. Calculated relative energies and activation energy
(above arrow) for the 1,7-electrocyclization reaction [SCS-MP2/6-
311G(d,p)//B3LYP/6-311G(d,p) including ZPE].
According to the calculations, the helical (conrotatory)
transition-state structure for the formation of the seven-
Scheme 14.
The formation of the dihydrodiazepinol derivatives from membered ring, as the NICS value (–11.6) and the charge
azadienones 5k,l without a methyl group at the 2-position separation between terminal atoms (0.17 e) indicate, can be
might be explained by the following mechanism. Again, the regarded as a Möbius-type aromatic system with 8π elec-
reaction starts with protonation of the carbonyl function of trons.[16]
Scheme 15.
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1,5- 1,6- or 1,7-Electrocyclization Reactions
Preparation of Trifluoromethyl Ketones 4:[17] tBuLi (1 equiv.) was
added dropwise at –25 °C under argon to a solution of the halo-
thiophene in THF (1 mmol of the compound in 2 mL of solvent).
After 30 min, CuBr·Me2S (1 equiv.) was added in one portion. Af-
ter 10 min, the flask was removed from the cooling bath and kept
at room temp. for 10 min. The flask was cooled to –25 °C and kept
at that temperature for another 30 min. The anhydride (1 equiv.)
was added dropwise and the reaction mixture was stirred at –15 °C
for 6 h. The reaction mixture was warmed to 0 °C and stirred at
this temperature for 20 min. Aqueous saturated NH4Cl (1 mL to
1 mmol of the compound) was added and the crude product ex-
tracted into ethyl acetate. The organic layer was washed with brine
and dried with MgSO4. The solvent was removed and the residue
was purified by using column chromatography.
Conclusions
We have found that 5,5-disubstituted 1-aza-1,4-dien-3-
ones containing an unsubstituted and 3-halogen-substituted
thienyl and a CF3 group at the 5-position under treatment
with an excess of triflic acid undergo 1,5- 1,6- or 1,7-electro-
cyclization reactions, depending on the substitution pattern,
to afford cyclopentenol, benzothiophenol or dihydrodiazep-
inol derivatives. The 1,5- and 1,7-electrocyclization path-
ways require tautomerism of the initially formed monoca-
tionic species, presumably via intermediate dications. The
1,6-cyclization necessarily also involves dicationic interme-
diates under superelectrophilic solvation. An excess of
strong triflic acid provides a medium favourable for the cre-
ation of such superelectrophilic species and opens up novel
possibilities for successful cyclization reactions. Quantum
chemical calculations have given a deeper insight into the
mechanisms of the presented transformations.
1-(3-Bromothiophen-2-yl)-2,2,2-trifluoroethanone (4a): Obtained by
following the general procedure. The subsequent chromatographic
purification (Et2O/pentane, 1:20) gave 0.720 g (2.78 mmol, 28%) of
1
4a as an orange oil. H NMR (300 MHz, CDCl3): δ = 7.28 (d, J
= 5.2 Hz, 1 H, β-H-thiophene), 7.78 (d, J = 5.2 Hz, 1 H, α-H-
thiophene) ppm. 13C NMR (75 MHz, CDCl3): δ = 115.9 (q, J =
290.7 Hz, CF3), 122.7 (CBr), 126.2 (C-ipso), 134.2 (CH), 135.4 (q,
J = 1.91 Hz, CH), 172.2 (q, J = 37.6 Hz, CO) ppm. 19F NMR
Experimental Section
(282 MHz, CDCl ): δ = –73.7 ppm. IR (film): ν = 3383 (w), 3113
˜
3
General: Melting points: Büchi Melting Point B-540; melting points
are uncorrected. 1H, 13C, 19F, 31P, GCOSY, GHSQC, GHMBC and
1D NOE NMR spectroscopy: Varian INOVA 500, AMX 400,
Bruker WM 300 spectrometers. TMS (1H; δ = 0.00 ppm), CDCl3
(13C; δ = 77.0 ppm), CFCl3 (19F; δ = 0.0 ppm) were used as internal
references and 85% H3PO4 (31P; δ = 0.0 ppm) was used as the ex-
ternal reference. IR: Nicolet FT-IR 5DXC spectrometer. Electron
ionization (EI) mass spectra: Finnigan MAT C 312 spectrometer
(70 eV). MS: Mass spectra were recorded with Finnigan MAT
4200S, a Bruker Daltonics micrOTOF and a Waters-Micromass
Quatro LCZ (ESI) spectrometers. Elemental analysis: Elementar
Vario EL III analyse automate. All solvents and reagents were rig-
orously dried and purified by standard methods or were used as
received from Aldrich, Acros or Fluka. When necessary, the experi-
ments were carried out with complete exclusion of moisture. Col-
umn chromatography: Merck silica gel 60 (0.040–0.063 mm). TLC:
Merck silica gel plates (silica gel 60 F254), detection with UV light.
Preparation of Hydrazones 2:[6] The hydrazones 2 were prepared
from α-keto esters 1 and the corresponding hydrazines. The α-keto
ester (1 equiv.) was dissolved in abs. ethanol (1 mmol of the com-
pound in 2 mL of solvent) and the hydrazine (1–1.1 equiv.) in abs.
ethanol (1 mmol of the compound in 0.5 mL of solvent) was added
slowly at 0 °C. In several cases acetic acid (1 equiv.) and a small
amount of sodium acetate were added to the reaction mixture in
order to maintain a pH of 5–6. The reaction mixture was stirred
at room temp. for 4 h, then filtered and the solvent evaporated. The
hydrazones 2 were purified by distillation under reduced pressure.
General Procedure for the Preparation of Ketophosphonates 3:[6] Di-
methyl methylphosphonate (1 equiv.; d = 1.161) was dissolved in
abs. THF (1 mmol of the compound in 1.5 mL of solvent), cooled
to –78 °C and nBuLi (1.6  in hexane, 1 equiv.) was added slowly.
The reaction mixture was stirred for 1 h at –78 °C. Then the respec-
tive hydrazone 2 (1 equiv.) in abs. THF (1 mmol of the compound
in 0.5 mL) was added. The reaction mixture was stirred for 4 h at
–78 °C and then quenched with AcOH (1 equiv.) and water (ca.
10 equiv.). After evaporation of most of the liquid phase, the resi-
due was dissolved in dichloromethane, washed with water and then
with saturated aqueous NaHCO3 solution and again with water.
The residue was dried with MgSO4 and purified by column
chromatography.
(w), 1699 (m), 1485 (m), 1400 (m), 1366 (w), 1292 (m), 1209 (m),
1175 (s), 1150 (s), 1084 (w), 943 (m), 878 (m), 812 (w), 768 (m),
739 (m), 650 (w), 582 (w), 532 (w) cm–1. HRMS (ESI): calcd. for
C6H2BrF3OS(CH3OH)Na 314.9101; found 314.9087. C6H2BrF3OS
(259.04): calcd. C 27.82, H 0.78; found C 28.11, H 1.11.
1-(3-Chlorothiophen-2-yl)-2,2,2-trifluoroethanone (4b): Obtained by
following the general procedure. The subsequent chromatographic
purification (Et2O/pentane, 1:20) gave 0.832 g (3.89 mmol, 39%) of
4b as a green oil. 1H NMR (300 MHz, CDCl3): δ = 7.18 (d, J
= 5.2 Hz, 1 H, β-H-thiophene), 7.80 (d, J = 5.2 Hz, 1 H, α-H-
thiophene) ppm. 13C NMR (75 MHz, CDCl3): δ = 115.9 (q, J =
290.5 Hz, CF3), 125.4 (C-ipso), 131.3 (CH), 134.8 (q, J = 1.73 Hz,
CH), 136.9 (CCl), 172.1 (q, J = 37.8 Hz, CO) ppm. 19F NMR
(282 MHz, CDCl ): δ = –74.0 ppm. IR (film): ν = 3383 (w), 3115
˜
3
(m), 2957 (w), 2918 (m), 2851 (w), 1701 (m), 1541 (w), 1491 (m),
1406 (m), 1369 (m), 1296 (m), 1211 (m), 1163 (s), 1148 (m), 1088
(m), 953 (m), 916 (w), 889 (m), 826 (w), 770 (m), 739 (m), 656 (m),
586 (w) cm–1. HRMS (ESI): calcd. for C6H2ClF3OS(CH3OH)Na
268.9627; found 268.9616.
General Procedure for the Preparation of Azadienones 5: tBuOK
(1 equiv.) was dissolved in abs. THF (1 mmol of the base in 10 mL
of solvent) and the keto phosphonate 3 (1 equiv.) in THF (1 mmol
of the compound in 2 mL of the solvent) was added. The reaction
mixture was stirred for 1 h at room temp. and the trifluoromethyl
ketone (1 equiv.) in THF was added. The reaction mixture was
stirred for 4 h at room temp. Then the solvent was evaporated. The
residue was dissolved in dichloromethane, washed with brine, dried
with MgSO4, concentrated and purified by column chromatog-
raphy. In all cases the product with CF3 and carbonyl group in the
trans position is the main isomer. 1H and 13C NMR signals have
been assigned for the main isomeric product. The stereochemistries
of the products were determined by comparing the 19F NMR
chemical shifts to compounds with known stereochemistry.[4c] The
ratio of E and Z isomers was determined from 19F NMR experi-
ments on the crude reaction mixture.
5-(Benzo[b]thiophen-2-yl)-2-(2,2-dimethylhydrazono)-6,6,6-trifluoro-
hex-4-en-3-one (5a): This compound was obtained from dimethyl
3-(2,2-dimethylhydrazono)-2-oxobutylphosphonate[6] (0.352 g,
1.50 mmol) and 2-(trifluoroacetyl)benzo[b]thiophene (0.345 g,
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N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
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1.50 mmol) according to the general procedure. The subsequent
chromatographic purification (Et2O/pentane, 1:3) gave 0.416 g
(1.22 mmol, 82%) of 5a as an orange oil. 1H NMR (300 MHz,
CDCl3): δ = 2.04 (s, 3 H, CH3), 3.11 (s, 6 H, CH3N), 7.30–7.33 (m,
2 H, H-thiophene), 7.36 (s, 1 H, H-thiophene), 7.39 (q, J = 1.4 Hz,
1 H, H-olef.), 7.73–7.77 (m, 2 H, H-thiophene) ppm. 13C NMR
(75 MHz, CDCl3): δ = 12.2 (CH3), 46.6 (CH3N), 121.9 (CH-thio-
phene), 122.7 (q, J = 274.6 Hz, CF3), 124.0 (CH-thiophene), 124.4
(CH-thiophene), 125.0 (CH-thiophene), 126.1 (CH-thiophene),
127.6 (q, J = 31.4 Hz, CCF3), 132.3, 134.5 (q, J = 5.2 Hz, CH-
olef.), 139.1, 139.8, 140.5, 189.7 (CO) ppm. 19F NMR (282 MHz,
CDCl3): δ = –66.6 (Z isomer), –60.6 (E isomer) ppm; ratio 13:1. IR
found 363.0749. C16H15F3N2OS (340.36): calcd. C 56.46, H 4.44,
N 8.23; found C 56.07, H 4.24, N 8.01.
4-(Benzo[b]thiophen-2-yl)-1-(2,2-dimethylhydrazono)-5,5,5-trifluoro-
1-(thiophen-2-yl)pent-3-en-2-one (5d): This compound was obtained
from dimethyl 3-(2,2-dimethylhydrazono)-2-oxo-3-(thiophen-2-yl)-
propylphosphonate[6] (0.196 g, 0.60 mmol) and 2-(trifluoroacetyl)-
benzo[b]thiophene (0.138 g, 0.60 mmol) according to the general
procedure. The subsequent chromatographic purification (Et2O/
pentane, 1:3) gave 0.126 g (0.31 mmol, 51%) of 5d as a brown oil.
1H NMR (300 MHz, CDCl3): δ = 2.99 (s, 6 H, CH3N), 6.80 (dd,
J = 3.5, 1.2 Hz, 1 H, H-arom.), 6.97 (dd, J = 5.1, 3.5 Hz, 1 H, H-
arom.), 7.31–7.38 (m, 4 H, H-arom.), 7.40 (br. s, 1 H, H-arom.),
7.73–7.79 (m, 2 H, H-arom.) ppm. 13C NMR (100 MHz, CDCl3):
δ = 46.7 (CH3N), 121.9 (CH-arom.), 122.8 (q, J = 274.3 Hz, CF3),
124.1 (CH-arom.), 124.4 (CH-arom.), 126.1 (CH-arom.), 126.4
(CH-arom.), 125.0 (CH-arom.), 127.7 (CH-arom.), 130.1 (CH-
arom.), 132.5, 134.7 (q, J = 5.3 Hz, CH-olef.), 139.1, 140.5, 189.5
(CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –66.5 (Z isomer),
(film): ν = 3435 (w), 3283 (w), 3059 (w), 2959 (w), 2922 (m), 2878
˜
(w), 2841 (w), 2793 (w), 1751 (w), 1657 (s), 1553 (s), 1458 (m), 1439
(m), 1427 (m), 1404 (w), 1369 (m), 1273 (s), 1252 (s), 1173 (s), 1124
(s), 1105 (s), 941 (w), 914 (w), 864 (m), 829 (m), 748 (s), 727 (m),
708 (w) cm–1. HRMS (ESI): calcd. for C16H15F3N2NaOS 363.0749;
found 363.0755.
2-(2,2-Dimethylhydrazono)-6,6,6-trifluoro-5-(thiophen-2-yl)hex-4-
en-3-one (5b): This compound was obtained from dimethyl 3-(2,2-
dimethylhydrazono)-2-oxobutylphosphonate[6] (0.220 g,
0.93 mmol) and 2-(trifluoroacetyl)thiophene (0.167 g, 0.93 mmol)
according to the general procedure. The subsequent chromato-
graphic purification (Et2O/pentane, 1:3) gave 0.223 g (0.77 mmol,
83%) of 5b as an orange oil. 1H NMR (300 MHz, CDCl3): δ =
2.04 (s, 3 H, CH3), 3.11 (s, 6 H, CH3N), 7.00 (dd, J = 5.1, 3.6 Hz,
1 H, H-thiophene), 7.13 (d, J = 3.6 Hz, 1 H, H-thiophene), 7.30
(q, J = 1.4 Hz, 1 H, H-olef.), 7.35 (dd, J = 5.1, 1 Hz, 1 H, H-
thiophene) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.3 (CH3), 46.6
(CH3N), 122.7 (q, J = 274.5 Hz, CF3), 126.8 (CH-thiophene), 127.5
(CH-thiophene), 129.3 (CH-thiophene), 131.8, 132.7 (q, J = 5.2 Hz,
CH-olef.), 140.4 (C=N), 189.9 (CO) ppm. 19F NMR (282 MHz,
CDCl3): δ = –67.0 (Z isomer), –61.1 (E isomer) ppm; ratio 18:1. IR
–60.6 (E isomer) ppm; ratio 9:1. IR (film): ν = 3391 (w), 3098 (m),
˜
3059 (m), 3030 (m), 2926 (m), 2872 (m), 2793 (w), 1636 (s), 1553
(s), 1508 (s), 1458 (m), 1435 (s), 1414 (s), 1352 (s), 1273 (s), 1250
(s), 1217 (s), 1171 (s), 1124 (s), 1082 (s), 1061 (s), 1032 (s), 947 (m),
901 (m), 860 (m), 849 (m), 833 (m), 806 (m), 777 (w), 748 (s), 725
(s), 704 (s), 644 (m), 617 (w), 588 (w), 559 (w) cm–1. HRMS (ESI):
calcd. for C19H15F3N2NaOS2 431.0470; found 431.0471.
5-(Benzo[b]thiophen-2-yl)-6,6,6-trifluoro-2-(morpholinoimino)hex-4-
en-3-one (5e): This compound was obtained from dimethyl 3-(mor-
pholinoimino)-2-oxobutylphosphonate[6] (0.278 g, 1.00 mmol) and
2-(trifluoroacetyl)benzo[b]thiophene (0.230 g, 1.00 mmol) accord-
ing to the general procedure. The subsequent chromatographic pu-
rification (Et2O/pentane, 1:2) gave 0.310 g (0.81 mmol, 81%) of 5e
as a yellow solid; m.p. 72–73 °C. 1H NMR (300 MHz, CDCl3): δ
= 1.98 (s, 3 H, CH3), 3.21–3.24 (m, 4 H, CH2N), 3.75–3.78 (m, 4
H, CH2O), 7.32–7.35 (m, 2 H, H-thiophene), 7.37 (s, 1 H, H-thio-
phene), 7.40 (q, J = 1.3 Hz, H-olef.), 7.74–7.79 (m, 2 H, H-thio-
phene) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.3 (CH3), 54.5
(CH2N), 66.1 (CH2O), 121.9 (CH-arom.), 122.5 (q, J = 274.9 Hz,
CF3), 124.5 (CH-arom.), 125.2 (CH-arom.), 126.5 (CH-arom.),
129.4 (q, J = 31.6 Hz, CCF3), 131.9, 133.0 (q, J = 5.2 Hz, CH-
olef.), 139.0, 140.5, 149.2, 190.0 (CO) ppm. 19F NMR (282 MHz,
CDCl3): δ = –66.8 (Z isomer), –60.4 (E isomer) ppm; ratio 11:1. IR
(film): ν = 3397 (w), 3103 (w), 2959 (w), 2920 (w), 2878 (w), 2851
˜
(w), 2795 (w), 1655 (w), 1553 (m), 1437 (w), 1369 (w), 1333 (w),
1273 (m), 1231 (m), 1173 (m), 1126 (m), 1094 (m), 1043 (w), 955
(w), 930 (w), 872 (w), 853 (w), 829 (w), 804 (w), 706 (w), 660 (w),
588 (w) cm–1. HRMS (ESI): calcd. for C12H13F3N2NaOS 313.0593;
found 313.0597. C12H13F3N2OS (290.30): calcd. C 49.65, H 4.51,
N 9.65; found C 49.69, H 4.29, N 9.58.
5-(Benzo[b]thiophen-3-yl)-2-(2,2-dimethylhydrazono)-6,6,6-trifluoro-
hex-4-en-3-one (5c): This compound was obtained from dimethyl
3-(2,2-dimethylhydrazono)-2-oxobutylphosphonate[6] (0.142 g,
0.60 mmol) and 3-(trifluoroacetyl)benzo[b]thiophene (0.138 g,
0.60 mmol) according to the general procedure. The subsequent
chromatographic purification (Et2O/pentane, 1:2) gave 0.152 g
(0.45 mmol, 75%) of 5c as an orange oil. 1H NMR (400 MHz,
CDCl3): δ = 2.05 (s, 3 H, CH3), 3.13 (s, 6 H, CH3N), 7.31–7.41
(m, 4 H, H-thiophene), 7.74–7.85 (m, 2 H, H-thiophene and H-
olef.) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.3 (CH3), 12.4
(CH3), 46.7 (CH3N), 46.8 (CH3N), 121.9 (CH-thiophene), 122.57
(CH-thiophene), 122.64 (CH-thiophene), 124.1 (CH-thiophene),
124.2 (CH-thiophene), 124.39 (CH-thiophene), 124.41 (CH-thio-
phene), 125.0 (CH-thiophene), 126.1 (CH-thiophene), 126.4 (CH-
thiophene), 132.4, 132.7 (q, J = 5.0 Hz, CH-olef.), 134.4 (q, J =
5.2 Hz, CH-olef.), 138.3, 139.1, 139.3, 140.1, 140.6, 142.1, 188.1
(CO), 189.7 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –67.0
(film): ν = 3445 (w), 3306 (w), 3063 (m), 3032 (w), 2972 (m), 2916
˜
(m), 2891 (m), 2853 (m), 1751 (w), 1666 (s), 1574 (s), 1450 (m),
1439 (s), 1364 (m), 1354 (m), 1331 (m), 1290 (s), 1252 (s), 1177 (s),
1157 (s), 1123 (s), 1105 (s), 1067 (s), 1015 (s), 941 (m), 930 (m), 920
(m), 899 (m), 862 (m), 833 (m), 808 (m), 752 (s), 729 (m), 706
(m) cm–1. HRMS (ESI): calcd. for C18H17F3N2NaO2S 405.0855;
found 405.0863.
4-(Benzo[b]thiophen-2-yl)-1-(2,2-dimethylhydrazono)-5,5,5-trifluoro-
1-phenylpent-3-en-2-one (5f): This compound was obtained from di-
methyl 3-(2,2-dimethylhydrazono)-2-oxo-3-phenylpropylphos-
phonate[6] (0.200 g, 0.67 mmol) and 2-(trifluoroacetyl)benzo[b]thio-
phene (0.154 g, 0.67 mmol) according to the general procedure. The
subsequent chromatographic purification (Et2O/pentane, 1:3) gave
0.230 g (0.57 mmol, 85 %) of 5f as an orange oil. 1H NMR
(400 MHz, CDCl3): δ = 2.89 (s, 6 H, CH3N), 7.05–7.07 (m, 2 H,
H-arom.), 7.27–7.29 (m, 3 H, H-arom.), 7.32–7.35 (m, 2 H, H-
arom.), 7.41 (br. s, 2 H, H-arom.), 7.73–7.80 (m, 2 H, H-
arom.) ppm. 13C NMR (100 MHz, CDCl3): δ = 47.0 (CH3N), 121.9
(E isomer), –59.9 (Z isomer) ppm; ratio 15:1. IR (film): ν = 3285
˜
(w), 3096 (w), 3059 (w), 2924 (m), 2876 (m), 2839 (w), 2793 (w),
1751 (w), 1661 (s), 1553 (s), 1458 (m), 1439 (m), 1429 (m), 1404
(m), 1369 (s), 1273 (s), 1236 (s), 1171 (s), 1124 (s), 970 (w), 937 (w), (CH-arom.), 122.8 (q, J = 274.3 Hz, CF3), 124.0 (CH-arom.), 125.0
905 (w), 876 (w), 829 (m), 804 (w), 758 (m), 748 (m), 729 (m), (CH-arom.), 126.3 (CH-arom.), 127.2 (q, J = 31.5 Hz, CCF3),
708 (w) cm–1. HRMS (ESI): calcd. for C16H15F3N2NaOS 363.0749; 127.6 (CH-arom.), 128.2 (CH-arom.), 130.2 (CH-arom.), 132.6,
1234
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 1228–1240

1,5- 1,6- or 1,7-Electrocyclization Reactions
133.7, 135.2 (q, J = 5.1 Hz, CH-olef.), 138.0, 139.1, 140.5, 189.5 3.40 (m, 4 H, CH2N), 6.99 (d, J = 5.3 Hz, 1 H, H-thiophene), 7.39
(CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –66.5 (Z isomer),
(d, J = 5.3 Hz, 1 H, H-thiophene), 7.91 (q, J = 1.3 Hz, 1 H, H-
–60.5 (E isomer) ppm; ratio 3.5:1. IR (film): ν = 3275 (w), 3059 (s),
olef.) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.2 (CH3), 24.0
˜
3024 (m), 2928 (s), 2874 (m), 2795 (m), 1811 (w), 1649 (s), 1599 (CH2), 25.5 (CH2), 55.6 (CH2N), 113.0 (CBr), 122.1 (q, J =
(m), 1545 (s), 1491 (s), 1458 (s), 1439 (s), 1425 (s), 1406 (m), 1360
(s), 1296 (s), 1273 (s), 1252 (s), 1173 (s), 1124 (s), 1080 (s), 1030 (s),
274.7 Hz, CF3), 127.6 (CH-arom.), 130.3 (CH-arom.), 134.9 (q, J =
4.8 Hz, CH-olef.), 142.5, 145.3 (C=N), 187.1 (CO) ppm. 19F NMR
974 (s), 939 (m), 918 (m), 897 (m), 866 (s), 833 (s), 793 (m), 748 (s), (282 MHz, CDCl3): δ = –67.7 (E isomer), –61.8 (Z isomer) ppm;
727 (s), 702 (s) cm–1. HRMS (ESI): calcd. for C21H17F3N2NaOS
425.0906; found 425.0905.
ratio 5:1. IR (film): ν = 3109 (w), 3090 (w), 2941 (m), 2856 (m),
˜
2835 (w), 1751 (w), 1666 (m), 1553 (m), 1468 (w), 1443 (m), 1354
(m), 1339 (m), 1294 (m), 1259 (m), 1231 (m), 1177 (s), 1130 (s),
1101 (m), 1061 (m), 1032 (w), 1015 (m), 988 (w), 947 (w), 868 (m),
858 (w), 820 (w), 804 (w), 772 (w), 714 (m), 665 (m), 623 (w) cm–1.
HRMS (ESI): calcd. for C15H16BrF3N2OSH 411.0171; found
411.0173. C15H16BrF3N2OS (409.26): calcd. C 44.02, H 3.94, N
6.84; found C 44.12, H 4.00, N 6.96.
5-(3-Bromothiophen-2-yl)-2-(2,2-dimethylhydrazono)-6,6,6-trifluoro-
hex-4-en-3-one (5g): This compound was obtained from dimethyl
3-(2,2-dimethylhydrazono)-2-oxobutylphosphonate[6] (0.164 g,
0.69 mmol) and 1-(3-bromothiophen-2-yl)-2,2,2-trifluoroethanone
(4a; 0.180 g, 0.69 mmol) according to the general procedure. The
subsequent chromatographic purification (Et2O/pentane, 1:2) gave
0.215 g (0.58 mmol, 84 %) of 5g as an orange oil. 1H NMR
(300 MHz, CDCl3): δ = 2.03 (s, 3 H, CH3), 3.19 (s, 6 H, CH3N),
6.99 (d, J = 5.3 Hz, 1 H, H-thiophene), 7.39 (d, J = 5.3 Hz, 1 H,
H-thiophene), 7.88 (q, J = 1.34 Hz, 1 H, H-olef.) ppm. 13C NMR
(75 MHz, CDCl3): δ = 12.5 (CH3), 46.8 (CH3N), 113.0 (CBr), 122.2
2-(Azepan-1-ylimino)-5-(3-bromothiophen-2-yl)-6,6,6-trifluorohex-4-
en-3-one (5j): This compound was obtained from dimethyl 3-
(azepan-1-ylimino)-2-oxobutylphosphonate[6] (0.203 g, 0.70 mmol)
and 1-(3-bromothiophen-2-yl)-2,2,2-trifluoroethanone (4a; 0.181 g,
0.70 mmol) according to the general procedure. The subsequent
(q, J = 274.6 Hz, CF3), 124.9, 127.5 (CH-arom.), 130.2 (CH- chromatographic purification (Et2O/pentane, 1:2) gave 0.225 g
arom.), 130.5, 131.5, 134.1, 135.0 (q, J = 4.7 Hz, CH-olef.), 141.3
(0.53 mmol, 77 %) of 5j as an orange oil. 1H NMR (300 MHz,
(C=N), 186.8 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –67.6 CDCl3): δ = 1.58–1.61 (m, 4 H, CH2), 1.75–1.77 (m, 4 H, CH2),
(E isomer), –61.8 (Z isomer) ppm; ratio 8:1. IR (film): ν = 3107
(w), 3090 (w), 2839 (w), 2795 (w), 2876 (m), 2920 (m), 1747 (w),
2.03 (s, 3 H, CH3), 3.67–3.70 (m, 4 H, CH2N), 6.98 (d, J = 5.3 Hz,
1 H, H-thiophene), 7.37 (d, J = 5.3 Hz, 1 H, H-thiophene), 7.91
˜
1661 (m), 1628 (m), 1547 (m), 1441 (m), 1425 (m), 1406 (m), 1367 (q, J = 1.4 Hz, 1 H, H-olef.) ppm. 13C NMR (75 MHz, CDCl3): δ
(m), 1354 (m), 1271 (m), 1173 (m), 1123 (m), 1096 (m), 1063 (m), = 12.4 (CH3), 27.0 (CH2), 28.1 (CH2), 57.0 (CH2N), 112.8 (CBr),
943 (w), 905 (m), 868 (m), 837 (m), 802 (w), 717 (m), 665 (m), 629
(w), 590 (w) cm–1. HRMS (ESI): calcd. for C12H12BrF3N2NaOS
392.9683; found 392.9664. C12H12BrF3N2OS (369.20): calcd. C
39.04, H 3.28, N 7.59; found C 39.30, H 3.22, N 7.52.
122.3 (q, J = 274.5 Hz, CF3), 127.4 (CH-arom.), 130.2 (CH-arom.),
136.3, 136.5 (q, J = 4.7 Hz, CH-olef.), 143.7 (C=N), 186.7
(CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –67.4 (E isomer),
–61.9 (Z isomer) ppm; ratio 3:1. IR (film): ν = 3285 (w), 3107 (w),
˜
3088 (w), 2930 (m), 2858 (m), 1657 (m), 1543 (s), 1450 (m), 1439
(m), 1366 (m), 1352 (m), 1339 (m), 1304 (m), 1283 (m), 1252 (m),
1234 (m), 1175 (m), 1128 (m), 1065 (m), 988 (w), 953 (w), 903 (w),
868 (w), 822 (w), 806 (w), 714 (w), 665 (w), 623 (w) cm–1. HRMS
(ESI) calcd. for C16H18BrF3N2NaOS 447.0148; found 447.0155.
C16H18BrF3N2OS (423.29): C 45.40, H 4.29, N 6.62; found C 45.68,
H 4.17, N 6.34.
5-(3-Bromothiophen-2-yl)-6,6,6-trifluoro-2-(morpholinoimino)hex-4-
en-3-one (5h): This compound was obtained from dimethyl 3-(mor-
pholinoimino)-2-oxobutylphosphonate[6] (0.084 g, 0.30 mmol) and
1-(3-bromothiophen-2-yl)-2,2,2-trifluoroethanone (4a; 0.078 g,
0.30 mmol) according to the general procedure. The subsequent
chromatographic purification (Et2O/pentane, 1:1) gave 0.092 g
(0.22 mmol, 75%) of 5h as an orange oil. 1H NMR (300 MHz,
CDCl3): δ = 1.98 (s, 3 H, CH3), 3.30 (m, 4 H, CH2N), 3.85 (m, 4 4-(3-Bromothiophen-2-yl)-1-(2,2-dimethylhydrazono)-5,5,5-trifluoro-
H, CH2O), 7.00 (d, J = 5.3 Hz, 1 H, H-thiophene), 7.42 (d, J = 1-(thiophen-2-yl)pent-3-en-2-one (5k): This compound was obtained
5.3 Hz, 1 H, H-thiophene), 7.88 (q, J = 1.34 Hz, 1 H, H-olef.) ppm. from dimethyl 3-(2,2-dimethylhydrazono)-2-oxo-3-(thiophen-2-yl)-
13C NMR (75 MHz, CDCl3): δ = 13.4 (CH3), 54.6 (CH2N), 66.2
propylphosphonate[6] (0.185 g, 0.61 mmol) and 1-(3-bromothio-
(CH2O), 113.1 (CBr), 121.9 (q, J = 274.9 Hz, CF3), 127.0, 127.8 phen-2-yl)-2,2,2-trifluoroethanone (4a; 0.158 g, 0.61 mmol) accord-
(CH-arom.), 129.3 (q, J = 32.9 Hz, CCF3), 130.3 (CH-arom.), ing to the general procedure. The subsequent chromatographic pu-
133.7 (q, J = 4.8 Hz, CH-olef.), 141.2, 150.6, 187.2 (CO) ppm. 19F rification (Et2O/pentane, 1:5) gave 0.130 g (0.30 mmol, 49%) of 5k
NMR (282 MHz, CDCl3): δ = –67.8 (E isomer), –61.5 (Z iso-
mer) ppm; ratio 4:1. IR (film): ν = 3310 (w), 3092 (m), 2966 (m), CH3), 6.85 (dd, J = 3.5, 1.2 Hz, 1 H, H-thiophene), 6.95–6.98 (m,
as an orange oil. 1H NMR (400 MHz, CDCl3): δ = 3.10 (s, 6 H,
˜
2922 (m), 2897 (m), 2855 (s), 2768 (w), 2733 (w), 2718 (w), 2687
2 H, H-thiophene), 7.34–7.37 (m, 2 H, H-thiophene), 7.86 (q, J =
(w), 1751 (w), 1720 (w), 1674 (s), 1618 (m), 1572 (m), 1516 (m), 1.4 Hz, 1 H, H-olef.) ppm. 13C NMR (100 MHz, CDCl3): δ = 46.7
1456 (m), 1445 (m), 1364 (m), 1352 (m), 1339 (m), 1290 (s), 1250 (CH2N), 113.0 (CBr), 122.2 (q, J = 274.7 Hz, CF3), 126.0 (CH-
(s), 1117 (s), 1067 (m), 1018 (m), 995 (w), 947 (m), 930 (w), 866
arom.), 127.57 (CH-arom.), 127.63 (CH-arom.), 130.2 (CH-arom.),
(m), 822 (w), 806 (w), 716 (m), 665 (m), 629 (w), 592 (w) cm–1. 130.3 (CH-arom.), 132.5 (C-ipso), 136.2 (q, J = 4.7 Hz, CH-olef.),
HRMS (ESI): calcd. for C14H14BrF3N2NaO2S 434.9784; found
434.9775.
142.2 (C=N), 186.3 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ =
–67.5 (E isomer), –61.9 (Z isomer) ppm; ratio 3.5:1. IR (film): ν =
˜
3279 (w), 3107 (m), 2930 (m), 2903 (m), 2874 (m), 2795 (m), 1659
(s), 1651 (s), 1557 (s), 1508 (s), 1439 (s), 1414 (s), 1354 (s), 1292 (s),
1180 (s), 1132 (s), 1082 (s), 1063 (s), 1034 (s), 961 (m), 934 (m), 868
(s), 851 (s), 833 (s), 806 (m), 779 (s), 712 (s), 627 (w), 577 (w) cm–1.
HRMS (ESI): calcd. for C15H12BrF3N2NaOS2 460.9398, found
460.9396.
5-(3-Bromothiophen-2-yl)-6,6,6-trifluoro-2-(piperidin-1-ylimino)hex-
4-en-3-one (5i): This compound was obtained from dimethyl 2-oxo-
3-(piperidin-1-ylimino)butylphosphonate[6] (0.110 g, 0.40 mmol)
and 1-(3-bromothiophen-2-yl)-2,2,2-trifluoroethanone (4a; 0.104 g,
0.40 mmol) according to the general procedure. The subsequent
chromatographic purification (Et2O/pentane, 1:2) gave 0.128 g
(0.31 mmol, 78 %) of 5i as an orange oil. 1H NMR (300 MHz, 4-(3-Chlorothiophen-2-yl)-1-(2,2-dimethylhydrazono)-5,5,5-trifluoro-
CDCl3): δ = 1.69–1.72 (m, 6 H, CH2), 1.98 (s, 3 H, CH3), 3.37– 1-(thiophen-2-yl)pent-3-en-2-one (5l): This compound was obtained
Eur. J. Org. Chem. 2009, 1228–1240
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1235

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
FULL PAPER
from dimethyl 3-(2,2-dimethylhydrazono)-2-oxo-3-(thiophen-2-yl)-
propylphosphonate[6] (0.200 g, 0.66 mmol) and 1-(3-chlorothio-
phen-2-yl)-2,2,2-trifluoroethanone (4b; 0.142 g, 0.66 mmol) accord-
ing to the general procedure. The subsequent chromatographic pu-
chromatographic purification (pentane/Et2O, 5:1) gave 0.040 g
(0.12 mmol, 14%) of 6a as a yellow solid; m.p. 144.5–145.5 °C. The
same product 6a (0.020 g, 0.06 mmol) was obtained from azadi-
enone 5e (0.153 g, 0.40 mmol) in 15% yield as a yellow solid. 1H
rification (Et2O/pentane, 1:2) gave 0.155 g (0.40 mmol, 60%) of 5l NMR (400 MHz, CDCl3): δ = 2.43 (s, 3 H, CH3COO), 2.77 (s, 3
1
as a red oil. H NMR (400 MHz, CDCl3): δ = 3.00 (s, 6 H, CH3),
6.76 (dd, J = 3.5, 1.2 Hz, 1 H, H-thiophene), 6.82 (d, J = 5.3 Hz,
1 H, H-Cl-thiophene), 6.88–6.91 (m, 2 H, H-thiophene), 7.26–7.29
H, CH3), 7.48 (s, 1 H, H-arom.), 7.50–7.56 (m, 2 H, H-arom.),
7.91–7.93 (m, 1 H, H-arom.), 8.40–8.42 (m, 1 H, H-arom.) ppm.
13C NMR (100 MHz, CDCl3): δ = 14.7 (CH3), 20.8 (CH3COO),
118.6 (q, J = 4.9 Hz, CH-arom.), 122.5, 122.7 (CH-arom.), 123.7
(q, J = 273.0 Hz, CF3), 124.7 (CH-arom.), 125.2 (CH-arom.), 126.9
(CH-arom.), 130.8, 134.2, 135.2, 136.8, 140.2 (q, J = 1.70 Hz),
145.8 (C-O), 169.4 (COO) ppm. 19F NMR (282 MHz, CDCl3): δ =
(m, 1 H, H-thiophene), 7.76 (q, J = 1.4 Hz, 1 H, H-olef.) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 46.7 (CH3), 122.3 (q, J = 274.5 Hz,
CF3), 125.1, 125.8, 126.0, 126.2, 126.5, 126.6, 127.6, 127.7, 127.8,
128.1, 130.1, 130.3, 131.0, 132.5, 136.1 (q, J = 4.8 Hz, CH-olef.),
186.5 (CO), 189.2 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ =
–63.7 ppm. IR (KBr): ν = 3439 (w), 3061 (w), 3009 (w), 2953 (w),
˜
–67.5 (E isomer), –61.9 (Z isomer) ppm; ratio 4:1. IR (film): ν = 2922 (w), 2870 (w), 2851 (w), 1763 (s), 1593 (w), 1483 (w), 1447
˜
3275 (m), 3109 (s), 2959 (m), 2930 (s), 2874 (m), 2795 (m), 1682 (w), 1433 (w), 1383 (s), 1369 (s), 1342 (s), 1300 (w), 1261 (s), 1234
(s), 1659 (s), 1651 (s), 1553 (s), 1510 (s), 1443 (s), 1414 (s), 1354 (s),
(s), 1207 (s), 1165 (s), 1150 (s), 1117 (s), 1070 (m), 1047 (m), 1016
1275 (s), 1248 (s), 1213 (s), 1178 (s), 1130 (s), 1082 (s), 1063 (s), (m), 966 (m), 908 (m), 880 (m), 799 (w), 770 (m), 729 (s), 714 (w),
1034 (s), 962 (m), 935 (m), 891 (s), 851 (s), 833 (m), 779 (m), 719 677 (w), 636 (w) cm–1. HRMS (ESI): calcd. for C16H11F3NaO2S
(s), 644 (w), 635 (w), 600 (w), 582 (w) cm–1. HRMS (ESI): calcd. 347.0324; found 347.0326.
X-ray Crystal Structure Analysis of 6a:[9] C16H11F3O2S, M =
for C15H12ClF3N2NaOS2 414.9924; found 414.9923.
324.31, colourless crystal, 0.30ϫ0.15ϫ0.10 mm, a = 5.5001(1), b
5-(Benzofuran-2-yl)-2-(2,2-dimethylhydrazono)-6,6,6-trifluorohex-4-
= 15.0059(3), c = 17.1975(4) Å, β = 92.260(1)°, V = 1418.27(3) Å3,
en-3-one (10): This compound was obtained from dimethyl 3-(2,2-
ρcalcd. = 1.519 gcm–3, µ = 0.266 mm–1, empirical absorption correc-
dimethylhydrazono)-2-oxobutylphosphonate[6] (0.352 g,
tion (0.925ՅTՅ0.974), Z = 4, monoclinic, space group P21/n (No.
1.50 mmol) and 2-(trifluoroacetyl)benzo[b]furan (0.321 g,
14), λ = 0.71073 Å, T = 223(2) K, ω and φ scans, 9373 reflections
1.50 mmol) according to the general procedure. The subsequent
chromatographic purification (Et2O/pentane, 1:3) gave 0.321 g
collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.66 Å–1, 3381 independent
(Rint = 0.049) and 2186 observed reflections [IՆ2σ(I)], 201 refined
(0.99 mmol, 66%) of 10 as an orange oil. 1H NMR (300 MHz,
parameters, R = 0.047, wR2 = 0.133, max. (min.) residual electron
CDCl3): δ = 2.18 (s, 3 H, CH3), 3.04 (s, 6 H, CH3N), 6.96 (s, 1 H,
density 0.32 (–0.34) eÅ–3, hydrogen atoms calculated and refined
H-furan), 7.18–7.37 (m, 4 H, H-furan, H-olef.), 7.55–7.58 (m, 1 H,
as riding atoms.
H-furan) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.4 (CH3), 46.5
5-Acetoxy-4-methyl-7-(trifluoromethyl)benzo[b]thiophene (6b): This
compound was obtained from azadienone 5b (0.115 g, 0.40 mmol)
according to the general procedure. The subsequent chromato-
graphic purification (pentane/Et2O, 4:1) gave 0.030 g (0.11 mmol,
(CH3N), 108.2 (q, J = 1.6 Hz, CH-furan.), 111.1 (CH-furan), 121.6
(CH-furan), 122.6 (q, J = 273.8 Hz, CF3), 123.1 (CH-furan), 123.2
(q, J = 31.7 Hz, CCF3), 125.4 (CH-furan), 127.9, 133.5 (q, J =
5.2 Hz, CH-olef.), 140.5, 147.6, 154.7, 190.7 (CO) ppm. 19F NMR
(282 MHz, CDCl3): δ = –65.4 (E isomer), –60.6 (Z isomer) ppm;
1
28%) of 6b as a yellow solid; m.p. 82–83 °C. H NMR (400 MHz,
CDCl3): δ = 2.39 (s, 3 H, CH3COO), 2.43 (s, 3 H, CH3), 7.36 (s, 1
H, H-arom.), 7.46 (d, J = 5.6 Hz, 1 H, β-H-thiophene), 7.61 (d, J
= 5.6 Hz, 1 H, α-H-thiophene) ppm. 13C NMR (100 MHz, CDCl3):
δ = 13.5 (CH3), 20.7 (CH3COO), 117.3 (q, J = 4.7 Hz, CH-arom.),
122.0 (β-CH-thiophene), 122.9 (q, J = 34.2 Hz, CCF3), 123.7 (q, J
= 272.5 Hz, CF3), 128.6, 128.8 (α-CH-thiophene), 133.3, 142.0,
145.2 (C-O), 169.3 (COO) ppm. 19F NMR (282 MHz, CDCl3): δ =
ratio 37:1. IR (film): ν = 3308 (w), 3128 (w), 3061 (w), 2961 (w),
˜
2922 (w), 2876 (w), 2793 (w), 1657 (m), 1616 (w), 1560 (s), 1510
(w), 1475 (w), 1450 (m), 1427 (m), 1404 (w), 1381 (m), 1369 (m),
1279 (s), 1246 (s), 1190 (m), 1169 (s), 1130 (s), 1094 (m), 1009 (w),
988 (m), 951 (w), 924 (w), 885 (w), 862 (w), 814 (m), 800 (w), 752
(m), 702 (w) cm–1. HRMS (ESI): calcd. for C16H15F3N2NaO2
347.0978; found 347.0980.
–63.5 ppm. IR (KBr): ν = 3431 (w), 3115 (m), 3096 (m), 3080 (w),
˜
General Procedure for the Cyclization of Azadienones Using Trifluoro-
methanesulfonic Acid: A solution of trifluoromethanesulfonic acid
(10 equiv.) in dry dichloromethane (1 mL of acid in 50 mL of sol-
vent) was cooled to –10 °C. A solution of the 1-azapenta-1,4-dien-
one 5 (1 equiv.) in dry dichloromethane (1 mmol of the compound
in 5 mL of solvent) was added dropwise with stirring. After com-
plete addition, stirring was continued for 1 h. Then the reaction
mixture was treated with acetic anhydride (20 equiv.) and stirred at
0 °C for 1 h. A saturated solution of sodium hydrogen carbonate
was added carefully to neutralize the acidic mixture. The organic
layer was washed with a saturated sodium hydrogen carbonate
solution until the aqueous layer became neutral. Then the organic
layer was washed with water, dried with MgSO4 and the solvent
was evaporated. The substances were purified by column
chromatography. For cases in which the CHN analysis results are
not indicated, product purity was determined from the NMR ex-
periments and is more than 90%.
2964 (m), 2932 (m), 2864 (m), 1761 (s), 1597 (m), 1584 (m), 1510
(m), 1501 (m), 1491 (m), 1487 (m), 1439 (m), 1435 (m), 1373 (s),
1360 (s), 1292 (s), 1261 (s), 1217 (s), 1192 (s), 1155 (s), 1121 (s),
1101 (s), 1076 (s), 1042 (s), 1016 (s), 970 (m), 941 (s), 905 (s), 868
(s), 841 (m), 799 (s), 772 (s), 741 (m), 710 (s), 700 (s), 665 (m), 638
( m ) , 6 2 7 ( m ) , 5 8 8 ( m ) c m– 1 . H R M S ( E S I ) : c a l cd . for
C12H9F3NaSO2 297.0168; found 297.0167.
X-ray Crystal Structure Analysis of 6b:[9] C12H9F3O2S, M = 274.25,
yellow crystal, 0.35ϫ0.25ϫ0.15 mm, a = 7.8501(1), b = 8.0588(1),
c = 9.3627(1) Å, α = 97.968(1), β = 92.639(1), γ = 90.503(1)°, V
= 585.90(1) Å3, ρcalcd. = 1.555 gcm–3, µ = 2.784 mm–1, empirical
absorption correction (0.442ՅTՅ0.680), Z = 2, triclinic, space
¯
group P1 (No. 2), λ = 1.54178 Å, T = 223(2) K, ω and φ scans,
5476 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.60 Å–1, 2033
independent (Rint = 0.036) and 1941 observed reflections [IՆ2σ(I)],
165 refined parameters, R = 0.050, wR2 = 0.145, max. (min.) resid-
ual electron density 0.43 (–0.25) eÅ–3, hydrogen atoms calculated
and refined as riding atoms.
2-Acetoxy-1-methyl-4-(trifluoromethyl)dibenzo[b,d]thiophene (6a):
This compound was obtained from azadienone 5a (0.335 g,
0.99 mmol) according to the general procedure. The subsequent
3-Acetoxy-4-methyl-1-(trifluoromethyl)dibenzo[b,d]thiophene (6c):
This compound was obtained from azadienone 5c (0.102 g,
1236
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 1228–1240

1,5- 1,6- or 1,7-Electrocyclization Reactions
0.30 mmol) according to the general procedure. The subsequent
chromatographic purification (pentane/Et2O, 4:1) gave 0.047 g
(0.15 mmol, 48%) of 6c as a yellow solid; m.p. 140–142 °C. 1H
NMR (400 MHz, CDCl3): δ = 2.43 (s, 3 H, CH3COO), 2.78 (s, 3
(CH-arom.), 125.0 (CH-arom.), 127.2 (CH-arom.), 128.7 (CH-
arom.), 128.9 (CH-arom.), 129.1 (CH-arom.), 134.2, 134.6, 135.1,
136.5, 140.2 (q, J = 1.50 Hz), 145.6 (C-O), 169.7 (COO) ppm. 19F
NMR (282 MHz, CDCl ): δ = –63.7 ppm. IR (KBr): ν = 3437 (w),
˜
3
H, CH3), 7.49 (s, 1 H, H-arom.), 7.51–7.55 (m, 2 H, H-arom.), 3074 (w), 3059 (w), 2955 (w), 2924 (m), 2853 (w), 1763 (s), 1591
7.92–7.94 (m, 1 H, H-arom.), 8.41–8.44 (m, 1 H, H-arom.) ppm. (w), 1506 (w), 1475 (w), 1447 (w), 1367 (s), 1342 (m), 1310 (w),
13C NMR (100 MHz, CDCl3): δ = 14.7 (CH3), 20.8 (CH3COO), 1275 (m), 1254 (m), 1234 (s), 1207 (s), 1163 (s), 1123 (s), 1069 (m),
118.6 (q, J = 4.8 Hz, CH-arom.), 122.7 (q, J = 33.9 Hz), 122.7
(CH-arom.), 123.7 (q, J = 272.9 Hz, CF3), 124.7 (CH-arom.), 125.2
1047 (m), 1022 (m), 1009 (m), 951 (m), 903 (m), 874 (m), 783 (m),
764 (m), 746 (m), 735 (m), 706 (s), 671 (w), 644 (w) cm–1. HRMS
(CH-arom.), 127.0 (CH-arom.), 130.9, 134.2, 135.2, 136.8, 140.2 (q, (ESI): calcd. for C21H13F3NaO2S 409.0481; found 409.0477.
J = 1.53 Hz), 145.8 (C-O), 169.4 (COO) ppm. 19F NMR (282 MHz,
X-ray Crystal Structure Analysis of 6e:[9] C21H13F3O2S, M =
CDCl ): δ = –63.6 ppm. IR (KBr): ν = 3443 (w), 2963 (w), 2922
˜
3
386.37, colourless crystal, 0.45ϫ0.35ϫ0.30 mm, a = 10.8846(2), b
= 9.8641(1), c = 16.6354(3) Å, β = 100.431(1)°, V = 1756.57(5) Å3,
ρcalcd. = 1.461 gcm–3, µ = 0.228 mm–1, empirical absorption correc-
tion (0.904ՅTՅ0.935), Z = 4, monoclinic, space group P21/c (No.
14), λ = 0.71073 Å, T = 223(2) K, ω and φ scans, 11779 reflections
collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.66 Å–1, 4169 independent
(Rint = 0.048) and 3192 observed reflections [IՆ2σ(I)], 245 refined
parameters, R = 0.058, wR2 = 0.153, max. (min.) residual electron
density 0.38 (–0.29) eÅ–3, hydrogen atoms calculated and refined
as riding atoms.
(m), 2851 (w), 1763 (s), 1593 (w), 1481 (m), 1447 (m), 1383 (m),
1369 (s), 1342 (m), 1300 (m), 1261 (s), 1234 (s), 1205 (s), 1165 (s),
1148 (s), 1117 (s), 1070 (s), 1045 (s), 1016 (s), 966 (m), 908 (m), 880
(m), 800 (s), 770 (m), 729 (m), 714 (m), 677 (w), 636 (w), 596 (w),
582 (w) cm–1. HRMS (ESI): calcd. for C16H11F3NaO2S 347.0324;
found 347.0330.
2-Acetoxy-1-(thiophen-2-yl)-4-(trifluoromethyl)dibenzo[b,d]thiophene
(6d): This compound was obtained from azadienone 5d (0.080 g,
0.20 mmol) according to the general procedure. The subsequent
chromatographic purification (pentane/Et2O, 4:1) gave 0.018 g
(0.05 mmol, 20%) of 6d as a yellow solid; m.p. 185–186 °C. 1H
NMR (400 MHz, CDCl3): δ = 2.07 (s, 3 H, CH3COO), 6.88 (d, J
= 8.3 Hz, 1 H, H-arom.), 7.09 (dd, J = 3.5, 1.2 Hz, 1 H, H-arom.),
7.17 (ddd, J = 8.3, 7.2, 1.1 Hz, 1 H, H-arom.), 7.26 (dd, J = 3.3,
3.0 Hz, 1 H, H-arom.), 7.43 (ddd, J = 8.3, 7.2, 1.1 Hz, 1 H, H-
arom.), 7.40 (br. s. 1 H, H-arom.), 7.61 (dd, J = 5.1, 1.2 Hz, 1
H, H-arom.), 7.85 (d, J = 8.0 Hz, 1 H, H-arom.) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.4 (CH3COO), 118.7 (q, J = 4.6 Hz, CH-
arom.), 122.4 (CH-arom.), 123.5 (q, J = 273.4 Hz, CF3), 124.6
(CH-arom.), 124.9 (CH-arom.), 127.5 (CH-arom.), 127.6 (CH-
arom.), 127.7 (CH-arom.), 128.3 (CH-arom.), 134.0, 137.9, 140.3,
147.1 (C-O), 169.7 (COO) ppm. 19F NMR (282 MHz, CDCl3): δ =
2,3-Diacetoxy-1-phenyl-4-(trifluoromethyl)dibenzo[b,d]thiophene (9):
This compound was obtained from azadienone 5f (0.190 g,
0.47 mmol) according to the general procedure. The subsequent
chromatographic purification (pentane/Et2O, 3:1) gave 0.013 g
(0.03 mmol, 6%) of 9 as a yellow solid; m.p. 148–149 °C. 1H NMR
(400 MHz, CDCl3): δ = 1.93 (s, 3 H, CH3COO), 2.37 (s, 3 H, CH3),
6.71 (d, J = 8.3 Hz, 1 H, H-arom.), 7.05 (ddd, J = 8.3, 7.2, 1.1 Hz,
1 H, H-arom.), 7.34–7.40 (m, 3 H, H-arom.), 7.54–7.56 (m, 3 H,
H-arom.), 7.82 (d, J = 7.9 Hz, 1 H, H-arom.) ppm. 13C NMR
(100 MHz, CDCl3): δ = 19.9 (CH3), 20.3 (CH3COO), 122.1 (CH-
arom.), 123.3 (q, J = 274.7 Hz, CF3), 124.4 (CH-arom.), 124.7
(CH-arom.), 125.0 (CH-arom.), 127.1 (CH-arom.), 128.9 (CH-
arom.), 129.1 (CH-arom.), 133.5, 133.7, 134.0, 135.5, 136.3, 139.3,
140.0, 145.6 (C-O), 167.9 (COO), 168.3(COO) ppm. 19F NMR
–63.8 ppm. IR (KBr): ν = 3437 (w), 3074 (w), 2957 (w), 2924 (m),
˜
2853 (w), 1765 (s), 1593 (w), 1475 (w), 1439 (w), 1367 (s), 1342 (m),
1258 (s), 1234 (s), 1204 (s), 1169 (s), 1155 (s), 1142 (m), 1121 (s),
1067 (m), 1040 (m), 1030 (m), 1009 (m), 1001 (m), 941 (m), 899
(m), 841 (w), 783 (m), 737 (m), 717 (s), 650 (w) cm–1. HRMS (ESI):
calcd. for C19H11F3NaO2S2 415.0050; found 415.0045.
(282 MHz, CDCl ): δ = –58.3 ppm. IR (KBr): ν = 3431 (w), 3067
˜
3
(w), 2959 (m), 2924 (m), 2853 (m), 1794 (s), 1771 (s), 1584 (m),
1491 (w), 1456 (m), 1445 (m), 1400 (m), 1369 (s), 1340 (m), 1310
(m), 1256 (s), 1234 (m), 1200 (s), 1190 (s), 1167 (s), 1124 (s), 1070
(m), 1043 (m), 1026 (m), 1011 (s), 968 (m), 937 (m), 918 (m), 885
(m), 864 (m), 847 (m), 797 (m), 781 (m), 754 (m), 735 (m), 723 (m),
702 (m), 692 (m), 683 (m) cm–1. HRMS (ESI): calcd. for
C23H15F3NaO4S 467.0541; found 467.0533.
X-ray Crystal Structure Analysis of 6d:[9] C19H11F3O2S2, M =
392.40, yellow crystal, 0.15ϫ0.10ϫ0.05 mm, a = 9.9471(4), b =
17.8738(8), c = 20.7005(10) Å, V = 3310.4(3) Å3, ρcalcd.
=
1.575 g cm–3, µ = 3.325 mm–1, empirical absorption correction
(0.635ՅTՅ0.851), Z = 8, orthorhombic, space group Pbca (No.
61), λ = 1.54178 Å, T = 223(2) K, ω and φ scans, 17012 reflections
collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.60 Å–1, 2920 independent
(Rint = 0.088) and 2129 observed reflections [IՆ2σ(I)], 249 refined
parameters, R = 0.059, wR2 = 0.138, max. (min.) residual electron
density 0.29 (–0.30) eÅ–3, hydrogen atoms calculated and refined
as riding atoms.
X-ray Crystal Structure Analysis of 9:[9] C23H15F3O4S, M = 444.41,
light-yellow crystal, 0.35 ϫ0.30ϫ 0.25 mm, a = 12.0643(2), b =
11.6026(2), c = 15.7715(4) Å, β = 99.678(1)°, V = 2176.23(7) Å3,
ρcalcd. = 1.356 gcm–3, µ = 0.200 mm–1, empirical absorption correc-
tion (0.933ՅTՅ0.952), Z = 4, monoclinic, space group P21/n (No.
14), λ = 0.71073 Å, T = 223(2) K, ω and φ scans, 14148 reflections
collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.66 Å–1, 5144 independent
(Rint = 0.041) and 3367 observed reflections [IՆ2σ(I)], 282 refined
parameters, R = 0.058, wR2 = 0.170, max. (min.) residual electron
density 0.33 (–0.42) eÅ–3, hydrogen atoms calculated and refined
as riding atoms.
2-Acetoxy-1-phenyl-4-(trifluoromethyl)dibenzo[b,d]thiophene (6e):
This compound was obtained from azadienone 5f (0.190 g,
0.47 mmol) according to the general procedure. The subsequent
chromatographic purification (pentane/Et2O, 3:1) gave 0.018 g
(0.05 mmol, 10%) of 6e as a yellow solid; m.p. 177–178 °C. 1H
2-Acetoxy-1-methyl-4-(trifluoromethyl)dibenzo[b,d]furan (11): This
compound was obtained from azadienone 10 (0.130 g, 0.40 mmol)
NMR (400 MHz, CDCl3): δ = 1.95 (s, 3 H, CH3COO), 6.76 (d, J according to the general procedure. The subsequent chromato-
= 8.3 Hz, 1 H, H-arom.), 7.07 (ddd, J = 8.3, 7.2, 1.1 Hz, 1 H, H- graphic purification (pentane/Et2O, 8:1) gave 0.022 g (0.07 mmol,
arom.), 7.33–7.41 (m, 3 H, H-arom.), 7.55–7.57 (m, 4 H, H-arom.),
18 %) of 11 as a colourless solid; m.p. 174–175 °C. 1H NMR
7.84 (d, J = 8.0 Hz, 1 H, H-arom.) ppm. 13C NMR (100 MHz, (400 MHz, CDCl3): δ = 2.41 (s, 3 H, CH3COO), 2.65 (s, 3 H, CH3),
CDCl3): δ = 20.3 (CH3COO), 110.0, 118.9 (q, J = 4.8 Hz, CH- 7.38 (s, 1 H, H-arom.), 7.39–7.43 (m, 1 H, H-arom.), 7.52–7.56 (m,
arom.), 122.4 (CH-arom.), 123.6 (q, J = 274.5 Hz, CF3), 124.3
1 H, H-arom.), 7.67 (d, J = 8.3 Hz, 1 H, H-arom.), 8.05 (d, J =
Eur. J. Org. Chem. 2009, 1228–1240
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1237

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
FULL PAPER
7.4 Hz, 1 H, H-arom.) ppm. 13C NMR (100 MHz, CDCl3): δ =
cedure. The subsequent chromatographic purification (Et2O/pen-
13.5 (CH3), 20.7 (CH3COO), 112.2 (CH-arom.), 118.6 (q, J = tane, 1:5) gave 0.036 g (0.08 mmol, 26%) of 7c as a yellow solid;
1
4.6 Hz, CH-arom.), 122.4 (CH-arom.), 122.8 (q, J = 272.1 Hz,
m.p. 96–97 °C. H NMR (300 MHz, CDCl3): δ = 1.00–1.05 (m, 1
CF3), 123.4 (CH-arom.), 123.6, 125.8, 128.0 (CH-arom.), 129.9, H, CH2), 1.22–1.43 (m, 2 H, CH2), 1.22–1.43 (m, 2 H, CH2), 1.56–
143.6 (CO), 149.5, 156.9, 169.4 (COO) ppm. 19F NMR (282 MHz,
CDCl ): δ = –61.5 ppm. IR (KBr): ν = 3501 (w), 3489 (w), 3445
1.63 (m, 3 H, CH2), 2.21–2.43 (m, 1 H, CH2), 2.29 (s, 3 H,
CH3COO), 3.14–3.27 (m, 3 H, CH2), 4.05 (m, 1 H, CH2), 4.21 (m,
˜
3
(w), 3082 (w), 2961 (w), 2926 (w), 2853 (w), 1794 (w), 1755 (s), 1 H, CH2), 6.38 (s, 1 H, H-olef.), 6.95 (d, J = 5.3 Hz, 1 H, β-H-
1638 (w), 1620 (w), 1587 (w), 1508 (m), 1477 (m), 1452 (m), 1406
thiophene), 7.35 (d, J = 5.3 Hz, 1 H, α-H-thiophene) ppm. 13C
(s), 1375 (s), 1360 (s), 1317 (s), 1281 (s), 1265 (m), 1232 (s), 1190 NMR (100 MHz, CDCl3): δ = 21.2 (CH3CO), 23.0 (CH2), 26.1
(s), 1165 (s), 1155 (s), 1121 (s), 1103 (s), 1051 (s), 1016 (s), 997 (m),
920 (s), 881 (m), 874 (m), 843 (w), 824 (m), 804 (w), 777 (m), 748
(s), 708 (w), 675 (w), 609 (m) cm–1. HRMS (ESI): calcd. for
C16H11F3NaO3 331.0552; found 331.0543.
(CH2), 26.5 (CH2), 50.3 (CH2N), 52.8 (CH2N), 73.5 (q, J =
29.3 Hz, C-quat.), 77.1 (CH2), 110.2 (CH-olef.), 110.9 (CBr), 124.5
(q, J = 288.2 Hz, CF3), 127.0 (α-CH-thiophene), 128.3 (C-ipso),
131.4 (β-CH-thiophene), 142.9 (C=CO), 146.2 (C=N), 166.9
(COO) ppm. 19F NMR (282 MHz, CDCl3): δ = –73.1 ppm. IR
1-Acetoxy-3-(3-bromothiophen-2-yl)-5-(2,2-dimethylhydrazono)-3-
(trifluoromethyl)cyclopent-1-ene (7a): This compound was obtained
from azadienone 5g (0.116 g, 0.31 mmol) according to the general
procedure. The subsequent chromatographic purification (Et2O/
pentane, 1:3) gave 0.047 g (0.11 mmol, 36%) of 7a as an orange oil.
1H NMR (400 MHz, CDCl3): δ = 2.29 (s, 3 H, CH3COO), 2.42 (s,
3 H, CH3N), 2.84 (s, 3 H, CH3N), 3.99 (m, 1 H, CH2), 4.25 (m, 1
H, CH2), 6.34 (br. s, 1 H, H-olef.), 6.96 (d, J = 5.4 Hz, 1 H, β-H-
thiophene), 7.35 (d, J = 5.4 Hz, 1 H, α-H-thiophene) ppm. 13C
(KBr): ν = 3445 (w), 3152 (w), 3121 (w), 3094 (w), 2939 (m), 2922
˜
(m), 2853 (m), 2837 (m), 1782 (s), 1767 (m), 1657 (m), 1620 (s),
1578 (w), 1558 (m), 1501 (w), 1443 (m), 1423 (m), 1406 (w), 1383
(m), 1371 (m), 1350 (w), 1310 (m), 1267 (m), 1252 (s), 1192 (s),
1155 (s), 1136 (s), 1103 (m), 1082 (m), 1055 (m), 1034 (m), 1007
(m), 939 (m), 905 (m), 885 (w), 874 (m), 858 (m), 837 (m), 810 (m),
773 (m), 727 (m), 694 (w), 646 (w), 629 (w), 581 (w) cm–1. HRMS
(ESI): calcd. for C17H18BrF3N2O2SNa 475.0097; found 475.0120.
NMR (100 MHz, CDCl3): δ = 21.2 (CH3CO), 40.8 (CH3N), 43.0 X-ray Crystal Structure Analysis of 7cЈ:[9] C17H18BrF3N2O2S, M =
(CH3N), 73.4 (q, J = 29.4 Hz, C-quat.), 77.0 (CH2), 109.9 (CH- 451.30, yellow crystal, 0.50ϫ0.40ϫ0.35 mm, a = 17.3521(1), b =
olef.), 111.1 (CBr), 124.4 (q, J = 288.3 Hz, CF3), 127.1 (α-CH-
thiophene), 128.0 (C-ipso), 131.4 (β-CH-thiophene), 141.8 (C=CO),
146.2 (C=N), 166.9 (COO) ppm. 19F NMR (282 MHz, CDCl3): δ
12.3995(1), c = 8.7866(1) Å, V = 1890.50(3) Å3, ρcalcd.
=
1.586 g cm–3, µ = 4.392 mm–1, empirical absorption correction
(0.217ՅTՅ0.309), Z = 4, orthorhombic, space group Pca21 (No.
= –72.9 ppm. IR (film): ν = 3136 (w), 3111 (w), 2995 (m), 2953 29), λ = 1.54178 Å, T = 223(2) K, ω and φ scans, 9181 reflections
˜
(m), 2922 (m), 2870 (m), 2793 (w), 1786 (s), 1659 (m), 1624 (s), collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] = 0.60 Å–1, 3040 independent
1501 (m), 1454 (m), 1439 (m), 1423 (m), 1402 (m), 1371 (s), 1350 (Rint = 0.041) and 3033 observed reflections [IՆ2σ(I)], 243 refined
(m), 1252 (s), 1192 (s), 1161 (s), 1134 (s), 1078 (m), 1045 (m), 1011 parameters, R = 0.037, wR2 = 0.100, max. (min.) residual electron
(m), 941 (m), 908 (m), 889 (m), 876 (m), 862 (m), 841 (m), 808 (m), density 0.44 (–0.38) eÅ–3, hydrogen atoms calculated and refined
789 (m), 729 (m), 665 (w), 646 (w), 600 (w), 584 (w) cm–1. HRMS as riding atoms, refined as racemic twin [Flack parameter: 0.34(2)].
(ESI): calcd. for C14H14BrF3N2NaO2S 432.9809; found 432.9788.
1-Acetoxy-5-(azepan-1-ylimino)-3-(3-bromothiophen-2-yl)-3-(trifluo-
1-Acetoxy-3-(3-bromothiophen-2-yl)-5-(morpholinoimino)-3-(trifluo-
romethyl)cyclopent-1-ene (7b): This compound was obtained from
azadienone 5h (0.090 g, 0.22 mmol) according to the general pro-
cedure. The subsequent chromatographic purification (Et2O/pen-
romethyl)cyclopent-1-ene (7d): This compound was obtained from
azadienone 5j (0.204 g, 0.48 mmol) according to the general pro-
cedure. The subsequent chromatographic purification (Et2O) gave
0.050 g (0.11 mmol, 22 %) of 7d as a yellow oil. 1H NMR
(400 MHz, CDCl3): δ = 0.69–0.73 (m, 1 H, CH2), 1.20–1.78 (m, 7
1
tane, 1:3) gave 0.060 g (0.13 mmol, 61%) of 7b as a yellow oil. H
NMR (400 MHz, CDCl3): δ = 2.05 (m, 1 H, CH2N), 2.30 (s, 3 H, H, CH2), 2.28 (s, 3 H, CH3COO), 2.64–2.71 (m, 1 H, CH2), 2.64–
CH3COO), 3.00 (m, 1 H, CH2N), 3.28 (dt, J = 10.7, 2.4 Hz, 1 H, 2.71 (m, 1 H, CH2), 3.11–3.24 (m, 2 H, CH2), 3.37–3.43 (m, 1 H,
CH2O), 3.49–3.64 (m, 1 H, CH2N, CH2O), 3.81 (m, 1 H, CH2O), CH2), 3.90 (dd, J = 1.6, 1.4 Hz, CH2), 4.18 (dd, J = 1.4, 0.5 Hz,
4.12 (br. s, 1 H, CH2), 4.29 (br. s, 1 H, CH2), 6.32 (s, 1 H, H-olef.),
6.96 (d, J = 5.4 Hz, 1 H, β-H-thiophene), 7.35 (d, J = 5.4 Hz, 1
H, α-H-thiophene) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.2
(CH3CO), 49.1 (CH2N), 51.8 (CH2N), 67.0 (CH2O), 67.5 (CH2O),
73.6 (q, J = 29.5 Hz, C-quat.), 78.0 (CH2), 110.0 (CH-olef.), 111.2
(CBr), 124.4 (q, J = 287.7 Hz, CF3), 127.0 (α-CH-thiophene), 128.0
CH2), 6.15 (d, J = 0.8 Hz, 1 H, H-olef.), 6.97 (d, J = 5.3 Hz, 1 H,
β-H-thiophene), 7.34 (d, J = 5.3 Hz, 1 H, α-H-thiophene) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 21.2 (CH3CO), 26.4 (CH2), 27.5
(CH2), 28.1 (CH2), 28.8 (CH2), 53.4 (CH2N), 55.7 (CH2N), 73.6
(q, J = 29.3 Hz, C-quat.), 75.7 (CH2), 109.8 (CH-olef.), 111.4
(CBr), 124.5 (q, J = 288.2 Hz, CF3), 126.5.0 (α-CH-thiophene),
(C-ipso), 131.6 (β-CH-thiophene), 142.4 (C=CO), 146.3 (C=N), 128.9 (C-ipso), 131.6 (β-CH-thiophene), 143.2 (C=CO), 146.8
166.8 (COO). 19F NMR (282 MHz, CDCl3): δ = –72.9 ppm. IR (C=N), 166.9 (COO) ppm. 19F NMR (282 MHz, CDCl3): δ =
(film): ν = 3134 (w), 3117 (w), 2963 (m), 2922 (m), 2899 (m), 2858 –72.6 ppm. IR (film): ν = 3142 (w), 3113 (w), 3092 (w), 2930 (m),
˜
˜
(m), 2754 (w), 2727 (w), 2681 (w), 1784 (m), 1657 (m), 1624 (m), 2853 (m), 1788 (m), 1659 (m), 1622 (m), 1578 (w), 1560 (w), 1501
1501 (m), 1456 (m), 1421 (m), 1371 (m), 1350 (m), 1304 (m), 1269 (w), 1448 (m), 1423 (w), 1369 (m), 1350 (w), 1308 (w), 1256 (m),
(m), 1254 (m), 1111 (m), 1088 (m), 1070 (m), 1036 (m), 1013 (m), 1194 (s), 1161 (s), 1136 (m), 1090 (m), 1047 (w), 1011 (m), 964 (w),
941 (m), 918 (w), 907 (m), 887 (m), 872 (m), 862 (m), 841 (m), 806 939 (m), 895 (w), 885 (w), 868 (w), 839 (m), 808 (w), 783 (m), 725
(m), 789 (m), 729 (m), 710 (w), 665 (w), 648 (w), 594 (w) cm–1. ( m ) , 6 6 5 ( w ) , 6 4 8 ( w ) c m – 1 . H R M S ( E S I ) : c a l c d . fo r
HRMS (ESI): calcd. for C16H16BrF3N2NaO3S 474.9909; found
474.9868. C16H16BrF3N2O3S (453.27): calcd. C 42.40, H 3.56, N
6.18; found C 42.81, H 3.60, N 5.95.
C 1 8 H 2 0 B r F 3 N 2 N a O 2 S 4 8 9 . 0 2 5 4 ; f o u n d 4 8 9 . 0 2 5 9 .
C18H20BrF3N2O2S (465.33): calcd. C 46.46, H 4.33, N 6.02; found
C 46.49, H 4.19, N 5.43.
1-Acetoxy-3-(3-bromothiophen-2-yl)-5-(piperidin-1-ylimino)-3-(trifluo- 4-Acetoxy-6-(3-bromothiophen-2-yl)-1-methyl-3-(thiophen-2-yl)-6-
romethyl)cyclopent-1-ene (7c): This compound was obtained from
azadienone 5i (0.128 g, 0.31 mmol) according to the general pro-
(trifluoromethyl)-6,7-dihydro-1H-1,2-diazepine (8a): This com-
pound was obtained from azadienone 5k (0.065 g, 0.15 mmol) ac-
1238
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© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 1228–1240

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Data sets were collected with Nonius-KappaCCD diffractome-
ters, in the case of Mo radiation, equipped with a rotating an-
ode generator. Programs used: data collection: COLLECT
(Nonius B. V., 1998); data reduction: Denzo-SMN (Z. Ot-
winowski, W. Minor, Methods Enzymol. 1997, 276, 307–326);
absorption correction: SORTAV (R. H. Blessing, Acta Crys-
tallogr., Sect. A 1995, 51, 33–37; R. H. Blessing, J. Appl. Crys-
tallogr. 1997, 30, 421–426) and Denzo (Z. Otwinowski, D.
Borek, W. Majewski, W. Minor, Acta Crystallogr., Sect. A 2003,
59, 228–234); structure solution: SHELXS-97 (G. M. Sheld-
rick, Acta Crystallogr., Sect. A 1990, 46, 467–473); structure
refinement: SHELXL-97 (G. M. Sheldrick, Acta Crystallogr.,
Sect. A 2008, 64, 112–122); graphics: SCHAKAL (E. Keller,
1997). CCDC-702967 (for 6a), -702968 (for 6b), -702969 (for
6e), -702970 (for 9), -702971 (for 6d) and -702972 (for 7cЈ) con-
tain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_r-
equest/cif.
a) A. L. Lira, M. Zolotukhin, L. Fomina, S. Fomine, J. Phys.
Chem. A 2007, 111, 13606–13610; b) M. Zolotukhin, S. Fom-
ine, R. Salcedo, L. Khalilov, Chem. Commun. 2004, 1030–1031.
M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr., T.
Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N.
Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K.
Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y.
Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P.
Hratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts,
R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pom-
elli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P.
Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich,
A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D.
Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui,
A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu,
A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J.
Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W.
Wong, C. Gonzalez, J. A. Pople, Gaussian 03, Revision C.01,
cording to the general procedure. The subsequent chromatographic
purification (Et2O) gave 0.011 g (0.02 mmol, 15%) of 8a as a yellow
oil. 1H NMR (400 MHz, CDCl3): δ = 2.02 (s, 3 H, CH3COO), 3.29
(s, 3 H, CH3N), 3.74 (d, J = 13.6 Hz, CH2), 4.44 (dd, J = 13.6,
1.8 Hz, CH2), 6.36 (d, J = 1.8 Hz, CH), 6.93 (dd, J = 5.1, 3.7 Hz,
CH-thiophene), 7.01 (d, J = 5.4 Hz, β-H-Br-thiophene), 7.15 (dd,
J = 3.7, 1.1 Hz, CH-thiophene), 7.19 (dd, J = 5.1, 1.1 Hz, CH-
thiophene), 7.32 (d, J = 5.4 Hz, α-H-Br-thiophene) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.8 (CH3CO), 49.4 (CH3N), 53.8 (q, J =
27.5 Hz, C-quat.), 59.1 (CH2), 120.9 (CBr), 122.2 (CH), 124.9 (q,
J = 284.8 Hz, CF3), 125.6 (CH-thiophene), 126.1 (CH-thiophene),
126.5 (CH-thiophene), 127.1 (CH-thiophene), 131.7, 133.1 (CH-
thiophene), 134.5, 141.0 (C=N), 143.4 (C-O), 168.8 (CO) ppm. 19F
[3]
[4]
[5]
NMR (282 MHz, CDCl ): δ = –72.6 ppm. IR (film): ν = 3381 (w),
˜
3
3107 (w), 3092 (w), 2963 (w), 2920 (m), 2851 (w), 1765 (s), 1736
(w), 1720 (w), 1655 (w), 1647 (w), 1639 (w), 1630 (w), 1508 (w),
1501 (w), 1460 (w), 1439 (w), 1412 (w), 1367 (w), 1350 (w), 1319
(w), 1259 (s), 1250 (s), 1190 (s), 1175 (s), 1153 (s), 1126 (s), 1105
(m), 1078 (m), 1061 (m), 1045 (m), 1015 (m), 961 (w), 926 (w), 899
(w), 866 (w), 851 (w), 800 (w), 704 (w), 665 (w), 644 (w) cm–1.
HRMS (ESI): calcd. for C17H14BrF3N2O2S2Na 502.9504; found
502.9503.
[6]
[7]
4-Acetoxy-6-(3-chlorothiophen-2-yl)-1-methyl-3-(thiophen-2-yl)-6-
(trifluoromethyl)-6,7-dihydro-1H-1,2-diazepine (8b): This com-
pound was obtained from azadienone 5l (0.097 g, 0.25 mmol) ac-
cording to the general procedure. The subsequent chromatographic
purification (Et2O) gave 0.028 g (0.06 mmol, 26%) of 8b as a yellow
[8]
oil. 1H NMR (400 MHz, CDCl3): δ = 2.02 (s, 3 H, CH3COO), 3.27 [9]
(s, 3 H, CH3N), 3.73 (d, J = 13.6 Hz, CH2), 4.42 (dd, J = 13.6,
1.8 Hz, CH2), 6.32 (d, J = 1.8 Hz, CH), 6.93 (dd, J = 5.1, 3.7 Hz,
CH-thiophene), 6.95 (d, J = 5.4 Hz, β-H-Cl-thiophene), 7.15 (dd,
J = 3.7, 1.1 Hz, CH-thiophene), 7.19 (dd, J = 5.1, 1.1 Hz, CH-
thiophene), 7.34 (d, J = 5.4 Hz, α-H-Cl-thiophene) ppm. 13C NMR
(100 MHz, CDCl3): δ = 20.8 (CH3CO), 49.4 (CH3N), 53.3 (q, J =
26.1 Hz, C-quat.), 58.8 (CH2), 122.1 (q, J = 2 Hz, CH), 122.9, 124.9
(q, J = 287.0 Hz, CF3), 125.6 (CH-thiophene), 126.1 (CH-thio-
phene), 126.4 (α-CH-thiophene), 126.5 (CH-thiophene), 130.2 (β-
CH-thiophene), 132.3, 133.5, 141.0 (C=N), 143.5 (C-O), 168.8
(CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –71.8 ppm. IR (film):
ν = 3379 (w), 3109 (w), 2961 (w), 2920 (m), 2872 (w), 2854 (w),
˜
2812 (w), 1766 (s), 1736 (w), 1655 (w), 1647 (w), 1639 (w), 1512
(w), 1460 (w), 1436 (w), 1414 (w), 1369 (m), 1354 (m), 1319 (w),
1250 (s), 1193 (s), 1176 (s), 1150 (s), 1132 (s), 1110 (s), 1080 (m),
1063 (m), 1045 (m), 1015 (m), 926 (w), 885 (m), 851 (w), 734 (m),
704
(w),
665
(w) cm–1.
HRMS
(ESI):
calcd.
for
[10]
[11]
C17H14ClF3N2NaO2S2 457.0030; found 457.003.
Acknowledgments
This work was supported by the NRW Graduate School of Chemis-
try Münster, the Deutsche Forschungsgemeinschaft (DFG) and the
Fonds der Chemischen Industrie.
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www.eurjoc.org
1239

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
FULL PAPER
Gaussian, Inc., Wallingford, CT, 2004. Details of the quantum
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[17]
Prepared in analogy to F. A. J. Kerdesky, A. Basha, Tetrahe-
dron Lett. 1991, 32, 2003–2004. In this publication a tempera-
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bromothiophene and for the transmetallation step and –15 °C
for the addition of the electrophile to give the 3-(trifluoroace-
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bromo-2-(trifluoroacetyl)thiophene (4a) by following this pro-
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experiments than indicated.
Received: December 1, 2008
Published Online: January 22, 2009
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1240
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Eur. J. Org. Chem. 2009, 1228–1240