2H-pyrrole derivatives from an aza-nazarov reaction cascade involving indole as the neutral leaving group

Article abstract of DOI:10.1002/ejoc.200800384

Trifluoromethyl-substituted N-indolinyl-1-aza-1,4-dien-3-ones 4, which are accessible in good yields from indolinylimino esters 6 in a two-step procedure, undergo a novel type of aza-Nazarov cyclization if treated with strong acids to give the hitherto unknown 3-hydroxy-5H-pyrrole derivatives 8a-p. The solvent-free polyphosphoric acid/acyl anhydride system as the acidic reaction medium is especially efficient and requires only short reaction times. According to quantum chemical calculations the key step in the reaction cascade is the cleavage of the N-N bond of the hydrazone fragment of a protonated N-(indolin-1-yl)-1-aza-1,4-dien-3-one intermediate such as 10. This intermediate releases 3H-indole as an unusual, but very efficient neutral leaving group. Several 1-aza-1,4-dien-3-ones 4 and some 3-hydroxy-5H-pyrrole derivatives 8 were characterized by X-ray diffraction. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800384

FULL PAPER
DOI: 10.1002/ejoc.200800384
2H-Pyrrole Derivatives from an Aza-Nazarov Reaction Cascade Involving
Indole as the Neutral Leaving Group
Nugzar Ghavtadze,[a] Roland Fröhlich,[a] and Ernst-Ulrich Würthwein*[a]
Keywords: Aza compounds / Cyclization / Pyrroles / Quantum chemical calculations / Cations / Nazarov reactions
Trifluoromethyl-substituted
N-indolinyl-1-aza-1,4-dien-3-
the cleavage of the N–N bond of the hydrazone fragment of
a protonated N-(indolin-1-yl)-1-aza-1,4-dien-3-one interme-
diate such as 10. This intermediate releases 3H-indole as an
unusual, but very efficient neutral leaving group. Several 1-
aza-1,4-dien-3-ones 4 and some 3-hydroxy-5H-pyrrole deriv-
atives 8 were characterized by X-ray diffraction.
ones 4, which are accessible in good yields from indolinyl-
imino esters 6 in a two-step procedure, undergo a novel type
of aza-Nazarov cyclization if treated with strong acids to give
the hitherto unknown 3-hydroxy-5H-pyrrole derivatives 8a–
p. The solvent-free polyphosphoric acid/acyl anhydride sys-
tem as the acidic reaction medium is especially efficient and
requires only short reaction times. According to quantum
chemical calculations the key step in the reaction cascade is
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
Introduction
Aza variants of the well-known and -established Nazarov
cyclization reaction for the synthesis of five-membered car-
bocycles[1] may be expected to be general and efficient
methods for the synthesis of five-membered nitrogen-con-
taining heterocycles. However, until now aza-Nazarov
routes[2,3] have been employed only very rarely in compari-
son with the Nazarov cyclization reaction. Recently, we
were able to identify the electronic and topological precon-
ditions for a successful application of the aza-Nazarov reac-
tion in heterocyclic synthesis involving a conrotatory 4π
electrocyclization reaction.[3]
Scheme 1.
Thus, by investigating the effect of a heteroatom on the
reactivity of charged polyenyl compounds we found, on the matic 3-hydroxypyrroles were observed, which were isolated
basis of ab initio and DFT quantum chemical calculations, as the corresponding stable esters after trapping with acidic
that only the cyclization of 3-hydroxy-1-azapentadienylium anhydrides. The necessary starting 1-amino- or 1-alkoxy-
ions 2 is a favourable exothermic process, which leads to 3- substituted 1-aza-1,4-dien-3-ones 1 were easily accessible by
hydroxypyrrole derivatives 3 (Scheme 1). This reaction is in aldol condensation of the corresponding diacetyl mono-
clear contrast to those of the corresponding 3-hydroxy-2- hydrazones with various aldehydes.
azapentadienylium ions, which are predicted not to be able
to undergo cyclization for thermodynamic reasons.[3]
We have checked the results of our theoretical calcula-
tions experimentally. The cations 2 should be accessible by
Results and Discussion
In order to extend the scope of this reaction to the syn-
protonation of the 1-azapenta-1,4-dien-3-ones 1. Indeed, al-
thesis of important non-aromatic compounds like 2H-pyr-
dehyde-derived 1-amino-1-aza-1,4-dien-3-ones 1 with only
roles, we became interested in 5,5-disubstituted 1-azapenta-
one substituent at the 5-position readily undergo aza-Naza-
1,4-dien-3-ones, which bear, as an additional very strong
rov cyclizations upon protonation with strong Brønsted ac-
ids.[3] After fast elimination of a proton, very sensitive aro-
electron-withdrawing substituent, a CF3 group at the 5-po-
sition of the 1-aza-1,4-dien-3-one. In this communication
we report on the special hydrazones 1-indenyl-1-aza-1,4-
dien-3-ones 4. They are accessible from the condensation
of ethyl pyruvates 5 and 1-aminoindoline, which gives the
corresponding hydrazones 6. Their conversion into the
[a] Westfälische Wilhelms-Universität Münster, Organisch-Che-
misches Institut,
Corrensstraße 40, 48149 Münster, Germany
Fax: +49-251-83-39772
E-mail: wurthwe@uni-muenster.de
3656
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3656–3667

2H-Pyrrole Derivatives from an Aza-Nazarov Reaction Cascade
corresponding phosphonates 7 and subsequent Horner– Table 1. Acid-induced formation of 2H-pyrroles 8a–p from 1-ind-
enyl-1-aza-1,4-dien-3-ones 4a–p (in PPA/acyl anhydride).
Wadsworth–Emmons reaction using various trifluorometh-
yl ketones gives the 1-aza-1,4-dien-3-ones 4 (Scheme 2).[4]
R1
R2
R3
Yield [%]
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
methyl
methyl
methyl
methyl
methyl
methyl
methyl
methyl
methyl
methyl
phenyl
thien-2-yl
thien-2-yl
thien-2-yl
methyl
methyl
phenyl
4-F-phenyl
acetyl
acetyl
acetyl
acetyl
acetyl
acetyl
acetyl
acetyl
acetyl
52[a]
46
63
36
55
53
56
42
49
37
79
17
53
61
53
30
4-Cl-phenyl
4-Br-phenyl
4-(Me2N)-phenyl
3-F-phenyl
3-CF3-phenyl
2-thienyl
benzo[b]furan-2-yl
benzo[b]thiophen-2-yl acetyl
phenyl
phenyl
acetyl
acetyl
acetyl
benzo[b]furan-2-yl
benzo[b]thiophen-2-yl acetyl
phenyl
2,4-dimethylphenyl
benzoyl
acetyl
[a] 55% when CF3SO3H/Ac2O in CH2Cl2 was used.
Scheme 2.
If these N-indolinyl-5-trifluoromethyl-1-aza-1,4-dien-3-
ones 4 are treated with strong acids they undergo a novel
and unusual type of aza-Nazarov reaction, offering a new
and very efficient pathway for the synthesis of non-aromatic
2H-pyrrole derivatives 8 (5-trifluoromethyl-3-hydroxy-5H-
pyrroles; Scheme 3) together with the corresponding 3-acyl-
indoles 9.[5]
Figure 1. Molecular structures of 8h and 8o in the solid state (X-
ray crystal structures).
Scheme 3.
Optimized conditions for the reaction were found to be
stirring of 4 for 15 min at 80–90 °C in an excess of a PPA/
acetic anhydride mixture. The reaction is tolerant to a wide
variety of substituents. The pyrrole moiety can be function-
alized with alkyl, aryl or heteroaromatic groups at the 2-
position (R1 = Me, Ph, 2-thienyl) and with different donor-
or acceptor-substituted aryl groups or oxygen- or sulfur-
containing heterocycles at the 5-position (substituent R2)
(Table 1). Acetic anhydride can be replaced by benzoic an-
hydride (8o), trifluoroacetic anhydride (TFAA) or pivaloyl
chloride (see below). Moderate-to-good yields were ob-
tained for the preparation of 18 functionalized 2H-pyrroles
4.
All the products 8 were fully characterized by spectro-
scopic methods. In several cases the structures in the solid
state were confirmed by X-ray diffraction (Figure 1).[6]
Based on quantum chemical calculations[7] [SCS-MP2/6-
311G(d,p)//B3LYP/6-311G(d,p), including zero-point cor-
rection (ZPE)[8]], we suggest the cascade mechanism shown
in Scheme 4 for this novel transformation. Protonation of
4, at least in equilibrium, of the carbonyl oxygen leads to
the 1-azapentadienylium ion 10. This protonation site is
also suggested by the calculations, which indicated a 3–
Scheme 4. Calculated pathway for the reaction cascade [SCS-MP2/
4 kcalmol–1 preference for O-protonation over the proton- 6-311G(d,p)//B3LYP/6-311G(d,p)] [kcalmol–1].
Eur. J. Org. Chem. 2008, 3656–3667
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3657

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
FULL PAPER
ation of the two hydrazone nitrogen atoms (Figure 2). Cat-
The new compounds are enol esters. Attempts to isolate
ion 10 may directly undergo a pericyclic 4π-electron aza- the free enols/ketones from the reaction mixture by proton-
Nazarov cyclization to form intermediate 11. The calculated ation were unsuccessful because only mixtures of several
barrier for this exothermic cyclization (ca. –7 kcalmol–1), unidentified decomposition and side-reaction products were
starting from the U-shaped 1-azapentadienylium ion, is obtained when the reaction was carried out without the an-
very low (only ca. 3 kcalmol–1). Cleavage of the N–N bond hydride component. This indicates the important role of the
and a proton shift generates cation 12 and 3H-indole, which anhydride in trapping the sensitive intermediates. However,
is quickly transformed into the more stable aromatic 1H- reactions of 4a using the PPA/TFAA system gave trifluo-
indole and trapped by the acylating agent to form the corre- roacetylated 2H-pyrrol-4-ol 15 and 2H-pyrrolone 16 as par-
sponding 3-acylindole. A second, although less likely pos- tial hydrolysis product of the ester. In order to complete
sibility, is that the 1-azapentadienylium ion 10 may first un- the hydrolysis process the reaction mixture was treated with
dergo a 1,3-hydrogen migration to give hydrazonium ion KOH and the corresponding keto form, 5-trifluoromethyl-
13. This will most probably be an intermolecular process 4,5-dihydropyrrol-3-one 16, was obtained in 30% overall
assisted by the chemical environment. Cation 13 may in yield (Scheme 5).
turn undergo elimination of the 3H-indole subunit to form
the 1H-1-azapentadienylium ion 14 in an endothermic pro-
cess with a barrier of around 17 kcalmol–1. Then the cycli-
zation step again proceeds through a very small barrier
to give the final cation 12 very exothermically (ca.
–38 kcalmol–1). Loss of a proton gives the observed 3-hy-
droxy-5H-pyrroles.
Scheme 5.
The same product 16 was obtained in 25% yield if
pivaloyl chloride instead of acetic anhydride was used to
trap the hydroxy intermediate after subsequent hydrolysis.
We also investigated the acid-induced cyclization of a vi-
Figure 2. DFT-optimized structures for the three isomers of pro-
nylogous compound 4q, which in principle has the potential
tonated 4a. Upper left: O-protonated (0.0 kcalmol–1); upper right:
to form either five- or seven-membered ring heterocycles.
indoline-protonated (3.4 kcalmol–1); bottom: N1-protonated
(3.9 kcalmol–1).
Experimentally, exclusive formation of the five-membered
ring 8q was observed (19% yield) (Scheme 6).
Experimentally, after addition of the acylating agent, the
final products are 3-acyloxy-5-trifluoromethyl-5H-pyrroles
8 and the corresponding 3-acylindoles 9,[9] as confirmed
both by mass spectrometry and NMR techniques.
On the basis of the theoretical and experimental results
we assume that the driving force of this unusual transfor-
mation is on the one hand the exothermic electrocyclization
of the azapentadienyl cation and on the other hand the for-
mation of the stable aromatic 1H-indole from the corre-
sponding less stable 3H isomer by tautomerization, which
shifts the equilibrium to the side of the products. Note that
the hydrazones of 1-aminoindoline behave uniquely in these
reactions as they are the only examples to show this N–N
fission reaction. All other hydrazones derived from acyclic
and cyclic hydrazines undergo classical Nazarov-type reac-
tions involving aryl substituents at the 5-position, which
lead to bicyclic and spiro compounds.[4]
Scheme 6.
3658
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Eur. J. Org. Chem. 2008, 3656–3667

2H-Pyrrole Derivatives from an Aza-Nazarov Reaction Cascade
CDCl3): δ = 2.25 (s, 3 H, CH3), 3.27 (t, J = 8.2 Hz, 2 H, CH2),
3.74 (d, J = 22.2 Hz, 2 H, CH2-P), 3.76 (d, J = 11.1 Hz, 6 H,
Conclusions
In summary, we have discovered that trifluoromethyl- CH3O), 4.23 (t, J = 8.2 Hz, 2 H, CH2N), 6.97–7.01 (m, 1 H,
Harom.), 7.17–7.27 (m, 3 H, Harom.) ppm. 13C NMR (100 MHz,
CDCl3): δ = 12.5 (CH3), 28.1 (CH2), 34.6 (d, J = 132.3 Hz, CH2-P),
52.8 (d, J = 6.3 Hz, CH3O), 52.9 (CH2N), 111.7 (CHarom.), 123.1
(CHarom.), 124.9 (CHarom.), 127.5, 128.1 (CHarom.), 140.1 (d, J =
1.9 Hz, C=N), 148.4 (CN), 191.2 (d, J = 6.5 Hz, CO) ppm. 31P
substituted N-(indolin-1-yl)-1-aza-1,4-dien-3-ones 4 un-
dergo aza-Nazarov cyclization reactions if treated with
strong acids to give novel 3-hydroxy-5H-pyrrole derivatives.
The solvent-free variant of the procedure, in which the PPA/
acyl anhydride system plays the role of the reaction me-
NMR (121.5 MHz, CDCl ): δ = 23.4 ppm. IR (KBr): ν = 3429 (w),
˜
3
dium, is especially efficient and requires only 15 min. The
key step is the cleavage of the N–N bond of the hydrazone
fragment of a protonated intermediate like 10, which re-
leases 3H-indole as an unusual but very efficient neutral
3308 (w), 3065 (w), 3047 (w), 2997 (w), 2949 (m), 2851 (m), 1813
(w), 1663 (s), 1609 (m), 1555 (s), 1481 (s), 1468 (s), 1435 (m), 1391
(s), 1367 (m), 1331 (m), 1294 (m), 1252 (s), 1202 (s), 1178 (m), 1140
(w), 1067 (m), 1045 (m), 1022 (s), 943 (m), 881 (m), 816 (m), 800
leaving group. Important reactive species and transition (m), 766 (m), 743 (m), 692 (w), 667 (w), 615 (w), 598 (w), 540
(w) cm–1. HRMS (ESI): calcd. for C14H19N2O4PNa 333.0975;
found 333.0973. C14H19N2O4P (310.29): calcd. C 54.19, H 6.17, N
order to elucidate the proposed mechanism of the multistep
9.03; found C 54.62, H 6.06, N 8.70.
cascade transformation.
states were modelled by quantum chemical calculations in
X-Ray Crystal Structure Analysis of 6a: Formula C14H19N2O4P, M
= 310.28, light-yellow crystal 0.36ϫ0.30ϫ0.20 mm, a = 8.311(1),
b = 8.718(1), c = 11.478(1) Å, α = 86.60(1), β = 69.35(1), γ =
Experimental Section
74.01(1)°,
V
=
747.44(14) Å3, ρcalcd.
=
1.379 gcm–3
, µ =
0.201 mm–1, empirical absorption correction (0.931 Յ T Յ 0.961),
General: Melting points: Büchi melting point apparatus, model B-
540; melting points are uncorrected. 1H, 13C, 19F, 31P, GCOSY,
GHSQC, GHMBC and 1D NOE NMR spectroscopy: Bruker
Unity plus 600, Varian INOVA 500, AMX 400, Bruker WM 300
¯
Z = 2, triclinic, space group P1 (No. 2), λ = 0.71073 Å, T = 223 K,
ω and φ scans, 8833 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ]
= 0.67 Å–1, 3598 independent (Rint = 0.053) and 2751 observed
spectrometers. TMS (1H) (δ
=
0.00 ppm), CDCl3 (13C) (δ
reflections [I Ն 2σ(I)], 193 refined parameters, R = 0.067, wR2
=
=77.0 ppm), and CFCl3 (19F) (δ = 0.0 ppm) were used as internal
references; 85% H3PO4 (31P) was used as an external reference.
IR: Nicolet FT-IR 5DXC spectrometer. Electron ionization mass
spectra (EI-MS): Finnigan MAT C 312 spectrometer (70 eV). MS:
Finnigan MAT 4200S, Bruker Daltonics micrOTOF and Waters-
Micromass Quatro LCZ (ESI) spectrometers. Elemental analysis:
Vario EL III automatic analyser. All solvents and reagents were
rigorously 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: Silica gel Merck 60 (0.040–0.063 mm). TLC:
Merck silica gel plates (silica gel 60 F254); detection with UV light.
0.210, max. (min.) residual electron density: 0.81 (–0.56) eÅ–3, hy-
drogen atoms calculated and refined as riding atoms.
Dimethyl [3-(Indolin-1-ylimino)-2-oxo-3-phenylpropyl]phosphonate
(7b): Obtained from imino ester 6b according to the general pro-
cedure. Chromatographic purification (Et2O/acetone, 2:1) gave
0.232 g (0.73 mmol, 21%) of 7b as yellow solid, m.p. 105–106 °C.1H
NMR (300 MHz, CDCl3): δ = 3.01 (t, J = 8.1 Hz, 2 H, CH2), 3.30
(t, J = 8.1 Hz, 2 H, CH2N), 3.79 (d, J = 11.1 Hz, 6 H, CH3O), 3.87
(d, J = 22.1 Hz, 2 H, CH2-P), 7.01 (td, J = 7.4, 0.8 Hz, 1 H, Harom.),
7.14 (d, J = 7.4 Hz, 1 H, Harom.), 7.24–7.42 (m, 7 H, Harom.) ppm.
13C N M R (100 M H z, CD Cl3): δ = 27.9 (CH 2), 35.2 (d, J =
131.8 Hz, CH2-P), 52.9 (d, J = 6.3 Hz, CH3O), 53.2 (CH2N), 111.5
(CHarom.), 123.6 (CHarom.), 125.1 (CHarom.), 128.1 (CHarom.), 128.6
(CHarom.), 130.5 (CHarom.), 133.6, 139.8 (d, J = 2.6 Hz, C=N),
147.4 (CN), 190.5 (d, J = 6.5 Hz, CO) ppm. 31P NMR (121.5 MHz,
Preparation of Indolinylimino Esters 6: Indolinylimino esters 6a–c
(6a: R1 = Me; 6b: R1 = Ph; 6c: R1 = 2-thienyl) were prepared from
the corresponding keto esters 5a–c. The keto ester 5 (10 mmol) was
dissolved in abs. ethanol (20 mL) and N-aminoindoline (11 mmol)
in abs. ethanol (5 mL) was added slowly at 0 °C. The reaction mix-
ture was stirred at room temp. for 4 h and then the solvent was
evaporated. The imino esters 6a–c were used in the next step of
synthesis without further purification.
CDCl ): δ = 22.8 ppm. IR (KBr): ν = 3431 (w), 3287 (w), 3065 (w),
˜
3
3020 (w), 2990 (m), 2955 (m), 2924 (m), 2903 (w), 2853 (m), 1655
(s), 1611 (m), 1597 (m), 1553 (s), 1535 (s), 1481 (s), 1468 (s), 1396
(m), 1381 (m), 1331 (m), 1306 (s), 1292 (s), 1275 (s), 1259 (s), 1246
(s), 1205 (s), 1177 (s), 1157 (s), 1096 (s), 1088 (s), 1057 (s), 1045 (s),
1018 (s), 945 (s), 910 (m), 874 (m), 806 (s), 785 (m), 764 (s), 754
(s), 733 (m), 706 (s), 663 (m), 644 (m), 596 (w), 582 (w), 548
(w) cm–1. HRMS (ESI): calcd. for C19H 21N2O4PN a 395.1131;
found 395.1140. C19H21N2O4P (372.35): calcd. C 61.29, H 5.68, N
7.52; found C 60.95, H 5.58, N 6.98.
General Procedure for the Preparation of Keto Phosphonates 7:[10]
Dimethyl methylphosphonate (d = 1.16, 110 mmol)) was dissolved
in abs. THF (15 mL), the mixture cooled to –78 °C and n-BuLi
(1.6  in hexanes, 10 mmol, 6.25 mL) was added slowly. The reac-
tion mixture was stirred for 1 h at –78 °C. Then, indolinylimino
ester 6 (10 mmol) in THF (5 mL) was added. The reaction mixture
was stirred for 4 h at –78 °C and then quenched with AcOH
(0.6 mL) and water (5 mL). After evaporation of the solvent the
residue was dissolved in dichloromethane, washed first with water,
then with a sat. aqueous NaHCO3 solution and again with water.
The residue was dried with MgSO4 and purified by column
chromatography.
Dimethyl [3-(Indolin-1-ylimino)-2-oxo-3-(thien-2-yl)propyl]phos-
phonate (7c): Obtained from imino ester 6c according to the general
procedure. Chromatographic purification (Et2O/acetone, 2:1) gave
0.319 g (0.84 mmol, 25%) of 7c as a yellow solid, 112–113 °C. 1H
NMR (300 MHz, CDCl3): δ = 3.10 (t, J = 8.1 Hz, 2 H, CH2), 3.57
(t, J = 8.1 Hz, 2 H, CH2N), 3.79 (d, J = 11.1 Hz, 6 H, CH3O), 3.85
(d, J = 22.1 Hz, 2 H, CH2-P), 7.00–7.09 (m, 3 H, Harom.), 7.17 (d,
J = 7.3 Hz, 1 H, Harom.), 7.28 (t, J = 7.6 Hz, 1 H, Harom.), 7.41 (d,
J = 7.9 Hz, 1 H, Harom.), 7.48 (d, J = 5.1 Hz, 1 H, Harom.) ppm.
13C N M R (100 M H z, CD Cl3): δ = 27.9 (CH 2), 35.3 (d, J =
132.3 Hz, CH2-P), 52.2 (CH2N), 53.0 (d, J = 6.3 Hz, CH3O), 111.8
Dimethyl [3-(Indolin-1-ylimino)-2-oxobutyl]phosphonate (7a): Ob-
tained from 6a according to the general procedure. Chromato-
graphic purification (Et2O/acetone, 2:1) gave 1.46 g (4.71 mmol,
1
55%) of 7a as yellow solid, m.p. 122–123 °C. H NMR (400 MHz,
Eur. J. Org. Chem. 2008, 3656–3667
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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3659

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
(CHarom.), 124.1 (CHarom.), 125.2 (CHarom.), 125.9 (CHarom.), 128.1 = 0.66 Å–1, 4058 independent (Rint = 0.062) and 2114 observed
FULL PAPER
(CHarom.), 128.2 (CHarom.), 128.5, 130.8 (CHarom.), 132.2, 132.3 (d,
J = 2.8 Hz, C=N), 147.1 (CN), 190.1 (d, J = 6.5 Hz, CO) ppm. 31P
reflections [I Ն 2σ(I)], 236 refined parameters, R = 0.057, wR2
=
0.175, max. (min.) residual electron density = 0.31 (–0.37) eÅ–3
,
NMR (121.5 MHz, CDCl ): δ = 22.5 ppm. IR (KBr): ν = 3422 (w),
hydrogen atoms calculated and refined as riding atoms.
˜
3
3310 (w), 3071 (w), 3059 (w), 2995 (w), 2949 (w), 2901 (w), 2887
(w), 2851 (w), 1665 (s), 1611 (w), 1597 (w), 1557 (s), 1506 (s), 1479
(s), 1466 (m), 1441 (m), 1423 (m), 1381 (m), 1350 (m), 1308 (m),
1250 (s), 1213 (m), 1186 (m), 1167 (m), 1146 (m), 1090 (m), 1059
(s), 1030 (s), 918 (m), 883 (m), 845 (m), 806 (m), 762 (m), 741 (m),
6,6,6-Trifluoro-5-(4-fluorophenyl)-2-(indolin-1-ylimino)hex-4-en-3-
one (4b): Obtained from keto phosphonate 7a according to the ge-
neral procedure. Chromatographic purification (Et2O/pentane, 2:5)
gave 0.198 g (0.53 mmol, 75%) of 4b as a yellow solid, m.p. 123–
1
124 °C. H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3 H, CH3), 3.27
714 (m), 653 (w), 642 (w), 615 (w), 596 (w), 581 (w), 544 (w) cm–1
.
(t, J = 8.2 Hz, 2 H, CH2), 4.21 (t, J = 8.2 Hz, 2 H, CH2N), 6.98–
7.06 (m, 3 H, Harom.), 7.19–7.32 (m, 5 H, Harom.), 7.68 (q, J =
1.4 Hz, 1 H, Holef.) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.2
(CH3), 28.0 (CH2), 52.8 (CH2), 111.4 (CHarom.), 115.2 (d, J =
21.7 Hz, CHarom.), 123.0 (q, J = 274.0 Hz, CF3), 123.5 (CHarom.),
125.1 (CHarom.), 127.6, 127.9 (d, J = 3.5 Hz), 128.3 (CHarom.), 131.0
(d, J = 8.3 Hz), 131.4 (q, J = 5.3 Hz, CHolef.), 135.3 (q, J = 30.4 Hz,
CCF3), 140.1 (C=N), 148.0 (C-N), 162.9 (d, J = 248.3 Hz, C-F),
189.1 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –113.0 [major
(E)], –100.1 [minor (Z )] (F ); –67.2 (major), –60.1 (minor)
H R M S (ESI): calcd. for C17H 19N 2PSO4N a 401.0695; found
401.0700. C17H19N2O4PS (378.38): calcd. C 53.96, H 5.06, N 7.40;
found C 53.88, H 5.05, N 7.06.
General Procedure for the Preparation of Azadienones 4:[10] tBuOK
(10 mmol) was dissolved in abs. THF (100 mL) and keto phos-
phonate 7 (10 mmol) in THF (20 mL) was added. The reaction
mixture was stirred for 1 h at room temp. and the trifluoroacetyl
ketone (10 mmol) 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 chromatography. In
all cases the product with the CF3 and carbonyl groups in the trans
position was the main isomer (in the case of compound 4q the E
(CF ) ppm; 29:1 ratio IR (KBr): ν = 3437 (w), 3285 (w), 3088 (w),
˜
3
3072 (w), 3018 (w), 2955 (w), 2930 (w), 2856 (w), 1655 (s), 1607
(s), 1556 (s), 1512 (s), 1483 (s), 1441 (m), 1375 (s), 1331 (m), 1306
(s), 1292 (s), 1269 (s), 1246 (s), 1238 (s), 1211 (m), 1167 (s), 1117
isomer was exclusively formed). 1H and 13C NMR signals were (s), 1078 (s), 1047 (m), 1032 (m), 966 (m), 937 (w), 916 (w), 883
assigned for the main isomeric product. The stereochemistry of the
olefination product 4h was determined by using the 1H–19F hetero-
(m), 866 (w), 841 (s), 806 (m), 762 (s), 725 (m), 708 (w), 685 (m),
665 (w), 644 (m), 617 (w), 594 (w), 582 (w), 544 (w) cm–1. HRMS
NOE technique, and for 4a, 4e and 4q by X-ray diffraction. The (ESI): calcd. for C20H 16F 4N 2ON a 399.1091; found 399.1090.
stereochemistries of the other products were determined by com-
paring the 19F chemical shifts with compounds of known stereo-
chemistry. The ratios of the E and Z isomers were determined from
19F NMR experiments on the crude reaction mixture.
C20H16F4N2O (376.35): calcd. C 63.83, H 4.29, N 7.44; found C
63.89, H 4.09, N 7.27.
5-(4-Chlorophenyl)-6,6,6-trifluoro-2-(indolin-1-ylimino)hex-4-en-3-
one (4c): Obtained from keto phosphonate 7a according to the ge-
6,6,6-Trifluoro-2-(indolin-1-ylimino)-5-phenylhex-4-en-3-one (4a): neral procedure. Chromatographic purification (Et2O/pentane, 2:5)
Obtained from keto phosphonate 7a according to the general pro-
cedure. Chromatographic purification (TBM E) gave 0.280 g
(0.78 mmol, 78%) of 4a as a yellow solid, m.p. 118–119 °C. 1H
NMR (300 MHz, CDCl3): δ = 2.12 (s, 3 H, CH3), 3.25 (t, J =
8.2 Hz, 2 H, CH2), 4.15 (t, J = 8.2 Hz, 2 H, CH2N), 7.02 (dt, J =
gave 0.189 g (0.48 mmol, 69%) of 4c as a yellow solid, m.p. 150.5–
151.5 °C. 1H NMR (400 MHz, CDCl3): δ = 2.15 (s, 3 H, CH3),
3.27 (t, J = 8.2 Hz, 2 H, CH2), 4.21 (t, J = 8.2 Hz, 2 H, CH2N),
7.03 (td, J = 7.4, 1.0 Hz, 1 H, Harom.), 7.19–7.21 (m, 4 H, Harom.),
7.26–7.31 (m, 3 H, Harom.), 7.69 (q, J = 1.4 Hz, 1 H, Holef.) ppm.
7.3, 1.0 Hz, 1 H, Harom.), 7.20 (t, J = 7.1 Hz, 1 H, Harom.), 7.25– 13C NMR (100 MHz, CDCl3): δ = 12.2 (CH3), 28.0 (CH2), 52.8
7.32 (m, 7 H, Harom.), 7.64 (q, J = 1.3 Hz, 1 H, Holef.) ppm. 13C
NMR (100 MHz, CDCl3): δ = 12.3 (CH3), 28.1 (CH2), 52.8 (CH2),
111.5 (CHarom.), 122.8 (CHarom.), 123.2 (q, J = 274.1 Hz, CF3),
125.0 (CHarom.), 127.6, 128.1 (CHarom.), 128.3 (CHarom.), 128.7
(CHarom.), 129.1 (CHarom.), 131.2 (q, J = 5.4 Hz, CHolef.), 132.1,
135.3 (q, J = 34.9 Hz, CCF3), 140.5 (C=N), 148.2 (C-N), 189.4
(CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –67.0 [major isomer
(CH 2), 111.5 (CH arom.), 123.0 (q, J = 274.0 H z, CF 3), 123.5
(CHarom.), 125.1 (CHarom.), 127.7, 128.3 (CHarom.), 128.4 (CHarom.),
130.45, 130.48 (CHarom.), 131.5 (q, J = 5.2 Hz, CHolef.), 134.9,
135.2 (q, J = 30.4 Hz, CCF3), 140.0 (C=N), 147.9 (C-N), 188.9
(CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –67.0 [major (E)],
–60.0 [minor (Z)] (CF ) ppm; 30:1 ratio. IR (KBr): ν = 3443 (w),
˜
3
3119 (w), 3092 (w), 3065 (w), 3051 (w), 2963 (w), 2924 (w), 2856
(E)], –59.8 [minor isomer (Z)] (CF ) ppm; 20:1 ratio. IR (KBr): ν (w), 1668 (s), 1632 (s), 1609 (m), 1597 (w), 1551 (s), 1495 (s), 1481
˜
3
= 3445 (w), 3289 (w), 3090 (w), 3063 (w), 3026 (w), 2966 (w), 2930 (s), 1439 (m), 1394 (w), 1375 (s), 1332 (m), 1308 (m), 1290 (s), 1269
(w), 2856 (w), 1958 (w), 1657 (s), 1611 (m), 1558 (s), 1483 (s), 1447 (s), 1238 (s), 1178 (m), 1115 (s), 1078 (m), 1072 (m), 1030 (m), 1015
(m), 1373 (s), 1290 (s), 1271 (s), 1242 (s), 1211 (m), 1167 (s), 1113
(m), 974 (m), 951 (m), 916 (m), 835 (m), 829 (m), 768 (w), 750 (m),
(s), 1078 (s), 1034 (m), 1013 (m), 966 (m), 937 (w), 872 (m), 835 733 (m), 712 (m), 675 (w), 642 (m), 594 (w), 538 (w) cm–1. HRMS
(w), 814 (w), 777 (m), 764 (s), 732 (w), 698 (s), 683 (w), 642 (m),
611 (w), 588 (w), 528 (w) cm –1 . H R M S (E SI ): ca lcd . fo r
C20H 17F 3N 2ON a 381.1185; found 381.1186. C20H 17F 3N 2O
(358.36): calcd. C 67.03, H 4.78, N 7.82; found C 66.83, H 4.71, N
7.73.
(ESI): calcd. for C20H16ClF3N2ONa 415.0795; found 415.0785.
C20H16ClF3N2O (392.80): calcd. C 61.15, H 4.10, N 7.13; found C
61.12, H 3.99, N 6.98.
5-(4-Bromophenyl)-6,6,6-trifluoro-2-(indolin-1-ylimino)hex-4-en-3-
one (4d): Obtained from keto phosphonate 7a according to the ge-
neral procedure. Chromatographic purification (Et2O/pentane, 1:2)
gave 0.102 g (0.23 mmol, 79%) of 4d as a yellow solid, m.p. 174.5–
X-Ray Crystal Structure Analysis of 4a: Formula C20H17F3N2O,
M = 358.36, yellow crystal 0.30ϫ0.30ϫ0.10 mm, a = 7.5506(2),
b = 10.5837(4), c = 11.5646(3) Å, α = 84.079(3), β = 78.161(3),
γ = 73.836(1)°, V = 867.71(5) Å3, ρcalcd. = 1.372 g cm–3, µ =
0.108 mm–1, empirical absorption correction (0.968 Յ T Յ 0.989),
1
175 °C. H NMR (300 MHz, CDCl3): δ = 2.15 (s, 3 H, CH3), 3.28
(t, J = 8.2 Hz, 2 H, CH2), 4.21 (t, J = 8.2 Hz, 2 H, CH2N), 7.03
(dt, J = 7.4, 1.0 Hz, 1 H, Harom.), 7.12–7.29 (m, 5 H, Harom.), 7.44–
7.47 (m, 2 H, Harom.), 7.69 (q, J = 1.3 Hz, 1 H, Holef.) ppm. 13C
¯
Z = 2, triclinic, space group P1 (No. 2), λ = 0.71073 Å, T = 198 K,
ω and φ scans, 8036 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ] NMR (75 MHz, CDCl3): δ = 12.2 (CH3), 28.0 (CH2), 52.8 (CH2),
3660 Eur. J. Org. Chem. 2008, 3656–3667
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

2H-Pyrrole Derivatives from an Aza-Nazarov Reaction Cascade
111.4 (CH arom.), 122.9 (q, J = 278.1 H z, CF 3), 123.2, 123.5
(CHarom.), 125.1 (CHarom.), 127.7, 128.3 (CHarom.), 130.7 (CHarom.),
131.4 (CH arom.), 131.4 (q, J = 5.0 H z, CH olef.), 135.7 (q, J =
32.2 Hz, CCF3), 140.0 (C=N), 147.9 (C-N), 188.8 (CO) ppm. 19F
= –113.3 [major(E)], –112.8 [minor (Z)] (F), –67.0 (major), –60.0
(minor) (CF ) ppm; 14:1 ratio. IR (KBr): ν = 3443 (w), 3298 (w),
˜
3
3065 (w), 3049 (w), 3020 (w), 2953 (w), 2920 (w), 2864 (w), 1659
(s), 1612 (s), 1564 (s), 1483 (s), 1441 (m), 1389 (m), 1371 (s), 1329
NMR (282 MHz, CDCl3): δ = –67.0 [major (E)], –60.0 [minor (Z)] (m), 1308 (s), 1290 (s), 1275 (s), 1246 (s), 1213 (s), 1169 (s), 1161
(CF ) ppm; 28:1 ratio. IR (KBr): ν = 3427 (w), 3119 (w), 3080 (w), (s), 1136 (s), 1115 (s), 1078 (s), 1034 (m), 1015 (m), 991 (m), 947
3061 (w), 3047 (w), 2949 (w), 2922 (w), 2853 (w), 1668 (m), 1632 (w), 935 (w), 907 (w), 891 (m), 872 (m), 833 (w), 806 (w), 793 (s),
˜
3
(m), 1609 (m), 1549 (m), 1502 (m), 1481 (s), 1437 (m), 1394 (m),
1375 (s), 1329 (w), 1308 (m), 1290 (s), 1269 (s), 1232 (s), 1217 (s),
1178 (s), 1115 (s), 1067 (s), 1030 (m), 1011 (s), 972 (m), 951 (m),
916 (s), 829 (s), 760 (m), 748 (s), 731 (m), 710 (m), 669 (m), 638 (m),
592 (w), 532 (w) cm–1. HRMS (ESI): calcd. for C20H16BrF3N2ONa
459.0290; found 459.0292.
758 (s), 729 (m), 700 (s), 681 (m), 652 (m), 613 (w), 586 (w), 555 (w),
521 (w) cm–1. HRMS (ESI): calcd. for C20H16F4N2ONa 399.1091;
found 399.1099. C20H16F4N2O (376.35): calcd. C 63.83, H 4.29, N
7.44; found C 63.61, H 4.36, N 7.18.
6,6,6-Trifluoro-2-(indolin-1-ylimino)-5-[3-(trifluoromethyl)phenyl]-
hex-4-en-3-one (4g): Obtained from keto phosphonate 7a according
to the general procedure. Chromatographic purification (Et2O/pen-
tane, 2:5) gave 0.227 g (0.53 mmol, 76%) of 4g as a yellow solid,
m.p. 107–108 °C. 1H NMR (400 MHz, CDCl3): δ = 2.14 (s, 3 H,
CH3), 3.27 (t, J = 8.2 Hz, 2 H, CH2), 4.21 (t, J = 8.2 Hz, 2 H,
CH2N), 7.04 (dt, J = 7.4, 1.0 Hz, 1 H, Harom.), 7.20–7.22 (m, 2 H,
5-[4-(Dimethylamino)phenyl]-6,6,6-trifluoro-2-(indolin-1-ylimino)-
hex-4-en-3-one (4e): Obtained from keto phosphonate 7a according
to the general procedure. Chromatographic purification (Et2O/pen-
tane, 2:5) gave 0.254 g (0.63 mmol, 79%) of 4e as an orange solid,
m.p. 142–143 °C. 1H NMR (400 MHz, CDCl3): δ = 2.16 (s, 3 H,
CH3), 2.95 (s, 6 H, CH3N), 3.24 (t, J = 8.2 Hz, 2 H, CH2), 4.16 (t,
J = 8.2 Hz, 2 H, CH2N), 6.66 (d, J = 7.5 Hz, 2 H, Harom.), 7.00
(dt, J = 7.4, 1.0 Hz, 1 H, Harom.), 7.16–7.29 (m, 5 H, Harom.), 7.52
(q, J = 1.2 Hz, 1 H, Holef.) ppm. 13C NMR (100 MHz, CDCl3): δ
= 12.4 (CH3), 28.0 (CH2), 52.8 (CH2), 111.5 (CHarom.), 120.2 (q, J
= 274.5 Hz, CF3), 123.1 (CHarom.), 124.9 (CHarom.), 127.5, 128.2
(CHarom.), 128.3 (CHarom.), 130.1 (CHarom.), 140.8 (C=N), 148.3
(C-N), 190.1 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –66.5
H
H
arom.), 7.30 (td, J = 7.4, 1.0 Hz, 1 H, Harom.), 7.46–7.47 (m, 2 H,
arom.), 7.51 (s, 1 H, Harom.), 7.60–7.62 (m, 1 H, Harom.), 7.77 (q,
J = 1.4 Hz, 1 H, Holef.) ppm. 13C NMR (100 MHz, CDCl3): δ =
12.2 (CH3), 28.0 (CH2), 52.8 (CH2), 111.4 (CHarom.), 122.9 (q, J =
274.2 Hz, CF3), 123.6 (CHarom.), 123.8 (q, J = 272.8 Hz, CF3),
125.1 (CHarom.), 125.5 (d, J = 3.7 Hz, CHarom.), 126.0 (d, J =
3.9 Hz, CHarom.), 127.7, 128.3 (CHarom.), 128.6 (CHarom.), 130.6 (d,
J = 32.5 Hz, CCF3), 132.0 (q, J = 5.2 Hz, CHolef.), 132.7 (CHarom.),
132.9, 134.9 (q, J = 30.5 Hz, CCF3), 140.0 (C=N), 147.8 (C-N),
188.5 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –67.0 [major
(E)], –59.9 [minor (Z)], –63.3 (minor), –63.2 (major) (CF3) ppm;
[major (E)], –59.6 [minor (Z)] (CF ) ppm; 11:1 ratio. IR (KBr): ν
˜
3
= 3439 (w), 3262 (w), 3084 (w), 3030 (w), 2916 (m), 2895 (m), 2864
(m), 2818 (m), 2806 (m), 1659 (s), 1611 (s), 1560 (s), 1526 (s), 1483
(s), 1447 (s), 1367 (s), 1329 (m), 1308 (s), 1290 (s), 1263 (s), 1242
(s), 1204 (s), 1165 (s), 1111 (s), 1069 (s), 1032 (s), 1011 (s), 989 (m),
968 (m), 945 (m), 930 (m), 887 (s), 820 (s), 781 (m), 762 (m), 754
(s), 741 (m), 712 (w), 694 (m), 683 (m), 640 (s), 627 (m), 594 (w),
573 (w), 538 (w) cm–1. HRMS (ESI): calcd. for C22H22F3N3ONa
424.1607; found 424.1616. C22H22F3N3O (401.42): calcd. C 65.82,
H 5.52, N 10.47; found C 65.66, H 5.64, N 10.43.
14:1 ratio. IR (KBr): ν = 3437 (w), 3269 (w), 3080 (w), 3065 (w),
˜
3042 (w), 2976 (w), 2941 (w), 2864 (w), 1666 (s), 1639 (s), 1611 (m),
1556 (s), 1483 (s), 1443 (m), 1389 (w), 1371 (s), 1325 (m), 1310 (m),
1290 (s), 1269 (s), 1236 (s), 1167 (m), 1123 (s), 1097 (m), 1072 (m),
1030 (m), 1013 (m), 980 (m), 945 (m), 932 (m), 903 (m), 889 (m),
847 (m), 800 (m), 754 (s), 733 (m), 700 (m), 679 (w), 660 (m), 652
(w), 625 (w), 602 (w), 590 (w), 521 (w) cm–1. HRMS (ESI): calcd.
for C21H16F6N2ONa 449.1059; found 449.1051. C21H16F6N2O
(426.35): calcd. C 59.16, H 3.78, N 6.57; found C 59.16, H 3.62, N
6.39.
X-Ray Crystal Structure Analysis of 4e: Formula C22H22F3N3O, M
= 401.43, yellow crystal 0.40ϫ0.30ϫ0.30 mm, a = 7.6204(2), b =
11.0762(3), c = 12.3024(4) Å, α = 95.242(1), β = 95.808(2), γ =
102.276(1)°, V = 1002.60(5) Å3, ρca lcd . = 1.330 g cm–3, µ =
0.102 mm–1, empirical absorption correction (0.960 Յ T Յ 0.970),
6,6,6-Trifluoro-2-(indolin-1-ylimino)-5-(thien-2-yl)hex-4-en-3-one
(4h): Obtained from keto phosphonate 7a according to the general
procedure. Chromatographic purification (Et2O/pentane, 2:5) gave
0.161 g (0.44 mmol, 63 %) of 4h as a yellow solid, m.p. 134.5–
¯
Z = 2, triclinic, space group P1 (No. 2), λ = 0.71073 Å, T = 223 K,
ω and φ scans, 10060 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ]
= 0.66 Å–1, 4738 independent (Rint = 0.056) and 3064 observed
1
135 °C. H NMR (400 MHz, CDCl3): δ = 2.23 (s, 3 H, CH3), 3.26
reflections [I Ն 2σ(I)], 265 refined parameters, R = 0.053, wR2
=
(t, J = 8.2 Hz, 2 H, CH2), 4.22 (t, J = 8.2 Hz, 2 H, CH2N), 6.98–
7.02 (m, 2 H, Harom.), 7.13–7.27 (m, 4 H, Harom), 7.34 (dd, J = 5.1,
1.2 Hz, 1 H, Harom.), 7.45 (q, J = 1.4 Hz, 1 H, Holef.) ppm. 13C
NMR (100 MHz, CDCl3): δ = 12.3 (CH3), 28.0 (CH2), 52.7 (CH2),
111.5 (CHarom.), 122.8 (q, J = 274.9 Hz, CF3), 123.4 (CHarom.),
125.0 (CHarom.), 126.9 (CHarom.), 127.6, 127.8 (CHarom.), 128.2
(CHarom.), 129.6 (CHarom), 132.7 (q, J = 5.2 Hz, CHolef.), 139.6
0.163, max. (min.) residual electron density: 0.27 (–0.25) eÅ–3, hy-
drogen atoms calculated and refined as riding atoms.
6,6,6-Trifluoro-5-(3-fluorophenyl)-2-(indolin-1-ylimino)hex-4-en-3-
one (4f): Obtained from keto phosphonate 7a according to the ge-
neral procedure. Chromatographic purification (Et2O/pentane, 2:5)
gave 0.181 g (0.48 mmol, 80%) of 4f as a yellow solid, m.p. 144–
1
145 °C. H NMR (300 MHz, CDCl3): δ = 2.16 (s, 3 H, CH3), 3.27 (C= N ), 147.9 (C-N ), 190.2 (CO) ppm. 19F N M R (282 M H z,
(t, J = 8.2 Hz, 2 H, CH2), 4.22 (t, J = 8.2 Hz, 2 H, CH2N), 6.96–
7.08 (m, 4 H, Harom.), 7.19–7.34 (m, 4 H, Harom.), 7.70 (q, J =
CDCl3): δ = –66.1 [major (Z)], –61.0 [minor (E)] (CF3) ppm; 11:1
ratio. IR (KBr): ν = 3441 (w), 3285 (w), 3103 (w), 3057 (w), 3018
˜
1.4 Hz, 1 H, Holef.) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.2 (w), 2930 (w), 2853 (w), 1655 (s), 1611 (m), 1557 (s), 1483 (s), 1470
(CH3), 28.0 (CH2), 52.8 (CH2), 111.4 (CHarom.), 115.7 (d, J =
20.9 Hz, CHarom.), 116.3 (d, J = 22.7 Hz, CHarom.), 122.9 (q, J =
274.0 Hz, CF3), 123.5 (CHarom.), 125.0 (d, J = 3.0 Hz, CHarom.),
125.1 (CHarom.), 127.7, 128.3 (CHarom.), 129.7 (d, J = 8.3 H z,
(m), 1437 (m), 1371 (m), 1333 (m), 1306 (m), 1292 (s), 1273 (s),
1246 (s), 1211 (s), 1167 (s), 1121 (s), 1078 (m), 1034 (m), 1013 (m),
945 (w), 939 (w), 908 (w), 881 (w), 853 (m), 837 (w), 806 (w), 766
(s), 706 (s), 681 (m), 671 (w), 654 (m), 596 (w) cm–1. HRMS (ESI):
CHarom.), 131.8 (q, J = 5.3 Hz, CHolef.), 134.0 (d, J = 8.0 Hz), 135.0 ca lcd . fo r C 18H 15F 3N 2O SN a 387.0749; fo u n d 387.0744.
(q, J = 30.0 Hz, CCF3), 140.1 (C=N), 148.0 (C-N), 162.3 (d, J =
246.5 Hz, C-F), 188.8 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ
C18H15F3N2OS (364.38): calcd. C 59.33, H 4.15, N 7.69; found C
59.26, H 3.97, N 7.46.
Eur. J. Org. Chem. 2008, 3656–3667
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3661

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
5-(Benzo[b]furan-2-yl)-6,6,6-trifluoro-2-(indolin-1-ylimino)hex-4-en- [major (E)], –59.7 [minor (Z)] (CF ) ppm; 13:1 ratio. IR (KBr): ν
FULL PAPER
˜
3
3-one (4i): Obtained from keto phosphonate 7a according to the
general procedure. Chromatographic purification (Et2O/pentane,
1:1) gave 0.225 g (0.57 mmol, 71%) of 4i as a yellow solid, m.p.
= 3416 (w), 3269 (w), 3057 (m), 3022 (m), 2959 (m), 2934 (m), 2914
(m), 2858 (m), 1659 (s), 1645 (s), 1612 (m), 1599 (m), 1547 (s), 1481
(s), 1468 (s), 1443 (s), 1369 (s), 1329 (s), 1308 (s), 1288 (s), 1271 (s),
1248 (s), 1171 (s), 1159 (s), 1136 (s), 1115 (s), 1072 (s), 1030 (s),
1015 (s), 1001 (m), 989 (m), 974 (s), 951 (m), 916 (m), 885 (m), 847
(m), 839 (m), 802 (m), 758 (s), 733 (s), 702 (s), 681 (s), 652 (s),
611 (m), 594 (w), 567 (w), 532 (m) cm–1. HRMS (ESI): calcd. for
C25H19F3N2ONa 443.1342; found 443.1334.
1
105–106 °C. H NMR (400 MHz, CDCl3): δ = 2.35 (s, 3 H, CH3),
3.16 (t, J = 8.2 Hz, 2 H, CH2), 4.15 (t, J = 8.2 Hz, 2 H, CH2N),
6.92–7.38 (m, 8 H, Harom.), 7.48–7.67 (m, 2 H, Harom.) ppm. 13C
NMR (100 MHz, CDCl3): δ = 12.3 (CH3), 27.9 (CH2), 52.6 (CH2),
108.4 (q, J = 1.7 Hz), 111.1 (CHarom.), 111.4 (CH arom.), 121.7
(CHarom.), 122.6 (q, J = 273.9 Hz, CF3), 123.2 (CHarom.) 124.9
(CHarom.), 125.6 (CHarom.), 127.4, 127.8, 128.1 (CHarom.), 133.2 (q,
J = 5.3 Hz, CHolef.), 139.4, 147.9, 154.7, 191.0 (CO) ppm. 19F
NMR (282 MHz, CDCl3): δ = –65.3 [major (E)], –60.4 [minor (Z)]
5,5,5-Trifluoro-1-(indolin-1-ylimino)-4-phenyl-1-(2-thienyl)pent-3-
en-2-one (4l): Obtained from keto phosphonate 7c according to the
general procedure. Chromatographic purification (Et2O/pentane,
1:2) gave 0.092 g (0.22 mmol, 72%) of 4l as a red solid, m.p. 131.5–
(CF ) ppm; 6:1 ratio. IR (KBr): ν = 3435 (w), 3317 (w), 3127 (w),
˜
3
1
133 °C. H NMR (300 MHz, CDCl3): δ = 3.04 (t, J = 8.0 Hz, 2 H,
3086 (w), 3063 (w), 2951 (w), 2920 (w), 2858 (w), 1666 (s), 1611
(m), 1557 (s), 1510 (w), 1483 (s), 1448 (m), 1373 (m), 1331 (m),
1306 (m), 1292 (s), 1269 (s), 1246 (s), 1207 (s), 1192 (s), 1163 (s),
1153 (s), 1138 (s), 1126 (s), 1074 (m), 1032 (m), 1013 (m), 937 (w),
924 (m), 887 (w), 862 (m), 826 (m), 797 (m), 754 (s), 700 (w), 677
CH2), 3.40 (t, J = 8.2 Hz, 2 H, CH2N), 6.77 (dd, J = 3.5, 1.2 Hz,
1 H, Harom), 6.98–7.19 (m, 3 H, Harom.), 7.27–7.34 (m, 7 H, Harom.),
7.41 (dd, J = 5.1, 1.1 Hz, 1 H, Harom.), 7.54 (q, J = 1.4 Hz, 1 H,
H
olef.) ppm. 13C NMR (100 MHz, CDCl3): δ = 27.8 (CH2), 52.3
(CH 2), 111.7 (CH arom.), 123.2 (q, J = 274.1 H z, CF 3), 124.3
(CH arom.), 125.2 (CHarom.), 126.0 (CH arom.), 127.8 (CHarom.),
128.13 (CHarom.), 128.16 (CHarom.), 128.5, 128.7 (CHarom.), 129.2
(CHarom.), 130.7 (CHarom.), 131.9 (q, J = 5.2 Hz, CHolef.), 132.1,
132.9, 136.2 (q, J = 30.4 Hz, CCF3), 147.0, 189.3 (CO) ppm. 19F
NMR (282 MHz, CDCl3): δ = –66.6 [major (E)], –59.8 [minor (Z)]
(m), 652 (m), 613 (w), 592 (w), 584 (w), 569 (w), 544 (w) cm–1
.
H R M S (ESI): calcd. for C22H 17F 3N 2O2N a 421.1134; found
421.1155. C22H17F3N2O2 (398.38): calcd. C 66.33, H 4.30, N 7.03;
found C 66.39, H 4.48, N 7.06.
5-(Benzo[b]thiophen-2-yl)-6,6,6-trifluoro-2-(indolin-1-ylimino)hex-4-
en-3-one (4j): Obtained from keto phosphonate 7a according to the
general procedure. Chromatographic purification (Et2O/pentane,
1:2) gave 0.126 g (0.30 mmol, 87%) of 4j as an orange solid, m.p.
(CF ) ppm; 16:1 ratio. IR (KBr): ν = 3439 (w), 3103 (w), 3103 (w),
˜
3
3084 (w), 3065 (w), 3044 (w), 3024 (w), 2951 (w), 2922 (w), 2855
(w), 1661 (m), 1641 (m), 1612 (w), 1599 (w), 1553 (s), 1501 (s), 1481
(s), 1466 (m), 1445 (w), 1425 (m), 1369 (m), 1348 (m), 1310 (m),
1271 (s), 1244 (s), 1215 (s), 1171 (s), 1115 (s), 1097 (s), 1038 (m),
1013 (m), 989 (w), 970 (m), 928 (w), 908 (w), 897 (w), 885 (w), 847
(w), 797 (w), 760 (m), 721 (m), 700 (s), 685 (m), 656 (w), 644 (w),
613 (w), 596 (w), 573 (w), 532 (w) cm–1. HRMS (ESI): calcd. for
C23H17F3N2OSNa 449.0906; found 449.0908.
1
133–134 °C. H NMR (300 MHz, CDCl3): δ = 2.22 (s, 3 H, CH3),
3.21 (t, J = 8.2 Hz, 2 H, CH2), 4.18 (t, J = 8.2 Hz, 2 H, CH2N),
7.01 (dt, J = 7.4, 0.9 Hz, 1 H, Harom.), 7.14–7.18 (m, 2 H, Harom.),
7.23–7.32 (m, 3 H, Harom), 7.37 (s, 1 H, Harom.), 7.51 (q, J = 1.3 Hz,
1 H, Holef.), 7.70–7.75 (m, 2 H, Harom.) ppm. 13C NMR (100 MHz,
CDCl3): δ = 12.2 (CH3), 28.0 (CH2), 52.6 (CH2), 111.6 (CHarom.),
121.9 (CHarom.), 122.7 (q, J = 274.7 Hz, CF3), 123.5 (CHarom.),
124.1 (CHarom.), 124.4 (CHarom.), 125.0 (CHarom.), 125.1 (CHarom.),
126.3 (CHarom.), 127.6, 128.2 (CHarom.), 132.1, 134.5 (q, J = 5.2 Hz,
CHolef.), 139.1, 139.4, 140.5 (C=N), 147.8 (C-N), 190.0 (CO) ppm.
19F NMR (282 MHz, CDCl3): δ = –66.5 [major (Z)], –60.4 [minor
4-(Benzo[b]furan-2-yl)-5,5,5-trifluoro-1-(indolin-1-ylimino)-1-(2-
thienyl)pent-3-en-2-one (4m): Obtained from keto phosphonate 7c
according to the general procedure. Chromatographic purification
(Et2O/pentane, 1:2) gave 0.133 g (0.29 mmol, 95%) of 4m as a red
solid, m.p. 55–56 °C. 1H NMR (300 MHz, CDCl3): δ = 2.98 (t, J
= 8.0 Hz, 2 H, CH2), 3.49 (t, J = 8.2 Hz, 2 H, CH2N), 6.97–7.01
(m, 2 H, Harom.), 7.05–7.30 (m, 8 H, Harom.), 7.40 (qd, J = 8.3,
0.8 Hz, 1 H), 7.52 (ddd, J = 7.7, 1.2, 0.7 Hz, 1 H), 7.55 (dd, J =
5.1, 1.2 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 27.8
(CH2), 52.3 (CH2), 108.4 (q, J = 1.6 Hz), 111.3 (CHarom.), 111.7
(CHarom.), 121.7 (CHarom.), 122.7 (q, J = 273.9 Hz, CF3), 123.2
(CHarom.) 124.2 (CHarom.), 125.1 (CHarom.), 125.6 (CHarom.), 126.2
(CHarom.), 127.9, 128.2 (CHarom.), 128.3 (CHarom.), 128.5, 130.9
(CHarom.), 132.1, 132.4, 133.9 (q, J = 5.3 Hz, CHolef.), 146.9, 147.6,
154.9, 190.3 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –65.2
(E)] (CF ) ppm; 7:1 ratio. IR (KBr): ν = 3437 (w), 3092 (w), 3074
˜
3
(w), 3057 (w), 3022 (w), 2966 (w), 2922 (w), 2853 (w), 1665 (m),
1638 (m), 1607 (m), 1553 (s), 1479 (s), 1460 (m), 1437 (m), 1385
(w), 1364 (w), 1329 (w), 1302 (m), 1286 (m), 1267 (s), 1232 (s), 1207
(s), 1134 (s), 1171 (s), 1103 (m), 1070 (m), 1028 (m), 1011 (m), 988
(m), 943 (m), 930 (m), 899 (m), 860 (w), 843 (w), 762 (m), 810 (m),
752 (s), 833 (w), 725 (m), 704 (w), 698 (w), 675 (m), 658 (m), 590
( w ) , 5 5 9 ( w ) , 5 0 0 ( w) cm – 1 . H R M S ( E S I ) : c a l cd . fo r
C22H 17F 3N 2OSN a 437.0906; found 437.0914. C22H 17F3N2OS
(414.44): calcd. C 63.76, H 4.13, N 6.76; found C 63.49, H 4.25, N
6.55.
[major (E)], –60.4 [minor (Z)] (CF ) ppm; 17:1 ratio. IR (KBr): ν
˜
3
5,5,5-Trifluoro-1-(indolin-1-ylimino)-1,4-diphenylpent-3-en-2-one
(4k): Obtained from keto phosphonate 7b according to the general
procedure. Chromatographic purification (Et2O/pentane, 2:5) gave
0.250 g (0.60 mmol, 77%) of 4k as a yellow solid, m.p. 155–156 °C.
1H NMR (300 MHz, CDCl3): δ = 2.98 (t, J = 8.2 Hz, 2 H, CH2),
3.15 (t, J = 8.2 Hz, 2 H, CH2N), 6.99–7.06 (m, 3 H, Harom.), 7.14
(d, J = 7.3 Hz, 1 H, Harom.), 7.28–7.34 (m, 10 H, Harom.), 7.59 (q,
J = 1.5 Hz, 1 H, Holef.) ppm. 13C NMR (100 MHz, CDCl3): δ =
27.9 (CH2), 53.2 (CH2), 111.4 (CHarom.), 123.3 (q, J = 274.2 Hz,
= 3424 (w), 3055 (w), 2926 (w), 2855 (w), 2363 (w), 1661 (s), 1614
(m), 1599 (w), 1555 (s), 1504 (s), 1481 (s), 1468 (m), 1450 (m), 1425
(m), 1379 (m), 1350 (m), 1310 (s), 1277 (s), 1250 (s), 1215 (s), 1192
(s), 1169 (s), 1126 (s), 1103 (s), 1074 (m), 1038 (m), 1013 (m), 986
(s), 932 (w), 920 (w), 885 (w), 851 (m), 814 (m), 779 (w), 750 (s),
704 (s), 683 (m), 613 (w), 598 (w), 565 (w), 532 (w) cm–1. HRMS
(ESI): calcd. for C25H17F3N2O2SNa 489.0855; found 489.0862.
4-(Benzo[b]thiophen-2-yl)-5,5,5-trifluoro-1-(indolin-1-ylimino)-1-(2-
CF3), 123.8 (CHarom.), 125.1 (CHarom.), 127.5 (CHarom.), 128.1 thienyl)pent-3-en-2-one (4n): Obtained from keto phosphonate 7c
(CH arom.), 128.2, 128.3 (CH arom.), 128.65 (CH arom.), 128.69 according to the general procedure. Chromatographic purification
(CHarom.), 129.3 (CHarom.), 130.3 (CHarom.), 132.3 (q, J = 5.5 Hz,
CHolef.), 133.3, 135.8 (q, J = 30.5 Hz, CCF3), 140.3 (C=N), 147.3
(C-N), 189.6 (CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –66.7
(Et2O/pentane, 2:5) gave 0.303 g (0.63 mmol, 79%) of 4n as a yel-
low solid, m.p. 132–133 °C. H NMR (400 MHz, CDCl3): δ = 3.00
(t, J = 8.2 Hz, 2 H, CH2), 3.42 (t, J = 8.2 Hz, 2 H, CH2N), 6.86
1
3662
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3656–3667

2H-Pyrrole Derivatives from an Aza-Nazarov Reaction Cascade
(dd, J = 3.5, 1.1 Hz, 1 H, CHarom.), 7.01–7.08 (m, 2 H, Harom), 7.15 1115 (s), 1067 (s), 1028 (s), 1013 (m), 972 (m), 930 (m), 910 (m),
(d, J = 7.4 Hz, 1 H, Harom.), 7.28–7.32 (m, 4 H, Harom.), 7.38 (s, 1 891 (m), 866 (m), 853 (m), 789 (m), 752 (s), 723 (m), 689 (m), 669
H, Harom.), 7.45 (dd, J = 5.1, 1.1 Hz, 1 H, CHarom.), 7.47 (q, J =
1.4 Hz, 1 H, Holef.), 7.69–7.75 (m, 2 H, Harom.) ppm. 13C NMR
(100 MHz, CDCl3): δ = 27.8 (CH2), 52.3 (CH2), 111.9 (CHarom.),
121.9 (CHarom.), 122.4 (q, J = 265.6 Hz, CF3), 124.1 (CHarom.),
124.5 (CHarom.), 125.1 (CHarom.), 125.2 (CHarom.), 126.1 (CHarom.),
126.6 (CHarom.), 128.3 (CHarom.), 128.7, 130.9 (CHarom.), 131.8,
132.3 (q, J = 8.9 Hz), 134.4 (q, J = 5.2 Hz, CHolef.), 139.1, 140.6
(C= N ), 146.8 (C-N ), 189.7 (CO) ppm. 19F N M R (282 M H z,
CDCl3): δ = –66.3 [major (Z)], –60.3 [minor (E)] (CF3) ppm; 8:1
(m), 619 (m), 590 (w), 563 (w), 542 (w) cm–1. HRMS (ESI): calcd.
for C22H19F3N2ONa 407.1342; found 407.1355.
X-Ray Crystal Structure Analysis of 4q: Formula C22H19F3N2O, M
= 384.39, yellow crystal 0.30ϫ0.20ϫ0.15 mm, a = 8.9391(2), b =
10.4078(3), c = 11.0426(4) Å, α = 68.075(1), β = 86.510(1), γ =
79.086(2)°, V = 935.77(5) Å3 , ρca lcd . = 1.364 g cm– 3, µ =
0.105 mm–1, empirical absorption correction (0.969 Յ T Յ 0.984),
¯
Z = 2, triclinic, space group P1 (No. 2), λ = 0.71073 Å, T = 223 K,
ω and φ scans, 9593 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ]
= 0.67 Å–1, 4479 independent (Rint = 0.042) and 2473 observed
ratio. IR (KBr): ν = 3424 (w), 3275 (w), 3098 (w), 3061 (w), 3032
˜
(w), 2976 (w), 2953 (w), 2941 (w), 2901 (w), 1647 (s), 1612 (m),
1555 (s), 1481 (s), 1464 (s), 1427 (s), 1379 (w), 1350 (s), 1310 (s),
1273 (s), 1248 (s), 1215 (s), 1194 (s), 1173 (s), 1157 (s), 1109 (s),
1074 (s), 1034 (s), 1013 (s), 980 (m), 939 (s), 880 (m), 862 (m), 849
(m), 837 (m), 760 (s), 748 (s), 729 (s), 708 (s), 681 (s), 648 (m),
602 (m), 579 (w), 559 (w), 548 (w) cm–1. HRMS (ESI): calcd. for
C25H17F3N2OS2Na 505.0627; found 505.0625.
reflections [I Ն 2σ(I)], 254 refined parameters, R = 0.058, wR2
=
0.170, max. (min.) residual electron density: 0.20 (–0.25) eÅ–3, hy-
drogen atoms calculated and refined as riding atoms.
General Procedure for the Preparation of 4-Hydroxy-2H-pyrroles 8:
Polyphosphoric acid, prepared from 1.8 parts of P4O10 and 1 part
of 85% H3PO4 (by mass), and acyl anhydride (1:1 mixture by mass)
was added to the azadienone 4 (20 part of PPA/anhydride to 1 part
of azadienone, by mass) and the mixture was stirred for 10–15 min
at 80–90 °C. The reaction mixture was cooled down, diluted with
water and extracted with dichloromethane. The organic layer was
washed first with sat. NaHCO3 and then with water, dried with
MgSO4 and concentrated in vacuo. The residue was purified by
column chromatography.
5-(2,4-Dimethylphenyl)-6,6,6-trifluoro-2-(indolin-1-ylimino)hex-4-
en-3-one (4p): Obtained from keto phosphonate 7a according to
the general procedure. Chromatographic purification (Et2O/pen-
tane, 2:5) gave 0.160 g (0.41 mmol, 78%) of 4p as a yellow solid,
1
m.p. 139–140 °C (main isomer). H NMR (400 MHz, CDCl3): δ =
2.14 (s, 3 H, CH3), 2.20 (s, 3 H, CH3), 2.32 (s, 4.5 H, CH3), 2.36
(s, 3 H, CH3), 3.26–3.31 (m, 3 H, CH2), 4.19–4.30 (m, 3 H, CH2N),
6.85 (s, 0.5 H, Holef.), 7.48–7.67 (m, 10.5 H, Harom.), 7.93 (q, J =
1.4 Hz, 1 H, Holef.) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.3
(CH3), 19.7 (CH3), 21.3 (CH3), 28.1 (CH2), 52.8 (CH2), 108.4 (q,
J = 1.7 Hz), 111.4 (CHarom.), 122.8 (q, J = 261.8 Hz, CF3), 123.3
(CHarom.), 125.1 (CHarom.), 126.1 (CHarom.), 127.6, 127.8 (CHarom.),
128.3 (CHarom.), 128.7 (CHarom.), 129.6 (CHarom.), 130.7 (CHarom.),
137.1, 138.3, 140.9, 148.2, 187.9 (CO) ppm. 19F NMR (282 MHz,
CDCl3): δ = –68.0 [major (E)], –61.3 [minor (Z)] (CF3) ppm; 2:1
4-Acetoxy-5-methyl-2-phenyl-2-(trifluoromethyl)-2H-pyrrole (8a):
Obtained from azadienone 4a according to the general procedure
(Ac2O as the anhydride component). Chromatographic purification
(Et2O/pentane, 2:5) gave 0.093 g (0.33 mmol, 52 %) of 8a as a
1
colourless solid, m.p. 87–88 °C. H NMR (600 MHz, CDCl3): δ =
2.28 (s, 3 H, CH3CO), 2.32 (s, 3 H, CH3), 7.36–7.37 (m, 3 H), 7.57
(s, 1 H, Hpyrrole), 7.69–7.70 (m, 2 H) ppm. 13C NMR (150 MHz,
CDCl3): δ = 16.0 (CH3), 21.0 (CH3CO), 82.8 (q, J = 27.0 H z,
C
quat.), 124.1 (q, J = 281.0 Hz, CF 3), 128.1 (CH pyrrole), 128.2
ratio. IR (KBr): ν = 3439 (w), 3020 (w), 2922 (w), 2855 (w), 1661
˜
(CHarom.), 128.9 (CHarom.), 129.2 (CHarom.), 133.1 (Cipso), 148.0
(C=N), 166.9 (COO), 173.3 (OC=C) ppm. 19F NMR (282 MHz,
(m), 1628 (w), 1611 (m), 1553 (s), 1483 (s), 1460 (m), 1441 (w),
1369 (m), 1331 (w), 1308 (m), 1290 (m), 1267 (s), 1234 (s), 1211 (s),
1178 (m), 1167 (s), 1124 (s), 1092 (m), 1070 (m), 1030 (m), 1013
(w), 970 (w), 908 (w), 876 (w), 835 (w), 766 (w), 754 (m), 706 (w),
644 (w), 594 (w), 500 (w) cm –1 . H R M S (E SI ): ca lcd . fo r
C22H 21F 3N 2ON a 409.1498; found 409.1497. C22H 21F 3N 2O
(386.41): calcd. C 68.38, H 5.48, N 7.25; found C 68.25, H 5.36, N
7.22.
CDCl ): δ = –73.6 (CF ) ppm. IR (KBr): ν = 3528 (w), 3414 (w),
˜
3
3
3121 (m), 3076 (w), 3044 (w), 2965 (m), 2930 (m), 2855 (w), 1782
(s), 1751 (m), 1643 (m), 1576 (s), 1493 (m), 1452 (m), 1433 (m),
1389 (m), 1371 (m), 1350 (s), 1271 (s), 1252 (s), 1186 (s), 1151 (s),
1067 (s), 1030 (s), 1011 (s), 976 (s), 945 (s), 918 (m), 878 (s), 854
(s), 841 (m), 818 (m), 766 (s), 723 (s), 700 (m), 683 (m), 654
(w) cm–1. HRMS (ESI): calcd. for C14H12F3NO2N a 306.0718;
found 306.0716. MS (EI): m/z = 283 [M]+, 241, 212, 198, 172, 151,
131, 102, 76, 51. C14H12F3NO2 (283.25): calcd. C 59.37, H 4.27, N
4.95; found C 59.77, H 4.07, N 4.94.
2-(Indolin-1-ylimino)-7-phenyl-5-(trifluoromethyl)hepta-4,6-dien-3-
one (4q): Obtained from keto phosphonate 7a according to the ge-
neral procedure. Chromatographic purification (Et2O/pentane, 1:1)
gave 0.252 g (0.66 mmol, 82 %) of 4q as a red solid, m.p. 138–
X-Ray Crystal Structure Analysis of 8a: Formula C14H12F3NO2, M
= 283.25, colourless crystal 0.35ϫ0.30ϫ0.10 mm, a = 10.5201(2),
b = 12.7088(2), c = 10.6746(2) Å , β = 113. 200(1)°, V =
1311.76(4) Å3, ρcalcd. = 1.434 gcm–3, µ = 0.124 mm–1, empirical ab-
sorption correction (0.958 Յ T Յ 0.988), Z = 4, monoclinic, space
group P21/n (No. 14), λ = 0.71073 Å, T = 198 K, ω and φ scans,
8974 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ] = 0.67 Å–1, 3174
independent (Rint = 0.026) and 2473 observed reflections [I Ն
2σ(I)], 183 refined parameters, R = 0.045, wR2 = 0.124, max. (min.)
residual electron density: 0.28 (–0.28) eÅ–3, hydrogen atoms calcu-
lated and refined as riding atoms.
1
139 °C. H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3 H, CH3), 3.28
(t, J = 8.2 Hz, 2 H, CH2), 4.26 (t, J = 8.2 Hz, 2 H, CH2N), 7.01
(dt, J = 7.4, 1.0 Hz, 1 H, Harom.), 7.10 (qd, J = 17.1, 1.9 Hz, 1 H,
Holef.), 7.18–7.20 (m, 2 H, Harom.), 7.25–7.38 (m, 4 H, Harom.), 7.54–
7.56 (m, 2 H, Harom.), 7.84 (s, 1 H, Holef.), 8.09 (q, J = 17.1 Hz, 1
H, Holef.) ppm. 13C NMR (100 MHz, CDCl3): δ = 12.6 (CH3), 28.1
(CH2), 53.0 (CH2), 111.5 (CHarom.), 119.2 (CHolef.), 123.28 (q, J =
276.4 Hz, CF3), 123.34 (CHarom.), 123.9 (q, J = 6.1 Hz, CHolef.),
125.0 (CHarom.), 127.5 (CHarom.), 127.7, 128.3 (CHarom.), 128.7
(CHarom.), 129.0 (CHarom.), 135.9 (q, J = 28.4 Hz, CCF3), 136.5,
137.2 (q, J = 1.6 Hz, CHolef.), 141.8 (C=N), 148.2 (C-N), 188.6
(CO) ppm. 19F NMR (282 MHz, CDCl3): δ = –63.7 (E isomer) 4-Acetoxy-2-(4-fluorophenyl)-5-methyl-2-(trifluoromethyl)-2H-
(CF ) ppm. IR (KBr): ν = 3435 (w), 3219 (w), 3105 (w), 3082 (w),
pyrrole (8b): Obtained from azadienone 4b according to the general
procedure (Ac2O as the anhydride component). Chromatographic
purification (Et2O/pentane, 2:5) gave 0.037 g (0.12 mmol, 46%) of
˜
3
3057 (w), 3040 (w), 2963 (w), 2920 (w), 2855 (w), 1641 (s), 1614
(m), 1587 (m), 1555 (s), 1481 (s), 1450 (m), 1379 (m), 1366 (m),
1331 (w), 1313 (s), 1290 (s), 1256 (s), 1227 (s), 1209 (s), 1169 (s),
1
8b as a yellowish oil. H NMR (400 MHz, CDCl3): δ = 2.30 (s, 3
Eur. J. Org. Chem. 2008, 3656–3667
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3663

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
FULL PAPER
H, CH3CO), 2.33 (s, 3 H, CH3), 7.06 (t, J = 8.7 Hz, 2 H), 7.55 (s,
1 H, Hpyrrole), 7.68 (dd, J = 8.7, 5.4 Hz, 1 H) ppm. 13C N MR
(100 MHz, CDCl3): δ = 16.0 (CH3), 21.0 (CH3CO), 82.2 (q, J =
27.8 Hz, Cquat.), 115.2 (d, J = 21.6 Hz, CHarom), 124.0 (q, J =
(400 MHz, CDCl3): δ = 2.28 (s, 3 H, CH3CO), 2.29 (s, 3 H, CH3),
2.95 (s, 6 H, NCH3), 6.72 (d, J = 7.8 Hz, 2 H, o-Harom.), 7.54 (d, J
= 7.8 Hz, 2 H, m-Harom), 7.55 (s, 1 H, Hpyrrole) ppm. 13C NMR
(100 MHz, CDCl3): δ = 15.9 (CH3), 21.1 (CH3CO), 40.4 (NCH3),
284.0 Hz, CF3), 127.9 (CHarom), 128.8 (d, J = 3.0 Hz, Cipso), 131.0 82.3 (q, J = 27.6 H z, Cquat.), 112.0 (o-CH arom), 124.4 (q, J =
(d, J = 8.1 Hz, CHarom), 148.1 (C=N), 163.0 (d, J = 248.5 Hz, C-F), 283.4 Hz, CF3), 128.5, 130.0, 147.8 (C=N), 150.4 (Carom-N), 166.9
166.9 (COO), 173.6 (OC=C) ppm. 19F NMR (282 MHz, CDCl3): δ (COO), 172.6 (OC=C) ppm. 19F NMR (282 MHz, CDCl3): δ =
= –113.1 (C-F), –73.8 (CF ) ppm. IR (film): ν = 3397 (w), 3351
–74.1 (CF ) ppm. IR (KBr): ν = 3429 (w), 3146 (w), 3126 (w), 3099
˜
˜
3
3
(w), 3382 (w), 3005 (w), 2961 (w), 2926 (m), 2851 (w), 1786 (s),
(w), 3082 (w), 2991 (w), 2936 (m), 2891 (m), 2856 (m), 2810 (m),
1647 (m), 1603 (m), 1578 (s), 1510 (s), 1437 (m), 1389 (m), 1373 1782 (s), 1645 (s), 1614 (s), 1576 (s), 1524 (s), 1485 (m), 1458 (m),
(m), 1350 (m), 1275 (m), 1252 (m), 1228 (m), 1190 (s), 1161 (s),
1084 (w), 1036 (m), 1013 (m), 980 (w), 947 (w), 935 (w), 880 (w),
735 (m), 710 (w), 665 (w) cm–1. H R M S (E SI ): ca lcd . fo r
1437 (s), 1394 (s), 1379 (s), 1352 (s), 1327 (m), 1277 (s), 1248 (s),
1215 (s), 1192 (s), 1173 (s), 1155 (s), 1128 (s), 1092 (s), 1063 (m),
1036 (m), 1015 (s), 978 (s), 949 (m), 941 (m), 926 (m), 883 (m), 847
(m), 818 (m), 808 (m), 754 (w), 735 (m), 710 (m), 681 (w), 663
(w) cm–1. HRMS (ESI): calcd. for C16H17F3N2O2Na 349.1134;
found 349.1134. MS (EI): m/z = 326 [M]+, 284, 255, 242, 215, 199,
174, 144, 129. C16H17F3N2O2 (326.31): calcd. C 58.89, H 5.25, N
8.58; found C 59.31, H 4.45, N 8.47.
C
14H11F4NO2Na 324.0618; found 324.0621. MS (EI): m/z = 301
[M]+, 259, 190, 169, 149, 120, 83. C14H11F4NO2 (301.24): calcd. C
55.82, H 3.68, N 4.65; found C 55.92, H 3.85, N 4.58.
4-Acetoxy-2-(4-chlorophenyl)-5-methyl-2-(trifluoromethyl)-2H-
pyrrole (8c): Obtained from azadienone 4c according to the general
procedure (Ac2O as the anhydride component). Chromatographic
purification (Et2O/pentane, 2:5) gave 0.051 g (0.16 mmol, 63%) of
8c as a yellowish oil. 1H NMR (400 MHz, CDCl3): δ = 2.29 (s, 3
H, CH3CO), 2.32 (s, 3 H, CH3), 7.35 (d, J = 8.8 Hz, 2 H), 7.53 (s,
1 H, Hpyrrole), 7.63 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 16.0 (CH3), 21.1 (CH3CO), 82.3 (q, J = 28.5 H z,
Cquat.), 123.9 (q, J = 283.4 H z, CF 3), 127.6 (CH arom.), 128.4
(CHarom.), 130.5 (CHarom.), 131.6 and 135.1 (Cipso and CCl), 148.2
(C=N), 166.8 (COO), 173.7 (OC=C) ppm. 19F NMR (282 MHz,
4-Acetoxy-2-(3-fluorophenyl)-5-methyl-2-(trifluoromethyl)-2H-
pyrrole (8f): Obtained from azadienone 4f according to the general
procedure (Ac2O as the anhydride component). Chromatographic
purification (acetone/pentane, 1:8) gave 0.062 g (0.21 mmol, 53%)
1
of 8f as a yellowish oil. H NMR (400 MHz, CDCl3): δ = 2.29 (s,
3 H, CH3CO), 2.33 (s, 3 H, CH3), 7.07 (ddt, J = 8.3, 2.4, 1.2 Hz,
1 H ), 7.31–7.36 (m, 1 H ), 7.43–7.46 (m, 2 H ), 7.51 (s, 1 H ,
H
pyrrole) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.0 (CH3), 21.0
(CH3CO), 82.4 (q, J = 27.1 Hz, Cquat.), 115.9 (d, J = 21.0 Hz, CH),
116.6 (d, J = 23.7 H z), 123.9 (q, J = 283.4 H z, CF 3), 124.8
(CHarom.), 127.5 (CHpyrrole), 129.6 (d, J = 8.1 Hz, CHarom.), 135.2
(d, J = 7.9 Hz, Cipso), 148.3 (C=N), 162.4 (J = 246.3 Hz, C-F),
166.8 (COO), 173.8 (OC=C) ppm. 19F NMR (282 MHz, CDCl3):
CDCl ): δ = –73.7 (CF ) ppm. IR (film): ν = 3412 (w), 3150 (w),
˜
3
3
3136 (w), 2959 (w), 2926 (m), 2853 (w), 1902 (w), 1786 (s), 1645
(m), 1595 (w), 1577 (s), 1491 (s), 1433 (m), 1398 (m), 1389 (m),
1373 (m), 1350 (m), 1275 (m), 1248 (m), 1190 (m), 1153 (m), 1094
(m), 1038 (m), 1016 (m), 980 (m), 945 (m), 937 (m), 878 (m), 847
(w), 827 (m), 816 (m), 739 (m), 723 (w), 673 (w) cm–1. HR MS
(ESI): calcd. for C14H11ClF3NO2Na 340.0323; found 340.0330. MS
(EI): m/z = 317 [M]+, 275, 246, 232, 206, 199, 185, 169, 136, 101,
75. C14H11ClF3NO2 (317.69): calcd. C 52.93, H 3.49, N 4.41; found
C 53.31, H 3.55, N 4.17.
δ = –112.9 (C-F), –73.5 (CF ) ppm. IR (film): ν = 3412 (w), 3152
˜
3
(w), 3136 (w), 3082 (w), 3007 (w), 2964 (w), 2930 (w), 2853 (w),
1786 (s), 1645 (m), 1614 (m), 1587 (s), 1578 (s), 1489 (m), 1443 (s),
1389 (m), 1373 (m), 1350 (m), 1267 (s), 1261 (s), 1229 (s), 1182 (s),
1155 (s), 1111 (m), 1074 (m), 1038 (m), 1011 (m), 974 (m), 880 (m),
860 (m), 833 (m), 787 (m), 730 (s), 690 (w), 677 (w), 665 (w), 588
(w) cm–1. HRMS (ESI): calcd. for C14H11F4NO2N a 324.0618;
found 324.0618. MS (EI): m/z = 301 [M]+, 259, 230, 190, 169, 149,
120, 75. C14H11F4NO2 (301.24): calcd. C 55.82, H 3.68, N 4.65;
found C 55.89, H 3.77, N 4.69.
4-Acetoxy-2-(4-bromophenyl)-5-methyl-2-(trifluoromethyl)-2H-
pyrrole (8d): Obtained from azadienone 4d according to the general
procedure (Ac2O as the anhydride component). Chromatographic
purification (Et2O/pentane, 2:5) gave 0.051 g (0.14 mmol, 36%) of
1
8d as a yellowish oil. H NMR (300 MHz, CDCl3): δ = 2.29 (s, 3
4-Acetoxy-5-methyl-2-(trifluoromethyl)-2-[3-(trifluoromethyl)-
phenyl]-2H-pyrrole (8g): Obtained from azadienone 4g according to
the general procedure (Ac2O as the anhydride component). Chro-
matographic purification (Et2O/pentane, 1:1) gave 0.070 g
(0.20 mmol, 56%) of 8g as a yellowish oil. 1H NMR (400 MHz,
CDCl3): δ = 2.31 (s, 3 H, CH3CO), 2.35 (s, 3 H, CH3), 7.51 (t, J =
7.9 Hz, 1 H), 7.58 (s, 1 H, Hpyrrole), 7.64 (d, J = 7.9 Hz, 1 H), 7.90
(d, J = 7.9 H z, 1 H ), 7.97 (s, 1 H) ppm. 13C N MR (100 MH z,
CDCl3): δ = 16.0 (CH3), 21.1 (CH3CO), 82.4 (q, J = 27.6 H z,
Cquat.), 123.8 (q, J = 279.3 Hz, CF3), 123.9 (q, J = 276.5 Hz, CF3),
125.8 (q, J = 3.8 Hz), 125.9 (q, J = 3.0 Hz), 127.2 (Cpyrrole), 128.7
(CHarom.), 130.8 (q, J = 32.5 Hz, CCF3), 132.5 (CHarom), 134.1
(Cipso), 148.5 (C=N), 166.8 (COO), 174.1 (OC=C) ppm. 19F NMR
(282 MHz, CDCl3): δ = –73.5 (CF3), –63.1 (CF3) ppm. IR (film):
H, CH3CO), 2.32 (s, 3 H, CH3), 7.48–7.59 (m, 5 H, includes singlet
from Hpyrrole) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.0 (CH3),
21.0 (CH3CO), 82.3 (q, J = 28.0 Hz, Cquat.), 123.3, 123.9 (q, J =
283.4 Hz, CF3), 127.5 (CHarom.), 130.8 (CHarom.), 131.4 (CHarom.),
131.8 and 132.1 (Cipso and CBr), 148.2 (C=N), 166.8 (COO), 173.7
(OC=C) ppm. 19F NMR (282 MHz, CDCl3): δ = –73.7 (CF3) ppm.
IR (film): ν = 3387 (w), 3150 (m), 3136 (m), 3103 (w), 3072 (w),
˜
3036 (w), 3005 (w), 2963 (m), 2927 (m), 2855 (w), 2793 (w), 1786
(s), 1645 (s), 1578 (s), 1489 (s), 1433 (m), 1398 (m), 1389 (m), 1373
(m), 1350 (m), 1273 (m), 1248 (s), 1193 (s), 1155 (s), 1086 (m), 1076
(m), 1036 (m), 1013 (s), 980 (m), 937 (s), 880 (m), 847 (m), 815 (s),
734 (m), 702 (m), 673 (w), 663 (w) cm–1. MS (EI): m/z = 321, 319
[M ]+ , 292, 290, 278, 276, 252, 250, 199, 170, 151, 101, 51.
C14H11BrF3NO2 (362.14): calcd. C 46.43, H 3.06, N 3.87; found C
46.71, H 3.31, N 3.72.
ν = 3398 (w), 3154 (w), 3138 (w), 3084 (w), 2959 (m), 2930 (m),
˜
2856 (m), 1788 (s), 1647 (m), 1578 (s), 1491 (m), 1436 (s), 1389 (s),
1373 (s), 1333 (s), 1271 (s), 1248 (s), 1194 (s), 1142 (s), 1130 (s),
4-Acetoxy-2-[4-(dimethylamino)phenyl]-5-methyl-2-(trifluorometh-
yl)-2H-pyrrole (8e): Obtained from azadienone 4e according to the 1078 (s), 1038 (m), 1011 (m), 982 (m), 964 (m), 902 (w), 877 (m),
general procedure (Ac2O as the anhydride component). Chromato-
graphic purification (Et2O/pentane, 1:1) gave 0.040 g (0.12 mmol,
55 %) of 8e as a yellowish solid, m.p. 106–107 °C. 1H N M R
849 (w), 804 (s), 787 (m), 731 (s), 702 (m), 692 (m), 665 (w) cm–1
.
H R M S (ESI): calcd. for C15H 11F 6N O2N a 374.0586; found
374.0588. MS (EI): m/z = 351 [M]+, 309, 280, 266, 240, 219, 170,
3664
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3656–3667

2H-Pyrrole Derivatives from an Aza-Nazarov Reaction Cascade
151, 83. C15H11F6NO2 (351.24): calcd. C 51.29, H 3.16, N 3.99; (s, 3 H, CH3CO), 2.35 (s, 3 H, CH3),7.31–7.37 (m, 2 H, Harom),
found C 51.23, H 3.19, N 3.95.
7.51 (s, 1 H, Hthiophen), 7.53 (s, 1 H, Hpyrrole), 7.75–7.81 (m, 2 H,
Harom) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.9 (CH3), 21.0
(CH3CO), 81.2 (q, J = 29.3 Hz, Cquat.), 122.0 (CHarom.), 123.6 (q,
J = 283.4 H z, CF 3), 123.8 (CH arom.), 124.4 (CH arom.), 124.9
(CHarom.), 125.2 (CHthiophen), 127.7 (CHpyrrole), 134.4, 138.8, 139.8,
148.3 (C= N ), 166.7 (COO), 174.7 (OC= C) ppm. 19F N M R
4-Acetoxy-5-methyl-2-(2-thienyl)-2-(trifluoromethyl)-2H-pyrrole
(8h): Obtained from azadienone 4h according to the general pro-
cedure (Ac2O as the anhydride component). Chromatographic pu-
rification (Et2O/pentane, 1:1) gave 0.030 g (0.10 mmol, 42%) of 8h
as a yellowish solid, m.p. 83–83.5 °C. 1H NMR (400 MHz, CDCl3):
δ = 2.30 (s, 3 H, CH3CO), 2.32 (s, 3 H, CH3), 7.03 (dd, J = 5.16,
3.66 Hz, 1 H, 2-Hthiophen), 7.27 (dd, J = 3.67, 0.48 Hz, 1 H, 1-
Hthiophen), 7.33 (dd, J = 5.16, 1.20 Hz, 1 H, 3-Hthiophen), 7.47 (s, 1
H, Hpyrrole) ppm. 13C NMR (100 MHz, CDCl3): δ = 15.9 (CH3),
21.0 (CH3CO), 80.9 (q, J = 29.2 Hz, Cquat.), 123.6 (q, J = 283.1 Hz,
CF3), 126.5 (Cthiophen), 126.7 (Cthiophen), 127.9 (CHpyrrole), 128.3
(Cthiophen), 148.2 (C=N), 166.7 (COO), 174.3 (OC=C) ppm. 19F
(282 MHz, CDCl ): δ = –73.8 (CF ) ppm. IR (film): ν = 3148 (m),
˜
3
3
3132 (m), 3101 (w), 3061 (m), 3004 (w), 2961 (w), 2927 (m), 2856
(w), 1786 (s), 1643 (s), 1576 (s), 1460 (m), 1387 (m), 1371 (m), 1348
(m), 1275 (m), 1242 (m), 1184 (s), 1159 (s), 1096 (m), 1028 (m),
1011 (m), 974 (m), 899 (m), 876 (m), 831 (m), 804 (w), 748 (m),
725 (m), 712 (w), 665 (w) cm–1. MS (EI): m/z = 339 [M]+, 297, 282,
269, 228, 207, 158, 134, 114. C16H12F3NO2S (339.33): calcd. C
56.63, H 3.56, N 4.13; found C 56.68, H 3.75, N 3.98.
NMR (282 MHz, CDCl ): δ = –74.5 (CF ) ppm. IR (KBr): ν =
˜
3
3
3391 (w), 3140 (w), 2959 (m), 2928 (m), 1786 (s), 1643 (m), 1576
(s), 1433 (m), 1389 (w), 1373 (m), 1348 (m), 1277 (m), 1250 (w),
1184 (s), 1155 (s), 1097 (w), 1047 (w), 1026 (w), 1011 (m), 974 (m),
4-Acetoxy-2,5-diphenyl-2-(trifluoromethyl)-2H-pyrrole (8k): Ob-
tained from azadienone 4k according to the general procedure
(Ac2O as the anhydride component). Chromatographic purification
(Et2O/pentane, 1:5) gave 0.110 g (0.32 mmol, 79%) of 8k as a pale-
899 (m), 878 (w), 853 (m), 816 (w), 727 (m), 708 (m), 665 (w) cm–1
.
1
H R M S (ESI): calcd. for C12H 10F 3N O2SN a 312.0277; found
312.0277. MS (EI): m/z = 289 [M]+, 247, 232, 218, 202, 198, 178,
157, 137, 108, 84, 69. C12H10F3NO2S (289.27): calcd. C 49.82, H
3.48, N 4.84; found C 50.09, H 3.38, N 4.62.
yellow solid, m.p. 102–102.5 °C. H NMR (400 MHz, CDCl3): δ =
2.32 (s, 3 H, CH3CO), 7.37–7.41 (m, 3 H), 7.47–7.54 (m, 3 H), 7.78–
7.80 (m, 2 H), 7.80 (s, 1 H, CHpyrrole), 8.06–8.08 (m, 2 H) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 21.4 (CH3CO), 82.1 (q, J = 27.9 Hz,
quat.), 124.2 (q, J = 283.5 Hz, CF3), 128.3, 128.5, 128.6, 128.9,
C
X-Ray Crystal Structure Analysis of 8h: Formula C12H10F3NO2S,
M = 289.27, colourless crystal 0.25 ϫ 0.20 ϫ 0.10 mm, a =
10.3903(2), b = 12.7875(2), c = 10.4442(4) Å, β = 112.971(1)°, V
= 1277.64(4) Å3, ρcalcd. = 1.504 gcm–3, µ = 0.287 mm–1, empirical
absorption correction (0.932 Յ T Յ 0.972), Z = 4, monoclinic,
space group P21/n (No. 14), λ = 0.71073 Å, T = 198 K, ω and φ
129.3, 130.5, 131.4 (all CHarom.), 131.6 (Cipso), 133.4 (Cipso), 147.9
(C=N), 166.7 (COO), 170.8 (OC=C) ppm. 19F NMR (282 MHz,
CDCl ): δ = –73.3 (CF ) ppm. IR (KBr): ν = 3441 (w), 3420 (w),
˜
3
3
3132 (m), 3093 (w), 3072 (m), 3044 (w), 3030 (w), 2936 (w), 1967
(w), 1788 (s), 1624 (s), 1601 (m), 1578 (w), 1541 (s), 1427 (w), 1369
(s), 1358 (s), 1339 (m), 1313 (m), 1275 (s), 1254 (s), 1223 (m), 1192
(s), 1173 (s), 1128 (s), 1109 (s), 1070 (s), 1038 (m), 1015 (s), 974
(w), 943 (m), 918 (m), 874 (s), 851 (m), 826 (m), 787 (s), 760 (s),
727 (s), 708 (s), 698 (s), 660 (m), 621 (w), 611 (w), 598 (w), 586
(w) cm–1. HRMS (ESI): calcd. for C19H14F3NN aO2 368.0869;
found 368.0873. MS (EI): m/z = 345 [M]+, 303, 274, 234, 198, 151,
131, 102, 77. C19H14F3NO2 (345.32): calcd. C 66.09, H 4.09, N
4.06; found C 65.99, H 4.13, N 3.85.
scans, 7432 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ] = 0.66 Å–1
,
3050 independent (Rint = 0.042) and 1973 observed reflections [I Ն
2σ(I)], 174 refined parameters, R = 0.050, wR2 = 0.130, max. (min.)
residual electron density: 0.31 (–0.40) eÅ–3, hydrogen atoms calcu-
lated and refined as riding atoms.
4-Acetoxy-2-(benzo[b]furan-2-yl)-5-methyl-2-(trifluoromethyl)-2H-
pyrrole (8i): Obtained from azadienone 4i according to the general
procedure (Ac2O as the anhydride component). Chromatographic
purification (Et2O/pentane, 1:1) gave 0.040 g (0.12 mmol, 49%) of
X-Ray Crystal Structure Analysis of 8k: Formula C19H14F3NO2, M
= 345.31, colourless crystal 0.35ϫ0.25ϫ0.15 mm, a = 10.0337(3),
b = 10.5743(3), c = 15.6856(6) Å , β = 100. 191(1)°, V =
1637.98(9) Å3, ρcalcd. = 1.400 gcm–3, µ = 0.114 mm–1, empirical ab-
sorption correction (0.961 Յ T Յ 0.983), Z = 4, monoclinic, space
group P21/n (No. 14), λ = 0.71073 Å, T = 223 K, ω and φ scans,
10718 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ] = 0.66 Å–1, 3893
independent (Rint = 0.062) and 2340 observed reflections [I Ն
2σ(I)], 227 refined parameters, R = 0.051, wR2 = 0.154, max. (min.)
residual electron density: 0.22 (–0.25) eÅ–3, hydrogen atoms calcu-
lated and refined as riding atoms.
1
8i as a yellow oil. H NMR (400 MHz, CDCl3): δ = 2.31 (s, 3 H,
CH3CO), 2.36 (s, 3 H, CH3), 6.91 (d, J = 0.88 Hz, 1 H, Hfuran),
7.23 (dt, J = 7.5, 0.99 Hz, 1 H, Harom.), 7.31 (ddd, J = 8.4, 7.3,
1.4 Hz, 1 H, Harom.), 7.50 (dd, J = 8.3, 0.76 Hz, 1 H, Harom.), 7.53
(s, 1 H, Hpyrrole), 7.55 (dq, J = 7.7, 1.2, 0.66 Hz, 1 H, Harom.) ppm.
13C NMR (100 MHz, CDCl3): δ = 16.0 (CH3), 21.0 (CH3CO), 80.2
(q, J = 29.5 Hz, Cquat.), 107.3 (Cfuran), 111.5 (CH arom.), 121.3
(CHarom.), 123.1 (CHarom.), 123.3 (q, J = 287.3 Hz, CF3), 125.0
(CHarom.), 126.0 (CHpyrrole), 127.3, 148.3, 148.9 (C=N), 155.1,
166.7 (COO), 175.6 (OC=C) ppm. 19F NMR (282 MHz, CDCl3):
δ = –72.9 (CF ) ppm. IR (film): ν = 3383 (w), 3156 (m), 3130 (m),
˜
3
4-Acetoxy-2-phenyl-5-(2-thienyl)-2-(trifluoromethyl)-2H-pyrrole
(8l): Obtained from azadienone 4l according to the general pro-
cedure (Ac2O as the anhydride component). Chromatographic pu-
rification (acetone/pentane, 1:8) gave 0.015 g (0.04 mmol, 17%) of
8l as a yellowish solid, m.p. 136–137 °C. 1H N MR (400 MH z,
CDCl3): δ = 2.39 (s, 3 H, CH3CO), 7.18 (dd, J = 5.00, 3.8 Hz, 1
H), 7.36–7.41 (m, 3 H), 7.61 (dd, J = 5.0, 0.97 Hz, 1 H), 7.77 [m,3
H (includes singlet from CHpyrrol)], 8.07 (dd, J = 3.7, 0.88 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.4 (CH3CO), 82.4
(q, J = 28.2 Hz, Cquat-pyrrole), 124.1 (q, J = 283.6 Hz, CF3), 128.0
(Cthiophen), 128.3 (CHarom), 129.0, 129.2, 131.4, 131.5 (all CHarom.),
133.3 (Cipso), 134.2 (Cipso,thiophen), 146.8 (C=N), 164.6 (COO), 166.3
(OC=C) ppm. 19F NMR (282 MHz, CDCl3): δ = –73.2 (CF3) ppm.
3069 (m), 2957 (w), 2928 (m), 2855 (m), 1788 (s), 1643 (m), 1576
(s), 1475 (w), 1454 (m), 1389 (m), 1373 (m), 1348 (m), 1313 (w),
1267 (s), 1234 (m), 1188 (s), 1161 (s), 1038 (m), 1011 (m), 988 (m),
972 (m), 934 (w), 899 (m), 880 (m), 843 (w), 818 (m), 779 (w),
752 (s), 731 (m), 677 (w), 658 (w) cm–1. HRMS (ESI): calcd. for
C16H12F3NO3Na 346.0661; found 346.0659. MS (EI): m/z = 323
[M]+, 281, 266, 253, 212, 142, 63. C16H12F3NO3 (323.27): calcd. C
59.45, H 3.74, N 4.33; found C 59.91, H 4.07, N 4.15.
4-Acetoxy-2-(benzo[b]thiophen-2-yl)-5-methyl-2-(trifluoromethyl)-
2H-pyrrole (8j): Obtained from azadienone 4j according to the ge-
neral procedure (Ac2O as the anhydride component). Chromato-
graphic purification (Et2O/pentane, 1:1) gave 0.060 g (0.18 mmol,
37%) of 8j as a greenish oil. 1H NMR (400 MHz, CDCl3): δ = 2.30
IR (KBr): ν = 3433 (w), 3138 (w), 3071 (w), 2961 (w), 2920 (w),
˜
Eur. J. Org. Chem. 2008, 3656–3667
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3665

N. Ghavtadze, R. Fröhlich, E.-U. Würthwein
FULL PAPER
2851 (w), 1782 (s), 1624 (s), 1560 (s), 1508 (w), 1450 (w), 1433 (m),
1366 (m), 1269 (m), 1244 (s), 1188 (s), 1175 (s), 1157 (s), 1124 (m),
1107 (m), 1069 (m), 1011 (s), 941 (m), 918 (w), 878 (m), 854 (m),
(m), 1360 (m), 1333 (w), 1315 (w), 1277 (m), 1248 (m), 1234 (m),
1188 (s), 1165 (s), 1146 (s), 1103 (s), 1086 (m), 1055 (m), 1045 (m),
1013 (m), 997 (s), 970 (w), 945 (m), 903 (m), 878 (m), 854 (m), 839
(m), 829 (m), 814 (m), 770 (m), 745 (m), 727 (s), 671 (w), 600 (w),
588 (w) cm–1. H R M S (ESI): calcd. for C19H 12F 3N O2S2N a
430.0154; found 430.0161. MS (EI): m/z = 407 [M]+, 365, 336, 296,
268, 228, 207, 158, 134, 110. C19H12F3NO2S2 (407.43): calcd. C
56.01, H 2.97, N 3.44; found C 56.24, H 3.09, N 3.29.
824 (w), 775 (w), 762 (m), 733 (m), 719 (s), 700 (m), 598 (w) cm–1
.
H R M S (ESI): calcd. for C17H 12F 3N O2SN a 374.0438; found
374.0434. MS (EI): m/z = 351 [M]+, 309, 280, 259, 240, 212, 151,
110, 102, 77. C17H12F3NO2S (351.34): calcd. C 58.11, H 3.44, N
3.99; found C 58.02, H 3.69, N 3.76.
X-Ray Crystal Structure Analysis of 8l: Formula C17H12F3NO2S,
M = 351.34, colourless crystal 0.20 ϫ 0.15 ϫ 0.07 mm, a =
10.0875(3), b = 8.8012(2), c = 16.1726(5) Å, β = 94.209(1)°, V =
1573.92(7) Å3, ρcalcd. = 1.483 gcm–3, µ = 0.248 mm–1, empirical ab-
4-Benzoxy-5-methyl-2-phenyl-2-(trifluoromethyl)-2H-pyrrole (8o):
Obtained from azadienone 4a according to the general procedure
(Bz2O as the anhydride component). Chromatographic purification
(Et2O/pentane, 1:2) gave 0.103 g (0.30 mmol, 53%) of 8o as a yel-
1
sorption correction (0.952 Յ T Յ 0.983), Z = 4, monoclinic, space low solid, m.p. 123.5–124.5 °C. H NMR (400 MHz, CDCl3): δ =
group P21/c (No. 14), λ = 0.71073 Å, T = 223 K, ω and φ scans,
10898 reflections collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ] = 0.66 Å–1, 3673
independent (Rint = 0.060) and 1727 observed reflections [I Ն
2σ(I)], 231 refined parameters, R = 0.052, wR2 = 0.123, max. (min.)
residual electron density: 0.21 (–0.28) eÅ–3, hydrogen atoms calcu-
lated and refined as riding atoms, disorder in the thiophene ring
was refined with split positions.
2.46 (s, 3 H, CH3), 7.37–7.41 (m, 3 H), 7.51–7.55 (m, 2 H), 7.65–
7.69 (m, 1 H), 7.74–7.76 (m, 2 H), 7.75 (s, 1 H, CHpyrrole), 8.12–
8.14 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.2 (CH3),
82.9 (q, J = 27.7 Hz, Cquat.), 124.1 (q, J = 283.3 Hz, CF3), 128.3,
128.5, 128.9, 129.0, 129.2, 130.9, 133.0, 134.3, 148.2 (C=N), 162.8
(COO), 173.6 (OC=C) ppm. 19F NMR (282 MHz, CDCl3): δ =
–73.5 (CF ) ppm. IR (KBr): ν = 3472 (w), 3387 (w), 3346 (w), 3198
˜
3
(w), 3152 (w), 3099 (w), 3072 (w), 3032 (w), 2995 (w), 2957 (w),
2920 (w), 2851 (w), 1881 (w), 1744 (s), 1705 (m), 1639 (m), 1601
(m), 1574 (s), 1499 (m), 1493 (m), 1450 (s), 1435 (m), 1389 (m),
1350 (m), 1313 (m), 1269 (s), 1254 (s), 1194 (s), 1163 (s), 1155 (s),
1078 (m), 1047 (s), 1020 (s), 1001 (m), 976 (m), 943 (s), 910 (m),
854 (m), 843 (m), 822 (m), 800 (m), 760 (m), 725 (m), 710 (s), 694
(s), 685 (s), 652 (w), 634 (w), 617 (w), 581 (w) cm–1. HRMS (ESI):
calcd. for C19H14F3NO2Na 368.0869; found 368.0863. MS (EI):
m/z = 345 [M]+, 212, 199, 192, 169, 151, 105, 77, 51. C19H14F3NO2
(345.32): calcd. C 66.09, H 4.09, N 4.06; found C 66.30, H 4.06, N
4.02.
4-Acetoxy-2-(benzo[b]furan-2-yl)-5-(2-thienyl)-2-(trifluoromethyl)-
2H-pyrrole (8m): Obtained from azadienone 4m according to the
general procedure (Ac2O as the anhydride component). Chromato-
graphic purification (Et2O/pentane, 1:2) gave 0.040 g (0.10 mmol,
53 %) of 8m as a yellowish solid, m.p. 128–129 °C. 1H N M R
(400 M H z, CD Cl3): δ = 2.41 (s, 3 H , CH 3CO), 6.96 (d, J =
0.86 Hz), 7.18–7.23 (m, 2 H), 7.31 (ddd, J = 8.4, 7.3, 1.4 Hz, 1 H),
7.50–7.55 (m, 2 H), 7.62 (dd, J = 5.0, 1.1 Hz, 1 H), 7.72 (s, 1 H,
CH p yr r o le), 8.04 (dd, J = 3.8, 1.1 H z, 1 H ) ppm. 13C N M R
(100 M H z, CD Cl3): δ = 21.4 (CH 3CO), 80.0 (q, J = 29.7 H z,
Cquat.), 107.4, 111.5, 121.4, 123.1 (all CHarom.), 123.4 (q, J =
284.4 H z, CF 3), 125.0, 127.4, 127.6, 128.1, 131.5, 131.7 (all X-Ray Crystal Structure Analysis of 8o: Formula C19H14F3NO2, M
CH a r o m.), 134.0 (Cipso, t h io p h en ), 147.8 (C= N ), 148.5, 155.0 = 345.31, yellow crystal 0.50ϫ0.25ϫ0.07 mm, a = 16.9766(3), b =
(Cipso, fu r a n ), 166.2 (COO), 166.5 (OC= C) pp m. 19F N M R
8.5769(1), c = 22.6929(5) Å, V = 3304.24(10) Å3, ρca lcd .
=
(282 MHz, CDCl ): δ = –72.6 (CF ) ppm. IR (KBr): ν = 3449 (w),
1.388 g cm–3, µ = 0.113 mm–1, empirical absorption correction
(0.946 Յ T Յ 0.994), Z = 8, orthorhombic, space group Pbca (No.
61), λ = 0.71073 Å, T = 223 K, ω and φ scans, 19466 reflections
˜
3
3
3152 (w), 3136 (w), 3105 (m), 3094 (m), 2949 (w), 1792 (s), 1776
(s), 1622 (s), 1578 (m), 1557 (s), 1541 (s), 1504 (m), 1474 (w), 1454
(s), 1429 (s), 1391 (m), 1369 (s), 1360 (s), 1350 (m), 1315 (m), 1286 collected (Ϯh, Ϯk, Ϯl), [(sin θ)/λ] = 0.66 Å–1, 3918 independent
(m), 1271 (m), 1258 (m), 1240 (m), 1190 (s), 1159 (s), 1103 (s), 1053 (Rint = 0.076) and 2275 observed reflections [I Ն 2σ(I)], 227 refined
(m), 1013 (s), 1005 (s), 978 (m), 943 (m), 903 (m), 878 (m), 854 (m),
839 (m), 820 (m), 783 (w), 770 (m), 756 (m), 745 (m), 737 (s), 727
parameters, R = 0.049, wR2 = 0.125, max. (min.) residual electron
density: 0.16 (–0.22) eÅ–3, hydrogen atoms calculated and refined
as riding atoms.
(s), 692 (w), 671 (w), 652 (w), 601 (m), 584 (m), 548 (w) cm–1
.
H R M S (ESI): calcd. for C19H 12F 3N O3SN a 414.0382; found
414.0379. MS (EI): m/z = 391 [M]+, 349, 321, 280, 252, 212, 142,
118. C19H12F3NO3S (391.36): calcd. C 58.31, H 3.09, N 3.58; found
C 58.16, H 3.31, N 3.65.
4-Acetoxy-2-(2,4-dimethylphenyl)-5-methyl-2-(trifluoromethyl)-2H-
pyrrole (8p): Obtained from azadienone 4p according to the general
procedure. Chromatographic purification (Et2O/pentane, 1:3) gave
0.023 g (0.07 mmol, 30%) of 8p as a yellow solid, m.p. 69–70 °C.
4-Acetoxy-2-(benzo[b]thiophen-2-yl)-5-(2-thienyl)-2-(trifluorometh- 1H NMR (400 MHz, CDCl3): δ = 2.28 (overlapped s, 9 H, CH3),
yl)-2H-pyrrole (8n): Obtained from azadienone 4n according to the 2.64 (s, 3 H, CH3), 7.00 (d, J = 7.9 Hz, 1 H), 7.02 (s, 1 H), 7.70 (d,
general procedure (Ac2O as the anhydride component). Chromato-
graphic purification (Et2O/pentane, 1:5) gave 0.088 g (0.22 mmol,
61 %) of 8n as a pale-yellow solid, m.p. 142–143 °C. 1H N MR
(400 MHz, CDCl3): δ = 2.40 (s, 3 H, CH3CO), 7.19 (dd, J = 5.0,
3.8 Hz, 1 H), 7.32–7.35 (m, 2 H), 7.56 (s, 1 H), 7.63 (dd, J = 5.0,
1.0 Hz, 1 H), 7.71 (s, 1 H, CHpyrrole), 7.76–7.81 (m, 2 H), 8.04 (dd,
J = 7.9 Hz, 1 H), 7.77 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 15.9 (CH3), 20.8 (CH3), 21.1 (CH3), 23.6 (q, J = 2.30 Hz, CH3),
83.8 (q, J = 27.6 Hz, Cquat.), 124.75 (q, J = 283.8 Hz, CF3), 126.3,
128.6, 128.7, 132.0, 133.6, 138.2, 138.7, 148.0 (C=N), 167.0 (COO),
172.0 (OC= C) ppm. 19F N M R (282 M H z, CD Cl3): δ = –72.8
(CF ) ppm. IR (film): ν = 3433 (w), 3209 (w), 3152 (m), 3030 (w),
˜
3
J = 3.8, 1.0 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.4 3015 (w), 2976 (m), 2932 (m), 2862 (w), 1778 (s), 1647 (s), 1612
(CH 3CO), 81.0 (q, J = 29.6 H z, Cquat.), 122.3, 123.7 (q, J =
284.3 Hz, CF3), 123.8, 124.4, 124.8, 125.1, 128.0, 129.3, 131.5,
(m), 1580 (s), 1501 (m), 1448 (m), 1437 (m), 1387 (m), 1373 (m),
1352 (m), 1302 (w), 1269 (s), 1240 (s), 1207 (s), 1171 (s), 1153 (s),
131.7 (all CHarom), 133.9, 135.0, 138.9, 139.9, 147.1 (C=N), 165.7 1128 (m), 1082 (m), 1040 (m), 1016 (m), 978 (m), 947 (m), 912 (m),
(OC=C), 166.3 (COO) ppm. 19F NMR (282 MHz, CDCl3): δ =
885 (m), 839 (w), 813 (m), 737 (m), 712 (m), 681 (w), 598 (w),
–73.5 (CF ) ppm. IR (KBr): ν = 3435 (w), 3169 (w), 3134 (w), 3105 560 (w) cm–1. HRMS (ESI): calcd. for C16H16F3NO2Na 334.1025;
˜
3
(w), 3084 (w), 3067 (w), 3034 (w), 2924 (w), 2853 (w), 1774 (s),
1620 (s), 1557 (s), 1504 (m), 1460 (w), 1433 (m), 1389 (w), 1367
found 334.1029. C16H16F3NO2 (311.30): calcd. C 61.73, H 5.18, N
4.50; found C 61.88, H 5.24, N 4.33.
3666
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 3656–3667

2H-Pyrrole Derivatives from an Aza-Nazarov Reaction Cascade
Miyata, T. Yamazaki, Chem. Pharm. Bull. 1983, 31, 476–481;
d) K. Matoba, T. Terada, M. Sugiuara, T. Yamazaki, Heterocy-
cles 1987, 26, 55–58; e) A. Aftfah, M. Y. Abu-Shuheil, J. Hill,
Tetrahedron 1990, 46, 6483–6500; f) D. A. Klumpp, Y. Zhang,
M. J. O’Connor, P. M. Estevens, L. S. Almeida, Org. Lett. 2007,
9, 3085–3088.
J. Dieker, R. Froehlich, E.-U. Würthwein, Eur. J. Org. Chem.
2006, 5339–5356.
N. Ghavtadze, Ph. D. Thesis, University Münster, in prepara-
4-Acetoxy-5-methyl-2-styryl-2-(trifluoromethyl)-2H-pyrrole (8q):
Obtained from azadienone 4q according to the general procedure
(Ac2O as the anhydride component). Chromatographic purification
(Et2O/pentane, 1:1) gave 0.017 g (0.06 mmol, 19 %) of 8q as a
1
brown viscous oil. H NMR (400 MHz, CDCl3): δ = 2.31 (s, 3 H,
CH3CO), 2.32 (s, 3 H, CH3), 6.51 (d, J = 16.1 Hz, 1 H, Holef.), 6.80
(d, J = 16.1 Hz, 1 H, Holef.), 7.27–7.34 (m, 4 H), 7.38–7.40 (m, 2
H ) ppm. 13C N M R (100 M H z, CD Cl3): δ = 16.1 (CH 3), 21.1
(CH3CO), 82.1 (q, J = 27.7 Hz, Cquat.), 119.7 (Colef.), 124.1 (q, J =
283.2 Hz, CF3), 126.8 (CH), 127.1 (CHpyrrole), 128.5 (CH), 128.6,
134.3 (Colef.), 135.8 (Cipso), 148.0 (C=N ), 166.9 (COO), 173.6
(OC=C) ppm. 19F NMR (282 MHz, CDCl3): δ = –73.8 (CF3) ppm.
[3]
[4]
[5]
tion, and unpublished results.
a) M. P. Sammes, Chem. Heterocycl. Compd. 1990, 48, 549–
728; b) K. Burger, W. D. Roth, K. Neumayer, Chem. Ber. 1976,
109, 1984–1990; c) F. Funke, M. Duetsch, F. Stein, M. Nolte-
meyer, A. de Meijere, Chem. Ber. 1994, 127, 911–920; d) P. J.
Campos, D. Sampedro, M. A. Rodríguez, J. Org. Chem. 2003,
68, 4674–4683; e) P. J. Campos, M. Caro, S. Lopez-Sola, D.
Sampedro, M. A. Rodríguez, J. Organomet. Chem. 2006, 691,
1075–1080; f) D. S. C. Black, A. B. Boscacci, Aust. J. Chem.
1976, 29, 2511–2524; g) U. Fischer, F. Schneider, Helv. Chim.
Acta 1983, 66, 971–988.
X-ray data sets were collected with a Nonius-Kappa CCD dif-
fractometer equipped with a rotating anode generator. Pro-
grams used: data collection: COLLECT (B. V. Nonius, 1998);
data reduction: Denzo-SMN (Z. Otwinowski, W. Minor, Meth-
ods Enzymol. 1997, 276, 307–326); absorption correction: SOR-
TAV (R. H. Blessing, Acta Crystallogr., Sect. A 1995, 51, 33–
37; R. H. Blessing, J. Appl. Crystallogr. 1997, 30, 421–426);
Denzo (Z. Otwinowski, D. Borek, W. Majewski, W. Minor,
Acta Crystallogr., Sect. A 2003, 59, 228–234); structure solu-
tion: SHELXS-97 (G. M. Sheldrick, Acta Crystallogr., Sect. A
1990, 46, 467–473); structure refinement: SHELXL-97 (G. M.
Sheldrick, University of Göttingen, 1997); graphics:
SCHAKAL (E. Keller, 1997). CCDC-675269 (for 8a), -675270
(for 8h), -675271 (for 8k), -675272 (for 8l), -675273 (for 8o),
-678848 (for 6a), -678849 (for 4a), -678850 (for 4q), and
-678851 (for 4e) contain the supplementary crystallographic
data. These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
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. Tom-
asi, 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. Hratch-
ian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E.
Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli,
J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Sal-
vador, 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. Ba-
boul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Lia-
shenko, 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,
Gaussian, Inc., Wallingford, CT, 2004. Details of the quantum
chemical calculations (Gaussian archive entries) may be ob-
tained from E.-U.W. upon request.
IR (KBr): ν = 3458 (w), 3344 (w), 3086 (w), 3063 (w), 3030 (w),
˜
2957 (m), 2926 (m), 2855 (m), 1786 (s), 1751 (m), 1701 (w), 1639
(m), 1573 (s), 1543 (w), 1497 (w), 1450 (w), 1433 (w), 1373 (m),
1348 (w), 1290 (m), 1263 (m), 1240 (m), 1184 (s), 1155 (s), 1074
(m), 1010 (m), 968 (s), 878 (m), 818 (m), 752 (s), 692 (s), 594 (w),
575 (w) cm–1. HRMS (ESI): calcd. for C16H14F3NNaO2 332.0869;
found 332.0871. MS (EI): m/z = 309 [M]+, 267, 252, 225, 198, 177,
146, 128, 91, 77, 57.
[6]
5-Methyl-2-phenyl-2-(trifluoromethyl)-2H-pyrrol-4-one (16)
Method A: The corresponding trifluoroacetyl ester was obtained
from azadienone 4a according to the general procedure (trifluoro-
acetic anhydride as the anhydride component) at 60–70 °C and then
hydrolyzed with aqueous KOH. Chromatographic purification
(Et2O/pentane, 1:1) gave 0.040 g (0.17 mmol, 30%) of 16 as a
brown oil.
Method B: Compound 16 was obtained from azadienone 4a ac-
cording to the general procedure (pivaloyl chloride as the anhydride
component). Chromatographic purification (Et2O/pentane, 1:10)
gave 0.030 g (0.12 mmol, 25%) of title compound. 1H NMR
(400 MHz, CDCl3): δ = 2.30 (s, 3 H, CH3), 2.80 (dq, J = 19.3,
0.83 Hz, 1 H, CH2), 3.17 (d, J = 19.3 Hz, 1 H, CH2), 7.40–7.43 (m,
3 H), 7.62–7.64 (m, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
13.7 (CH3), 41.8 (CH2), 75.3 (q, J = 27.5 Hz, Cquat-pyrrole), 124.8
(q, J = 282.8 Hz, CF3), 127.9, 128.6, 129.1 (all CHarom.), 136.6
(Cipso), 173.6 (C=N), 199.4 (C=O) ppm. 19F NMR (282 MHz,
[7]
CDCl ): δ = –77.4 (CF ) ppm. IR (film): ν = 3481 (w), 3387 (w),
˜
3
3
3074 (w), 3032 (w), 2980 (w), 2936 (w), 2918 (w), 2851 (w), 1751
(s), 1637 (w), 1499 (w), 1490 (w), 1450 (m), 1406 (m), 1381 (w),
1292 (m), 1261 (w), 1231 (w), 1175 (s), 1155 (s), 1124 (s), 1080 (m),
1057 (m), 1026 (w), 959 (m), 916 (w), 856 (w), 795 (m), 761 (m),
729 (w), 710 (m), 665 (m), 642 (w) cm–1. HRMS (ESI): calcd. for
C12H10F3NNaO 264.0607; found 264.0611. MS (EI): m/z = 241
[M]+, 198, 194, 172, 103, 96, 77, 69, 51, 42.
Acknowledgments
This work was supported by the NRW Graduate School of Chemis-
try, Münster, the Deutsche Forschungsgemeinschaft (DFG) and
the Fonds der Chemischen Industrie.
[1] a) K. Habermas, S. E. Denmark, Organic Reactions (Ed.: L. A
Paquette), Wiley, New York, 1994, vol. 45, pp. 1–158; b) M.
Harmata, Chemtracts – Org. Chem. 2004, 17, 416–435; c) H.
Pellisier, Tetrahedron 2005, 61, 6479–6517; d) M. A. Thius, Eur.
J. Org. Chem. 2005, 2193–2206; e) A. J. Frontier, C. Collison,
Tetrahedron 2005, 61, 7577–7606.
[2] a) M. A. Ciufolini, F. Roschangar, Tetrahedron 1997, 53,
11049–11060; b) K. Matoba, K. Itoh, T. Yamazaki, M. Nagata,
Chem. Pharm. Bull. 1981, 29, 2442–2450; c) K. Matoba, Y.
[8]
[9]
S. Grimme, J. Chem. Phys. 2003, 118, 9095.
G. Hart, D. R. Liljegren, K. T. Potts, J. Chem. Soc. 1961, 267–
268.
R. R. Neidlein, H. Feistauer, Helv. Chim. Acta 1996, 79, 895–
912.
[10]
Received: April 16, 2008
Published Online: June 13, 2008
Eur. J. Org. Chem. 2008, 3656–3667
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3667