Synthesis of pyrrole derivatives by palladium-catalyzed cyclization of γ,δ-unsaturated ketone o-pentafluorobenzoyloximes

Article abstract of DOI:10.1246/bcsj.75.1451

Various pyrrole derivatives are synthesized from γ,δ-unsaturated ketone O-pentafluorobenzoyloximes by treatment with catalytic amounts of Pd(PPh₃)₄ and triethylamine via alkylideneaminopalladium(II) intermediates generated by oxidative addition of the oximes to the Pd(0) complex.

Full text of DOI:10.1246/bcsj.75.1451

c. Jpn.
© 2002 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 75, 1451–1460 (2002) 1451
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Headline Articles
Synthesis of Pyrrole Derivatives by Palladium-Catalyzed Cyclization of
02
51
60
SJA8
09-2673
003
γ δ
, -Unsaturated Ketone O-Pentafluorobenzoyloximes
Synthesis of Pyrrole Derivatives
H. Tsutsui et al.
Hironori Tsutsui, Mitsuru Kitamura, and Koichi Narasaka*
Department of Chemistry, Graduate School of Science, The University of Tokyo,
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
02
(Received January 7, 2002)
02
.3
Various pyrrole derivatives are synthesized from γ,δ-unsaturated ketone O-pentafluorobenzoyloximes by treatment
with catalytic amounts of Pd(PPh3)4 and triethylamine via alkylideneaminopalladium(Ⅱ) intermediates generated by oxi-
dative addition of the oximes to the Pd(0) complex.
Though oxime derivatives generally undergo the Beckmann
rearrangement,1–3 there have been reports of some other types
of reactions which realize direct intramolecular cyclization on
the sp2 nitrogen atom of oximes with the N–O bond cleavage.
One of the typical examples is SN2-type reaction of oxime de-
rivatives with intramolecular hetero atoms and carbon nucleo-
philes, affording a variety of nitrogen-heterocycles such as
benzoisoxazoles,4 tetrahydropyrido[1,2-b]indazoles,5 1,2-ben-
bis(trifluoromethyl)benzophenone O-methylsulfonyloxime (1)
and Pd(PPh3)4 was examined firstly. After stirring a tetrahy-
drofuran (THF) solution of the above reagents at room temper-
ature for 20 min, bis[(4-trifluoromethyl)phenyl]methanimine
(3) was obtained as a crude product after quenching with pH 9
buffer; this was hydrolyzed to benzophenone 4 in 94% overall
yield with acidic treatment. The generation of diphenylmetha-
nimine 3 indicated that diarylmethylideneaminopalladium(Ⅱ)
species 2a was formed by oxidative addition of 1 to Pd(PPh3)4
(Eq. 1).
zothiazines,6
2,3,7,8-tetrahydrocyclopent[ij]isoquinolines,7
decahydroquinolines,8 quinolines,9 and dihydropyrroles.10 An-
other representative reaction is the formation of alkylideneam-
inyl radical species and their equivalents to synthesize phenan-
thridines,11 dihydropyrroles,12–14 and α-carbolines.15 Transi-
tion metal-mediated and -catalyzed cyclizations of oxime have
been also reported. Murahashi et al. reported that aminopalla-
dations occurs on γ,δ-unsaturated oximes with the action of an
equimolar amount of palladium(Ⅱ) complex; the successive
elimination of the hydroxy group gave pyridines.16 The palla-
dium(Ⅱ)-catalyzed cyclization of δ,ε-unsaturated oximes was
reported by Grigg et al. to afford cyclic nitrones.17 Recently,
we communicated a new type of synthesis of nitrogen-contain-
ing heterocycles by palladium(0)-catalyzed cyclization of ole-
finic ketone O-pentafluorobenzoyloximes via alkylideneami-
nopalladium species.18–20 This paper contains full accounts of
this catalytic pyrrole synthesis.
(1)
Trials to isolate the amino complex 2a have been unsuccess-
ful, so we monitored the reaction of 1 and Pd(PPh3)4 in CD2Cl2
by 31P NMR spectroscopy using 85% H3PO4 as an external
standard. After 0.5 h at 25 °C, the peak of Pd(PPh3)4 at 14.5
ppm22 disappeared and two broad peaks at 29.3 and 34.5 ppm,
a singlet peak at 21.9 ppm, and a peak at −5.1 ppm as free
PPh3 were observed. When the reaction mixture were heated
to 50 °C, two broad peaks disappeared and only two singlet
peaks were observed at 21.2 and −4.3 ppm. Thus, we con-
cluded that O-methylsulfonyloxime 1 readily reacts with
Pd(PPh3)4 and some palladium complexes were generated.
Although we could not confirm the formation of alkylidene-
aminopalladium(Ⅱ) species 2a by the NMR study, Pombeiro et
Results and Discussion
Reaction of O-Methylsulfonyloximes and Palladium(0)
Complex. During our study on SN2-type reaction of oxime
derivatives with intermolecular nucleophilic moieties,21 we ex-
pected that low-valent transition metal compounds, good elec-
tron donors, would react with oxime derivatives to give oxida-
tive addition compounds, such as alkylideneaminometal spe-
cies. Accordingly, an equimolar amount reaction of 4,4ꢀ-

1452 Bull. Chem. Soc. Jpn., 75, No. 7 (2002)
HEADLINE ARTICLES
al. recently reported the isolation of an oxidative addition
product of acetone oxime to a rhenium(Ⅰ) complex.23 In addi-
tion, the formation of alkylideneaminopalladium(Ⅱ) species
was also suggested in a recent report on the ring cleavage of
cyclobutanone oximes by Uemura et al. with a palladium(0)
complex.24 Accordingly, the reaction of 1 and Pd(PPh3)4 is
likely to afford an oxidative addition species like 2a. Recently,
alkylideneaminopalladium(Ⅱ) species, which have been uti-
lized scarcely in organic synthesis, have attracted attention as
synthetic intermediates. Based on the generation of these spe-
cies from diphenylmethanimine, palladium-catalyzed amina-
tion of aryl halides were reported by Buchwald et al.25 and
Hartwig et al.26 In contrast to unstable diphenylmethanimine,
oxime derivatives are generally stable enough to handle, and
the oxidative addition of oximes thus provides another conve-
nient method for generation of alkylideneaminopalladium(Ⅱ)
species.
products. In a similar reaction of 2-allyl-1-tetralone O-methyl-
sulfonyloxime (5b), the Beckmann product 8b was obtained as
a major product and the desired pyrrole derivative 7b was
formed only in 11% yield (Eq. 4). Though some pyrrole syn-
theses have been reported by using palladium-mediated and -
catalyzed cyclization of alkenes and alkynes containing nitro-
gen nucleophiles,30 such as amines31,32 and hydrazones,33 the
present method is the first example in which using imine
equivalent from oximes as nitrogen nucleophiles.
(3)
(4)
Then, in order to utilize the alkylideneaminopalladium(Ⅱ)
species in organic synthesis, we examined palladium-catalyzed
cyclization of 1-phenyl-6-hepten-3-one O-methylsulfonyl-
oxime (5a), which is a 1:1 mixture of E- and Z-forms, expect-
ing that intramolecular amination would proceed similarly to
the Heck (Mizoroki–Heck) reaction.27–29 That is, addition of
alkylideneaminopalladium(Ⅱ) species 2b generated by the oxi-
dative addition of 5a to the olefinic moiety and the successive
β-hydride elimination would afford 2-methylidene-5-pheneth-
yl-3,4-dihydro-2H-pyrrole (6a) (Eq. 2).
γ δ
Synthesis of Pyrrole Derivatives from , -Unsaturated
Ketone O-Pentafluorobenzoyloximes. To suppress the
Beckmann rearrangement, several O-substituted oximes of 1-
phenyl-6-hepten-3-one were prepared and submitted to the
palladium-catalyzed amino Heck-type cyclization. The cy-
clization proceeded very slowly in the reactions of O-benzo-
yloxime and O-diphenylphosphinoyloxime. Though O-trifluo-
roacetyloxime smoothly reacted, it was hydrolyzed very easily.
1-Phenyl-6-hepten-3-one O-pentafluorobenzoyloxime (9a)
was found to be stable enough for isolation by silica gel col-
umn chromatography, and the cyclization proceeded within 1 h
to afford pyrrole 7a in 56% yield without the Beckmann rear-
rangement. In the absence of palladium catalyst, the cycliza-
tion did not occur and the starting material 9a was recovered
(Eq. 5).
(2)
In fact, after heating a mixture of O-methylsulfonyloxime
5a, triethylamine, and a catalytic amount of Pd(OAc)2/PPh3 in
N,N-dimethylformamide (DMF) at 80 °C, 2-methyl-5-phen-
ethylpyrrole (7a), the aromatization product of the initially
formed 3,4-dihydro-2H-pyrrole 6a, was obtained in 40% yield
(Eq. 3). The desired amino Heck-type reaction thus occurred,
while the Beckmann products 8a and 8aꢀ were formed as side
(5)
This amino Heck-type reaction of 9a was screened under
various reaction conditions concerning bases, ligands, and
temperature (Table 1). The use of potassium carbonate as a
base instead of triethylamine gave pyrrole 7a in only 13%
yield, but gave diketone 11 as a major product in 43% yield
(entry 2). Presumably, 3,4-dihydro-2H-pyrrole 6a, a prelimi-
nary product of the cyclization, hardly aromatized to pyrrole
7a under potassium carbonate conditions, and 6a was hydro-
lyzed to diketone 11 during work-up. In fact, by addition of
triethylamine at 80 °C for 1 h after the palladium-catalyzed cy-
clization in the presence of potassium carbonate, the yield of
(3)

H. Tsutsui et al.
Bull. Chem. Soc. Jpn., 75, No. 7 (2002) 1453
Table 1. The Palladium-Catalyzed Cyclization of 9aa)
Yield/%c)
Entry
Cat. Pd
Pd(PPh3)4
Baseb)
Temp/°C
Time/h
7a
65
10
17
16
18
9
1
2
3
4
5
6
7
8
9
Et3N
K2CO3
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
80
80
80
80
80
80
80
80
80
80
50
1
1
1
1
1
1
1
1
1
1
5
Pd(PPh3)4
13d)
60
Pd(OAc)2 + 3PPh3
Pd(OAc)2 + 3P(o-tol)3
Pd(OAc)2 + 3P(n-Bu)3
Pd(OAc)2 + 3P(OPh)3
Pd(OAc)2 + dppe
Pd(OAc)2 + dppp
Pd(OAc)2 + dppb
Pd(OAc)2
60
47
29
12
11
6
58e)
66
59
58
15
15
27
10
11
10f)
45
Pd(PPh3)4
a) 9a:cat. Pd = 1.0 : 0.1. The concentration of 9a was 0.1 mol dm−3. b) 5 molar amounts of
1
Et3N or 2.5 molar amounts of K2CO3 was used. c) Yield was determined by H NMR spec-
troscopy with anthracene as an internal standard. d) 11 was isolated in 43% yield. e) 9a was
recovered in 20% yield. f) 9a was recovered in 47% yield.
Table 2. Influence of Solvent and Concentration in the Pal-
pyrrole 7a was 54% with a small amount (4%) of diketone 11.
Without a phosphine ligand, palladium black was deposited
(entry 10). The use of phosphine ligand was thus indispens-
able, and mono and bidentate aryl-phosphines exhibited almost
similar effect on the product yield (entries 3,4,7-9). At lower
reaction temperature (50 °C), the yield of 7a decreased (entry
11).
ladium-Catalyzed Cyclization of 9aa)
Polar solvents, such as DMF and N,N-dimethylacetamide
(DMA), were found to be more suitable than toluene, acetoni-
trile, and THF (Table 2, entries 1–5). In almost all cases, ke-
tone 10 was the main side product; it was probably formed by
hydrolysis of the initially formed ketimine of 10. It is note-
worthy that the concentration of the mixture considerably in-
fluences the product yield and that 7a was obtained in 81%
yield by the reaction at a concentration of 0.02 mol dm−3 (en-
try 6). Based on the above screening, the following experi-
ments were examined by using Pd(PPh3)4 as a catalyst and tri-
ethylamine as a base in DMF at the concentration of 0.02 mol
Yield/%d)
Entry
Solvent
Conc.c)
Time/h
7a
10
17
19
28
15
26
7
1
2
3
4
5
6
DMF
0.1
0.1
0.1
0.1
0.1
0.02
1
2
2
3
2
3
65
66
42
44
22
DMAb)
Toluene
MeCN
THF
dm−3
.
DMF
81 (72)e)
In the reaction of the above phenethyl ketone oxime 9a, pyr-
role 7a was isolated as a single cyclization product without any
particular operation after a common work-up. The reaction of
1-phenyl-4-penten-1-one (E)-O-pentafluorobenzoyloxime (E-
9c), however, gave a mixture of 2-methylidene-5-phenyl-3,4-
dihydro-2H-pyrrole (6c) and 2-methyl-5-phenylpyrrole (7c).
To isomerize cyclic imine 6c to pyrrole 7c, the crude mixture
was treated with 1.5 molar amounts of chlorotrimethylsilane to
afford pyrrole 7c as a sole product (Table 3, entry 1). Stere-
ochemistry of the oxime 9c did not exhibit any significant in-
a) 9a:Pd(PPh3)4:Et3N = 1.0 : 0.1:5.0. b) N,N-dimethyl-
acetamide. c) The concentration (mol dm−3) of 9a. d)
Yield was determined by 1H NMR spectroscopy with
anthracene as an internal standard. e) Isolated yield is in
parentheses.
fluence on the product yield (entries 1 and 2). Therefore, (E)-
and (Z)-alkylideneaminopalladium(Ⅱ) species seem to readily
isomerize under the present reaction conditions. This is a keen

1454 Bull. Chem. Soc. Jpn., 75, No. 7 (2002)
HEADLINE ARTICLES
Table 3. The Palladium-Catalyzed Cyclization of 9ca)
proceeded smoothly even in the presence of radical scavengers
such as 1,4-cyclohexadiene and 2,2,6,6-tetramethyl-1-pip-
eridyloxyl (TEMPO) to afford pyrrole 7c in 84% and 85%
yield, respectively. Accordingly, the cyclization does not occur
via alkylideneaminyl radical intermediate, but proceeded by
intramolecular insertion of the olefinic moiety to aminopalladi-
um species.
The palladium-catalyzed cyclization of O-pentafluoroben-
zoyloximes having a terminal vinyl group proceeded smoothly
and the results are listed in Table 4. Like 9a, bis(homoallyl)
ketone oxime 9d cyclized to pyrrole 7d in 79% yield without
the isomerization procedure with silyl chloride (method A). In
the reactions of phenyl and ethoxycarbonyl ketone oximes, the
isomerization step with chlorotrimethylsilane was required af-
ter the palladium-catalyzed cyclization to obtain pyrroles 7b,
7e, and 7f (method B). 2-Allyl-1-tetralone O-pentafluoroben-
zoyloxime (9b) was successfully transformed into tricyclic
pyrrole 7b in 89% yield without the Beckmann product (entry
2), whereas the Beckmann rearrangement mainly proceeded in
the reaction of the corresponding O-methylsulfonyloxime 5b,
as mentioned previously.
Several disubstituted olefinic ketone O-pentafluorobenzoyl-
oximes were cyclized to pyrroles on treatment with the palladi-
um catalyst as described in Table 5. It is well known that elec-
tron-deficient alkenes are suitable for the Heck reaction.28,29
Similar phenomena were also observed in this amino Heck-re-
action (entries 1–3). For example, α-keto ester oxime 9g hav-
ing ethoxycarbonyl group on the olefinic moiety gave pyrrole
7g in better yield (78%, entry 1) as compared with the cycliza-
Entry
9c
Pd(PPh3)4/mol amt. Time/h Yield/%c)
1
2
3
4
(E)-9c
(Z)-9c
(E)-9c
(E)-9c
0.1
1
1
1
2
86
83
82
75
0.1
0.03
0.01b)
a) 9c:Et3N = 1.0 : 5.0. The concentration of 9c was 0.02
mol dm−3. b) PPh3 (0.04 mol amt.) was added to the reac-
tion mixture. c) Isolated yield.
contrast to vinylpalladium species such as (E)- and (Z)-bro-
mo(styryl)bis(triphenylphosphine)palladium(Ⅱ), which do not
isomerize under the coupling reaction conditions.34 The cy-
clization could also be carried out in good yield even by the
use of a 0.03 or 0.01 molar amount of Pd(PPh3)4 (entries 3 and
4).
Zard et al. have reported the synthesis of 2H-3,4-dihydropy-
rroles by the cyclization of γ,δ-unsaturated ketone O-pivalo-
yloximes with nickel(0) metal in acetic acid and 2-propanol,13b
in which alkylideneaminyl radical is proposed as an intermedi-
ate. The present palladium-catalyzed cyclization of (E)-9c
Table 4. Synthesis of Pyrrole Derivatives by Palladium-Catalyzed Cyclization of
O-Pentafluorobenzoyloximes 9 Having Terminal Vinyl Groupa)
Entry
Oxime
Methodb)
Time/h
Product (Yield/%)c)
1
A
2
2
3
4
B
B
B
1
1
1
a) Oxime:Pd(PPh3)4:Et3N = 1.0 : 0.1:5.0. The reaction was conducted in DMF at 80
°C. The concentration of oxime was 0.02 mol dm−3. b) Method A: The isomerization
of dihydropyrrole to pyrrole occurred under the palladium-catalyzed cyclization condi-
tion. Method B: Dihydropyrrole isomerized to pyrrole by treatment of 1.5 molar
amounts of Me3SiCl in CH2Cl2 for 0.5 h after the palladium-catalyzed cyclization. c)
Isolated yield.

H. Tsutsui et al.
Bull. Chem. Soc. Jpn., 75, No. 7 (2002) 1455
Table 5. Synthesis of Pyrrole Derivatives by Palladium-Catalyzed Cyclization of Disubstituted
Olefinic Ketone O-Pentafluorobenzoyloximes 9a)
Entry
Oxime
Methodb)
Time/h
Product (Yield/%)c)
1
B
1
2
3
4
A
B
C
3
1
2
a) Oxime:Pd(PPh3)4 : Et3N = 1.0 : 0.1:5.0. The reaction was conducted in DMF at 80 °C.
The concentration of oxime was 0.02 mol dm−3. b) Method A: The isomerization of dihy-
dropyrrole to pyrrole occurred under the palladium-catalyzed cyclization condition.
Method B: Dihydropyrrole isomerized to pyrrole by treatment of 1.5 molar amounts of
Me3SiCl in CH2Cl2 for 0.5 h after the palladium-catalyzed cyclization. Method C: Dihy-
dropyrrole isomerized to pyrrole by treatment of SiO2 in CH2Cl2 for 6 h after the palla-
dium-catalyzed cyclization. c) Isolated yield.
tion of vinyl oxime 9f (Table 4 entry 4). In the cyclization of
O-pentafluorobenzoyloxime 9j having a methyl group on ole-
finic moiety, the formation 3,4-dihydro-2-ethylidene-2H-pyr-
role 6j and 2-vinyl-2H-3,4-dihydropyrrole 12 was confirmed
of E-9k and Pd(PPh3) had a structure a like alkylideneamino-
palladium(Ⅱ) species 2k (Eq. 6).
1
by H NMR spectrum as a mixture after palladium-catalyzed
cylization, but 3,4-dihydropyrrole 6j hardly isomerized by
method B to 2-ethylpyrrole 7j.18 On the other hand, the
isomerization of 3,4-dihydropyrrole 6j to 2-ethylpyrrole 7j by
treatment with SiO2 (method C) gave a good result, and 2-eth-
ylpyrrole 7j and 2-vinyl-2H-3,4-dihydropyrrole 12 were ob-
tained in 65% and 8% yield, respectively (entry 4). Dihydro-
pyrrole 12 could not be converted to pyrrole 7j under these re-
action conditions.
(6)
On the whole, the transformation of γ,δ-unsaturated ketone
O-pentafluorobenzoyloximes to pyrrole derivatives has been
achieved by using the palladium catalyst, based on the inter-
mediate formation of alkylideneaminopalladium(Ⅱ) species.
The structure of the oxidative addition products of O-pentaflu-
orobenzoyloximes of alkyl ketones to Pd(PPh3)4 is not clear;
alkylideneaminopalladium structure or the isomerized-N-pal-
ladaenamine (aza-allylpalladium) structure.35 To clarify this,
Experimental
General. 1H NMR (500 and 300 MHz) spectra were recorded
on Bruker AM 500, Bruker DRX 500, Bruker AVANCE 500, and
Bruker DPX 300 spectrometers in CDCl3 [using CHCl3 (for 1H, δ
1
= 7.24) as internal standard] or C6D6 [using C6HD5 (for H, δ =
7.15) as internal standard]. 13C NMR (125 and 75 MHz) spectra
were recorded on Bruker AM 500, Bruker DRX 500, Bruker
AVANCE 500, and Bruker DPX 300 spectrometers in CDCl3 us-
ing CDCl3 (for 13C, δ = 77.00) as internal standard. 31P NMR
(121.5 MHz) spectra were recorded on Bruker DPX 300 spec-
trometer in CD2Cl2 using 85% H3PO4 (for 31P, δ = 0) as external
standard. IR spectra were recorded on a Horiba FT 300-S and
Perkin Elmer SPECTRUM 1000 spectrophotometer. High-resolu-
tion mass spectra were obtained with a JEOL JMS-SX102A mass
1
we measured the H NMR of the equimolar mixture of ace-
tophenone O-pentafluorobenzoyloxime (E-9k) and Pd(PPh3)4
in C6D6. After 1 h at 50 °C, no peak was observed at olefinic
proton region but new methyl peaks were detected at 2.15,
1.81, and 1.64 ppm. Although these new methyl peaks could
not be assigned, the result suggested that the reaction products

1456 Bull. Chem. Soc. Jpn., 75, No. 7 (2002)
HEADLINE ARTICLES
spectrometer. The melting points were uncorrected. Elemental
analyses were carried out at The Elemental Analysis Laboratory,
Department of Chemistry, Faculty of Science, The University of
Tokyo. Flash column chromatography was performed on silica
gel (Merck Silica gel 60, and Kanto Chemical Co., Inc. Silica gel
60N (spherical, neutral)) and Florisil® (Wako Pure Chemical In-
dustries, Ltd.), and preparative thin-layer chromatography was
carried out using Wakogel B-5F. N,N-Dimethylformamide (DMF)
was distilled under reduced pressure from CaH2, and stored over
Molecular Sieves 4A under an argon atmosphere. Dichlo-
romethane was distilled from P2O5 and then from CaH2, and was
stored over Molecular Sieves 4A. Triethylamine was distilled
from NaH and stored over KOH. Pd(PPh3)4 was purchased from
Tokyo Chemical Industry Co., Ltd. and used without purification.
Pentafluorobenzoyl chloride was purchased from Tokyo Chemical
Industry Co., Ltd. and used without purification. Chlorotrimethyl-
silane was distilled from CaH2.
(5a): E:Z = 1:1 mixture; Pale yellow oil; IR (KBr) 1644, 1604,
1496, 1455, 1361, 1180, 970, 788, 701, 526 cm−1; 1H NMR (500
MHz, CDCl3) δ 2.24-2.35 (3H, m), 2.51 (1H, t, J = 7.8 Hz), 2.64
(1H, t, J = 7.8 Hz), 2.69 (1H, t, J = 7.8 Hz), 2.85 (1H, t, J = 7.8
Hz), 2.90 (1H, t, J = 7.8 Hz), 3.00 (1.5H, s), 3.06 (1.5H, s), 4.98–
5.08 (2H, m), 5.70–5.81 (1H, m), 7.15–7.23 (3H, m), 7.25–7.31
(2H, m); 13C NMR (125 MHz, CDCl3) δ 28.98, 29.48, 29.63,
31.45, 31.70, 31.78, 33.65, 35.66, 36.25 (overlapped), 115.99,
116.31, 126.39, 126.60, 128.28, 128.29, 128.54, 128.62, 135.95,
126.29, 139.67, 140.08, 169.50, 169.72; FABHRMS Found: m/z
282.1176. Calcd for C14H20NO3S: M + H, 282.1165.
2-Allyl-1-tetralone (E)-O-Methylsulfonyloxime (E-5b):
Pale yellow plates; mp 71–72 °C (isopropyl ether–hexane); IR
(KBr) 1640, 1594, 1453, 1417, 1360, 1172, 988, 937, 863, 824,
797, 732, 716, 633, 603, 547, 523, 493 cm−1; 1H NMR (500 MHz,
CDCl3) δ 1.88-2.01 (2H, m), 2.24 (1H, dt, J = 13.9, 8.9 Hz),
2.32–2.40 (1H, m), 2.72 (1H, dt, J = 17.1, 4.1 Hz), 2.90–2.99
(1H, m), 3.22 (3H, s), 3.55–3.62 (1H, m), 5.02–5.09 (2H, m),
5.75–5.84 (1H, m), 7.18 (1H, d, J = 7.8 Hz), 7.21 (1H, t, J = 7.8
Hz), 7.36 (1H, t, J = 7.8 Hz), 7.99 (1H, d, J = 7.8 Hz); 13C NMR
(125 MHz, CDCl3) δ 24.04, 24.22, 32.91, 33.43, 36.36, 117.27,
125.55, 126.35, 126.84, 129.02, 131.17, 134.79, 139.78, 165.26;
The Reaction of O-Methylsulfonyloxime (1) and Pd(PPh3)4:
(Eq. 1): Into a flask containing Pd(PPh3)4 (289 mg, 0.250 mmol)
was added a solution of 4,4ꢀ-bis(trifluoromethyl)benzophenone O-
methylsulfonyloxime (1)21 (103 mg, 0.250 mmol) in THF (2.5
mL) at room temperature under an argon atmosphere. After the
reaction mixture was stirred at the same temperature for 20 min,
the mixture was quenched with pH 9 buffer at 0 °C. The mixture
was extracted twice with ether, and the combined extracts were
washed successively with sat. NaHCO3 and brine, and the ether
solution was dried over anhydrous magnesium sulfate. The ether
was removed in vacuo, and bis(4-trifluoromethylphenyl)metha-
Anal. Found: C, 60.02; H, 5.97; N, 4.74%.
C14H17NO3S: C, 60.19; H, 6.13; N, 5.01%.
Calcd for
γ δ
Preparation of , -Unsaturated Ketone O-Pentafluoroben-
zoyloximes: Experimental procedures for the preparation of
γ,δ-unsaturated ketone O-pentafluorobenzoyloximes are shown
below as a typical example for the synthesis of 1-phenyl-6-hepten-
3-one O-pentafluorobenzoyloxime (9a).
1
nimine (3)21 was confirmed by H NMR spectrum of the crude
product. The crude imine was dissolved in acetone (2.5 mL) and
water (0.5 mL), and 1 M HCl (1 M = 1.00 mol dm−3, 0.375 mL,
0.375 mmol) was added to the solution. After the resulting solu-
tion was stirred at room temperature for 30 min, the reaction was
quenched with water. The mixture was extracted twice with ethyl
acetate, and the combined extracts were washed successively with
sat. NaHCO3 and brine. The ethyl acetate solution was dried over
anhydrous sodium sulfate, and the ethyl acetate was removed in
vacuo. The crude materials were purified by thin-layer chroma-
tography (silica gel, dichloromethane:hexane = 1:1) to give 4,4ꢀ-
bis(trifluoromethyl)benzophenone (4)36 (75.0 mg, 94%). 1H NMR
(500 MHz, CDCl3) δ 7.77 (4H, d, J = 8.3 Hz), 7.89 (4H, d, J =
8.3 Hz).
To an ice-cold solution of 1-phenyl-6-hepten-3-one oxime37
(1.02 g, 5.02 mmol) and triethylamine (0.909 mL, 6.52 mmol) in
dichloromethane (15 mL) was slowly added a solution of pentaflu-
orobenzoyl chloride (1.27 g, 5.52 mmol) in dichloromethane (5
mL), and this mixture was stirred at the same temperature for 1 h.
After the reaction was quenched with water, the mixture was ex-
tracted twice with dichloromethane. The combined extracts were
washed with sat. NaHCO3, and the dichloromethane solution was
dried over anhydrous sodium sulfate. Solvent was removed in
vacuo, and the crude materials were purified by flash column
chromatography (silica gel, hexane:ethyl acetate = 9:1) to give 1-
phenyl-6-hepten-3-one O-pentafluorobenzoyloxime (9a) (1.87 g,
94%).
γ δ
γ δ
Spectral Data for , -Unsaturated Ketone O-Pentafluo-
robenzoyloximes. 1-Phenyl-6-hepten-3-one O-Pentafluo-
Preparation of , -Unsaturated Ketone O-Methylsulfonyl-
oximes: Experimental procedures for the preparation of γ,δ-un-
saturated ketone O-methylsulfonyloximes are shown below as a
typical example for the synthesis of 1-phenyl-6-hepten-3-one O-
methylsulfonyloxime (5a).
robenzoyloxime (9a): E:Z = 1:1 mixture; White solid; mp 45–
72 °C; IR (KBr) 1760, 1656, 1504, 1454, 1420, 1327, 1198, 1094,
1001, 949, 915, 866, 752, 702 cm−1; 1H NMR (500 MHz, CDCl3)
δ 2.25–2.42 (3H, m), 2.53 (1H, t, J = 7.8 Hz), 2.67–2.74 (2H, m),
2.85 (1H, t, J = 7.8 Hz), 2.94 (1H, t, J = 7.8 Hz), 4.99–5.08 (2H,
m), 5.71–5.83 (1H, m), 7.14 (1H, d, J = 7.6 Hz), 7.17–7.23 (2H,
m), 7.24–7.32 (2H, m); 13C NMR (125 MHz, CDCl3) δ 29.56,
29.83, 29.92, 31.87, 31.91, 32.11, 33.77, 36.06, 106.85–107.24
(overlapped, m), 115.90, 116.19, 126.33, 126.51, 128.08, 128.24,
128.53, 128.56, 135.99, 136.37, 136.50–136.85 and 138.53–
138.89 (overlapped, m d), 139.83, 140.31, 142.09–142.48,
144.10–144.53, and 146.24–146.54 (overlapped, m), 156.45,
156.55, 170.56, 170.73; Anal. Found: C, 60.24; H, 4.13; N,
3.50%. Calcd for C20H16F5NO2: C, 60.46; H, 4.06; N, 3.53%.
2-Allyl-1-tetralone (E)-O-Pentafluorobenzoyloxime (E-9b):
Colorless needles; mp 75–76 °C (hexane); IR (KBr) 1764, 1652,
To an ice-methanol cold solution of 1-phenyl-6-hepten-3-one
oxime37 (908 mg, 4.47 mmol) and triethylamine (0.934 mL, 6.70
mmol) in dichloromethane (13 mL) was slowly added a solution
of methanesulfonyl chloride (563 mg, 4.91 mmol) in dichlo-
romethane (5 mL), and this mixture was stirred at the same tem-
perature for 2 h. After the reaction was quenched with water, the
mixture was extracted twice with dichloromethane. The com-
bined extracts were washed with sat. NaHCO3, and the dichlo-
romethane solution was dried over anhydrous sodium sulfate. The
dichloromethane was removed in vacuo, and the crude materials
were purified by flash column chromatography (Florisil®,
hexane:ethyl acetate = 10:1) at 0 °C to give 1-phenyl-6-hepten-3-
one O-methylsulfonyloxime (5a) (1.17 g, 93%).
1526, 1501, 1418, 1323, 1198, 1097, 1004, 926, 866, 772 cm−1
1H NMR (500 MHz, CDCl3) δ 1.90–2.02 (2H, m), 2.25 (1H, dt, J
;
γ δ
Spectral Data for , -Unsaturated Ketone O-Methylsulfo-
nyloximes. 1-Phenyl-6-hepten-3-one O-Methylsulfonyloxime

H. Tsutsui et al.
Bull. Chem. Soc. Jpn., 75, No. 7 (2002) 1457
= 14.0, 8.9 Hz), 2.32–2.39 (1H, m), 2.73 (1H, dt, J = 16.7, 4.0
Hz), 2.91–3.00 (1H, m), 3.55–3.61 (1H, m), 5.01–5.08 (2H, m),
5.71–5.81 (1H, m), 7.18 (1H, d, J = 7.6 Hz), 7.23 (1H, t, J = 7.6
Hz), 7.36 (1H, t, J = 7.6 Hz), 8.14 (1H, d, J = 7.6 Hz); 13C NMR
(125 MHz, CDCl3) δ 24.20, 24.34, 33.57, 33.73, 106.72–107.24
(m), 117.37, 126.21, 126.56, 127.36, 129.01, 131.29, 134.96,
136.52–136.97 and 138.54–138.96 (m d), 139.95, 142.15–142.54,
144.18–144.61, and 146.22–146.69 (overlapped, m), 156.51,
166.22; Anal. Found: C, 60.46; H, 3.49; N, 3.34%. Calcd for
C20H14F5NO2: C, 60.76; H, 3.57; N, 3.54%.
1-Phenyl-4-penten-1-one (E)-O-Pentafluorobenzoyloxime
(E-9c): Colorless crystals; mp 82–84 °C; IR (KBr) 1755, 1655,
1524, 1501, 1418, 1330, 1198, 1002, 922, 890, 773, 696 cm−1; 1H
NMR (500 MHz, CDCl3) δ 2.28–2.36 (2H, m), 2.98 (2H, t, J =
7.8 Hz), 4.98–5.05 (2H, m), 5.73–5.83 (1H, m), 7.42 (2H, t, J =
7.2 Hz), 7.48 (1H, t, J = 7.2 Hz), 7.72 (2H, d, J = 7.2 Hz); 13C
NMR (125 MHz, CDCl3) δ 28.13, 30.62, 107.01–107.15 (m),
116.01, 127.39, 128.74, 131.03, 132.97, 136.01, 136.55–136.97
and 138.54–138.98 (m d), 142.18–142.66, 144.26–144.69, and
146.31–146.68 (overlapped, m), 156.45, 168.10; Anal. Found: C,
58.48; H, 3.32; N, 3.85%. Calcd for C18H12F5NO2: C, 58.54; H,
3.28; N, 3.79%.
1-Phenyl-4-penten-1-one (Z)-O-Pentafluorobenzoyloxime
(Z-9c): Colorless oil; IR (KBr) 1767, 1652, 1505, 1423, 1327,
1197, 1083, 1005, 922, 871, 767, 700 cm−1; 1H NMR (500 MHz,
CDCl3) δ 2.23–2.30 (2H, m), 2.83 (2H, t, J = 7.6 Hz), 4.98–5.05
(2H, m), 5.74–5.84 (1H, m), 7.27–7.31 (2H, m), 7.39–7.43 (3H,
m); 13C NMR (125 MHz, CDCl3) δ 30.02, 34.84, 106.71–107.01
(m), 115.84, 126.86, 128.22, 129.69, 132.12, 136.00, 136.22–
136.68 and 138.27–138.65 (m d), 141.89–142.28, 143.87–144.34,
and 145.96–146.30 (overlapped, m), 156.48, 168.95; FABHRMS
Found: m/z 370.0876. Calcd for C18H13F5NO2: M + H, 370.0867.
146.58–146.86 (overlapped, m), 155.48, 161.47, 162.19; Anal.
Found: C, 49.20; H, 3.24; N, 3.74%. Calcd for C15H12F5NO4: C,
49.32; H, 3.31; N, 3.83%.
1-Ethyl 7-Methyl (E)-6-[(E)-Pentafluorobenzoyloxyimino]-
2-heptenedioate (E-9g): Colorless plates; mp 75–76 °C (hex-
ane); IR (KBr) 1789, 1728, 1652, 1501, 1446, 1326, 1253, 1178,
1126, 1078, 1002, 951, 901, 849, 766 cm−1; 1H NMR (300 MHz,
CDCl3) δ 1.25 (3H, t, J = 7.2 Hz), 2.42–2.53 (2H, m), 3.91 (3H,
s), 4.14 (2H, q, J = 7.2 Hz), 5.82 (1H, dt, J = 15.6, 1.4 Hz), 6.86
(1H, dt, J = 15.6, 7.0 Hz); 13C NMR (75 MHz, CDCl3) δ 13.70,
25.84, 28.16, 53.10, 59.94, 105.08–105.67 (m), 122.56, 135.61–
136.22 and 138.94–139.62 (m d), 141.70–142.41 and 145.11–
145.78 (m d), 143.59–144.14 and 146.93–147.53 (m d), 144.86,
154.94, 159.83, 162.25, 165.52; Anal. Found: C, 48.32; H, 3.32;
N, 3.09%. Calcd for C17H14F5NO6: C, 48.24; H, 3.33; N, 3.31%.
Ethyl
(E)-6-(Pentafluorobenzoyloxyimino)-8-phenyl-2-
octenoate (9h): E:Z = 3:1 mixture; White solid; mp 41–55 °C;
IR (KBr) 1757, 1714, 1651, 1494, 1453, 1416, 1368, 1326, 1254,
1190, 1090, 1033, 1000, 942, 865, 772, 716 cm−1; 1H NMR (500
MHz, CDCl3) E-isomer: δ 1.26 (3H, t, J = 7.1 Hz), 2.37–2.44
(2H, m), 2.57 (2H, t, J = 7.4 Hz), 2.67–2.74 (2H, m), 2.94 (2H, t,
J = 7.7 Hz), 4.16 (2H, q, J = 7.1 Hz), 5.80 (1H, dt, J = 15.6, 1.4
Hz), 6.85 (1H, dt, J = 15.6, 6.9 Hz), 7.17–7.23 (3H, m), 7.24–
7.31 (2H, m); Z-isomer: δ 1.27 (3H, t, J = 7.1 Hz), 2.37–2.44 (2H,
m), 2.45–2.52 (2H, m), 2.67–2.74 (2H, m), 2.85 (2H, t, J = 7.7
Hz), 4.17 (2H, q, J = 7.1 Hz), 5.81 (1H, dt, J = 15.7, 1.5 Hz),
6.88 (1H, dt, J = 15.7, 6.4 Hz), 7.13 (2H, d, J = 7.6 Hz), 7.17–
7.23 (1H, m), 7.24–7.31 (2H, m); 13C NMR (125 MHz, CDCl3) E-
isomer: δ 13.77, 27.88, 28.44, 31.73, 35.72, 60.00, 106.48–106.70
(m), 122.37, 126.05, 127.96, 128.22, 136.23–136.65 and 138.23–
138.67 (m d), 139.90, 141.86–142.31, 143.90–144.24, and
145.96–146.35 (overlapped, m), 145.36, 156.00, 165.63, 169.49;
Z-isomer: δ 13.81, 27.63, 31.63, 31.96, 32.79, 59.93, 106.48–
106.70 (m), 122.15, 126.25, 127.83, 128.27, 136.23–136.65 and
138.23-138.67 (m d), 139.43, 141.86–142.31, 143.90–144.24, and
145.96–146.35 (overlapped, m), 146.04, 156.00, 165.83, 169.49;
1,8-Nonadien-5-one
O-Pentafluorobenzoyloxime
(9d):
White solid; mp < 30 °C; IR (KBr) 1766, 1652, 1525, 1505,
1
1419, 1327, 1202, 1093, 1004, 919, 867 cm−1; H NMR (500
MHz, CDCl3) δ 2.25–2.32 (2H, m), 2.33–2.40 (2H, m), 2.46–2.54
(4H, m), 4.99–5.11 (4H, m), 5.71–5.87 (2H, m); 13C NMR (125
MHz, CDCl3) δ 29.08, 29.70, 29.83, 33.36, 106.83–107.24 (m),
115.63, 115.87, 135.94, 136.29, 136.38–136.77 and 138.37–
138.89 (m d), 141.86–142.39, 144.02–144.41, and 146.10–146.41
(overlapped, m), 156.35, 170.72; Anal. Found: C, 55.21; H, 4.00;
N, 4.01%. Calcd for C16H14F5NO2: C, 55.34; H, 4.06; N, 4.03%.
3-Methyl-1-phenyl-4-penten-1-one (E)-O-Pentafluoroben-
zoyloxime (E-9e): White powder; mp 69–73 °C; IR (KBr)
1755, 1652, 1526, 1498, 1417, 1328, 1203, 1004, 950, 924, 874,
Anal. Found: C, 58.85; H, 4.37; N, 2.96%.
C23H20F5NO4: C, 58.85; H, 4.29; N, 2.98%.
Calcd for
Ethyl (E)-6-[(E)-Pentafluorobenzoyloxyimino]-6-phenyl-2-
hexenoate (E-9i): Colorless crystals; mp 93–95 °C; IR (KBr)
1760, 1716, 1652, 1528, 1494, 1324, 1284, 1196, 895, 769, 697
1
cm−1; H NMR (500 MHz, CDCl3) δ 1.25 (3H, t, J = 7.2 Hz),
2.42–2.50 (2H, m), 3.04 (2H, t, J = 7.7 Hz), 4.15 (2H, q, J = 7.2
Hz), 5.81 (1H, dt, J = 15.6, 1.4 Hz), 6.89 (1H, dt, J = 15.6, 6.9
Hz), 7.43 (2H, dt, J = 1.5, 7.2 Hz), 7.49 (1H, dt, J = 1.5, 7.2 Hz),
7.71 (2H, dd, J = 1.5, 7.2 Hz); 13C NMR (125 MHz, CDCl3) δ
14.03, 27.09, 28.92, 60.25, 106.52–106.83 (m), 122.58, 127.28,
128.83, 131.22, 132.49, 136.55–136.93 and 138.56–138.93 (m d),
142.25–142.66, 144.27–144.70, and 146.31–146.68 (overlapped,
m), 145.51, 156.18, 165.93, 167.05; Anal. Found: C, 57.02; H,
3.63; N, 2.95%. Calcd for C21H16F5NO4: C, 57.15; H, 3.65; N,
3.17%.
1
744, 695 cm−1; H NMR (300 MHz, CDCl3) δ 1.02 (3H, d, J =
6.8 Hz), 2.37–2.52 (1H, m), 2.84–2.99 (2H, m), 4.85–4.95 (2H,
m), 5.59–5.73 (1H, m), 7.35–7.52 (3H, m), 7.69 (2H, dd, J = 1.8,
7.7 Hz); 13C NMR (75 MHz, CDCl3) δ 19.77, 35.12, 35.96,
106.74–107.39 (m), 113.87, 127.54, 128.70, 130.90, 133.32,
135.75–136.38 and 139.14–139.70 (m d), 141.41–142.10 and
144.78–145.52 (m d), 141.78, 143.47–143.94 and 146.85–147.46
(m d), 156.47, 167.76; Anal. Found: C, 59.35; H, 3.65; N, 3.68%.
Calcd for C19H14F5NO2: C, 59.53; H, 3.68; N, 3.65%.
1-Phenyl-4-hexen-1-one
(E)-O-Pentafluorobenzoyloxime
(E-9j): E:Z = 2:1 mixture; White solid; mp 59–70 °C; IR
Ethyl 2-[(E)-Pentafluorobenzoyloxyimino]-5-hexenoate (E-
9f): Colorless oil; IR (KBr) 1779, 1732, 1652, 1505, 1418,
(KBr) 1754, 1653, 1607, 1525, 1498, 1466, 1444, 1324, 1200,
1
1097, 1040, 1002, 971, 951, 888, 774, 745, 695, 627 cm−1; H
1
1375, 1326, 1185, 1078, 1006, 901, 767 cm−1; H NMR (500
NMR (500 MHz, CDCl3) δ 1.48 (1H, dd, J = 0.9, 6.8 Hz), 1.60
(2H, dd, J = 1.0, 6.0 Hz), 2.20–2.27 (1.33H, m), 2.28–2.36
(0.67H, m), 2.88–2.96 (2H, m), 5.31–5.52 (2H, m), 7.36–7.50
(3H, m), 7.67–7.76 (2H, m); 13C NMR (125 MHz, CDCl3) δ
12.45, 17.65, 24.05, 28.45, 28.85, 29.59, 106.82–107.51 (m, over-
lapped), 125.65, 126.81, 127.40 (overlapped), 127.60, 128.60,
MHz, CDCl3) δ 1.37 (3H, t, J = 7.2 Hz), 2.29–2.36 (2H, m), 2.81
(2H, t, J = 7.6 Hz), 4.36 (2H, q, J = 7.2 Hz), 4.98–5.08 (2H, m),
5.70–5.80 (1H, m); 13C NMR (125 MHz, CDCl3) δ 13.83, 27.00,
30.05, 62.78, 105.73–106.12 (m), 116.38, 135.52, 136.55–136.97
and 138.57–138.97 (m d), 142.59–142.96, 144.43–145.07, and

1458 Bull. Chem. Soc. Jpn., 75, No. 7 (2002)
HEADLINE ARTICLES
128.69, 128.71, 130.93, 130.98, 133.03, 133.10, 136.52–136.94
and 138.52–138.94 (overlapped, m d), 142.12–142.55, 144.23–
144.62, and 146.24–146.67 (overlapped, m), 156.50 (overlapped),
168.30, 168.32; Anal. Found: C, 59.32; H, 3.75; N, 3.35%. Calcd
for C19H14F5NO2: C, 59.53; H, 3.68; N, 3.65%.
(4H, m), 5.76 (1H, dd, J = 2.9, 2.9 Hz), 5.81 (1H, dd, J = 2.9, 2.9
Hz), 7.17–7.23 (3H, m), 7.29 (2H, d, J = 7.4 Hz), 7.45 (1H, br s);
13C NMR (125 MHz, CDCl3) δ 12.88, 29.63, 36.17, 105.10,
105.57, 125.99, 126.06, 128.33, 128.35, 130.50, 141.70.
2-Methyl-4,5-dihydro-1H-benz[g]indole (7b):
Colorless
Typical Procedure for the Synthesis of Pyrroles. (Method
A). (Table 4, entry 1): Into a flask containing Pd(PPh3)4 (119
mg, 0.103 mmol) was added a solution of 1,8-nonadien-5-one O-
pentafluorobenzoyloxime (9d) (358 mg, 1.03 mmol) in DMF (51
mL) and triethylamine (0.718 mL, 5.15 mmol) under an argon at-
mosphere, and the mixture was heated to 80 °C for 2 h. The mix-
ture was quenched with water at 0 °C, and organic materials were
extracted twice with ether. The combined extracts were washed
successively with water and with brine two times, and the ether
solution was dried over anhydrous magnesium sulfate. The ether
was removed in vacuo, and the crude materials were purified by
flash column chromatography (silica gel, hexane:ethyl acetate =
15:1) to give 2-(3-butenyl)-5-methylpyrrole (7d) (110 mg, 79%).
Typical Procedure for the Synthesis of Pyrroles. (Method
B). (Table 4, entry 2): Into a flask containing Pd(PPh3)4 (68.7
mg, 0.0595 mmol) was added a solution of 2-allyl-1-tetralone (E)-
O-pentafluorobenzoyloxime (E-9b) (235 mg, 0.594 mmol) in
DMF (30 mL) and triethylamine (0.414 mL, 2.97 mmol) under an
argon atmosphere, and the mixture was heated to 80 °C for 1 h.
The mixture was quenched with water at 0 °C, and organic materi-
als were extracted twice with ether. The combined extracts were
washed successively with water and with brine two times, and the
ether solution was dried over anhydrous magnesium sulfate. The
ether was removed in vacuo, and the crude products were dis-
solved in dichloromethane (12 mL) under an argon atmosphere,
then chlorotrimethylsilane (0.113 mL, 0.892 mmol) was added to
the solution. After the resulting solution was stirred at room tem-
perature for 30 min, the mixture was neutralized with sat.
NaHCO3 at 0 °C. Organic materials were extracted twice with
dichloromethane, and the dichloromethane solution was dried
over anhydrous sodium sulfate. The dichloromethane was re-
moved in vacuo, and the crude materials were purified by flash
column chromatography (silica gel, hexane:ethyl acetate = 9:1)
to give 2-methyl-4,5-dihydro-1H-benz[g]indole (7b) (97.2 mg,
89%).
crystals; mp 93–95 °C (hexane); IR (KBr) 3420, 1610, 1588,
1509, 1442, 1404, 1287, 1251, 1158, 789, 758, 731, 695, 637, 493
cm−1; 1H NMR (500 MHz, CDCl3) δ 2.31 (3H, s), 2.67 (2H, t, J =
7.6 Hz), 2.89 (2H, t, J = 7.6 Hz), 5.79 (1H, d, J = 1.6 Hz), 6.99
(1H, dt, J = 1.1, 7.4 Hz), 7.06 (1H, d, J = 7.4 Hz), 7.11–7.17 (2H,
m), 7.95 (1H, br s); 13C NMR (125 MHz, CDCl3) δ 13.28, 21.83,
30.05, 106.22, 117.54, 120.80, 124.34, 126.36, 126.42, 128.19,
128.62, 129.44, 134.31; Anal. Found: C, 85.32; H, 7.28; N,
7.54%. Calcd for C13H13N: C, 85.21; H, 7.15; N, 7.64%.
2-Methyl-5-phenylpyrrole (7c):39 Pale yellow crystals; 1H
NMR (500 MHz, CDCl3) δ 2.32 (3H, s), 5.94 (1H, dd, J = 3.0, 3.0
Hz), 6.39 (1H, dd, J = 3.0, 3.0 Hz), 7.15 (1H, t, J = 7.5 Hz), 7.32
(2H, t, J = 7.5 Hz), 7.41 (2H, d, J = 7.5 Hz), 8.09 (1H, br s); 13
C
NMR (125 MHz, CDCl3) δ 13.15, 106.14, 107.90, 123.30, 125.61,
128.78, 129.02, 130.74, 132.91.
2-(3-Butenyl)-5-methylpyrrole (7d): Pale yellow oil; IR
(KBr) 3372, 1640, 1593, 1514, 1402, 1183, 1038, 994, 913, 767,
666 cm−1; 1H NMR (500 MHz, CDCl3) δ 2.23 (3H, s), 2.33–2.40
(2H, m), 2.65 (2H, t, J = 7.6 Hz), 4.99–5.12 (2H, m), 5.75 (1H,
dd, J = 2.9, 2.9 Hz), 5.78 (1H, dd, J = 2.9, 2.9 Hz), 5.84–5.94
(1H, m), 7.62 (1H, br s); 13C NMR (125 MHz, CDCl3) δ 12.89,
27.04, 33.73, 104.94, 105.50, 115.06, 126.03, 130.58, 138.15;
HRMS Found: m/z 135.1031. Calcd for C9H13N: M, 135.1049.
1
2,3-Dimethyl-5-phenylpyrrole (7e):40 Colorless crystals; H
NMR (500 MHz, CDCl3) δ 2.03 (3H, s), 2.22 (3H, s), 6.26 (1H, d,
J = 2.7 Hz), 7.12 (1H, t, J = 7.8 Hz), 7.30 (2H, t, J = 7.8 Hz),
7.38 (2H, d, J = 7.8 Hz), 7.91 (1H, br s); 13C NMR (125 MHz,
CDCl3) δ 10.90, 11.09, 107.75, 116.20, 123.15, 125.16, 125.40,
128.74, 129.27, 132.95.
Ethyl 5-Methylpyrrole-2-carboxylate (7f):41
Pale yellow
crystals; 1H NMR (500 MHz, CDCl3) δ 1.32 (3H, t, J = 7.1 Hz),
2.29 (3H, s), 4.27 (2H, q, J = 7.1 Hz), 5.93 (1H, dd, J = 3.0, 3.0
Hz), 6.79 (1H, dd, J = 3.0, 3.0 Hz), 8.81 (1H, br s); 13C NMR
(125 MHz, CDCl3) δ 13.10, 14.46, 60.04, 108.82, 116.04, 121.30,
133.89, 161.40.
2-Ethyl-5-phenylpyrrole (7j) and 3,4-Dihydro-5-phenyl-2-
vinyl-2H-pyrrole (12) (Method C). (Table 5, entry 4): Into a
flask containing Pd(PPh3)4 (108 mg, 0.0934 mmol) was added a
solution of 1-phenyl-4-hexen-1-one (E)-O-pentafluorobenzoyl-
oxime (E-9j) (358 mg, 0.934 mmol) in DMF (47 mL) and triethyl-
amine (0.651 mL, 4.67 mmol) under an argon atmosphere, and the
mixture was heated to 80 °C for 2 h. The mixture was quenched
with water at 0 °C, and organic materials were extracted twice
with ether. The combined extracts were washed successively with
water and with brine two times, and the ether solution was dried
over anhydrous magnesium sulfate. The ether was removed in
vacuo, and the crude products were dissolved in dichloromethane
(9.3 mL) under an argon atmosphere, and silica gel (1.8 g) was
added to the solution. After the resulting solution was stirred at
room temperature for 6 h, silica gel was filtered off. The filtrate
was removed in vacuo, and the crude materials were purified by
flash column chromatography (silica gel, hexane:ethyl acetate =
15:1) to give 2-ethyl-5-phenylpyrrole (7j) (104 mg, 65%) and 3,4-
dihydro-5-phenyl-2-vinyl-2H-pyrrole (12) (12.9 mg, 8%), respec-
tively.
Ethyl 5-Methoxycarbonyl-2-pyrroleacetate (7g): Pale yel-
low plates; mp 70–72 °C (hexane); IR (KBr) 3307, 1739, 1680,
1497, 1449, 1332, 1275, 1239, 1178, 1042, 1002, 801, 778 cm−1
;
1H NMR (300 MHz, CDCl3) δ 1.27 (3H, t, J = 7.1 Hz), 3.66 (2H,
s), 3.82 (3H, s), 4.18 (2H, q, J = 7.1 Hz), 6.05 (1H, dd, J = 2.8,
3.5 Hz), 6.81 (1H, dd, J = 2.8, 3.5 Hz), 9.53 (1H, br s); 13C NMR
(75 MHz, CDCl3) δ 14.07, 33.26, 51.33, 61.34, 109.82, 115.69,
122.27, 129.20, 161.46, 170.04; Anal. Found: C, 56.64; H, 6.02;
N, 6.40%. Calcd for C10H13NO4: C, 56.86; H, 6.20; N, 6.63%.
Ethyl 5-Phenethyl-2-pyrroleacetate (7h): Pale yellow sol-
id; mp < 30 °C; IR (KBr) 3374, 1731, 1592, 1498, 1454, 1370,
1256, 1188, 1031, 765, 699 cm−1; 1H NMR (500 MHz, CDCl3) δ
1.26 (3H, t, J = 7.1 Hz), 2.85–2.95 (4H, m), 3.59 (2H, s), 4.15
(2H, q, J = 7.1 Hz), 5.83 (1H, dd, J = 2.8, 2.8 Hz), 5.88 (1H, dd,
J = 2.8, 2.8 Hz), 7.16–7.22 (3H, m), 7.28 (2H, t, J = 7.6 Hz), 8.29
(1H, br s); 13C NMR (125 MHz, CDCl3) δ 14.12, 29.72, 33.34,
36.05, 60.99, 105.11, 107.17, 121.80, 126.00, 128.33, 128.37,
132.03, 141.57, 171.31; FABHRMS Found: m/z 258.1487. Calcd
for C16H20NO2: M + H, 258.1495.
Ethyl 5-Phenyl-2-pyrroleacetate (7i):42 Colorless crystals;
1H NMR (500 MHz, CDCl3) δ 1.29 (3H, t, J = 7.1 Hz), 3.70 (2H,
s), 4.19 (2H, q, J = 7.1 Hz), 6.05 (1H, dd, J = 3.0, 3.0 Hz), 6.40
Spectral Data. 2-Methyl-5-phenethylpyrrole (7a):38
yellow oil; 1H NMR (500 MHz, CDCl3) δ 2.20 (3H, s), 2.83–2.95
Pale

H. Tsutsui et al.
Bull. Chem. Soc. Jpn., 75, No. 7 (2002) 1459
Narasaka, Heterocycles, 52, 681 (2000).
11 A. R. Forrester, M. Gill, J. S. Sadd, and R. H. Thomson, J.
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12 K. Uchiyama, Y. Hayashi, and K. Narasaka, Synlett, 1997,
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S. Z. Zard, Synlett, 1996, 1148. c) F. Gagosz and S. Z. Zard, Syn-
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(1H, dd, J = 3.0, 3.0 Hz), 7.17 (1H, t, J = 7.6 Hz), 7.33 (2H, t, J
= 7.6 Hz), 7.45 (2H, d, J = 7.6 Hz), 8.99 (1H, br s); 13C NMR
(125 MHz, CDCl3) δ 14.11, 33.30, 61.20, 105.79, 109.09, 123.58,
124.48, 125.94, 128.75, 132.07, 132.68, 171.18.
2-Ethyl-5-phenylpyrrole (7j):39 Colorless crystals; 1H NMR
(500 MHz, CDCl3) δ 1.28 (3H, t, J = 7.6 Hz), 2.67 (2H, q, J = 7.6
Hz), 5.70 (1H, dd, J = 3.0, 3.0 Hz), 6.40 (1H, dd, J = 3.0, 3.0
Hz), 7.15 (1H, t, J = 7.6 Hz), 7.32 (2H, t, J = 7.6 Hz), 7.42 (2H,
d, J = 7.6 Hz), 8.10 (1H, br s); 13C NMR (125 MHz, CDCl3) δ
13.58, 20.98, 105.97, 106.21, 123.37, 125.64, 128.78, 130.57,
132.97, 135.60.
3,4-Dihydro-5-phenyl-2-vinyl-2H-pyrrole (12):
Pale yel-
low oil; IR (KBr) 1688, 1643, 1614, 1576, 1499, 1449, 1341,
1268, 1026, 992, 920, 763, 693, 558 cm−1; H NMR (500 MHz,
1
CDCl3) δ 1.73–1.82 (1H, m), 2.24–2.32 (1H, m), 2.86–2.95 (1H,
m), 2.99–3.08 (1H, m), 4.69–4.75 (2H, m), 5.11 (1H, dt, J = 10.3,
1.4 Hz), 5.25 (1H, dt, J = 17.1, 1.4 Hz), 5.98 (1H, ddd, J = 6.7,
10.3, 17.1 Hz), 7.34–7.46 (3H, m), 7.86 (2H, dd, J = 1.5, 7.8 Hz);
13C NMR (125 MHz, CDCl3) δ 29.17, 35.01, 74.83, 114.60,
127.76, 128.38, 130.50, 134.43, 140.12, 173.27; FABHRMS
Found: m/z 172.1108. Calcd for C12H14N: M + H, 172.1127.
Acetophenone (E)-O-Pentafluorobenzoyloxime (E-9k):
White powder; IR (KBr) 1766, 1649, 1500, 1332, 1203, 995, 885,
694 cm−1; 1H NMR (500 MHz, CDCl3) δ 2.46 (3H, s), 7.42–7.46
14 X. Lin, D. Stien, and S. M. Weinreb, Org. Lett., 1, 637
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15 A. Ono and K. Narasaka, Chem. Lett., 2001, 146.
16 T. Hosokawa, N. Shimo, K. Maeda, A. Sonoda, and S.-I.
Murahashi, Tetrahedron Lett., 1976, 383.
17 M. Frederickson, R. Grigg, J. Markandu, M. Thornton-
Pett, and J. Redpath, Tetrahedron, 53, 15051 (1997).
18 H. Tsutsui and K. Narasaka, Chem. Lett., 1999, 45.
19 M. Kitamura, S. Zaman, and K. Narasaka, Synlett, 2001,
974.
1
(2H, m), 7.47–7.51 (1H, m), 7.77–7.80 (2H, m); H NMR (500
MHz, C6D6) δ 1.90 (3H, s), 6.97–7.05 (2H, m), 7.06–7.09 (1H,
m), 7.57–7.60 (2H, m); 13C NMR (125 MHz, CDCl3) δ 14.9,
107.1 (m), 127.2, 128.7, 131.1, 134.0, 136.9 (m), 138.9 (m), 142.4
(m), 144.5 (m), 146.5 (m), 156.4, 165.0; Anal. Found: C, 54.67; H,
2.64; N, 4.26%. Calcd for C15H18F5NO2: C, 54.72; H, 2.45; N,
4.25%.
20 H. Tsutsui and K. Narasaka, Chem. Lett., 2001, 526.
21 H. Tsutsui, Y. Hayashi, and K. Narasaka, Chem. Lett.,
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22 The chemical shift of Pd(PPh3)4 is 15.8 ppm in THF, see:
E. Negishi, T. Takahashi, and K. Akiyoshi, J. Chem. Soc., Chem.
Commun., 1986, 1338.
23 C. M. P. Ferreira, M. F. C. Guedes da Silva, V. Y.
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Chem. Soc., Dalton Trans., 1998, 325.
24 T. Nishimura and S. Uemura, J. Am. Chem. Soc., 122,
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