Efficient Regio- And Stereoselective Synthesis of 5-Alkyl(aryl)idene- and 5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5//)-ones via Electrophilic Cyclization

Article abstract of DOI:10.1055/s-0028-1083257

A variety of substituted 5-alkyl(aryl)idene-and 5-[1o-doalkyl(aryl)idene]- 1ff-pyrrol-2(5H)-ones were readily prepared with good yields under very mild reaction conditions by the iodocy- clization of (2Z,4E)-dienamides and (Z)-alk-2-en-4-ynamides with iod

Full text of DOI:10.1055/s-0028-1083257

PAPER
257
Efficient Regio- and Stereoselective Synthesis of 5-Alkyl(aryl)idene- and
5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones via Electrophilic Cyclization
S
ynthesis of 5-Alk
h
yl(aryl)idene
a
-
and 5-[Io
l
doalky
i
l
e
ne]-1
H
-pyr
C
H
)
-ones herry,a Alain Duchêne,a Jérôme Thibonnet,a Jean-Luc Parrain,b Elsa Anselmi,a Mohamed Abarbri*a
a
Laboratoire de Physicochimie des Matériaux et de Biomolécules, EA 4244, Faculté des Sciences de Tours,
Parc de Grandmont, Université de Tours, 37200 Tours, France
Fax +33(2)47367073; E-mail: mohamed.abarbri@univ-tours.fr
Institut des Sciences Moléculaires de Marseille, équipe Stéréo UMR-CNRS 6263, Université Paul Cézanne,
b
Campus Scientifique de Saint Jérôme, Avenue Escadrille Normandie-Niemen, Service 532, 13397 Marseille cedex 20, France
Received 29 July 2008; revised 21 August 2008
Isoindolinones have previously been prepared via
Grignard22 or lithiation23 procedures, as well as by
Wittig,24 Diels–Alder,21,25 rearrangement26 and photo-
chemical reactions.27 The reduction of N-substituted
Abstract: A variety of substituted 5-alkyl(aryl)idene- and 5-[io-
doalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones were readily prepared
with good yields under very mild reaction conditions by the iodocy-
clization of (2Z,4E)-dienamides and (Z)-alk-2-en-4-ynamides with
iodine monochloride. 3-Ylidene-isoindolin-1-ones were also syn- phthalimides28 and the condensation of phthalaldehyde29
thesized in moderate to good yields under the same conditions. The
also affords isoindolinones. Besides the classical meth-
methodology proceeded with total regioselectivity in all cases and
ods, metal-catalyzed synthesis of isoindolinones has also
was applied to the synthesis of new unsaturated lactam compounds.
been reported. Cobalt, rhodium, and palladium complexes
Key words: alkylidene-pyrrolones, electrophilic cyclization, di-
enamides, regioselectivity, iodocyclization
can be used as catalysts for the synthesis of isoindolin-
ones.30,31
We recently reported the regioselective synthesis of a-py-
rones, a-pyridones, and isoquinolinones under palladium
The iodocyclization of heteroatoms such as oxygen, nitro-
complex catalysis by coupling (tributylstannyl)allenes
gen, and sulfur with tethered alkynes has proved to be an
with (Z)-iodovinylic acid or (Z)-iodovinylic amide deriv-
effective method for the preparation of a wide variety of
atives.32,33 We have also described the synthesis of dienoic
heterocyclic ring systems.1–7 Important heterocycles such
acids and enynoic acids from b-iodovinylic acids and vi-
as furans,1 pyrroles,2 thiophenes,3 indoles,4 quinolines,8
nyltins and alkynylzinc reagents, respectively.34 This
and others5–7 have been accessed using this protocol.
methodology was then applied to the synthesis of 5-
alkyl(aryl)idene-substituted furan-2(5H)-ones.9 In addi-
tion, we have also described our first results for the
regioselective synthesis of 5-alkyl(aryl)idene- and 5-
[iodoalkyl(aryl)idene)]-1H-pyrrol-2(5H)-ones by iodolac-
tamization of (2Z,4E)-dienamides and (Z)-alk-2-en-4-
ynamides, respectively.35 In continuation of these studies,
we report here full details of a successful electrophilic cy-
clization strategy as a convenient and general regioselec-
tive method for the synthesis of 5-ylidene- or 5-(iodo-
ylidene)-substituted 1H-pyrrol-2(5H)-ones 4 and the ex-
tension of this method to the synthesis of 3-ylidene-
substituted isoindolin-1-ones 5 (Figure 1).
Our success in employing this process for the synthesis of
5-alkyl(aryl)idenefuran-2(5H)-ones9 led us to explore the
possibility of preparing 5-ylidene-1H-pyrrol-2(5H)-ones
(1,5-dihydro-2H-pyrrol-2-ones) and derivatives thereof
by the same approach. The 5-ylidene-1H-pyrrol-2(5H)-
one structural unit 4 (Figure 1) is found in a range of bio-
logically important natural products including holomy-
cin,10 pukeleimide,11 isoampullicin,12 and the bile pigment
bilirubin.13 Although extensive methodology has been de-
veloped for the construction of 5-ylidene-furan-2(5H)-
ones and 4-ylidene-tetronic acids,14 few synthetic studies
have been published involving 5-ylidene-1H-pyrrol-
2(5H)-ones 4.15 In particular, 5-ylidene-1H-pyrrol-2(5H)-
ones have been obtained through the reaction of transi-
tion-metal-coordinated bis(imidoyl) chlorides with car-
bon nucleophiles16 maleimides and from 1H-pyrrol-
2(5H)-ones.17 The isoindolin-1-one (2,3-dihydro-1H-in-
dol-1-one) ring system represents a key structural subunit
in numerous natural and synthetic products exhibiting a
wide range of biological activity, including antihyperten-
sive,18 anti-inflammatory,19 antiulcer,20 and anti-
leukemic21 properties.
O
N
O
N
4
5
5-ylidene pyrrol-2(5H)-ones
3-ylidene isoindolin-1-ones
Figure 1
Synthesis of 5-Ylidene-1H-pyrrol-2(5H)-ones 4 and 3-
Ylidene-isoindolin-1-ones 5
SYNTHESIS 2009, No. 2, pp 0257–0270
Advanced online publication: 01.12.2008
DOI: 10.1055/s-0028-1083257; Art ID: Z17608SS
© Georg Thieme Verlag Stuttgart · New York
x
x
.
x
x
.2
0
0
8
We began by examining the halolactamization of (2Z,4E)-
dienamides 3 using several electrophilic halogen sources

258
K. Cherry et al.
PAPER
(ICl, I2, I2/KI, NBS, etc.);36 for the synthesis of 3 see A wide variety of unsaturated amides 3 were examined in
Schemes 1 and 2. Iodine monochloride was found to be this cyclization process. Excellent yields of amides 3a–k
the best reagent to obtain fair to good yields of 5-alky- were obtained by treatment of the corresponding (2Z,4E)-
lidene-1H-pyrrol-2(5H)-ones 4a–h as the sole product dienoic acids 2a–i with oxalyl chloride followed by the
(Scheme 3, Table 1, entries 1–9). In all cases, the five- addition of a primary or secondary amine (Scheme 1).37
membered ring products were obtained without any trace
The results varied according to the degree of substitution
of the six-membered ring lactam, giving a regioselective
on the nitrogen. Attempts to cyclize unsubstituted
character to the electrophilic cyclization strategy where
(Table 1, entry 10) or disubstituted amides (Table 1, entry
11) under our conditions proved unsuccessful. Moreover,
the reaction of pentadienamide 3k in the presence of io-
dine monochloride afforded only trace amounts of the
only 5-exo mode cyclization was observed (Scheme 3).
The use of other sources (NIS, NBS, I2/KI, etc.) as the
electrophilic reagents led to lower yields (<50%).
The influence of the reaction solvents were examined at product 4k, with the recovery of significant amounts of
room temperature using diethyl ether, tetrahydrofuran, the starting material and polymerization of the product
acetonitrile, toluene, and dichloromethane. The latter (Table 1, entry 12).
gave the best results, which we believe may be due to a
greater ability to solubilize iodine monochloride. Diethyl
Other halogen sources used did not affect the exo selectiv-
ity of these iodocyclization reactions. After experiment-
ether, tetrahydrofuran, and toluene were found to be inef-
ing with a variety of conditions and methods, it was found
fective, and acetonitrile afforded a poor yield (<40%) of
that the best result of the final electrophilic cyclization
cyclized product. Similar regioselectivity was also ob-
step was obtained by using iodine monochloride as elec-
served in all cases, and only the five-membered ring prod-
trophilic halogen source in dichloromethane at room tem-
ucts were obtained.
perature, providing good yields of 5-alkyl(aryl)idene-1H-
Interestingly, the cyclization reaction was followed by a pyrrol-2(5H)-ones 4a–h (Scheme 3, Table 1).
spontaneous in situ dehydrohalogenation reaction provid-
This method was then applied to the synthesis of 3-
ing 5-ylidene-1H-pyrrol-2(5H)-ones 4a–h. This took
ylidene-isoindolin-1-ones 5. Indeed, (E)-2-alk-1-enyl-N-
place without the necessity for a base (Scheme 3,
benzylbenzamides 3l–n reacted with iodine monochloride
to produce the corresponding 3-alkyl(aryl)idene-2-ben-
Table 1), in contrast to our previously reported results in
the 5-alkylidenefuran-2(5H)-ones series (DBU induced
zylisoindolin-1-ones 5a–c as the sole products in fair to
dehydrohalogenation to form the exocyclic double
good yields (Scheme 3, Table 1). Good yields of (E)-2-
alk-1-enyl-N-benzylbenzamides 3l–n were obtained by
treatment of the corresponding (E)-2-alk-1-enylbenzoic
acids 2j–l with oxalyl chloride followed by addition of
bond).9 The addition of sodium hydrogen carbonate im-
proved the yield in this reaction (Table 1, cf. entries 1 and
2), although it was only a marginal effect.
benzylamine (Scheme 2). Acids 2j–l were prepared by
R1
R1
R1
Bu3Sn
R2
R2
1) (COCl)2
2) R3NH2
R2
I
PdCl2(MeCN)2, DMF
(R4)HN
R3
O
HO
O
HO
O
2a R1 = R2 = Ph
3a R1 = R2 = Ph, R3 = Bn
1a R1 = Ph
1b R1 = H
2b R1 = Ph, R2 = SiMe3
2c R1 = H, R2 = SiMe3
3b R1 = Ph, R2 = SiMe3, R3 = Bn
3c R1 = Ph, R2 = SiMe3, R3 = CH(i-Pr)Me
3d R1 = H, R2 = SiMe3, R3 = CH(Ph)Me
3e R1 = CH2OMe, R2 = SiMe3, R3 = m-MeOC6H4
3f R1 = Me, R2 = SiMe3, R3 = Bn
3g R1 = Me, R2 = SiMe3, R3 = m-MeOC6H4
3h R1 = Me, R2 = Ph, R3 = Bn
1c R1 = CH2OMe
1d R1 = Me
2d R1 = CH2OMe, R2 = SiMe3
2e R1 = Me, R2 = SiMe3
2f R1 = Me, R2 = (CH2)4Me
2g R1 = Me, R2 = i-Pr
2h R1 = Me, R2 = Ph
2i R1 = Me, R2 = H
3i R1 = Me, R2 = i-Pr, R3 = H
3j R1 = Me, R2 = Ph, R3 = R4 = i-Pr
3k R1 = Me, R2 = H, R3 = Bn
Scheme 1
O
I
O
O
Bu3Sn
OH
1) (COCl)2
2) BnNH2
R
NHBn
R
OH
PdCl2(MeCN)2
DMF, 25 °C
R
2j R = Ph (77%)
2k R = (CH2)4Me (75%)
2l R = SiMe3 (79%)
3l R = Ph (85%)
3m R = (CH2)4Me (82%)
3n R = SiMe3 (84%)
Scheme 2
Synthesis 2009, No. 2, 257–270 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-Alkyl(aryl)idene- and 5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones
259
R1
O
N
R3
or
I+
R2
(Z)-4a–h
R2
R2
R2
– HI
i
I
3a–k
O
O
O
N+
N
R3
N
R3
HN
R3
O
H
R3
R2
(Z)-5a–c
O
N
R2
Bn
Scheme 3 Reagents and conditions: (i) ICl, CH2Cl2, 0 to 25 °C, 12 h.
Stille coupling of the 2-iodobenzoic acid with tributyl(vi- 1–9 and 13–15). The selectivity observed was largely in
nyl)tins.34
favor of E stereochemistry of the exocyclic double bond.
Nevertheless, selectivity was highly dependent on tem-
perature and the nature of the substituent. For the first
time, (silylmethylene)-1H-pyrrol-2(5H)-ones 4b–g were
obtained with mainly E stereochemistry for the exocyclic
double bond, which was confirmed by NOESY experi-
ments. It should be noted that 4b–g isomerized rapidly at
25 °C, largely in favor of Z stereochemistry during chro-
matography on silica gel. In the case of the formation of
4a and 4h, the desired 5-benzylidene-1H-pyrrol-2(5H)-
ones were obtained with only Z configuration of the exo-
cyclic double bond (Table 1, entries 1 and 9). This can be
explained by the greater thermodynamic stability of the Z-
isomers of 4a and 4h compared to the E-isomers, in which
The isoindolinones were distinguishable from the iso-
quinolinones on the basis of their IR spectra. The five-
membered ring products generally exhibited a carbonyl
absorption band at 1710–1690 cm–1, while in the six-
membered ring products the carbonyl absorption was ob-
served at 1640–1650 cm–1.23b,33,38 The results are summa-
rized in Table 1.
The reactions of a range of unsaturated amides 3a–n with
iodine monochloride in dichloromethane under regio- and
stereo control provided fair to good yields of 5-alkyl(ar-
yl)idene-1H-pyrrol-2(5H)-ones 4a–h or 3-ylidene-iso-
indolin-1-ones 5a–c as the sole products (Table 1, entries
Table 1 Synthesis of 5-Alkyl(aryl)idene-1H-pyrrol-2(5H)-ones 4 and 3-Ylidene-isoindolin-1-ones 5
Entry
1
R1
R2
R3
Product
4a
Yield (%)
Ratioa Z/E
100:0
100:0
10:90
5:95
6:94
3:97
5:95
7:93
100:0
–
Ratiob Z/E
100:0
100:0
100:0
100:0d
78:22
100:0
100:0
100:0
100:0
–
Ph
Ph
Bn
55
56
80
77
58
78
50
51
70
0
2c
3
Ph
Ph
Bn
4a
Ph
SiMe3
SiMe3
SiMe3
SiMe3
SiMe3
SiMe3
Ph
Bn
4b
4c
4
Ph
CH*(i-Pr)Me (S)
5
H
CH(Ph)Me
4d
4e
6
Me
Me
CH2OMe
Me
Me
Me
Me
Me
Me
Me
Bn
7
3-MeOC6H4
4f
8
3-MeOC6H4
4g
9
Bn
H
4h
4i
10
11e
12
13
14
15
i-Pr
Ph
i-Pr
Bn
Bn
Bn
Bn
4j
0
–
–
H
4k
5a
trace
50
60
60
–
–
Ph
11:89
23:77
17:83
100:0
100:0
100:0
(CH2)4Me
SiMe3
5b
5c
a Before isomerization reaction.
b After spontaneous isomerization.
c Using 2 equiv of NaHCO3.
d [a]D25 +29 (c 1.82, CH2Cl2).
e (2Z,4E)-N,N-Diisopropyl-3-methyl-5-phenylpenta-2,4-dienamide was used in this case.
Synthesis 2009, No. 2, 257–270 © Thieme Stuttgart · New York

260
K. Cherry et al.
PAPER
the extensive interaction of the ortho hydrogens of the Indeed, good yields of 5-[iodoalkyl(aryl)idene]-1H-pyr-
phenyl group and the substituent group prevent conjuga- rol-2(5H)-ones 7a–d were easily prepared upon exposure
tion. As shown in Table 1, we obtained enantiomerically of 6a,b and 6d,e to 3.1 equivalents of iodine monochlo-
pure (silylmethylene)-1H-pyrrol-2(5H)-one 4c from the ride in dichloromethane at room temperature for four
available optically active dienamide 3c (Table 1, entry 4), hours in the presence of three equivalents of sodium hy-
and in all cases the 5-ylidene-1H-pyrrol-2(5H)-ones 4 and drogen carbonate (Scheme 4, Table 3). A wide variety of
3-ylidene-isoindolin-1-ones 5 were obtained without any alkynylcarboxamides were examined in this cyclization
trace of 2-pyridones and isoquinolinones, respectively.
process. In all cases, this iodocyclization reaction pro-
ceeded via the 5-exo-dig process, and the corresponding
six-membered ring lactams were not observed in any case.
The exocyclic double bond formed had mainly the E con-
figuration, except in the case of 7b (Table 3, entry 2)
where significant amounts of Z-isomer were observed.
This stereochemistry of pyrrolones 7a–d was assigned us-
ing a NOESY experiment. The E-isomer compounds ex-
hibited a cross-peak between the CH2 of the benzyl group
and the protons of the substituent R2 group. No products
involving the simple addition of the electrophile iodine
monochloride to the alkyne triple bond were observed
with any of these alkynes. As shown in Table 3, the prod-
uct 7d was obtained after spontaneous deprotection on a
silica gel column.
We believe that such 5-exo-trig cyclization proceeds by
anti attack of the electrophile and the nitrogen atom on the
alkene, resulting in a presumed intermediate product. De-
hydrohalogenation of the presumed intermediate product
to the 5-alkyl(aryl)idene-1H-pyrrol-2(5H)-ones and 3-
ylidene-isoindolin-1-ones is evidently rapid, even in the
absence of a base, since intermediates were not observed.
It should be noted that the 5-ylidene-1H-pyrrol-2(5H)-
ones and 3-ylidene-isoindolin-1-ones were not stable and
gradually decomposed upon heating or exposure to air. It
was also necessary to neutralize the silica gel during chro-
matography using a base such as triethylamine to avoid
their decomposition.
We propose the following mechanism to explain this elec-
trophilic cyclization (Scheme 4): nucleophilic attack by
the nitrogen of the amide group on the C≡C bond activat-
ed by coordination with I+ is followed by deprotonation to
yield the cyclized products.
Synthesis and Reactivity of 5-[Iodoalkyl(aryl)idene]-
1H-pyrrol-2(5H)-ones 7a–e
We next chose to extend our method by investigating sim-
ilar cyclization of (Z)-alk-2-en-4-ynamides 6a–e. Alk-2-
en-4-ynamides 6a–e were prepared via the Sonogashira
cross-coupling reactions39 of terminal alkynes with (Z)-N-
benzyl-3-iodoalk-2-enamides (Table 2). The yields of this
process ranged from 69% to 81%, and no polymerization
or cyclized products were detected in this procedure.
Reactivity of 1-Benzyl-5-(iodoarylidene)-1H-pyrrol-
2(5H)-one 7b
The 5-(iodo-ylidene)-1H-pyrrol-2(5H)-ones produced by
this method will be very valuable for the synthesis of a
Table 2 Synthesis of (Z)-Enynamides 6a–e
R1
R1
PdCl2(PPh3)2 (2.5 mol%), CuI (5 mol%)
R2
I
+
6a–e
Et3N, DMF, 25 °C
R2
HN
Bn
O
HN
Bn
O
Entry
R1
R2
Product
6a
Yield (%)
1
2
3
4
5
H
Ph
69
81
70
73
75
Me
Ph
Me
Me
Ph
6b
Ph
6c
SiMe3
6d
C(OTHP)Me2
6e
R1
R1
R1
R1
I+
I+
– H+
I
I
O
O
N+
N
R2
R2
H
R2
Bn
R2
HN
Bn
O
HN
Bn
O
Bn
6a,b,d,e
7a–d
Scheme 4
Synthesis 2009, No. 2, 257–270 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-Alkyl(aryl)idene- and 5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones
261
Table 3 Synthesis of 5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-
ones 7a–d
enamides or (Z)-enynamides was developed under very
mild experimental conditions. A wide range of dien-
amides and enynamides readily underwent cyclization us-
ing iodine monochloride. The resulting iodine-containing
products can be readily developed to more complex prod-
ucts using the Suzuki cross-coupling reaction. This meth-
odology was general and was extended to the regio-
selective synthesis of 3-alkyl(aryl)idene-isoindolin-1-
ones with good yields. Investigations into synthetic ap-
plications for biologically active natural products are cur-
rently in progress.
Entry
R1
R2
Product Ratio E/Z Yielda (%)
1
2
3
4
H
Ph
7a
7b
7c
7d
90:10
65:35
85:15
90:10
65
79
75
70b
Me
Me
Me
Ph
SiMe3
C(OH)Me2
a Isolated yield.
b After subsequent deprotection on silica gel.
All reactions were carried out under inert atmosphere (Ar or N2).
THF and Et2O were dried and freshly distilled from Na/benzophe-
none. DMF and CH2Cl2 were dried by distillation over CaH2. The
petroleum ether (PE) used was the fraction boiling in the range 60–
90 °C. Flash chromatography was carried out with Merck silica gel
wide variety of 5-ylidene-1H-pyrrol-2(5H)-ones. For ex-
ample, the 1-benzyl-5-(iodoarylidene)-1H-pyrrol-2(5H)-
one 7b produced by this strategy can be further function-
alized by applying palladium-catalyzed coupling reac-
tions. Suzuki cross coupling40 of 7b with vinyl- or
arylboronic acids, using toluene as solvent, ethanol as co-
solvent and 3 mol% of tetrakis(triphenylphosphine)palla-
dium(0) as catalyst provided good yields of stereoselec-
tive synthesis of the desired products 8a–f (Table 4).
1
(silica gel, 230–400 mesh). H NMR spectra were recorded at 200
or 300 MHz using CDCl3 as solvent. Findings, reported using the
residual solvent proton resonance of CDCl3 (dH = 7.25) as internal
reference. 13C NMR was recorded at 50.3 MHz using the CDCl3 sol-
vent peak at dC = 77.0 as reference. Mass spectra were obtained in
the GC/MS (70 eV) mode. Melting points were uncorrected. The
acids 2a–i were prepared via the Stille cross-coupling reaction of vi-
nyltin reagents with (Z)-3-iodoalk-2-enoic acids.41 (Z)-N-Benzyl-3-
iodoalk-2-enamides were prepared from (Z)-3-iodoalkenoic acids
by a previously described procedure.42
Table 4 Suzuki Cross-Coupling of 7b
Pd(PPh3)4, toluene/EtOH
I
R
RB(OH)
+
2
O
O
Na2CO3, 50 °C, 12 h
Dienoic Acids 2a–l; General Procedure
N
N
Ph
Ph
(Z)-3-Iodoalk-2-enoic acid (10 mmol) diluted in DMF (5 mL) was
added dropwise soln of the vinyltin reagent (12 mmol) in DMF. At
the end of the addition, PdCl2(MeCN)2 (129 mg, 0.5 mmol) was
added. The mixture was stirred at 25 °C for 3 h then hydrolyzed with
1 M KF soln and filtered. The organic layer was washed with sat.
NH4Cl soln and treated with 1 M NaOH soln. After washing with
Et2O, the aqueous layer was acidified with 1 M HCl soln and ex-
tracted with Et2O and the combined extracts were dried (MgSO4).
The solvent was removed and the crude products were purified us-
ing column chromatography (silica gel, PE–Et2O, 70:30) or by crys-
tallization (Et2O).
Bn
Bn
7b (E/Z = 65:35)
8a–f
Entry
R
Product
8a
Ratio E/Z
90:10
75:25
10:90
88:12
85:15
–
Yield (%)
1
2
3
4
5
6
4-MeC6H4
3-thienyl
CH=CHt-Bu
4-BrC6H4
3-ClC6H4
Ph
71
65
62
67
60
75
8b
8c
8d
(2E,4E)-3,5-Diphenylpenta-2,4-dienoic Acid (2a)43
Mp 142 °C (Lit. 140–142 °C).
IR (KBr): 3444, 3057, 1681, 1613, 1585, 1409, 1265 cm–1.
8e
8f
1H NMR (200 MHz, CDCl3): d = 5.91 (s, 1 H), 6.71 (d, J = 16.2 Hz,
The use of (E)-tert-butylvinylboronic acid reagent permit- 1 H), 7.42 (m, 10 H), 8.54 (d, J = 16.2 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 116.9, 125.7, 127.6, 128.3, 128.7,
ted the transfer of a vinyl group with retention of the con-
figuration of the double bond, and no polymerization
products were observed (Table 4, entry 3). As shown in
Table 4, the selectivity of products 8 observed was largely
in favor of E stereochemistry of the exocyclic double
bond, except in the case of 8c, which was obtained with
mainly Z configuration. It should be possible to prepare
128.8, 128.9, 129.0, 136, 139, 140.8, 159, 171.9.
MS (EI): m/z (%) = 250 [M+, 16], 205 (100), 190 (13), 178 (6), 165
(6), 127 (13), 101 (17), 77 (15).
HRMS (EI): m/z [M]+ calcd for C17H14O2: 250.0994; found:
250.0991.
many other substituted pyrrolones using these iodo sub- (2E,4E)-3-Phenyl-5-(trimethylsilyl)penta-2,4-dienoic Acid (2b)
Mp 160 °C.
strates and other known palladium methodology.
IR (KBr): 3400, 3025, 2978, 2868, 1697, 1616, 1595, 1550, 1415,
The aim of this research was to develop an efficient and
inexpensive method for the synthesis of a library of (Z)-5-
ylidene-1H-pyrrol-2(5H)-ones under mild and sample
conditions.
1250 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.07 (s, 9 H), 5.89 (d, J = 18.6 Hz,
1 H), 5.95 (s, 1 H), 6.76 (d, J = 18.6 Hz, 1 H), 7.08–7.10 (m, 2 H),
7.35–7.40 (m, 3 H).
13C NMR (50 MHz, CDCl3): d = –1.6, 119.6, 127.6 (3 C), 128.4 (2
C), 135.9, 142.9, 145.7, 157.2, 171.6.
Efficient, regio- and stereoselective synthesis of 5-
alkyl(aryl)idene-1H-pyrrol-2(5H)-ones from (2Z,4E)-di-
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K. Cherry et al.
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MS (EI): m/z (%) = 246 [M+, 3], 231 (7), 173 (100), 156 (14), 128
IR (KBr): 3160, 1675, 1615, 1595, 1090 cm–1.
(24), 75 (56).
1H NMR (200 MHz, CDCl3): d = (s, 3 H), 5.75 (br s, 1 H), 6.89 (d,
J = 17.0 Hz, 1 H), 7.15–7.39 (m, 3 HAr), 7.42–7.44 (m, 2 HAr), 8.29
(d, J = 17.0 Hz, 1 H), 11.46 (br s, 1 H).
HRMS (EI): m/z [M]+ calcd for C14H18O2Si: 246.1076; found:
246.1081.
13C NMR (50 MHz, CDCl3): d = 21.2, 117.3, 126.0, 127.6, 128.8,
(2Z,4E)-5-(Trimethylsilyl)penta-2,4-dienoic Acid (2c)44,45
Mp 102 °C.
IR (KBr): 3430, 3049, 2957, 2856, 1680, 1618, 1244 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.18 (s, 9 H), 5.73 (d, J = 11.4 Hz,
1 H), 6.38 (d, J = 18.4 Hz, 1 H), 6.69 (dd, J = 11.4, 11 Hz, 1 H), 7.79
(dd, J = 18.4, 11 Hz, 1 H), 11.1 (br s, 1 H).
129.0, 136.3, 136.7, 153.2, 171.8.
MS (EI): m/z (%) = 188 (M+, 24), 143 (100), 142 (37), 141 (30), 77
(24).
(Z)-3-Methylpenta-2,4-dienoic Acid (2i)46
Mp 78–80 °C.
13C NMR (50 MHz, CDCl3): d = –1.71 (d, JSi-C = 53 Hz), 116.6,
IR (neat): 3140, 1686, 1610, 1264, 1190 cm–1.
139.1, 147.3, 148.8, 171.6.
1H NMR (200 MHz, CDCl3): d = 2.04 (s, 3 H), 5.49 (d, J = 10.8 Hz,
1 H), 5.64 (d, J = 17.5 Hz, 1 H), 5.76 (s, 1 H), 7.80 (dd,
J = 17.5, 10.8 Hz, 1 H).
MS (EI): m/z (%) = 97 [M+ – (SiMe3), 12], 75 (56), 71 (100), 43
(79), 42 (82).
13C NMR (50 MHz, CDCl3): d = 20.6, 117.6, 121.5, 134.0, 153.4,
(2Z,4E)-3-(Methoxymethyl)-5-(trimethylsilyl)penta-2,4-dieno-
172.0.
ic Acid (2d)44,46
MS (EI): m/z (%) = 112 (M+, 8), 41 (18), 39 (18), 18 (100), 17 (38).
Mp 83 °C.
IR (KBr): 3400, 3081, 3024, 1685, 1622, 1288 cm–1.
(E)-2-Styrylbenzoic Acid (2j)49
Mp 159 °C.
1H NMR (200 MHz, CDCl3): d = 0.17 (s, 9 H), 3.45 (s, 3 H), 4.29
(s, 2 H), 6.05 (s, 1 H), 6.34 (d, J = 19.7 Hz, 1 H), 7.87 (d, J = 19.7
Hz, 1 H), 9.80 (br s, 1 H).
13C NMR (CDCl3, 50 MHz): d = –1.20 (d, JSi-C = 57 Hz), 59.0, 72.2,
116.0, 138.3, 138.4, 152.4, 172.3.
IR (KBr): 3430, 1684, 1565, 1481, 1447, 1405, 1300, 1275, 1250
cm–1.
1H NMR (200 MHz, CDCl3): d = 7.05 (d, J = 16 Hz, 1 H), 7.29–
7.51 (m, 4 H), 7.57–7.59 (m, 3 H), 7.77 (d, J = 8 Hz, 1 H), 8.05–8.14
(m, 2 H).
MS (EI): m/z (%) = 199 [M+ – Me, 5], 110 (83), 75 (100), 73 (47),
45 (78).
13C NMR (50 MHz, CDCl3): d = 126.9, 127.3, 127.4, 127.5, 127.9,
128.7, 131.7, 131.8, 133.2, 137.3, 140.2, 141.9, 173.1.
(2Z,4E)-3-Methyl-5-(trimethylsilyl)penta-2,4-dienoic Acid
(2e)46
2-[(E)-Hept-1-enyl]benzoic Acid (2k)
Mp 110 °C.
IR (neat): 3400–3300, 1637, 1577, 1464, 1376, 1338 cm–1.
IR (KBr): 3427, 3061, 3024, 2924, 2760, 1685, 1614, 1213 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.86 (t, J = 7 Hz, 3 H), 1.30–1.47
(m, 6 H), 2.20 (q, J = 6.5 Hz, 2 H), 6.11 (dt, J = 16, 7 Hz, 1 H),
7.15–7.37 (m, 3 H), 7.50 (d, J = 7.7 Hz, 1 H), 7.83 (dd, J = 7.6, 2
Hz, 1 H).
1H NMR (200 MHz, CDCl3): d = 0.18 (s, 9 H), 2.08 (s, 3 H), 5.81
(s, 1 H), 6.43 (d, J = 19.2 Hz, 1 H), 8.02 (d, J = 19.2 Hz, 1 H), 9.56
(s, 1 H).
13C NMR (50 MHz, CDCl3): d = –1.62 (d, JSi-C = 53 Hz), 20.7,
116.7, 139.1, 140.1, 154.0, 171.5.
13C NMR (50 MHz, CDCl3): d = 14.0, 22.5, 29.0, 31.5, 33.2, 126.3,
126.5, 129.0, 130.6, 130.8, 132.8, 138.7, 140.7, 173.0.
MS (EI): m/z (%) = 184 (M+, 8), 111 (47), 75 (45), 45 (60), 31 (100).
MS (EI): m/z (%) = 218 (M+, 2), 175 (28), 147 (11), 75 (100).
HRMS (EI): m/z [M]+ calcd for C14H18O2: 218.1307; found:
218.1310.
(2Z,4E)-3-Methyldeca-2,4-dienoic Acid (2f)44,47
IR (neat): 3415, 3052, 2930, 1690, 1618 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.93 (t, J = 6.5 Hz, 3 H), 1.32–
1.37 (m, 6 H), 2.05 (s, 3 H), 2.23–2.27 (m, 2 H), 5.65 (s, 1 H), 6.22
(dt, J = 15.8, 7 Hz, 1 H), 7.59 (d, J = 15.8 Hz, 1 H).
2-[(E)-2-(Trimethylsilyl)vinyl]benzoic Acid (2l)
IR (neat): 3400–3300, 2955–2855, 1692, 1635, 1563, 1464, 1336,
1247 cm–1.
13C NMR (50 MHz, CDCl3): d = 14.4, 21.7, 22.9, 29.1, 31.9, 33.8,
1H NMR (200 MHz, CDCl3): d = 0.24 (s, 9 H), 6.44 (d, J = 19 Hz,
1 H), 7.31 (td, J = 7.4, 1.3 Hz, 1 H), 7.47 (t, J = 7.6 Hz, 1 H), 7.66
(d, J = 6.9 Hz, 1 H), 7.80 (d, J = 19 Hz, 1 H), 7.96 (d, J = 7.2 Hz, 1
H), 11.7 (br s, 1 H).
115.5, 128.0, 140.7, 154.3, 172.3.
MS (EI): m/z (%) = 182 (M+, 6), 111 (100), 55 (10), 41 (12).
(2Z,4E)-3,6-Dimethylhepta-2,4-dienoic Acid (2g)48
Mp 90–92 °C.
13C NMR (50 MHz, CDCl3): d = –1.3, 126.7, 127.2, 130.6, 131.3,
131.9, 132.0, 139.9, 142.9, 173.2.
IR (KBr): 3380–2500, 3081, 3024, 1688, 1620, 1288 cm–1.
MS (EI): m/z (%) = 220 (M+, 7), 205 (10), 147 (33), 75 (100).
1H NMR (200 MHz, CDCl3): d = 1.60 (d, J = 8 Hz, 6 H), 2.06 (s, 3
H), 2.48–2.62 (m, 1 H), 5.67 (s, 1 H), 6.16 (dd, J = 16, 8 Hz, 1 H),
7.56 (d, J = 16 Hz, 1 H), 10.3 (s, 1 H).
HRMS (EI): m/z [M]+ calcd for C12H16O2Si: 220.0920; found:
220.0922.
Dienamides 3a–n; General Procedure
13C NMR (50 MHz, CDCl3): d = 21.8, 22.6 (2 C), 32.4, 115.7,
Oxalyl chloride (3 mmol) was added dropwise, at 0 °C, to acid 2 (1
mmol) dissolved in a minimum amount of CH2Cl2. The mixture was
stirred at r.t. for 3 h and then the excess of oxalyl chloride and the
solvent were removed under reduced pressure. The acyl chlorides
were sufficiently pure to be used without further purification. At
125.3, 147.2, 154.5, 172.4.
MS (EI): m/z (%) = 154 (M+, 5), 111 (100), 55 (17), 43 (17), 41 (23).
(2Z,4E)-3-Methyl-5-phenylpenta-2,4-dienoic Acid (2h)46
Mp 151–153 °C.
Synthesis 2009, No. 2, 257–270 © Thieme Stuttgart · New York

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Synthesis of 5-Alkyl(aryl)idene- and 5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones
263
–60 °C, amine (1.2 mmol) (freshly distilled over CaH2) were added
dropwise to the acyl chloride (1 mmol) diluted in Et2O (10 mL). The
temperature was slowly allowed to rise to 10 °C. After 1 h at 10 °C,
the mixture was quenched with sat. NH4Cl and extracted with Et2O
(3 × 25 mL) and the combined extracts were washed with brine and
dried (MgSO4). The crude amides 3 were purified by crystallization
(hexane–Et2O, 90:10) or by chromatography (silica gel, PE–Et2O,
70:30).
13C NMR (50 MHz, CDCl3): d = 1.0, 22.2, 49.1, 121.0, 126.7 (2 C),
128.1, 129.1 (2 C), 140.0, 143.6, 143.9, 144.4, 165.6.
MS (EI): m/z (%) = 273 (M+, 4), 200 (60), 154 (22), 120 (16), 105
(56), 96 (100), 79 (24), 77 (23).
HRMS (EI): m/z [M]+ calcd for C16H23NOSi: 273.1549; found:
273.1547.
(2E,4E)-3-(Methoxymethyl)-N-(3-methoxyphenyl)-5-(trimeth-
ylsilyl)penta-2,4-dienamide (3e)
White solid; mp 188–190 °C.
(2E,4E)-N-Benzyl-3,5-diphenylpenta-2,4-dienamide (3a)
White solid; mp 152 °C.
IR (KBr): 3276, 3020, 2954, 1640, 1619, 1573 cm–1.
IR (KBr): 3283, 3097, 2963, 2836, 1664, 1604, 1524, 1484, 1214
cm–1.
1H NMR (200 MHz, CDCl3): d = 0.09 (s, 9 H), 3.40 (s, 3 H), 3.73
(s, 3 H), 4.22 (s, 2 H), 6.00 (s, 1 H), 6.16 (d, J = 19.7 Hz, 1 H), 6.63
(br s, 1 H), 6.96–7.37 (m, 4 HAr), 7.86 (d, J = 19.2 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = –0.10, 54.1, 59.1, 72.2, 119.3,
128.0, 128.3 (2 C), 129.2 (2 C), 135.8, 138.6, 138.8, 146.2, 166.6.
MS (EI): m/z (%) = 246 (M+ – SiMe3, 3), 244 (71), 151 (9), 73 (100),
45 (12).
HRMS (EI): m/z [M]+ calcd for C17H25NO3Si: 319.1614; found:
319.1619.
1H NMR (200 MHz, CDCl3): d = 4.56 (d, J = 5.7 Hz, 2 H), 5.71 (s,
1 H), 6.09 (br s, NH), 6.55 (d, J = 16.3 Hz, 1 H), 7.28–7.48 (m, 15
HAr), 8.64 (d, J = 16.3 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 43.5, 120.6, 126.1, 127.3, 127.5,
127.8, 128.2, 128.5, 128.7, 128.9, 136.6, 138.3, 140.2, 152.4, 165.9.
MS (EI): m/z (%) = 339 (M+, 8), 262 (31), 248 (76), 205 (89), 106
(79), 91 (100).
HRMS (EI): m/z [M]+ calcd for C24H21NO: 339.1623; found:
339.1619.
(2E,4E)-N-Benzyl-3-phenyl-5-(trimethylsilyl)penta-2,4-dien-
amide (3b)
White solid; mp 118 °C.
IR (KBr): 3276, 3020, 2954, 1640, 1619, 1573 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.14 (s, 9 H), 4.59 (d, J = 5.7 Hz,
2 H), 5.76 (s, 1 H), 5.85 (br s, NH), 6.05 (d, J = 19.2 Hz, 1 H), 7.27–
7.41 (m, 10 HAr), 8.15 (d, J = 19.2 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = –0.95, 44.1, 121.5, 128.0, 128.4 (2
C), 128.5 (3 C), 129.2 (2 C), 129.5 (2 C), 138.7, 140.6, 140.7, 142.1,
153.1, 166.4.
MS (EI): m/z (%) = 335 (M+, 2), 262 (10), 91 (39), 73 (17).
HRMS (EI): m/z [M]+ calcd for C21H25NOSi: 335.1705; found:
(2Z,4E)-N-Benzyl-3-methyl-5-(trimethylsilyl)pent-2,4-dien-
amide (3f)
White solid; mp 116–118 °C.
IR (KBr): 3271, 3025, 2955, 1642, 1618, 1569, 1522 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.08 (s, 9 H), 1.91 (s, 3 H), 4.46
(d, J = 5.7 Hz, 2 H), 5.64 (s, 1 H), 5.80 (br s, 1 H), 6.20 (d, J = 19.2
Hz, 1 H), 7.26–7.29 (m, 5 H), 7.94 (d, J = 19.2 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = –0.9, 20.9, 43.9, 121.1, 127.9,
128.3, 129.2 (2 C), 137.0 (2 C), 138.7, 141.1, 147.3, 166.6.
MS (EI): m/z (%) = 273 (M+, 3), 201 (13), 200 (92), 91 (100), 75
(13).
HRMS (EI): m/z [M]+ calcd for C16H23NOSi: 273.1549; found:
273.1546.
335.1708.
(2E,4E)-N-(1,2-Dimethylpropyl)-3-phenyl-5-(trimethyl-
silyl)penta-2,4-dienamide (3c)
White solid; mp 172 °C.
IR (KBr): 3275, 3023, 2957, 1645, 1620, 1570, 1524 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.14 (s, 9 H), 0.97 (d, J = 6.8 Hz,
3 H), 0.98 (d, J = 6.8 Hz, 3 H), 1.17 (d, J = 6.7 Hz, 3 H), 1.70–1.83
(m, 1 H), 3.99–4.09 (m, 1 H), 5.45 (br s, NH), 5.74 (s, 1 H), 6.03 (d,
J = 19.2 Hz, 1 H), 7.32–7.41 (m, 5 HAr), 8.06 (d, J = 19.2 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = –0.9, 18.1, 18.9, 19.1, 33.4, 50.3,
122.5, 128.4, 128.5 (2 C), 129.5 (2 C), 140.5, 140.6, 140.8, 152.1,
165.9.
(2Z,4E)-N-(3-Methoxyphenyl)-3-methyl-5-(trimethylsilyl)pen-
ta-2,4-dienamide (3g)
White solid; mp 84–86 °C.
IR (KBr): 3252, 3097, 2953, 1645, 1609, 1496, 1211 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.08 (s, 9 H), 1.95 (s, 3 H), 3.74
(s, 3 H), 5.75 (s, 1 H), 6.26 (d, J = 19.2 Hz, 1 H), 6.61 (br s, 1 H),
7.00–7.27 (m, 3 HAr), 7.41–7.46 (m, 1 HAr), 7.98 (d, J = 19.2 Hz, 1
H).
13C NMR (50 MHz, CDCl3): d = –0.50, 21.1, 55.7, 106.1, 110.7,
112.8, 121.5, 130.0, 138.0, 139.9, 141.1, 149.1, 160.6, 166.8.
MS (EI): m/z (%) = 289 (M+, 5), 216 (70), 123 (14), 75 (11), 73
(100).
HRMS (EI): m/z [M]+ calcd for C16H23NO2Si: 289.1498; found:
289.1492.
MS (EI): m/z (%) = 315 (M+, 2), 242 (100), 229 (23), 172 (49), 73
(17).
HRMS (EI): m/z [M]+ calcd for C19H29NOSi: 315.2018; found:
315.2021.
(2Z,4E)-N-Benzyl-3-methylpenta-2,4-dienamide (3h)
White solid; mp 104–106 °C.
(2Z,4E)-N-(1-Phenylethyl)-5-(trimethylsilyl)penta-2,4-dien-
amide (3d)
White solid; mp 94–96 °C.
IR (KBr): 3305, 3064, 3031, 2927, 2857, 1644, 1602, 1538, 1454,
1378, 1268 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.13 (s, 3 H), 4.57 (d, J = 5.7 Hz,
2 H), 5.70 (s, 1 H), 6.88 (d, J = 16.4 Hz, 1 H), 7.31–7.58 (m, 10 H),
8.51 (d, J = 16.4 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 21.3, 43.9, 121.0, 126.7, 127.7,
128.0, 128.3, 128.8, 129.0, 129.2, 134.5, 137.3, 139.0, 147.2, 166.7.
IR (KBr): 3268, 3034, 2958, 1635, 1615, 1562, 1538, 1265, 1243
cm–1.
1H NMR (200 MHz, CDCl3): d = 0.07 (s, 9 H), 1.49 (d, J = 7 Hz, 3
H), 5.18 (dq, J = 7.1, 7 Hz, 1 H), 5.53 (d, J = 11.3 Hz, 1 H), 5.78 (br
s, 1 H), 6.13 (d, J = 18.4 Hz, 1 H), 6.35 (dd, J = 11.3, 10.7 Hz, 1 H),
7.25–7.32 (m, 5 HAr), 7.80 (dd, J = 18.4, 10.7 Hz, 1 H).
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MS (EI): m/z (%) = 277 (M+, 12), 128 (58), 91 (100), 65 (30).
HRMS (EI): m/z [M]+ calcd for C19H19NO: 277.36; found: 277. 35.
IR (neat): 3305, 3027, 1648, 1560 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.92 (t, J = 7.0 Hz, 3 H), 1.23–
1.27 (m, 6 H), 2.09–2.13 (m, 2 H), 4.44 (d, J = 6 Hz, 2 H), 6.10 (dt,
J = 16.6, 7.6 Hz, 1 H), 6.66 (d, J = 16.6 Hz, 1 H), 6.75–6.78 (m, 1
H), 7.05–7.45 (m, 9 H).
(2Z,4E)-3,6-Dimethylhepta-2,4-dienamide (3i)
White solid; mp 100–102 °C.
IR (KBr): 3310, 3097, 2965, 2833, 1658, 1612, 1214 cm–1.
13C NMR (50 MHz, CDCl3): d = 13.7, 22.2, 28.5, 31.1, 32.7, 43.4,
125.8, 126.2, 126.8, 126.9, 127.1, 127.4, 128.1, 129.5, 133.6, 134.3,
135.5, 138.0, 169.2.
1H NMR (200 MHz, CDCl3): d = 1.07 (d, J = 6 Hz, 6 H), 1.99 (s, 3
H), 2.45–2.55 (m, 1 H), 5.55 (br s, 2 H), 5.60 (s, 1 H), 6.03 (dd,
J = 16, 6 Hz, 1 H), 7.53 (d, J = 16 Hz, 1 H).
MS (EI): m/z (%) = 307 (M+, 5), 236 (15), 216 (15), 115 (15), 91
(100).
13C NMR (50 MHz, CDCl3): d = 21.5, 22.8 (2 C), 32.3, 118.4,
125.3, 145.2, 148.7, 169.4.
HRMS (EI): m/z [M]+ calcd for C21H25NO: 307.1936; found:
307.1939.
MS (EI): m/z (%) = 153 (M+, 2), 110 (100), 109 (3), 95 (7), 67 (14).
HRMS (EI): m/z [M]+ calcd for C9H15NO: 153.1154; found:
153.1158.
N-Benzyl-2-[(E)-2-(trimethylsilyl)vinyl]benzamide (3n)
White solid; mp 107 °C.
IR (KBr): 3285, 3064, 2954, 2870, 1638, 1528, 1455, 1247 cm–1.
(2Z,4E)-N,N-Diisopropyl-3-methyl-5-phenylpenta-2,4-dien-
amide (3j)
White solid; mp 78–80 °C.
IR (KBr): 3024, 2972, 1616, 1444, 1379, 1324 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.01 (d, J = 6.4 Hz, 6 H), 1.39 (d,
J = 6.4 Hz, 6 H), 1.92 (s, 3 H), 3.39–3.43 (m, 1 H), 3.95–3.99 (m, 1
H), 5.82 (s, 1 H), 6.56 (d, J = 16.2 Hz, 1 H), 7.05–7.33 (m, 6 H).
1H NMR (200 MHz, CDCl3): d = 0.12 (s, 9 H), 4.35 (d, J = 6 Hz, 2
H), 6.36 (d, J = 19 Hz, 1 H), 7.07–7.31 (m, 9 HAr), 7.49 (d, J = 7.8
Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = –1.7, 43.2, 125.4, 127.7, 126.8,
126.9, 127.2, 128.0, 129.2, 132.0, 134.8, 136.0, 138.0, 140.6, 169.0.
MS (EI): m/z (%) = 309 (M+, 3), 236 (54), 222, 178, 91 (100).
13C NMR (50 MHz, CDCl3): d = 19.0, 19.9, 45.1, 49.2, 124.2,
125.9, 126.1 (2 C), 127.1, 127.9 (2 C), 130.7, 136.3, 138.2, 166.7.
HRMS (EI): m/z [M]+ calcd for C19H23NOSi: 309.1549; found:
309.1553.
MS (EI): m/z (%) = 271 (M+, 8), 256 (18), 228 (19), 171 (100), 128
(84).
Enynamides 6a–e; General Procedure
PdCl2(PPh3)2 (0.1 mmol) was added to a stirred DMF soln (10 mL)
of alkyne (2.4 mmol) and Et3N (4.8 mmol) then after 5 min (Z)-N-
benzyl-3-iodoalk-2-enamide (2 mmol) and CuI (0.2 mmol) were
added to the soln. The mixture was stirred at r.t. for 4 h then hydro-
lyzed with sat. NH4Cl (20 mL). After the usual workup the crude
product was purified by column chromatography (silica gel, PE–
Et2O, 60:40).
HRMS (EI): m/z [M]+ calcd for C18H25NO: 271.1936; found:
271.1933.
(2Z)-N-Benzyl-3-methylpenta-2,4-dienamide (3k)
White solid; mp 80–82 °C.
IR (KBr): 3275, 3019, 2949, 1647, 1612, 1558 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.92 (s, 3 H), 4.42 (d, J = 5.6 Hz,
2 H), 5.33 (d, J = 11 Hz, 1 H), 5.47 (d, J = 17.5 Hz, 1 H), 5.61 (s, 1
H), 5.90 (br s, NH), 7.19–7.33 (m, 5 HAr), 7.81 (dd, J = 11, 17.5
Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 21.0, 44.0, 119.7, 121.2, 128.0,
129.3 (2 C), 129.3 (2 C), 134.8, 138.5, 147.0, 166.5.
(Z)-N-Benzyl-5-phenylpent-2-en-4-ynamide (6a)
White solid; mp 108–110 °C.
IR (KBr): 3490, 3045, 2245, 1670, 1620 cm–1.
1H NMR (200 MHz, CDCl3): d = 4.62 (d, J = 5.3 Hz, 2 H), 6.27 (s,
2 H), 7.04–7.41 (m, 10 HAr).
13C NMR (50 MHz, CDCl3): d = 44.6, 85.6, 101.2, 116.1, 122.0,
128.3, 128.9, 129.1 (2 C), 129.5, 130.1 (2 C), 132.3 (2 C), 134.1 (2
C), 138.3, 165.1.
MS (EI): m/z (%) = 261 (M+, 100), 260 (66), 91 (90), 77 (55), 65
(25).
HRMS (EI): m/z [M]+ calcd for C18H15NO: 261.1154; found:
261.1159.
MS (EI): m/z (%) = 201 (M+, 9), 186 (23), 106 (89), 95 (92), 91
(100), 77 (78).
HRMS (EI): m/z [M]+ calcd for C13H15NO: 201.1154; found:
201.1160.
(E)-N-Benzyl-2-styrylbenzamide (3l)10,
White solid; mp 126 °C.
IR (KBr): 3309, 3057, 2924, 1644, 1531, 1422, 1304 cm–1.
1H NMR (200 MHz, CDCl3): d = 4.64 (d, J = 5.7 Hz, 2 H), 6.2 (br
s, 1 H), 7.03 (d, J = 16 Hz, 1 H), 7.26–7.55 (m, 14 HAr), 7.69 (d,
J = 7.8 Hz, 1 H).
(Z)-N-Benzyl-3-methyl-5-phenylpent-2-en-4-ynamide (6b)
White solid; mp 116–118 °C.
IR (KBr): 3485, 3045, 2240, 1665, 1615 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.16 (d, J = 1.4 Hz, 3 H), 4.61 (d,
J = 5.6 Hz, 2 H), 6.15 (d, J = 1.4 Hz, 1 H), 7.06–7.39 (m, 10 HAr).
13C NMR (50 MHz, CDCl3): d = 25.4, 44.4, 87.5, 100.3, 121.8
126.8, 128.0, 128.6 (2 C), 128.9 (2 C), 129.2 (2 C), 129.7, 130.2,
132.0 (2 C), 138.5, 165.3.
MS (EI): m/z (%) = 275 (M+, 64), 274 (44), 115 (92), 91 (100), 51
(17).
13C NMR (50 MHz, CDCl3): d = 44.7, 126.5, 126.8, 127.4, 128.1,
128.2, 128.3, 128.5, 128.6, 129.3, 129.4, 130.8, 132.1, 136.0, 136.1,
137.5, 138.8, 171.0.
MS (EI): m/z (%) = 313 (M+, 27), 222 (82), 208 (32), 178 (72), 91
(100), 77 (30).
HRMS (EI): m/z [M]+ calcd for C22H19NO: 313.1467; found:
313.1471.
HRMS (EI): m/z [M]+ calcd for C19H17NO: 275.1310; found:
275.1317.
N-Benzyl-2-[(E)-hept-1-enyl]benzamide (3m)
White liquid.
Synthesis 2009, No. 2, 257–270 © Thieme Stuttgart · New York

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Synthesis of 5-Alkyl(aryl)idene- and 5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones
265
(Z)-N-Benzyl-3,5-diphenylpent-2-en-4-ynamide (6c)
Colorless prisms; mp 128–130 °C.
1H NMR (200 MHz, CDCl3): d = 4.90 (s, 2 H), 7.39–7.88 (m, 16 H),
8.29 (s, 1 H).
IR (KBr): 3487, 3045, 2245, 1670, 1615 cm–1.
1H NMR (200 MHz, CDCl3): d = 4.68 (d, J = 5.8 Hz, 2 H), 6.72 (s,
1 H), 7.14–7.75 (m, 15 HAr).
13C NMR (50 MHz, CDCl3): d = 44.6, 86.3, 102.0, 121.7, 127.3,
128.0, 128.2, 128.7 (2 C), 128.9 (2 C), 129.1 (2 C), 129.3 (2 C),
129.5 (2 C), 130.0 (2 C), 132.0, 137.5, 138.4, 165.4.
13C NMR (50 MHz, CDCl3): d = 46.5, 105.6, 106.4, 126.4 (2 C),
127.9 (2 C), 128.3 (2 C), 129, 129.6 (2 C), 129.7, 130 (2 C), 130.3
(2 C), 133.1, 133.3, 133.6, 135.1, 156.4, 160, 165.
MS (EI): m/z (%) = 337 (M+, 6), 220 (21), 91 (100), 77 (17), 65 (16).
HRMS (EI): m/z [M]+ calcd for C24H19NO: 337.1467; found:
337.1471.
MS (EI): m/z (%) = 337 (M+, 21), 246 (73), 202 (100), 201 (26), 91
(72).
HRMS (EI): m/z [M]+ calcd for C24H19NO: 337.1467; found:
337.1470.
(Z)-1-Benzyl-4-phenyl-5-[(trimethylsilyl)methylene]-1,5-dihy-
dro-2H-pyrrol-2-one [(Z)-4b]
White liquid; yield: 80%.
IR (neat): 2957, 1680, 1613 cm–1.
(Z)-N-Benzyl-3-methyl-5-(trimethylsilyl)pent-2-en-4-ynamide
(6d)
1H NMR (200 MHz, CDCl3): d = 0.3 (s, 9 H), 4.79 (s, 2 H), 5.15 (s,
1 H), 6.52 (s, 1 H), 7.33–7.49 (m, 9 H).
White solid; mp 131–133 °C.
IR (KBr): 3488, 3040, 2241, 1673, 1618 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.08 (s, 9 H), 2.05 (d, J = 1.2 Hz,
3 H), 4.57 (d, J = 5.4 Hz, 2 H), 6.11 (q, J = 1.2 Hz, 1 H), 7.26–7.37
(m, 5 HAr), 7.7 (br s, NH).
13C NMR (50 MHz, CDCl3): d = –0.2 (3 C), 53, 106, 124, 128.2,
129.5 (2 C), 129.8 (2 C), 130 (2 C), 130.2 (2 C), 131, 132.3, 140.7,
149.7, 159.8, 162.6.
MS (EI): m/z (%) = 333 (M+, 10), 305 (52), 91 (100), 73 (26), 65
(16).
13C NMR (50 MHz, CDCl3): d = –0.2 (3 C), 25.2, 44.0, 103.1,
107.1, 126.4, 128.0, 128.3 (2 C), 129.1 (2 C), 131.4, 138.5, 165.1.
HRMS (EI): m/z [M]+ calcd for C21H23NOSi: 333.1549; found:
333.1544.
MS (EI): m/z (%) = 271 (M+, 8), 180 (27), 106 (44), 91 (100), 77
(15).
HRMS (EI): m/z [M]+ calcd for C16H21NOSi: 271.1392; found:
271.1396.
(E)-1-Benzyl-4-phenyl-5-[(trimethylsilyl)methylene]-1,5-dihy-
dro-2H-pyrrol-2-one [(E)-4b]
1H NMR (200 MHz, CDCl3): d = 0.34 (s, 9 H), 4.88 (s, 2 H), 6.29
(s, 1 H), 7.35–7.60 (m, 9 H), 7.72 (s, 1 H).
13C NMR (50 MHz, CDCl3): d = –0.1 (3 C), 50.8, 110.3, 119.8,
127.6, 128.5 (2 C), 129 (2 C), 129.2 (2 C), 129.5 (2 C), 130.7, 131,
137, 152.4, 161.6, 164.4.
(Z)-N-Benzyl-3,6-dimethyl-6-(tetrahydro-2H-pyran-2-
yloxy)hept-2-en-4-ynamide (6e)
White solid; mp 71–73 °C.
IR (KBr): 3475, 3050, 2243, 1660, 1610 cm–1.
(Z)-1-(1,2-Dimethylpropyl)-4-phenyl-5-[(trimethylsilyl)methyl-
ene]-1,5-dihydro-2H-pyrrol-2-one [(Z)-4c]
White liquid; yield: 77%.
IR (neat): 2960, 1677, 1612 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.36 (s, 9 H), 1.10 (d, J = 6.7 Hz,
3 H), 1.12 (d, J = 6.7 Hz, 3 H), 1.55 (d, J = 6.7 Hz, 3 H), 2.10–2.27
(m, 1 H), 3.93–4.08 (m, 1 H), 6.27 (s, 1 H), 7.52–7.62 (m, 5 H), 7.75
(s, 1 H).
13C NMR (50 MHz, CDCl3): d = –0.03 (3 C), 17.2, 19.0, 19.6, 33.3,
59.0, 115.1, 125.5, 129, 129.3 (2 C), 130 (2 C), 132.3, 156.1, 160.1,
170.3.
1H NMR (200 MHz, CDCl3): d = 1.34–1.79 (m, 12 H), 2.04 (s, 3 H),
3.44–3.48 (m, 1 H), 3.87–3.91 (m, 1 H), 4.56 (d, J = 5.5 Hz, 2 H),
4.90–4.93 (m, 1 H), 6.07 (s, 1 H), 7.20–7.35 (m, 5 HAr), 7.57 (br s,
NH).
13C NMR (50 MHz, CDCl3): d = 20.4, 25.5, 25.7, 29.6, 30.2, 32.1,
43.9, 63.3, 71.0, 82.1, 96.1, 103.4, 126.2, 127.8, 128.3 (2 C), 129.0
(2 C), 130.5, 139.0, 165.1.
MS (EI): m/z (%) = 341 (M+, 4), 240 (28), 150 (27), 134 (33), 91
(100).
HRMS (EI): m/z [M]+ calcd for C21H27NO3: 341.1396; found:
341.1388.
MS (EI): m/z (%) = 313 (M+, 2), 270 (60), 75 (48), 73 (75), 43 (100).
HRMS (EI): m/z [M]+ calcd for C19H27NOSi: 313.1862; found:
313.1859.
5-Alkyl(aryl)idene-1,5-dihydro-2H-pyrrol-2-ones 4a–k, 5a–c
and 5-[Iodoalkyl(aryl)idene]-1,5-dihydro-2H-pyrrol-2-ones
7a–d; General Procedure
(E)-1-(1,2-Dimethylpropyl)-4-phenyl-5-[(trimethylsilyl)methyl-
ene]-1,5-dihydro-2H-pyrrol-2-one [(E)-4c]
ICl (1.7 g, 10.5 mmol) in anhyd CH2Cl2 (10 mL) was added drop-
wise at 0 °C to dienamide 3a–k (or enynamide 6a–e) (10 mmol).
Stirring was then maintained at r.t. for 3 h in darkness, the mixture
was hydrolyzed by dropwise addition of 5% Na2S2O3 soln until the
mixture became clear. The soln was then extracted with CH2Cl2
(3 × 15 mL) and dried (MgSO4). After evaporation of the solvent,
the products were obtained after purification by flash column chro-
matography (silica gel, PE–Et2O–Et3N, 80:19:1) or by crystalliza-
tion (Et2O) to yield 4a–k or 7a–e.
1H NMR (200 MHz, CDCl3): d = 0.34 (s, 9 H), 0.95 (d, J = 6.7 Hz,
3 H), 0.96 (d, J = 6.7 Hz, 3 H), 1.46 (d, J = 6.7 Hz, 3 H), 2.10–2.27
(m, 1 H), 3.91–4.05 (m, 1 H), 5.8 (s, 1 H), 7.54–7.65 (m, 5 H), 7.35
(s, 1 H).
(Z)-1-(1-Phenylethyl)-5-[(trimethylsilyl)methylene]-1,5-dihy-
dro-2H-pyrrol-2-one [(Z)-4d]
White liquid; yield: 58%; mixture of isomers.
(Z)-1-Benzyl-5-benzylidene-4-phenyl-1,5-dihydro-2H-pyrrol-2-
IR (neat): 2953, 2918, 1673, 1617, 1256 cm–1.
one (4a)
Colorless liquid; yield: 55%.
IR (neat): 2955, 1679, 1610 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.21 (s, 9 H), 1.52 (d, J = 6.7 Hz,
3 H), 4.84 (s, 1 H), 5.03 (q, J = 6.7 Hz, 1 H), 6.40 (d, J = 5.5 Hz, 1
H), 6.74 (d, J = 5.5 Hz, 1 H), 7.31–7.33 (m, 5 H).
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13C NMR (50 MHz, CDCl3): d = –0.04 (3 C), 25, 57.4, 105.8, 126.9,
127, 127.2, 129, 137.1, 146, 160.2, 163.2.
13C NMR (50 MHz, CDCl3): d = 1.7 (3 C), 55.7, 59.4, 67, 104.6,
109.7, 111.4 114.7, 116.7, 129.5, 147.2, 149.3, 158.3, 161.7, 164.1.
MS (EI): m/z (%) = 271 (M+, 6), 105 (100), 79 (13), 77 (11).
MS (EI): m/z (%) = 317 (M+, 21), 288 (25), 92 (27), 77 (36), 73
(100).
(E)-1-(1-Phenylethyl)-5-[(trimethylsilyl)methylene]-1,5-dihy-
dro-2H-pyrrol-2-one [(E)-4d]
HRMS (EI): m/z [M]+ calcd for C17H23NO3Si: 317.1447; found:
317.1454.
1H NMR (200 MHz, CDCl3): d = 0.17 (s, 9 H), 1.52 (d, J = 6.7 Hz,
3 H), 4.84 (s, 1 H), 5.03 (q, J = 6.7 Hz, 1 H), 6.49 (d, J = 5.7 Hz, 1
H), 6.96 (d, J = 5.7 Hz, 1 H), 7.31–7.51 (m, 5 H).
(E)-4-(Methoxymethyl)-1-(3-methoxyphenyl)-5-[(trimethylsi-
lyl)methylene]-1,5-dihydro-2H-pyrrol-2-one [(E)-4g]
1H NMR (200 MHz, CDCl3): d = 0.10 (s, 9 H), 3.06 (s, 3 H), 3.36
(s, 3 H), 4.24 (s, 2 H), 4.97 (s, 1 H), 6.14 (s, 1 H), 6.37–7.22 (m, 4
HAr).
13C NMR (50 MHz, CDCl3): d = –0.03, 24.7, 57.0, 104.5, 126.8,
126.7 (2 C), 127, 129.2 (2 C), 135.2, 146, 159.4, 161.6.
(Z)-1-Benzyl-4-methyl-5-[(trimethylsilyl)methylene]-1,5-dihy-
dro-2H-pyrrol-2-one [(Z)-4e]
White liquid; yield: 78%.
13C NMR (50 MHz, CDCl3): d = 0.2, 55.7, 59.5, 67.1, 105.6, 108.2,
110.2, 115.5, 124.1, 130.1, 147.4, 149.5, 160.3, 160.6, 164.2.
IR (neat): 2954, 1672, 1611 cm–1.
(Z)-1-Benzyl-5-benzylidene-4-methyl-1,5-dihydro-2H-pyrrol-2-
one [(Z)-4h]
Yield: 70%.
1H NMR (200 MHz, CDCl3): d = 0.21 (s, 9 H), 1.98 (s, 3 H), 4.64
(s, 2 H), 4.85 (s, 1 H), 6.18 (s, 1 H), 7.19–7.31 (m, 5 H).
IR (neat): 3063, 2929, 1668, 1531, 1455, 1261 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.20 (s, 3 H), 4.80 (s, 2 H), 6.30
(s, 1 H), 7.20–7.55 (m, 9 H), 7.62–7.75 (m, 2 H).
13C NMR (50 MHz, CDCl3): d = 21.5, 51.7, 102.5, 116.35, 121.6,
125.2, 126.0, 126.8, 127.2, 129.8, 130.5, 132.8, 143.9, 147.5, 153.7,
156.1.
13C NMR (50 MHz, CDCl3): d = –0.04 (3 C), 12.3, 52.2, 103.5,
117.8, 127.2, 128.4 (2 C), 129 (2 C), 139.8, 147.5, 161.6, 164.3.
MS (EI): m/z (%) = 271 (M+, 4), 243 (22), 91 (100), 73 (16), 65 (20).
HRMS (EI): m/z [M]+ calcd for C16H21NOSi: 271.1392; found:
271.1397.
(E)-1-Benzyl-4-methyl-5-[(trimethylsilyl)methylene]-1,5-dihy-
dro-2H-pyrrol-2-one [(E)-4e]
MS (EI): m/z (%) = 275 (M+, 31), 91 (100), 65 (15).
HRMS (EI): m/z [M]+ calcd for C19H17NO: 275.1310; found:
1H NMR (200 MHz, CDCl3): d = 0.20 (s, 9 H), 2.05 (s, 3 H), 4.65
(s, 2 H), 5.23 (s, 1 H), 6.56 (s, 1 H), 7.21–7.33 (m, 5 H).
275.1307.
13C NMR (50 MHz, CDCl3): d = –0.17 (3 C), 14.1, 51, 108.4, 121.1,
127.9, 128.4 (2 C), 129.1 (2 C), 138.2, 150, 163.8, 164.6.
(Z)-2-Benzyl-3-benzylidene-2,3-dihydro-1H-isoindol-1-one
[(Z)-5a]50
Colorless liquid; yield: 50%.
(Z)-1-(3-Methoxyphenyl)-4-methyl-5-[(trimethylsilyl)methyl-
ene]-1,5-dihydro-2H-pyrrol-2-one [(Z)-4f]
White liquid; yield: 50%.
IR (neat): 2941, 1670, 1614, 1589, 1476, 1310 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.10 (s, 9 H), 2.02 (s, 3 H), 3.75
(s, 3 H), 4.93 (s, 1 H), 6.25 (s, 1 H), 6.65 (dd, J = 8.2, 2.6 Hz, 1 H),
6.76 (dd, J = 2.6, 2.0 Hz, 1 H), 6.84 (dd, J = 8, 2.0 Hz, 1 H), 7.21
(dd, J = 8.2, 8 Hz, 1 H).
IR (neat): 3418, 3062, 1663, 1635, 1605, 1494, 1452, 1340 cm–1.
1H NMR (200 MHz, CDCl3): d = 4.92 (s, 2 H), 6.67 (s, 1 H), 7.28–
7.60 (m, 11 H), 7.79 (m, 2 H), 8.36 (d, J = 7.6 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 50.0, 100.8, 124.1, 124.6, 125.4,
126.4, 126.8, 127.6, 127.8, 128.3, 128.6, 129.3, 131.6, 132.9, 133.1,
142.0, 151.1, 154.0.
MS (EI): m/z (%) = 311 (M+, 35), 147 (26), 105 (31), 91 (100).
13C NMR (50 MHz, CDCl3): d = 0.10 (3 C), 12.3, 55.5, 103.5,
(E)-2-Benzyl-3-benzylidene-2,3-dihydro-1H-isoindol-1-one
[(E)-5a]
109.7, 111, 114.8, 116.7, 129.5, 147.0, 149.6, 158.6, 160.2, 164.5.
MS (EI): m/z (%) = 287 (M+, 52), 272 (28), 258 (93), 77 (36), 73
(100).
IR (neat): 3422, 3062, 1705, 1655, 1637, 1613, 1493, 1450, 1347
cm–1.
HRMS (EI): m/z [M]+ calcd for C16H21NO2Si: 287.1342; found:
287.1338.
1H NMR (200 MHz, CDCl3): d = 5.01 (s, 2 H), 6.22 (s, 1 H), 7.32–
7.85 (m, 14 H).
13C NMR (50 MHz, CDCl3): d = 52.2, 102.2, 119.5, 123.3, 126.8,
127.3, 127.9, 128.4, 128.7, 129.0, 129.2, 129.5, 131.7, 134.1, 136.0,
140.3, 148.0, 156.0.
(E)-1-(3-Methoxyphenyl)-4-methyl-5-[(trimethylsilyl)methyl-
ene]-1,5-dihydro-2H-pyrrol-2-one [(E)-4f]
1H NMR (200 MHz, CDCl3): d = 0.28 (s, 9 H), 2.0 (s, 3 H), 3.75 (s,
3 H), 5.01 (s, 1 H), 6.25 (s, 1 H), 6.48–6.66 (m, 2 H), 7.11–7.22 (m,
2 H).
(Z)-2-Benzyl-3-hexylidene-2,3-dihydro-1H-isoindol-1-one [(Z)-
5b]51
13C NMR (50 MHz, CDCl3): d = –0.10 (3 C), 12.3, 55.5, 104.6,
108.3, 111.0, 115.6, 123.5, 130.1, 147.8, 149.1, 160.6, 163.8, 164.5.
White liquid; yield: 60%.
IR (neat): 3422, 3062, 2928, 2858, 1702, 1664, 1472, 1351, 1265
cm–1.
1H NMR (200 MHz, CDCl3): d = 0.96 (m, 3 H), 1.38–1.47 (m, 6 H),
2.46–2.56 (m, 2 H), 4.86 (s, 2 H), 5.67 (t, J = 8 Hz, 1 H), 7.27–7.60
(m, 7 H), 7.75 (d, J = 7.6 Hz, 1 H), 7.95 (d, J = 7.1 Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = 13.9, 22.4, 25.6, 29.5, 31.4, 51.3,
108.2, 122.6, 123.2, 126.4, 127.8, 128.2, 128.9, 131.4, 135.9, 140.5,
148.8, 155.5.
(Z)-4-(Methoxymethyl)-1-(3-methoxyphenyl)-5-[(trimethylsi-
lyl)methylene]-1,5-dihydro-2H-pyrrol-2-one [(Z)-4g]
White liquid; yield: 51%.
IR (neat): 2953, 1664, 1612, 1588, 1473, 1254 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.34 (s, 9 H), 3.41 (s, 3 H), 3.76
(s, 3 H), 4.30 (s, 2 H), 4.93 (s, 1 H), 6.14 (s, 1 H), 6.37–7.22 (m, 4
HAr).
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267
MS (EI): m/z (%) = 305 (M+, 17), 238 (22), 160 (23), 91 (100).
13C NMR (50 MHz, CDCl3): d = 19.0, 52.5, 74.3, 127.1, 127.2,
128.3 (2 C), 128.5 (2 C), 128.8 (2 C), 129.8, 130.3 (2 C), 140.5,
141.6, 147.2, 152.3, 157.7.
(E)-2-Benzyl-3-hexylidene-2,3-dihydro-1H-isoindol-1-one
[(E)-5b]
MS (EI): m/z (%) = 401 (M+, 1), 91 (100), 65 (18), 64 (17).
1H NMR (200 MHz, CDCl3): d = 0.96 (m, 3 H), 1.38–1.47 (m, 6 H),
2.46–2.56 (m, 2 H), 4.89 (s, 2 H), 5.38 (t, J = 8.2 Hz, 1 H), 7.27–
7.60 (m, 7 H), 7.75 (d, J = 7.6 Hz, 1 H), 7.80 (d, J = 7.6 Hz, 1 H).
(Z)-1-Benzyl-5-(a-iodobenzylidene)-4-methyl-1,5-dihydro-2H-
pyrrol-2-one [(Z)-7b]
13C NMR (50 MHz, CDCl3): d = 13.9, 22.4, 25.4, 29.0, 31.4, 51.7,
103.5, 119.1, 123.0, 126.5, 127.9, 128.2, 128.8, 131.3, 135.9, 140.5,
148.8, 155.5.
1H NMR (200 MHz, CDCl3): d = 2.61 (s, 3 H), 4.51 (s, 2 H), 6.34
(s, 1 H), 7.22–7.56 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 19.1, 54.6, 74.2, 126.9, 127.3,
128.0 (2 C), 128.6 (2 C), 128.8 (2 C), 129.3, 130.5 (2 C), 140.4,
141.1, 146.1, 152, 157.6.
(Z)-2-Benzyl-3-[(trimethylsilyl)methylene]-2,3-dihydro-1H-
isoindol-1-one [(Z)-5c]52
White liquid; yield: 60%.
1-Benzyl-5-[iodo(trimethylsilyl)methylene]-4-methyl-1,5-dihy-
dro-2H-pyrrol-2-one (7c)
Colorless liquid; yield: 75%; mixture of isomers, E/Z (85:15).
IR (neat): 3426, 2955, 2898, 1780, 1701, 1623, 1495, 1472, 1347,
1250 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.35 (s, 9 H), 4.84 (s, 2 H), 5.47
(s, 1 H), 7.27–7.57 (m, 7 H), 7.73 (d, J = 8 Hz, 1 H), 7.92 (d, J = 7
Hz, 1 H).
13C NMR (50 MHz, CDCl3): d = –0.5, 51.1, 99.8, 122.1, 122.8,
126.1, 127.4, 127.8, 129.3, 130.7, 133.0, 135.4, 139.8, 154.8, 157.4.
MS (EI): m/z (%) = 307 (M+, 100), 279 (10), 219 (8), 147 (10), 91
(64).
(E)-1-Benzyl-5-[iodo(trimethylsilyl)methylene]-4-methyl-1,5-
dihydro-2H-pyrrol-2-one [(E)-7c]
IR (neat): 3063, 2967, 1673, 1602 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.36 (s, 9 H), 2.42 (s, 3 H), 4.67
(s, 2 H), 6.43 (s, 1 H), 7.31–7.36 (m, 5 H).
13C NMR (50 MHz, CDCl3): d = –0.86, 17.0, 52.6, 118.5, 125.7,
127.2, 128.2 (2 C), 129.0 (2 C), 140.4, 147.0, 158.8, 159.3.
(E)-2-Benzyl-3-[(trimethylsilyl)methylene]-2,3-dihydro-1H-
isoindol-1-one [(E)-5c]
MS (EI): m/z (%) = 397 (M+, 1), 277 (10), 91 (100), 65 (15).
1H NMR (200 MHz, CDCl3): d = 0.35 (s, 9 H), 4.91 (s, 2 H), 5.99
(s, 1 H), 7.27–7.57 (m, 8 H), 7.70–7.75 (m, 1 H), 7.90–7.93 (m, 1
H).
(Z)-1-Benzyl-5-[iodo(trimethylsilyl)methylene]-4-methyl-1,5-
dihydro-2H-pyrrol-2-one [(Z)-7c]
1H NMR (200 MHz, CDCl3): d = 0.34 (s, 9 H), 2.37 (s, 3 H), 4.68
(s, 2 H), 6.15 (s, 1 H), 7.31–7.36 (m, 5 H).
1-Benzyl-5-(a-iodobenzylidene)-1,5-dihydro-2H-pyrrol-2-one
(7a)
Colorless liquid; yield: 65%; mixture of isomers, E/Z (90:10).
13C NMR (50 MHz, CDCl3): d = –0.60, 17.5, 54.6, 116.3, 123.0,
127.8, 128.0 (2 C), 129.0 (2 C), 140.5, 148.3, 158.6, 160.1.
1-Benzyl-5-(2-hydroxy-1-iodo-2-methylpropylidene)-4-methyl-
1,5-dihydro-2H-pyrrol-2-one (7d)
Colorless liquid; yield: 70%; mixture of isomers, E/Z (90:10).
(E)-1-Benzyl-5-(a-iodobenzylidene)-1,5-dihydro-2H-pyrrol-2-
one [(E)-7a]
IR (neat): 3063, 2967, 1673, 1605 cm–1.
1H NMR (200 MHz, CDCl3): d = 4.67 (s, 2 H), 6.60 (d, J = 5.6 Hz,
(E)-1-Benzyl-5-(2-hydroxy-1-iodo-2-methylpropylidene)-
4-methyl-1,5-dihydro-2H-pyrrol-2-one [(E)-7d]
IR (neat): 3410, 3060, 2957, 2927, 1681, 1603 cm–1.
1 H), 7.28–7.46 (m, 8 H), 7.53 (d, J = 5.6 Hz, 1 H), 7.71–7.76 (m, 2
H).
13C NMR (50 MHz, CDCl3): d = 52.8, 79.8, 127.6, 128.4, 128.6 (2
1H NMR (200 MHz, CDCl3): d = 1.61 (s, 6 H), 2.38 (d, J = 1.3 Hz,
3 H), 3.36 (s, OH), 4.67 (s, 2 H), 6.27 (q, J = 1.3 Hz, 1 H), 7.31–7.38
(m, 5 HAr).
13C NMR (50 MHz, CDCl3): d = 17.6, 29.2, 52.4, 75, 115.2, 124.6,
127.3, 128.0 (2 C), 129 (2 C), 140.1, 148, 148.6, 157.7.
C), 128.8 (2 C), 129.1 (2 C), 129.5 (2 C), 131.2, 141.0, 153.3, 161.4.
MS (EI): m/z (%) = 387 (M+, 10), 260 (16), 91 (100), 65 (10), 77
(36).
(Z)-1-Benzyl-5-(a-iodobenzylidene)-1,5-dihydro-2H-pyrrol-2-
MS (EI): m/z (%) = 383 (M+, 3), 238 (11), 91 (100), 65 (14).
one [(Z)-7a]
1H NMR (200 MHz, CDCl3): d = 4.72 (s, 2 H), 6.80 (d, J = 5.6 Hz,
1 H), 7.28–7.46 (m, 8 H), 7.65 (d, J = 5.6 Hz, 1 H), 7.71–7.76 (m, 2
H).
13C NMR (50 MHz, CDCl3): d = 53.3, 77.4, 128, 128.3, 128.8 (2 C),
129.0 (2 C), 129.2 (2 C), 129.4 (2 C), 131.0, 142.0, 156.8, 159.4.
(Z)-1-Benzyl-5-(2-hydroxy-1-iodo-2-methylpropylidene)-
4-methyl-1,5-dihydro-2H-pyrrol-2-one [(Z)-7d]
1H NMR (200 MHz, CDCl3): d = 1.61 (s, 6 H), 2.42 (d, J = 1.3 Hz,
3 H), 3.36 (s, OH), 4.63 (s, 2 H), 6.43 (q, J = 1.3 Hz, 1 H), 7.31–7.38
(m, 5 H).
13C NMR (50 MHz, CDCl3): d = 17.9, 29.3, 54.5, 75.2, 109.5,
123.3, 127.4, 128.3 (2 C), 129.2 (2 C), 140, 148.1, 149.5, 159.2.
1-Benzyl-5-(a-iodobenzylidene)-4-methyl-1,5-dihydro-2H-pyr-
rol-2-one (7b)
Colorless liquid; yield: 79%; mixture of isomers, E/Z (65:35).
Synthesis of 8a–f; General Procedure
An oven-dried Schlenk flask was evacuated and back-filled with ar-
gon and charged with EtOH (8 mL), toluene (10 mL), pyrrolone 7b
(5 mmol), and arylboronic acid (6 mmol). The flask was evacuated
and back-filled with argon and then 1 M Na2CO3 (0.6 mL) and
Pd(PPh3)4 (173 mg, 0.15 mmol, 3 mol%) were added. The mixture
was stirred at 50 °C for 12 h, the soln was filtered through a Celite
pad and the solvents were evaporated. The residue was extracted
(E)-1-Benzyl-5-(a-iodobenzylidene)-4-methyl-1,5-dihydro-2H-
pyrrol-2-one [(E)-7b]
IR (neat): 3065, 2964, 1677, 1603 cm–1.
1H NMR (200 MHz, CDCl3): d = 2.55 (s, 3 H), 4.46 (s, 2 H), 6.47
(s, 1 H), 7.22–7.56 (m, 10 H).
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268
K. Cherry et al.
PAPER
with Et2O and dried (anhyd MgSO4). Products 8a–f were obtained
after purification by flash column chromatography (silica gel, PE–
Et2O–Et3N, 80:19:1).
MS (EI): m/z (%) = 357 (M+, 17), 300 (12), 266 (17), 91 (100), 65
(15).
(E)-1-Benzyl-4-methyl-5-(4,4-dimethyl-1-phenylpent-2-
enylidene)-1,5-dihydro-2H-pyrrol-2-one [(E)-8c]
1-Benzyl-4-methyl-5-[a-(4-tolyl)benzylidene]-1,5-dihydro-2H-
pyrrol-2-one (8a)
White liquid; yield: 71%; mixture of isomers, E/Z (90:10).
1H NMR (200 MHz, CDCl3): d = 1.03 (s, 9 H), 1.39 (d, J = 1.3 Hz,
3 H), 4.65 (s, 2 H), 5.33 (d, J = 16 Hz, 1 H), 6.32 (d, J = 1.3 Hz, 1
H), 7.06 (d, J = 16 Hz, 1 H), 7.21–7.51 (m, 10 H).
(E)-1-Benzyl-4-methyl-5-[a-(4-tolyl)benzylidene]-1,5-dihydro-
2H-pyrrol-2-one [(E)-8a]
1-Benzyl-5-[a-(4-bromophenyl)benzylidene]-4-methyl-1,5-di-
hydro-2H-pyrrol-2-one (8d)
IR (neat): 3060, 3028, 2964, 1673, 1604 cm–1.
Colorless liquid: yield: 67%; mixture of isomers, E/Z (88:12).
1H NMR (200 MHz, CDCl3): d = 1.53 (d, J = 1.4 Hz, 3 H), 2.45 (s,
3 H), 4.74 (s, 2 H), 6.29 (q, J = 1.4 Hz, 1 H), 7.23–7.46 (m, 14 H).
13C NMR (50 MHz, CDCl3): d = 15.8, 21.8, 52.5, 115.8, 124.4,
127.1, 128.0, 128.3 (2 C), 128.4 (2 C), 128.8 (2 C), 129.5 (2 C),
130.6 (2 C), 131.6 (2 C), 135.3, 138.5, 139.3, 141.0, 148.0, 150.5,
160.1.
(E)-1-Benzyl-5-[a-(4-bromophenyl)benzylidene]-4-methyl-1,5-
dihydro-2H-pyrrol-2-one [(E)-8d]
IR (neat): 3061, 3029, 2967, 1678, 1601 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.56 (d, J = 1.3 Hz, 3 H), 4.77 (s,
2 H), 6.35 (q, J = 1.3 Hz, 1 H), 7.00–7.58 (m, 14 H).
13C NMR (50 MHz, CDCl3): d = 15.6, 52.5, 119.5, 120.0, 122.8,
125.2, 127.2, 128.5 (2 C), 128.6 (2 C), 129.0 (2 C), 130.3 (2 C),
130.4 (2 C), 130.6 (2 C), 131.8, 138.5, 140.4, 147.5, 151.0, 160.0.
MS (EI): m/z (%) = 429 (M+, 13), 340 (14), 338 (14), 259 (16), 91
(100).
MS (EI): m/z (%) = 365 (M+, 35), 275 (21), 274 (100), 105 (22), 65
(24).
(Z)-1-Benzyl-4-methyl-5-[a-(4-tolyl)benzylidene]-1,5-dihydro-
2H-pyrrol-2-one [(Z)-8a]
1H NMR (200 MHz, CDCl3): d = 1.55 (d, J = 1.4 Hz, 3 H), 2.44 (s,
3 H), 4.73 (s, 2 H), 6.34 (q, J = 1.4 Hz, 1 H), 7.20–7.49 (m, 14 H).
(Z)-1-Benzyl-5-[a-(4-bromophenyl)benzylidene]-4-methyl-1,5-
dihydro-2H-pyrrol-2-one [(Z)-8d]
1-Benzyl-4-methyl-5-[a-(3-thienyl)benzylidene]-1,5-dihydro-
2H-pyrrol-2-one (8b)
Colorless liquid; yield: 65%; mixture of isomers, E/Z (75:25).
1H NMR (200 MHz, CDCl3): d = 1.50 (d, J = 1.3 Hz, 3 H), 4.71 (s,
2 H), 6.50 (q, J = 1.3 Hz, 1 H), 7.0–7.58 (m, 14 H).
(E)-1-Benzyl-4-methyl-5-[a-(3-thienyl)benzylidene]-1,5-dihy-
dro-2H-pyrrol-2-one [(E)-8b]
1-Benzyl-5-[a-(3-chlorophenyl)benzylidene]-4-methyl-1,5-di-
hydro-2H-pyrrol-2-one (8e)
Colorless liquid; yield: 60%; mixture of isomers, E/Z, (85:15).
IR (neat): 3065, 3032, 2956, 1674, 1607 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.61 (d, J = 1.3 Hz, 3 H), 4.74 (s,
2 H), 6.29 (q, J = 1.3 Hz, 1 H), 7.01 (d, J = 5 Hz, 1 H), 7.24–7.53
(m, 12 H).
13C NMR (50 MHz, CDCl3): d = 15, 52.6, 115.8, 124.8, 126.4,
126.7, 127.1, 128.1, 128.4, 129.0 (2 C), 130.2 (2 C), 130.5, 138,
138.5, 141.0, 147.8, 151.0, 159.6.
(E)-1-Benzyl-5-[a-(3-chlorophenyl)benzylidene]-4-methyl-1,5-
dihydro-2H-pyrrol-2-one [(E)-8e]
IR (neat): 3064, 3031, 2965, 1673, 1604 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.55 (d, J = 1.3 Hz, 3 H), 4.76 (s,
2 H), 6.32 (q, J = 1.3 Hz, 1 H), 6.70 (d, J = 8.7 Hz, 1 H), 7.12 (d,
J = 8.7 Hz, 1 H), 7.23–7.52 (m, 12 H).
13C NMR (50 MHz, CDCl3): d = 16.0, 52.4, 120.6, 124.8, 127.2,
128.4 (2 C), 128.5 (2 C), 128.9 (2 C), 129.1 (2 C), 129.6, 130.6,
131.6, 132.0, 133.0, 135.0, 136.7, 138.6, 140.6, 147.8, 150.7, 156.5.
MS (EI): m/z (%) = 357 (M+, 77), 266 (100), 234 (31), 91 (79), 65
(22).
(Z)-1-Benzyl-4-methyl-5-[a-(3-thienyl)benzylidene]-1,5-dihy-
dro-2H-pyrrol-2-one [(Z)-8b]
MS (EI): m/z (%) = 385 (M+, 28), 296 (25), 294 (72), 91 (100), 65
(22).
1H NMR (200 MHz, CDCl3): d = 1.49 (d, J = 1.3 Hz, 3 H), 4.85 (s,
2 H), 6.24 (q, J = 1.3 Hz, 1 H), 7.22 (d, J = 5 Hz, 1 H), 7.32–7.48
(m, 12 H).
(Z)-1-Benzyl-5-[a-(3-chlorophenyl)benzylidene]-4-methyl-1,5-
dihydro-2H-pyrrol-2-one [(Z)-8e]
13C NMR (50 MHz, CDCl3): d = 15.5, 52.8, 116.5, 124, 125.2, 127,
127.2, 128.3 (2 C), 128.7, 128.8 (2 C), 129.0 (2 C), 129.4, 131.3 (2
C), 138.0, 140.3, 141.0, 148.1, 149.6, 159.7.
1H NMR (200 MHz, CDCl3): d = 1.59 (d, J = 1.3 Hz, 3 H), 4.70 (s,
2 H), 6.48 (q, J = 1.3 Hz, 1 H), 6.80 (d, J = 8.7 Hz, 1 H), 7.02 (d,
J = 8.7 Hz, 1 H), 7.23–7.52 (m, 12 H).
1-Benzyl-4-methyl-5-(4,4-dimethyl-1-phenylpent-2-enylidene)-
1,5-dihydro-2H-pyrrol-2-one (8c)
White liquid; yield: 62%; mixture of isomers, E/Z (10:90).
1-Benzyl-5-(diphenylmethylene)-4-methyl-1,5-dihydro-2H-
pyrrol-2-one (8f)
White liquid; yield: 75%; mixture of isomers, E/Z (88:12).
(Z)-1-Benzyl-4-methyl-5-(4,4-dimethyl-1-phenylpent-2-
enylidene)-1,5-dihydro-2H-pyrrol-2-one [(Z)-8c]
IR (neat): 3061, 3029, 2967, 1678, 1601 cm–1.
1H NMR (200 MHz, CDCl3): d = 0.08 (s, 9 H), 1.36 (d, J = 1.3 Hz,
3 H), 4.80 (s, 2 H), 5.37 (d, J = 16 Hz, 1 H), 6.14 (d, J = 1.3 Hz, 1
H), 6.96 (d, J = 16 Hz, 1 H), 7.21–7.51 (m, 10 H).
13C NMR (50 MHz, CDCl3): d = 15, 30 (3 C), 34.3, 52.4, 121.3,
123.1, 124, 127, 128.3, 128.5 (2 C), 128.6 (2 C), 128.8 (2 C), 131.3
(2 C), 135.7, 141.2, 146.8, 148.6, 149.4, 159.5.
IR (neat): 3059, 3029, 2964, 1677, 1603 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.50 (d, J = 1.3 Hz, 3 H), 4.76 (s,
2 H), 6.29 (q, J = 1.3 Hz, 1 H), 7.26–7.48 (m, 15 H).
13C NMR (50 MHz, CDCl3): d = 15.7, 52.5, 115.3, 124.7, 127.1,
128.0, 128.4 (2 C), 128.6 (2 C), 128.8 (2 C), 129.9 (2 C), 130.6 (2
C), 131.7 (2 C), 138.3, 139.1, 141.1, 148.0, 150.6, 160.0.
MS (EI): m/z (%) = 351 (M+, 24), 260 (91), 165 (29), 91 (100).
HRMS (EI): m/z [M]+ calcd for C25H21NO: 351.1623; found:
351.1621.
Synthesis 2009, No. 2, 257–270 © Thieme Stuttgart · New York

PAPER
Synthesis of 5-Alkyl(aryl)idene- and 5-[Iodoalkyl(aryl)idene]-1H-pyrrol-2(5H)-ones
269
R.; Bellina, F.; Bechini, C.; Mannina, L.; Vergamini, P.
Acknowledgment
Tetrahedron 1998, 54, 135. (n) Marshall, J. A.; Wolf, M. A.;
Wallace, E. M. J. Org. Chem. 1997, 62, 367. (o) Kotora,
M.; Negishi, E.-I. Synthesis 1997, 121. (p) Negishi, E.-I.;
Kotora, M. Tetrahedron 1997, 53, 6707. (q) Marshall, J. A.;
Wolf, M. A. J. Org. Chem. 1996, 61, 3238. (r) Marshall, J.
A.; Wallace, E. M. J. Org. Chem. 1995, 60, 796..
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Kataoka, T. J. Chem. Soc., Perkin Trans. 1 1996, 1839.
(b) Abell, A. D.; Oldham, M. D.; Taylor, J. M. J. Chem. Soc.,
Perkin Trans. 1 1995, 953. (c) Murakami, M.; Hayashi, M.;
Ito, Y. J. Org. Chem. 1994, 59, 7910. (d) Gill, G. B.; James,
G. D.; Oates, K. V.; Pattenden, G. J. Chem. Soc., Perkin
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A.; Taddei, M. J. Org. Chem. 1984, 49, 551. (f) Walton, H.
M. J. Org. Chem. 1957, 22, 315.
We thank MESR and CNRS for providing financial support and the
‘Service d’analyse chimique du vivant de Tours’ for recording
NMR and mass spectra.
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