CuI/amino acid-catalyzed coupling and cyclization of β-bromo-α, β-unsaturated amides with terminal alkynes leading to (3Z)-3- alkylidenepyrrol-1-ones

Article abstract of DOI:10.1002/aoc.2990

β-Bromo-α,β-unsaturated amides are coupled and cyclized with terminal alkynes in DMF at 110 °C in the presence of a catalytic amount of CuI and amino acid along with a base to give the corresponding (3Z)-3-alkylidenepyrrol-1-ones in moderate to good yield

Full text of DOI:10.1002/aoc.2990

Full Paper
Received: 13 January 2013
Revised: 24 February 2013
Accepted: 9 March 2013
Published online in Wiley Online Library: 30 May 2013
(wileyonlinelibrary.com) DOI 10.1002/aoc.2990
CuI/amino acid-catalyzed coupling and
cyclization of b-bromo-a,b-unsaturated
amides with terminal alkynes leading to
(3Z)-3-alkylidenepyrrol-1-ones
Jong Ik Son, Chan Sik Cho* and Heung-Jin Choi
b-Bromo-a,b-unsaturated amides are coupled and cyclized with terminal alkynes in DMF at 110 ꢀC in the presence of a
catalytic amount of CuI and amino acid along with a base to give the corresponding (3Z)-3-alkylidenepyrrol-1-ones in
moderate to good yields. Copyright © 2013 John Wiley & Sons, Ltd.
Keywords: (3Z)-3-alkylidenepyrrol-1-one; amino acid; b-bromo-a,b-unsaturated amide; terminal alkyne; coupling and cyclization
Introduction
Results and Discussion
Palladium- and CuI-catalyzed sp-carbon-sp2-carbon bond forma-
tion by the cross-coupling of terminal alkynes with aryl and vinyl
halides is known as the Sonogashira coupling reaction.[1–3] Many
elegant catalytic systems which facilitate Sonogashira coupling
under milder conditions have been developed by the tuning of
phosphine ligand combined with palladium[4–7] or the addition of
promoter.[8–10] Recently, Ma and co-workers also reported that
CuI combined with amino acid effectively catalyzes cross-
coupling reaction of aryl halides with terminal alkynes in the
absence of palladium and phosphine.[11,12] The Sonogashira
coupling protocol has been widely used as a powerful synthetic tool
for the formation of conjugated acetylenic compounds, which
frequently play an important role as an intermediate for the design
of pharmaceuticals and organic materials.[3] Furthermore, the
coupling reaction followed by intramolecular cyclization has
also been used for the construction of various heterocyclic
compounds.[3] In connection with this report, several groups have
reported that 2-halobenzamides are coupled and cyclized with
terminal alkynes under usual palladium catalyst systems to give
(3Z)-3-alkylideneisoindolin-1-ones (Scheme 1).[13–15] For another
synthetic method for 3-alkyl(aryl)ideneisoindolin-1-ones see County
et al.[16] Such a similar coupling followed by cyclization was also
exemplified by the reaction of 2-bromobenzamides and terminal al-
kynes in the presence of CuI and L-proline.[17] On the other hand,
during the course of our ongoing studies on palladium-catalyzed
cyclization reactions using b-bromo-a,b-unsaturated aldehydes and
their derivatives, which are readily prepared from a-methylene
containing ketones under bromination conditions of Vilsmeier–
Haack reaction and subsequent transformation,[18,19] we have
disclosed several new synthetic methods for the synthesis of carbo-
and heterocyclic compounds.[20–51]Under these circumstances, this
report describes CuI/amino acid-catalyzed coupling and cyclization
of b-bromo-a,b-unsaturated amides with terminal alkynes leading
to (3Z)-3-alkylidenepyrrol-1-ones.
The substrates (4) were prepared by three steps from the
corresponding ketones (1) as shown in Scheme 2. Treatment of
1 under bromination conditions of Vilsmeier–Haack reaction
affords b-bromo-a,b-unsaturated aldehydes 2.[18,19] b-Bromo-
a,b-unsaturated carboxylic acids (3) synthesized by oxidation of
2[52] were converted into amides (4) by treatment with oxalyl
chloride and DMF, followed by addition of primary amines and
Et3N.[53]
The initial study attempted to achieve direct three-component
cyclization toward (3Z)-3-alkylidenepyrrol-1-ones. Treatment of 2-
bromocyclohex-1-enecarboxylic acid (3a) with 1.5 equiv. of ani-
line (5) and 2 equiv. of phenylacetylene (6a) in dioxane at 110 ꢀC
for 40 h in the presence of 10% Pd/C (10 mol%) and CuI (20 mol
%) afforded regio- and stereoselective 5-exo-dig cyclized product,
(3Z)-3-benzylidene-2,3,4,5,6,7-hexahydro-2-phenylisoindol-1-one
(7a)[17] and (3Z)-4,5,6,7-tetrahydro-3-benzylideneisobenzofuran-1
[49]
(3H)-one (8)
in 2% and 34% yields, respectively (Scheme 3).
This result excludes three-component cyclization because of
higher reaction rate for direct coupling and cyclization of 3a with
6a, leading to 8. Thus, in order to produce an allowable yield of 7a,
we attempted similar coupling and cyclization of 2-bromo-N-
phenylcyclohex-1-enecarboxamide (4a) and 6a as a model sub-
strate (Table 1). Performing the reaction of 4a with 1.5 equiv. of
6a under Pd/C/PPh3/CuI/Bu3N or PdCl2(PPh3)2/CuI/Bu3N did not
produce 7a at all (entries 1 and 2). However, surprisingly, when
4a was subjected to reaction with 6a in the presence of a catalytic
*
Correspondence to: Chan Sik Cho, Department of Applied Chemistry,
Kyungpook National University, Daegu 702-701, South Korea. E-mail:
cscho@knu.ac.kr
Department of Applied Chemistry, Kyungpook National University, Daegu
702-701, South Korea
Appl. Organometal. Chem. (2013), 27, 380–386
Copyright © 2013 John Wiley & Sons, Ltd.

CuI/amino acid-catalyzed coupling and cyclization
Scheme 1. Pd/CuI-catalyzed synthesis of (3Z)-3-alkylideneisoindolin-1-ones.
Scheme 2. Synthesis of b-bromo-a,b-unsaturated amides.
Scheme 3. Palladium-catalyzed three-component cyclization.
Table 1. Optimization of conditions for the reaction of 4a with 6aa
Entry
Catalyst
Base
Solvent
Time (h)
Yield (%)
1b
2b
3
10% Pd/C, CuI, PPh3
PdCl2(PPh3)2, CuI
CuI, L-proline
Bu3Nc
Bu3Nc
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
dioxane
DMF
20
20
40
40
40
40
40
40
40
40
0
0
DMF
56
38
41
3
4
CuI, L-phenylalanine
CuI, glycine
DMF
5
DMF
6
CuI, cysteine
DMF
7
CuI, N,N-dimethylglycine
CuI, L-proline
DMF
35
30
36
2
8
Propanol
Toluene
Dioxane
9
CuI, L-proline
10
CuI, L-proline
aReaction conditions: 4a (0.3 mmol), 6a (0.45 mmol), CuI (0.03), amino acid (0.09 mmol), base (0.6 mmol), solvent (3 ml), 110 ꢀC.
b0.015 mmol palladium catalyst was used.
c1.5 mmol.
amount of CuI and L-proline, 7a was obtained in 56% isolated
yield with 75% conversion of 4a (entry 3). The reaction proceeded
using other amino acids such as L-phenylalanine, glycine and N,N-
dimethylglycine, but the yield of 7a was generally lower than that
by the use of L-proline (entries 4–7). Among solvents examined
under the employed conditions, DMF was shown to be the
solvent of choice (entries 3, 8–10). As a result, the best yield of
7a was accomplished by the standard set of reaction conditions
shown in entry 3 of Table 1.
After the reaction conditions had been optimized, various
b-bromo-a,b-unsaturated amides (4) were subjected to the
reaction with terminal alkynes (6) in order to investigate the
reaction scope, and several representative results are summa-
rized in Table 2. The coupling and cyclization of amide 4a
with alkyl alkyne 6b also proceeded to give the corresponding
alkylidenehydroisoindolin-1-one (7b). However, the product yield
was lower than when 4a was subjected to the reaction with 6a.
From the reaction between N-benzyl-substituted amide 4b and
Appl. Organometal. Chem. (2013), 27, 380–386
Copyright © 2013 John Wiley & Sons, Ltd.
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J. I. Son et al.
Table 2. Palladium-catalyzed coupling and cyclization of b-bromo-a,b-unsaturated amides with alkynes.a
b-Bromo-a,b-unsaturated amides 4
1-Alkynes 6
Alkylidenepyrrolones 7
Yieldb (%)
4a
6a
6b
7a
7b
53
38
4b
6a
7c
62
4c
4d
4e
4f
6a
6a
6a
6a
7d
7e
7f
47c
43
63
30
7 g
4 g
7 h
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2013), 27, 380–386

CuI/amino acid-catalyzed coupling and cyclization
Table 2. (Continued).
6a
68
59
37
4 h
6a
6a
7i
7j
4i
4j
6a
7 k
0
aReaction conditions: 4 (0.3 mmol), 6 (0.45 mmol), CuI (0.03 mmol), L-proline (0.09 mmol), K2CO3 (0.6 mmol), DMF (3 ml), 110 ꢀC, 40 h.
bDialkyne homo-coupling products (<15%) were formed.
c(Z)-isomer/(E)-isomer = 7.5.
6a, the corresponding alkylidenehydroisoindolin-1-one (7c) was
also produced in similar yield. The reaction of N-alkyl-substituted
amide 4c with 6a also took place to give coupled and cyclized
product 7d in 47% yield as a mixture of (E)- and (Z)-isomers [(Z)-iso-
mer/(E)-isomer= 7.5]. The configuration and molar ratio of isomers
was confirmed by comparing the chemical shift and peak areas of
vinyl proton signals in 1H NMR. It is known that the chemical shifts
of (Z)-isomers of analogues of 7d, 3-methyleneisoindolin-1-ones
are shifted downfield from those of (E)-isomers.[17] Methyl-
and phenyl-substituted six-membered b-bromo-a,b-unsaturated
amides (4d and 4e) were also coupled and cyclized with 5a to give
the corresponding alkylidenehydroisoindolin-1-ones (7e and 7f).
With b-bromo-a,b-unsaturated amides (4f–i) having various ring
sizes, the coupled and cyclized products (7 g–j) were formed in
the range of 30–68% yield without any identifiable side product,
and the product yield was considerably affected by the ring size
of 4f–i. Lower reaction rate and yield were observed with 4f
and 4i. On the other hand, the reaction of benzo-fused b-bromo-
a,b-unsaturated amide 4j with 6a did not proceed toward coupled
and cyclized product 7 k under the employed conditions, a small
amount of homo-coupled 1,4-diphenyl-1,3-diyne being formed as
an identifiable product.
the synthesis of valuable heterocycles from readily available
starting ketones. Further study of synthetic applications to
heterocycles using this ketone as starting compound
and CuI/amino acids catalytic system is currently under
investigation.
Experimental
1H and 13C NMR (400 and 100 MHz) spectra were recorded on a
Bruker Avance Digital 400 spectrometer using tetramethylsilane
as an internal standard. Melting points were determined on a
Stanford Research Inc. MPA100 automated melting point appa-
ratus. High-resolution mass spectrometry (HRMS) was performed
at the Korea Basic Science Institute (Daegu). The isolation of pure
products was carried out via thin-layer (silica gel 60 GF254, Merck)
chromatography. The starting b-bromo-a,b-unsaturated amides
were synthesized via three steps from the corresponding
ketones according to literature procedures.[18,19,52,53] Commer-
cially available organic and inorganic compounds were used
without further purification.
General Experimental Procedure for CuI/Amino Acid-Catalyzed
Coupling and Cyclization of b-Bromo-a,b-Unsaturated Amides
with Terminal Alkynes
Conclusion
In summary, it has been shown that b-bromo-a,b-unsaturated
amides, which are readily prepared from a-methylene-
containing ketones by three steps, undergo coupling and
cyclization with terminal alkynes in the presence of CuI and
L-proline along with K2CO3 to give (3Z)-3-alkylidenepyrrol-1-
ones. The present reaction provides a promising route for
Α mixture of b-bromo-a,b-unsaturated amide 4 (0.3 mmol),
terminal alkyne 6 (0.45 mmol), CuI (0.006 g, 0.03 mmol), amino
acid (0.09 mmol) and base (0.6 mmol) in solvent (3 ml) was placed
in a 5 ml screw-capped vial (Wheaton) and the reaction mixture
was allowed to react at 110 ꢀC for 40 h. The reaction mixture was
filtered through a short silica gel column (ethyl acetate–hexane
Appl. Organometal. Chem. (2013), 27, 380–386
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J. I. Son et al.
mixture) to eliminate inorganic salts. Removal of the solvent
left a crude mixture, which was separated by thin-layer
chromatography (silica gel, ethyl acetate–hexane mixture) to
give (3Z)-3-alkylidenepyrrol-1-ones 7. All new products prepared
by the above procedure were characterized spectroscopically
as shown below.
Solid; m.p. 115–116 ꢀC. 1H NMR (400 MHz, CDCl3) d 1.75–1.85 (m,
4H, 2CH2), 2.38–2.46 (m, 4H, 2CH2), 4.71 (s, 2H, benzyl CH2), 6.10 (s,
1H, vinyl CH), 6.50–6.53 (m, 2H, 2CH), 7.01–7.09 (m, 5H, 5CH),
7.20–7.27 (m, 3H, 3CH). 13C NMR (100 MHz, CDCl3) d 20.54 (C6),
21.46 (C5), 22.17 (C7), 22.42 (C4), 44.66 (C10), 109.55 (C15),
126.71 (C12 and C17), 127.52 (C14), 128.04 (C13), 128.07 (C19),
129.73 (C18), 130.35 (C8), 135.01 (C16), 137.78 (C11), 138.74
(C3), 146.26 (C9), 172.65 (C1), assignments to C4 and C7 are inter-
changeable, assignments to C5 and C6 are interchangeable,
assignments to C12, C13, C17 and C18 are interchangeable,
assignments to C14 and C19 are interchangeable. HRMS (EI). Anal.
+
•
Calcd for C22H21NO (M ): 315.1623. Found: 315.1620. Anal. Calcd
for C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.70; H, 6.60; N,
4.42.
(3Z)-3-Benzylidene-2,3,4,5,6,7-hexahydro-2-phenylisoindol-1-one (7a)
Solid; m.p. 154–155 ꢀC. 1H NMR (400 MHz, DMSO-d6) d 1.74–1.80
(m, 4H, 2CH2), 2.56 (s, 2H, CH2), 2.59 (s, 2H, CH2), 6.42 (s, 1H, vinylic
CH), 6.86–6.98 (m, 7H, 7CH), 7.01–7.10 (m, 3H, 3CH). 13C NMR
(100 MHz, DMSO-d6) d 20.03 (C5), 20.94 (C6), 21.55 (C7), 21.72
(C4), 109.91 (C14), 125.95 (C13), 126.70 (C11), 126.75 (C18),
127.10 (C16), 127.96 (C17), 128.48 (C8), 129.21 (C12), 133.45
(C10), 136.30 (C15), 137.54 (C3), 147.23 (C9), 170.35 (C1), assign-
ments to C5 and C6 are interchangeable, assignments to C4 and
C7 are interchangeable, assignments to C11,12,16 and 17 are
interchangeable, assignments to C13 and C18 are interchange-
(3Z)-3-Benzylidene-2-hexyl-2,3,4,5,6,7-hexahydroisoindol-1-one (7d)
1
As a mixture of (E)- and (Z)-isomers. H NMR (400 MHz, CDCl3)
d 0.87–0.91 (m, 3H, CH3), 1.30–1.38 (m, 6H, 3CH2), 1.46–1.52
(m, 2H, CH2), 1.59–1.68 (m, 4H, 2CH2), 1.90-1.94 (m, 2H, CH2),
2.30–2.33 (m, 2H, CH2), 3.42 (t, JHH = 7.8 Hz, ≒ 0.24H, NCH2,
E-isomer), 3.67 (t, JHH = 7.5 Hz, ≒ 1.76 H, NCH2, Z-isomer), 6.16
(s, ≒ 0.12H, vinyl CH, E-isomer), 6.40 (s, ≒ 0.88H, vinyl CH, Z-
isomer), 7.26–7.37 (m, 5H, 5CH). 13C NMR (100 MHz, CDCl3) d
14.28 (C15), 20.95 (C14), 21.67 (C6), 22.81 (C5), 22.93 (C7),
25.52 (C12), 26.90 (C11), 29.10 (C4), 31.81 (C13), 39.29 (C10),
111.22 (C16), 127.67 (C20), 128.26 (C18), 129.89 (C19), 133.87
(C8), 135.54 (C17), 140.06 (C3), 141.80 (C9), 169.67 (C1), assign-
ments to C4, C11 and C13 are interchangeable, assignments
to C5–C7 and C14 are interchangeable. HRMS (EI). Anal. Calcd
+
•
able. HRMS (EI). Anal. Calcd for C21H19NO (M ): 301.1467. Found:
301.1467. Anal. Calcd for C21H19NO: C, 83.69; H, 6.35; N, 4.65.
Found: C, 83.55; H, 6.30; N, 4.62.
(3Z)-2,3,4,5,6,7-Hexahydro-3-pentylidene-2-phenylisoindol-1-one (7b)
+
•
for C21H27NO (M ): 309.2093. Found: 309.2094. Anal. Calcd for
Solid; m.p. 126–128 ꢀC. 1H NMR (400 MHz, CDCl3) d 0.72 (t, JHH
=
C
21H27NO: C, 81.51; H, 8.79; N, 4.53. Found: C, 81.48; H, 8.70;
7.3 Hz, 3H, CH3), 1.02–1.11 (m, 2H, CH2), 1.15–1.23 (m, 2H, CH2),
1.58–1.64 (m, 2H, CH2), 1.72–1.83 (m, 4H, 2CH2), 2.33–2.36 (m,
2H, CH2), 2.40–2.43 (m, 2H, CH2), 5.08 (t, JHH = 8.0 Hz, 1H, vinyl
CH), 7.23–7.26 (m, 2H, 2CH), 7.32–7.36 (m, 1H, CH), 7.39–7.43
(m, 2H, 2CH). 13C NMR (100 MHz, CDCl3) d 13.88 (C18), 20.49
(C17), 21.43 (C6), 22.31 (C5), 22.38 (C15), 22.46 (C7), 26.52 (C4),
31.94 (C16), 112.54 (C14), 127.82 (C13), 128.80 (C11), 129.00
(C8), 129.14 (C12), 137.82 (C10), 139.10 (C3), 145.40 (C9), 171.29
(C1), assignments to C5, C6 and C17 are interchangeable, assign-
ments to C7 and C15 are interchangeable, assignments to C11
and C12 are interchangeable. HRMS (EI). Anal. Calcd for
N, 4.43.
(3Z)-3-Benzylidene-2,3,4,5,6,7-hexahydro-2,6-diphenylisoindol-1-one (7e)
+
•
C
C
19H23NO (M ): 281.1780. Found: 281.1778. Anal. Calcd for
19H23NO: C, 81.10; H, 8.24; N, 4.98. Found: C, 81.02; H, 8.10;
Solid; m.p. 168–170 ꢀC. 1H NMR (400 MHz, CDCl3) d 1.95–2.05 (m,
1H, 1/2CH2), 2.23–2.28 (m, 1H, 1/2CH2), 2.45–2.53 (m, 1H, 1/2CH2),
2.64–2.74 (m, 1H, 1/2CH2), 2.78–2.86 (m, 2H, CH2), 2.96–3.04 (m,
1H, CH), 6.27 (s, 1H, vinyl CH), 6.84–6.86 (m, 2H, 2CH), 6.89–6.94
(m, 2H, 2CH), 6.95–7.08 (m, 6H, 6CH), 7.22–7.27 (m, 1H, CH),
7.29–7.31 (m, 2H, 2CH), 7.34–7.38 (m, 2H, 2CH). 13C NMR
(100 MHz, CDCl3) d 22.20 (C4), 28.33 (C5), 30.00 (C7), 40.14 (C6),
110.35 (C14), 126.26 (C13), 126.69 (C22), 126.95 (C11), 127.02
(C18), 127.09 (C16), 127.41 (C20), 128.28 (C17), 128.79 (C21),
129.46 (C12), 129.75 (C8), 133.77 (C10), 136.44 (C15), 138.15
(C19), 145.57 (C3), 146.56 (C9), 171.03 (C1), assignments to C13,
C18 and C22 are interchangeable, assignments to C11, C12,
N, 4.90.
(3Z)-2-Benzyl-3-benzylidene-2,3,4,5,6,7-hexahydroisoindol-1-one (7c)
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Appl. Organometal. Chem. (2013), 27, 380–386

CuI/amino acid-catalyzed coupling and cyclization
C16, C17, C20 and C21 are interchangeable. HRMS (EI). Anal.
Solid; m.p. 140–141 ꢀC. 1H NMR (400 MHz, CDCl3) d 1.68–1.73 (m,
2H, CH2), 1.78–1.83 (m, 2H, CH2), 1.87–1.93 (m, 2H, CH2), 2.58–2.61
(m, 2H, CH2), 2.70–2.73 (m, 2H, CH2), 6.39 (s, 1H, vinyl CH), 6.83–7.04
(m, 10H, 10CH). 13C NMR (100 MHz, CDCl3) d 24.64 (C7), 26.27 (C5),
26.94 (C8), 27.06 (C6), 31.31 (C4), 110.19 (C15), 126.10 (C14),
126.82 (C19), 126.99 (C12), 127.35 (C17), 128.15 (C18), 129.43
(C13), 132.71 (C9), 134.23 (C11), 136.67 (C16), 138.60 (C3), 149.11
(C10), 171.66 (C1), assignments to C4–C8 are interchangeable,
assignments to C12, C13, C17 and C18 are interchangeable, assign-
ments to C15 and C20 are interchangeable, assignments to C14
and C19 are interchangeable. HRMS (EI). Anal. Calcd for C22H21NO
+
•
Calcd for C27H23NO (M ): 377.1780. Found: 377.1781. Anal. Calcd
for C27H23NO: C, 85.91; H, 6.14; N, 3.71. Found: C, 85.70; H, 6.09;
N, 3.70.
+
•
(M ): 315.1623. Found: 315.1620. Anal. Calcd for C22H21NO: C,
83.78; H, 6.71; N, 4.44. Found: C, 83.69; H, 6.58; N, 4.38.
(3Z)-3-Benzylidene-2,3,4,5,6,7-hexahydro-6-methyl-2-phenylisoindol-1-one
(7f)
1
Solid; m.p. 160–162 ꢀC. H NMR (400 MHz, CDCl3) d 1.12 (d, JHH
=
6.3 Hz, 3H, CH3), 1.42–1.52 (m, 1H, 1/2CH2), 1.82–2.01 (m, 3H,
CH2 and CH), 2.49–2.58 (m, 2H, CH2), 2.65–2.72 (m, 1H, 1/2CH2),
6.23 (s, 1H, vinyl CH), 6.82–6.84 (m, 2H, 2CH), 6.88–6.92 (m, 2H,
2CH), 6.95–7.08 (m, 6H, 6CH). 13C NMR (100 MHz, CDCl3) d 21.48
(C19), 21.56 (C4), 28.76 (C6), 28.78 (C5), 30.70 (C7), 109.90 (C14),
126.17 (C13), 126.89 (C18), 126.96 (C11), 127.37 (C16), 128.23
(C17), 129.42 (C12), 129.80 (C8), 133.89 (C10), 136.51 (C15),
138.36 (C3), 146.60 (C9), 171.35 (C1), assignments to C4 and C19
are interchangeable, assignments to C5 and C6 are interchange-
able, assignments to C13 and C18 are interchangeable, assign-
ments to C11, C12, C16 and C17 are interchangeable. HRMS (EI).
(3Z)-3-Benzylidene-2,3,4,5,6,7,8,9-octahydro-2-phenylcycloocta[c]pyrrol-1-
one (7i)
Solid; m.p. 137–138 ꢀC. 1H NMR (400 MHz, CDCl3) d 1.54–1.62
(m, 4H, 2CH2), 1.70–1.76 (m, 2H, CH2), 1.81–1.87 (m, 2H, CH2),
2.58–2.61 (m, 2H, CH2), 2.78–2.81 (m, 2H, CH2), 6.35 (s, 1H, vinyl
CH), 6.84–7.06 (m, 10H, 10CH). 13C NMR (100 MHz, CDCl3) d
22.73 (C7), 23.44 (C6), 26.04 (C8), 26.27 (C5), 29.07 (C9), 29.27
(C4), 109.98 (C16), 126.06 (C15), 126.86 (C20), 126.90 (C13),
127.33 (C18), 128.15 (C19), 129.50 (C14), 131.37 (C10), 134.08
(C12), 136.65 (C17), 138.02 (C3), 147.83 (C11), 171.65 (C1),
assignments to C4–C9 are interchangeable, assignments to
C13, C14, C18 and C19 are interchangeable, assignments to
C15 and C20 are interchangeable. HRMS (EI). Anal. Calcd for
+
•
Anal. Calcd for C22H21NO (M ): 315.1623. Found: 315.1624. Anal.
Calcd for C22H21NO: C, 83.78; H, 6.71; N, 4.44. Found: C, 83.71; H,
6.60; N, 4.40.
+
•
C23H23NO (M ): 329.1780. Found: 329.1779. Anal. Calcd for
C23H23NO: C, 83.85; H, 7.04; N, 4.25. Found: C, 83.70; H, 6.90;
N, 4.20.
(3Z)-3-Benzylidene-2,3,5,6-tetrahydro-2-phenylcyclopenta[c]pyrrol-1(4H)-
one (7 g)
1
Solid; m.p. 141–143 ꢀC. H NMR (400 MHz, CDCl3) d 2.44–2.51 (m,
2H, CH2), 2.69–2.73 (m, 2H, CH2), 2.80–2.85 (m, 2H, CH2), 6.17 (s,
1H, vinyl CH), 6.81–6.84 (m, 2H, 2CH), 6.87–6.91 (m, 2H, 2CH),
6.93–7.06 (m, 6H, 6CH). 13C NMR (100 MHz, CDCl3) d 26.59 (C5),
27.20 (C6), 27.96 (C4), 112.47 (C13), 126.23 (C12), 126.98 (C10),
127.16 (C17), 127.41 (C15), 128.31 (C16), 129.49 (C11), 133.54 (C7),
135.21 (C9), 136.84 (C14), 139.68 (C3), 160.02 (C8), 167.80 (C1),
assignments to C4–C6 are interchangeable, assignments to C12
and C17 are interchangeable, assignments to C10, C11, C15 and
C16 are interchangeable. HRMS (EI). Anal. Calcd for C20H17NO
(3Z)-3-Benzylidene-2,3,4,5,6,7,8,9,10,11,12,13-dodecahydro-2-phenylcyclo
dodeca[c]pyrrol-1-one (7j)
Solid; m.p. 134–136 ꢀC. 1H NMR (400 MHz, CDCl3) d 1.32–1.54 (m,
12H, 6CH2), 1.75–1.87 (m, 4H, 2CH2), 2.44–2.47 (m, 2H, CH2),
2.64–2.68 (m, 2H, CH2), 6.36 (s, 1H, vinyl CH), 6.83–7.05 (m, 10H,
10CH). 13C NMR (100 MHz, CDCl3) d 21.91 (C11), 22.33 (C8), 22.36
(C9), 22.53 (C7), 24.81 (C10), 24.91 (C6), 25.37 (C12), 26.04 (C5),
26.25 (C13), 28.74 (C4), 110.78 (C20), 126.09 (C19), 126.81 (C24),
126.95 (C17), 127.35 (C22), 128.14 (C23), 129.46 (C18), 131.46
(C14), 134.21 (C16), 136.48 (C21), 138.52 (C3), 147.70 (C15),
171.93 (C1), assignments to C17, C18, C22 and C23 are inter-
changeable, assignments to C19 and C24 are interchangeable.
+
•
(M ): 287.1310. Found: 287.1310. Anal. Calcd for C20H17NO: C,
83.59; H, 5.96; N, 4.87. Found: C, 83.50; H, 6.03; N, 4.50.
+
•
HRMS (EI). Anal. Calcd for C27H31NO (M ): 385.2406. Found:
385.2406. Anal. Calcd for C27H31NO: C, 84.11; H, 8.10; N, 3.63.
Found: C, 84.04; H, 8.00; N, 3.52.
(3Z)-3-Benzylidene-2,3,5,6,7,8-hexahydro-2-phenylcyclohepta[c]pyrrol-1(4H)-
one (7h)
Appl. Organometal. Chem. (2013), 27, 380–386
Copyright © 2013 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

J. I. Son et al.
[23] S. K. Mal, D. Ray, J. K. Ray, Tetrahedron Lett. 2004, 45, 277.
[24] M. G. Banwell, D. W. Lupton, X. Ma, J. Renner, M. O. Sydnes, Org. Lett.
Acknowledgments
2004, 6, 2741.
[25] D. Ray, S. K. Mal, J. K. Ray, Synlett 2005, 2135.
[26] S. Some, B. Dutta, J. K. Ray, Tetrahedron Lett. 2006, 47, 1221.
[27] D. Ray, J. K. Ray, Tetrahedron Lett. 2007, 48, 673.
[28] S. Some, J. K. Ray, M. G. Banwell, M. T. Jones, Tetrahedron Lett.
2007, 48, 3609.
This research was supported by Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education, Science and Technology (2012-
0002856) and Kyungpook National University Research Fund, 2012.
[29] S. Some, J. K. Ray, Tetrahedron Lett. 2007, 48, 5013.
[30] D. Ray, S. Paul, S. Brahma, J. K. Ray, Tetrahedron Lett. 2007,
48, 8005.
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Copyright © 2013 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2013), 27, 380–386