Palladium-catalyzed three-component cyclization: Synthesis of hydroisoindol-1-ones from 2-bromocyclohex-1-enecarbaldehydes, anilines and carbon monoxide

Article abstract of DOI:10.1016/j.jorganchem.2010.03.025

2-Bromocyclohex-1-enecarbaldehydes react with anilines under carbon monoxide pressure in DMF at 60 °C in the presence of a catalytic amount of PdCl₂(PhCN)₂ to afford the corresponding hydroisoindol-1-ones in good yields.

Full text of DOI:10.1016/j.jorganchem.2010.03.025

Journal of Organometallic Chemistry 695 (2010) 1744e1748
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Note
Palladium-catalyzed three-component cyclization: Synthesis of
hydroisoindol-1-ones from 2-bromocyclohex-1-enecarbaldehydes, anilines and
carbon monoxide
*
Chan Sik Cho , Hyo Bo Kim, Sang Yeon Lee
Department of Applied Chemistry, Kyungpook National University, Daegu 702-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
2-Bromocyclohex-1-enecarbaldehydes react with anilines under carbon monoxide pressure in DMF at
60 ꢀC in the presence of a catalytic amount of PdCl2(PhCN)2 to afford the corresponding hydroisoindol-1-
ones in good yields.
Received 7 January 2010
Received in revised form
16 March 2010
Accepted 23 March 2010
Available online 21 April 2010
Ó 2010 Elsevier B.V. All rights reserved.
Keywords:
Anilines
2-Bromocyclohex-1-enecarbaldehydes
Carbonylation
Cyclization
Hydroisoindol-1-ones
Palladium catalyst
1. Introduction
to give isoindol-1-ones which have no substituents at position 3
(Scheme 1, route b) [6]. This protocol led us to extend to the reac-
Palladium-catalyzed cascade carbonylation and intramolecular
cyclization (carbonylative cyclization) methodology has been
recognized as a powerful synthetic tool for lactones and lactams,
which plays an important role as an intermediate for the design of
pharmaceuticals [1,2]. As part of our ongoing studies toward tran-
sition metal-catalyzed carbonylative cyclizations, several lactams
could be synthesized via an intramolecular acylpalladation to car-
bonenitrogen double bond followed by final substitution with
nucleophiles as a key mechanistic step (Scheme 1, route a). For
example, it is reported that 2-(2-bromophenyl)-2-oxazolines are
carbonylatively cyclized with aliphatic primary alcohols in the
presence of a bimetallic palladiumenickel catalyst to give tricyclic
isoindol-1-ones [3]. Such a similar palladium-catalyzed carbon-
ylative cyclization was also exemplified by the reaction of 2-bro-
mobenzaldehyde with aminoalcohols and ethylenediamines under
carbon monoxide pressure to give tricyclic isoindol-1-ones [4,5]. In
connection with this report, 2-bromobenzaldehyde was also found
to be carbonylatively cyclized with primary amines under carbon
monoxide pressure in DMF in the presence of a palladium catalyst
tion with 2-bromocyclohex-1-enecarbaldehydes, which are readily
prepared from cyclohexanones via the bromo analogue of Vilsme-
ier reaction [7e14]. Herein we describe an expedient synthesis of
hydroisoindol-1-ones via such a palladium-catalyzed carbonylative
cyclization of 2-bromocyclohex-1-enecarbaldehydes with anilines
and carbon monoxide [15].
2. Results and discussion
Based on our recent report on palladium-catalyzed synthesis of
isoindol-1-ones from 2-bromobenzaldehyde and primary amines
[6], the results of several attempted carbonylative cyclizations of 2-
bromocyclohex-1-enecarbaldehyde (1a) with aniline (2a) are listed
in Table 1. When 1a was generally treated with 2a in DMF under
carbon monoxide pressure in the presence of a catalytic amount of
a palladium catalyst, hydroisoindol-1-one 3a was produced with
concomitant formation of 1,2,3,4-tetrahydroacridine (4). It is
known that
b-halovinyl aldehydes are easily cyclized with primary
arylamines to give quinolines via N-arylenaminoimine hydrochlo-
rides [16]. The yield and distribution of the mixture of 3a and 4 was
determined from the intensity of a clearly separated signal in 1H
NMR since it was difficult to separate these two products by simple
* Corresponding author. Tel.: þ82 53 950 5586; fax: þ82 53 950 6594.
E-mail address: cscho@knu.ac.kr (C.S. Cho).
0022-328X/$ e see front matter Ó 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2010.03.025

C.S. Cho et al. / Journal of Organometallic Chemistry 695 (2010) 1744e1748
1745
Nu
N R
PdX
route a
R
R
acylpalladation
HNu
N
N
Pd, CO
N R
-Pd, -HX
PdX
X
O
O
O
route b
N R
O
Scheme 1.
elution on TLC without the loss of 4. The yield of 3a was formed
invariably irrespective of the reaction temperature under
PdCl2(PhCN)2 catalysis, however, higher reaction temperature
resulted in a slightly increased yield of 4 (entries 1e3). Further
addition of PPh3 did not give any significant change in the yield of
3a and product distribution (entry 4). Higher carbon monoxide
pressure also did not affect the product yield and distribution
(entries 5 and 6). The PdCl2 catalytic system was revealed to be
moderately effective for the formation of 3a (entry 7). The reaction
using other solvents such as toluene, dioxane and THF proceeded
with complete selectivity of 3a, but the yield was unsatisfactory
(entries 8e10).
was generally higher than that when anilines having meta- and
para-substituents were used. 2-Bromo-5-methylcyclohex-1-ene-
carbaldehyde
(1b)
and
2-bromo-5-phenylcyclohex-1-ene-
carbaldehyde (1c) react similarly with ortho-substituted anilines
(2b and 2e) to afford the corresponding hydroisoindol-1-ones
(3meo) in high yields. To test for the effect of the position of formyl
group and bromide on cyclic b-bromovinyl aldehydes, 1d and 1e
were employed. The three-component cyclization readily took
place with 1d, whereas the reaction with 1e did not proceed toward
the desired carbonylative cyclization and gave unidentifiable
products on TLC.
The reaction seems to proceed in a similar way as 2-bromo-
benzaldehyde case [6]. Oxidative addition of the carbon-bromide
bond of imine, initially formed by condensation between 1a and 2a,
to palladium(0) produces a vinylpalladium(II) complex 5 (Scheme
2). This is followed by carbonylation to form intermediate 6
which triggers intramolecular acylpalladation to give cyclized
allylpalladium(II) intermediate 7. Protonation of intermediate 7 by
H2O generated in the initial condensation stage as well as present in
solvent gives 3a [17]. We confirmed that similar treatment of 1a
with 2a and further addition of D2O (0.5 mL) under the conditions
shown in run 1 of Table 1 afforded ca. 81% deuterated 3a in 45%
Having reaction conditions being established, various six-
membered b-bromovinyl aldehydes 1 were subjected to the reac-
tion with primary aromatic amines 2 in order to investigate the
reaction scope and several representative results are summarized
in Table 2. The reaction of 1a with anilines (2bel) having electron
donating and withdrawing substituents proceeds to give the cor-
responding hydroisoindol-1-ones (3bel) in the range of 35e88%
yields with predominant selectivity to quinolines. As is the case for
the reaction of 2-bromobenzaldehyde with anilines [6], the product
yield had relevance to the position of the substituent on the
aromatic ring of 2bel rather than the electronic nature of that. With
anilines having ortho-substituent, the hydroisoindol-1-one yield
yield. Deuterated 3a was characterized with signal of
d 53.36 (t,
1JCeD ¼ 21.5 Hz) of 13C NMR spectrum and the distribution was
Table 1
Optimization of conditions for the reaction of 1a with 2aa.
CHO
cat. [Pd]
N Ph
+
+
H2N Ph
DMF
N
Br
O
1a
2a
3a
4
Entry
Palladium catalysts
Solvents
Temp (ꢀC)
CO (atm)
Yieldb (%)
3a
4
1
2
3
4
5
6
7
8
9
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2/2PPh3
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2
PdCl2(PhCN)2
PdCl2(PhCN)2
PdCl2(PhCN)2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Toluene
Dioxane
THF
60
100
130
100
100
60
60
60
60
60
10
10
10
10
20
20
10
10
10
10
68 (55)
64
66
62 (51)
70
65
17
26
31
36 (30)
23
13
22
0
41
(14)
(30)
(32)
0
0
10
a
Reaction conditions: 1a (0.6 mmol), 2a (0.5 mmol), palladium catalyst (0.02 mmol), solvent (10 mL), for 10 h.
b
Determined by 1H NMR. Isolated yield is shown in parentheses.

1746
C.S. Cho et al. / Journal of Organometallic Chemistry 695 (2010) 1744e1748
Table 2
Palladium-catalyzed synthesis of hydroisoindol-1-ones 3 from 1 and 2a.
β-Bromovinyl aldehydes
Anilines
1
2
Hydroisoindolin-1-ones
Isolated yield (%)
3
CHO
N
H2N
R
R
Br
O
1a
R = H
2a
2b
3a
3b
3c
3d
3e
3f
3g
3h
3i
55
75
43
35
88
75
78
53
R = 2-Me
2c R = 3-Me
R = 4-Me
2d
2e R = 2-Et
2f R = 2,3-(Me)2
R = 2,5-(Me)
R = 2-OMe
R = 4-OMe
2g
2h
2i
2
37
51
81
59
R = 2,5-(OMe)
R = 2-Cl
2j
3j
2
2k
2l
3k
3l
R = 4-Cl
CHO
N
R
Br
O
83
93
1b
3m
3n
2b
2e
Ph
Ph
CHO
Br
N
Et
O
97
1c
3o
2e
CHO
N
R
Br
O
72
76
1d
3p
3q
2b
2e
CHO
Br
N
O Me
0
1e
3r
2b
a
Reaction conditions: 1 (0.6 mmol), 2 (0.5 mmol), PdCl2(PhCN)2 (0.02 mmol), CO (10 atm), DMF (10 mL), 60 ꢀC, for 10 h.
determined from the comparison of the peak area of a clearly
separated signal with benzylic signal in 1H NMR spectrum.
Ph
Ph
N
CO
Pd
-H2O
N
1a
2a
+
PdBr
PdBr
3. Conclusion
O
5
6
We have demonstrated that 2-bromocyclohex-1-enecarbalde-
hydes are carbonylatively cyclized with various anilines in DMF
under carbon monoxide pressure in the presence of a catalytic
amount of a palladium catalyst to give the corresponding hydro-
isoindol-1-ones in good yields. The present reaction is a straight-
forward methodology for the synthesis of hydroisoindol-1-ones
from cyclohexanones. Further study of synthetic applications for
heterocycles of this reaction is currently under investigation.
PdBr
Ph
H2O
N
Ph
N
O
O
3a
7
Scheme 2.

C.S. Cho et al. / Journal of Organometallic Chemistry 695 (2010) 1744e1748
1747
4. Experimental
4.1.5. 2-(2-Ethylphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-one
(3e)
Oil; 1H NMR (CDCl3):
1H and 13C NMR (400 and 100 MHz) spectra were recorded on
a Bruker Avance Digital 400 spectrometer using TMS as an internal
standard. Melting points were determined on a Standford Research
Inc. MPA100 automated melting point apparatus. The isolation of
pure products was carried out via thin layer chromatography (silica
d
1.19 (t, J ¼ 7.6 Hz, 3H), 1.73e1.83 (m, 4H),
2.28e2.34 (m, 4H), 2.58 (q, J ¼ 7.6 Hz, 2H), 4.10 (t, J ¼ 2.0 Hz, 2H),
7.12 (dd, J ¼ 1.2 and 7.8 Hz, 1H), 7.20e7.24 (m, 1H), 7.26e7.33 (m,
2H); 13C NMR (CDCl3):
d 14.51, 20.60, 22.01, 22.25, 24.39, 24.47,
56.88, 126.76, 128.03, 128.11, 129.22, 132.07, 137.02, 142.46, 150.94,
171.54. Anal. Calc. for C16H19NO: C, 79.63; H, 7.94; N, 5.80. Found: C,
79.34; H, 7.84; N, 5.81.
gel 60 GF254, Merck). b-Bromovinyl aldehydes 1 were synthesized
from the corresponding ketones by treatment of PBr3/DMF/CHCl3
[7]. Commercially available organic and inorganic compounds were
used without further purification.
4.1.6. 2-(2,3-Dimethylphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-
1-one (3f)
4.1. Typical procedure for palladium-catalyzed carbonylative
cyclization of 2-bromocyclohex-1-enecarbaldehydes with anilines
Solid, m.p. 156.1e157.8 ꢀC (from hexane); 1H NMR (CDCl3):
d
1.75e1.81 (m, 4H), 2.09 (s, 3H), 2.31e2.34 (m, 4H), 2.31 (s, 3H),
4.09 (s, 2H), 6.98e7.01 (m, 1H), 7.12 (d, J ¼ 4.8 Hz, 2H); 13C NMR
To a 50 mL stainless steel autoclave were added 2-bromocy-
clohex-1-enecarbaldehyde (1a) (0.113 g, 0.6 mmol), aniline (2a)
(0.047 g, 0.5 mmol), PdCl2(PhCN)2 (0.008 g, 0.02 mmol) and DMF
(10 mL). After the system was flushed and then pressurized with
carbon monoxide to 10 atm, the reaction mixture was allowed to
react at 60 ꢀC for 10 h. The reaction mixture was filtered through
a short silica gel column (ethyl acetateehexane mixture) to elimi-
nate inorganic salts. Removal of the solvent left a crude mixture,
which was separated by thin layer chromatography (silica gel, ethyl
acetateehexane mixture) to give 2-phenyl-2,3,4,5,6,7-hexahydro-
1H-isoindol-1-one (3a) (0.059 g, 55%). All products prepared by the
above procedure were characterized spectroscopically as shown
below.
(CDCl3): d 14.80, 20.64, 20.65, 22.07, 22.31, 24.52, 56.53, 125.29,
126.18, 129.36, 132.16, 135.28, 137.50, 138.38, 150.79, 171.34. Anal.
Calc. for C15H17NO: C, 79.63; H, 7.94; N, 5.80. Found: C, 79.60; H,
8.06; N, 5.82.
4.1.7. 2-(2,5-Dimethylphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-
1-one (3g)
Oil; 1H NMR (CDCl3):
d 1.74e1.80 (m, 4H), 2.18 (s, 3H), 2.30e2.33
(m, 4H), 2.30 (s, 3H), 4.09 (s, 2H), 6.96 (s, 1H), 7.03 (d, J ¼ 7.6 Hz, 1H),
7.15 (d, J ¼ 7.6 Hz, 1H); 13C NMR (CDCl3):
d 17.94, 20.59, 20.92, 22.01,
22.25, 24.47, 56.19, 128.18, 128.56, 130.96, 132.11, 133.19, 136.45,
137.28, 150.83, 171.21. Anal. Calc. for C16H19NO: C, 79.63; H, 7.94; N,
5.80. Found: C, 79.55; H, 7.85; N, 5.78.
4.1.1. 2-Phenyl-2,3,4,5,6,7-hexahydro-1H-isoindol-1-one (3a)
4.1.8. 2-(2-Methoxyphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-
Solid, m.p. 115 ꢀC (from hexane); 1H NMR (CDCl3):
d
1.69e1.79
(m, 4H), 2.24e2.31 (m, 4H), 4.16 (s, 2H), 7.05e7.08 (m, 1H),
7.71e7.35 (m, 2H), 7.69e7.71 (m, 2H); 13C NMR (CDCl3):
20.28,
one (3h)
Oil; 1H NMR (CDCl3):
d 1.73e1.81 (m, 4H), 2.29e2.34 (m, 4H),
d
3.82 (s, 3H), 4.21 (s, 2H), 6.95e7.01 (m, 2H), 7.23e7.27 (m, 1H), 7.35
21.84, 22.12, 24.24, 53.56, 118.27, 123.40, 129.08, 133.09, 139.85,
149.98, 170.88. Anal. Calc. for C14H15NO: C, 78.84; H, 7.09; N, 6.57.
Found: C, 78.45; H, 7.14; N, 6.52.
(dd, J ¼ 1.6 and 7.7 Hz, 1H); 13C NMR (CDCl3):
d 20.67, 22.12, 22.37,
24.58, 55.51, 55.83, 112.22, 121.10, 127.41, 128.14, 128.89, 131.99,
151.28, 155.05, 171.66. Anal. Calc. for C15H17NO2: C, 74.05; H, 7.04; N,
5.76. Found: C, 73.94; H, 7.02; N, 5.70.
4.1.2. 2-(2-Methylphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-
one (3b)
4.1.9. 2-(4-Methoxyphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-
one (3i)
Solid, m.p. 73e75 ꢀC (from hexaneeCHCl3); 1H NMR (CDCl3):
d
1.73e1.83 (m, 4H), 2.23 (s, 1H), 2.28e2.35 (m, 4H), 4.11 (t,
J ¼ 2.0 Hz, 2H), 7.12e7.16 (m, 1H), 7.20e7.24 (m, 2H), 7.26e7.29 (m,
1H); 13C NMR (CDCl3):
18.45, 20.57, 22.00, 22.24, 24.47, 56.18,
Solid, m.p. 145 ꢀC (from hexaneeCHCl3); 1H NMR (CDCl3):
d
1.70e1.81 (m, 4H), 2.25e2.29 (m, 2H), 2.31e2.33 (m, 2H), 3.80 (s,
d
3H), 4.18 (t, J ¼ 2.1 Hz, 2H), 6.87e6.91 (m, 2H), 7.57e7.61 (m, 2H); 13C
126.74, 127.52, 127.71, 131.18, 132.09, 136.48, 137.54, 150.95, 171.13.
Anal. Calc. for C15H17NO: C, 79.26; H, 7.54; N, 6.16. Found: C, 78.88;
H, 7.56; N, 6.09.
NMR (CDCl3): d20.41, 21.96, 22.25, 24.33, 54.14, 55.64,114.35,120.52,
133.11, 133.24, 149.55, 156.00, 170.71. Anal. Calc. for C15H17NO2: C,
74.05; H, 7.04; N, 5.76. Found: C, 73.82; H, 6.95; N, 5.69.
4.1.3. 2-(3-Methylphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-
one (3c)
4.1.10. 2-(2,5-Dimethoxyphenyl)-2,3,4,5,6,7-hexahydro-1H-
isoindol-1-one (3j)
Solid, m.p. 131 ꢀC (from hexaneeCHCl3); 1H NMR (CDCl3):
Solid, m.p. 122.9e124.2 ꢀC (from hexane); 1H NMR (CDCl3):
d
1.71e1.82 (m, 4H), 2.26e2.30 (m, 2H), 2.33e2.36 (m, 2H), 2.36 (s,
3H), 4.22 (t, J ¼ 2.3 Hz, 2H), 6.91 (d, J ¼ 7.6 Hz, 1H), 7.24 (t, J ¼ 7.8 Hz,
1H), 7.48e7.50 (m, 1H), 7.58 (s, 1H); 13C NMR (CDCl3):
20.39, 21.88,
d 1.74e1.80 (m, 4H), 2.28e2.33 (m, 4H), 3.76 (s, 3H), 3.77 (s, 3H),
4.23 (s, 2H), 6.79 (dd, J ¼ 3.0 and 9.1 Hz, 1H), 6.89 (d, J ¼ 9.1 Hz, 1H),
d
6.98 (d, J ¼ 3.0 Hz, 1H); 13C NMR (CDCl3):
d 20.62, 22.09, 22.33,
21.98, 22.27, 24.38, 53.85, 115.66, 119.32, 124.44, 129.03, 133.33,
139.03, 139.91, 149.84, 170.95. Anal. Calc. for C15H17NO: C, 79.26; H,
7.54; N, 6.16. Found: C, 79.08; H, 7.50; N, 5.94.
24.54, 55.49, 56.00, 56.56, 113.40, 113.47, 114.06, 128.05, 131.90,
149.07, 151.44, 153.85, 171.59. Anal. Calc. for C16H19NO3: C, 70.31; H,
7.01; N, 5.12. Found: C, 69.93; H, 6.93; N, 5.06.
4.1.4. 2-(4-Methylphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-
one (3d)
4.1.11. 2-(2-Chlorophenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-
one (3k)
Solid, m.p. 117 ꢀC (from hexaneeCHCl3); 1H NMR (CDCl3):
Solid, m.p. 101.7e102.7 ꢀC (from hexane); 1H NMR (CDCl3):
d
1.69e1.79 (m, 4H), 2.23e2.27 (m, 2H), 2.29e2.33 (m, 2H), 2.31 (s,
d 1.75e1.82 (m, 4H), 2.30e2.35 (m, 4H), 4.21 (s, 2H), 7.24e7.36 (m,
3H), 4.16 (s, 2H), 7.13 (d, J ¼ 8.1 Hz, 2H), 7.56e7.59 (m, 2H); 13C NMR
3H), 7.46 (dd, J ¼ 1.5 and 8.5 Hz, 1H); 13C NMR (CDCl3):
d 20.58,
(CDCl3):
d
20.31, 20.90, 21.88, 22.16, 24.26, 53.74, 118.51, 129.61,
21.99, 22.24, 24.57, 55.40, 127.79, 128.84, 130.13, 130.61, 131.81,
132.53, 136.45, 151.68, 171.58. Anal. Calc. for C14H14ClNO: C, 67.88;
H, 5.70; N, 5.65. Found: C, 67.83; H, 5.71; N, 5.64.
133.01, 133.09, 137.36, 149.71, 170.78. Anal. Calc. for C15H17NO: C,
79.26; H, 7.54; N, 6.16. Found: C, 78.90; H, 7.52; N, 6.03.

1748
C.S. Cho et al. / Journal of Organometallic Chemistry 695 (2010) 1744e1748
4.1.12. 2-(4-Chlorophenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-
(s, 2H), 7.19e7.32 (m, 8H), 8.34 (d, J ¼ 7.9 Hz, 1H); 13C NMR (CDCl3):
one (3l)
d 18.51, 23.28, 28.09, 54.95, 123.99, 126.93, 127.16, 127.78, 128.04,
Solid, m.p. 157.5 ꢀC (from hexane); 1H NMR (CDCl3):
d
1.70e1.81
(m, 4H), 2.23e2.26 (m, 2H), 2.31e2.34 (m, 2H), 4.15 (s, 2H),
7.27e7.30 (m, 2H), 7.64e7.68 (m, 2H); 13C NMR (CDCl3):
20.29,
128.11, 129.12, 129.19, 131.33, 134.65, 136.72, 137.31, 151.40, 168.91.
Anal. Calc. for C19H17NO: C, 82.88; H, 6.22; N, 5.09. Found: C, 82.71;
H, 6.23; N, 5.39.
d
21.84, 22.12, 24.32, 53.54, 119.32, 128.34, 129.09, 133.14, 138.49,
150.22, 170.89. Anal. Calc. for C14H14ClNO: C, 67.88; H, 5.70; N, 5.65.
Found: C, 67.88; H, 5.71; N, 5.61.
4.1.17. 2-(2-Ethylphenyl)-2,3,4,5-tetrahydro-1H-benzo[e]isoindol-
1-one (3q)
Solid, m.p. 143.5e144.1 ꢀC (from hexane); 1H NMR (CDCl3):
4.1.13. 5-Methyl-2-(2-methylphenyl)-2,3,4,5,6,7-hexahydro-1H-
d
1.21 (t, J ¼ 7.6 Hz, 3H), 2.61 (t, J ¼ 7.6 Hz, 2H), 2.68 (t, J ¼ 8.2 Hz,
isoindol-1-one (3m)
2H), 3.03 (t, J ¼ 8.2 Hz, 2H), 4.29 (s, 2H), 7.17e7.36 (m, 7H), 8.33 (d,
Solid, m.p. 121.1e121.9 ꢀC (from hexane); 1H NMR (CDCl3):
d
1.08
J ¼ 7.3 Hz, 1H); 13C NMR (CDCl3):
d 14.57, 23.23, 24.49, 28.04, 55.58,
(d, J ¼ 6.3 Hz, 3H), 1.30e1.40 (m, 1H), 1.85e2.01 (m, 3H), 2.20e2.29
123.94, 126.89, 127.09, 127.75, 128.07, 128.20, 128.35, 129.02, 129.17,
129.32, 134.63, 136.77, 142.64, 151.37, 169.21. Anal. Calc. for
C20H19NO: C, 83.01; H, 6.62; N, 4.84. Found: C, 82.97; H, 6.66; N,
4.66.
(m, 1H), 2.23 (s, 3H), 2.40e2.44 (m, 2H), 4.04e4.15 (m, 2H),
7.13e7.28 (m, 4H); 13C NMR (CDCl3):
d 18.50, 20.52, 21.61, 28.80,
30.41, 32.78, 56.03, 126.78, 127.56, 127.75, 131.23, 131.91, 136.53,
137.59, 150.80, 170.98. Anal. Calc. for C16H19NO: C, 79.63; H, 7.94; N,
5.80. Found: C, 79.45; H, 8.04; N, 5.82.
Acknowledgements
4.1.14. 2-(2-Ethylphenyl)-5-methyl-2,3,4,5,6,7-hexahydro-1H-
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 (2009-
0072207).
isoindol-1-one (3n)
Solid, m.p. 77.7e78.6 ꢀC (from hexane); 1H NMR (CDCl3):
d 1.08
(d, J ¼ 6.3 Hz, 3H), 1.19 (t, J ¼ 7.6 Hz, 3H), 1.30e1.40 (m, 1H),
1.86e1.98 (m, 3H), 2.20e2.29 (m, 1H), 2.40e2.44 (m, 2H), 2.58 (q,
J ¼ 7.6 Hz, 2H), 4.03e4.14 (m, 2H), 7.12 (d, J ¼ 7.6 Hz, 1H), 7.23 (dt,
J ¼ 1.5 and 7.5 Hz, 1H), 7.26e7.33 (m, 2H); 13C NMR (CDCl3):
d 14.55,
References
20.57, 21.64, 24.45, 28.84, 30.45, 32.82, 56.74,126.82, 128.09, 128.15,
129.29, 131.95, 137.13, 142.52, 150.73, 171.37. Anal. Calc. for
C17H21NO: C, 79.96; H, 8.29; N, 5.49. Found: C, 79.87; H, 8.28; N,
5.55.
[1] E. Negishi (Ed.), Handbook of Organopalladium Chemistry for Organic
Synthesis, vol. II, Wiley, New York, 2002.
[2] H.M. Colquhoun, D.J. Thompson, M.V. Twigg, Carbonylation: Direct Synthesis
of Carbonyl Compounds. Plenum Press, New York, 1991.
[3] C.S. Cho, J.W. Lee, D.Y. Lee, S.C. Shim, T.J. Kim, Chem. Commun. (1996) 2115.
[4] C.S. Cho, D.Y. Chu, D.Y. Lee, S.C. Shim, T.-J. Kim, W.T. Lim, N.H. Heo, Synth.
Commun. 27 (1997) 4141.
4.1.15. 2-(2-Ethylphenyl)-5-phenyl-2,3,4,5,6,7-hexahydro-1H-
isoindol-1-one (3o)
[5] C.S. Cho, L.H. Jiang, S.C. Shim, Synth. Commun. 28 (1998) 849.
[6] C.S. Cho, W.X. Ren, Tetrahedron Lett. 50 (2009) 2097.
[7] R.M. Coates, P.D. Senter, W.R. Baker, J. Org. Chem. 47 (1982) 3597.
[8] J.K. Ray, M.K. Haldar, S. Gupta, G.K. Kar, Tetrahedron 56 (2000) 909.
[9] Y. Zhang, J.W. Herndon, Org. Lett. 5 (2003) 2043.
[10] S.K. Mal, D. Ray, J.K. Ray, Tetrahedron Lett. 45 (2004) 277.
[11] D. Ray, S.K. Mal, J.K. Ray, Synlett (2005) 2135.
[12] S. Some, B. Dutta, J.K. Ray, Tetrahedron Lett. 47 (2006) 1221.
[13] D. Ray, J.K. Ray, Tetrahedron Lett. 48 (2007) 673.
Solid, m.p. 110.4e111.2 ꢀC (from hexane); 1H NMR (CDCl3):
d 1.22
(t, J ¼ 7.6 Hz, 3H), 1.82e1.93 (m, 1H), 2.13e2.17 (m, 1H), 2.39e2.43
(m, 1H), 2.47e2.66 (m, 5H), 2.96e3.03 (m, 1H), 4.09e4.23 (m, 2H),
7.14e7.16 (m, 1H), 7.22e7.37 (m, 8H); 13C NMR (CDCl3):
d 14.56,
21.35, 24.46, 29.64, 32.62, 40.40, 56.61, 126.71, 126.84, 127.03,
128.07, 128.23, 128.82, 129.30, 132.13, 136.97, 142.49, 145.76, 150.54,
171.08. Anal. Calc. for C22H23NO: C, 83.24; H, 7.30; N, 4.41. Found: C,
82.90; H, 7.28; N, 4.36.
[14] S. Some, J.K. Ray, Tetrahedron Lett. 48 (2007) 5013.
[15] (a) For our report on palladium-catalyzed cyclization reactions using
b-bro-
movinyl aldehydes C.S. Cho, D.B. Patel, S.C. Shim. Tetrahedron 61 (2005) 9490;
(b) C.S. Cho, H.S. Shim, Tetrahedron Lett. 47 (2006) 3835;
(c) C.S. Cho, D.B. Patel, Tetrahedron 62 (2006) 6388;
4.1.16. 2-(2-Methylphenyl)-2,3,4,5-tetrahydro-1H-benzo[e]
isoindol-1-one (3p)
(d) C.S. Cho, J.U. Kim, H.-J. Choi, J. Organomet. Chem. 693 (2008) 3677.
[16] P. Karthikeyan, A. Meena Rani, R. Saiganesh, K.K. Balasubramanian, S. Kabilan,
Tetrahedron 65 (2009) 811.
Solid, m.p. 161.3e162.5 ꢀC (from hexane); 1H NMR (CDCl3):
d
2.27 (s, 3H), 2.69 (t, J ¼ 8.2 Hz, 2H), 3.04 (t, J ¼ 8.2 Hz, 2H), 4.32
[17] J. Takaya, K. Sangu, N. Iwasawa, Angew. Chem. Int. Ed. Engl. 48 (2009) 7090.