The Heck reaction of β-arylacrylamides: An approach to 4-aryl-2-quinolones

Article abstract of DOI:10.1055/s-2006-951505

The Heck reaction of β-arylacrylamides with aryl iodides afforded the corresponding vinylic substitution products usually in high yields. The nature of β-substituents, aryl iodides and substituents at the nitrogen atom influences the stereochemical outcome. N,N-Dimethyl-β-arylacrylamides gave vinylic substitution products with higher stereoselectivity than the corresponding N-unsubstituted β-arylacrylamides. β-Arylacrylamides containing ortho-substituents led to the formation of only one stereoisomer. The procedure was used to prepare 4-aryl-2-quinolones from β-(obromophenyl) acrylamide through a sequential Heck reaction and copper-catalyzed cyclization process. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-951505

LETTER
2947
The Heck Reaction of b-Arylacrylamides: An Approach to 4-Aryl-
2-quinolones
H
a
eck
R
eactionof
o
b
-Arylacryl
b
amides erta Bernini,a Sandro Cacchi,*b Ilse De Salve,b Giancarlo Fabrizi*b
Dipartimento A.B.A.C, Università degli Studi della Tuscia, Via S. Camillo De Lellis, 01100 Viterbo, Italy
b
Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università degli Studi ‘La Sapienza’,
P. le A. Moro 5, 00185 Rome, Italy
Fax +39(06)49912780.; E-mail: sandro.cacchi@uniroma1.it
Received 4 April 2006
Dedicated to Professor Richard Heck
Heck reactions of a,b-unsaturated carbonyl compounds in
aqueous media.5 On the other hand, the b,b-diarylacryl-
amide motif is present in a variety of biologically active
molecules.6 Therefore, it appeared to us of interest to ex-
Abstract: The Heck reaction of b-arylacrylamides with aryl io-
dides afforded the corresponding vinylic substitution products usu-
ally in high yields. The nature of b-substituents, aryl iodides and
substituents at the nitrogen atom influences the stereochemical out-
come. N,N-Dimethyl-b-arylacrylamides gave vinylic substitution plore in more detail the Heck reaction of this class of com-
products with higher stereoselectivity than the corresponding N-un-
pounds.
substituted b-arylacrylamides. b-Arylacrylamides containing
Herein we report the results of this study.
ortho-substituents led to the formation of only one stereoisomer.
The reaction of p-iodoanisole with cinnamamide7 (1a) in
The procedure was used to prepare 4-aryl-2-quinolones from b-(o-
bromophenyl)acrylamide through a sequential Heck reaction and
the presence of 0.05 equivalents of Pd(OAc)2 was initially
examined as the model system (Scheme 1).
copper-catalyzed cyclization process.
Key words: cinnamamides, 2-quinolones, cyclization, palladium
catalysis, copper catalysis
OMe
O
Pd cat.
R1
N
R2
R2
The Heck reaction of b-substituted a,b-unsaturated carbo-
nyl compounds with aryl halides may serve as a valuable
method for the preparation of highly functionalized olefin
systems. Because of this, the preparation of b,b-disubsti-
tuted derivatives from b-substituted a,b-enals and -en-
ones,1 and a,b-unsaturated esters2 have been the subject of
several investigations, with the achievement of a stereose-
lective synthesis being a major target. Indeed, whereas ex-
cellent regioselectivity was always observed (with vinylic
substitution products at the b-position being usually the
sole products), the stereochemistry of the reaction was
found to depend strongly on reaction conditions.
OMe
I
1a: R1 = Ph; R2 = H
MeO
R2
N
O
R2
N
R2
R1
R2
R1
O
2a: R1 = Ph; R2 = H
3a: R1 = Ph; R2 = H
Scheme 1
Part of our optimization work using different bases, sol-
vents and additives is displayed in Table 1. Under a vari-
ety of reaction conditions, good chemical yields were
observed but the stereochemical outcome was only mod-
erate (Table 1, entries 1–3). Under Jeffery conditions8 no
vinylic substitution product was isolated (Table 1, entry
4). Using KOAc as base and omitting Bu4NCl produced
the vinylic substitution product in good yield and satisfac-
tory stereoselectivity (Table 1, entry 5). Switching to a
Bu4NOAc/Bu4NBr molten salt mixture (these conditions
gave excellent conversions and stereochemical control
with cinnamate esters)2g led to a moderate conversion and
low 2a:3a molar ratio (Table 1, entry 8). The best result in
terms of yield and 2a:3a molar ratio was obtained when
the reaction was carried out in triethylamine (Table 1, en-
try 7).
Surprisingly, very little has been done with b-substituted
acrylamides. We described the tendency of cinnamamide
to afford preferentially the corresponding vinylic substitu-
tion product in the palladium-catalyzed reaction with io-
dobenzene in the presence of triethylamine and formic
acid as compared to cinnamaldehyde and benzalacetone
(and a variety of a,b-enones), which gave conjugate addi-
tion-type derivatives as the main products under the same
conditions.3 A b,b-diarylacrylamide was prepared adapt-
ing the Heck reaction to solid-phase conditions, but the
stereochemistry of the Heck product was not established.4
More recently, Nájera et al. described the preparation of
two b,b-diarylacrylamides via vinylic substitution of b-
substituted acrylamides in a study devoted to explore
The stereochemistry of 2a and 3a [obtained as an approx-
imately 20:80 mixture when prepared from iodobenzene
and b-(p-methoxyphenyl)acrylamide] was assigned by
SYNLETT 2006, No. 18, pp 2947–2952
Advanced online publication: 25.10.2006
DOI: 10.1055/s-2006-951505; Art ID: S05406ST
© Georg Thieme Verlag Stuttgart · New York
0
3
.1
1
.2
0
0
6

2948
R. Bernini et al.
LETTER
Table 1 Bases, Additives, and Solvents in the Palladium-Catalyzed Reaction of Cinnamamide (1a) with p-Iodoanisolea
Entry
Base
Additive
Solvent
Time (h)
Overall yield (%) 2a:3a
Yield (%) of
recovered 1a
1
2
3
4
5
6
7
8
Et3N (3 equiv)
–
DMF
THF
EtOAc
DMF
DMF
DMF
–
48
24
24
96
96
48
12
24
82
70
67
–
76:24
74:26
74:26
15
25
27
68
20
18
–
Et3N (3 equiv)
–
Et3N (3 equiv)
–
K2CO3 (2 equiv)
KOAc (2 equiv)
Bu4NOAc (2 equiv)
Et3N (5 equiv)
Bu4NCl (1 equiv)
–
71
54
92
60
84:16
68:32
83:17
70:30
–
–
Bu4NOAc (3 equiv)
Bu4NBr (3 equiv)
–
20
a All reactions were carried out on a 0.5-mmol scale at 100 °C under an argon atmosphere using 1 equiv of 1a, 1.5 equiv of p-iodoanisole and
0.05 equiv of Pd(OAc)2 in 1.5 mL of solvent.
NOE experiments. That of the other vinylic substitution Using p-iodoanisole as the aryl partner, b,b-diarylacryl-
products (vide infra) has been assigned based on these amides were produced in high yields and with satisfactory
data.
stereoselectivity, the highest stereoselectivity being ob-
served with the N,N-dimethyl-b-arylacrylamides
(Table 2, entries 2, 3, 6, 9, 11, 13, 14) and b-(o-substituted
aryl)acrylamides (Table 2, entries 4, 7–9).
Thus, these conditions were used when the procedure was
extended to the reaction of other b-arylacrylamides9 with
p-iodoanisole (Table 2) and ethyl p-iodobenzoate
(Table 3), models of electron-rich and electron-poor aryl Reactions with ethyl p-iodobenzoate, under the conditions
iodides, respectively. used with p-iodoanisole, showed a strong tendency to give
Table 2 The Palladium-Catalyzed Heck Reaction of b-Arylacrylamides 1 with p-Iodoanisolea
Entry
b-Arylacrylamide 1
Time (h)
Yield of 2 (%)b
Yield of 3 (%)b
R1
R2
H
1
2
Ph
1a
1b
1c
1d
1e
1f
24
12
48
12
24
48
24
12
24
24
48
24
48
36
2a, 66
2b, 74
2c, 79
2d, 91
2e, 56
2f, 64
2g, 74
2h, 87
2i, 70
2j, 57
2k, 80
2l, 68
2m, 83
2n, 84
3a, 16
3b, 8
3c, 17
–
Ph
Me
Me
H
3
p-Me-C6H4
o-MeO-C6H4
m-MeO-C6H4
m-MeO-C6H4
o-Me-C6H4
o-Br-C6H4
o-Br-C6H4
m-F-C6H4
m-F-C6H4
m-CF3-C6H4
m-CF3-C6H4
p-MeCO-C6H4
4
5
H
3e, 14
3f, 24
–
6
Me
H
7
1g
1h
1i
8
H
–
9
Me
H
–
10
11
12
13
14
1j
3j, 18
3k, 8
3l, 12
3m, 9
3n, 10
Me
H
1k
1l
Me
Me
1m
1n
a All reactions were carried out on a 0.5-mmol scale at 100 °C under an argon atmosphere using 1 equiv of 1, 1.5 equiv of p-iodoanisole, 3 equiv
of Et3N and 0.05 equiv of Pd(OAc)2.
b Yields are given for isolated products.
Synlett 2006, No. 18, 2947–2952 © Thieme Stuttgart · New York

LETTER
Heck Reaction of b-Arylacrylamides
2949
p,p¢-diethoxycarbonyl biphenyl, the biaryl product vinylic substitution event through the well-known elimi-
formed via a homocoupling process. With the N-unsubsti- nation–reverse-addition–elimination of HPd species and
tuted b-arylacrylamides that we have tested, p,p¢-dieth- that no equilibration occurs after the vinylic substitution
oxycarbonyl biphenyl was isolated in 20–37% yields and products are formed.
the desired vinylic substitution products were obtained in
moderate yields (Table 3, entries 2, 5 and 10).
This view is supported by the following experiment. A
pure sample of 2ae, prepared via the reaction of 1l with p-
Since it has been reported that formation of homocoupling iodotoluene, was subjected to the conditions producing vi-
biaryl products – a competitive side reaction assumed to nylic substitution products in the presence of 1a and p-io-
require a bimolecular transmetalation of s-arylpalladium doanisole (Scheme 2). The 3,3-diarylacrylamide product,
intermediates – can be limited by decreasing the catalyst formed via the reaction of 1a with p-iodoanisole, was iso-
loading,10 we decided to conduct the reaction using lower lated in 80% yield as an approximately 85:15 E/Z mixture
amounts of catalyst. Indeed, decreasing the catalyst load- (a result similar to that reported in Table 2, entry 1). Com-
ing to 0.01 equivalent led to a remarkable increase of pound 2ae was recovered in almost quantitative isolated
yields at the expense of biaryl formation (Table 3, com- yield and its stereochemistry was maintained, even under
pare entries 3, 6, 11 with entries 2, 5, 10, respectively).11
prolonged heating.
As to the stereochemical outcome, equilibration following Electronic effects due to the b-aryl groups in the carbopal-
the Heck arylation might account for the formation of ladation adduct appear to play a role in controlling the ste-
mixtures of stereoisomers. In the present reaction, howev- reochemical outcome. In particular, it seems that b-
er, it appears that stereoisomers are generated during the substituents containing electron-withdrawing groups tend
Table 3 The Palladium-Catalyzed Heck Reaction of b-Arylacrylamides 1 with Ethyl p-Iodobenzoatea
Entry
b-Arylacrylamide 1
Yield of 2 (%)
Yield of 3 (%)b,c
R1
R2
H
1
2d
3
o-MeO-C6H4
m-MeO-C6H4
m-MeO-C6H4
m-MeO-C6H4
p-MeO-C6H4
p-MeO-C6H4
p-MeO-C6H4
o-Me-C6H4
o-Me-C6H4
Ph
1d
1e
1e
1f
2o, 78
2p, 56
2p, 68
2q, 74
2r, 37
2r, 62
2s, 88
2t, 90
–
H
3p, 14 (5)
3p, 13 (–)
3q, 6
H
4
Mee
H
5d
6
1j
3r, 11 (20)
3r, 14 (–)
3s, 7
H
1j
7
Mee
H
1o
1g
1g
1a
1a
1b
1j
8d
9
–
H
2t, 91
–
10d
11
12
13d
14
15d
16
17
18
H
2u, 36
2u, 74
2v, 91
2w, 60
2y, 86
2z, 48
2ab, 82
2ac, 82
2ad, 65
3u, 16 (30)
3u, 13 (–)
2v, 6
Ph
H
Ph
Mee
H
m-F-C6H4
m-F-C6H4
m-CF3-C6H4
m-CF3-C6H4
o-Br-C6H4
p-MeCO-C6H4
3w, 10 (32)
3y, 10
3z, 9 (37)
3ab, 8
–
Me
H
1k
1l
Mee
H
1m
1h
1n
Mee
–
a Unless otherwise stated, reactions were carried out on a 0.5-mmol scale at 100 °C for 24 h under an argon atmosphere using 1 equiv of 1, 2.5
equiv of ethyl p-iodobenzoate, 5 equiv of Et3N and 0.01 equiv of Pd(OAc)2.
b Yields are given for isolated products.
c Figures in parentheses refer to isolated homocoupling products.
d In the presence of 1.5 equiv of ethyl p-iodobenzoate, 3 equiv of Et3N and 0.05 equiv of Pd(OAc)2.
e 36 h.
Synlett 2006, No. 18, 2947–2952 © Thieme Stuttgart · New York

2950
R. Bernini et al.
LETTER
CF3
O
tion of 2-quinolone derivatives, a class of compounds
abundant in many biologically active compounds,13
through a process involving a Heck reaction followed by
an intramolecular carbon–nitrogen bond-forming step
(Scheme 3).
OMe
O
NH2
Ph
NH2
1a
2ae
Me
I
Ar
O
Pd(OAc)2
Et3N, 100 °C
30 h
NH2
ArI
Ph
O
O
Br
Br
2ae
NH2
NH2
80% (2a:3a = 85:15)
recovered in
90% yield
1h
MeO
Ar
Scheme 2
N
O
H
to afford higher stereoselectivity. For example, a relative-
ly low stereoselectivity was observed in the reaction of 1c
with p-iodoanisole – the carbopalladation adduct contains
two electron-rich b-substituents (Table 2, entry 3) –
whereas 2ad was formed as the sole stereoisomer in the
reaction of 1n with ethyl p-iodobenzoate (Table 3, entry
18). In the latter case, the carbopalladation adduct con-
tains two electron-poor b-substituents.
4
Scheme 3
With regard to the cyclization step, the economic attrac-
tiveness of copper-based methods and the growing inter-
est in copper-catalyzed syntheses14 stimulated us to
develop a copper-catalyzed protocol.
The general higher diastereoselectivity observed with
N,N-dimethyl-b-arylacrylamides as compared to N-un-
substituted b-arylacrylamides may be due to the stronger
tendency of the disubstituted amide group to coordinate to
palladium12 (Figure 1). This coordinating effect could dis-
favor the reverse addition of HPdX generating the carbo-
palladation adduct with the palladium atom close to the b-
substituents.
Using the vinylic substitution product 2h as the model
system, the cyclization reaction was attempted under a va-
riety of reaction conditions. As shown in Table 4, the
highest yield was obtained in the presence of 0.2 equiva-
lent of CuI, 2 equivalents of NaI,15 2 equivalents of
K3PO4, 0.4 equivalent N,N-dimethylethylendiamine
(DMEDA) in dioxane at 120 °C.
To make this overall approach to 2-quinolones more at-
tractive from a synthetic standpoint, we explored the vi-
nylic substitution and cyclization of 1f through a process
that would omit the isolation of vinylic substitution inter-
mediates. After some experimentation, we were pleased
to find that adding CuI, NaI, K3PO4, N,N-dimethylethyl-
endiamine and dioxane to the crude mixture derived from
the Heck reaction after work-up gave quinolone products
in good to high overall isolated yields with neutral, elec-
tron-rich and electron-poor aryl iodides (Table 5).16 None
of the quinolone derivative was obtained when the vinylic
substitution–cyclization protocol was attempted under op-
timized conditions omitting CuI.
X
H
Pd
O
Ar'
Ar
NMe2
Figure 1
The exclusive formation of the trisubstituted olefin con-
taining the original b-substituent on the same side of the
carbon–carbon double bond as the amide group when b-
(o-substituted aryl)acrylamides are used as substrates is
also remarkable. Most probably it is due to the relative in-
stability of the adduct B, which would form from A via
elimination–reverse-addition of HPdX, in the presence of
an ortho-substituent (Figure 2).
In conclusion, we have shown that the palladium-cata-
lyzed reaction of b-arylacrylamides with aryl iodides in
the presence of triethylamine affords vinylic substitution
products usually in high yield. The nature of b-substitu-
ents, aryl iodides and substituents at the nitrogen atom
was found to influence the stereochemical outcome of the
reaction. In particular, the presence of b-substituents con-
taining electron-withdrawing groups in the carbopallada-
tion adduct appear to afford higher diastereoselectivity;
N,N-dimethyl-b-arylacrylamides tend to give a higher
diastereoselectivity than the corresponding N-unsubsti-
tuted b-arylacrylamides; b-arylacrylamides containing
ortho-substituents lead to the formation of only one ste-
R
R
H
PdX
CONH2
XPd
Ar
H
H
CONH2
Ar
H
A
B
Figure 2
The results obtained with 3-(o-bromophenyl)acrylamide
1f (Table 2, entry 8; Table 3, entry 17) prompted us to in-
vestigate the utilization of this chemistry for the prepara-
Synlett 2006, No. 18, 2947–2952 © Thieme Stuttgart · New York

LETTER
Heck Reaction of b-Arylacrylamides
2951
Table 4 Examination of the Copper-Catalyzed Cyclization of 2h to the Quinolone Product 4ba
Entry
Catalyst system Base
Additive
Ligand
Temp (°C)
110
Time (h)
Yield of 4b (%)b,c
50 (–)
1
2
3
4
5
6
CuCl(PPh3)
CuI
K3PO4
–
–
20
96
48
96
48
24
K3PO4
K3PO4
K3PO4
–
NaI
–
1,3-DAPd
DMEDA
DMEDA
DMEDA
DMEDA
110
50 (50)
CuI
110
66 (34)
CuI
–
120
56 (40)
CuI
NaI
NaI
120
16 (83)
CuI
K3PO4
120
85 (–)
a All reactions were carried out on a 0.5-mmol scale using 1 equiv of 1h, 0.2 equiv of the copper catalyst, 2 equiv of NaI (when added), 2 equiv
of K2CO3 (when added), 0.4 equiv of 1,3-DAP or DMEDA (when added) in 2 mL of dioxane.
b Yields are given for isolated products.
c Figures in parentheses refer to the recovered starting material.
d 1,3-Diaminopropane.
Table 5 Synthesis of 4-Aryl-2-quinolones 4 through a Sequential Heck Reaction–Copper-Catalyzed Cyclization of b-(o-Bromophenyl)acry-
lamide 1ha
Entry
ArI
Time (h)
Overall yield of 4 (%, procedure)b
Heck reaction
Cyclization
1
2
3
4
5
m-MeO-C6H4-I
p-MeO-C6H4-I
Ph-I
48
12
48
48
48
24
24
24
24
24
4a, 71 (A)
4b, 77 (A)
4c, 77 (A)
4d, 71 (B)
4e, 60 (B)
m-F-C6H4-I
p-EtOOC-C6H4-I
a Reactions were carried out on a 0.5-mmol scale as follows. Procedure A: 1 equiv of 1, 1.5 equiv of aryl iodide, 3 equiv of Et3N and 0.05 equiv
of Pd(OAc)2 at 100 °C, work-up, and then 0.2 equiv of CuI, 2 equiv of NaI, 2 equiv of K2CO3, 0.4 equiv of DMEDA and 2 mL of dioxane at
120 °C; procedure B: 1 equiv of 1, 2.5 equiv of aryl iodide, 5 equiv of Et3N and 0.01 equiv of Pd(OAc)2 at 100 °C, work-up, and then as for
procedure A.
b Yields are given for isolated products.
reoisomer. The procedure was used to develop an efficient
approach to 4-aryl-2-quinolones from b-(o-bromophen-
yl)acrylamide through a sequential Heck-reaction–cop-
per-catalyzed-cyclization process.
References and Notes
(1) (a) Amorese, A.; Arcadi, A.; Bernocchi, E.; Cacchi, S.;
Cerrini, S.; Fedeli, W.; Ortar, G. Tetrahedron 1989, 45, 813.
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Morera, E.; Pace, P. Synlett 1996, 545. (d) Arcadi, A.;
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Acknowledgment
Work carried out in the framework of the National Projects ‘Stereo-
selezione in Sintesi Organica. Metodologie ed Applicazioni’ and
supported by the Ministero dell’Università e della Ricerca Scienti-
fica e Tecnologica, Rome, and by the University ‘La Sapienza’, Ro-
me.
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Synlett 2006, No. 18, 2947–2952 © Thieme Stuttgart · New York

2952
R. Bernini et al.
LETTER
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(7) b-Arylacrylamides were prepared in almost quantitative
yields from 1 equiv of aryl iodides and 1.1 equiv of acryl-
amide or N,N-dimethylacrylamide in MeCN at 100 °C in the
presence of 0.01 equiv of the Herrmann catalyst and 3 equiv
of Et3N: Herrmann, W. A.; Brossmer, K.; Reisinger, C.-P.;
Priermeier, T.; Beller, M.; Fischer, H. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1844.
(8) Jeffery, T. Tetrahedron Lett. 1985, 26, 2667.
(9) Typical Procedure for the Reaction of b-Arylacrylamides
with p-Iodoanisole.
To a stirred solution of 1h (0.113 g, 0.50 mmol), p-iodo-
anisole (0.093 mg, 0.75 mmol) and Et3N (348 mL, 2.5
mmol), Pd(OAc)2 (0.006 g, 0.025 mmol) was added. The
reaction mixture was stirred for 12 h at 100 °C. Then, the
mixture was diluted with EtOAc and washed with H2O. The
organic layer was dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by chromatog-
raphy (silica gel, 35 g; n-hexane–EtOAc, 30:70) to give
0.144 g (87% yield) of 2h: mp 163–165 °C. IR (KBr): 3294,
3177, 1654 cm–1. 1H NMR (CDCl3): d = 7.69 (dd, J = 8.4,
1.33 Hz, 1 H), 7.43 (m, 1 H), 7.32–7.27 (m, 3 H), 7.23–7.21
(m, 2 H), 6.87–6.85 (m, 2 H), 6.49 (s, 1 H) 5.28–5.16 (d, 2
H),1.61 (s, 3 H). 13C NMR (CDCl3): d = 167.2, 160.1, 148.6,
139.0, 132.8, 130.3, 130.2, 129.4, 128.1, 127.4, 122.3,
119.7, 113.6, 54.8. MS: m/z (rel. int.) = 332 (100) [M+], 334
(73), 252 (54). Anal. Calcd for C16H14BrNO2: C, 57.85; H,
4.25; Br, 24.05; N; 4.22. Found: C, 57.77; H, 4.28; Br, 24.02;
N, 4.26.
(14) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003, 42,
5400.
(15) Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
14844.
(16) Typical Procedure for the Preparation of
2-Quinolones 4.
To a stirred solution of 1h (0.113 g, 0.50 mmol), p-iodo-
anisole (0.093 g, 0.75 mmol) and Et3N (348 mL, 2.5 mmol),
Pd(OAc)2 (0.006 g, 0.025 mmol) was added. The reaction
mixture was stirred for 12 h at 100 °C. Then, the mixture was
diluted with EtOAc and washed with H2O. The organic layer
was dried over Na2SO4 and concentrated under reduced
pressure. Then, 2 mL of dioxane, CuI (0.019 g, 0.1 mmol),
NaI (0.149 g, 1 mmol), K3PO4 (0.212 g, 1 mmol), N,N-
dimethylethylendiammine (21.3 mL, 0.2 mmol) and were
added to the crude mixture. The mixture was stirred for 24 h
at 120 °C. Then, the mixture was diluted with EtOAc and
washed with a sat. NH4Cl solution. The organic layer was
dried over Na2SO4 concentrated under reduced pressure. The
residue was purified by chromatography (silica gel, 35 g; n-
hexane–EtOAc, 30:70) to give 0.97 g (77% yield) of 4b: mp
196–198 °C. IR (KBr): 3131, 1672 cm–1. 1H NMR (DMSO-
d6): d = 11.82 (s, 1 H), 7.51 (t, J = 8 Hz, 1 H), 7.44–7.36 (m,
(10) Lane, B. S.; Sames, D. Org. Lett. 2004, 6, 2897.
(11) Typical Procedure for the Reaction of b-Arylacrylamides
with Ethyl p-Iodobenzoate.
To a stirred solution of 1h (0.113 g, 0.50 mmol), ethyl p-
iodobenzoate (209 mL, 1.25 mmol) and Et3N (348 mL, 2.5
mmol), Pd(OAc)2 (0.001 g, 0.005 mmol) was added. The
reaction mixture was stirred for 24 h at 100 °C. Then, the
mixture was diluted with EtOAc and washed with H2O. The
organic layer was dried over Na2SO4 and concentrated under
reduced pressure. The residue was purified by chromatog-
raphy (silica gel, 35 g; n-hexane–EtOAc, 25:75) to give
0.152 g (82% yield) of 2ac: mp 235–237 °C. IR (KBr): 3338,
3181, 1668 cm–1. 1H NMR (CDCl3): d = 8.03 (d, J = 8.3 Hz,
2 H), 7.69 (d, J = 8.4 Hz, 1 H), 7.45 (t, J = 7.6 Hz, 1 H),
7.35–7.30 (m, 4 H), 6.61 (s, 1 H) 5.32–5.25 (d, 2 H), 4.37 (q,
J = 7.1 Hz, 2 H), 1.38 (t, J = 7.1 Hz, 3 H). 13C NMR
(CDCl3): d = 166.5, 165.5, 147.9, 142.1, 138.2, 132.9, 130.4,
130.3, 129.8, 129.3, 127.5, 126.6, 123.5, 122.2, 60.6,
4 H), 7.13–7.07 (m, 3 H), 6.34 (s, 1 H), 3.82 (s, 3 H). 13
C
NMR (DMSO-d6): d = 161.3, 159.6, 151.1, 139.3, 130.4,
130.1, 128.8, 126.2, 121.7, 120.9, 118.5, 115.8, 114.1, 55.2.
MS: m/z (rel. int.) = 251 (100) [M+], 252 (25), 236 (25) 220
(12). Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N; 5.57.
Found: C, 76.55; H, 5.18; N, 5.53.
Synlett 2006, No. 18, 2947–2952 © Thieme Stuttgart · New York