Synthesis of 2-naphthylacrylamides and 2-naphthylacrylates via homogeneous catalytic carbonylation of 1-iodo-1-naphthylethene derivatives

Article abstract of DOI:10.1016/j.tet.2009.04.056

Two highly reactive iodoalkenes (1-iodo-1-(2-naphthyl)ethene and 1-iodo-1-(1-naphthyl)ethene) were prepared from the corresponding acetonaphthone isomers via their hydrazones and used as substrates in palladium-catalysed carbonylations. Both iodoalkenyl s

Full text of DOI:10.1016/j.tet.2009.04.056

Tetrahedron 65 (2009) 4795–4800
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Synthesis of 2-naphthylacrylamides and 2-naphthylacrylates via homogeneous
catalytic carbonylation of 1-iodo-1-naphthylethene derivatives
*
´
´
´
´
Attila Takacs, Roland Farkas, Andrea Petz, Laszlo Kollar
Department of Inorganic Chemistry, University of Pe´cs, H-7624 P´ecs, PO Box 266, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Two highly reactive iodoalkenes (1-iodo-1-(2-naphthyl)ethene and 1-iodo-1-(1-naphthyl)ethene) were
prepared from the corresponding acetonaphthone isomers via their hydrazones and used as substrates in
palladium-catalysed carbonylations. Both iodoalkenyl substrates proved to be highly reactive in the
presence of various N-nucleophiles and the corresponding N-substituted naphthylacrylamides were
formed chemoselectively in nearly quantitative yields. High isolated yields (up to 93%) were achieved
with all types of amines under mild reaction conditions. The alkoxycarbonylation of the above
iodoalkenes resulted in esters of unexpectedly good isolated yields (up to 77%).
Received 30 January 2009
Received in revised form 1 April 2009
Accepted 17 April 2009
Available online 24 April 2009
Keywords:
Aminocarbonylation
Carbon monoxide
Amino acid
Ó 2009 Elsevier Ltd. All rights reserved.
Palladium
Iodoalkene
1. Introduction
halide–carboxamide route can be synthesised from easily available
starting materials.5
Conjugated unsaturated carboxamides represent an important
family of building blocks in synthetic chemistry.1 Among them 2-
acetamidoacrylamides and 2-acetamidocinnamic amides are
widely used substrates in enantioselective hydrogenation for the
synthesis of alanine amides and phenylalanine amides, re-
spectively.2 Their synthetic applicability and chemical properties
can be tuned by structural variation both on the amide nitrogen and
on the carbon–carbon double bond.
In spite of the close structural relation to phenylacrylic acid
derivatives, relatively little is known on synthesis and application
of naphthylacrylates and naphthylacrylamides. Conformational
studies and photochemical behaviour of ethyl 2-naphthylacrylate
and N,N-dimethyl-2-naphthylacrylamide were carried out.6
Encouraged by the fact that the palladium-catalysed amino-
carbonylation reaction of the iodoalkene or enol-triflate intermediate
might provide an efficient route for the synthesis of 2-naph-
thylacryloyl amides, we decided to investigate their synthesis by
using the corresponding 1-iodo-1-naphthylethene derivatives as
substrates. The synthetic utility of the aminocarbonylation reaction
for the synthesis of unsaturated carboxamides or aryl carboxamides
with various structures has been demonstrated recently also in our
group.7,8 Accordingly, a clean and almost quantitative synthetic
methodology is reported here for the aminocarbonylation of 1-iodo-
1-naphthylethene isomers with simple primary and secondary
amines, as well as with functionalised amines like amino acid methyl
esters as N-nucleophiles.
The palladium-catalysed carbonylation reactions of haloaro-
matics or haloalkenes (preferably iodo derivatives) as well as those
of the corresponding triflate surrogates are important and widely
used reactions for the synthesis of aromatic or a-unsaturated car-
boxylic acid derivatives, respectively. For example, in the presence
of various nucleophiles such as amines and alcohols the efficient
synthesis of carboxamides and esters can be carried out, re-
spectively.3 The efficacy of these reactions can be demonstrated
both by the synthesis of simple model compounds and by the
functionalisation of biologically important skeletons.4 The key to
their wide application lies in the fact that even those carboxamides,
which are difficult to prepare (or not available in yields of practical
importance) via the conventional carboxylic acid–carboxylic
2. Results and discussion
2.1. Synthesis of 1-iodo-1-(1-naphthyl)ethene (5)
and 1-iodo-1-(2-naphthyl)ethene (7)
The above two iodoalkenes have been synthesised in the con-
ventional ketone–hydrazone–iodo-alkene route by using BaO and
* Corresponding author.
E-mail address: kollar@ttk.pte.hu (L. Kollar).
´
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.056

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A. Takacs et al. / Tetrahedron 65 (2009) 4795–4800
4796
TMG (N,N,N0,N0-tetramethylguanidine) in the two consecutive steps
(Scheme 1).9 As in case of previous preparations, the hydrazone
derivatives (3 and 4) were not isolated. Since 1-ethynyl- and
2-ethynyl-naphthalenes (6 and 8, respectively) were formed as
undesired side-products in the iodination step aiming at the syn-
thesis of 5 and 7, respectively, several modifications had to be done
concerning the original paper. By using TMG in ninefold excess as
usual in case of cyclic ketones,1 was transformed also to 6 (the ratio
of 5/6 was ca. 2/1). It was necessary to decrease the TMG/hydrazone
ratio to 3/1 in order to obtain the target iodoalkene compounds (5
and 7) as major products. The yields of 5 and 7 were also increased
by decreasing the reaction temperature of the iodine-TMG step, i.e.,
the reaction temperature was kept between 5 and 10 ꢀC throughout
O
I
NR'R''
CO, HNR'R''
Pd(OAc)2 / PPh3
5
9
CO, HNR'R''
Pd(OAc)2 / PPh3
NR'R''
I
O
7
10
R'
R''
a
b
H
H
t-Bu
Ph
I
X
c
d
e
f
-(CH2)5-
-(CH2)2O(CH2)2-
I , TMG
2
+
H
H
CH2COOCH3
CH(CH3)COOCH3
CH(CH(CH3)2)COOCH3
X = O
1
3
5
(96 %)
6
N2H4, BaO
g
h
H
X = NNH2
-CH(COOCH3)(CH2)3-
Scheme 2. Palladium-catalysed aminocarbonylation of 5 and 7.
X
I2, TMG
I
+
such as sterically hindered secondary amines (h), which have
shown decreased reactivity in aminocarbonylation of various
iodoalkenes in previous studies, provided excellent isolated yields
(Table 1). It is worth noting that no 2-ketocarboxamide formation,
due to double carbon monoxide insertion, was observed.
X = O
2
4
7
8
(92 %)
N2H4, Et3N
X = NNH2
Scheme 1. Synthesis of the iodoalkenes (5 and 7) from the corresponding ketones via
Detailed GC–MS analyses have shown that high conversions
have been obtained with different amines even after a short re-
action time. For example, the reaction of 5 with a towards 9a
resulted in 70%, 98.7% and 99.6% conversions in 15 min, 30 min and
45 min, respectively. In the same reactions times, the reaction of 5
with c towards 9c resulted in 47%, 76% and 97% conversions, re-
spectively. It is worth noting that the full conversions, obtained in
seemingly excessive reaction times, such as 20 h (Table 1), enabled
the facile isolation of the amide products.
The enhanced reactivity of the substrates was also reflected in
alkoxycarbonylation. In addition to the widely used methanol (i)
even the less reactive alcohols (isopropyl alcohol (j) and benzyl
alcohol (l)) brought about yields of synthetic interest (Scheme 3).
their hydrazones.
the reaction. When the addition of the hydrazone-TMG mixture to
iodine in dichloromethane was completed, the solution was
allowed to warm up to room temperature. It has to be noted that
the high isolated yields, given for the iodoalkenes in the Experi-
mental section, could be obtained only when the ‘iodovinyl’ prod-
uct-forming step was carried out under argon providing strictly
moisture- and oxygen-free conditions. Optimised experimental
conditions for the synthesis of 5 and 7 are given below in the
Experimental section.
2.2. Amino- and alkoxycarbonylation of 5 and 7
The iodo-naphthylethene isomers (1-iodo-1-(1-naphthyl)ethene,
5 and 1-iodo-1-(2-naphthyl)ethene, 7) were reacted with tert-
butylamine (a), aniline (b), piperidine (c), morpholine (d), methyl
glycinate (e), methyl alaninate (f), methyl valinate (g) and methyl
prolinate (h) under atmospheric carbon monoxide in the presence
of in situ generated palladium(0)-triphenylphosphine catalysts
(Scheme 2). The palladium(0) complexes, able to activate iodoal-
kenes, were prepared in situ from palladium(II) acetate as described
previously in detail.10,11
The reactivity of both iodo-naphthylethene isomers, 5 and 7,
compared to several types of iodoalkenes, such as linear (e.g.,1-iodo-
1-dodecene8) and cyclic iodoalkenes (e.g., 1-iodo-1-cyclohexene12
and similar compounds of pharmacological importance1,5), proved to
be exceptionally high. Due to the presence of an activating aryl-
group at the sp2 carbon atom bearing the iodide as good leaving group,
all of the resulting N-substituted 2-naphthylacrylamides (9a–h
and 10a–h) have been obtained with practically complete conver-
sion and isolated in 70–93% yields after column chromatography
(Experimental) except for b. It has to be noted that 10b could not be
isolated as a pure substance for full characterisation. The decreased
reactivity of b could be explained by its lower basicity compared to
the primary and secondary alkylamines used. Even those amines,
Table 1
Palladium-catalysed aminocarbonylation of 5 and 7a
Entry
Substrate
Amine
Isolated yieldb (amide) [%]
1
2
3
4
5
6
7
8
5
7
5
7
5
7
5
7
5
7
5
7
5
7
5
7
t-BuNH2 (a)
t-BuNH2 (a)
Aniline (b)
87 (9a)
85 (10a)
13 (9b)
n.d. (10b)
93 (9c)
90 (10c)
88 (9d)
85 (10d)
80 (9e)
77 (10e)
80 (9f)
75 (10f)
76 (9g)
75 (10g)
70 (9h)
73 (10h)
Aniline (b)
Piperidine (c)
Piperidine (c)
Morpholine (d)
Morpholine (d)
GlyOMe (e)
GlyOMe (e)
AlaOMe (f)
9
10
11
12
13
14
15
16
AlaOMe (f)
ValOMe (g)
ValOMe (g)
ProOMe (h)
ProOMe (h)
a
Reaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3, 1 mmol substrate
(5 or 7); 3 mmol non-functionalised amine (or 1.1 mmol amino acid methyl ester
hydrochloride); 1 bar CO; 10 mL DMF, reaction time: 20 h.
b
Practically complete conversion (>99.8%) has been obtained in all cases except
for b (27% for 9b, 12% for 10b (not isolated)). Isolated yields are based on the sub-
strates (5 and 7).

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A. Takacs et al. / Tetrahedron 65 (2009) 4795–4800
4797
COOR
combined organic layers were washed with 1 N aqueous HCl
(3ꢁ50 mL), water (50 mL), 5% aqueous NaHCO3 (2ꢁ50 mL), water
(50 mL), saturated aqueous Na2S2O3 (10 mL) and water (3ꢁ50 mL)
again, dried over sodium sulfate and evaporated. The iodoalkene (5)
was obtained as a brown viscous material and used for carbonyla-
tion experiments without further purification. Yield: 7.86 g; 96%.
I
CO, ROH
Pd(OAc)2 / PPh3
5
11
R
i
j
Me
iPr
4.2.1. 1-Iodo-1-(1-naphthyl)ethene (5)
dH (400 MHz, CDCl3) 8.21 (dd, 8.4 Hz, 0.8 Hz, 1H, Naph); 7.88 (d,
8.1 Hz, 1H, Naph); 7.83 (d, 8.1 Hz, 1H, Naph); 7.59 (t, 7.2 Hz, 1H,
Naph); 7.45–7.54 (m, 2H, Naph); 7.41 (t, 7.2 Hz, 1H, Naph); 6.37 (d,
1.2 Hz, 1H, ]CH); 6.33 (d, 1.2 Hz, 1H, ]CH). dC (100.6 MHz, CDCl3)
141.5; 133.7; 131.1; 129.8; 128.8; 128.2; 126.3; 126.1; 125.7; 125.4;
125.2; 102.3. IR (KBr (cmꢂ1)): 1616 (C]C). MS m/z (rel.int. %): 280
(10), 153 (100), 127 (7). Anal. Calcd for C12H9I (280.11): C, 51.46; H,
3.24; Found: C, 51.62; H, 3.39; Rf (petroleum ether 40/70) 0.77;
brown viscous material.
k
l
tBu
Bn
Scheme 3. Palladium-catalysed alkoxycarbonylation of 5.
The corresponding esters were produced in 77%, 63% and 69%
yields, respectively. The only alcohol resulting in extremely low
conversions, and therefore no isolated yields, was tert-butanol (k).
3. Conclusion
4.3. Synthesis of 1-iodo-1-(2-naphthyl)ethene (7)
The activated geminally disubstituted iodoalkenes, 1-naphthyl-
1-iodoethenes, proved to be excellent substrates in palladium-
catalysed aminocarbonylation providing the corresponding
naphthylacrylamides in nearly quantitative yields. High tolerance
towards N-nucleophiles were observed, i.e., even those amines
with steric hindrance or less basicity brought about the products
in yields of practical importance.
It could be stated, that the exceptional reactivity of the 1-
naphthyl-1-iodoethenes, compared to the aliphatic analogues,
resulted in 2-naphthylacrylamide type synthetic building blocks in
clean aminocarbonylation.
The above protocol described for 5 was followed. A brown solid
material with appropriate purity was obtained and used without
further purification as a substrate for carbonylation reactions.
Yield: 14.79 g; 92%.
4.3.1. 1-Iodo-1-(20-naphthyl)ethene (7)
dH (400 MHz, CDCl3) 7.98 (br s, 1H, Naph); 7.80–7.88 (m, 2H,
Naph); 7.75 (d, 8.4 Hz,1H, Naph); 7.64 (dd, 8.6 Hz,1.9 Hz,1H, Naph);
7.47–7.52 (m, 2H, Naph); 6.60 (d, 1.8 Hz, 1H, ]CH); 6.18 (d, 1.8 Hz,
1H, ]CH). dC (100.6 MHz, CDCl3) 138.8; 133.4; 132.9; 128.4; 128.3;
127.8; 127.6; 127.5; 126.8; 126.6; 124.9; 107.6. MS m/z (rel.int. %):
280 (15), 153 (100), 127 (9). Anal. Calcd for C12H9I (280.11): C, 51.46;
H, 3.24; Found: C, 51.57; H, 3.36; Rf (petroleum ether 40/70) 0.60;
mp 70–75 ꢀC.
4. Experimental
4.1. General procedures
4.4. Aminocarbonylation experiments at normal pressure
1H and 13C NMR spectra were recorded in CDCl3 on a Varian
Inova 400 spectrometer at 400.13 MHz and 100.62 MHz, re-
In
a typical experiment a solution of Pd(OAc)2 (5.6 mg,
spectively. Chemical shifts
d are reported in parts per million rela-
0.025 mmol), PPh3 (13.1 mg, 0.05 mmol), 0.5 mmol iodo substrate
(5 or 7), 1.5 mmol nonfunctionalized amine (a–d) (or 0.55 mmol
amino acid methyl ester (e–h) hydrochloride) were dissolved in
10 mL of DMF under argon. Triethylamine (0.5 mL) was added to
the homogeneous yellow solution and the atmosphere was
changed to carbon monoxide. The colour changed to dark red. The
reaction was conducted for 20 h at 50 ꢀC. Some metallic palladium
was formed at the end of the reaction, which was filtered off. A
sample of this solution was immediately analysed by GC–MS. The
mixture was then concentrated to dryness. The residue was dis-
solved in chloroform (20 mL) and washed with water (20 mL). The
organic phase was thoroughly washed with 5% HCl (2ꢁ20 mL),
saturated NaHCO3 (20 mL), brine (20 mL), dried over Na2SO4 and
concentrated to a yellow waxy material or a thick oil. Chromatog-
raphy (silica, chloroform, then chloroform/ethyl acetate mixtures)
yielded the desired compounds typically as pale brown viscous
materials or yellow solids.
tive to residual CHCl3 (7.26 and 77.00 ppm for 1H and 13C,
respectively). Elemental analyses were measured on a 1108 Carlo
Erba apparatus. Samples of the catalytic reactions were analysed
with a Hewlett Packard 5830A gas chromatograph fitted with
a capillary column coated with OV-1. The amines and amino acid
derivatives were purchased from Aldrich.
4.2. Synthesis of 1-iodo-1-(1-naphthyl)ethene (5)
1-Acetonaphthone (1) (5 g, 29.4 mmol), freshly distilled hydra-
zine hydrate (98%, 1.62 g, 32.3 mmol) and barium oxide (1.18 g,
7.7 mmol) in absolute ethanol (50 mL) were heated for 24 h at
90 ꢀC. After completion of the reaction, iced water (200 mL) and
dichloromethane (150 mL) were added, and the white precipitate
was filtered. The organic phase was separated, dried over sodium
sulfate for a day and concentrated to give the hydrazone (3) de-
rivative. The product was used in the next step without further
purification.
4.5. Alkoxycarbonylation experiments at high pressure
To a stirred solution of iodine (15.43 g, 60.8 mmol) in dichloro-
methane (50 mL) the mixture of 1,1,3,3-tetramethylguanidine
(TMG, 10.15 g, 88.1 mmol) and 1-acetonaphthone hydrazone (3)
(5.41 g, 29.4 mmol) in dichloromethane (30 mL) was added drop-
wise between 0 and 15 ꢀC by using an ice-bath. After the addition
was complete, the mixture was stirred for half an hour. Then the
solvent was evaporated and the residue was heated at 90 ꢀC under
an argon atmosphere for 2 h. The mixture was poured into water
(300 mL) and extracted with dichloromethane (3ꢁ80 mL). The
A mixture of 5 (or 7) (1 mmol), palladium(II) acetate (5.6 mg,
0.025 mmol) and PPh3 (13.1 mg, 0.05 mmol) was dissolved in 10 mL
of DMF under argon, and NEt3 (0.5 mL) and methanol (0.13 mL,
5 mmol) or (isopropylalcohol, 0.38 mL, 5 mmol; benzyl alcohol,
0.52 mL, 5 mmol) as O-nucleophiles were added. The reaction
mixture was then transferred under argon into a 100 mL stainless
steel autoclave, which was pressurised to 55 bar with CO and the
magnetically stirred mixture was heated in an oil bath at 50 ꢀC for

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A. Takacs et al. / Tetrahedron 65 (2009) 4795–4800
4798
Table 2
(br s, 1H, ]CH); 3.97 (d, 5.5 Hz, 2H, CH2); 3.62 (s, 3H, OCH3). dC
Palladium-catalysed alkoxycarbonylation of 5a
(100.6 MHz, CDCl3) 169.8; 166.3; 141.8; 134.5; 133.6; 131.7;
129.1; 128.3; 127.5; 127.3; 126.6; 126.3; 125.4; 125.3; 52.1, 41.4.
IR (KBr (cmꢂ1)): 3411 (NH); 1753 (COO); 1668 (CON); 1612
(C]C). MS m/z (rel.int. %): 269 (14), 180 (38), 153 (100), 152 (80),
127 (4). Anal. Calcd for C16H15NO3 (269.30): C, 71.36; H, 5.61; N,
5.20; Found: C, 71.12; H, 5.84; N, 5.01; Rf (20% EtOAc/CHCl3) 0.58;
pale brown viscous material.
Entry
Alcohol
Conversion [%]
Isolated yieldb (ester) [%]
1
2
3
4
Methanol (i)
>99
>98
<2
77 (11i)
63 (11j)
n.d. (11k)
69 (11l)
Isopropyl alcohol (j)
tert-Butanol (k)
Benzyl alcohol (l)
>98
a
Reaction conditions: 0.025 mmol Pd(OAc)2; 0.05 mmol PPh3, 1 mmol substrate
(5); 5 mmol alcohol; 55 bar CO; 10 mL DMF; r.time: 66 h.
b
Isolated yields are based on the substrate (5).
4.6.6. 2-(2-(1-Naphthyl)acryloylamino)propionic acid
methyl ester (9f)
the reaction time given in Table 2. The work-up procedure was
identical with that given above for the carboxamides.
dH (400 MHz, CDCl3) 7.82–7.92 (m, 3H, Naph); 7.41–7.52 (m, 4H,
Naph); 6.70 (br s, 1H, ]CH); 5.93 (br s, 1H, NH); 5.66 (br s, 1H,
]CH); 4.61 (quintet, 7.2 Hz, 1H, CHCH3); 3.62 (s, 3H, OCH3); 1.22 (d,
7.2 Hz, 3H, CHCH3). dC (100.6 MHz, CDCl3) 172.8; 165.7; 142.2;
134.5; 133.6; 131.6; 129.1; 128.3; 127.5; 127.1; 126.5; 126.3; 125.4
(double intensity); 52.2; 48.3; 17.9. IR (KBr (cmꢂ1)): 3331 (NH);
1743 (COO); 1668 (CON); 1613 (C]C). MS m/z (rel.int. %): 283 (14),
224 (10), 180 (20), 153 (100), 152 (55), 127 (2). Anal. Calcd for
C17H17NO3 (283.33): C, 72.07; H, 6.05; N, 4.94; Found: C, 71.90; H,
6.20; N, 4.71; Rf (10% EtOAc/CHCl3) 0.60; pale brown viscous
material.
4.6. Characterisation of the amide and ester products
4.6.1. N-tert-Butyl-2-(1-naphthyl)acrylamide (9a)
dH (400 MHz, CDCl3) 7.80–7.86 (m, 3H, Naph); 7.41–7.46 (m, 3H,
Naph); 7.39 (d, 6.8 Hz, 1H, H-2); 6.60 (d, 1.1 Hz, 1H, ]CH); 5.58 (d,
1.1 Hz, 1H, ]CH); 5.20 (br s, 1H, NH); 1.20 (s, 9H, tBu). dC
(100.6 MHz, CDCl3) 165.5; 143.9; 135.3; 133.5; 131.5; 128.9; 128.3;
127.3; 126.4; 126.2; 125.6; 125.5; 125.4; 51.2; 28.3. IR (KBr (cmꢂ1)):
3262 (NH); 1644 (CON); 1613 (C]C). MS m/z (rel.int. %): 253 (30),
238 (6), 196 (14), 153 (100), 127 (3). Anal. Calcd for C17H19NO
(253.34): C, 80.60; H, 7.56; N, 5.53; Found: C, 80.52, H, 7.75; N, 5.33;
Rf (3% EtOAc/CHCl3) 0.64; off-white solid, mp 108–110 ꢀC.
4.6.7. 3-Methyl-2-(2-(1-naphthyl)acryloylamino)butyric acid
methyl ester (9g)
dH (400 MHz, CDCl3) 7.78–7.87 (m, 3H, Naph); 7.40–7.50 (m, 4H,
Naph); 6.66 (br s, 1H, ]CH); 5.80 (br d, 8.4 Hz, 1H, NH); 5.67 (br s,
1H, ]CH); 4.50–4.57 (m, 1H, CHNH); 3.54 (s, 3H, OCH3); 1.90–2.00
(m, 1H, CH(CH3)2); 0.73 (d, 6.9 Hz, 3H, CHCH3); 0.52 (d, 6.9 Hz, 3H,
CHCH3). dC (100.6 MHz, CDCl3) 171.8; 166.0; 142.4; 134.6; 133.5;
131.6; 129.1; 128.3; 127.4; 126.8; 126.5; 126.3; 125.4; 125.3; 57.3;
51.9; 31.0; 18.8; 17.3. IR (KBr (cmꢂ1)): 3420 (NH); 1743 (COO); 1677
(CON; 1615 (C]C)). MS m/z (rel.int. %): 311 (10), 252 (23), 197 (20),
180 (12), 153 (100), 128 (3). Analysis calculated for C19H21NO3
(311.38): C, 73.29; H, 6.80; N, 4.50; Found: C, 73.19; H, 6.92; N, 4.29;
Rf (10% EtOAc/CHCl3) 0.64; pale brown viscous material.
4.6.2. N-Phenyl-2-(1-naphthyl)acrylamide (9b)
dH (400 MHz, CDCl3) 7.90–7.99 (m, 3H, Naph); 7.47–7.59 (m, 4H,
Naph); 7.32 (d, 7.9 Hz, 2H, o-Ph); 7.22 (t, 7.9 Hz, 2H, m-Ph); 7.16 (br
s, 1H, NH); 7.05 (t, 7.9 Hz, 3H); 6.85 (br s, 1H, ]CH); 5.77 (br s, 1H,
]CH). dC (100.6 MHz, CDCl3) 164.3; 143.0; 137.5; 134.5; 133.8;
131.7; 129.5; 128.8; 128.6; 127.8; 127.7; 127.1; 126.6; 125.6; 125.3;
124.6; 120.1. IR (KBr (cmꢂ1)): 1648 (CON). MS m/z (rel.int. %): 273
(55), 207 (1), 168 (25), 153 (100), 152 (90), 127 (7). Anal. Calcd for
C19H15NO (273.33): C, 83.49; H, 5.53; N, 5.12; Found: C, 83.33; H,
5.39; N, 4.94; Rf (5% EtOAc/CHCl3) 0.75; brown solid, mp 75–76 ꢀC.
4.6.8. 1-(2-(1-Naphthyl)acryloyl)pyrrolidine-2-carboxylic acid
methyl ester (9h, two rotational isomers, 80/20)
4.6.3. 2-(1-Naphthyl)-1-piperidin-1-ylpropenone (9c)
dH (400 MHz, CDCl3) 8.26 (d, 7.8 Hz, 1H, Naph); 7.82 (d, 7.8 Hz,
1H, Naph); 7.79 (d, 7.8 Hz, 1H, Naph); 7.40–7.55 (m, 4H, Naph); 5.91
(br s, 1H, ]CH); 5.68 (br s, 1H, ]CH); 3.55–3.63 (m, 2H, NCH2);
3.28–3.34 (m, 2H, NCH2); 1.52 (br s, 4H, (CH2)2); 1.10 (br s, 2H, CH2).
dC (100.6 MHz, CDCl3) 169.5; 145.0; 135.7; 133.9; 130.8; 128.5;
126.4; 126.1; 125.9; 125.2; 125.1; 121.8; 113.6; 47.8; 43.1; 25.7;
25.4; 24.4. IR (KBr (cmꢂ1)): 1631 (CON). MS m/z (rel.int. %): 265 (96),
182 (18), 153 (98), 152 (100), 112 (51). Anal. Calcd for C18H19NO
(265.35): C, 81.48; H, 7.22; N, 5.28; Found: C, 81.20; H, 7.03; N, 5.10;
Rf (10% EtOAc/CHCl3) 0.56; pale brown viscous material.
dH (400 MHz, CDCl3) 8.12 (d, 7.9 Hz, 1H, Naph); 7.73–7.81 (m, 2H,
Naph); 7.38–7.48 (m, 4H, Naph); 6.20/5.97 (major/minor) (br s,
1H, ]CH); 5.68/5.60 (major/minor) (br s, 1H, ]CH); 4.47–4.52/
4.03–4.09 (major/minor) (m, 1H, NCH); 3.70/3.27 (major/minor) (s,
3H, OCH3); 3.00–3.07 (m, 2H, NCH2); 1.60–2.08 (m, 4H, (CH2)2). dC
(100.6 MHz, CDCl3) 172.4/172.0 (major/minor); 169.5/168.9 (minor/
major); 145.5/144.8 (minor/major); 135.3/134.6 (major/minor);
133.7; 131.0; 128.9/128.7 (minor/major); 128.6/128.4 (minor/ma-
jor); 126.6; 126.4; 126.0; 125.3; 125.1; 124.3/123.8 (major/minor);
59.8/59.4 (minor/major); 52.0/51.8 (major/minor); 48.3/46.7 (ma-
jor/minor); 31.4/28.8 (minor/major); 25.0/21.8 (major/minor). IR
(KBr (cmꢂ1)): 1744 (COO); 1637 (CON). MS m/z (rel.int. %): 309 (14),
250 (22), 181 (9), 153 (100), 152 (45), 128 (10). Anal. Calcd for
C19H19NO3 (309.36): C, 73.77; H, 6.19; N, 4.53; Found: C, 73.68; H,
6.34; N, 4.31; Rf (20% EtOAc/CHCl3) 0.53; pale brown viscous
material.
4.6.4. 1-(Morpholin-4-yl)-2-(1-naphthyl)propenone (9d)
dH (400 MHz, CDCl3) 8.18 (d, 7.9 Hz, 1H, Naph); 7.81 (d, 7.8 Hz,
1H, Naph); 7.79 (d, 7.8 Hz, 1H, Naph); 7.38–7.51 (m, 4H, Naph); 5.92
(br s, 1H, ]CH); 5.72 (br s, 1H, ]CH); 3.60 (br s, 2H, OCH2); 3.55 (br
s, 2H, OCH2); 3.30 (br s, 2H, CH2); 3.21 (br s, 2H, CH2). dC
(100.6 MHz, CDCl3) 169.7; 144.2; 135.3; 133.9; 130.6; 128.9; 128.6;
126.6; 126.1; 125.3; 124.8; 123.2 (double intensity); 66.3 (br, double
intensity); 47.1; 42.5. IR (KBr (cmꢂ1)): 1636 (CON). MS m/z (rel.int.
%): 267 (57), 180 (18), 153 (100), 152 (80), 127 (6), 114 (24). Anal.
Calcd for C17H17NO2 (267.33): C, 76.38; H, 6.41; N, 5.24; Found: C,
76.22; H, 6.55; N, 5.01; Rf (30% EtOAc/CHCl3) 0.43; pale brown
viscous material.
4.6.9. N-tert-Butyl-2-(2-naphthyl)acrylamide (10a)
dH (400 MHz, CDCl3) 7.78–7.85 (m, 4H, Naph); 7.43–7.50 (m, 3H,
Naph); 6.08 (d, 1.2 Hz, 1H, ]CH); 5.68 (d, 1.2 Hz, 1H, ]CH); 5.62 (br
s, 1H, NH); 1.40 (s, 9H, tBu). dC (100.6 MHz, CDCl3) 167.0; 146.1;
134.6; 133.3; 133.1; 128.3; 128.2; 127.7; 127.3; 126.5 (double in-
tensity); 125.5; 121.0; 51.6; 28.8. IR (KBr (cmꢂ1)): 3346 (NH); 1647
(CON). MS m/z (rel.int. %): 253 (47), 238 (10), 196 (42), 153 (100),
127 (8). Anal. Calcd for C17H19NO (253.34): C, 80.60; H, 7.56; N, 5.53;
Found: C, 80.45, H, 7.72; N, 5.40; Rf (3% EtOAc/CHCl3) 0.74; Rf (10%
EtOAc/CHCl3) 0.84; yellow solid, mp 93–95 ꢀC.
4.6.5. (2-(1-Naphthyl)acryloylamino)acetic acid methyl ester (9e)
dH (400 MHz, CDCl3) 7.82–7.91 (m, 3H, Naph); 7.41–7.53
(m, 4H, Naph); 6.72 (br s, 1H, ]CH); 5.87 (br s, 1H, NH); 5.69

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4.6.10. N-Phenyl-2-(2-naphthyl)acrylamide (10b, obtained
as impure material not suitable for full characterisation)
Found: C, 73.10; H, 7.02; N, 4.35; Rf (10% EtOAc/CHCl3) 0.77; Rf (1%
EtOAc/CHCl3) 0.54; dark yellow highly viscous material.
dH (400 MHz, CDCl3) 7.05–7.90 (m, 12H, Ar); 6.25 (br s, 1H, NH);
5.82 (br s, 1H, ]CH); 5.42 (br s, 1H, ]CH). MS m/z (rel.int. %): 273
(60), 207 (66),153 (100),152 (92),127 (29). Rf (5% EtOAc/CHCl3) 0.75.
4.6.16. 1-(2-(2-Naphthyl)acryloyl)pyrrolidine-2-carboxylic acid
methyl ester (10h, two rotational isomers 80/20)
dH (400 MHz, CDCl3) 7.98 (s, 1H, Naph); 7.75–7.85 (m, 3H, Naph);
7.63 (d, 8.1 Hz,1H, Naph); 7.40–7.46 (m, 2H, Naph); 5.86/5.80 (major/
minor) (br s, 1H, ]CH); 5.55/5.42 (major/minor) (br s, 1H, ]CH);
4.60–4.67/4.23–4.28 (major/minor) (m,1H, NCH); 3.80 (s, 3H, OCH3);
3.34 (t, 7.4 Hz, 2H, NCH2); 1.70–2.30 (m, 4H, (CH2)2). dC (100.6 MHz,
CDCl3) 172.6; 169.4; 145.6/145.5 (minor/major); 133.5; 133.3; 132.5;
128.6; 128.5; 127.6; 126.5; 126.4; 125.8; 123.3; 115.6/115.3 (minor/
major); 60.4/58.5 (minor/major); 52.3/52.1 (major/minor); 48.6/46.1
(major/minor); 31.2/29.5 (minor/major); 24.9/22.6 (major/minor). IR
(KBr (cmꢂ1)): 1744 (COO); 1639 (CON). MS m/z (rel.int. %): 309 (19),
250 (22), 181 (11), 153 (100), 152 (38), 127 (6). Anal. Calcd for
C19H19NO3 (309.36): C, 73.77; H, 6.19; N, 4.53; Found: C, 73.60; H,
6.31; N, 4.28; Rf (10% EtOAc/CHCl3) 0.45; Rf (20% EtOAc/CHCl3) 0.65;
dark yellow highly viscous material.
4.6.11. 2-(2-Naphthyl)-1-piperidin-1-ylpropenone (10c)
dH (400 MHz, CDCl3) 7.76–7.82 (m, 4H, Naph); 7.60 (d, 8.2 Hz, 1H,
Naph); 7.4–7.46 (m, 2H, Naph); 5.80 (br s, 1H, ]CH); 5.41 (br s, 1H,
]CH); 3.68–3.75 (m, 2H, NCH2); 3.28–3.33 (m, 2H, NCH2); 1.60 (br s,
4H, (CH2)2); 1.34 (br s, 2H, CH2). dC (100.6 MHz, CDCl3) 169.2; 145.3;
133.4; 133.2; 133.0; 128.5; 128.4; 127.6; 126.4; 125.3; 123.1; 113.6;
48.0; 42.5; 26.3; 25.7; 24.5. IR (KBr (cmꢂ1)): 1633 (CON). MS m/z
(rel.int. %): 265 (100),182 (26),153 (80),152 (79),127 (13). Anal. Calcd
for C18H19NO (265.35): C, 81.48; H, 7.22; N, 5.28; Found: C, 81.29; H,
7.01; N, 5.05; Rf (10% EtOAc/CHCl3) 0.65; yellow solid, mp 71–72 ꢀC.
4.6.12. 1-(Morpholin-4-yl)-2-(2-naphthyl)propenone (10d)
dH (400 MHz, CDCl3) 7.76–7.82 (m, 4H, Naph); 7.58 (d, 8.2 Hz,
1H, Naph); 7.40–7.46 (m, 2H, Naph); 5.83 (br s, 1H, ]CH); 5.42 (br
s, 1H, ]CH); 3.80 (br s, 2H, OCH2); 3.71 (br s, 2H, OCH2); 3.42 (br s,
2H, CH2); 3.34 (br s, 2H, CH2). dC (100.6 MHz, CDCl3) 169.5; 144.5;
133.4; 133.3; 132.6; 128.8; 128.4; 127.7; 126.7; 126.6; 125.3;
122.9; 114.8; 66.8 (double intensity); 47.4; 42.0. IR (KBr (cmꢂ1)):
1623 (CON). MS m/z (rel.int. %): 267 (70), 182 (20), 153 (100), 152
(81), 127 (11). Anal. Calcd for C17H17NO2 (267.33): C, 76.38; H, 6.41;
N, 5.24; Found: C, 76.33; H, 6.28; N, 5.07; Rf (30% EtOAc/CHCl3)
0.54; Rf (10% EtOAc/CHCl3) 0.37; yellow solid, mp 127–128 ꢀC.
4.6.17. 2-(1-Naphthyl)acryloic acid methyl ester (11i)
dH (400 MHz, CDCl3) 7.82–7.90 (m, 2H; Naph); 7.74 (d, 7.1 Hz, 1H,
Naph); 7.45–7.51 (m, 3H, Naph); 7.37 (d, 7.0 Hz, 1H, Naph); 6.72 (br
s, 1H, ]CH); 5.89 (br s, 1H, ]CH); 3.72 (s, 3H, OMe). dC (100.6 MHz,
CDCl3) 167.5; 140.7; 135.3; 133.4; 131.8; 129.9; 128.6; 128.3; 126.9;
126.2; 125.8; 125.2 (double intensity); 52.2. IR (KBr (cmꢂ1)): 1721
(CON); 1629 (C]C). MS m/z (rel.int. %): 212 (23), 197 (3), 153 (100),
128 (6). Anal. Calcd for C14H12O2 (212.25): C, 79.23; H, 5.70; Found:
C, 79.05, H, 5.50. Rf (CHCl3) 0.65; highly viscous yellow material.
4.6.13. (2-(2-Naphthyl)-acryloylamino)acetic acid
methyl ester (10e)
4.6.18. 2-(1-Naphthyl)acryloic acid isopropyl ester (11j)
dH (400 MHz, CDCl3) 7.80–7.90 (m, 4H, Naph); 7.48–7.53 (m, 3H,
Naph); 6.33 (br s,1H, NH); 6.21 (br s,1H, ]CH); 5.77 (br s,1H, ]CH);
4.12 (d, 5.6 Hz, 2H, CH2); 3.73 (s, 3H, OCH3). dC (100.6 MHz, CDCl3)
170.2; 167.6; 144.3; 133.9; 133.3; 133.2; 128.4; 128.3; 127.7; 127.6;
126.6; 126.5; 125.6; 122.7; 52.3; 41.5. IR (KBr (cmꢂ1)): 3374 (NH);
1751 (COO); 1644 (CON). MS m/z (rel.int. %): 269 (42), 210 (6), 196 (8),
181 (11), 153 (100), 152 (62), 127 (6). Anal. Calcd for C16H15NO3
(269.30): C, 71.36; H, 5.61; N, 5.20; Found: C, 71.20; H, 5.80; N, 5.03;
Rf (10% EtOAc/CHCl3) 0.48; Rf (20% EtOAc/CHCl3) 0.63; yellow solid,
mp 147–148 ꢀC.
dH (400 MHz, CDCl3) 7.72–7.86 (m, 3H, Naph); 7.45–7.50 (m, 3H,
Naph); 7.35 (d, 7.0 Hz, 1H, Naph); 6.63 (br s, 1H, ]CH); 5.86 (br s,
1H, ]CH); 5.09 (heptet, 6.4 Hz, 1H, CH(CH3)2); 1.19 (d, 6.4 Hz, 6H,
CH(CH3)2). dC (100.6 MHz, CDCl3) 166.7; 141.8; 135.8; 133.6; 132.0;
129.2; 128.6; 128.5; 127.2; 126.2; 125.9; 125.6; 125.4; 68.8; 21.8. IR
(KBr (cmꢂ1)): 1714 (CON); 1627 (C]C). MS m/z (rel.int. %): 240 (13),
198 (10), 153 (100), 128 (3). Anal. Calcd for C16H16O2 (240.30): C,
79.97; H, 6.71; Found: C, 79.81, H, 6.88. Rf (CHCl3) 0.59; highly
viscous yellow material.
4.6.19. 2-(1-Naphthyl)acryloic acid benzyl ester (11l)
4.6.14. 2-(2-(2-Naphthyl)acryloylamino)propionic acid
methyl ester (10f)
dH (400 MHz, CDCl3) 7.82–7.88 (m, 2H, Naph); 7.72 (d, 7.1 Hz, 1H,
Naph); 7.18–7.50 (m, 9H, NaphþPh); 6.73 (br s,1H, ]CH); 5.92 (br s,
1H, ]CH); 5.21 (s, 2H, CH2Ph). dC (100.6 MHz, CDCl3) 167.0; 141.1;
136.1; 135.5; 133.6; 132.0; 130.2; 128.8; 128.6 (double intensity);
128.5; 128.3; 128.1 (double intensity); 127.2; 126.4; 126.0; 125.6;
125.5; 66.9. IR (KBr (cmꢂ1)): 1720 (COO). MS m/z (rel.int. %): 288
(18), 197 (12), 153 (100), 128 (4), 91 (65). Anal. Calcd for C20H16O2
(288.35): C, 83.31; H, 5.59; Found: C, 83.20, H, 5.71. Rf (CHCl3) 0.74;
highly viscous yellow material.
dH (400 MHz, CDCl3) 7.80–7.91 (m, 4H, Naph); 7.48–7.53 (m, 3H,
Naph); 6.40 (br s,1H, NH); 6.18 (br s,1H, ]CH); 5.76 (br s,1H, ]CH);
4.72 (quintet, 7.2 Hz, 1H, CHCH3); 3.72 (s, 3H, OCH3); 1.41 (d, 7.2 Hz,
3H, CHCH3). dC (100.6 MHz, CDCl3) 173.2; 167.0; 144.5; 134.0; 133.3;
133.2; 128.4; 128.3; 127.7; 127.5; 126.6; 126.5; 125.5; 122.3; 52.4;
48.4; 18.2. IR (KBr (cmꢂ1)): 3302 (NH); 1744 (COO); 1655 (CON). MS
m/z (rel.int. %): 283 (24), 224 (18), 181 (17), 153 (100), 152 (41), 127
(4). Anal. Calcd for C17H17NO3 (283.33): C, 72.07; H, 6.05; N, 4.94;
Found: C, 71.88; H, 6.22; N, 4.76; Rf (10% EtOAc/CHCl3) 0.70; golden
highly viscous material.
Acknowledgements
The authors thank the Hungarian Research Fund (OTKA
NI61591), the Joint Project of the European Union – Hungarian
National Development Program (GVOP-3.2.1-2004-04-0168/3) for
the financial support and Johnson Matthey for the generous gift of
palladium(II) acetate.
4.6.15. 3-Methyl-2-(2-(2-naphthyl)acryloylamino)butyric acid
methyl ester (10g)
dH (400 MHz, CDCl3) 7.80–7.93 (m, 4H, Naph); 7.49–7.54 (m, 3H,
Naph); 6.22 (br s,1H, NH); 6.19 (br s,1H, ]CH); 5.80 (br s,1H, ]CH);
4.70–4.77 (m, 1H, CHNH); 3.75 (s, 3H, OCH3); 2.17–2.24 (m, 1H,
CH(CH3)2); 0.98 (d, 6.8 Hz, 3H, CHCH3); 0.85 (d, 6.8 Hz, 3H, CHCH3). dC
(100.6 MHz, CDCl3) 172.2; 167.3; 144.6; 134.0; 133.3; 133.2; 128.4;
128.3; 127.7; 127.5; 126.6; 126.5; 125.5; 122.5; 57.5; 52.1; 31.3; 19.1;
17.8. IR (KBr (cmꢂ1)): 3334 (NH); 1742 (COO); 1666 (CON). MS m/z
(rel.int. %): 311 (11), 252 (20),197 (26),181 (4),153 (100),152 (42),127
(4). Anal. Calcd for C19H21NO3 (311.38): C, 73.29; H, 6.80; N, 4.50;
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ganic Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998; Vol. I-II.

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4800
3. Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbonylation. Direct Syn-
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8. Takacs, A.; Acs, P.; Farkas, R.; Kokotos, G.; Kollar, L. Tetrahedron 2008, 64, 9874–
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