Synthesis of N-picolylcarboxamides via palladium-catalysed aminocarbonylation of iodobenzene and iodoalkenes

Article abstract of DOI:10.1016/j.tet.2013.11.087

A systematic investigation of the palladium-catalysed aminocarbonylation of iodobenzene, 1-iodocyclohexene and 1′-iodostyrene in the presence of N-nucleophiles containing pyridyl moieties (2-, 3- and 4-picolylamine, N-ethyl-4-picolylamine, di-(2-picolyl)amine) was carried out. The two types of iodo substrates differ substantially regarding the selectivity towards carbonylation: while the aminocarbonylation of iodobenzene resulted in the formation of carboxamide and ketocarboxamide mixtures under various conditions, with the predominant formation of ketocarboxamide even at low carbon monoxide pressure, the aminocarbonylation of iodoalkenes under same conditions gave the corresponding unsaturated carboxamide exclusively. Most of the carboxamides and phenylglyoxylamides, obtained via single and double carbon monoxide insertion, respectively, were isolated in yields of synthetic interest (up to 86%). Low reaction rates and unexpected chemoselectivity towards carboxamide formation have been observed with di-(2-picolyl)amine as N-nucleophile in the aminocarbonylation of iodobenzene.

Full text of DOI:10.1016/j.tet.2013.11.087

Tetrahedron 70 (2014) 218e224
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of N-picolylcarboxamides via palladium-catalysed
aminocarbonylation of iodobenzene and iodoalkenes
a
a
b
a
a,b,
*
ꢀ ꢀ
ꢀ
ꢀ
ꢀ
ꢀ
Mate Gergely , Roland Farkas , Attila Takacs , Andrea Petz , Laszlo Kollar
a
ꢀ
ꢀ
ꢀ
Department of Inorganic Chemistry, University of Pecs and Szentagothai Research Centre, H-7624 Pecs, P.O. Box 266, Hungary
MTA-PTE Research Group for Selective Chemical Syntheses, H-7624 Pecs, Ifjusag u. 6., Hungary
b
ꢀ
ꢀ ꢀ
a r t i c l e i n f o
a b s t r a c t
Article history:
A
systematic investigation of the palladium-catalysed aminocarbonylation of iodobenzene, 1-
iodocyclohexene and 10-iodostyrene in the presence of N-nucleophiles containing pyridyl moieties (2-,
3- and 4-picolylamine, N-ethyl-4-picolylamine, di-(2-picolyl)amine) was carried out. The two types of
iodo substrates differ substantially regarding the selectivity towards carbonylation: while the amino-
carbonylation of iodobenzene resulted in the formation of carboxamide and ketocarboxamide mixtures
under various conditions, with the predominant formation of ketocarboxamide even at low carbon
monoxide pressure, the aminocarbonylation of iodoalkenes under same conditions gave the corre-
sponding unsaturated carboxamide exclusively. Most of the carboxamides and phenylglyoxylamides,
obtained via single and double carbon monoxide insertion, respectively, were isolated in yields of syn-
thetic interest (up to 86%). Low reaction rates and unexpected chemoselectivity towards carboxamide
formation have been observed with di-(2-picolyl)amine as N-nucleophile in the aminocarbonylation of
iodobenzene.
Received 13 September 2013
Received in revised form 6 November 2013
Accepted 25 November 2013
Available online 3 December 2013
Keywords:
Carbonylation
Palladium
Homogeneous catalysis
Picolylamine
Carbon monoxide
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
metal complexes possessing pam as ligand are of key importance
were used for various purposes: Ir(III) complexes in luminescence
Since the discovery of the carbonylation of aryl halides in the
presence of O- and N-nucleophiles,1 several reactions of synthetic
importance have been carried out by the variation of both the
substrate and nucleophile structures.2e6 Even the potential of these
reactions industrial applications leading to carboxamides and es-
ters were shown recently.7,8 Furthermore, the synthetic analogues
to aryl halides, iodo- and bromoalkenes as well as the corre-
sponding enol-triflates of various structures have also been syn-
thesised and widely used as substrates in the synthesis of
mechanochromism,10 Cu(II) complexes as chemosensors,11 chem-
ical nucleases,12 magnetic studies,13 Fe(II) complexes for theoret-
17
ical14e16 and Mossbauer spectroscopy studies, Pd(II) and Pt(II)
€
complexes for the selective cleavage of the amide bond,18 Cr(III)
complexes in luminescence spectroscopy,19 crystallographic20 and
equilibrium21 studies, Ni(II) complexes as precursors of nuclear
magnets.22
2-Picolylamine served also as a precursor in the synthesis of
various hetero-multidentate ligands. Its N-2-mercaptoethyl23 and
2-hydroxycyclohexyl24 derivatives showed N,N0,S- and N,N0,O-do-
nor properties, respectively, in Zn complexes. Dinuclear Pt-
complexes were stabilised with bidentate N,N-donors possessing
N-(2-pyridylmethyl) substituents.25 2-Picolylamine served as re-
actant in the synthesis of ligands accessible through Schiff-base
condensation.26,27 2-Picolylamine-derived sulfonamides and li-
gands with methoxyalkyl arm(s) were used in Cu(II) and Mn(II)
complexes, respectively.12,28 The coordination of the potentially
N,N0,N00-tridentate ligand dpa to Cu(II),29,30 Zn(II)31,32 and Ir(III)33
was also reported.
a,b-unsaturated esters and carboxamides in palladium-catalysed
alkoxy- and aminocarbonylations, respectively.5,6
As a part of our continuing research in the carbonylation and
coupling reactions of iodoarenes and iodoalkenes, we turned our
attention towards the systematic variation of the N-nucleophiles. It
has to be added that in case of various compounds with practical
interest, the above catalytic reactions provide synthetic methods
superior to conventional ones.6 Since several N-picolylcarbox-
amides possess pharmacological importance,9 the application of
picolylamine isomers in aminocarbonylation was considered.
Both 2-picolylamine (pam) and di-(2-picolyl)amine (dpa) are
favoured ligands in coordination chemistry. A variety of transition
The application of Irepam complexes resulted in active catalysts
in CeH borylation.34 Ose and Ruepam systems proved to be active
catalysts in transfer hydrogenation.35
Novel pam-based synthetic routes were also published. Dicar-
bonyldiimides were synthesised via oxidation of the methylene
ꢀ
* Corresponding author. E-mail address: kollar@ttk.pte.hu (L. Kollar).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.087

M. Gergely et al. / Tetrahedron 70 (2014) 218e224
219
group and NeC(O) coupling in the presence of copper(II) acetate.36
I
H
N
CO
The carbonylative coupling of 1,8-naphthalimide and dpa resulted
in a compound displaying fluorescence enhancement.37 Pyridyl-
substituted imidazoles were obtained in base-catalysed reaction
of pam and 2-cyanopyridine.38 Highly asymmetric copper-
catalysed Henry-reaction has been developed using a chiral li-
gand derived from camphor and pam.39,40
In the present study, initiated also by the potential of N-pico-
lylamides in various fields, e.g., compounds with pharmaceutical
interest, such as tropicamide41 and picotamide,42 the palladium-
catalysed synthesis of carboxamides and 2-ketocarboxamides
bearing N-2-, N-3- and N-4-picolyl moieties is reported.
+
+
NH2
NH2
N
N
Pd(OAc)2 / PPh3
O
b
1b
1
O
I
N
H
CO
N
Pd(OAc)2 / PPh3
N
b
2b
2
H
N
NH2
2. Results and discussion
I
O
CO
2.1. Aminocarbonylation of iodobenzene and iodocyclohex-
ene in the presence of picolylamine isomers as primary
amines
+
Pd(OAc)2 / PPh3
N
N
b
3b
3
Scheme 2. Aminocarbonylation of iodocyclohexene (b) in the presence of picolyl-
amines (1e3) as N-nucleophiles.
Iodobenzene (a) and 1-iodocyclohexene (b) were amino-
carbonylated in the presence of palladium catalysts formed in situ
by the reaction of palladium(II) acetate and 2 M equiv of triphe-
nylphosphine. 2-Picolylamine (2-aminomethylpyridine) (1), 3-
picolylamine (2) and 4-picolylamine (3) were used as N-nucleo-
philes (Schemes 1 and 2).
accompanied by the oxidation of 1 equiv of PPh3 to triphenyl-
phosphine
oxide,
i.e.,
Pd(OAc)2þ2PPh3/‘Pd(PPh3)’þP(O)
Ph3þAc2O redox reaction takes place.43e45 In general, ‘Sol’ stands
for donor solvent (DMF), but in our case the coordination of
a picolylamine as a hemilabile (heterobidentate) ligand cannot be
excluded (vide infra).
H
N
1a
I
The aminocarbonylation of iodobenzene (a) resulted in a two-
component reaction mixture of the corresponding carboxamide
(1a) and 2-ketocarboxamide (1a0) using 2-picolylamine (1) as N-
nucleophile (Scheme 1). Practically complete conversions have
been achieved within 48 h reaction time under mild reaction
conditions (1 bar CO, 50 ꢀC) (Table 1, entry 1). It has to be noted that
even under these conditions the formation of 1a0, arising from
double CO insertion, is favoured. Moderate yields for 1a0 were
N
CO
+
O
NH2
N
Pd(OAc)2 / PPh3
H
N
O
a
1
1a'
N
O
O
N
H
2a
I
N
NH2
CO
Table 1
+
O
Aminocarbonylation of iodobenzene (a) in the presence of palladiumePPh3 in situ
N
Pd(OAc)2 / PPh3
N
H
catalystsa
2a'
a
2
O
Entry Amine p(CO) R. Time Conv.b Ratio of
Isolated yield [%]
amide/ketoamide (compound)
N
[bar] [h]
[%]
1
2
3
4
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
1
20
25
40
40
40
60
1
1
1
1
1
40
40
40
40
40
1
48
48
48
48
48
48
48
2
>98
>98
>98
>98
50
>98
>98
20
44
76
>98
>98
28
38
59
89
>98
>98
>98
41/59
26/74
28/72
21/79
56/44
15/85
23/77
37/63
39/61
36/65
31/69
25/75
16/84
8/92
16 (1a)
60 (1a0)
n.d.
H
N
52 (1a0)
n.d.
NH2
3a
5c
6d
7
O
75 (1a0)
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
80 (2a0)
62 (2a0)
50 (2a0)
46 (3a0)
77 (3a0)
I
CO
+
N
8
9
Pd(OAc)2 / PPh3
H
N
O
N
6
3a'
10
11
12
13
14
15
16
17
18
19
10
24
48
2
a
3
O
N
6
10
24
48
48
48
6/94
Scheme 1. Aminocarbonylation of iodobenzene (a) in the presence of picolylamines
(1e3) as N-nucleophiles.
16/84
18/82
31/69
8/92
40
It is worth mentioning that in addition to the ‘pre-formed’,
commercially available Pd(0) catalyst, Pd(PPh3)4, the above
Pd(OAc)2/2 PR3-type ‘in situ’ catalyst is widely used as a precursor
of highly active palladium(0) catalytic systems. In our case,
the formation of coordinatively highly unsaturated palla
dium(0)emonophosphine complex Pd(PPh3)(Sol)n is supposed. It
has been proved that the reduction of Pd(II) to Pd(0) occurs,
a
Reaction conditions (unless otherwise stated):
1
mmol of substrate (a);
0.025 mmol of Pd(OAc)2; 0.05 mmol of PPh3; 2 mmol of N-nucleophile (1, 2 or 3);
0.5 mL of triethylamine; solvent: 10 mL of DMF, reaction temperature: 50 ꢀC; n.d.:
not determined.
b
Determined by GC and GCeMS (naphthalene as internal standard).
c
Reaction temperature: 30 ꢀC.
d
Reaction temperature: 70 ꢀC.

220
M. Gergely et al. / Tetrahedron 70 (2014) 218e224
obtained under higher carbon monoxide pressure without opti-
misation of the work-up procedure (entry 4).
2.2. Aminocarbonylation of iodobenzene and 1-
iodocyclohexene in the presence of secondary amines (4-
(ethylaminomethyl)pyridine (4) and di(2-pyridyl)amine (5))
Similarly, carboxamide/2-ketocarboxamide mixtures (2a/2a0
and 3a/3a0) were obtained with 3-picolylamine (2) and 4-
picolylamine (3), respectively. As above, also these reactions
proved to be chemoselective towards ketocarboxamides (2a0 and
3a0) (Scheme 1, Table 1, entries 8e19). Although carboxamide/2-
ketocarboxamide mixtures were formed in all cases, the two
components were isolated (Experimental section). The yields of
the compounds obtained in analytical purity (>98%) are given in
Table 1.
The further investigations were prompted by the fact that car-
boxamides of practical importance (e.g., tropicamide) bear sec-
ondary amines with 4-picolylamine moiety.41 Both iodoalkene (b)
and iodoaromatic (a) substrates were aminocarbonylated in the
presence of 4-(ethylaminomethyl)pyridine (4) as N-nucleophile
(Scheme 3). As above, the aminocarbonylation of 1-iodo-cyclo-
hexene (b) and iodobenzene (a) resulted in the formation of car-
boxamide (4b) and carboxamide (4a)/ketocarboxamide (4a0)
mixtures, respectively. Carboxamide (4b) was formed exclusively
using b as substrate at 1 bar CO pressure and isolated as pure
compound in 72% yield (not optimised). 4a/4a0 mixtures (22/78 and
50/50) were formed in the aminocarbonylation of a at high (40 bar)
and atmospheric pressure, respectively. Both 4a and 4a0 were iso-
lated and characterised.
The detailed analysis of the influence of the reaction conditions
can be summarised as follows.
(i) Regarding the effect of the carbon monoxide pressure, a quick
growth in chemoselectivity towards ketocarboxamides was ob-
served in the range of 1e20 bar CO. A slight increase in the double
carbonylation selectivity was only observed above 20 bar CO
pressure (Table 1, entries 1e4, 7). (ii) The reaction temperature has
an even more pronounced effect on chemoselectivity. At 30 ꢀC,
although with low conversion (50%), the formation of the carbox-
amide (1a) is slightly favoured. At higher temperatures the ex-
pected dominance of the corresponding ketocarboxamide (1a0) was
observed (entries 4e6). (iii) Interestingly, the selectivity towards
ketocarboxamide is increasing by the reaction time, i.e., by the in-
creasing conversion, when the reaction was carried out at 1 bar CO
pressure (entries 8e12). However, investigating the reaction at
40 bar CO pressure, a maximum of the chemoselectivity plotted
against reaction time was observed. That is, the ketocarboxamide
selectivity increases from 84% to 94% in 10 h, when conversion of
59% was reached. Close to full conversion, a decrease in double
carbonylation was observed (entries 13e17). It is worth mentioning
that the latter sets of chemoselectivities obtained at 40 bar are
higher by ca. 20%. These data reflect to the slight but continuous
change of the structure of the catalyst during the reaction. It can be
explained by the different type of coordination of the picolylamine
and that of the N-acylated picolylamine (N-picolylcarboxamide or
N-picolylglyoxylamide). (iv) Screening the further picolylamines in
aminocarbonylation, similar dependence of chemoselectivity on
carbon monoxide pressure (See (i)) has been observed with 2 and 3
resulting in 75% (1 bar), 82% (40 bar) and 69% (1 bar), 92% (40 bar)
chemoselectivities, respectively (entries 12,17 and 18,19,
respectively).
N
N
O
O
O
H
N
4a
I
CO
+
Pd(OAc)2 / PPh3
N
4
N
a
4a'
N
O
H
N
N
N
I
CO
4b
+
Pd(OAc)2 / PPh3
N
4
b
Scheme 3. Aminocarbonylation of iodobenzene and 1-iodocyclohexene in the pres-
ence of 4-(ethylaminomethyl)pyridine (4) as N-nucleophile.
The aminocarbonylation of 1-iodocyclohexene (b) is chemo-
specific (Scheme 2, Table 2). Carboxamides (1b, 2b and 3b), formed
via single carbon monoxide insertion, have been detected only by
GCeMS even at high CO pressure (entry 3). Isolated products in
yields of practical interest have been obtained without optimisa-
tion of the reaction conditions and work-up procedure. It is due to
a perfectly ‘clean’ reaction and to a complete conversion of the
substrate under mild conditions.
It is worth noting that unexpectedly, in the presence of di-(2-
picolyl)amine (5) as N-nucleophile, exclusive formation of
the benzamide derivative (5a), that is, no double carbon mon-
oxide insertion leading to the corresponding 2-ketocarboxamide
was observed (Scheme 4). Additionally, the reaction was
rather slow related to all the above aminocarbonylations, i.e., 78%
conversion was achieved at 40 bar CO pressure in 72 h. No re-
action occurred at CO pressures lower than 20 bar. This phe-
nomenon can be explained by the coordination of the 2-pyridyl
moieties of 5 to palladium either in a bidentate or tridentate
manner.29,30
Table 2
Aminocarbonylation of 1-iodocyclohexene (b) in the presence of palladiumePPh3 in
situ catalystsa
Entry
Amine
p(CO) [bar]
R. Time [h]
Conv.b [%]
Isolated yield [%]
(compound)
1
2
3
4
5
1
1
1
2
3
1
1
40
1
1
3
3
1
1
96
>98
>98
>98
>98
n.d.
71 (1b)
81 (1b)
85 (2b)
80 (3b)
N
I
O
40 bar CO
H
N
N
1
+
Pd(OAc)2 / PPh3
N
a
N
N
Reaction conditions:
1 mmol of substrate (b); 0.025 mmol of Pd(OAc)2;
a
5
5a
0.05 mmol of PPh3; 2 mmol of N-nucleophile (1, 2 or 3); 5 mL of triethylamine;
solvent: 10 mL of DMF, reaction temperature: 50 ꢀC; carboxamides (1be3b) were
obtained exclusively.
Scheme 4. Aminocarbonylation of iodobenzene in the presence of di-(2-picolyl)amine
(5) as N-nucleophile.
b
Determined by GC and GCeMS (naphthalene as internal standard).

M. Gergely et al. / Tetrahedron 70 (2014) 218e224
221
2.3. Aminocarbonylation of 10-iodostyrene (c) in the presence
of amines (1e5) with picolyl moieties
compounds with moderate to high yields. The reactivity of the
amines differs thoroughly. Regarding the primary amines (1e3), it
can be stated that 4-picolylamine (3) (entry 7) shows the highest
reactivity providing complete conversion in 0.5 h while the re-
action with 2-picolylamine (1) with chelating ability is the slowest
(entries 1e3). As observed above, di-(2-picolyl)amine (5), with
two picolyl moieties able to coordinate to palladium, shows
low reactivity leading to completion in a week (entries 10e13).
The increase in the CO pressure resulted in higher activity accom-
panied with complete chemoselectivity towards carboxamide (5c)
(entry 14).
An iodoalkene with aryl substituent at the carbon possessing
iodo-leaving group (10-iodostyrene (c)) has been amino-
carbonylated using the set of picolylamines. This research was
prompted by the fact that the target carboxamides can be consid-
ered as intermediates of tropicamide.
As for the 1-iodocyclohexene (Section 2.1), the amino-
carbonylation is chemospecific using c as well (Scheme 5, Table 3).
Atropamides with picolyl substituents (1ce5c), formed via single
carbon monoxide insertion, have been detected only by GCeMS.
The formation of a single product enabled isolation of the target
3. Conclusions
Aminomethylpyridines (2-, 3- and 4-picolylamine, N-ethyl-N-4-
picolylamine, di-(2-picolyl)amine) can be used in palladium-
catalysed aminocarbonylation as N-nucleophiles. Iodoalkenes (1-
iodocyclohexene, 10-iodostyrene) and iodoaromatics (iodoben
zene) undergo aminocarbonylation towards carboxamides as ex-
clusive products and ketocarboxamides as major products,
respectively.
H
N
N
NH2
O
N
1
1c
H
N
NH2
N
N
O
O
N
2
4. Experimental
2c
NH2
H
N
4.1. General procedures
I
CO
+
1H and 13C NMR spectra were recorded in CDCl3 on a Bruker
Avance III 500 spectrometer at 500 and 125.7 MHz, respectively.
N
3
Pd(OAc)2 / PPh3
c
3c
Chemical shifts d are reported in parts per million relative to CHCl3
(7.26 and 77.00 ppm for 1H and 13C, respectively). Elemental anal-
yses 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
(internal standard: naphthalene; injector temp 250 ꢀC; oven:
H
N
N
N
N
O
O
4c
N
4
starting temp 50 ꢀC (hold-time 1 min), heating rate 15 ꢀC minꢁ1
,
N
N
final temp 320 ꢀC (hold-time 11 min); detector temp 280 ꢀC; carrier
gas: helium (rate: 1 mL minꢁ1)). The FT-IR spectra were taken in
KBr pellets using an IMPACT 400 spectrometer (Nicolet) applying
a DTGS detector in the region of 400e4000 cmꢁ1, the resolution
was 4 cmꢁ1. The amount of the samples was ca. 0.5 mg.
H
N
N
N
5
5c
1-Iodocyclohexene46 (b) and 10-iodostyrene47 (c) were syn-
thesised by the modified Barton-procedure.48,49 Iodobenzene and
the amine nucleophiles were purchased from SigmaeAldrich and
were used without further purification.
Scheme 5. Aminocarbonylation of 10-iodostyrene (c) in the presence of amines (1e5).
Table 3
Aminocarbonylation of 10-iodostyrene (c) with amines (1e5) in the presence of
palladiumePPh3 in situ catalystsa
4.2. Aminocarbonylation of iodobenzene (a) (or 1-
iodocyclohexene (b)) in the presence of picolylamines under
high carbon monoxide pressure
Entry
Amine
R. Time [h]
Conv.b [%]
Isolated yield [%]
(compound)
1
2
3
4
5
6
7
8
1
1
1
2
2
2
3
4
4
5
5
5
5
5c
0.5
1
4
0.5
1
2
0.5
0.5
20
4
24
96
144
24
27
58
>98
88
n.d.
n.d.
76 (1c)
n.d.
n.d.
73 (2c)
81 (3c)
n.d.
86 (4c)
n.d.
In a typical experiment Pd(OAc)2 (5.6 mg, 0.025 mmol), tri-
phenylphosphine (13.2 mg, 0.05 mmol), iodobenzene (or 1-iodocy
clohexene) (1 mmol), 2-picolylamine (or 3- or 4-picolylamine)
(2 mmol) and triethylamine (0.5 mL) were dissolved in DMF
(10 mL) under argon in a 100 mL autoclave. The autoclave was
pressurised to the given pressure by carbon monoxide. (Caution:
High pressure carbon monoxide should only be used with adequate
ventilation (hood) using CO sensors as well.) The reaction was
conducted for the given reaction time upon stirring at 50 ꢀC (or at
the temperature specified in Tables 1 and 2) and analysed by GC
and GCeMS. The mixture was then concentrated and evaporated to
dryness. The residue was dissolved in chloroform (20 mL) and
washed with water (3ꢂ20 mL). The organic phase was dried over
Na2SO4, filtered and evaporated to a crystalline material or to
a waxy residue. All compounds were subjected to column chro-
matography (Silicagel 60 (Merck), 0.063e0.200 mm), MeOH/EtOAc/
94
>98
>98
75
>98
5
32
51
>98
>98
9
10
11
12
13
14
n.d.
n.d.
63 (5c)
80 (5c)
a
Reaction conditions:
1 mmol of substrate (c); 0.025 mmol of Pd(OAc)2;
0.05 mmol of PPh3; 2 mmol of N-nucleophiles (1e5); 5 mL of triethylamine; solvent:
10 mL of DMF, 1 bar CO; reaction temperature: 50 ꢀC.
b
Determined by GC and GCeMS (naphthalene as internal standard).
c
40 bar CO.

222
M. Gergely et al. / Tetrahedron 70 (2014) 218e224
CHCl3 (the exact ratios are specified in Characterisation (4.4) for
C14H12N2O2 requires C, 69.99; H, 5.03; N, 11.66%]; Rf (5% MeOH, 95%
each compound).
CHCl3) 0.54; dH (500 MHz, CDCl3) 8.53 (2H, d, 5.6 Hz, H-2,6(Py)),
8.32 (2H, d, 5.6 Hz, H-3,5(Py)), 7.97 (1H, s, NH), 7.64 (1H, t, 7.3 Hz,
4.3. Aminocarbonylation of iodobenzene (a) (or 1-iodocyclo
hexene (b)) in the presence of picolylamines under atmo-
spheric carbon monoxide pressure
Hpara(Ph)), 7.49 (2H, t, 7.3 Hz, Hmeta(Ph)), 7.25 (2H, d, 7.3 Hz, Hor-
tho(Ph)), 4.59 (2H, d, 6.1 Hz, CH2); dC (125.7 MHz, CDCl3) 187.4, 162.2,
149.8 (double intensity), 146.7, 134.7, 133.1, 131.2 (double intensity),
128.6 (double intensity), 122.4 (double intensity), 42.2. IR (KBr,
n
In a typical experiment Pd(OAc)2, triphenylphosphine, iodo-
benzene (or 1-iodocyclohexene), amine nucleophile and triethyl-
amine were dissolved in DMF (for the quantity of the reagents See
Section 4.2) under argon in a 100 mL three-necked flask equipped
with a gas inlet, reflux condenser with a balloon (filled with argon)
at the top. The atmosphere was changed to carbon monoxide. The
reaction was conducted for the given reaction time upon stirring at
50 ꢀC and analysed by GC and GCeMS. The mixture was then
concentrated and evaporated to dryness and worked-up as de-
scribed in Section 4.2.
(cmꢁ1)) 3339 (NH), 1669 (br, CO, CON); MS m/z (rel int.): 240 (Mþ,
<1), 105 (100), 92 (14), 77 (47).
4.4.7. N-Ethyl-N-(4-picolyl)-benzamide (4a). Yield: 45.2 mg (17%);
colourless viscous substance; [Found: C, 74.76; H, 6.80; N, 11.51;
C15H16N2O requires C, 74.97; H, 6.71; N, 11.66%]; Rf (2% MeOH, 98%
CHCl3) 0.44; (ca. 1/2 mixture of two C(O)N rotamers) dH (500 MHz,
CDCl3) 8.61 (2H, d, 4.7 Hz, H-2,6(Py)), 7.50e7.15 (7H, m, H-3,5(Py),
H-(Ph)), 4.78/4.53 (major/minor) (2H, br s, NCH2(Py)), 3.54/3.31
(minor/major) (2H, br s, NCH2CH3), 1.23/1.12 (minor/major) (3H, br
s, CH3).; dC (125.7 MHz, CDCl3) 172.2, 150.1/149.6 (minor/major),
147.4,136.1,129.8,128.6,126.4,122.7/121.7 (major/minor), 51.3/46.8
(minor/major), 43.9/42.3 (major/minor), 13.9/12.3 (major/minor).
4.4. Characterisation of the products
4.4.1. N-(2-picolyl)benzamide (1a). Yield: 64 mg (30%); brown
viscous substance; [Found: C, 73.45; H, 5.91; N, 13.01; C13H12N2O
requires C, 73.57; H, 5.70; N, 13.20%]; Rf (5% MeOH, 45% EtOAc, 50%
CHCl3) 0.42; dH (500 MHz, CDCl3) 8.55 (1H, d, 4.7 Hz, H-6(Py)), 7.89
(2H, d, 7.4 Hz, Hortho(Ph)), 7.78 (1H, s, NH), 7.70 (1H, dt, 1.6 Hz,
7.6 Hz, H-4(Py)), 7.50 (1H, d, 7.6 Hz, H-3(Py)), 7.44 (2H, t, 7.3 Hz,
IR (KBr n
(cmꢁ1)) 1635 (CON); MS m/z (rel int.): 240 (32, Mþ), 239
(44), 135 (11), 105 (100), 77 (46).
4.4.8. N-Ethyl-N-(4-picolyl)-phenylglyoxylamide
(4a0). Yield:
45.7 mg (19%); yellow viscous material; [Found: C, 71.53; H, 5.88; N,
10.30; C16H16N2O2 requires C, 71.62; H, 6.01; N, 10.44%]; Rf (2%
MeOH, 98% CHCl3) 0.60; (ca. 1/2 mixture of two C(O)N rotamers) dH
(500 MHz, CDCl3) 8.67/8.62 (major/minor) (2H, br s, H-2,6(Py)),
7.98e7.96 (2H, m, H-3,5(Py)), 7.77e7.65 (1H, m, Hpara(Ph)), 7.55/
7.52 (major/minor) (2H, t, 7.8 Hz, Hmeta(Ph)), 7.35/7.28 (major/mi-
Hmeta(Ph)), 7.35 (1H, dd, 4.7 Hz, 7.8 Hz, H-5(Py)), 7.23 (1H, t, 6.2 Hz,
Hpara(Ph)), 4.77 (2H, d, 4.9 Hz, CH2); dC (125.7 MHz, CDCl3) 167.4,
156.2, 148.7, 137.2, 134.3, 131.5, 128.5 (double intensity), 127.1
(double intensity), 122.5, 122.4, 44.7. IR (KBr,
n
(cmꢁ1)) 3310 (NH),
1647 (CON); MS m/z (rel int.): 212 (Mþ, 12), 135 (3), 107 (100), 105
nor) (2H, br s, Hortho(Ph)), 4.76/4.42 (major/minor) (2H, s,
(26), 77 (36).
NCH2(Py)), 3.52/3.27 (minor/major) (2H, q, 7.2 Hz, NCH2CH3), 1.25/
1.15 (minor/major) (3H, t, 7.2 Hz, CH3); dC (125.7 MHz, CDCl3) 191.1/
191.0 (minor/major), 167.6/167.1 (major/minor), 149.8/149.5 (mi-
nor/major), 146.5/145.2 (major/minor), 135.0/134.9 (minor/major),
133.0/132.9 (minor/major), 129.8/129.7 (minor/major), 129.2/129.1
(major/minor), 122.9, 49.9/46.2 (minor/major), 42.8/39.6 (major/
4.4.2. N-(2-Picolyl)phenylglyoxylamide (1a0). Yield: 180 mg (75%);
orange viscous substance; [Found: C, 69.81; H, 5.22; N, 11.47;
C
14H12N2O2 requires C, 69.99; H, 5.03; N, 11.66%]; Rf (5% MeOH, 45%
EtOAc, 50% CHCl3) 0.62; dH (500 MHz, CDCl3) 8.55 (1H, d, 4.5 Hz, H-
6(Py)), 8.31 (2H, d, 7.9 Hz, Hortho(Ph)), 7.66 (1H, dt, 1.5 Hz, 7.4 Hz, H-
4(Py)), 7.60 (1H, t, 7.5 Hz, NH), 7.53 (1H, d, 7.4 Hz, H-3(Py)), 7.46 (2H,
t, 7.5 Hz, Hmeta(Ph)), 7.30 (1H, dt, 4.5 Hz, 7.4 Hz, H-5(Py)), 7.20 (1H, t,
5.7 Hz, Hpara(Ph)), 4.69 (2H, d, 5.5 Hz, CH2); dC (125.7 MHz, CDCl3)
187.6, 162.1, 155.5, 149.1, 136.9, 134.2, 131.0 (double intensity), 128.4
minor), 13.8/12.3 (major/minor). IR (KBr
n
(cmꢁ1)) 1678 (CO), 1645
(CON); MS m/z (rel int.): 268 (0.5, Mþ), 197 (50), 163 (11), 135 (4),
105 (100), 92 (79), 77 (44).
4.4.9. N,N-Di-(2-picolyl)-benzamide (5a). Yield: 197 mg (65%);
yellow viscous material; [Found: C, 75.05; H, 5.81; N, 13.59;
C19H17N3O requires C, 75.23; H, 5.65; N, 13.85%]; Rf (2% MeOH, 48%
(double intensity), 128.3, 122.5, 121.9, 44.2. IR (KBr,
n
(cmꢁ1)) 3327
(NH), 1667 (br, CO, CON); MS m/z (rel int.): 240 (Mþ, <1), 135 (100),
105 (31), 92 (76), 77 (23).
EtOAc, 50% CHCl3) 0.44; dH (500 MHz, CDCl3) 8.60 (1H, d, 4.6 Hz, H-
6(Py)), 8.44 (1H, d, 5.0 Hz, H-6(Py)), 8.14 (2H, d, 8.2 Hz, Hortho(Ph)),
7.71 (1H, dt, 2.6 Hz, 7.6 Hz, H-4(Py)), 7.64 (1H, dt, 2.6 Hz, 7.1 Hz, H-
4(Py)), 7.63 (1H, t, 7.3 Hz, Hpara(Ph)), 7.52 (2H, t, 7.8 Hz, Hmeta(Ph)),
7.40 (1H, d, 7.8 Hz, H-3(Py)), 7.35 (1H, d, 7.8 Hz, H-3(Py)), 7.23 (1H,
dd, 4.6 Hz, 7.6 Hz, H-5(Py)), 7.16 (1H, dd, 5.0 Hz, 7.1 Hz, H-5(Py)),
4.90 (2H, s, CH2), 4.67 (2H, s, CH2); dC (125.7 MHz, CDCl3) 191.3,
168.1, 155.8, 155.4, 149.4, 149.3, 137.0, 136.9, 134.6, 133.4, 130.3,
4.4.3. N-(3-Picolyl)benzamide (2a). MS m/z (rel int.): 212 (Mþ, 75),
135 (9), 107 (26), 105 (100), 77 (68).
4.4.4. N-(3-Picolyl)phenylglyoxylamide (2a0). Yield: 192 mg (80%);
Pale yellow viscous substance; [Found: C, 69.85; H, 5.20; N, 11.52;
C
14H12N2O2 requires C, 69.99; H, 5.03; N, 11.66%]; Rf (5% MeOH, 95%
CHCl3) 0.58; dH (500 MHz, CDCl3) 8.56 (1H, s, H-2(Py)), 8.51 (1H, d,
4.7 Hz, H-6(Py)), 8.31 (2H, d, 8.0 Hz, Hortho(Ph)), 7.89 (1H, s, NH),
7.68 (1H, d, 7.8 Hz, H-4(Py)), 7.63 (1H, dd, 4.7 Hz, 7.8 Hz, H-5(Py)),
7.48 (2H, t, 7.6 Hz, Hmeta(Ph)), 7.27 (1H, t, 7.4 Hz, Hpara(Ph)), 4.58 (2H,
d, 6.3 Hz, CH2); dC (125.7 MHz, CDCl3) 187.5, 162.1, 149.2, 149.1,
135.8, 134.6, 133.2, 133.1, 131.2 (double intensity), 128.6 (double
128.8, 122.8, 122.6, 122.2, 53.0, 49.5. IR (KBr n
(cmꢁ1)) 1646; MS m/z
(rel int.): 303 (0.5, Mþ), 226 (100), 198 (21), 183 (31), 105 (45), 92
(67), 77 (41).
4.4.10. N-(2-Picolyl)cyclohexene-1-carboxamide (1b). Yield: 175 mg
(81%); pale yellow viscous substance; [Found: C, 72.31; H, 7.60; N,
12.77; C13H16N2O requires C, 72.19; H, 7.46; N, 12.95%]; Rf (5%
MeOH, 45% EtOAc, 50% CHCl3) 0.45; dH (500 MHz, CDCl3) 8.55 (1H,
d, 4.3 Hz, H-6(Py)), 7.67 (1H, td, 7.6 Hz, 1.5 Hz, H-4(Py)), 7.29 (1H, d,
7.6 Hz, H-3(Py)), 7.21 (1H, dd, 7.6 Hz, 4.3 Hz, H-5(Py)), 7.07 (1H, s,
NH), 6.75 (1H, br s, CH), 4.62 (2H, d, 4.8 Hz, NHCH2), 2.32 (2H, br s,
CH2), 2.19 (2H, br s, CH2), 1.71 (2H, qi, 5.9 Hz, CH2), 1.62 (2H, qi,
5.9 Hz, CH2); dC (125.7 MHz, CDCl3) 168.6, 156.8, 148.9, 136.7, 133.9,
intensity), 123.7, 40.9. IR (KBr, n
(cmꢁ1)) 3180 (NH), 1677 (CO), 1663
(CON); MS m/z (rel int.): 240 (Mþ, <1), 105 (100), 92 (18), 77 (48).
4.4.5. N-(4-Picolyl)benzamide (3a). MS m/z (rel int.): 212 (67, Mþ),
105 (100), 77 (62).
4.4.6. N-(4-Picolyl)phenylglyoxylamide (3a0). Yield: 185 mg (77%);
yellow viscous substance; [Found: C, 69.80; H, 5.18; N, 11.50;
132.8, 122.2,122.1, 44.4, 25.4, 24.2, 22.1, 21.5. IR (KBr, n
(cmꢁ1)) 3326

M. Gergely et al. / Tetrahedron 70 (2014) 218e224
223
(NH), 1661 (CON); MS m/z (rel int.): 216 (17, Mþ), 107 (100), 92 (21),
79 (32).
requires C, 75.61; H, 5.92; N, 11.76%]; Rf (3% MeOH, 97% CHCl3) 0.60;
dH (500 MHz, CDCl3) 8.52 (2H, d, 5.3 Hz, H-2,6(Py)), 7.39 (5H, br s, H-
(Ph)), 7.17 (2H, d, 5.3 Hz, H-3,5(Py)), 6.39 (1H, s, NH), 6.21 (1H, s, ]
CH), 5.68 (1H, s, ]CH), 4.53 (2H, d, 6.1 Hz, CH2); dC (125.7 MHz,
CDCl3) 167.5, 150.0, 147.3, 144.2, 136.8, 128.9, 128.7, 128.2, 123.1,
4.4.11. N-(3-Picolyl)cyclohexene-1-carboxamide (2b). Yield: 175 mg
(85%); yellow viscous substance, [Found: C, 72.33; H, 7.65; N, 12.74;
C
13H16N2O requires C, 72.19; H, 7.46; N, 12.95%]; Rf (7% MeOH, 93%
122.2, 42.7. IR (KBr n
(cmꢁ1)) 3302 (NH), 1643 (CON); MS m/z
CHCl3) 0.65; dH (500 MHz, CDCl3) 8.50 (1H, br s, H-2(Py)), 8.49 (1H,
d, 4.7 Hz, H-6(Py)), 7.64 (1H, d, 7.7 Hz, H-4(Py)), 7.25 (1H, dd, 7.7 Hz,
4.7 Hz, H-5(Py)), 6.68 (1H, br s, CH), 6.39 (1H, s, NH), 4.50 (2H, d,
6.1 Hz, NHCH2), 2.24 (2H, br s, CH2), 2.16 (2H, br s, CH2), 1.67 (2H, qi,
5.9 Hz, CH2), 1.59 (2H, qi, 5.9 Hz, CH2); dC (125.7 MHz, CDCl3) 168.9,
148.9, 148.3, 135.6, 134.7, 134.2, 132.5, 123.5, 40.8, 25.3, 24.2, 22.1,
(rel int.): 238 (100, Mþ), 103 (80), 92 (17), 77 (38).
4.4.17. N-Ethyl-N-(4-picolyl)-atropamide (4c). Yield: 229 mg (86%);
orange viscous material; [Found: C, 76.50; H, 6.93; N, 10.33;
C17H18N2O requires C, 76.66; H, 6.81; N, 10.52%]; Rf (3% MeOH, 97%
CHCl3) 0.55; (ca. 1/2 mixture of two C(O)N rotamers) dH (500 MHz,
CDCl3) 8.60/8.55 (major/minor) (2H, d, 4.1 Hz, Hortho(Py)), 7.48/7.44
(major/minor) (2H, d, 7.0 Hz, Hmeta(Py)), 7.42e7.35 (3H, m, Hpar-
a(Ph), Hmeta(Ph)), 7.25/7.03 (major/minor) (2H, d, 5.0 Hz, Hortho(Ph)),
5.77/5.68 (major/minor) (1H, s, ]CH), 5.45/5.37 (major/minor) (1H,
s, ]CH), 4.73/4.44 (major/minor) (2H, s, NCH2(Py)), 3.52/3.26
(minor/major) (2H, q, 7.0 Hz, NCH2CH3), 1.22/1.00 (minor/major)
(3H, t, 7.0 Hz, CH3); dC (125.7 MHz, CDCl3) 171.2/171.0 (major/mi-
nor), 150.1/150.0 (minor/major), 146.7/146.2 (major/minor), 145.1/
144.8 (major/minor), 135.6/135.4 (major/minor), 132.5/132.4 (ma-
jor/minor), 129.0/128.9 (minor/major), 128.8/128.7 (minor/major),
125.7/125.6 (major/minor), 122.7/121.8 (major/minor), 114.2/114.1
(minor/major), 50.6/46.2 (minor/major), 43.2/39.7 (major/minor),
21.4. IR (KBr, n
(cmꢁ1)) 3310 (NH), 1660 (CON); MS m/z (rel int.): 216
(100, Mþ), 187 (26), 173 (26), 159 (19), 109 (37), 92 (31), 81 (69), 79
(53).
4.4.12. N-(4-Picolyl)cyclohexene-1-carboxamide (3b). Yield: 173 mg
(80%); pale yellow needle-like crystal, mp 90e91 ꢀC; [Found: C,
72.01; H, 7.55; N, 12.71; C13H16N2O requires C, 72.19; H, 7.46; N,
12.95%]; Rf (7% MeOH, 93% CHCl3) 0.63; dH (500 MHz, CDCl3) 8.53
(2H, d, 5.3 Hz, H-2,6(Py)), 7.20 (2H, d, 5.3 Hz, H-3,5(Py)), 6.72 (1H, s,
CH), 6.36 (1H, s, NH), 4.51 (2H, d, 6.0 Hz, NHCH2), 2.28 (2H, br s,
CH2), 2.19 (2H, br s, CH2) 1.71 (2H, qi, 5.9 Hz, CH2), 1.62 (2H, qi,
5.9 Hz, CH2); dC (125.7 MHz, CDCl3) 168.8, 149.8 (double intensity),
148.1, 134.4, 132.7, 122.2 (double intensity), 42.2, 25.4, 24.3, 22.1,
13.6/12.2 (major/minor). IR (KBr
n
(cmꢁ1)) 1638 (CON); MS m/z
21.5. IR (KBr
n
(cmꢁ1)) 3319 (NH), 1660 (CON); MS m/z (rel int.):
(rel int.): 266 (100, Mþ), 251 (17), 188 (5), 174 (2), 149 (7), 135 (8),
131 (9), 103 (92), 92 (23), 77 (28).
216 (100, Mþ), 187 (24), 173 (18), 159 (12), 109 (61), 92 (26), 81 (76),
79 (54).
4.4.18. N,N-Di-(2-picolyl)-atropamide (5c). Yield: 264 mg (80%);
4.4.13. N-Ethyl-N-(4-picolyl)-cyclohexene-1-carboxamide
(4b). Yield 176 mg (72%); orange solid, mp 68.8 ꢀC; [Found: C,
73.70; H, 8.16; N, 11.30; C15H20N2O requires C, 73.74; H, 8.25; N,
11.47%]; Rf (3% MeOH, 97% CHCl3) 0.44; dH (500 MHz, CDCl3) 8.45
(2H, br s, H-2,6(Py)), 7.06 (1H, d, 4.4 Hz, H-3,5(Py)), 5.77 (1H, br s,
CH), 4.51 (2H, s, NCH2(Py)), 3.28 (2H, q, 7.0 Hz, NCH2CH3), 2.15 (2H,
br s, CH2), 2.00 (2H, br s, CH2), 1.60 (2H, br s, CH2), 1.53 (2H, br s,
CH2), 1.03 (3H, t, 7.0 Hz, CH3); dC (125.7 MHz, CDCl3) 173.5, 149.9,
147.0,134.3,127.2,122.2, 46.1, 43.2, 26.1, 24.5, 22.0, 21.5,13.9. IR (KBr
dark green solid, mp 93.0 ꢀC; [Found: C, 76.42; H, 5.88; N, 13.59;
C21H19N3O requires C, 76.57; H, 5.81; N, 13.76%]; Rf (3% MeOH, 97%
CHCl3) 0.65; dH (500 MHz, CDCl3) 8.55 (1H, d, 4.7 Hz, H-6(Py)), 8.53
(1H, d, 4.7 Hz, H-6(Py)), 7.68 (1H, t, 7.8 Hz, H-4(Py)), 7.60 (1H, t,
7.8 Hz, H-4(Py)), 7.53 (2H, d, 8.1 Hz, Hortho(Ph)), 7.38 (1H, d, 7.8 Hz,
H-3(Py)), 7.35e7.30 (3H, m, Hmeta(Ph), Hpara(Ph)), 7.20 (1H, dd,
4.7 Hz, 7.8 Hz, H-5(Py)), 7.16 (1H, t, 4.7 Hz, 7.8 Hz, H-5(Py)), 7.08 (1H,
d, 7.8 Hz, H-3(Py)), 5.71 (1H, s, ]CH), 5.47 (1H, s, ]CH), 4.91 (2H, s,
CH2), 4.69 (2H, s, CH2); dC (125.7 MHz, CDCl3) 171.7, 156.9, 156.6,
149.6, 149.3, 144.5, 136.8, 136.6, 135.6, 128.8, 128.6, 126.0, 122.6,
n
(cmꢁ1)) 1617 (br, C]C, CON); MS m/z (rel int.): 244 (93, Mþ), 215
(29), 201 (16), 187 (9), 135 (25), 109 (100), 92 (22), 81 (93), 79 (51).
122.4, 122.3, 121.2, 114.5, 53.9, 49.9. IR (KBr n
(cmꢁ1)) 1642 (CON);
MS m/z (rel int.): 329 (16, Mþ), 237 (33), 198 (30), 103 (56), 93 (100),
4.4.14. N-(2-Picolyl)-atropamide (1c). Yield: 181 mg (76%); orange
viscous material; [Found: C, 75.44; H, 5.99; N, 11.60; C15H14N2O
requires C, 75.61; H, 5.92; N, 11.76%]; Rf (2% MeOH, 98% CHCl3) 0.58;
dH (500 MHz, CDCl3) 8.48 (1H, d, 4.9 Hz, H-6(Py)), 7.67 (1H, t,
7.6 Hz, H-4(Py)), 7.34e7.44 (5H, m, H-(Ph)), 7.30 (1H, d, 7.6 Hz, H-
3(Py)), 7.19 (1H, dd, 7.3 Hz, 4.9 Hz, H-5(Py)), 7.03 (1H, s, NH), 6.18
(1H, s, ]CH) 5.68 (1H, s, ]CH), 4.67 (2H, d, 5.3 Hz, CH2); dC
(125.7 MHz, CDCl3) 167.5, 156.4, 149.0, 144.8, 137.0, 136.8, 132.1,
92 (33), 77 (24).
Acknowledgements
The authors thank the Hungarian Research Fund (CK78553) and
Developing Competitiveness of Universities in the Transdanubian
Region (SROP-4.2.1.B-10/2/KONV-2010-0002 and SROP-4.2.2.A-11/
1/KONV-2012-0065) for the financial support. This research of A.T.
was supported by the European Union and the State of Hungary, co-
128.7, 128.5, 128.2, 122.4, 122.1, 44.9. IR (KBr
1656 (CON); MS m/z (rel int.): 238 (8), 237 (15), 146 (2), 135 (40),
107 (42), 103 (36), 93 (100), 92 (75), 77 (31).
n
(cmꢁ1)) 3294 (NH),
ꢀ
financed by the European Social Fund in the framework of TAMOP
4.2.4. A/2-11-1-2012-0001 ‘National Excellence Program’.
4.4.15. N-(3-Picolyl)-atropamide (2c). Yield: 174 mg (73%); orange
solid, mp 92.6 ꢀC; [Found: C, 75.81; H, 5.98; N, 11.56; C15H14N2O
requires C, 75.61; H, 5.92; N, 11.76%]; Rf (5% MeOH, 95% CHCl3) 0.59;
dH (500 MHz, CDCl3) 8.51 (2H, br s, H-2(Py), H-6(Py)), 7.65 (1H, d,
7.8 Hz, H-4(Py)), 7.38 (5H, br s, H-(Ph)), 7.27 (1H, dd, 5.0 Hz, 7.8 Hz,
H-5(Py)), 6.27 (1H, s, NH), 6.21 (1H, s, ]CH), 5.66 (1H, s, ]CH), 4.54
(2H, d, 6.1 Hz, CH2); dC (125.7 MHz, CDCl3) 167.4, 149.0, 148.9, 144.3,
References and notes
1. Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974, 39, 3327e3331.
2. Applied Homogeneous Catalysis with Organometallic Compounds; Cornils, B.,
Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, 1996.
3. Transition Metals for Organic Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH:
Weinheim, 1998; Vols. IeII.
4. Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbonylation. Direct Synthesis
of Carbonyl Compounds; Plenum: New York, NY and London, 1991.
5. Arcadi, A. Carbonylation of Enolizable Ketones (Enol Triflates) and Iodoalkenes
136.8, 135.6, 133.9, 128.8, 128.7, 128.2, 123.6, 123.1, 41.4. IR (KBr
n
(cmꢁ1)) 3308 (NH), 1642 (CON); MS m/z (rel int.): 238 (100, Mþ),
ꢀ
In Modern Carbonylation Methods; Kollar, L., Ed.; Wiley-VCH: Weinheim, 2008;
Chapter 9, pp 223e250.
6. Skoda-Foldes, R.; Kollar, L. Curr. Org. Chem. 2002, 6, 1097e1119.
103 (66), 92 (18), 77 (35).
€
ꢀ
7. Wu, X. F.; Neumann, H.; Beller, M. Chem.dEur. J. 2002, 16, 9750e9753.
8. Brennfuhrer, A.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2009, 48,
4114e4133 and references cited therein.
4.4.16. N-(4-Picolyl)-atropamide (3c). Yield: 193 mg (81%); orange
€
solid, mp 79.4 ꢀC; [Found: C, 75.50; H, 5.78; N, 11.49; C15H14N2O

224
M. Gergely et al. / Tetrahedron 70 (2014) 218e224
30. Choudhury, C. R.; Dey, S. K.; Mitra, S.; Gramlich, V. Dalton Trans. 2003,
9. Dei, S.; Bellucci, G.; Ghelardini, C.; Romanelli, M. N.; Spampinato, S. Life Sci.
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