Palladium-mediated 11C-carbonylative cross-coupling of alkyl/aryl iodides with organostannanes: An efficient synthesis of unsymmetrical alkyl/aryl [11C-carbonyl]ketones

Article abstract of DOI:10.1002/ejoc.200400883

[¹¹C]Carbon monoxide in low concentration, palladium complexes, alkyl/aryl iodides, and organostannanes are utilized in the synthesis of twenty alkyl [carbonyl-¹¹C]ketones. The activated palladium(0) species [Pd{P(o-Tol)₃}

Full text of DOI:10.1002/ejoc.200400883

FULL PAPER
11
Palladium-Mediated C-Carbonylative Cross-Coupling of Alkyl/Aryl Iodides
with Organostannanes: An Efficient Synthesis of Unsymmetrical Alkyl/Aryl
11
[
C-carbonyl]Ketones
[a]
[b]
[a,b]
Farhad Karimi, Julien Barletta and Bengt Långström*
Keywords: Carbonylation / Cross-coupling / Isotopic labelling / Palladium
[11
C]Carbon monoxide in low concentration, palladium com- specific radioactivity up to 300 GBqμmol–1. Using this
13
plexes, alkyl/aryl iodides, and organostannanes are utilized
method, 4Ј-aminoacetophen[ C-arbonyl)one 6 was synthe-
sised in order to confirm the position of labelling (δ =
1
1
in the synthesis of twenty alkyl [carbonyl- C]ketones. The
activated palladium(0) species [Pd{P(o-Tol) ] was generated
tris(dibenzylideneacetone)palladium(0)
] and a large excess of tri-o-tolylphosphane [P(o-
3
}
2
3
196.7 ppm, CDCl ). The presented approach is an efficient
in
Pd
Tol)
situ
(dba)
3
from
way for synthesising 11C-labelled alkyl/aryl ketones with ac-
ceptable radiochemical yield and is generally applicable in
[
2
13
3
]. The Stille coupling reactions were performed in a
C-labelling syntheses.
11
micro-autoclave system. Radiochemical yields of C-lab-
elled alkyl/aryl ketones were in the range of 37–98% with
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
Introduction
phane)palladium(0) and the appropriate organostannanes
resulted in 10% yield of the total amount of radioactivity.[
This low efficiency was significantly improved by concen-
6]
The increasing application of positron emitting tomogra-
phy (PET) has stimulated the development of rapid
and efficient methods for the incorporation of positron-
11
trating [ C]carbon dioxide, followed by local reduction to
11
[
C]carbon monoxide, and then using a recirculation tech-
1
1
emitting radionuclides with a short half-life like C (t1/2
=
11
nique with [ C]carbon monoxide. This approach increased
the trapping efficiency to 70% but the radiochemical yields
were still low. For example, 1-phenylethan[ C-carbonyl]one
[
1]
2
0.3 min) into the target molecule. The most used precur-
1
1
sors for the introduction of C in a bioactive molecule are
11
1
1
11
[
C]iodomethane and [ C]methyl triflate used in methyla-
[7]
(1) was obtained in a radiochemical yield of 36%.
1
1
tion reactions, [ C]carbon dioxide in the Grignard reac-
In another study using a micro-autoclave technique, the
[
2]
11
tion and, more recently, [ C]carbon monoxide in carbon-
ylation reactions.
influence of various ligands and temperature on the radio-
11
[8]
chemical yield of C-ketones was investigated.
Due to the short half-life, low reactivity and solubility of
An alternative route to organostannanes, the use of or-
[11
C]carbon monoxide, one-pot carbonylation reactions
[3]
[9]
ganoboronic acid, was studied recently. However, the ra-
[4]
using a micro-autoclave are preferred, and various types
11
diochemical yield of these alkyl/aryl [ C-carbonyl]ketones
1
1
of C-carbonyl compounds have been synthesised by this
was in the range of 15 to 45% using triflates in a Suzuki
[
5]
approach.
[10]
cross-coupling reaction in a micro-autoclave system.
1
1
In this paper, [ C]carbon monoxide at low concentra-
tion, palladium complexes, alkyl/aryl iodides and organo-
stannanes are utilized in the synthesis of twenty alkyl [ C-
11
[
C]Carbon monoxide at low concentration, an aryl/al-
kyl iodide, [Pd{P(o-Tol) } ] (formed in situ) and organo-
3
2
11
stannanes have been used for the synthesis of alkyl/aryl
carbonyl]ketones.
11
[
C-carbonyl]ketones with a micro-autoclave-based tech-
[
4]
nique. There is still, however, a need for a rapid efficient
alternative method for C-labelling of ketones owing to the
variation in reported radiochemical yields. In our attempts
11
Results and Discussion
1
1
The first published report on [ C-carbonyl]ketones
11
to synthesis 1-phenylethan[ C-carbonyl]one (1) from iodo-
1
1
based on [ C]carbon monoxide, tetrakis(triphenylphos-
benzene and tetramethyltin, a series of palladium com-
plexes were used and all reactions were performed at 125 °C
[
a] Uppsala Imanet AB,
(Table 1). A standard reaction time of 5 min was selected.
7
5185 Uppsala, Sweden
Fax: +46-18-666-819
The results indicated that the choice of ligand and solvent
have a major impact on the radiochemical yield. For in-
stance, using DMSO instead of DMF increased the radio-
chemical yield from 8% to 49%. This may be due to the
E-mail: bengt.langstrom@uppsala.imanet.se
b] Department of Organic Chemistry, Institute of Chemistry,
BMC, Uppsala University,
[
Box 599, 75124 Uppsala, Sweden
2374
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400883
Eur. J. Org. Chem. 2005, 2374–2378

Palladium-Mediated Carbonylative Cross-Coupling of Alkyl/Aryl Iodides with Organostannanes
FULL PAPER
higher dielectric constant and solubility of DMSO.[11] The
impact of the ligand ratio was further investigated for
[
Pd (dba) ]/AsPh and [Pd (dba) ]/P(o-Tol) (Table 2). In
2 3 3 2 3 3
the former case, increasing the amount of ligand resulted in
a lower radiochemical yield. However, the opposite out-
come was obtained using an excess of P(o-Tol) . As the P(o-
3
Tol) was not completely dissolved in DMSO (500 μL), a
3
saturated solution was most probably obtained.
Table 1. Impact of the ligand nature on the radiochemical yield and
11
trapping efficiency of 1-phenylethan[ C-carbonyl]one. The reac-
tions were performed at 125 °C for 5 min with iodobenzene and
tetramethyltin.
RCY[ c][%]
a]
Ratio
Solvent
Trapping
[
efficiency [%]
(n)
[b]
[
[
[
[
[
[
[
[
[
[
PdCl
Pd(PPh
PdCl P(o-Tol)
2
(dppe)]
–
–
–
1:4
1:4
1:4
1:1
1:4
1:4
1:4
THF/NMP
THF
THF/NMP
THF
THF
THF/NMP
THF
THF
DMF
DMSO
85± 3 (2)
91± 2 (4)
92
95± 2 (2)
5± 2 (2)
7± 2 (4)
3
)
4
]
2
2
]
6
Pd
2
Pd
2
Pd
2
Pd
2
Pd
2
Pd
2
Pd
2
(dba)
(dba)
(dba)
(dba)
(dba)
(dba)
(dba)
3
3
3
3
3
3
3
]/AsPh
3
50± 3 (2)
]/P(tBu)
]/dppe
]/dppf
]/TFP
]/P(o-Tol)
]/P(o-Tol)
3
75
91
92
93
90
1
6
40
6
8
3
3
95± 1 (2)
49± 1 (2)
[
a] RCY = radiochemical non-isolated yield. [b] Decay-corrected
trapping efficiency, the fraction of radioactivity left in the crude
product after purge with nitrogen; the value in parentheses is the
number of runs. [c] The value in parentheses is the number of runs.
Table 2. Impact of palladium/ligand ratio on radiochemical yield
11
and trapping efficiency of 1-phenylethan[ C-carbonyl]one. The re-
actions were performed at 125 °C for 5 min with iodobenzene and
tetramethyltin.
Figure 1. Target compounds (* = 11C).
Palladium
complexes
Ratio
Solvent
Trapping
RCY[a]
[c]
efficiency [%][
b]
[%] (n)
[Pd
2
[Pd
2
[Pd
2
[Pd
2
[Pd
2
(dba)
(dba)
(dba)
(dba)
(dba)
3
3
3
3
3
]/AsPh
]/AsPh
]/AsPh
]/P(o-Tol)
]/P(o-Tol)
3
3
3
1:4
1:8
1:12
1:4
THF
THF
THF
DMSO
DMSO
95± 2 (2)
50± 3 (2)
95
89
95± 1 (2)
99
46
15
49± 1 (2)
67
3
3
1:12
[
a] RCY = radiochemical non-isolated yield. [b] Decay-corrected
trapping efficiency, the fraction of radioactivity left in the crude
product after purging with nitrogen; the value in parentheses is the
number of runs. [c] The value in parentheses is the number of runs.
The reaction between [Pd (dba) ] and P(o-Tol) generates
2
3
3
0
the active Pd species [Pd{P(o-Tol) } ]. The bulkiness of
3
2
Figure 2. Halides.
P(o-Tol) (cone angle = 194°) is assumed to contribute to
3
0
[12,13]
the reactivity of the Pd species formed.
Furthermore,
the assumption was made that an excess of ligand P(o-Tol)3
may stabilise the activated palladium complex.
11
1-Phenylethan[ C-carbonyl]one (1) was synthesised
The scope and limitations of this system were explored from either iodobenzene (21) and tetramethyltin (35) or
by choosing various aliphatic/aromatic iodides and ali- iodomethane (44) and tributylphenyltin (36). In the former
phatic organostannanes (Figure 1, Figure 2 and Figure 3). case, the analytical radiochemical yield was in the region of
The results are shown in Table 3 and 4.
72% (isolated radiochemical yield 68%). However, in the
Eur. J. Org. Chem. 2005, 2374–2378
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2375

F. Karimi, J. Barletta, B. Långström
FULL PAPER
1
1
Table 4. Radiochemical yields for the [ C]ketones shown in Fig-
ure 1.
En- Halide
try
Stannyl
compound
Product T [°C] Trapping
efficiency [%][b] [%] (n)
RCY[a]
[c]
35
36
37
38
39
40
41
42
43
44
45
46
47
48
30
34
30
30
30
31
31
32
32
32
33
34
34
34
35
40
37
37
38
35
35
35
35
35
35
41
42
35
13
13
14
14
15
16
16
17
17
17
18
18
19
20
100
100
100
150
150
100
150
rt
91± 3 (4)
97± 1 (3)
78± 1 (2)
86± 1 (2)
91± 1 (2)
93
92± 1 (2)
53
68± 3 (5)
93
61± 1 (4)
93± 2 (3)
45± 1 (2)
59± 2 (2)
47± 1 (2)
7
63± 2 (2)
48
46± 10 (5)
18
71± 1 (3)
98± 1 (4)
95± 1 (4)
97± 1 (2)
Figure 3. Organostannyl compounds.
50
100
100
100
100
100
98± 1 (3)
95± 1 (4)
96± 1 (4)
95± 1 (2)
latter case the radiochemical yield was increased to 91%.
The analytical radiochemical yields of 2 and 3 were 60 and
6
5%, respectively. However, the yield of 4 was 37%. This
may be due to the low purity of the tetrabutyltin used
93%). This study was further expanded by choosing vari- product after purging with nitrogen; the value in parentheses is the
[
a] RCY = radiochemical non-isolated yield. [b] Decay-corrected
trapping efficiency, the fraction of radioactivity left in the crude
(
ous electron-donating and -accepting substituted iodo- number of runs. [c] The value in parentheses is the number of runs.
benzenes.
11
Table 3. Radiochemical yields for the [ C]ketones shown in Figure 1.
Entry
Halide
Organostannyl
compound
Product
T
[°C]
Trapping efficiency
[%][
RCY[a]
[%] (n)
b]
[c]
1
2
3
4
5
6
7
8
9
21
21
21
34
21
21
21
21
21
21
21
22
23
35
35
35
36
37
37
38
38
39
39
39
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
35
1
1
150
125
100
100
150
100
100
150
50
100
150
100
100
100
100
100
100
50
100
150
100
150
100
100
100
150
100
140
100
80
98
99
98± 1 (7)
98± 1 (3)
98
98± 1 (3)
98
97± 1 (3)
98
97± 1 (2)
97± 1 (3)
96± 2 (3)
96± 1 (3)
95
98± 1 (3)
95± 2 (3)
93
75
96
94
91± 3 (3)
90
94± 1 (3)
94
92
89
88± 1 (2)
82
60
67
72± 3 (7)
91± 3 (3)
50
60± 1 (3)
22
65± 2 (3)
2
8± 2 (2)
37± 1 (3)
68± 2 (3)
75± 1 (3)
48
62± 5 (3)
73± 2 (3)
1
1
1
2
2
3
3
4
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
4
4
5
6
[
e]
23
6
24
25
26
7
8
9
[
[
[
d]
26
26
26
9
5
7
d]
d]
9
9
10
75± 4 (3)
48
56± 1 (3)
11
21
[
e]
26
27
27
9
10
10
10
10
11
11
12
12
12
12
12
12
12
[
d]
27
[
e]
27
28
28
29
29
29
29
29
29
29
9
49± 1 (2)
40
41
49± 1 (2)
41± 4 (2)
40
28± 1 (2)
65
87
92± 3 (2)
88± 1 (2)
66
76± 4 (2)
41
60
30
30[
f]
r.t.
[
a] RCY = radiochemical non-isolated yield. [b] Decay-corrected trapping efficiency, the fraction of radioactivity left in the crude product
after purging with nitrogen; the value in parentheses is the number of runs. [c] The value in parentheses is the number of runs. [d]
Tetrabutylammonium salt of the corresponding halide. [e] HCl salt of the corresponding halide. [f] Reaction time: 8 min.
2376
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 2374–2378

Palladium-Mediated Carbonylative Cross-Coupling of Alkyl/Aryl Iodides with Organostannanes
FULL PAPER
In the synthesis of compounds 5–8, the use of halides Conclusions
2
2–25 gave good radiochemical yields. In an attempt to in-
[11
C]Carbon monoxide at low concentration has been
crease the radiochemical yield of 6, the HCl salt of halide
3 was used (entry 14). This resulted in a decrease of the
used in the palladium-mediated carbonylative coupling of
2
organic iodides with organostannanes to form 11C-labelled
radiochemical yield from 75% (isolated = 69%) to 48%.
When 26 was used, despite a good trapping efficiency,
only a trace amount of 9 was obtained. The analytical ra-
diochemical yield increased slightly on using the tetrabu-
tylammonium salt of 26. However, the radiochemical yield
was increased to 75% when the HCl salt of 26 was used
ketones. An excess of tri-o-tolylphosphane [P(o-Tol) ] may
be essential in order to increase the radiochemical yield of
3
11
alkyl/aryl [ C-carbonyl]ketones. It has been shown that
iodomethane has a higher reactivity than aromatic iodides
in the 11C-carbonyl cross-coupling. The present method is
rapid, mild, general and can be conducted in a one-pot pro-
cedure that is probably suitable for automation.
(
entries 18–21).
The lower radiochemical yields of 10–12 may be due to
the electron-accepting nature of the substituted halides 27–
9. The substituent effect on the aromatic ring may have an
impact on the reactivity of the corresponding iodobenzene
in the palladium-mediated C-carbonylation reactions.
The investigation was further extended by studying the
synthesis of 13–15 from 3-iodopyridine (30) and the corre-
sponding organostannyl compound. The radiochemical
yield of 13 was increased when iodomethane (34) and 3-
2
Experimental Section
1
1
1
1
General: [ C]Carbon dioxide was produced at Uppsala Imanet via
1
4
11
the N(p,α) C reaction in a gas target containing nitrogen (AGA,
Nitrogen 6.0) and 0.1% oxygen (AGA, Oxygen 4.8), bombarded
with 17 MeV protons using a Scanditronix MC-17 cyclotron. [ C]
11
Carbon dioxide was trapped on a Silica column at –196 °C. The
concentrated gas was released into a slow stream of helium gas
(tributylstannyl)pyridine (40) were used (entry 36). This
–
1
might be due to the higher reactivity of iodomethane than (10 mLmin ) by heating. The gas flow was passed through a small
tube containing zinc at 400 °C.[ The [ C]carbon monoxide pro-
14]
11
the aromatic halides (Table 4).
In the case of 1-pyrazin-2-ylethanone (17), a good radio- duced was trapped again on a short silica column at –196 °C. The
1
1
[
C]carbon monoxide was released by warming the silica column
chemical yield was obtained at rather low temperature (en-
try 42). The lower yield of 17 at higher temperature may
indicate that the compound is unstable under these condi-
tions.
A good radiochemical yield of 18 was obtained when autoclave was washed with 10–15 mL of DMSO, followed by heat-
performing the reaction at 100 °C (entry 44). However, the
to about 60 °C and transferring the radioactivity into a micro-auto-
clave.
At the start of the experimental sessions, the stainless-steel micro-
ing at 100–150 °C for 5 min, and then washed with an additional
5–10 mL of DMSO. It was also washed with 1–2 mL of DMSO
radiochemical yield increased considerably when iodome-
thane was used instead of 33 (entry 45).
after each experiment.
These results (entries 4 and 36) indicate that iodome- Liquid chromatographic analysis (LC) was performed with a
1
1
thane is more reactive towards C-carbonylative cross Beckman 126 gradient pump and a Beckman 166 variable wave-
+
length UV-detector (Fullerton, CA, USA) in series with a β -flow
coupling than aromatic or heteroaromatic iodides. The ra-
diochemical yields of 19 (95%) and 20 (97%) confirmed
detector.[ The following mobile phases were used: 0.01 m formic
15]
acid (A), acetonitrile/water (50:7) (B), 0.01 m potassium hydrogen
phosphate (C) and acetonitrile (D). For analytical LC, a Jones
this assumption.
11
The effective specific radioactivity value for the [ C]car-
Chromatography Genesis C18 (4 μm, 250×4.6 mm i.d.) column was
5
–1
bon is below the theoretical figure (3.4×10 GBqμmol )
because of the dilution by stable isotopes originating from
the target, delivery lines, chemical reagents, etc. However,
–1
used with a flow of 1.5 mLmin . For semi-preparative LC, a Jones
Chromatography Genesis C18 (4 μm, 250×10 mm i.d.) column was
–1
used with a flow of 4 mLmin . Synthia, an automated synthesis
1
1
[16]
when using [ C]carbon monoxide, as described in the pres- system, was used for LC injection and fraction collection. Data
1
1
ent approach, C-labelled compounds with high specific collection and LC control were performed with the Beckman Sys-
radioactivity are obtained. Generally, the amount of lab- tem Gold chromatography software package (USA).
elled product is in the range of 10–100 nmol. The
Radioactivity was measured in an ion chamber (Veenstra Instru-
1
1
specific radioactivity of [ C]4Ј-aminoacetophenone (6) was
menten bv, VDC-202). For coarse estimations of radioactivity dur-
determined to be 298 GBqμmol upon irradiation at ing synthesis, a portable dose-rate meter was used.
–
1
2
0 μAh.
In analyses of the 11C-labelled compounds, unlabelled reference
substances were used for comparison in all LC runs. The identity
The 11C-labelled ketones were characterised by analytical
HPLC (equipped with radio- and UV-detectors) with co-
injection of non-radioactive reference compounds and com-
13
of the synthesised C-labelled compound 6 was determined bby
13
C NMR spectroscopy. NMR spectra were recorded on a Varian
paring the retention times for the UV and radioactive XL 400 (400 MHz) and deuterated chloroform was used as internal
peaks.
standard. LC-MS was performed with a Micromass VG Quattro
The identity and the confirmation of the labelling posi- with electrospray ionisation, a Beckman 126 pump, a CMA 240
autosampler and Beckman Ultrasphere ODS C18 (5 μm,
100×4.6 mm i.d.) column using mobile phases C and D.
to the carbonyl carbon of authentic 4Ј-aminoaceto- All chemicals were purchased from Sigma-Aldrich or Chemtronica
1
3
13
a
tion were confirmed by C NMR analysis of C-labelled
6
1
3
. The C NMR signal at δ = 196.7 ppm corresponds
phenone.
(Sweden).
Eur. J. Org. Chem. 2005, 2374–2378
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2377

F. Karimi, J. Barletta, B. Långström
FULL PAPER
General Method: A capped vial (1 mL) containing a solution of
tris(dibenzylideneacetone)palladium(0) (2.1 mg, 2.3 μmol) and tri-
o-tolylphosphane (16 mg, 52.6 μmol) in anhydrous DMSO
Acc. Chem. Res. 1997, 30, 181–188; c) B. Långström, T.
Kilhberg, M. Bergström, G. Antoni, M. Björkman, B. Forn-
gren, T. Forngren, P. Hartvig, K. Markides, U. Yngve, M.
Ögren, Acta Chem. Scand. 1999, 59, 651–669; d) M. Bergström,
A. Grahnén, B. Långström, Eur. J. Clin. Pharmacol. 2003, 59,
(500 μL) was flushed with argon. The reaction mixture was kept at
room temperature for 10 min. The appropriate halide (18 μmol)
was added and the resulting mixture kept at room temperature for
an additional 5 min. The reaction mixture was filtered (ThermoHy-
persil F2513-3, PTFE syringe filter 0.45 μm) before addition of the
organostannane just before injection into the micro-autoclave pre-
357–366.
[
2] a) R. J. Davenport, J. A. McCarron, K. Dowsett, D. R. Turton,
K. G. Poole, V. W. Pike, J. Labelled Compd. Radiopharm. 1997,
40, S309–S311; b) C. Perrio-Huard, C. Aubert, M. C. Lasne, J.
Chem. Soc., Perkin Trans. 1 2000, 3, 311–316.
11
charged with [ C]carbon monoxide. The micro-autoclave was
heated at the desired temperature for 5 min. The crude product was
transferred to a vial (3 mL) at reduced pressure. The radioactivity
was measured before and after the vial was flushed with nitrogen.
The identity of the crude product was determined by analytical LC
using a reference compound.
[3] a) M. R. Kilbourn, P. A. Jarabek, M. J. Welch, J. Chem. Soc.,
Chem. Commun. 1983, 861–862; b) S. K. Zeisler, M. Nader, A.
Theobald, F. Oberdorfer, Appl. Radiat. Isot. 1997, 48, 1091–
1095.
[
4] T. Kihlberg, B. Långström, “Method and Apparatus for Pro-
11
duction and Use of [ C]carbon monoxide in labelling synthe-
sis”, Swedish Pending Patent Application N. 0102174-0.
[
5] a) T. Kilhberg, B. Långström, J. Org. Chem. 1999, 64, 9201–
Compounds 1–5, 7, 8, 11, 12, 16 and 18 were analysed using the
9205; b) F. Karimi, B. Långström, J. Chem. Soc., Perkin Trans.
following HPLC method: Solvent A/B (70:30), linear gradient to
1
2002, 2111–2115; c) F. Karimi, B. Långström, Eur. J. Org.
–
1
0
:100 during 6 min, then 7 min at 100% B, flow 1.5 mLmin .
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Compounds 6, 9, 10, 13–15, 17 and 19 were analysed using the
following HPLC method: Solvent A/B (90:10), linear gradient to
–
1
0
:100 during 8 min, then 5 min at 100% B, flow 1.5 mLmin .
2256–2259; g) O. Rahman, T. Kihlberg, B. Långström, J. Chem.
Compound 20 was analysed using the following HPLC method:
Solvent C/B (95:5), isocratic at 5% B for 5 min, linear gradient to
Soc., Perkin Trans. 1 2002, 2699–2703; h) O. Rahman, T.
Kihlberg, B. Långström, J. Org. Chem. 2003, 68, 3558–3562; i)
T. Kilhberg, F. Karimi, B. Långström, J. Org. Chem. 2002, 67,
–
1
0
:100 during 8 min, then 1 min at 100% B, flow 1.5 mLmin .
(13
C)4Ј-Aminoacetophenone (6): Tris(dibenzylideneacetone)palla-
dium(0) (2.1 mg, 2.3 μmol), tri-o-tolylphosphane (16 mg,
2.6 μmol), 4-iodoaniline (23; 5 mg, 22.8 μmol) and tetramethyltin
140 μL, 1.01 mmol) were used. The reaction was performed as de-
3
687–3692.
6] Y. Andersson, B. Långström, J. Chem. Soc., Perkin Trans. 1
995, 287–289.
[
1
5
(
[7] P. Lidström, T. Kihlberg, B. Långström, J. Chem. Soc., Perkin
Trans. 1 1997, 2701–2706.
[8] J. Barletta, M. Björkman, M. Ögren, B. Langström, J. Labelled
Compd. Radiopharm. 2001, 44, S979–S980.
1
1
scribed before but the micro-autoclave was pre-charged with [ C]
carbon monoxide and ( C)carbon monoxide, and then heated at
20 °C for 25 min. 4Ј-Aminoacetophenone was purified using the
13
[
9] M. Nader, A. Theobald, S. K. Zeisler, S. K. Oberdorfer, J. Lab-
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1
following preparative HPLC method: solvent A/D (70:30), isocratic
at 30% B for 1 min, linear gradient to 0.100 during 7 min, then
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9
min at 100% D. The radioactive fraction was collected and evapo-
Org. Chem. 2004, manuscript accepted for publication.
11] H. E. Zaugg, J. Am. Chem. Soc. 1961, 83, 837.
rated under reduced pressure to yield the desired compound (89%).
[
13
CNMR (400 MHz, CDCl
3
): δ = 196.7 ppm.
[12] M. Suzuki, M. Björkman, Y. Andersson, B. Långström, Y. Wa-
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[
Acknowledgments
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[
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We thank the Swedish Research Council for financial support
grant K3464) for B.L.
1
(
[
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Chemistry, Vancouver, Canada, 1995, 282–284.
Received: December 14, 2004
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www.eurjoc.org
Eur. J. Org. Chem. 2005, 2374–2378