Palladium-catalysed synthesis of pyrimidines

Article abstract of DOI:10.3987/COM-05-10469

Satisfactory yields of 4-substituted pyrimidines and bicyclic pyrimidines are produced from α-methyl or α-methylene ketones when reacted with formamide and tetrakis(triphenylphosphine)palladium(0) or a 1:2 mixture of palladium(II) acetate and triphenylphosphine as catalysts. Under the same reaction conditions pyridines or imidazole are formed from 1,3- or 1,2-diketones.

Full text of DOI:10.3987/COM-05-10469

HETEROCYCLES, Vol. 65, No. 11, 2005
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HETEROCYCLES, Vol. 65, No. 11, 2005, pp. 2593 - 2603
Received, 2nd June, 2005, Accepted, 18th August, 2005, Published online, 19th August, 2005
PALLADIUM-CATALYSED SYNTHESIS OF PYRIMIDINES
a
b
a
Truls Ingebrigtsen, Irene Helland, and Tore Lejon *
a
Faculty of Science, Department of Chemistry, University of Tromsø, N-9037
b
Tromsø, Norway. Borealis AS, N-3960 Stathelle, Norway. E-mail:
tore.lejon@chem.uit.no
Abstract – Satisfactory yields of 4-substituted pyrimidines and bicyclic
pyrimidines are produced from α-methyl or α-methylene ketones when reacted
with formamide and tetrakis(triphenylphosphine)palladium(0) or a 1:2 mixture of
palladium(II) acetate and triphenylphosphine as catalysts. Under the same reaction
conditions pyridines or imidazole are formed from 1,3- or 1,2-diketones.
INTRODUCTION
Pyrimidines constitute an interesting group of naturally occurring diazines being found as pyrimidine and
purine bases in nucleic acids and in the vitamin thiamine. Already in 1963 a number of pyrimidines were
1
investigated with respect to their cytotoxic effect and since then important drugs e.g. the nucleoside
analogue AZT used in AIDS therapy, acyclovir used in treatment of herpes infections and the prodrug
capecitabine used in cancer therapy have been developed.
The intriguing properties and synthetic challenges of pyrimidines have fascinated chemists for a long time.
2
Indeed a synthesis of 4-phenylpyrimidine was reported more than a hundred years ago by Reich.
3
Unsurprisingly a multitude of synthetic methods have been developed since. Our interest stems from the
4
discovery that pyrimidine was produced as a by-product in the Leuckart synthesis (Scheme 1).
Scheme 1
CHO
+
CHO
O
HN
N
N
N
H NCHO
H NCHO
2
2
∆
∆
1
2b
3a
2
a
When optimizing the yield of the N-alkylformamide it was evident that the addition of water was
advantageous and consequently, when water was omitted, more pyrimidine was produced. This agrees well

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HETEROCYCLES, Vol. 65, No. 11, 2005
5
6
with the results of Wakamatsu et al. and Ochiai et al. who reported the synthesis of adenine under water
free conditions from hydrogen cyanide and formamide respectively. Based on all of the above observations,
together with the results showing that N-alkylformamide (2b) when treated with formamide did not
produce any pyrimidine, we propose that four reactions are involved in the process (eqs. 1 – 4).
CHO
O
N
H NCHO
H O
+
+
2
+
(1)
(2)
2
Ph
Ph
-
+
H O
H NCHO
HCO NH
2
2
2
4
CHO
CHO
CHO
N
HN
Ph
-
+
+
+
HCO NH
(3)
(4)
2
4
Ph
N
N
N
H NCHO
2 H O
2
+
2
Ph
Ph
Based on this hypothesis three different approaches can be employed in order to increase the yield of
pyrimidine; (i) removal water formed in the reaction and thus inhibiting formation of ammonium formate,
(
eq. 2), (ii) increasing the rate of reaction between initially formed N-alkylideneformamide (2a) and
formamide, making the amount of water found in the reaction mixture of minor importance (eq. 4) or (iii)
removal of ammonium formate produced in the reaction, thus inhibiting the competing formation of
N-alkylformamide (2b) (eq. 3). Attempts to remove water from the reaction mixture by drying agents such
as molecular sieves or sodium carbonate failed, probably due to the high temperatures needed for the
condensation. As a result a number of oxidizing agents were instead scanned in order to create sufficiently
oxidizing conditions to prevent reduction of the intermediate N-alkylideneformamide (2a) to
N-alkylformamide (2b). Utilizing cuprous chloride and molecular oxygen in the absence or presence of
7
8
1
,10-phenanthroline, an oxidizing system described by Marco et al., seemed to solve this problem.
However, yields were not satisfactory, large amounts of catalyst were needed and reactions only took place
at high temperatures. We determined therefore to reinvestigate the reaction.
The fact that formic acid and formates can be employed in catalytic hydrogen transfer hydrogenations
9
10
11
catalysed by Pd/C, Raney Ni or magnesium led us to look for a suitable catalytic system that could
assist in removing ammonium formate formed in the reaction. Akazome et al. have reported the
condensation of formamide with 2-nitrophenyl ketones by a palladium(II) chloride and triphenylphosphine
1
2
13
catalyst together with a co-catalyst. Furthermore, reports by Rajagopal and Spatola show that α-chloro-

HETEROCYCLES, Vol. 65, No. 11, 2005
2595
1
4
toluene can be hydrodehalogenated by formates with Pd/C catalysis and papers by Amatore et al. report
the activation of aryl iodides by palladium(II) acetate/triphenylphosphine. Consequently, we decided to
investigate palladium catalysis with iodobenzene as the hydrogen acceptor.
RESULTS AND DISCUSSION
The first successful homogenous catalyst employed was tetrakis(triphenylphosphine)palladium(0)
resulting in 68% of 4-phenylpyrimidine (Table 1). The yield was higher than that in the case of cuprous
o
o
chloride catalysis and the temperature could be lowered from 180 C to 160 C. However, high
temperatures were still necessary and we interpret this as the catalyst is not interacting with the actual
formation of the N-alkylideneformamide or the pyrimidine but instead acts as hydrogen transfer catalyst
(
Scheme 2).
Scheme 2
NH HCO
CO2
4
2
Pd0
Ph
I
Ph Pd I
NH I + Ph Pd H
Pd
0
+ Ph
H
4
This is in agreement with the reports stating that palladium(II) acetate/triphenylphosphine results in a Pd(0)
14
catalyst that activates iodobenzene and that formates are donating hydride to palladium followed by
1
3, 15
reduction of the hydrogen acceptor.
Other methyl ketones also reacted under the same reaction
conditions, e.g. methyl cyclohexyl ketone (1b), indicating that the reaction is not limited only to aromatic
1
6
ketones as has earlier been reported. Moreover, cyclic ketones, e.g. α-tetralone (1c), also gave bicyclic
product proving that a methylene functionality was tolerated. Since rigid ketones such as cycloheptanone
(
1d) reacted analogously it was surprising that cyclopentanone (1e) only gave small amounts of the
expected product. We therefore wanted to investigate other palladium catalysts in order to see if yields
could be improved and began by employing palladium(II) acetate together with triphenylphosphine. Under
these changed conditions the yield of 6,7-dihydro-5H-cyclopentapyrimidine (3e) increased to 51% and a
number of other ketones were thus investigated under the same conditions giving pyrimidines in 22 - 82%
yield (Table 1). It was also found that reactions could be performed at somewhat lower temperatures than
with the previous protocol and with lower loadings of catalyst. However, the prolonged reaction time
combined with the sensitivity of the catalyst, sometimes causing the reaction to stop, led to our continuing
with the previous conditions. As it seemed that there was no pronounced difference in the yield, whether a
methyl- or a methylene group was situated at one side of the ketone, it was decided to investigate the
regioselectivity of the reaction by reacting 2-acetyl cyclohexanone (4a) with formamide and palladium
acetate catalysis. To our surprise it was neither of the expected products that were formed, but instead the

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HETEROCYCLES, Vol. 65, No. 11, 2005
4
-methyl-5,6,7,8-tetrahydroquinazoline (5a) was found as the main product in 58% yield (Table 2). The
stoichiometry of the reaction implies that one equivalent of formamide and one equivalent of ammonia
have reacted with the ketone and three equivalents of water have been expelled. Bredereck and co-workers
have reported the same reaction, although in lower yield, proposing that the reaction proceeds through a
1
7
β-ketoimine intermediate. A similar reaction has also been reported by Miller et al. where bis-(α-bromo
18
ketones) gave imidazoles when reacted with formamide at elevated temperatures. However, the reaction
of acetylacetone (4b) only gave traces of the symmetrical dimethylpyrimidine in some experiments and
instead resulted in the formation of 1-(2,4,6-trimethylpyridin-3-yl)ethanone (5b).
Table 1. Isolated yield of products using different catalytic systems.
Ketone
Product
Pd(PPh
3
)
4
Pd(OAc)
2 3
/ PPh
O
N
N
6
5
4
4
8 %
0 %
7 %
6 %
80 %
1
1
a
3a
O
N
N
N
60 %
82 %
54 %
51 %
54 %
b
3b
3c
3d
3e
3f
O
N
1
1
1
1
1
c
d
e
f
O
N
N
N
O
N
<
-
5 %
O
N
N
O
N
N
a
-
22 %
g
3g
a
Starting material was recovered in 50% yield

HETEROCYCLES, Vol. 65, No. 11, 2005
2597
Other diketones with varying distance between the keto functionalities were also investigated, but results
were not very encouraging except for the reaction of benzil (4c) that resulted in the formation of
triphenylimidazole (5c) in 25% yield. The product is believed to be formed by a Heck coupling to
intermediately formed diphenylimidazole (Scheme 3).
Table 2. Isolated yield of products from reaction of diketones.
Ketone
Product
2 3
Pd(OAc) / PPh
O
O
N
N
5
5
2
8 %
0 %
5 %
4
4
a
5a
O
O
O
N
b
5
b
H
N
O
Ph
Ph
O
N
Ph
4
c
5c
Scheme 3
Ph
O
H NCHO
2
HN
Ph
N
PhI
Pd"
Ph
HN
Ph
N
Ph
"
O
Ph
Ph
4
c
5
c
In view of the above results the reaction of cyclopentanone (1e) was re-examined. The resulting pyrimidine
from reaction of cyclopentanone was isolated from the reaction mixture by chromatography on silica, but in
order to obtain an analytically pure sample it was necessary to use HPLC. This also gave a new compound
that according to mass spectral analysis and NMR spectroscopy was the tricyclic pyrimidine (6), in 14%
1
9
yield which was later confirmed by X-Ray crystallography (Figure 1).

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HETEROCYCLES, Vol. 65, No. 11, 2005
An explanation for this may be that the aldol product is formed followed by condensation with
formaldehyde (Scheme 4). Similarly, the reactions between formamide and cyclohexanone (1f) or
cycloheptanone (1d) gave tricyclic pyridines and work is in progress in investigating this reaction in more
detail. It should however be noted that simple α,β-unsaturated ketones, e.g. cyclopentenone and
cyclohexenone did not give any expected product.
Figure 1. X-Ray structure of trifluoroacetic acid salt of
1
9
1
,2,3,6,7,8-hexahydrodicyclopenta[b,d]pyridine (6).
C19
C110
F12
C18
C17
O11
F17
F13
C111
C113
F11
N11
C112
C16
C11
F15
C12
F16
C15
O12
F14
C14
C13
Scheme 4
O
O
N
H+
H NCHO
2
1e
6
In our experience a limitation to the method is that only traces of pyrimidine have been detected when
subjecting aldehydes or less rigid ketones to the same reaction conditions. Also, employing other nitrogen
containing moieties such as benzonitrile did not yield any product similar to that what was reported by
2
0
Herrera et al.
EXPERIMENTAL
Cycloheptanone (>99%) and 4-phenylpyrimidine (>96%) were supplied by Aldrich, 2-acetylnaphthalene
(
>99%) was supplied by EGA Chemie and formamide (>99%) was supplied by Merck. All other chemicals
were supplied by Fluka and were of minimum 99% purity except for, 2-acetylcyclohexanone (>97%),
palladium(II) acetate (purum), triphenylphosphine(>97%), α-tetralone (>95%). All chemicals were used as

HETEROCYCLES, Vol. 65, No. 11, 2005
2599
delivered. Melting points were measured on a Büchi 535. GC analyses were performed on a Varian 3300
gas chromatograph equipped with a Supelco Equity-5 (30 m, 0.25 mm i.d.) column. IR spectra were
recorded on a Perkin Elmer model 1600 FT-IR. NMR spectra were recorded on a Varian Mercury 400 plus
(
3
399.65 /100.54 MHz) spectrometer with CDCl as solvent. MS analyses were performed on a VG Quatro
mass spectrometer connected to a Hewlett Packard 5890 gas chromatograph equipped with an Agilent
HP-5 (30 m, 0.25mm i.d.) column. Compounds (3d) and (3e) were purified by preparative reversed phase
high performance liquid chromatography (RP-HPLC) using a C18-column (Delta-Pak™ C18, 100 Å, 15 µm,
2
5 x 100 mm, Waters Corp., Milford, MA, USA) with a mixture of water and acetonitrile (both containing
.1% v/v trifluoroacetic acid) as the mobile phase, a flow rate of 7.0 mL/min and UV-detection at 254 nm.
0
A linear gradient varying from 10% to 30% acetonitrile in 30 min effected separation and fractions
containing the pure (3d) and (3e) were pooled and the solvent was removed under reduced pressure. The
TFA-salt of (3d), (3e) and (6) were diluted with a 10% sodium hydrogen carbonate solution and extracted
into an ether phase, dried over magnesium sulfate before solvent removal under reduced pressure.
General procedure
To a round bottomed flask charged with palladium(II) acetate (40 mg, 0.18 mmol) and triphenylphosphine
(
(
95 mg, 0.36 mmol) were added formamide (5.0 g, 110 mmol), iodobenzene (2.0 g, 10 mmol) and ketone
3.6 mmol) and the resulting mixture was heated at 160 ºC for 8 hrs. The reaction mixture was diluted with
ether (50 mL) and extracted with three 25 mL portions of a 2M aqueous solution of hydrogen chloride. The
combined aqueous phase was basified by addition of solid sodium hydroxide or a 4M aqueous solution of
sodium hydroxide. The combined layers were extracted with ether (2 x 50 mL) and washed with water and
brine before drying over sodium carbonate. The solvent was removed under vacuum to give the clean
crude yield. Analytically pure samples were obtained by flash chromatography with ethyl acetate or
dichlormethane:methanol (19:1) except for compounds (3d) and (3e) which were purified by RP-HPLC.
4
-Phenylpyrimidine (3a)
Isolated as slightly discolored white crystals (530mg, 80 %), with spectral properties as for commercial
material.
4
-Cyclohexylpyrimidine (3b)
Isolated as a slightly brown oil (320 mg, 60%), IR and MS spectra in accordance with earlier reported
21 1
3
material. H NMR (400 MHz, CDCl , δ, ppm): 9.12 (1H, s), 8.61 (1H, d, J = 4.8 Hz), 7.18 (1H, dd, J = 1.0,
1
3
5
.0 Hz), 2.66 (1H, m), 1.95 (2H, m), 1.88 (2H, m), 1.77 (1H, m), 1.46 (4H, m), 1.30 (1H, m); C NMR (100
3
MHz, CDCl , δ, ppm): 174.62, 158.61, 156.86, 118.87, 45.97, 32.06, 26.22, 25.87

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HETEROCYCLES, Vol. 65, No. 11, 2005
5
,6-Dihydrobenzo[h]quinazoline (3c)
22
Isolated as a light yellow crystals (530 mg, 82%); mp 47-49 ºC (from ethyl acetate) lit., 54-55 ºC; MS
(
m/z): 183 (25), 182 (88), 181 (100), 180 (14), 179 (5), 155 (12), 154 (57), 153 (11), 152 (7), 140 (6), 129
6), 128(37), 127(65), 126(36), 117 (8), 116 (11), 102 (8), 101 (7), 90 (6), 89 (12), 78 (8), 77 (27), 76 (13),
(
1
20
7
3
5(13), 74 (9), 64(27), 63 (23), 62 (6), 52 (6), 51 (19), 50 (9); H NMR (400 MHz, CDCl , δ, ppm): 9.13
13
(
1H, s), 8.56 (1H, s), 8.36 (1H, m), 7.42 (2H, m), 7.27 (1H, m), 2.97 (4H, m); C NMR (100 MHz, CDCl
3
,
δ, ppm): 159.32, 157.48, 155.39, 139.23, 132.19, 131.32, 128.40, 128.21, 127.47, 125.56, 27.35, 24.50; IR
-1
19
(
film ν, cm ): 3052, 2983, 1576, 1544, 1446, 1423, 1397, 750; X-Ray.
6
,7,8,9-Tetrahydro-5H-cycloheptapyrimidine (3d)
1
Isolated as a yellow oil (280 mg, 54%). H NMR spectrum in accordance with that of earlier reported
21
material. A pure sample was prepared by RP-HPLC (t 19.8 min); MS: (m/z) 149 (12), 148 (100), 147
R
(
44), 134(4), 133(38), 131(8), 121 (7), 120 (28), 119 (63), 118 (5), 94 (11), 93 (9), 92 (15), 91 (12), 81 (9),
0 (41), 79 (35), 78 (12), 77 (19), 67 (16), 66 (29), 65 (47), 64 (13), 63 (16), 54 (12), 53 (27), 52 (39), 51
8
13
(
3
28), 50 (11); C NMR (100 MHz, CDCl , δ, ppm): 171.36, 156.40, 155.52, 135.56, 39.08, 32.35, 31.96,
-1
2
7.48, 25.79; IR (film ν, cm ): 2922, 2851, 1572, 1552, 1450, 1397, 1159, 958, 919, 779, 718.
6
,7-Dihydro-5H-cyclopentapyrimidine (3e)
2
1
Isolatedasayellowoil(240mg, 51%). A pure sample was prepared by RP-HPLC (t 9.4 min); MS (m/z):
R
1
1
21 (11), 120 (100), 119 (71), 94 (3), 93 (28), 92 (20), 80 (8), 67 (8), 66 (36), 65 (31), 64 (14), 63 (14); H
1
3
3
NMR (400 MHz, CDCl , δ, ppm): 8.97 (1H, s), 8.53 (1H, s), 3.00 (4H, m), 2.16 (2H, m); C NMR (100
-1
MHz, CDCl , δ, ppm): 174.78, 156.93, 151.99, 135.00, 34.09, 28.41, 22.48; IR (film ν, cm ): 3037, 2956,
3
1
590, 1557, 1454, 1393, 732.
5
,6,7,8-Tetrahydroquinazoline (3f)
2
1
Isolated as a slightly yellow oil (260 mg, 54%). MS (m/z): 135 (14), 134 (100), 133 (46), 119 (13), 107
1
(
19), 106 (20), 105 (8), 92 (6), 80 (38), 79 (33), 78 (9), 77 (16), 66 (7), 66 (7); H NMR (400 MHz, CDCl
3
,
δ, ppm):8.89(1H, s), 8.37 (1H, s), 2.85 (2H, t, J = 6.9 Hz), 2.73 (2H, t, J = 6.3 Hz), 1.89 (2H, m), 1.82 (2H,
1
3
m); CNMR (100 MHz, CDCl
3
, δ, ppm): 165.93, 156.80, 156.0, 130.34, 31.78, 25.57, 22.13, 21.97; IR
-1
(
film ν, cm ): 3028, 2936, 2861, 1579, 1553, 1454, 1453, 1396, 726.
4
-Naphthalen-2-ylpyrimidine (3g)
Isolated as white crystals (160 mg, 22%); mp 122.5-124 ºC (from ethyl acetate); MS (m/z): 207 (17), 206
100), 205 (20), 180 (3), 179 (13), 178 (9), 177 (3), 154 (3), 153 (9), 152 (19), 151 (10), 150 (4), 127 (6),
(

HETEROCYCLES, Vol. 65, No. 11, 2005
2601
1
1
25(6), 103(8), 89(6), 77(3), 76 (8), 75 (5); H NMR (400 MHz, CDCl , δ, ppm): 9.37 (1H, d, J = 1.2 Hz),
3
8
.85(1H, d, J = 5.2Hz), 8.68 (1H, d, J = 2.0 Hz), 8.22 (1H, dd, J = 1.8, 8.6 Hz), 8.02 (2H, m), 7.93 (2H, m),
1
3
7
.61 (2H, m); C NMR (100 MHz, CDCl
29.10, 128.94, 127.82, 127.63, 127.60, 126.79, 123.78, 117.28; IR (film ν, cm ): 3052, 2984, 1577, 1421,
389, 895; Anal. Calcd for C14 : C, 81.53; H, 4.89; N, 13.58. Found: C, 79.80; H, 4.96; N, 13.19;
3
, δ, ppm): 163.85, 159.20, 157.56, 134.69, 133.74, 133.27,
-1
1
1
10 2
H N
1
9
X-Ray.
4
-Methyl-5,6,7,8-tetrahydroquinazoline (5a)
Isolated as red-brown crystals (290 mg, 58%); mp 56-60 ºC (from ethyl acetate); MS (m/z): 149 (24), 148
(
(
(
100), 147(72), 145(8), 133(33), 132 (6), 121 (8), 120 (48), 119 (8), 108 (9), 107 (48), 106 (16), 95 (6), 94
38), 93 (22), 91 (6), 81 (42), 80 (42), 79 (66), 78 (16), 77 (36), 68 (6), 67 (11), 66 (14), 65 (15), 64 (6), 63
1
8), 54 (8), 53 (29), 52 (50), 51 (29), 50 (12); H NMR (400 MHz, CDCl , δ, ppm): 8.84 (1H, s), 2.92 (2H,
3
1
3
s), 2.70 (2H, s), 2.48 (3H, s), 1.91 (4H, m); C NMR (100 MHz, CDCl
3
, δ, ppm): 165.35, 164.94, 154.52,
28.76, 32.10, 24.97, 22.26, 21.96, 21.42; IR (film ν, cm ): 3048, 2938, 1566, 1424, 1264, 739; Anal.
Calcd for C : C, 72.94; H, 8.16; N, 18.90. Found: C, 72.62; H, 8.37; N, 18.49.
-1
1
9
12 2
H N
1
-(2,4,6-Trimethylpyridin-3-yl)ethanone (5b)
Isolatedas yellowoil (203 mg, 50%);MS (m/z): 164 (11), 163 (72), 149 (23), 148 (100), 121 (19), 120 (93),
1
4
18 (6), 104 (5), 93 (24), 91 (16), 80 (6), 79 (32), 78 (51), 65 (11), 63 (9), 53 (19), 52 (12), 51 (19), 50 (6),
1
3(26); H NMR(400MHz, CDCl
3
, δ, ppm):6.28 (1H, s), 2.48 (3H, s), 2.46 (3H, s), 2.42 (3H, s), 2.19 (3H,
1
3
s); C NMR (100 MHz, CDCl
3
, δ, ppm): 206.59, 157.74, 151.66, 142.64, 135.04, 122.34, 32.19, 24.10,
-1
2
2.43, 18.78; IR (film ν, cm ): 2960, 2922, 1696, 1590, 1443, 1383, 1256, 1184; Anal. Calcd for
13NO: C, 73.59; H, 8.03; N, 8.58; O, 9.80. Found: C, 68.79; H, 6.96; N, 8.80; O, 15.44.
10
C H
2
,4,5-Triphenyl-1H-imidazole (5c)
23
Isolated as white crystals (210 mg, 25%) with spectral data similar to earlier reported material.
1
,2,3,6,7,8-Hexahydrobicyclopenta[b,d]pyridine (6)
The compound was found as a by-product in the synthesis of 3e and was purified by RP-HPLC (t
R
16.6
min). Isolated as a colorless oil (36 mg, 14%) after treatment with sodium hydrogen carbonate; MS (m/z):
1
1
60 (9), 159 (72), 158 (100), 157 (6), 156 (10), 143 (5), 131 (13), 130 (19), 117 (5), 115 (5) 77 (10); H
13
3
NMR (400 MHz, CDCl , δ, ppm): 8.21 (1H, s), 3.0-2.77 (8H, m), 2.16-2.05 (4H, m); C NMR (100 MHz,
CDCl
3
, δ, ppm): 163.33, 149.82, 143.44, 137.82, 133.11, 34.23, 31.42, 30.49, 29.48, 25.50, 23.48; X-Ray
1
9
of TFA-salt.

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HETEROCYCLES, Vol. 65, No. 11, 2005
ACKNOWLEDGEMENTS
Professor Lars Kristian Hansen is gratefully acknowledged for the X-Ray analysis and Frederick Leeson
for linguistic assistance.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
H. M. Rauen and R. Nonhof, Arzneimittel-Forschung, 1963, 13, 558.
M. Reich, Monatsh. Chem., 1904, 966.
For a comprehensive review see e.g. S. von Angerer, Methods of Synthesis, 2004, 16, 379.
R. Carlson, T. Lejon, T. Lundstedt, and E. Le Clouérec, Acta Chem. Scand., 1993, 47, 1046.
H. Wakamatsu, Y. Yamada, T. Saito, I. Kumashiro, and T. Takenishi, J. Org. Chem., 1966, 31, 2035.
M. Ochiai, R. Marumoto, S. Kobayashi, H. Shimazu, and K. Morita, Tetrahedron, 1968, 24, 5731.
a. I. E. Marko, A. Gautier, I. Chelle-Regnaut, P. R. Giles, M. Tsukazaki, C. J. Urch, and S. M. Brown,
J. Org. Chem., 1998, 63, 7576, b. I. E. Marko, P. R. Giles, M. Tsukazaki, I. Chelle-Regnaut, A.
Gautier, S. M. Brown, and C. J. Urch, J. Org. Chem. 1999, 64, 2433.
8
9
1
1
1
1
.
I. Helland and T. Lejon, Heterocycles, 1999, 51, 611.
.
P. Haldar and V. V. Mahajani, Chem. Eng. J. 2004, 104, 27.
0. B. K. Banik, K. J. Barakat, D. R. Wagle, M. S.Manhas, and A. K. Bose, J. Org. Chem. 1999, 64, 5746.
1. K. Abiraj and D. C. Gowda, Syn. Comm., 2004, 34, 599.
2. M. Akazome, J. Yamamoto, T. Kondo and Y. Watanabe, J. Organomet. Chem. 1995, 494, 229.
3. a. S. Rajagopal and A. F. Spatola, Applied Catalysis, A: General, 1997, 152, 69, b. S. Rajagopal and
A. F. Spatola, J. Org. Chem., 1995, 60, 1347.
1
4. a. C. Amatore, E. Carre, A. Jutand, M. A. M'Barki, and G. Meyer, Organometallics, 1995, 14, 5605,
b. C. Amatore, A. Jutand, F. Khalil, M. A. M'Barki, and L. Mottier, Organometallics, 1993, 12, 3168.
5. M. L. S. Cristiano, R. A. W. Johnstone, and P. J. Price, J. Chem. Soc., Perkin Trans. 1, 1996, 1453.
6. A. E. A. Porter, in Comprehensive Organic Chemistry, Vol. 4; Heterocyclic compounds, ed. by P. G.
Sammes, Pergamon Press, 1979, pp. 92-93.
1
1
1
1
1
7. H. Bredereck, R. Gompper, and G. Morlock, Chem. Ber., 1957, 90, 942.
8. B. Miller, J. Altman, and W. Beck, Synthesis, 1997, 347.
9. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as
supplementary publications CCDC 273297 (3c), CCDC 273295 (3g) and CCDC 273296 (6). Copies
of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2
1
EZ, UK (Fax: (+44) 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk).
2
0. A. Herrera, R. Martinez-Alvarez, R. Chioua, and M. Chioua, Tetrahedron Let., 2003, 44, 2149.

HETEROCYCLES, Vol. 65, No. 11, 2005
2603
2
2
2
1. D. L. Boger, J. Schumacher, M. D. Mullican, M. Patel, and J. S. Panek, J. Org. Chem., 1982, 47, 2673.
2. R. M. Wagner and C. Jutz, Chem. Ber., 1971, 104, 2975.
3. C.-H. Chou, L.-T. Chu, S.-J. Chiu, C.-F. Lee, and Y.-T. She, Tetrahedron, 2004, 60, 6581.