New three-component glyoxylation-decarbonylative stille coupling sequence to Acyl heterocycles under mild conditions

Article abstract of DOI:10.1055/s-0029-1218802

A consecutive sequence of glyoxylation of 1-methyl-1H-indole, 1-(4-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine or N-substituted pyrroles with oxalyl chloride and subsequent decarbonylative Stille coupling under very mild, Lewis acid free conditions using all reactants in equimolar quantities is reported. As an illustration, this glyoxylation-decarbonylative coupling sequence was elaborated into a consecutive, four-component synthesis of 1-methyl-3-(1-methyl-4,5-dihydro-1H-pyrazol-3-yl)-1H-indole. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218802

PAPER
2139
New Three-Component Glyoxylation–Decarbonylative Stille Coupling
Sequence to Acyl Heterocycles under Mild Conditions
G
lyoxylation–D
e
o
carbonylativ
r
e
Stille
C
i
ouplin
s
gSequenc
e
O. A. Tasch,a Eugen Merkul,a Walter Frank,b Thomas J. J. Müller*a
a
Heinrich-Heine-Universität Düsseldorf, Institut für Organische Chemie und Makromolekulare Chemie, Universitätsstr. 1,
40225 Düsseldorf, Germany
b
Heinrich-Heine-Universität Düsseldorf, Institut für Anorganische Chemie und Strukturchemie, Universitätsstr. 1, 40225 Düsseldorf,
Germany
Fax +49(211)8114324; E-mail: ThomasJJ.Mueller@uni-duesseldorf.de
Received 15 April 2010
Dedicated to Prof. Dr. Dr. h.c. mult. Rolf Huisgen on the occasion of his 90th birthday
as an easy-to-handle carbon monoxide surrogate. In a one-
Abstract: A consecutive sequence of glyoxylation of 1-methyl-1H-
indole, 1-(4-methoxybenzyl)-1H-pyrrolo[2,3-b]pyridine or N-sub-
stituted pyrroles with oxalyl chloride and subsequent decarbonyla-
tive Stille coupling under very mild, Lewis acid free conditions
pot sequence of Friedel–Crafts acylation of electron-rich
heterocycles with oxalyl chloride (glyoxylation), fol-
lowed by decarbonylative Sonogashira coupling,
using all reactants in equimolar quantities is reported. As an illus- alkynones are obtained in good to excellent yields under
tration, this glyoxylation–decarbonylative coupling sequence was
mild conditions.
elaborated into a consecutive, four-component synthesis of 1-meth-
yl-3-(1-methyl-4,5-dihydro-1H-pyrazol-3-yl)-1H-indole.
The Stille reaction is known to proceed under mild reac-
tion conditions with high tolerance for many functional
Key words: glyoxylation, decarbonylative Stille reaction, multi-
component reaction, C–C coupling, acyl heterocycles
groups. Moreover, Stille couplings of acid chlorides are
well precedented.8 In addition, a-oxo acid chlorides have
been successfully applied in the synthesis of 1,2-dike-
tones.9 Here, we report an extension of the glyoxylation–
The selective formation of unsymmetrical ketones by
decarbonylative coupling methodology in which we have
cross-coupling reactions is of significant interest in organ-
devised a consecutive three-component synthesis of ke-
ic chemistry.1 Therefore, many different ways to intro-
tones by a glyoxylation–decarbonylative Stille coupling
duce the carbonyl group have been developed. Besides the
sequence using electron-rich heterocycles, oxalyl chloride
well-established Friedel–Crafts-type acylations,2 cross-
and organostannanes.
coupling reactions have been introduced as catalytic alter-
First, we tested the glyoxylation–decarbonylative Stille
coupling of 1-methyl-1H-indole (1) with tributyl(phenyl-
ethynyl)stannane (2a) and tributyl(thiophen-2-yl)stan-
nane (2b) via the in situ generated indole-3-glyoxylyl
chloride, which gives rise to the formation of the N-meth-
ylindolyl ketones 3 (Scheme 1, Table 1).
natives. Most of the methods directly start from acid chlo-
rides due to their easy availability. In cases where the acid
chlorides are either not readily available or difficult to
handle, cross coupling cannot prevail. An obvious solu-
tion to this problem are carbonylative cross-coupling re-
actions starting from aryl halides and carbon monoxide3
or other carbon monoxide sources such as molybdenum
hexacarbonyl.4 Although mild carbonylations utilizing
carbon monoxide at ambient pressure have been reported,
the effective concentration of carbon monoxide in the re-
action mixture is of crucial importance for full conversion
and still represents a limitation of the method. Alterna-
tively, decarbonylative cross coupling of a-dicarbonyl
compounds can be considered. In particular, catalytic de-
carbonylations are highly desirable and have recently re-
ceived considerable attention. For instance, palladium-
catalyzed decarbonylative carbostannylations under mild
conditions5 and decarbonylative Heck reactions6 at high
temperatures and long reaction times have been reported.
O
R1
(COCl)2 (1.0 equiv)
THF, 0 °C to r.t., 4 h
then: [Pd]
Bu3SnR1 2 (1.0 equiv)
Et3N, conditions
N
N
Me
Me
3a R1 = C CPh
1
3b R1 = thiophen-2-yl
Scheme 1 Optimization of the glyoxylation–decarbonylative Stille
coupling of 1-methyl-1H-indole (1) with stannanes 2
By applying 1 mol% of the air-stable precatalyst
PdCl2(PPh3)2, a 36% yield of the desired product 3a could
be isolated (Table 1, entry 1). One equivalent of triethyl-
amine is stoichiometrically necessary to scavenge the hy-
drochloric acid generated in the glyoxylation step.
Interestingly, addition of a second equivalent of triethyl-
amine suppresses the formation of the non-decarbonylat-
ed byproduct (as detected by TLC) and also leads to an
increase in the overall yield (Table 1, entries 2 and 3). In
Recently, we established
a
new decarbonylative
Sonogashira coupling of glyoxylyl chlorides,7 which are
in situ generated at room temperature from oxalyl chloride
SYNTHESIS 2010, No. 13, pp 2139–2146
x
x.
x
x
.
2
0
1
0
Advanced online publication: 27.05.2010
DOI: 10.1055/s-0029-1218802; Art ID: C01410SS
© Georg Thieme Verlag Stuttgart · New York

2140
B. O. A. Tasch et al.
PAPER
the absence of triethylamine, the formation of the desired sionally been known to hamper the isolation of pure reac-
product 3b cannot be detected by TLC (Table 1, entry 8). tion products. Besides trituration of the flash-
It is known that the addition of copper iodide often in- chromatographed product in n-pentane under sonication
creases the yield in Stille coupling reactions (‘copper ef- in an ultrasound bath, neither removal of tin residues by
fect’).10 Indeed, with stannane 2a as a substrate, the fluoridation with aqueous potassium fluoride solution or
‘copper effect’ could be confirmed (Table 1, entry 4); tetrabutylammonium fluoride,11 nor flash chromatogra-
however, with tributyl(thiophen-2-yl)stannane (2b), the phy on silica gel containing potassium fluoride (10:1),12
addition of copper iodide did not exert any effect (Table 1, furnished completely organotin-free products. The best
entries 5 and 6). Presumably, in the case of the coupling workup protocol is to stir the reaction mixture after the de-
with tributyl(phenylethynyl)stannane (2a) in the presence carbonylative Stille coupling step with an excess of potas-
of copper iodide, transmetalation produces a copper sium hydroxide in methanol13 overnight at room
acetylide for a terminating Sonogashira coupling. As a temperature, followed by aqueous workup, to obtain an
consequence, tributyl(thiophen-2-yl)stannane (2b) was essentially tin-free product.
chosen as the model stannane for further optimization of
the decarbonylative Stille coupling (Table 1, entries 7–
15). After 20 hours at room temperature, the decarbonyla-
tive Stille coupling was essentially complete (Table 1, en-
try 7). A rapid precatalyst screening revealed that none of
the other precursors gave a higher yield of 3b than
PdCl2(PPh3)2 (Table 1, entries 9–12). Upon stirring the
With this convenient method in hand and starting from 1-
methyl-1H-indole (1), 1-(4-methoxybenzyl)-1H-pyrro-
lo[2,3-b]pyridine (4) or the N-substituted pyrroles 6 and 8,
the glyoxylation–decarbonylative Stille coupling se-
quence furnished various acyl heterocycles 3, 5, 7 and 9 in
moderate to good yields (Scheme 2, Table 2).
The structures of compounds 3, 5, 7 and 9 were unambig-
mixture at 60 °C, complete conversion was achieved
uously supported by NMR spectroscopy, mass spectrom-
within one hour (Table 1, entry 13). The coupling without
etry and combustion analysis, and later corroborated by an
X-ray crystal structure analysis of compound 3b
(Figure 1).14
decarbonylation9 was attempted under palladium-free
conditions (Table 1, entry 14) and with copper iodide
(Table 1, entry 15), but the TLC control showed no con-
version, even after 20 hours.
For the indole derivatives, 1-methyl-1H-indole (1) and 7-
azaindole 4, the glyoxylation occurs at the most electron-
rich 3-position (Table 2, entries 1–7). The N-substituted
Despite the general smoothness of the Stille reaction, the
separation of organotin residues during workup has occa-
Table 1 Optimization of the Decarbonylative Stille Coupling Step of 1-Methyl-1H-indole (1) with Stannanes 2a and 2ba
Entry
1
Catalyst system
Conditions
Ketone 3 (% isolated yield)
3a (36b)
3a (43b)
3a (52)
PdCl2(PPh3)2 (1 mol%)
PdCl2(PPh3)2 (5 mol%)
PdCl2(PPh3)2 (5 mol%)
PdCl2(PPh3)2 (5 mol%), CuI (5 mol%)
PdCl2(PPh3)2 (5 mol%)
PdCl2(PPh3)2 (5 mol%), CuI (5 mol%)
PdCl2(PPh3)2 (5 mol%)
PdCl2(PPh3)2 (5 mol%)
PdCl2 (5 mol%)
2a (1.0 equiv), Et3N (1.0 equiv), r.t., 1 h
2a (1.0 equiv), Et3N (1.0 equiv), r.t., 1 h
2a (1.0 equiv), Et3N (2.0 equiv), r.t., 1 h
2a (1.0 equiv), Et3N (2.0 equiv), r.t., 1 h
2b (1.0 equiv), Et3N (2.0 equiv), r.t., 1 h
2b (1.0 equiv), Et3N (2.0 equiv), r.t., 1 h
2b (1.0 equiv), Et3N (2.0 equiv), r.t., 20 h
2b (1.0 equiv), r.t., 20 h
2
3
4
3a (67)
5
3b (15)
6
3b (16)
7
3b (69)
8
3b (–c)
9
2b (1.0 equiv), Et3N (2.0 equiv), r.t., 20 h
2b (1.0 equiv), Et3N (2.0 equiv), r.t., 20 h
2b (1.0 equiv), Et3N (2.0 equiv), r.t., 20 h
2b (1.0 equiv), Et3N (2.0 equiv), 60 °C, 1 h
2b (1.0 equiv), Et3N (2.0 equiv), 60 °C, 1 h
2b (1.0 equiv), Et3N (2.0 equiv), 60 °C, 20 h
2b (1.0 equiv), Et3N (2.0 equiv), 60 °C, 20 h
3b (77d)
3b (–c)
10
11
12
13
14
15
Pd/C (5 mol%), Ph3P (10 mol%)
Pd(PPh3)4 (5 mol%)
3b (23)
PdCl2dppf (5 mol%)
PdCl2(PPh3)2 (5 mol%)
–
3b (–c)
3b (81)
3b (–c)
CuI (5 mol%)
3b (–c)
a See Scheme 1. The reactions were performed on a 5.00 mmol scale in THF [c(1) = 0.2 M].
b TLC indicated the formation of the non-decarbonylated product as a byproduct.
c The formation of the desired product could not be detected by TLC.
d The crude reaction mixture was contaminated with a polar byproduct.
Synthesis 2010, No. 13, 2139–2146 © Thieme Stuttgart · New York

PAPER
Glyoxylation–Decarbonylative Stille Coupling Sequence
2141
O
7a (Table 2, entries 1 and 8). Interestingly, with tribu-
tyl(vinyl)stannane (2e), enones such as 3e and 9 can be
prepared in a one-pot fashion as highly reactive Michael
systems (Table 2, entries 5 and 12). Upon extending the
reaction time to 20 hours, the yield for the sequence with
1-methyl-1H-indole (1) and tributyl(phenyl)stannane (2f)
could be increased from 16% to 68% of 3f (Table 2, entry
6); however, in the case of stannane 2e, an extension of the
reaction time to 20 hours brought no significant increase
in the yield (Table 2, entry 5).
R1
(COCl)2 (1.0 equiv)
THF, 0 °C to r.t., 4 h
or DME, 0 °C to 100 °C, 2 h
then:
N
R2
N
X
X
PdCl2(PPh3)2 (5 mol%)
Bu3SnR1 2 (1.0 equiv)
Et3N (2.0 equiv)
60 °C, 1–20 h
R2
1 X = CH, R2 = Me
4 X = N, R2 = PMB
3 X = CH, R2 = Me, 58–81%
5 X = N, R1 = thiophen-2-yl,
R
2 = PMB, 62%
O
R1
N
N
(COCl)2 (1.0 equiv)
THF, 0 °C to r.t., 4 h
Encouraged by the ease and broad versatility of the se-
quence, we probed the extension to a consecutive four-
component pyrazoline synthesis (Scheme 3). Starting
from 1-methyl-1H-indole (1), the glyoxylation–decarbon-
ylative Stille coupling sequence with vinylstannane 2e
furnishes enone 3e, which was reacted in situ with meth-
ylhydrazine (10) to give the pyrazoline 11 in 66% yield.
Indeed, the isolated yield of 11 was higher than the isolat-
ed yield of 3e, emphasizing the advantage of the one-pot
sequence over a stepwise protocol with isolation of reac-
tive, intermediate products.
R2
6 R2 = Me,
CH2CH2CN, Bn
or
R2
7 (81–88%)
then:
or
O
PdCl2(PPh3)2 (5 mol%)
Bu3SnR1 2 (1.0 equiv)
Et3N (2.0 equiv)
60 °C, 1 h
N
N
Me
Me
9 (57%)
8
Scheme 2 Three-component glyoxylation–decarbonylative Stille
coupling synthesis of ketones 3, 5, 7 and 9
Me
N
N
(COCl)2 (1.0 equiv)
THF, 0 °C to r.t., 4 h
then:
N
N
PdCl2(PPh3)2 (5 mol%)
2e (1.0 equiv)
Et3N (2.0 equiv)
60 °C, 1 h
Me
Me
1
11 (66%)
then:
MeNHNH2 10 (2.0 equiv)
60 °C, 1 h
Scheme 3 An illustrative, consecutive four-component synthesis of
pyrazoline 11 by the glyoxylation–decarbonylative Stille coupling–
cyclocondensation sequence
The structure of the pyrazoline 11 was unambiguously
supported by NMR spectroscopy, mass spectrometry and
combustion analysis.
Figure 1 Molecular structure of compound 3b in the crystal; 30%
probability ellipsoids; only one orientation of the disordered thiophe-
nyl group is shown14
In conclusion, we have developed a straightforward, nov-
el, one-pot three-component synthesis of unsymmetrical
heterocyclic ketones by glyoxylation of 1-methyl-1H-in-
dole (1), the 7-azaindole 4 or the N-substituted pyrrole de-
rivatives 6 and 8 with oxalyl chloride and subsequent
decarbonylative Stille coupling of the in situ generated
heteroareneglyoxylyl chlorides with various stannanes in-
cluding vinyl and alkynyl, as well as N- and S-heterocy-
clic derivatives. As already demonstrated for
glyoxylation–decarbonylative alkynylation,7 this se-
quence can be performed on a 5 mmol scale under mild
conditions and with only equimolar quantities of reagents
and a high tolerance for various substituents. In addition,
our consecutive, four-component synthesis of 1-methyl-3-
(1-methyl-4,5-dihydro-1H-pyrazol-3-yl)-1H-indole (11)
illustrates the conceptual versatility of the glyoxylation–
decarbonylative cross-coupling methodology as an entry
to multicomponent syntheses of densely functionalized
heterocycles.
pyrroles 6 are regioselectively glyoxylated at the 2-posi-
tion (Table 2, entries 8–11). If the 2- and 5-positions are
blocked, as in the case of 1,2,5-trimethyl-1H-pyrrole (8),
expectedly, the glyoxylation occurs at the 3-position
(Table 2, entry 12). The application of the N-substituted
indole 1, the 7-azaindole 4 and the pyrrole derivatives 6
and 8 supports the tolerance of the glyoxylation–decarbo-
nylative Stille coupling sequence for a variety of N-het-
erocycles as substrates. In contrast to findings by Milstein
and Stille,8b the decarbonylative Stille coupling is not in-
hibited by the formation of unreactive palladium carbonyl
complexes but rather proceeds smoothly under mild con-
ditions. Upon application of a wide range of unsaturated,
aromatic and even heterocyclic stannanes 2, the glyoxyla-
tion–decarbonylative Stille coupling sequence furnishes
various acyl heterocycles 3, 5, 7 and 9. Tributyl(phenyl-
ethynyl)stannane (2a) gives rise to the alkynones 3a and
Synthesis 2010, No. 13, 2139–2146 © Thieme Stuttgart · New York

2142
B. O. A. Tasch et al.
PAPER
Table 2 Three-Component Glyoxylation–Decarbonylative Stille Coupling Synthesis of Ketones 3, 5, 7 and 9a
Entry Starting
electron-rich heterocycle
Stannane 2
Reaction time
(decarbonylative Stille coupling step)
Ketone product
Isolated yield
(%)
O
Ph
1
2
2a: R1 = C≡CPh
1 h
81
81
N
N
Me
Me
1
1
3a
S
O
2b: R1 = thiophen-2-yl 1 h
N
Me
3b
3c
S
O
3
4
5
6
1
1
1
1
2c: R1 = thiophen-3-yl
2d: R1 = pyridin-2-yl
2e: R1 = CH=CH2
2f: R1 = Ph
1 h
66
75
58
68
N
Me
N
O
1 h
N
Me
3d
3e
3f
O
20 hb
N
Me
O
20 h
N
Me
S
O
N
N
2b: R1 = thiophen-2-yl 1 h
62c
N
N
7
MeO
4
MeO
5
O
6a: R2 = Me
2a: R1 = C≡CPh
1 h
82
N
8
Me
Ph
7a
Synthesis 2010, No. 13, 2139–2146 © Thieme Stuttgart · New York

PAPER
Glyoxylation–Decarbonylative Stille Coupling Sequence
2143
Table 2 Three-Component Glyoxylation–Decarbonylative Stille Coupling Synthesis of Ketones 3, 5, 7 and 9a (continued)
Entry Starting
electron-rich heterocycle
Stannane 2
Reaction time
(decarbonylative Stille coupling step)
Ketone product
Isolated yield
(%)
O
9
10
11
12
6a: R2 = Me
2b: R1 = thiophen-2-yl 1 h
2b: R1 = thiophen-2-yl 1 h
2b: R1 = thiophen-2-yl 1 h
88
85
81
57
N
S
S
Me
7b
O
N
6b: R2 = CH2CH2CN
CN
7c
O
6c: R2 = Bn
N
S
Bn
7d
O
2e: R1 = CH=CH2
1 h
N
Me
N
8
Me
9
a See Scheme 2. The reactions were performed in THF [c(1, 6 or 8) = 0.2 M] using 5.00 mmol of 1-methyl-1H-indole (1) or N-substituted pyr-
roles 6 or 8 under the optimized reaction conditions.
b After 1 h (for the decarbonylative Stille coupling step), ketone 3e could be isolated in 52% yield.
c The glyoxylation step was performed in DME [c(4) = 0.2 M] using 5.00 mmol of 7-azaindole 4 at 100 °C for 2 h.
All reactions were carried out in oven-dried Schlenk glassware us-
ing septa and syringes under argon atmosphere. THF was dried us-
ing an MBraun MB SPS-800 system. Et3N was refluxed under
argon over ketyl sodium, distilled and stored in a Schlenk flask over
KOH pellets under argon atmosphere. 1-Methyl-1H-indole (1), 1-
methyl-1H-pyrrole (6a), 3-(1H-pyrrol-1-yl)propanenitrile (6b), 1-
benzyl-1H-pyrrole (6c), 1,2,5-trimethyl-1H-pyrrole (8), tri-
butyl(phenylethynyl)stannane (2a), tributyl(thiophen-2-yl)stannane
(2b), tributyl(pyridin-2-yl)stannane (2d), tributyl(vinyl)stannane
(2e) and tributyl(phenyl)stannane (2f) are commercially available
and were purchased from Acros Organics N. V., Aldrich Chemie
GmbH, Fluka AG, ABCR GmbH & Co. KG, and Merck Serono
KGaA. Oxalyl chloride was purchased from Merck Serono KGaA.
All commercial grade reagents were used as supplied without fur-
ther purification. Tributyl(thiophen-3-yl)stannane (2c) was pre-
pared according to literature procedures.15 MeOH (p.a.) and KOH
(p.a.) used for the removal of tin residues were purchased from
Aldrich Chemie GmbH and Roth GmbH & Co. KG. The purifica-
tion of products was performed on silica gel 60 (0.015–0.040 mm)
from Merck Serono KGaA using a Biotage SP1 Flash Purification
System (SP-SNAP 340-g cartridges) and petroleum ether (boiling
range 40–60 °C)–EtOAc as eluent (isocratic or gradient). The crude
mixtures were adsorbed onto Celite® 545 (0.02–0.10 mm) from
Merck Serono KGaA before chromatographic purification. The re-
action progress was monitored qualitatively using TLC silica gel 60
F254 aluminum sheets (5 × 7.5 cm) obtained from Merck Serono
KGaA. The spots were detected with UV light at 254 nm and using
aq KMnO4 soln. 1H, 13C and 135-DEPT NMR spectra were record-
ed on a Bruker DRX 500 spectrometer; CDCl3 was used as solvent
and TMS was used as reference (d = 0.0). The type of carbon atoms
was determined on the basis of the 135-DEPT NMR spectra. EI
mass spectra were measured on Varian MAT 311A and Finnigan
MAT 8200 spectrometers. IR spectra were obtained on a Bruker
Vector 22 FT-IR instrument; solids were measured as KBr pellets
and oils as films on KBr plates. Melting points (uncorrected) were
measured on a Reichert-Jung Thermovar apparatus. Elemental anal-
yses were carried out in the microanalytical laboratory of the Insti-
tut für Pharmazeutische Chemie in Düsseldorf. The X-ray crystal
structure was measured on a Stoe IPDS diffractometer.
Glyoxylation–Decarbonylative Stille Coupling Sequence; Gen-
eral Procedure
1-Methyl-1H-indole (1), 7-azaindole 4 (see analytical data for 5) or
N-substituted pyrroles 6 or 8 (5.00 mmol) in anhyd THF (25 mL)
was placed under argon atmosphere in a screw-cap vessel with a
septum, and the mixture was degassed with argon for 5 min and
cooled to 0 °C (ice water). After 15 min, oxalyl chloride (0.44 mL,
5.00 mmol) was added dropwise to the mixture at 0 °C. The mixture
was allowed to warm to r.t. (water bath) and was stirred for 4 h.
Then, PdCl2(PPh3)2 (177 mg, 0.25 mmol), anhyd Et3N (1.39 mL,
10.0 mmol) and a stannane 2 (5.00 mmol) were successively added
to the mixture which was stirred at 60 °C for 1 h. The evolution of
carbon monoxide was observed. After complete conversion (the
product formation was monitored by TLC), the mixture was al-
lowed to cool to r.t. and MeOH (25 mL) and KOH (0.66 g, 10.0
mmol) were added. The mixture was stirred at r.t. for 20 h. Then,
H2O (25 mL) was added and the mixture was extracted with CH2Cl2
(4 × 50 mL, monitored by TLC). The combined organic layers were
dried (anhyd Na2SO4). The solvents were removed under reduced
pressure, and the residue was absorbed onto Celite® and purified by
Synthesis 2010, No. 13, 2139–2146 © Thieme Stuttgart · New York

2144
B. O. A. Tasch et al.
PAPER
chromatography on silica gel [petroleum ether (40–60 °C)–EtOAc]
to give the ketones 3, 5, 7 or 9 after drying under reduced pressure.
In some cases, it was necessary to additionally purify the product by
suspending it in n-pentane, sonication in an ultrasound bath, filtra-
tion and drying under reduced pressure.
MS (EI, 70 eV): m/z (%) = 242 (10), 241 (58) [M]+, 159 (11), 158
(100) [M – C4H3S]+, 130 (9) [C9H8N]+, 111 (6) [C5H3OS]+, 103 (9),
77 (11).
Anal. Calcd for C14H11NOS (241.3): C, 69.68; H, 4.59; N, 5.80.
Found: C, 69.51; H, 4.42; N, 5.80.
1-(1-Methyl-1H-indol-3-yl)-3-phenylprop-2-yn-1-one (3a)
According to the standard procedure, the reaction with stannane 2a
(1.84 mL, 5.00 mmol) gave 3a as a yellow solid; yield: 1.05 g
(81%); mp 111–113 °C.
(1-Methyl-1H-indol-3-yl)(pyridin-2-yl)methanone (3d)
According to the standard procedure, the reaction with stannane 2d
(1.70 mL, 5.00 mmol) gave 3d as a yellow solid; yield: 882 mg
(75%); mp 103–105 °C.
IR (KBr): 3053, 2204, 1593, 1525, 1490, 1469, 1398, 1377, 1339,
1272, 1250, 1198, 1149, 1123, 1088, 1049, 1011, 950, 794, 769,
751, 689, 567, 529, 430 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.85 (s, 3 H), 7.31–7.46 (m, 6 H),
7.63–7.66 (m, 2 H), 7.93 (s, 1 H), 8.40–8.44 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 33.7 (CH3), 87.6 (Cq), 87.9 (Cq),
109.9 (CH), 118.4 (Cq), 120.8 (Cq), 122.5 (CH), 123.1 (CH), 123.9
(CH), 125.8 (Cq), 128.6 (CH), 130.1 (CH), 132.7 (CH), 137.7 (Cq),
138.9 (CH), 171.1 (Cq).
MS (EI, 70 eV): m/z (%) = 260 (21), 259 (100) [M]+, 232 (14), 231
(69), 230 (14), 216 (11), 158 (16) [M – C8H5]+, 129 (7) [C9H5O]+,
116 (18) [C8H6N]+.
IR (KBr): 3139, 3050, 1736, 1686, 1617, 1578, 1563, 1511, 1460,
1365, 1270, 1230, 1156, 1123, 1074, 1033, 1012, 872, 748, 692,
624, 574, 428 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.84 (s, 3 H), 7.28–7.38 (m, 3 H),
7.42 (ddd, J = 7.6, 4.8, 1.2 Hz, 1 H), 7.86 (td, J = 7.8, 1.8 Hz, 1 H),
8.14–8.17 (m, 1 H), 8.61 (dt, J = 7.2, 1.5 Hz, 1 H), 8.68–8.70 (m, 1
H), 8.71 (s, 1 H).
13C NMR (125 MHz, CDCl3): d = 34.0 (CH3), 110.0 (CH), 114.2
(Cq), 123.3 (CH), 123.4 (CH), 123.8 (CH), 124.0 (CH), 126.1 (CH),
128.6 (Cq), 137.4 (Cq), 137.5 (CH), 141.0 (CH), 148.5 (CH), 157.2
(Cq), 186.7 (Cq).
MS (EI, 70 eV): m/z (%) = 237 (13), 236 (67) [M]+, 235 (16), 159
(12), 158 (100) [M – C5H4N]+, 130 (5) [C9H8N]+, 118 (10), 103 (10),
77 (8) [C5H3N]+, 43 (11).
Anal. Calcd for C18H13NO (259.3): C, 83.37; H, 5.05; N, 5.40.
Found: C, 83.57; H, 4.97; N, 5.41.
Anal. Calcd for C15H12N2O (236.3): C, 76.25; H, 5.12; N, 11.86.
Found: C, 76.00; H, 5.29; N, 11.72.
(1-Methyl-1H-indol-3-yl)(thiophen-2-yl)methanone (3b)
According to the standard procedure, the reaction with stannane 2b
(1.64 mL, 5.00 mmol) gave 3b as a yellow solid; yield: 981 mg
(81%); mp 243–246 °C. Crystallization (CH2Cl2–n-pentane) gave
yellow crystals.
1-(1-Methyl-1H-indol-3-yl)prop-2-en-1-one (3e)
According to the standard procedure (20 h for the Stille coupling
step), the reaction with stannane 2e (1.54 mL, 5.00 mmol) gave 3e
as a yellow solid; yield: 534 mg (58%); mp 101–104 °C.
IR (KBr): 3110, 2930, 1686, 1586, 1572, 1522, 1465, 1421, 1388,
1370, 1266, 1238, 1186, 1156, 1125, 1086, 1063, 1011, 934, 868,
846, 811, 771, 750, 735, 670, 568 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.84 (s, 3 H), 7.14 (dd, J = 5.0, 3.7
Hz, 1 H), 7.30–7.38 (m, 3 H), 7.59 (dd, J = 5.0, 1.1 Hz, 1 H), 7.72
(dd, J = 3.7, 1.1 Hz, 1 H), 7.77 (s, 1 H), 8.39–8.43 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 34.0 (CH3), 110.1 (CH), 115.9
(Cq), 123.0 (CH), 123.0 (CH), 124.1 (CH), 127.7 (Cq), 127.9 (CH),
131.4 (CH), 131.7 (CH), 136.5 (CH), 137.8 (Cq), 145.8 (Cq), 181.8
(Cq).
MS (EI, 70 eV): m/z (%) = 242 (18), 241 (100) [M]+, 240 (20), 159
(10), 158 (90) [M – C4H3S]+, 149 (11), 130 (8) [C9H8N]+, 111 (4)
[C5H3OS]+, 71 (11), 57 (15), 43 (15).
IR (KBr): 3107, 1645, 1588, 1574, 1530, 1468, 1414, 1371, 1335,
1299, 1233, 1146, 1125, 1089, 1011, 983, 956, 924, 801, 753, 695,
571, 428 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.75–3.79 (m, 3 H), 5.70–5.74 (m,
1 H), 6.39–6.44 (m, 1 H), 6.93–7.01 (m, 1 H), 7.27–7.35 (m, 3 H),
7.66–7.68 (m, 1 H), 8.45–8.49 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 33.5 (CH3), 109.7 (CH), 116.7
(Cq), 122.7 (CH), 122.9 (CH), 123.7 (CH), 126.3 (CH2), 126.7 (Cq),
133.7 (CH), 135.9 (CH), 137.6 (Cq), 184.7 (Cq).
MS (EI, 70 eV): m/z (%) = 186 (10), 185 (80) [M]+, 159 (12), 158
(100) [M – C2H3]+, 130 (9) [C9H8N]+, 77 (12).
Anal. Calcd for C12H11NO (185.2): C, 77.81; H, 5.99; N, 7.59.
Found: C, 77.59; H, 6.27; N, 7.48.
Anal. Calcd for C14H11NOS (241.3): C, 69.68; H, 4.59; N, 5.80.
Found: C, 69.66; H, 4.72; N, 5.55.
(1-Methyl-1H-indol-3-yl)(phenyl)methanone (3f)
(1-Methyl-1H-indol-3-yl)(thiophen-3-yl)methanone (3c)
According to the standard procedure, the reaction with stannane 2c
(1.86 g, 5.00 mmol) gave 3c as a yellow solid; yield: 802 mg (66%);
mp 115 °C.
According to the standard procedure (20 h for the Stille coupling
step), the reaction with stannane 2f (1.68 mL, 5.00 mmol) gave 3f
as a yellow solid; yield: 800 mg (68%); mp 111–113 °C.
IR (KBr): 3051, 1619, 1574, 1524, 1471, 1372, 1267, 1233, 1126,
1077, 1025, 875, 751, 719, 697, 669, 573, 435 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.82 (s, 3 H), 7.31–7.37 (m, 3 H),
7.44–7.56 (m, 4 H), 7.72–7.78 (m, 2 H), 8.41–8.45 (m, 1 H).
IR (KBr): 3129, 3096, 3050, 2910, 1799, 1686, 1606, 1573, 1526,
1463, 1413, 1376, 1359, 1339, 1262, 1238, 1200, 1178, 1151, 1128,
1080, 1040, 1009, 936, 866, 839, 820, 800, 756, 646, 619, 591, 579,
562 cm–1.
13C NMR (125 MHz, CDCl3): d = 33.5 (CH3), 109.6 (CH), 115.6
(Cq), 122.7 (CH), 122.7 (CH), 123.6 (CH), 127.2 (Cq), 128.3 (CH),
128.6 (CH), 131.0 (CH), 137.5 (Cq), 137.9 (CH), 140.9 (Cq), 190.8
(Cq).
MS (EI, 70 eV): m/z (%) = 236 (16), 235 (86) [M]+, 159 (11), 158
(100) [M – C6H5]+, 130 (5) [C9H8N]+, 77 (11), 71 (10), 57 (23), 43
(10), 43 (18).
1H NMR (500 MHz, CDCl3): d = 3.82 (s, 3 H), 7.30–7.37 (m, 4 H),
7.56 (m, 1 H), 7.63 (s, 1 H), 7.86 (m, 1 H), 8.40–8.43 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 33.5 (CH3), 109.6 (CH), 116.3
(Cq), 122.6 (CH), 122.6 (CH), 123.6 (CH), 125.9 (CH), 127.1 (Cq),
128.1 (CH), 129.6 (CH), 136.8 (CH), 137.5 (Cq), 143.7 (Cq), 184.2
(Cq).
Synthesis 2010, No. 13, 2139–2146 © Thieme Stuttgart · New York

PAPER
Glyoxylation–Decarbonylative Stille Coupling Sequence
2145
Anal. Calcd for C16H13NO (235.3): C, 81.68; H, 5.57; N, 5.95.
Found: C, 81.39; H, 5.73; N, 5.74.
3-[2-(Thiophen-2-ylcarbonyl)-1H-pyrrol-1-yl]propanenitrile
(7c)
According to the standard procedure, the reaction with stannane 2b
(1.64 mL, 5.00 mmol) gave 7c as a yellow oil; yield: 977 mg (85%).
[1-(4-Methoxybenzyl)-1H-pyrrolo[2,3-b]pyridin-3-
yl](thiophen-2-yl)methanone (5)
The sequence was performed according to the standard procedure,
but in DME (25 mL) at 100 °C for 2 h for the glyoxylation step. The
reaction with stannane 2b (1.64 mL, 5.00 mmol) gave 5 as a color-
less solid; yield: 1.09 g (62%); mp 106 °C.
IR (film): 3108, 2961, 2251, 1732, 1601, 1527, 1466, 1416, 1354,
1337, 1257, 1180, 1133, 1089, 1048, 889, 868, 853, 813, 740, 663,
611 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.00 (t, J = 6.3 Hz, 2 H), 4.55 (t,
J = 6.3 Hz, 2 H), 6.28 (dd, J = 3.8, 2.7 Hz, 1 H), 7.08–7.18 (m, 3 H),
7.64 (d, J = 5.0 Hz, 1 H), 7.76 (d, J = 3.8 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 20.9 (CH2), 45.8 (CH2), 109.9
(CH), 118.1 (Cq), 122.6 (CH), 128.0 (CH), 129.7 (Cq), 131.7 (CH),
132.94 (CH), 133.0 (CH), 144.6 (Cq), 177.6 (Cq).
MS (EI, 70 eV): m/z (%) = 231 (13), 230 (100) [M]+, 197 (32), 190
(42) [C10H8NOS]+, 189 (21), 157 (10), 147 (8) [C8H7N2O]+, 111
(35) [C5H3OS]+, 97 (20).
IR (KBr): 2926, 2833, 1609, 1572, 1524, 1509, 1448, 1428, 1416,
1396, 1349, 1306, 1252, 1245, 1190, 1175, 1107, 1036, 871, 828,
809, 769, 735, 710, 648, 584, 537, 510 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.78 (s, 3 H), 5.50 (s, 2 H), 6.84–
6.89 (m, 2 H), 7.12–7.15 (m, 1 H), 7.22–7.31 (m, 3 H), 7.57–7.70
(m, 2 H), 7.92 (s, 1 H), 8.45–8.47 (m, 1 H), 8.64–8.67 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 48.4 (CH2), 55.7 (CH3), 114.7
(Cq), 114.8 (CH), 119.2 (CH), 120.2 (Cq), 128.1 (CH), 128.7 (Cq),
129.7 (CH), 131.5 (CH), 131.7 (CH), 132.3 (CH), 134.7 (CH),
145.1 (Cq), 145.4 (CH), 148.6 (Cq), 159.9 (Cq), 181.6 (Cq).
Anal. Calcd for C12H10N2OS (230.3): C, 62.59; H, 4.38; N, 12.16.
Found: C, 62.49; H, 4.17; N, 11.87.
MS (EI, 70 eV): m/z (%) = 349 (2), 348 (11) [M]+, 237 (9) [M –
(1-Benzyl-1H-pyrrol-2-yl)(thiophen-2-yl)methanone (7d)
According to the standard procedure, the reaction with stannane 2b
(1.64 mL, 5.00 mmol) gave 7d as a milky, colorless oil; yield: 1.08
g (81%).
C5H3OS]+, 122 (9), 121 (100) [C8H9O]+.
Anal. Calcd for C20H16N2O2S (348.4): C, 68.94; H, 4.63; N, 8.04.
Found: C, 68.71; H, 4.57; N, 8.07.
IR (film): 3105, 3031, 2927, 1605, 1524, 1496, 1462, 1415, 1354,
1332, 1246, 1130, 1085, 1048, 869, 853, 816, 716, 675, 611 cm–1.
1-(1-Methyl-1H-pyrrol-2-yl)-3-phenylprop-2-yn-1-one (7a)
According to the standard procedure, the reaction with stannane 2a
(1.84 mL, 5.00 mmol) gave 7a as a dark yellow oil; yield: 855 mg
(82%).
1H NMR (500 MHz, CDCl3): d = 5.60 (s, 2 H), 6.24 (dd, J = 4.0, 2.6
Hz, 1 H), 6.98–7.01 (m, 1 H), 7.08 (dd, J = 4.0, 1.6 Hz, 1 H), 7.11
(dd, J = 4.9, 3.8 Hz, 1 H), 7.14–7.17 (m, 2 H), 7.20–7.25 (m, 1 H),
7.26–7.31 (m, 2 H), 7.58 (dd, J = 5.0, 1.1 Hz, 1 H), 7.73 (dd, J = 3.7,
1.1 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 52.6 (CH2), 109.3 (CH), 122.0
(CH), 127.6 (CH), 127.9 (CH), 128.0 (CH), 129.1 (CH), 130.3 (Cq),
131.1 (CH), 132.5 (CH), 132.9 (CH), 138.6 (Cq), 145.2 (Cq), 177.6
(Cq).
IR (film): 3108, 3060, 2997, 2951, 2459, 2202, 1608, 1524, 1489,
1465, 1443, 1401, 1330, 1270, 1234, 1206, 1177, 1159, 1090, 1058,
984, 920, 884, 791, 757, 734, 690, 632, 603, 548 cm–1.
1H NMR (500 MHz, CDCl3): d = 3.97 (s, 3 H), 6.19 (dd, J = 4.1, 2.4
Hz, 1 H), 6.87–6.88 (m, 1 H), 7.29 (dd, J = 4.1, 1.7 Hz, 1 H), 7.35–
7.45 (m, 3 H), 7.59–7.63 (m, 2 H).
13C NMR (125 MHz, CDCl3): d = 37.8 (CH3), 88.0 (Cq), 88.1 (Cq),
109.5 (CH), 121.1 (Cq), 124.2 (CH), 129.0 (CH), 130.6 (CH), 132.7
(Cq), 133.0 (CH), 133.2 (CH), 167.3 (Cq).
MS (EI, 70 eV): m/z (%) = 267 (23) [M]+, 156 (36) [M – C5H3OS]+,
111 (41) [C5H3OS]+, 91 (50) [C7H7]+, 83 (48) [C4H3S]+, 57 (100)
[C2HS]+.
MS (EI, 70 eV): m/z (%) = 210 (18), 209 (100) [M]+, 208 (71), 181
Anal. Calcd for C16H13NOS (267.3): C, 71.88; H, 4.90; N, 5.24.
Found: C, 71.96; H, 5.11; N, 5.02.
(29), 180 (45), 129 (11) [C9H5O]+, 115 (17).
Anal. Calcd for C14H11NO (209.2): C, 80.36; H, 5.30; N, 6.69.
Found: C, 80.10; H, 5.13; N, 6.71.
1-(1,2,5-Trimethyl-1H-pyrrol-3-yl)prop-2-en-1-one (9)
According to the standard procedure, the reaction with stannane 2e
(1.54 mL, 5.00 mmol) gave 9 as a yellow solid; yield: 468 mg
(57%); mp 73–75 °C.
(1-Methyl-1H-pyrrol-2-yl)(thiophen-2-yl)methanone (7b)
According to the standard procedure, the reaction with stannane 2b
(1.64 mL, 5.00 mmol) gave 7b as a yellow oil; yield: 843 mg (88%).
IR (KBr): 3096, 2912, 1639, 1594, 1570, 1521, 1429, 1415, 1372,
1344, 1295, 1220, 1187, 1154, 1044, 1006, 989, 951, 790, 728, 691,
561 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.21 (s, 3 H), 2.58 (s, 3 H), 3.41
(s, 3 H), 5.64–5.68 (m, 1 H), 6.26–6.35 (m, 2 H), 6.97 (dd, J = 17.1,
10.4 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 12.5 (CH3), 12.8 (CH3), 30.5
(CH3), 107.7 (CH), 120.0 (Cq), 126.4 (CH2), 128.4 (Cq), 135.3
(CH), 137.2 (Cq), 186.4 (Cq).
MS (EI, 70 eV): m/z (%) = 164 (11), 163 (100) [M]+, 162 (74), 147
(24) [M – CH4]+, 136 (81) [M – C2H3]+, 134 (15), 108 (12), 67 (10),
56 (14) [C3H4O]+.
IR (film): 3106, 2950, 2464, 1614, 1525, 1463, 1417, 1379, 1329,
1254, 1141, 1094, 1049, 904, 869, 853, 816, 785, 739, 666, 606, 566
cm–1.
1H NMR (500 MHz, CDCl3): d = 3.97 (s, 3 H), 6.18 (dd, J = 4.1, 2.5
Hz, 1 H), 6.89–6.92 (m, 1 H), 7.03 (dd, J = 4.1, 1.7 Hz, 1 H), 7.12
(dd, J = 5.0, 3.7 Hz, 1 H), 7.60 (dd, J = 5.0, 1.2 Hz, 1 H), 7.75 (dd,
J = 3.7, 1.2 Hz, 1 H).
13C NMR (125 MHz, CDCl3): d = 37.6 (CH3), 108.7 (CH), 121.3
(CH), 128.0 (CH), 130.6 (Cq), 131.8 (CH), 132.4 (CH), 132.7 (CH),
145.2 (Cq), 177.6 (Cq).
MS (EI, 70 eV): m/z (%) = 192 (17), 191 (100) [M]+, 190 (51), 158
(20), 111 (20), 108 (25) [M – C4H3S]+, 94 (15), 53 (14), 39 (16).
Anal. Calcd for C10H13NO (163.2): C, 73.59; H, 8.03; N, 8.58.
Found: C, 73.45; H, 8.03; N, 8.36.
Anal. Calcd for C10H9NOS (191.3): C, 62.80; H, 4.74; N, 7.32.
Found: C, 62.51; H, 4.79; N, 7.06.
Synthesis 2010, No. 13, 2139–2146 © Thieme Stuttgart · New York

2146
B. O. A. Tasch et al.
PAPER
1-Methyl-3-(1-methyl-4,5-dihydro-1H-pyrazol-3-yl)-1H-indole
(11)
References
(1) For a review on palladium-catalyzed carbonylative
1-Methyl-1H-indole (1; 669 mg, 5.00 mmol) in anhyd THF (25 mL)
was placed under an argon atmosphere in a screw-cap vessel with a
septum, and the mixture was degassed with argon for 5 min and
cooled to 0 °C (ice water). After 15 min, oxalyl chloride (0.44 mL,
5.00 mmol) was added to the mixture at 0 °C. The mixture was al-
lowed to warm to r.t. (water bath) and was stirred for 4 h. Then,
PdCl2(PPh3)2 (177 mg, 0.25 mmol), anhyd Et3N (1.39 mL, 10.0
mmol) and tributyl(vinyl)stannane (2e; 1.54 mL, 5.00 mmol) were
successively added to the mixture which was stirred at 60 °C for 1
h. The evolution of carbon monoxide was observed. Then, methyl-
hydrazine (10; 0.54 mL, 10.0 mmol) was added and the mixture was
stirred at 60 °C for 1 h. After complete conversion (the product for-
mation was monitored by TLC), the mixture was allowed to cool to
r.t. and MeOH (25 mL) and KOH (0.66 g, 10.0 mmol) were added.
The mixture was stirred at r.t. for 20 h. Then, H2O (25 mL) was add-
ed and the mixture was extracted with CH2Cl2 (4 × 50 mL). The
combined organic layers were dried (anhyd Na2SO4). The solvents
were removed under reduced pressure, and the residue was ab-
sorbed onto Celite® and purified by chromatography on silica gel
[petroleum ether (40–60 °C)–EtOAc] to give the pyrazoline 11. It
was necessary to additionally purify the product by suspending it in
n-pentane, sonication in an ultrasound bath, filtration and drying un-
der reduced pressure.
couplings, see: Brennführer, A.; Neumann, H.; Beller, M.
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(2) Wynne, J. H.; Lloyd, C. T.; Jensen, S. D.; Boson, S.; Stalick,
W. M. Synthesis 2004, 2277.
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Angew. Chem. Int. Ed. 2005, 44, 6951. (b) Ahmed, M. S.
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Utkina, L. M. Synlett 2008, 100.
(5) Nakao, Y.; Satoh, J.; Shirakawa, E.; Hiyama, T. Angew.
Chem. Int. Ed. 2006, 45, 2271.
(6) (a) Gooßen, L. J.; Paetzold, J. Angew. Chem. Int. Ed. 2004,
43, 1095. (b) Gooßen, L. J.; Paetzold, J. Angew. Chem. Int.
Ed. 2002, 41, 1237.
(7) Merkul, E.; Oeser, T.; Müller, T. J. J. Chem. Eur. J. 2009, 15,
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(8) (a) Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100,
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1613. (c) Labadie, J. W.; Stille, J. K. J. Am. Chem. Soc.
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(10) (a) Liebeskind, L. S.; Fengl, R. W. J. Org. Chem. 1990, 55,
5359. (b) Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.;
Liebeskind, L. S. J. Org. Chem. 1994, 59, 5905.
(c) Casado, A. L.; Espinet, P. Organometallics 2003, 22,
1305. (d) Han, X.; Stolz, B. M.; Corey, E. J. J. Am. Chem.
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Lett. 1997, 38, 7673. (f) Ye, J.; Bhatt, R. K.; Falck, J. R.
J. Am. Chem. Soc. 1994, 116, 1. (g) Wang, Y.; Burton, D. J.
Org. Lett. 2006, 8, 1109.
Yield: 704 mg (66%); yellow solid; mp 110–112 °C.
IR (KBr): 3060, 2945, 2834, 2803, 2776, 1719, 1655, 1591, 1543,
1524, 1473, 1442, 1422, 1403, 1367, 1336, 1293, 1237, 1167, 1139,
1113, 1013, 956, 884, 851, 805, 768, 742, 630, 568, 528 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.94 (s, 3 H), 3.00–3.12 (m, 4 H),
3.77 (s, 3 H), 7.18–7.34 (m, 4 H), 8.27 (m, 1 H).
13C NMR (125 MHz, CDCl3): d = 33.0 (CH3), 35.2 (CH2), 44.3
(CH3), 55.7 (CH2), 109.1 (CH), 109.9 (Cq), 120.6 (CH), 122.6 (CH),
122.7 (CH), 125.6 (Cq), 128.9 (CH), 137.5 (Cq), 149.2 (Cq).
MS (EI, 70 eV): m/z (%) = 213 (100) [M]+, 212 (37), 211 (57), 210
(12), 170 (15) [M – C2H5N]+, 156 (13) [M – C2H5N2]+, 155 (17), 144
(15), 128 (12), 106 (18), 105 (15).
(11) Leibner, J. E.; Jacobus, J. J. Org. Chem. 1979, 44, 449.
(12) Harrowven, D. C.; Guy, I. L. Chem. Commun. 2004, 1968.
(13) Renaud, P.; Lacote, E.; Quaranta, L. Tetrahedron Lett. 1998,
39, 2123.
(14) CCDC 775726 (compound 3b) contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge via http://www.ccdc.cam.ac.uk/
conts/retrieving.html [or from the Cambridge
Anal. Calcd for C13H15N3 (213.3): C, 73.21; H, 7.09; N, 19.70.
Found: C, 73.41; H, 6.87; N, 19.53.
Crystallographic Data Centre, 12 Union Road, Cambridge
CB2 1EZ, UK; fax: +44(1223)336033; e-mail:
deposit@ccdc.cam.ac.uk].
Acknowledgment
(15) (a) Adam, M. J.; Ruth, T. J.; Jivan, S.; Pate, B. D. J. Fluorine
Chem. 1984, 25, 329. (b) Arnswald, M.; Neumann, W. P.
J. Org. Chem. 1993, 58, 7022.
This work was supported by Merck Serono, Darmstadt, and the
Fonds der Chemischen Industrie (scholarship to B.O.A.T.).
Synthesis 2010, No. 13, 2139–2146 © Thieme Stuttgart · New York