Palladium-catalyzed synthesis of quinoxaline derivatives

Article abstract of DOI:10.1016/j.tet.2008.07.083

A palladium-catalyzed reductive N-heteroannulation of enamines derived from 2-nitrobenzenamines forming mixtures of 1,2-dihydroquinoxalines and 3,4-dihydroquinoxalin-2-ones is described. The reactions are performed using bis(dibenzylideneacetone)palladium(0), 1,3-bis(diphenylphosphino)propane, and 1,10-phenanthroline in DMF under 6 atm of carbon monoxide at 70 °C.

Full text of DOI:10.1016/j.tet.2008.07.083

Tetrahedron 64 (2008) 9675–9684
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Tetrahedron
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Palladium-catalyzed synthesis of quinoxaline derivatives
,
b
a
Jeffery M. Wallace a, Bjo¨rn C.G. So¨derberg a , Joaquın Tamariz , Novruz G. Akhmedov ,
*
´
Mathew T. Hurleya
a C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506-6045, USA
b Department of Organic Chemistry, Escuela Nacional de Ciencias Biolo´gicas, I.P.N. Prol. Carpio y Plan de Ayala, 11340 Me´xico, D.F., Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 June 2008
Received in revised form 10 July 2008
Accepted 18 July 2008
Available online 24 July 2008
A palladium-catalyzed reductive N-heteroannulation of enamines derived from 2-nitrobenzenamines
forming mixtures of 1,2-dihydroquinoxalines and 3,4-dihydroquinoxalin-2-ones is described. The
reactions are performed using bis(dibenzylideneacetone)palladium(0), 1,3-bis(diphenylphosphino)pro-
pane, and 1,10-phenanthroline in DMF under 6 atm of carbon monoxide at 70 ꢀC.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Palladium-catalyzed annulation
Quinoxaline
1. Introduction
been reported to mediate the transformation of 1 to 2 in low
isolated yield.17
A variety of heterocyclic compounds have been prepared by
transition metal-catalyzed reductive N-heteroannulation of
2-substituted nitrobenzenes.1 Examples of heterocycles obtained
in this fashion include indoles,2 2H-indazoles,3 quinolines,3 4(1H)-
quinolones,4 quinazolines,5 4(3H)-quinazolinones,6 pyrrolines,7
benzimidazoles,8–10 benzotriazoles,11 1,4-dihydro-2H-3,1-benzox-
azin-2-ones,12 and 2,1-benzoisoxazole.3 Palladium has pre-
dominantly been used as the catalyst of choice. However, other
transition metals, such as iron,13 manganese,6b cobalt,6b ruthe-
nium,14 platinum,14 selenium,15 rhodium,14 and molybdenum16
have successfully been employed in reductive N-heteroannulations
of 2-substituted nitrobenzenes.
Cenini et al. have reported a ruthenium-catalyzed reductive
N-heteroannulation of intermediately formed 2-nitro-N-(phenyl-
methylene)benzenamines forming 2-substituted benzimidazoles.9
For example, reaction of 2-nitro-N-(phenylmethylene)benzen-
amine (1) with carbon monoxide (50 atm, 220 ꢀC), in the presence
of a catalytic amount of triruthenium dodecacarbonyl, gave 2-
phenylbenzimidazole (2) in 86% yield (Scheme 1). In situ formation
of enamines from 2-nitrobenzenamine and aromatic aldehydes or
heptanal, using the same catalyst and reaction conditions, also
furnished 2-substituted benzimidazoles. Palladium complexes also
catalyzed this reaction using aromatic aldehydes but failed using
heptanal.8 In addition to the palladium- and ruthenium-catalyzed
reactions, potassium tetracarbonyl-hydridoferrate (KHFe(CO)4) has
N
Ph
N
N
Ru3(CO)11
CO (50 atm)
220 °C, 86%
Ph
NO2
H
1
2
Scheme 1.
In a systematic effort to expand our palladium-catalyzed
methodology for the formation of indoles to the synthesis of
benzimidazoles and other heterocycles containing two or more
nitrogen atoms, we turned our attention to reactions of imines.
2-Nitro-N-(4-nitrophenylmethylene)benzenamine (3),18 formed
by condensation between 2-nitrobenzenamine and 4-nitro-
benzaldehyde, was reacted with carbon monoxide (4 atm, 70 ꢀC) in
the presence of a catalytic amount of palladium diacetate and tri-
phenylphosphine (Scheme 2). To our disappointment, 2-(2-nitro-
phenyl)benzimidazole (4) was not observed under the reaction
conditions; only recovered imine, and hydrolysis products thereof
were isolated. We have previously noted that some substituted
2-nitrostyrenes do not undergo annulation to form indoles under
the above conditions, but could be cyclized using a catalytic amount
of bis(dibenzylidenacetone)palladium (Pd(dba)2), 1,3-bis(diphen-
ylphosphino)propane (dppp), and 1,10-phenanthroline (phen) in
DMF under 6 atm of carbon monoxide at temperatures between
70 and 120 ꢀC.19,20 However, the latter conditions also failed to
produce the expected benzimidazole 4 from 3.
The failure to produce a 2-substituted benzimidazole was ini-
tially thought to be a consequence of the size and/or electronics of
* Corresponding author. Tel.: þ1 3042933435; fax: þ1 3042934904.
E-mail address: bjorn.soderberg@mail.wvu.edu (B.C.G. So¨derberg).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.083

9676
J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
NO2
In addition, the yield of quinoxaline products is substantially
higher. Thus, the scope and limitations of this novel cyclization to
give quinoxaline derivatives from 2-nitrobenzenamine-derived
enamines were examined and the results are reported herein.24
N
N
N
NO2
See text
NO2
H
3
4 (not observed)
2. Results and discussion
Scheme 2.
Optimization of the reaction conditions for the synthesis of
quinoxalines was examined first. Two different enamines 14
(R¼Me) and 15 (R¼OMe) were prepared by condensation of com-
mercially available 4-methyl-2-nitrobenzenamine and 4-methoxy-
2-nitrobenzenamine with 2-methylpropanal, and used in this
optimization (Table 1). The choice of solvent proved to be of im-
portance. For example, reaction of enamine 14 in acetonitrile using
the original condition seen in Scheme 4 did, surprisingly, not pro-
duce any quinoxaline product even at twice the catalyst load (entry
1). However, simply changing the solvent to DMF gave under the
same reaction conditions 16 and 17 in 35% and 21% yield, re-
spectively (entry 2). Raising the reaction temperature to 150 ꢀC and
pressure to 6 atm of CO proved detrimental (entry 3). As has been
observed previously, a higher yield of products 16 and 17 was re-
alized from 14 when 1,10-phenanthroline monohydrate was added
as a co-ligand in addition to dppp (entry 4).25 Not only was the
overall yield higher, but also all starting material was consumed
after 2 h. The same effect but to a much higher extent was observed
for 15. For 15, unsatisfactory yield were obtained both at 70 and
150 ꢀC at 6 atm of CO (entries 5 and 6). However, addition of 1,10-
phenanthroline monohydrate gave 18 in high yield and selectivity
(entry 7). It is presently unclear why two bidentate ligands are
required to obtain an optimum yield. As expected, no reaction
occurred in the absence of carbon monoxide (entry 8). The CO
pressure did affect both the yield and product distribution using 15,
and a higher ratio of quinoxaline to quinoxalinone (18 to 19) was
observed at higher CO pressures. Almost no quinoxalinone 19 was
isolated at 16 atm of CO (entry 12). Although a higher ratio of
the 4-nitrophenyl group. Thus, the formation and cyclization of
imines derived from smaller aliphatic aldehydes was examined
next. However, reaction of 2-nitrobenzenamine with 2-methyl-
propanal furnished enamine 5 and not the expected imine 6
(Scheme 3). The enamine 5 was subjected to the N-hetero-
annulation conditions consisting of Pd(dba)2 (0.07 mol %) and dppp
(0.07 mol %) in DMF (w0.1 M) under 4 atm of carbon monoxide
with the anticipation of a rapid enamine–imine tautomerization
followed by cyclization to give 2-(1-methylethyl)benzimidazole.21
However, after complete consumption of starting material and
purification, two new products, 1,2-dihydroquinoxaline 7 and
3,4-dihydroquinoxalinone 8, were isolated in place of the expected
benzimidazole (Scheme 4).
H
N
NH2
NO2
N
CHO
Benzene
4 Å MS, -20 °C
+
NO2
NO2
5 (73%)
6 (not observed)
Scheme 3.
H
N
H
N
O
N
Pd(dba)2, dppp, MeCN
CO (4 atm), 70 °C
N
H
N
H
NO2
Table 1
5
7 (71%)
8 (11%)
Optimization of reaction conditions
Scheme 4.
H
N
H
N
O
N
Pd(dba)2, L1, L2
Quinoxalines have been isolated in two cases from N-hetero-
annulations of N-(2-propen-1-yl)-2-nitrobenzenamine (9)22 or
N-phenyl-N-(2-methyl-2-propen-1-yl)-2-nitrobenzenamine (10)23
pressure CO
temp °C, solvent
R
N
H
R
NO2
R
N
H
R = Me (14)
R = OMe (15)
16
18
17
19
using
a triruthenium dodecacarbonyl (7 mol %) or palladium
diacetate (60 mol %), respectively (Schemes 5 and 6). 2-Ethenyl-
benzimidazole 11 was the major product from the ruthenium-
catalyzed reaction.
The reaction conditions for the annulation seen in Scheme 4 are
significantly milder compared to the ruthenium-catalyzed reaction.
Entry 14/ Solventa L1¼
L2¼
CO
Temperature Time Yield
15
dpppb phenc
pressured (ꢀC)
(h)
16:17 or
18:19 (%)
(mol %) (mol %) (atm)
1
2
3
4
5
6
7
8
14 MeCN
14 DMF
14 DMF
14 DMF
15 DMF
15 DMF
15 DMF
15 DMF
15 DMF
15 DMF
15 DMF
15 DMF
15 DMF
15 DMF
13
6
7
7
9
8
6
6
6
6
6
6
6
d
d
d
d
14
d
d
12
12
12
12
12
12
12
12
4
4
6
6
6
6
6
70
70
140
70
70
150
70
70
70
70
70
70
70
70
68
0
120 35:21
60 20:3
H
N
N
N
N
Ru3(CO)12, 170 °C
2
120
17
36
18
50:45
1:6
0:13
88:1
0
CO (60 atm), cyclooctene
NO2
N
H
9
11 (42%)
12 (14%)
No CO
2
4
8
16
6
9
18 60:9
18 83:3
18 88:3
18 99:1
18 60:6
18 50:3
Scheme 5.
10
11
12
13e
14e
Ph
N
Ph
N
6
Pd(OAc)2, 1,10-phenanthroline
140 °C, CO (5 atm), DMF
a
Substrate concentration w0.1 M for entries 1–6 and w0.3 M for entries 7–14;
N
H
NO2
10
ratio Pd(dba)2/L1¼w1:1.
b
dppp¼1,3-bis(diphenylphosphino)propane.
c
phen¼1,10-phenanthroline monohydrate.
13 (53%)
d
Initial CO pressure.
e
Scheme 6.
Pd(OAc)2 was used as the catalyst in place of Pd(dba)2.

J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
9677
products was obtained at higher pressures, 6 atm was selected as
the standard pressure (entry 7) due to the ease of manipulations
using simple glass pressure equipment compared to the steel re-
action vessel required at pressures above 8 atm. Finally, palladium
diacetate could be used as the catalyst, however lower yields were
observed (entries 13 and 14).
A variety of enamines were prepared by condensation of
substituted 2-nitrobenzenamines with aliphatic aldehydes, usually
2-methylpropanal. The results of the condensation reactions are
summarized in Table 2. Most condensation reactions were carried
out in benzene or dichloromethane at ambient temperature, under
an inert atmosphere, in the presence of 4 Å molecular sieves. The
yield of 22 was substantially improved by heating the reaction
mixture in a standard microwave oven. In general, the condensa-
tion reactions produced the desired enamines in good yields. It
should be noted that all enamines prepared underwent noticeable
hydrolysis upon standing at ambient temperature for a short period
of time. Enamine 22 was particularly unstable and was therefore
used immediately after purification in the next step. The low
isolated yield of 22 is likely a reflection of its instability. Attempts to
generate 22 in situ and immediately submit the compound to the
annulation conditions without purification failed to give quinoxa-
line products.
We were unable to prepare enamines from
a 2-nitro-
aminobenzene and unbranched aliphatic aldehydes such as
heptanal by this methodology, again probably a reflection of the
sensitivity of the enamines to hydrolysis. In addition to pursuing
ring-substituted 2-nitroaminobenzenes, a pyridine-derived en-
amine was also prepared. Thus, condensation of 2-amino-3-nitro-
pyridine and 2-methylpropanal gave the desired compound 30, but
in low yield. The mainproduct of the reactionwas the corresponding
aminal formed from two molecules of 2-amino-3-nitropyridine.
With a variety of enamines available, the N-heteroannulation
was examined next. Enamines having an electron-rich aromatic
ring gave varying ratios of quinoxaline and quinoxalinone products
in all cases examined (Table 2, entries 1–6). The expected spi-
rocyclic products were obtained from enamine 27 (entry 10), and in
the case of the diphenyl-substituted enamine 28 only the corre-
sponding quinoxaline 42 was isolated (entry 11). In contrast, en-
amines having an electron-poor aromatic ring gave lower or no
yield of cyclized products. Impure material was obtained from the
phenylketo-substituted enamine 24. The product consisting mainly
of the quinoxaline 39 could not be further purified. Although
completely consumed during the reaction, both the carbomethoxy-
and nitro-substituted enamines (25 and 26) did not produce any
identifiable products (entries 8 and 9). The fully aromatic qui-
noxaline 43 and corresponding N-oxide 44 were obtained using the
mono-phenyl substituted enamine 29, albeit in lower yields (entry
12). Finally, low yields of products were also obtained from the
pyridine-derived enamine 30 (entry 13).
Table 2
Synthesis of quinoxalines and quinoxalinones
Entry
Enaminea
Quinoxalineb
Quinoxalinoneb
H
N
H
N
N
O
N
H
N
R
NO2
R
R
H
17 (45%)
19 (1%)
32 (16%)
33 (45%)
34 (42%)
35 (12%)
1
2
3
4
5
6
7
8
9
14 (R¼4-Me, 89%)
15 (R¼4-OMe, 94%)
20 (R¼4-Cl, 99%)
16 (50%)
18 (88%)
31 (56%)
33 (29%)
35 (27%)
37 (63%)
39 (<52%)
d
21 (R¼5-Cl, 88%)
In addition to the enamines described in Table 1, one additional
enamine was examined. Condensation of 1,3-cyclohexanedione
with 2-nitrobenzenamine gave enamine 47 in 70% isolated yield
(Scheme 7). N-heteroannulation of 47 gave the fully aromatic
compound 48 in low isolated yield.
22 (R¼6-Me, 5%)
23 (R¼3-Me, 36%)
24 (R¼4-COPh, 20%)
25 (R¼4-CO2Me, 74%)
26 (R¼4-NO2, 77%)
d
H
N
The initial hypothesis that imines derived from 2-nitrobenzen-
amines would undergo palladium-catalyzed reductive N-hetero-
annulation to afford 2-substituted benzimidazoles, was revisited.
Since the condensation reactions between 2-nitrobenzenamines
and aldehydes did not furnish any observable amount of imines, the
well-documented aza-Wittig reaction between organic azides and
aldehydes was examined.26 In the event, aryl-azide 49 was treated
with triphenylphosphine followed by addition of a large excess of
2-methylpropanal affording a deep red reaction mixture. 1H NMR of
this mixture was inconclusive with broad unresolved signals. Thus,
the crude product was immediately submitted to the annulation
conditions, from which three products were obtained, the azide-
reduction product, 2-methyl-6-nitrobenzeneamine, the expected
2-(1-methylethyl)-4-methylbenzimidazole 50, and dihydroquin-
oxaline 35 (Scheme 8). The benzimidazole was the major product
from this reaction and was probably formed by annulation of the
imine. This is the first example of a palladium-catalyzed reductive
H
N
N
O
MeO
MeO
Cl
N
H
MeO
N
H
MeO
NO2
27 (88%)
10
40 (70%)
41 (13%)
H
N
Ph
N
Ph
Ph
Ph
N
H
MeO
NO2
11
12
28 (91%)
42 (69%)
H
N
N
N
N
Ph
N
O
Ph
Cl
Ph
Cl
NO2
N-heteroannulation forming
a benzimidazole from an imine
29 (85%)c
43 (25%)
44 (14%)
derived from an aliphatic aldehyde.27
The parent compound, 1-azido-2-nitrobenzene, was reacted in
a similar fashion with triphenylphosphine and heptanal followed
by annulation (Scheme 9). Three products were again isolated
and characterized, 2-hexylbenzimidazole (51), 2-pentylquinoxaline
(52), and 2-pentylquinoxaline-1-oxide (53). The latter type of
product was also observed using compound 29 (Table 2, entry 12).
Considering that mixtures of products were obtained by the aza-
Wittig-annulation sequence, this approach to benzimidazoles was
not further pursued.
H
N
H
N
N
N
N
O
N
N
H
N
H
NO2
13
30 (20%)d
45 (34%)
46 (6%)
a
Isolated yield of enamine from the corresponding 2-nitrobenzenamine and
aldehyde.
b
Isolated yield of 1,2-dihydroquinoxaline and 3,4-dihydroquinoxalinone.
As a 6:4 E/Z mixture.
c
Water in the solvent, or in the carbon monoxide, was initially
considered a possible source of the 3,4-dihydroquinoxalinone
d
21% of an aminal was also isolated.

9678
J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
H
N
O
NH2
NO2
N
N
Pd(dba)2, dppp, phen
Benzene
H2SO4
+
CO (6 atm), 120 °C, DMF
O
NO2
O
OH
47 (70%)
48 (26%)
Scheme 7.
N
N3
N
N
1) PPh3
2) OHC
50 (62%)
NO2
NO2
H
Pd(dba)2, dppp
phen, CO (6 atm)
70 °C, DMF
49
H
N
N
35 (11%)
N
H
NO2
Scheme 8.
1) PPh3, Et2O
N
N
N3
NO2
N
N
N
2) C6H13CHO, CHCl3
C6H13
3) Pd(dba)2, dppp, phen
CO (6 atm), 70 °C, DMF
C5H11
N
O
C5H11
H
51 (14%)
Scheme 9.
52 (25%)
53 (8%)
oxygen. However, reaction of enamine 5 in a 1:1 DMF–water
mixture gave only the 1,2-dihydroquinoxaline 7 in 37% yield in
addition to a small amount of starting material. No trace of 3,4-
dihydroquinoxalinone 8 was observed by 1NMR of the crude
reaction mixture. It should be noted that only hydrolysis of the
enamine was observed using water as the solvent.
Oxidation of the 1,2-dihydroquinoxaline to the 3,4-dihydro-
quinoxalinone was not observed under standard reaction condi-
tions. For example, no trace of oxidation of 1,2-dihydroquinoxaline
21 could be detected after prolonged treatment with the catalytic
system. The reverse reaction, i.e., reduction of 3,4-dihydroquin-
oxalinone to 1,2-dihydroquinoxaline, was also disproved under
the same conditions. These results suggest that the 3,4-dihydro-
quinoxalinone oxygen is derived from the nitro group.
The mechanism of the annulation reaction is presently unclear;
however, a few possible sequences of events are outlined in Scheme
10. The true mechanism is most likely more complex. Transition
metal-catalyzed deoxygenation of organic nitro-compounds has
H
N
H
N
N
N
N
N
a
Pd(0), CO
-CO2
H
N
N
O
N
O
54
H
OH
56
Pd(0), CO
-CO2
Pd
NO2
H
N
H
N
H
N
CO
b
-CO2
O
57
N
Pd
Pd
N
O
N
Pd
55
O
O
H
H
H
N
N
N
N
N
β-elim.
-CO2
O
CO
c
O
Pd
60
Pd
N
PdH
Pd
N
N
61
58
59
d
β-elim.
H
N
H
N
O
O
N
H
N
PdH
62
Scheme 10.

J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
9679
been proposed to proceed via the formation of a free or metal-
complexed nitrosoarene, in this case compounds 54 and 55, re-
spectively.28 The nitrosoarene can undergo cyclization with the
adjacent enamine to give an N-hydroxy-1,2-dihydroquinoxaline 56
(path a). This intermediate is finally deoxygenated by the catalyst
system to give a 1,2-dihydroquinoxaline, a reaction with pre-
cedence in literature.29 A second deoxygenation may occur from
the metal-bound nitrosoarenes, affording a free or metal-bound
nitrene (57, path b). An intramolecular [2þ2] cycloaddition be-
tween the intermediately formed palladium-bound nitrene 57 and
the alkene would furnish the bicyclic compound 58. Sequential
respectively. However, it is unclear how the nitroso-oxygen is lost
in the reaction.
N
NH2
NO
N
N
Me2CHCHO, CH2Cl2, RT
4Å MS, CSA, 40 d
N
H
H
63
7 (5%)
64 (3%)
Scheme 12.
In conclusion,
a novel synthesis of functionalized 1,2-di-
b
-hydride elimination, at least formally, to give 59 followed by re-
hydroquinoxalines and 3,4-dihydro-2-quinoxalinones has been
developed. Some mechanistic insights lending support for nitro-
soarene/nitrene intermediates have been presented. Current efforts
are focused on the selective synthesis of either 1,2-dihydro-
quinoxalines or 3,4-dihydro-2-quinoxalinones.
ductive elimination would again produce a 1,2-dihydroquinoxaline
and regenerate the active palladium(0) catalyst. It should be
pointed out that no reaction apart from hydrolysis of the enamine
was observed in the absence of carbon monoxide. The regio-
selectivity of the cycloaddition parallels the selectivity observed
for intramolecular ketene–alkene cycloadditions of terminally di-
substituted alkenes. A related mechanism has been suggested for
thermal decompositions of arylamino-substituted Fischer carbene
complexes forming quinolines.30 In addition the formation of a
palladium-bound nitrene was suggested for the formation of the
tetrahydroquinoxaline seen in Scheme 6.23
It is also possible that the enamine inserts into the palladium-
bound nitroarene forming a bicyclic complex 60. Insertion of car-
bon monoxide forming 61 and deinsertion of carbon dioxide would
furnish 58, the intermediate suggested in path b. Finally, formation
of intermediate 62 is possible if insertion of carbon monoxide is
slower compared to
ductive elimination of 62 would then furnish a quinoxalinone. It
should be noted that the -elimination step from 58 and 60 is not
a one-step reaction since the hydrogen and the metal cannot
achieve a syn relationship. The mechanistic picture is supported
by the observation that the ratio of 1,2-dihydroquinoxaline to 3,4-
dihydro-2-quinoxalinone is significantly increased at higher carbon
monoxide pressures (Table 1, entries 7–11), i.e., the rate of
deoxygenation is increased (paths b and c).
3. Experimental section
3.1. General procedures
NMR spectra were determined in CDCl3 at 270 MHz (1H NMR)
and 67.5 MHz (13C NMR) unless otherwise noted. The chemical
shifts are expressed in d
values relative to (CH3)4Si (0.00, 1H and 13C)
or CDCl3 (7.26, 1H and 77.0, 13C) internal standards. 1H–1H coupling
constants are reported as calculated from spectra; thus, a slight
difference in Ja,b and Jb,a is usually obtained. Results of APT
(attached proton test) 13C NMR experiments are shown in paren-
theses, where relative to CDCl3, (ꢁ) denotes CH3 or CH and (þ)
denotes CH2 or C.
b-hydride elimination from 60 (path d). Re-
b
Benzene and diethyl ether were distilled from sodium benzo-
phenone ketyl prior to use. Hexanes, acetonitrile, ethyl acetate, and
dichloromethane were distilled from calcium hydride. Chemicals
prepared according to literature procedures have been referenced
the first time they are used; all other reagents were obtained from
commercial sources and used as received. Silica gel (200–400
mesh) was used for flash chromatography. Solvents were removed
using a rotary evaporator at water aspirator pressure unless
otherwise noted.
A phosphorus-bound nitrene has been suggested as an in-
termediate for trialkylphosphite-mediated reductive annulations of
2-nitrostyrenes to give indoles (Cadogan–Sundberg reaction). This
type of reducing agent was also examined in this study, however,
reaction of 20 with triethylphosphite at 170–180 ꢀC did not furnish
any identifiable product (Scheme 11). The absence of quinoxaline
product(s) is not so surprising considering the thermal instability of
the starting enamines.
3.1.1. 2-Nitro-N-(2-methyl-1-propene-1-yl)benzenamine (5)
To a solution of 2-nitrobenzenamine (502 mg, 3.63 mmol) and
2-methylpropanal (330 mL, 3.64 mmol) dissolved in benzene
(10 mL) at ꢁ20 ꢀC under argon atmosphere was added 4 Å mole-
cular sieves (4 g); the molecular sieves were activated by heating
to 120 ꢀC under vacuum overnight and then stored under argon
atmosphere. The reaction was allowed to sit without stirring or
agitation at ꢁ20 ꢀC for 14 days. The molecular sieves were removed
by filtration and rinsed with CH2Cl2. The filtrate was concentrated
and the crude product was purified by chromatography (hexanes/
EtOAc, 95:5) to give 5 (510 mg, 2.65 mmol, 73%) as a red solid. Mp
H
N
P(OEt)3
no identified product
Δ
Cl
NO2
20
38–40 ꢀC; 1H NMR
d
9.64 (br s, 1H), 8.18 (d, J¼8.4, 1.5 Hz, 1H), 7.44
Scheme 11.
(dt, J¼8.6, 1.5 Hz, 1H), 7.05 (d, J¼8.7 Hz, 1H), 6.70 (dt, J¼6.9, 1.2 Hz,
In order to probe into the involvement of a free or a metal-
bound 2-nitrosoarene as an intermediate in the annulation re-
action, 2-nitrosobenzenamine 63 was prepared according to the
procedure reported by Haddadin et al.31,32 Unfortunately, all
attempts to isolate the corresponding 2-nitrosoenamine by con-
densation with 2-methylpropanal, as described above, failed.
Surprisingly, reaction of 2-nitrosobenzenamine with 2-methyl-
1H), 6.27 (dm, J¼8.2, 1.2 Hz, 1H), 1.82 (s, 3H), 1.80 (s, 3H); 13C NMR
d
141.3 (þ), 136.0 (ꢁ), 131.6 (þ), 126.7 (ꢁ), 118.4 (þ), 118.2 (ꢁ), 116.3
(ꢁ), 114.1 (ꢁ), 22.5 (ꢁ), 16.6 (ꢁ); IR (neat) 1639 cmꢁ1; HRMS (EI)
calcd for C10H12N2O2 (Mþ) 192.0899, found 192.0899.
3.1.2. 4-Methyl-2-nitro-N-(2-methyl-1-propene-1-yl)-
benzenamine (14)
propanal gave dihydroquinoxaline
7
and 2-(1-methylethyl)-
Reaction of 4-methyl-2-nitrobenzenamine (501 mg, 3.29 mmol),
benzimidazole (64), albeit in very low yields and after prolonged
reaction times (Scheme 12). Although the starting material was
consumed in the reaction, no other products were identified. It is
likely that the dihydroquinoxaline and benzimidazole are formed
from the corresponding enamine and imine intermediate,
2-methylpropanal (300 mL, 3.3 mmol), and 4 Å molecular sieves
(4 g) in benzene (10 mL) at ambient temperature(20 h), as described
for 5, gave after chromatography (hexanes/EtOAc, 95:5),14 (601 mg,
2.91 mmol, 89%) as a red solid. Mp 53–55 ꢀC; 1H NMR
d
9.56 (br s,
1H), 7.98 (s, 1H), 7.27 (dd, J¼8.6, 2.2 Hz, 1H), 6.96 (d, J¼8.9 Hz, 1H),

9680
J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
6.27 (dm, J¼9.6 Hz,1H), 2.28 (s, 3H),1.81 (s, 3H),1.79 (s, 3H); 13C NMR
product was purified by chromatography (hexanes/EtOAc, 9:1) to
give 22 (71 mg, 0.34 mmol, 5%) as a red paste.33 1H NMR
8.75 (d,
d
139.4 (þ), 137.5 (ꢁ), 131.1 (þ), 126.0 (þ), 125.8 (ꢁ), 118.4 (ꢁ), 117.4
d
(þ), 114.1 (ꢁ), 22.4 (ꢁ), 19.9 (ꢁ), 16.6 (ꢁ); IR (neat) 1632 cmꢁ1. Anal.
J¼5.9 Hz, 1H), 7.95 (d, J¼8.6 Hz, 1H), 7.30 (d, J¼7.4 Hz, 1H), 6.76 (t,
Calcd for C11H16N2O2: C, 64.06; H, 6.84. Found: C, 64.18; H, 6.70.
J¼7.7 Hz, 1H), 5.98 (d, J¼8.4 Hz, 1H), 2.40 (s, 3H), 1.76 (s, 3H), 1.72 (s,
3H); 13C NMR
d
141.5 (þ), 138.2 (ꢁ), 137.3 (þ), 129.4 (þ), 124.2 (ꢁ),
3.1.3. 4-Methoxy-2-nitro-N-(2-methyl-1-propene-1-yl)-
benzenamine (15)
124.1 (ꢁ), 118.5 (ꢁ), 114.6 (þ), 22.2 (ꢁ), 20.9 (ꢁ), 16.3 (ꢁ); IR (neat)
1634, 1598, 1339 cmꢁ1
.
4-Methoxy-2-nitrobenzenamine (506 mg, 3.01 mmol) was
added to an airless flask under a stream of argon. 2-Methylpropanal
(300 mL, 3.29 mmol) was added via syringe. Freshly distilled ben-
3.1.7. 3-Methyl-2-nitro-N-[(2-methyl)-1-propene-1-yl]-
benzenamine (23)
zene (10 mL) was then added to the flask. The flask was gently
heated with a heat-gun to dissolve the benzenamine. Approxi-
mately 5 g of 4 Å molecular sieves (the sieves were activated by
heating at 120 ꢀC under vacuum overnight) was added under
a stream of argon. The reaction was allowed to sit for 20 h without
stirring; a slow color change from yellow to deep purple was
observed. The solution was filtered and the molecular sieves were
washed with CH2Cl2. The solvents were removed from the filtrate
at water aspirator pressure. The crude product was purified by
column chromatography (hexanes/ethyl acetate, 98:2) to give 15
(635 mg, 2.86 mmol, 95%) as a deep red solid. Mp 57–59 ꢀC; 1H
Reaction of 3-methyl-2-nitrobenzenamine (500 mg, 3.29 mmol),
2-methylpropanal (500 mL, 5.5 mmol), and 4 Å molecular sieves
(15 g) in benzene (20 mL) at ambient temperature (3 days), as de-
scribed for 5, gave after chromatography (hexanes), 23 (241 mg,
1.17 mmol, 36%) as a red paste.33 1H NMR
d
8.24 (d, J¼8.4 Hz, 1H),
7.23 (t, J¼7.9 Hz, 1H), 6.84 (d, J¼8.6 Hz, 1H), 6.58 (d, J¼7.4 Hz, 1H),
6.12 (d, J¼9.4 Hz, 1H), 2.49 (s, 3H), 1.78 (s, 3H), 1.73 (s, 3H); 13C NMR
d
140.3 (þ), 135.9 (þ), 135.5,133.3 (ꢁ), 120.5 (ꢁ),119.4 (ꢁ),116.8 (þ),
112.3 (ꢁ), 22.5 (ꢁ), 21.6 (ꢁ), 16.6 (ꢁ).
3.1.8. [4-(2-Methylpropenylamino)-3-nitrophenyl]phenyl-
methanone (24)
Reaction of 3-nitro-4-aminobenzophenone (500 mg, 2.06 mmol),
2-methylpropanal (300 mL, 3.3 mmol), and 4 Å molecular sieves
NMR
3.0 Hz, 1H), 7.02 (d, J¼9.4 Hz, 1H), 6.27 (dm, J¼9.6 Hz, 1H), 3.81 (s,
3H), 1.81 (s, 3H), 1.79 (s, 3H); 13C NMR
d
9.61 (d, J¼8.2 Hz, 1H), 7.60 (d, J¼2.7 Hz, 1H), 7.15 (dd, J¼9.4,
d
150.2 (þ), 137.0 (þ), 130.6
(þ), 127.1 (ꢁ), 118.5 (ꢁ), 117.5 (þ), 115.5 (ꢁ), 106.5 (ꢁ), 55.6 (ꢁ), 22.4
(15 g) in CH2Cl2 (40 mL) at ambient temperature (12 days), as
(ꢁ), 16.6 (ꢁ); IR (neat) 1638, 1520, 1162, 1122 cmꢁ1. Anal. Calcd for
described for 5, gave after chromatography (hexanes/EtOAc, 9:1),
C
11H14N2O3: C, 59.45; H, 6.35. Found: C, 59.18; H, 6.42.
24 (120 mg, 0.41 mmol, 20%) as a red paste.33 1H NMR
d 9.96 (d,
J¼9.4 Hz,1H), 8.66 (d, J¼2.0 Hz,1H), 8.04 (dd, J¼9.1, 2.0 Hz,1H), 7.75
3.1.4. 4-Chloro-2-nitro-N-(2-methyl-1-propene-1-yl)-
benzenamine (20)
Reaction of 4-chloro-2-nitrobenzenamine (505 mg, 2.93 mmol),
2-methylpropanal (270 mL, 2.9 mmol), and4 Å molecularsieves (4 g)
in benzene (10 mL) at ambient temperature (26 h), as described for
5, gave without further purification 20 (660 mg, 2.91 mmol, 99%)
(dd, J¼8.4, 1.5 Hz, 2H), 7.60 (t, 1H), 7.50 (t, 2H), 7.14 (d, J¼9.1 Hz, 1H),
6.34 (d, J¼9.4 Hz, 1H), 1.86 (s, 3H), 1.84 (s, 3H); 13C NMR
193.4 (þ),
d
143.4 (þ), 137.4 (þ), 136.8 (ꢁ), 132.3 (ꢁ), 130.7 (ꢁ), 130.5 (þ), 129.4
(ꢁ), 128.5 (ꢁ), 125.5 (þ), 121.8 (þ), 117.6 (ꢁ), 114.3 (ꢁ), 22.6 (ꢁ), 16.9
(ꢁ); IR (neat) 1650, 1612, 1209, 1132 cmꢁ1
.
as a red solid. Mp 109–110 ꢀC; 1H NMR
d
9.58 (d, J¼8.2 Hz, 1H), 8.17
3.1.9. Methyl 4-(N-2-methyl-1-propene-1-yl)amino-3-nitro-
benzoate (25)
Reaction of methyl 4-amino-3-nitrobenzoate (500 mg,
2.55 mmol), 2-methylpropanal (500 mL, 55.1 mmol), camphor sul-
fonic acid (10 mg), 4 Å molecular sieves (50 g) in CH2Cl2 (150 mL) at
ambient temperature (11 days), as described for 5, gave after
chromatography (hexanes/EtOAc, 95:5) 25 (470 mg, 1.88 mmol,
(d, J¼2.7 Hz, 1H), 7.38 (dd, J¼9.2, 2.5 Hz, 1H), 7.01 (d, J¼9.1 Hz, 1H),
6.22 (dm, J¼9.6,1.2 Hz,1H),1.82 (s, 3H),1.79 (s, 3H); 13C NMR
d
140.0
(þ),136.2 (ꢁ),131.5 (þ),125.9 (ꢁ),121.2 (þ),119.9 (þ),118.0 (ꢁ),115.7
(ꢁ), 22.5 (ꢁ), 16.8 (ꢁ); IR (neat) 1641 cmꢁ1. Anal. Calcd for
C
10H11ClN2O2: C, 52.99; H, 4.89. Found: C, 53.08; H, 4.82.
3.1.5. 5-Chloro-2-nitro-N-(2-methyl-1-propene-1-yl)-
benzenamine (21)
74%) as a red solid. Mp 121–124 ꢀC; 1H NMR
d
9.87 (d, J¼11.4 Hz,
1H), 8.89 (d, J¼2.0 Hz, 1H), 8.05 (dd, J¼9.2, 1.5 Hz, 1H), 7.06 (d,
Reaction of 5-chloro-2-nitrobenzenamine (504 mg, 2.92 mmol),
J¼9.2 Hz, 1H), 6.30 (d, J¼9.4 Hz, 1H), 3.91 (s, 3H), 1.85 (s, 3H), 1.82 (s,
2-methylpropanal (300
mL, 3.3 mmol), and 4 Å molecular sieves
3H); 13C NMR
d
165.4 (þ), 143.4 (þ), 136.1 (ꢁ), 131.0 (þ), 129.4 (ꢁ),
(4 g) in CH2Cl2 (15 mL) at ambient temperature (24 h), as described
121.2 (þ), 118.1 (þ), 117.6 (ꢁ), 113.9 (ꢁ), 52.1 (ꢁ), 22.6 (ꢁ), 16.8 (ꢁ);
IR (neat) 1707, 1615, 1523, 1437, 1287, 1217 cmꢁ1; HRMS (EI) calcd
for C12H14N2O4 (Mþ) 250.0954, found 250.0960.
for 5, gave without further purification, 21 (585 mg, 2.58 mmol,
88%) as a red solid. Mp 99–100 ꢀC; 1H NMR
d 9.60 (br s, 1H), 8.13 (d,
J¼9.2 Hz,1H), 7.02 (d, J¼2.2 Hz,1H), 6.66 (dd, J¼9.2, 2.2 Hz,1H), 6.19
(d, J¼9.4 Hz,1H), 1.83 (s, 3H), 1.79 (s, 3H); 13C NMR
d
142.8 (þ), 141.8
3.1.10. 2,4-Dinitro-N-(2-methyl-1-propene-1-yl)benzenamine (26)
The same procedure as described for 22 was repeated except
that a mixture of 2,4-dinitrobenzenamine (1.00 g, 5.46 mmol), 2-
methylpropanal (1.00 mL, 13.9 mmol), and 1,2-dichloroethane
(20 mL) was reacted for a total of 15 min. Purification by chroma-
tography (hexanes/EtOAc, 9:1) gave 26 (1.00 g, 4.21 mmol, 77%) as
(þ), 130.3 (þ), 128.2 (ꢁ), 120.5 (þ), 117.8 (ꢁ), 116.9 (ꢁ), 113.8 (ꢁ),
22.5 (ꢁ), 16.8 (ꢁ); IR (neat) 3112, 1570 cmꢁ1; HRMS (EI) calcd for
C
10H11ClN2O2 (Mþ) 226.0509, found 226.0500.
3.1.6. 6-Methyl-2-nitro-N-(2-methyl-1-propene-1-yl)-
benzenamine (22)
a red solid. Mp 113–115 ꢀC; 1H NMR
d
10.06 (d, J¼8.2 Hz, 1H), 9.16
To
a
solution of 2-methyl-6-nitrobenzenamine (1.03 g,
(d, J¼2.5 Hz, 1H), 8.27 (dd, J¼9.6, 2.7 Hz, 1H), 7.12 (d, J¼9.6 Hz, 1H),
6.77 mmol) and 2-methylpropanal (2.00 mL, 22.0 mmol) dissolved
in 1,2-dichloroethane (20 mL) in an ACE-Glass threaded pressure
tube was added 4 Å molecular sieves until the level of the sieves
was just below that of the solvent. The pressure tube was capped
tightly with a threaded Teflon plug. The reaction was heated in
a standard microwave oven for 30 s and then allowed to cool for
3-5 min. This was repeated until the total heating time reached
15 min. The molecular sieves were removed by filtration and
washed with CH2Cl2. The filtrate was concentrated and the crude
6.32 (d, J¼9.4 Hz, 1H), 1.88 (s, 3H), 1.85 (s, 3H); 13C NMR
143.8 (þ),
d
136.5 (þ), 130.0 (ꢁ), 129.9 (þ), 124.1 (ꢁ), 124.0 (þ), 117.0 (ꢁ), 114.4
(ꢁ), 22.5 (ꢁ), 16.8 (ꢁ); IR (neat) 1590, 1426 cmꢁ1. Anal. Calcd for
C
10H11N3O4: C, 50.63; H, 4.67. Found: C, 50.79; H, 4.77.
3.1.11. 4-Methoxy-2-nitro-N-(cyclohexylmethylene)-
benzenamine (27)
Reaction of 4-methoxy-2-nitrobenzenamine (508 mg, 3.02 mmol),
formylcyclohexane (360 mL, 3.2 mmol), and 4 Å molecular sieves

J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
9681
(4 g) in benzene (10 mL), at ambient temperature (2.5 h), as de-
1245 cmꢁ1; HRMS (EI) calcd for C14H18N6O4 (MþþHþ) 333.1311,
scribed for 5, gave without further purification 27 (696 mg,
found 333.1300.
2.65 mmol, 88%) as a red solid. Mp 46–48 ꢀC; 1H NMR
d 9.68 (br s,
1H), 7.60 (d, J¼2.7 Hz, 1H), 7.15 (dd, J¼9.4, 3.2 Hz, 1H), 7.05 (d,
3.1.15. 1,2-Dihydro-2,2-dimethylquinoxaline34 (7) and 3,4-dihydro-
3,3-dimethyl-2-quinoxalinone35 (8)
J¼9.2 Hz, 1H), 6.22 (d, J¼9.4 Hz, 1H), 3.81 (s, 3H), 2.3–1.5 (m, 10H);
13C NMR
d
150.3 (þ), 137.4 (þ), 130.6 (þ), 127.2 (ꢁ), 126.1 (þ), 115.6
2-Nitro-N-[(2-methyl)-1-propenyl]benzenamine (5) (102 mg,
0.53 mmol), Pd(dba)2 (20 mg, 0.035 mmol), 1,3-bis(diphenyl-
phosphino)propane (dppp) (15 mg, 0.036 mmol), and acetonitrile
(5 mL) were combined in an ACE-Glass threaded pressure tube
fitted with a pressure head. The tube was flushed three times with
carbon monoxide and then pressurized to 4 atm. The reaction was
heated and stirred at 70 ꢀC under CO (4 atm, 20 h). The reaction
mixture was filtered through Celite and washed with CH2Cl2. The
solvent was removed at reduced pressure and the product was
purified by chromatography (hexanes/EtOAc, 7:3) to give 7 (60 mg,
0.375 mmol, 71%) and 8 (10 mg, 0.057 mmol, 11%) as off-white
solids. Mp for 7: 103–104 ꢀC (lit.34 107 ꢀC). Mp for 8: 178–179 ꢀC
(lit.35 179–181 ꢀC).
(ꢁ), 115.5 (ꢁ), 106.6 (ꢁ), 55.7 (ꢁ), 33.6 (þ), 28.3 (þ), 27.5 (þ), 26.9
(þ), 26.6 (þ); IR (neat) 2929, 1517 cmꢁ1; HRMS (EI) calcd for
C
14H18N2O3 (Mþ) 262.1317, found 262.1310.
3.1.12. 4-Methoxy-2-nitro-N-(2,2-diphenylethenyl)-
benzenamine (28)
Reaction of 4-methoxy-2-nitrobenzenamine (304 mg,1.80 mmol),
diphenylethanal (400 mL, 2.3 mmol), 4 Å molecular sieves (15 g) in
CH2Cl2 (30 mL) at ambient temperature (3 days), as described for
5, gave after chromatography (hexanes/EtOAc, 9:1) 28 (572 mg,
1.65 mmol, 92%) as a red solid. Mp 152–153 ꢀC; 1H NMR
d
9.93 (d,
J¼11.6 Hz, 1H), 7.53 (d, J¼2.7 Hz, 1H), 7.48–7.05 (m, 13H), 3.74 (s,
3H); 13C NMR
d
151.3 (þ), 140.7 (þ), 137.4 (þ), 135.1 (þ), 132.2 (þ),
129.7 (ꢁ), 129.3 (ꢁ), 128.4 (ꢁ), 127.9 (ꢁ), 126.6 (ꢁ), 126.5 (two
3.1.16. 1,2-Dihydro-2,2,7-trimethylquinoxaline (16) and 3,4-
dihydro-3,3,6-trimethyl-2-quinoxalinone35 (17)
overlapping peaks; both ꢁ), 124.0 (þ),121.6 (ꢁ),115.8 (ꢁ), 107.4 (ꢁ),
55.8 (ꢁ); IR (neat) 3055, 1517 cmꢁ1
;
HRMS (ESI) calcd for
Reaction of 14 (102 mg, 0.49 mmol), Pd(dba)2 (18 mg,
0.031 mmol), dppp (14 mg, 0.034 mmol), and phen (12 mg,
0.067 mmol) in DMF (5 mL) at 70 ꢀC under CO (6 atm, 2 h), as
described for 7, gave after chromatography (hexanes/EtOAc, 7:3)
16 (43 mg, 0.25 mmol, 50%) and 17 (42 mg, 0.22 mmol, 45%) as
off-white solids. Analytical data for 16: mp 112–115 ꢀC; 1H NMR
C
21H19N2O3 (MþHþ) 347.1390, found 347.1391.
3.1.13. (E)-4-Chloro-2-nitro-N-(2-phenylethen-1-yl)benzenamine
(29-E) and (Z)-4-chloro-2-nitro-N-(2-phenylethen-1-yl)benzen-
amine (29-Z)
Reaction of 4-chloro-2-nitrobenzenamine (1.00 g, 5.79 mmol),
d
7.23 (s, 1H), 7.13 (d, J¼7.7 Hz, 1H), 6.53 (d, J¼7.7 Hz, 1H), 6.31 (s,
phenylethanal (700
mL, 6.0 mmol), and 4 Å molecular sieves (15 g)
1H), 3.87 (d, J¼4.2 Hz,1H), 2.24 (s, 3H),1.30 (s, 6H); 13C NMR
d 159.5
in CH2Cl2 (35 mL) at ambient temperature (20 h), as described for 5,
gave after solvent removal 29-E and 29-Z (1.35 g, 4.99 mmol, 86%,
E/Z¼6:4, by 1H NMR) as a red solid. The compounds partially de-
compose/hydrolyze upon column chromatography. Small amount
of pure 29-Z was obtained having the following analytical data: mp
(ꢁ), 139.0 (þ), 136.4 (þ), 129.2 (þ), 127.4 (ꢁ), 119.2 (ꢁ), 114.1 (ꢁ),
50.3 (þ), 27.1 (ꢁ), 21.4 (ꢁ); IR (neat) 3240, 2964, 1610, 1482, 1453,
1322, 1246 cmꢁ1; HRMS (EI) calcd for C11H14N2 174.1157, found
174.1163.
Analytical data for 17: mp 140–141 ꢀC (lit.35 mp 140 ꢀC).
104–106 ꢀC; 1H NMR
d
10.41 (d, J¼10.6 Hz, 1H), 8.20 (d, J¼2.5 Hz,
1H), 7.5–7.4 (m, 5H), 7.27 (tt, J¼6.9, 1.7 Hz, 1H), 7.18 (d, J¼9.2 Hz,
3.1.17. 1,2-Dihydro-2,2-dimethyl-7-methoxyquinoxaline (18) and
3,4-dihydro-3,3-dimethyl-6-methoxy-2-quinoxalinone36 (19)
1H), 6.64 (dd, J¼11.1, 9.4 Hz, 1H), 5.83 (d, J¼9.2 Hz, 1H); 13C NMR
d
138.9 (þ), 136.3 (ꢁ), 135.2 (þ), 132.7 (þ), 129.1 (ꢁ), 127.7 (ꢁ), 127.1
Reaction of 15 (200 mg, 0.90 mmol), Pd(dba)2 (31 mg,
0.05 mmol), dppp (22 mg, 0.05 mmol), 1,10-phenanthroline (19 mg,
0.10 mmol) in DMF (3 mL) at 70 ꢀC under CO (6 atm, 36 h), as de-
scribed for 7, gave after chromatography (hexanes/EtOAc, 85:15
followed by 6:4) 18 (151 mg, 0.80 mmol, 88%) and 19 (2.0 mg,
0.0097 mmol, 1%) both as off-white solids. Analytical data for 18:
(ꢁ), 126.1 (ꢁ), 122.9 (þ), 122.5 (ꢁ) 115.8 (ꢁ), 111.5 (ꢁ); IR (neat)
3317, 1640 cmꢁ1; HRMS (EI) calcd for C14H11ClN2O2 (Mþ) 274.0509,
found 274.0513.
Partial data for the E isomer: 1H NMR
d
9.87 (d, J¼11.9 Hz, 1H),
9.14 (d, J¼2.5 Hz, 1H), 7.6–7.2 (m, 6H), 7.06 (d, J¼15.8 Hz, 1H), 6.98
(d, J¼11.4 Hz, 1H), 6.16 (d, J¼15.6 Hz, 1H).
mp 65–66 ꢀC; 1H NMR
d
7.20–7.10 (m, 2H), 6.26 (dd, J¼8.6, 2.5 Hz,
1H), 6.02 (d, J¼2.5 Hz, 1H), 3.85 (s, 1H), 3.74 (s, 3H), 1.30 (s, 6H); 13
C
3.1.14. 3-Nitro-N-[(2-methyl)-1-propen-1-yl]-2-pyridinamine (30)
and N-(1-(3-nitropyridin-2-ylamino)-2-methylpropyl)-3-
nitropyridin-2-amine
NMR
d
160.1 (þ), 157.7 (ꢁ), 137.8 (þ), 128.6 (ꢁ), 125.7 (þ), 103.4 (ꢁ),
98.9 (ꢁ), 55.2 (ꢁ), 50.1 (þ), 27.1 (ꢁ); IR (neat) 3362, 3260, 2963,
1619, 1583, 1454, 1249, 1209, 1166, 1035 cmꢁ1; HRMS (EI) calcd for
Reaction of 2-amino-3-nitropyridine (505 mg, 3.63 mmol), 2-
C
11H14N2O 190.1106, found 190.1103.
methylpropanal (350
mL, 3.9 mmol), and 4 Å molecular sieves (15 g)
Analytical data for 19: mp 210–213 ꢀC (lit.36 200 ꢀC).
in CH2Cl2 (35 mL) at ambient temperature (5 days), as described
for 5, gave after chromatography (hexanes/EtOAc, 9:1), in order of
elution, 30 (139 mg, 0.72 mmol, 20%) as a red solid and N-(1-(3-
nitropyridin-2-ylamino)-2-methylpropyl)-3-nitropyridin-2-amine
(258 mg, 0.78 mmol, 43%) as a yellow solid. Analytical data for 30:
3.1.18. 7-Chloro-1,2-dihydro-2,2-dimethylquinoxaline (31) and
6-chloro-3,4-dihydro-3,3-dimethyl-2-quinoxalinone37 (32)
Reaction of 20 (100 mg, 0.44 mmol), Pd(dba)2 (17 mg,
0.029 mmol), dppp (12 mg, 0.029 mmol), and phen (12 mg,
0.067 mmol) in DMF (5 mL) at 70 ꢀC under CO (6 atm, 2 h), as de-
scribed for 7, gave after chromatography (hexanes/EtOAc, 7:3) in
order of elution 31 (48 mg, 0.25 mmol, 56%) and 32 (15 mg,
0.070 mmol, 16%) as off-white solids. Analytical data for 31: mp
mp 62–64 ꢀC; 1H NMR
d 9.87 (br s, 1H), 8.5–8.4 (m, 2H), 7.08 (d,
J¼8.2 Hz, 1H), 6.8–6.6 (m, 1H), 1.84 (s, 3H), 1.82 (s, 3H); 13C NMR
d
155.8 (ꢁ), 148.4 (þ), 135.4 (ꢁ), 127.6 (þ), 117.3 (ꢁ), 116.8 (þ), 112.8
(ꢁ), 22.7 (ꢁ), 16.8 (ꢁ); IR (neat) 2917, 1604 cmꢁ1. Anal. Calcd for
C9H11N3O2: C, 55.95; H, 5.74. Found: C, 56.06; H, 5.69.
136–138 ꢀC; 1H NMR
J¼8.4, 2.2 Hz, 1H), 6.48 (d, J¼2.2 Hz, 1H), 3.75 (s, 1H), 1.33 (s, 6H);
13C NMR
d
7.26 (s, 1H), 7.14 (d, J¼8.2 Hz, 1H), 6.67 (dd,
Analytical data for N-(1-(3-nitropyridin-2-ylamino)-2-methyl-
propyl)-3-nitropyridin-2-amine: mp 101–103 ꢀC; 1H NMR
d
8.81 (d,
d
160.3 (ꢁ), 137.6 (þ), 133.8 (þ), 129.9 (þ), 128.7 (ꢁ), 118.2
J¼7.9 Hz, 2H), 8.45–8.35 (m, 4H), 6.73–6.67 (m, 2H), 6.29 (quartet,
(ꢁ), 113.3 (ꢁ), 50.3 (ꢁ), 27.2 (ꢁ); IR (neat) 3229, 2972, 1600, 1480,
1451, 1238 cmꢁ1; HRMS (EI) calcd for C10H11ClN2 194.0611, found
194.0611.
J¼7.6 Hz, 1H), 2.63 (octet, J¼6.9 Hz, 1H), 1.11 (d, J¼6.7 Hz, 6H);
13C NMR
d
155.2 (ꢁ), 151.7 (þ), 135.1 (ꢁ), 128.1 (þ), 112.4 (ꢁ), 64.2
(ꢁ), 32.0 (ꢁ), 18.4 (ꢁ); IR (neat) 3372, 1600, 1569, 1481, 1443,
Analytical data for 32: mp 175–176 ꢀC (lit.37 166–170 ꢀC).

9682
J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
3.1.19. 6-Chloro-1,2-dihydro-2,2-dimethylquinoxaline (33) and 7-
chloro-3,4-dihydro-3,3-dimethyl-2-quinoxalinone38 (34)
0.105 mmol) in DMF (10 mL) at 70 ꢀC under CO (6 atm, 4.5 h), as
described for 7, gave after chromatography (hexanes/EtOAc, 7:3) 40
(123 mg, 0.534 mmol, 70%) and 41 (24 mg, 0.097 mmol, 13%) as off-
Reaction of 21 (200 mg, 0.88 mmol), Pd(dba)2 (30 mg,
0.052 mmol), dppp (23 mg, 0.056 mmol), and phen (21 mg,
0.117 mmol) in DMF (10 mL) at 70 ꢀC under CO (6 atm, 5.5 h), as
described for 7, gave after chromatography (hexanes/EtOAc, 8:2) 33
(50 mg, 0.26 mmol, 29%) and 34 (84 mg, 0.40 mmol, 45%) as off-
white solids. Analytical data for 40: mp 141–142 ꢀC; 1H NMR
d 7.23
(s, 1H), 7.15 (d, J¼8.4 Hz, 1H), 6.27 (dd, J¼8.4, 2.5 Hz, 1H), 6.08 (d,
J¼2.7 Hz, 1H), 4.06 (br s, 1H), 3.76 (s, 3H), 1.80–1.30 (m, 10H); 13C
NMR
d
160.0 (þ), 157.7 (ꢁ), 137.7 (þ), 128.5 (ꢁ), 126.5 (þ), 103.4 (ꢁ),
white solids. Analytical data for 33: mp 112–114 ꢀC; 1H NMR
d
7.29
99.0 (ꢁ), 55.1 (ꢁ), 51.4 (þ), 34.7 (þ), 25.1 (þ), 20.3 (þ); IR (neat)
3243, 2927, 1612, 1582, 1466, 1308, 1257, 1102 cmꢁ1; HRMS (EI)
calcd for C14H18N2O 230.1419, found 230.1410.
(d, J¼1.7 Hz, 1H), 7.23 (d, J¼2.5 Hz, 1H), 6.96 (dd, J¼8.4, 2.2 Hz, 1H),
6.42 (d, J¼8.4 Hz, 1H), 3.78 (br s, 1H), 1.31 (s, 6H); 13C NMR
d 161.5
(ꢁ), 135.3 (þ), 132.1 (þ), 128.4 (ꢁ), 127.3 (ꢁ), 122.5 (þ), 114.5 (ꢁ),
Analytical data for 41: mp 260–263 ꢀC; 1H NMR (DMSO-d6)
50.4 (þ), 27.0 (ꢁ); IR (neat) 3249, 2970, 1600, 1485, 1455 cmꢁ1
;
d
9.93 (s, 1H), 6.59 (d, J¼8.4 Hz, 1H), 6.52 (d, J¼2.5 Hz, 1H), 6.17 (dd,
HRMS (EI) calcd for C10H11ClN2 194.0611, found 194.0619.
J¼8.6, 2.5 Hz, 1H), 5.96 (s, 1H), 3.63 (s, 3H), 1.7–1.4 (m, 10H); 13C
NMR (DMSO-d6)
d
169.5 (þ), 155.3 (þ), 134.4 (þ), 120.0 (þ), 116.6
3.1.20. 1,2-Dihydro-2,2,5-trimethylquinoxaline (35) and 3,4-
dihydro-3,3,8-trimethyl-2-quinoxalinone36 (36)
(ꢁ), 102.8 (ꢁ), 100.3 (ꢁ), 55.6 (þ), 54.9 (ꢁ), 31.4 (þ), 25.0 (þ), 19.9
(þ); IR (neat) 3368, 2929, 1672, 1518, 1259, 1015 cmꢁ1; HRMS (EI)
calcd for C14H18N2O2 246.1368, found 246.1371.
Reaction of 22 (43 mg, 0.21 mmol), Pd(dba)2 (7 mg, 0.012 mmol),
dppp (7 mg, 0.017 mmol), and phen (7 mg, 0.039 mmol) in DMF
(5 mL) at 70 ꢀC under CO (6 atm, 2 h), as described for 7, gave after
chromatography (hexanes/EtOAc, 8:2) 35 (10 mg, 0.057 mmol, 27%)
and 36 (17 mg, 0.089 mmol, 42%) as off-white solids. Analytical
3.1.24. 1,2-Dihydro-2,2-diphenyl-7-methoxyquinoxaline (42)
Reaction of 28 (96 mg, 0.28 mmol), Pd(dba)2 (10 mg,
0.017 mmol), dppp (7 mg, 0.017 mmol), and phen (7 mg,
0.039 mmol) in DMF (4 mL) at 70 ꢀC under CO (6 atm, 18 h), as
described for 7, gave after chromatography (hexanes/EtOAc, 8:2) 42
(60 mg, 0.19 mmol, 69%) as a tan solid. Mp 164–166 ꢀC; 1H NMR
data for 35: mp 79–81 ꢀC; 1H NMR
d
7.29 (s, 1H), 6.91 (t, J¼7.7 Hz,
1H), 6.58 (d, J¼7.7 Hz,1H), 6.35 (d, J¼7.7 Hz,1H), 3.65 (br s,1H), 2.41
(s, 3H), 1.31 (s, 6H); 13C NMR (150 MHz)
d
158.8 (ꢁ), 136.5 (þ), 135.6
(þ), 129.8 (þ), 128.1 (ꢁ), 119.9 (ꢁ), 111.6 (ꢁ), 49.5 (þ), 26.7 (ꢁ), 17.2
(ꢁ); IR (neat) 3275, 2960, 1590, 1464, 1289, 1160 cmꢁ1; HRMS (EI)
calcd for C11H14N2 (Mþ) 174.1157, found 174.1150.
d
7.59 (d, J¼2.5 Hz, 1H), 7.40–7.25 (m, 10H), 7.19 (d, J¼8.7 Hz, 1H),
6.27 (dd, J¼8.4, 2.5 Hz, 1H), 6.09 (d, J¼2.5 Hz, 1H), 4.43 (br s, 1H),
3.75 (s, 3H); 13C NMR
d
160.5 (þ), 153.3 (ꢁ), 144.1 (þ), 136.5 (þ),
Analytical data for 36: mp 140–141 ꢀC (lit.36 140 ꢀC).
129.1 (ꢁ), 128.6 (ꢁ), 127.6 (ꢁ), 127.4 (ꢁ), 124.7 (þ), 103.8 (ꢁ), 98.4
(ꢁ), 62.5 (þ), 55.2 (ꢁ); IR (neat) 3232, 2998, 2930, 1594, 1486, 1293,
1224, 1174, 1033 cmꢁ1; HRMS (EI) calcd for C21H18N2O 314.1419,
found 314.1409.
3.1.21. 1,2-Dihydro-2,2,8-trimethylquinoxaline (37) and 3,4-
dihydro-3,3,5-trimethyl-2-quinoxalinone38 (38)
Reaction of 23 (228 mg, 1.10 mmol), Pd(dba)2 (38 mg,
0.067 mmol), dppp (27 mg, 0.065 mmol), and phen (24 mg,
0.13 mmol) in DMF (3 mL) at 70 ꢀC under CO (6 atm, 14 h), as de-
scribed for 7, gave after chromatography (hexanes/EtOAc, in order
9:1, 8:2, 7:3 and 1:1) in order of elution 37 (120 mg, 0.69 mmol,
63%) and 38 (26 mg, 0.14 mmol, 12%) as off-white solids. Analytical
3.1.25. 7-Chloro-2-phenylquinoxaline40 (43) and 7-chloro-2-
phenylquinoxaline-1-N-oxide (44)
Reactionof29 (106 mg,0.39 mmol),Pd(dba)2 (13 mg, 0.023 mmol),
dppp (10 mg, 0.024 mmol), and phen (10 mg, 0.055 mmol) in
DMF (10 mL) at 70 ꢀC under CO (6 atm, 48 h), as described for 7,
gave after chromatography (hexanes/EtOAc, 9:1) 43 (23 mg,
0.096 mmol, 25%) and 44 (14 mg, 0.055 mmol, 14%) as off-white
solids. Analytical data for 43: mp 146–148 ꢀC41 (lit.42 130–132 ꢀC).
data for 37: mp 95–97 ꢀC; 1H NMR
J¼7.9 Hz, 1H), 6.93 (d, J¼7.4 Hz, 1H), 6.65 (t, J¼7.7 Hz, 1H), 3.53 (br s,
1H), 2.10 (s, 3H), 1.34 (s, 6H); 13C NMR
d
7.28 (d, J¼2.0 Hz, 1H), 7.14 (d,
d
159.7 (ꢁ), 134.5 (þ), 130.7
(þ), 129.8 (ꢁ), 125.5 (ꢁ), 120.8 (þ), 117.3 (ꢁ), 50.2 (þ), 27.3 (ꢁ), 16.0
(ꢁ); IR (neat) 2964, 1624, 1600, 1497, 1280, 1082 cmꢁ1; HRMS (EI)
calcd for C10H14N2 (Mþ) 174.1157, found 174.11150.
Analytical data for 44: mp 121–123 ꢀC; 1H NMR
d 9.32 (s, 1H),
8.22–8.18 (m, 2H), 8.16 (d, J¼2.2 Hz, 1H), 8.06 (d, J¼8.9 Hz, 1H), 7.69
(dd, J¼8.9, 2.2 Hz, 1H), 7.60–7.56 (m, 3H); 13C NMR (150 MHz)
Analytical data for 38: mp 182–184 ꢀC (lit.38 182 ꢀC).
d 152.6, 143.4, 142.7, 140.1, 136.3, 136.1, 130.6, 130.5, 130.4, 129.2,
128.5, 127.6; IR 1486, 1352, 1310, 1091, 915 cmꢁ1; HRMS (ESI) calcd
3.1.22. (3,4-Dihydro-3,3-dimethylquinoxalin-6-yl)phenyl-
methanone (39)
for C14H10ClN2O (MþHþ) 257.0576, found 257.0476.
Amixtureof24 (120 mg, 0.40 mmol), Pd(dba)2 (14 mg, 0.024 mmol),
dppp (10 mg, 0.024 mmol), and phen (9 mg, 0.048 mmol) in DMF
(5 mL) was reacted as described for 7 at 70 ꢀC under CO (6 atm,18 h).
The reaction mixture was filtered through Celite, the Celite was
washedwith EtOAc, andthe filtratewas concentratedunderreduced
pressure. After numerous attempts to purify the product by flash
chromatography, the yellow solid isolated was tentatively deter-
3.1.26. 1,2-Dihydro-2,2-dimethylpyrido[2,3-b]pyrazine (45) and
1,2-dihydro-2,2-dimethylpyrido[2,3-b]pyrazin-3-one (46)
Reaction of 30 (100 mg, 0.52 mmol), Pd(dba)2 (18 mg,
0.031 mmol), dppp (14 mg, 0.034 mmol), and phen (13 mg,
0.072 mmol) in DMF (5 mL) at 70 ꢀC under CO (6 atm, 6 h), as de-
scribed for 7, gave after chromatography (hexanes/EtOAc, 7:3) in
order of elution 45 (28 mg, 0.17 mmol, 34%) and 46 (5 mg,
0.028 mmol, 6%) as off-white solids. Analytical data for 45: mp 131–
mined to be 39 (56 mg of solid, <0.2 mmol, <52%). 1H NMR
d 7.79
(dd, J¼8.4,1.5 Hz, 2H), 7.57 (t, J¼7.4 Hz,1H), 7.46 (t, J¼7.6 Hz, 2H), 7.39
132 ꢀC; 1H NMR
(m, 2H), 4.03 (br s, 1H), 1.81 (s, 6H); 13C NMR
d
9.28 (s, 1H), 7.57 (dd, J¼4.7, 1.5 Hz, 1H), 6.85–6.70
(d, J¼1.7 Hz, 1H), 7.30 (d, J¼7.9 Hz, 1H), 7.08 (dd, J¼7.9, 1.8 Hz, 1H),
d
157.5 (ꢁ), 146.2 (þ),
7.03 (d, J¼1.7 Hz,1H), 4.08 (br s,1H),1.34 (s, 6H); 13C NMR
d
196.4 (þ),
137.5 (ꢁ), 131.9 (þ), 119.6 (ꢁ), 115.2 (ꢁ), 80.0 (þ), 27.5 (ꢁ); IR (neat)
2976, 1674, 1609, 1444, 1343, 1245 cmꢁ1; HRMS (EI, NH3) calcd for
C9H12N3 (MþHþ) 162.1031, found 162.1037.
163.0 (ꢁ), 137.6 (þ), 137.5 (þ), 136.8 (þ), 134.3 (þ), 132.2 (ꢁ), 129.9
(ꢁ), 128.1 (ꢁ), 127.1 (ꢁ), 120.8 (ꢁ), 115.0 (ꢁ), 50.5 (þ), 27.1 (ꢁ).
Analytical data for 46: mp 202–205 ꢀC; 1H NMR
d 9.24 (br s, 1H),
3.1.23. 70-Methoxy-spiro[cyclohexane-1,20(10H)quinoxaline] (40)
and 10,40-dihydro-70-methoxy-spiro[cyclohexane-
7.83 (dd, J¼4.9, 1.5 Hz, 1H), 6.94 (dd, J¼7.9, 1.5 Hz, 1H), 6.84 (dd,
J¼7.7, 4.9 Hz, 1H), 3.72 (br s, 1H), 1.45 (s, 6H); 13C NMR
d
171.0 (þ),
1,20(30H)quinoxalin]30-one (41)39
140.3 (þ), 137.9 (ꢁ), 128.5 (þ),120.2 (ꢁ), 119.1 (ꢁ), 56.0 (þ), 26.1(ꢁ);
IR (neat) 3310, 1683, 1558, 1458, 1289 cmꢁ1; HRMS (EI) calcd for
C9H11N3O 177.0902, found 177.0899.
Reaction of 27 (201 mg, 0.77 mmol), Pd(dba)2 (27 mg,
0.047 mmol), dppp (19 mg, 0.046 mmol), and phen (19 mg,

J.M. Wallace et al. / Tetrahedron 64 (2008) 9675–9684
9683
3.1.27. 2-(2-Nitrophenylamino)-2-cyclohexen-1-one (42)
0.25 mmol, 8%) as an off-white solid, and 51 (84 mg, 0.42 mmol,
14%) as a tan solid. Analytical data for 52: 1H NMR
8.75 (s, 1H), 8.06
2-Nitrobenzenamine (2.00 g, 14.5 mmol), 1,2-cyclohexanedione
(1.90 g, 16.9 mmol), benzene (40 mL), and concentrated H2SO4 (five
drops) were combined in a round-bottomed flask fitted with
a Dean–Stark trap and a reflux condenser. The reaction was heated
and stirred at reflux for 21 h. The reaction mixture was then con-
centrated and the crude product was purified by chromatography
(hexanes/EtOAc, 9:1, then 8:2) to give 42 (1.07 g, 4.6 mmol, 32%) as
d
(apparent triplet with further fine splitting, J¼9.4 Hz, 2H), 7.76 (dt,
J¼6.7, 1.7 Hz, 1H) partially overlapping, 7.71 (dt, J¼6.9, 1.7 Hz, 1H),
3.02 (t, J¼7.7 Hz, 2H), 1.86 (p, J¼7.6 Hz, 2H), 1.47–1.32 (m, 4H), 0.91
(t, J¼7.0 Hz, 3H); 13C NMR (150 MHz)
d
157.6 (þ), 145.7 (ꢁ), 142.1
(þ), 141.1 (þ), 129.8 (ꢁ), 129.1 (ꢁ), 128.8 (ꢁ), 128.7 (ꢁ), 36.4 (þ), 31.5
(þ), 29.1 (þ), 22.4 (þ), 13.9 (ꢁ); IR (neat) 2957, 2927, 2857, 1561,
1492, 1126, 761 cmꢁ1; HRMS (EI) calcd for C13H17N2 (MþHþ)
201.1392, found 262.1371.
an orange solid. Mp 75–77 ꢀC; 1H NMR
d 9.38 (br s, 1H), 8.18 (dd,
J¼8.7, 1.5 Hz, 1H), 7.43 (ddd, J¼8.7, 7.4, 1.7 Hz, 1H), 7.31 (dd, J¼8.7,
1.5 Hz, 1H), 6.87–6.77 (m, 2H), 2.65–2.54 (m, 4H), 2.10 (p, J¼6.2 Hz,
Analytical data for 53: mp 32–34 ꢀC; 1H NMR
d 8.69 (s, 1H), 8.61
2H); 13C NMR
d
194.6 (þ), 140.6 (þ), 135.2 (ꢁ), 134.8 (þ), 134.6 (þ),
(apparent doublet with further fine splitting, J¼10.1 Hz, 1H), 8.10
(apparent doublet with further fine splitting, J¼9.7 Hz, 1H), 7.81–
7.71 (m, 2H), 3.08 (t, J¼7.7 Hz, 2H), 1.84 (p, J¼7.4 Hz, 2H), 1.48–1.38
129.7 (ꢁ), 126.7 (ꢁ), 118.1 (ꢁ), 116.8 (ꢁ), 37.7 (þ), 25.0 (þ), 22.4 (þ);
IR (neat) 3294, 2944, 1672, 1571, 1430, 1246, 1155 cmꢁ1. Anal. Calcd
for C12H12N2O3: C, 62.06; H, 5.21; N, 12.06. Found: C, 62.58; H, 5.74;
N, 12.28.
(m, 4H), 0.93 (t, J¼6.9 Hz, 3H); 13C NMR (150 MHz)
d
146.8 (ꢁ),
144.4 (þ), 143.0 (þ), 137.0 (þ), 130.5 (ꢁ), 130.0 (ꢁ), 129.9 (ꢁ), 118.7
(ꢁ), 31.7 (þ), 28.7 (þ), 25.2 (þ), 22.3 (þ), 13.9 (ꢁ); IR (neat) 2957,
2927, 2860, 1579, 1494, 1359, 1302, 766 cmꢁ1; HRMS (EI) calcd for
3.1.28. 3-(2-Nitrophenylamino)-2-cyclohexen-1-one (47)43
2-Nitrobenzenamine (1.26 g, 8.92 mmol), 1,3-cyclohexanedione
(1.00 g, 8.92 mmol), benzene (30 mL), and concentrated H2SO4 (five
drops) were combined in a round-bottomed flask fitted with
a Dean–Stark trap and a reflux condenser. The reaction was heated
and stirred at reflux for 22 h. The reaction mixture was then con-
centrated and the crude product was recrystallized from EtOAc to
give 47 (1.45 g, 6.30 mmol, 70%) as a yellow solid.
C
13H17N2O (MþHþ) 217.1335, found 217.1334.
3.1.32. 2,2-Dimethyl-1,2-dihydroquinoxaline (7) and 2-(1-methyl-
ethyl)benzimidazole (64)44
Reaction of 2-nitrosoaminobenzene31,32 (63) (326 mg,
2.67 mmol), 2-methylpropanal (440 mL, 4.85 mmol), camphor sul-
fonic acid (10 mg), 4 Å molecular sieves (30 g) in CH2Cl2 (50 mL) at
ambient temperature (40 days), as described for 5, gave after
chromatography (hexanes/EtOAc, in order 9:1, 8:2, 6:4,1:1, and 3:7)
in order of elution, 7 (20 mg, 0.12 mmol, 5%) and 64 (13 mg,
0.081 mmol, 3%). For 64: mp 220–225 ꢀC (lit.49 mp 223–225 ꢀC).
3.1.29. 1-Hydroxyphenazine (48)44
Reaction of 3-(2-nitrophenylamino)-2-cyclohexen-1-one (47)
(302 mg, 1.30 mmol), Pd(dba)2 (45 mg, 0.078 mmol), dppp (33 mg,
0.080 mmol), and phen (30 mg, 0.17 mmol) in DMF (4 mL), as de-
scribed above for 7 (6 atm CO, 120 ꢀC, 22 h), gave after purification
by chromatography (hexanes/EtOAc, 8:2, 7:3, 1:1, and EtOAc) 48
(67 mg, 0.34 mmol, 26%) as a brown solid. Mp 155–156 ꢀC (lit.45
157–159 ꢀC).
Acknowledgements
This work was supported by research grants from the National
Science Foundation (CHE 0611096), the National Institute of Gen-
eral Medical Sciences, National Institutes of Health (RO1 GM57416),
and the American Chemical Society Petroleum Research Fund
(40665-AC1). NSF-EPSCoR (Grant #1002165R) is gratefully ac-
knowledged for the funding of a 600 MHz Varian Inova NMR and
a Thermo-Finnegan LTQ-FT Mass Spectrometer and the NMR and
MS facilities in the C. Eugene Bennett Department of Chemistry at
West Virginia University. J.T. is grateful to OAS (F54111), CONACYT
(250099), and COFAA-IPN (9711220214) for financial support
during his sabbatical leave in the USA (1997–1998).
3.1.30. 2-Methyl-6-nitroaminobenzene,45 1,2-dihydro-2,2,5-
trimethylquinoxaline (35), and 4-methyl-2-(1-methylethyl)-
benzimidazole (50)46
To
a
solution of 2-azido-3-nitrotoluene (49)47 (1.00 g,
5.61 mmol) dissolved in diethyl ether (anhydrous, 40 mL) was
added triphenylphosphine (1.50 g, 5.72 mmol). The mixture was
stirred under argon atmosphere at ambient temperature for 1 h.
The solvent was removed under reduced pressure and the resulting
solid was dissolved in CHCl3 (40 mL) and 2-methylpropanal
(7.0 mL, 77.0 mmol) was added. The reaction mixture was stirred at
reflux under an argon atmosphere for 6 days. The solvent was re-
moved under reduced pressure to give a crude reaction mixture.
Reaction of the crude mixture with Pd(dba)2 (190 mg, 0.33 mmol),
dppp (140 mg, 0.34 mmol), and phen (120 mg, 0.66 mmol), in DMF
(8 mL), as described for 7 (6 atm CO, 21 h), gave after chromato-
graphy (hexanes/EtOAc, in order 9:1, 8:2, 1:1, 3:7, and EtOAc), 2-
methyl-6-nitroaminobenzene (71 mg, 0.47 mmol, 8%) as a yellow
solid, 35 (106 mg, 0.61 mmol, 11%) as a pale yellow solid, and 50
(603 mg, 3.46 mmol, 62%) as a tan solid.
Supplementary data
1H NMR, 13C NMR, and IR (for one compound) data for com-
pounds 17, 19, 32, 34, 36, 38, 43, and 47 previously described but
without reported data. Supplemental data associated with this
article can be found in the online version, at doi:10.1016/
j.tet.2008.07.083.
References and notes
3.1.31. 2-Pentylquinoxaline (52), 2-pentylquinoxaline-1-oxide (53),
and 2-hexylbenzimidazole44 (51)
1. For reviews, see: (a) Ragaini, F.; Cenini, S.; Gallo, E.; Caselli, A.; Fantauzzi, S. Curr.
Org. Chem. 2006, 10, 1479–1510; (b) Tsoungas, P. G.; Diplas, A. I. Curr. Org. Chem.
2004, 8, 1579–1606.
2. For a recent application and references, see: So¨derberg, B. C. G.; Banini, S. R.;
Turner, M. R.; Minter, A. R.; Arrington, A. K. Synthesis 2008, 903–912.
3. Akazome, M.; Kondo, T.; Watanabe, Y. J. Org. Chem. 1994, 59, 3375–3380.
4. (a) Annunziata, R.; Cenini, S.; Palmisano, G.; Tollari, S. Synth. Commun. 1996, 26,
495–501; (b) Tollari, S.; Cenini, S.; Ragaini, F.; Cassar, L. J. Chem. Soc., Chem.
Commun. 1994, 1741–1742.
5. Akazome, M.; Yamamoto, J.; Kondo, T.; Watanabe, Y. J. Organomet. Chem. 1995,
494, 229–233.
6. (a) Nishiyama, Y.; Hirose, M.; Kitagaito, W.; Sonoda, N. Tetrahedron Lett. 2002,
43, 1855–1858; (b) Akazome, M.; Kondo, T.; Watanabe, Y. J. Org. Chem. 1993, 58,
310–312.
2-Azidonitrobenzene48 (500 mg, 3.05 mmol) was reacted with
first triphenylphosphine (800 mg, 3.05 mmol) in diethyl ether
(anhydrous, 20 mL) followed by heptanal (4.0 mL, 29.8 mmol) in
CHCl3 (25 mL), as described for reaction of 49 (1 h, then 7 days) to
give a crude reaction mixture. Reaction of the crude mixture with
Pd(dba)2 (110 mg, 0.19 mmol), dppp (80 mg, 0.19 mmol), and phen
(70 mg, 0.39 mmol) in DMF (10 mL), as described for 7 (6 atm CO,
72H), gave after chromatography (hexanes/EtOAc, 8:2, 7:3, 6:4, 1:1,
and 3:7) 52 (153 mg, 0.76 mmol, 25%) as a yellow oil, 53 (54 mg,

9684
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