Pt(IV)-catalyzed hydroamination triggered cyclization: A strategy to fused pyrrolo[1,2- a ]quinoxalines, Indolo[1,2- a ]quinoxalines, and Indolo[3,2- c ]quinolines

Article abstract of DOI:10.1021/jo100373w

A PtCl₄-catalyzed hydroamination-triggered cyclization strategy to access biologically interesting N-containing heterocycles such as pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]quinoxalines, and indolo[3,2-c] quinolines is described. The reaction makes use of aminoaromatics such as 1-(2-aminophenyl)pyrroles, N-(2-aminophenyl)indoles, 2-(2-aminophenyl)indoles, and alkynes having a tethered hydroxyl group. Mechanistically, the reaction is very appealing since it involves multiple catalytic cycles catalyzed by a single metal catalyst PtCl₄. We observed a remarkable enhancement of the rate when reactions were run under microwave-assisted conditions.

Full text of DOI:10.1021/jo100373w

pubs.acs.org/joc
Pt(IV)-Catalyzed Hydroamination Triggered Cyclization: A Strategy to
Fused Pyrrolo[1,2-a]quinoxalines, Indolo[1,2-a]quinoxalines,
and Indolo[3,2-c]quinolines
Nitin T. Patil,*,† Rahul D. Kavthe,† Valmik S. Shinde,† and Balasubramanian Sridhar‡
†Organic Chemistry Division II and ‡Laboratory of X-ray Crystallography, Indian Institute of Chemical
Technology, Hyderabad 500 607, India
nitin@iict.res.in; patilnitint@yahoo.com
Received March 3, 2010
A PtCl4-catalyzed hydroamination-triggered cyclization strategy to access biologically interesting
N-containing heterocycles such as pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]quinoxalines, and indolo-
[3,2-c]quinolines is described. The reaction makes use of aminoaromatics such as 1-(2-aminophenyl)-
pyrroles, N-(2-aminophenyl)indoles, 2-(2-aminophenyl)indoles, and alkynes having a tethered hydroxyl
group. Mechanistically, the reaction is very appealing since it involves multiple catalytic cycles catalyzed
by a single metal catalyst PtCl4. We observed a remarkable enhancement of the rate when reactions were
run under microwave-assisted conditions.
Introduction
Among heterocyclic compounds, the nitrogen-containing
heterocycles such as pyrrolo[1,2-a]quinoxalines,3 indolo[1,2-a]-
quinoxalines,4 and indolo[3,2-c]quinolines5 form one of the
most important class of compounds due to their diverse range
of pharmacological properties. The importance of these mole-
cules has stimulated many synthetic chemists to develop effi-
cient synthetic routes to highly functionalized molecules for
structure activity relationship studies.3-5 Despite numerous
reports on their syntheses, to date, a highly efficient route to
Carbophilic transition metal-catalyzed cascade1 reactions
are highly attractive and significant in the synthesis of
polycyclic compounds owing to their immense power of
forming many bonds in a single step.2 In general, these
reactions are triggered by the attack of nucleophile to the
C-C triple bond, which possesses an enhanced electrophili-
city due to its π-coordination with a transition metal. Inter-
estingly, most of the processes involve the use of substrates
having alkyne and nucleophile in the same molecule. How-
ever, the strategies that involve alkynes and nucleophiles in
two different substrates are much more appealing.
€
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DOI: 10.1021/jo100373w
r
Published on Web 04/14/2010
J. Org. Chem. 2010, 75, 3371–3380 3371
2010 American Chemical Society

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TABLE 1. Catalysts Screeninga
yield
yield
entry
catalyst
temp, °C time, h (3a),b % (3a0),b %
1
2
3
4
5
PtBr2
PtCl2
PtCl4
PtCl4
80
80
80
100
100
24
24
24
48
24
00
00
71
78
10
94
92
15
10
80
FIGURE 1. Concept of metal-catalyzed hydroamination-triggered
cyclization.
Au(PPh3)Cl/AgOTf
aReactions were performed in methanol (2 mL) employing 1a
(0.6 mmol), 2a (0.6 mmol), and 5 mol % of catalyst. bIsolated yields.
these classes of compounds remains a challenge. In this context,
a general and concise route for their synthesis would be a
valuable tool for the exploration of chemistry and biology.
We recently disclosed efficient double hydroamination6 and
hydroamination-hydroarylation7 reactions of terminal al-
kynes bearing a hydroxyl group in the proximity. The process
involves the use of alkynes and nucleophiles in two different
substrates and therefore this type of reaction is quite uncom-
mon compared to known literature processes.8 Inspired by
these results, we envisaged that the metal-catalyzed intermole-
cular hydroamination reaction between aminoaromatics and
alkynols would generate imines which after Mannich-type
reaction and dehydrative cyclization afford cyclic products
(Figure 1).9 We term this strategy as hydroamination-triggered
cyclization and are delighted to report its proof of concept,
namely, a PtCl4-catalyzed, one-pot, tandem hydroamination-
Mannich-dehydrative cyclization for the synthesis of pyrrolo-
[1,2-a]quinoxalines, indolo[3,2-c]quinolines, and indolo[1,2-a]-
quinoxalines. It should be noted that a conceptually different
strategy for the synthesis of polycyclic heterocyclic compounds
is known in the literature.10
catalyst for this cascade transformation was carried out with
differentcatalystsandtheresultsobtainedareoutlinedinTable1.
The reaction was conducted between 2-aminophenyl pyrrole 1a
and 4-pentyn-1-ol 2a in the presence of 5 mol % of PtBr2 and
PtCl2 in methanol, independently at 80 °C; the hydroamina-
tion-hydroarylation product 3a0 was obtained exclusively
(entries 1 and 2). Formation of the desired product 3a was not
detected albeit the reaction mixture was heated for a prolonged
time. Surprisingly, under the same reaction conditions, PtCl4
catalyst afforded 3a in 71% yield along with 3a0 in 15% yield
(entry 3). When the reaction time was increased to 48 h, 3a was
isolated in 78% yield (entry 4). The use of Ph3PAuOTf catalyst,
prepared in situ from 5 mol % of Ph3PAuCl and 5 mol % of
AgOTf, proved not to be satisfactory (entry 5). To optimize the
reaction further, we examined various transition metal catalysts
and a combination11 of transition metal catalysts with Lewis/
Brønsted acids in methanol.12 However, none of these conditions
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Meyers, C.; Rombouts, G.; Loones, K. T. J.; Coelho, A.; Maes, B. U. W. Adv.
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Results and Discussions
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(12) A detailed optimization table is given in the Supporting Information.
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TABLE 2. Hydroamination-Triggered Cyclization Strategy for the Synthesis of Fused Pyrrolo[1,2-a]quinoxalinesa
aReactions were performed in methanol (2 mL) employing 1 (0.6 mmol), 2 (0.6 mmol), and 5 mol % of catalyst at 100 °C for 48 h. bIsolated yields. cIn
all cases, nearly 10-20% product resulting from formal hydroamination-hydroarylation of alkyne was obtained. d3:1 mixture of diastereomers.
were found to be superior in comparison to the result obtained
with PtCl4 (compare entry 4).
as chloro substituents in 2-aminophenylpyrroles were all well
tolerated.13 The internal alkynes such as 3-hexyn-1-ol 2f and
3-decyn-1-ol 2g on reaction with 1a gave 3k and 3l in 68% and
74% yields, respectively (entries 11 and 12). 5-Hexyn-1-ol 2h on
reaction with 1a gave 3m in 71% yield (entry 13).
Next, the scope of the hydroamination-triggered cycliza-
tion was extended to the synthesis of fused indolo[1,2-a]-
quinoxalines. As outlined in Table 3, it can be seen that a
wide range of substituents on N-(2-aminophenyl)indoles
reacted well to furnish desired products 5a-i14 in moderate
to high yields (59-70%). Particularly noteworthy is the fact
Having optimized the reaction conditions, we then explored
the scope of this hydroamination-triggered cyclization for vari-
ous aminoaromatics and alkynols. First, the reaction of 1-(2-
aminophenyl)pyrroles with alkynols were studied and the results
are outlined in Table 2. Treatment of 1a with 3-pentyn-1-ol 2b in
the presence of 5 mol % of PtCl4 in methanol at 100 °C gave
pyrrolo[1,2-a]quinoxalines 3a in 75% yield (entry 1). Methyl-
substituted 1-(2-aminophenyl)pyrroles also reacted well with 2a,
for this cascade transformation, to give 3b and 3c in good yields
(entries 2 and 3). The alkynols 2c, 2d, and 2e on reaction with 1a
gave the expected products 3d, 3e, and3f in 65%, 59%, and 55%
yields, respectively (entries 4, 5, and 6). As can be judged from
entries 7-10, electron withdrawing and donating groups as well
(13) X-ray crystallographic data of 3g are given in the Supporting
Information.
(14) X-ray crystallographic data of 5a are given in the Supporting
Information.
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TABLE 3. Hydroamination-Triggered Cyclization Strategy for the Synthesis of Fused Indolo[1,2-a]quinoxalinesa
aReactions were performed in methanol (2 mL) employing 4 (0.6 mmol), 2 (0.6 mmol), and 5 mol % of catalyst at 100 °C for 48 h. bIsolated yields. cIn
all cases, nearly 10-20% product resulting from formal hydroamination-hydroarylation of alkyne was obtained.
SCHEME 1. Synthesis of Fused Indolo[3,2-c]quinolines
Starting Directly from 8 and 2a
that electron withdrawing/donating substituents on the
aromatic rings were not detrimental to the reactivity as
-COOMe, -OMe, and -Cl groups were all well tolerated
(entries 5, 6, and 7).
Similarly, various fused indolo[3,2-c]quinolines 7a-k
were obtained from 2-(2-aminophenyl)indoles 6 and alky-
nols 2, regardless of the electronic nature of the aromatic
rings, in yields ranging from 59% to 85% (Table 4, entries
1-12). However, unlike previous cases, the reaction between
6a and 5-hexyn-1-ol 2h under the established conditions did
not give the desired product 7l (entry 13).
We were pleased to findthat symmetricaldiamines8a, 8b, and
8c on reaction with 2a, under Ph3PAuOTf catalysis,15 gave
corresponding indolo[3,2-c]quinolines 7a, 7b, and 7f in 60%,
59%, and 51% yields, respectively (Scheme 1). It is worth
mentioning that this process involving multiple catalytic cycles,16
assisted by a single metal catalyst, involves the formation of four
bonds, that is, two C-C and two C-N bonds.
Mechanistic Studies
A plausible mechanism for this multicatalytic process is
described using 8a and 2a as examples (Figure 2). In essence,
a total of four catalytic cycles A (hydroalkoxylation),17
B (hydroamination),18 C (coupling), and D (dehydrative
cyclization) were proposed. As shown in catalytic cycle A,
the complexation of metal catalyst to the alkyne function
in 2a would lead to intermediate 9. The cyclization step
may then occur directly by the attack of proximal hydroxyl
group leading to vinylmetal19 intermediate 10, which on
(15) The catalyst Ph3PAuOTf was found to be superior compared to
PtCl4 for this multicatalytic process.
(16) Review: Wasilke, J.-C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C.
Chem. Rev. 2005, 105, 1001–1020.
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TABLE 4. Hydroamination-Triggered Cyclization Strategy for the Synthesis of Fused Indolo[3,2-c]quinolinesa
aReactions were performed in methanol (2 mL) employing 6 (0.6 mmol), 2(0.6 mmol), and 5 mol % of PtCl4 for 100 °C for 48 h. bIsolated yields. cIn all
cases, nearly 10-20% productresulting from formal hydroamination-hydroarylation of alkyne was obtained. dUncharecterized material was obtained.
protonation and regeneration of catalyst would afford
2-methylenetetrahydrofuran 11. At the same time, 2-aminophe-
nylindole 6a would be generated by intramolecular hydroami-
nation of alkynylamine 8a via intermediates 12 and 13 (cycle
B). As described in cycle C, the metal complex catalyzes the
formation of oxonium ion 14 from 2-methylenetetrahydro-
furan 11. Intermolecular nucleophilic addition of the indole
6a to 14 might result in the formation of metal-coordinated
N,O-ketal 15 from which formal hydroamination-
hydroarylation product 16 (vide infra) was obtained with re-
generation of catalyst. The compound 16, thus obtained, would
undergo dehydrative cyclization, under the catalysis of PtCl4, to
afford fused indolo[3,2-c]quinolines 7a (cf. 17 and 18, cycle D).
It is well-known in the literature that hydroalkoxylation17
and hydroamination18 processes are catalyzed by metals and
there is no role of residual Brønsted acid generated during
the course of reaction. With this background and based on
our earlier work,6,7,9a we propose that cycles A and B are
catalyzed by PtCl4. We were curious to ascertain the effect of
HCl for the catalytic cycles C and D. To examine the
involvement of HCl in cycle C, a controlled experiment
was performed with 2-tert-butylimino-2-diethylamino-1,3-
dimethyl-perhydro-1,3,2-diazaphosphorine (BEMP) as a
(17) Selected recent examples on hydroalkoxylation: (a) Harkat, H.; Blanc,
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^
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FIGURE 2. The plausible mechanism.
SCHEME 2. Mechanistic Studies (cycle D)
yield. This suggests that residual HCl is not responsible for
cycle C.21 To determine the role of HCl as a catalyst in cycle
D, a few control experiments were conducted (Scheme 2).
The hydroamination-hydroarylation product 16 was pre-
pared from 6a and 2a by using our previously reported
Pt(II)-catalyzed procedure.7 The product 16, thus obtained,
when treated with PtCl4 in methanol at 100 °C afforded
the desired product in 90% yield (path a). On the other
hand, using a catalytic amount of HCl, product 7a was
obtained in only 20% yield under the same reaction condi-
tions (path b). The outcome of this study suggests that the Pt
species might have provided significant activation for the
dehydrative cyclization. Accordingly, it became clear that
PtCl4 is involved in all the proposed catalytic cycles
(Figure 2).
proton scavenger.20 When 1a was treated with 2a in the
presence of 5 mol % of PtCl4 and 2 mol % of BEMP in
MeOH at 100 °C for 48 h, 3a was obtained, albeit in 15%
Notably, these cyclization reactions could also be con-
ducted under microwave condition,22 rather than conven-
tional heating. Reactions of 2a and 2b with 1a in the presence
of 5 mol % of PtCl4 under microwave conditions (T=150 °C,
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Fananas, F. J. Chem.-Eur. J. 2009, 15, 11660–11667. (b) Yang, T.;
Campbell, L.; Dixon, D. J. J. Am. Chem. Soc. 2007, 129, 12070–12071.
(21) The possibility of Brønsted acid catalysis assisted by a Lewis acid,
which results from the use of platinum catalysts in the presence of methanol
as the solvent, cannot be ruled out completely. For an example of this type of
catalysis, see: Ishihara, K.; Ishibashi, H.; Yamamoto, H. J. Am. Chem. Soc.
2002, 124, 3647–3655.
(22) For selected reviews on microwave assisted reactions in organic
synthesis, see: (a) Appukkuttan, P.; Mehta, V. P.; Van der Eycken, E. V. Chem.
Soc. Rev. 2010. DOI: 10.1039/b815717k. (b) Kappe, C. O.; Dallinger, D. Mol.
Diversity 2009, 13, 71–193. (c) Appukkuttan, P.; Van der Eycken, E. V. Eur. J.
Org. Chem. 2008, 1133–1155. (d) Kappe, C. O. Chem. Soc. Rev. 2008, 37, 1127–
ꢀ
1139. (e) Das, S. K. Synlett 2004, 6, 915–932. (f) de la Hoz, A.; Díaz-Ortiz, A.;
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3376 J. Org. Chem. Vol. 75, No. 10, 2010

Patil et al.
JOCArticle
TABLE 5. PtCl4-Catalyzed Hydroamination-Triggered Cyclization
under Microwave Conditionsa
Hz, 1H), 7.05 (br t, J=1.5 Hz, 1H), 6.98 (t, J=8.3 Hz, 1H), 6.73
(t, J=7.5 Hz, 1H), 7.56 (d, J=6.7 Hz, 1H), 6.22 (t, J=3.0 Hz,
1H), 5.83 (dd, J=2.2, 1.5 Hz, 1H), 3.38 (t, J=6.7 Hz, 2H),
2.38-2.10 (m, 4H), 1.11 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
135.1, 125.7, 124.9, 117.1, 114.1, 113.7, 110.0, 101.1, 44.4, 36.9,
29.7, 23.0, 21.6; IR (KBr) νmax 2957, 2921, 2842, 1606, 1513,
1469, 1366, 1167, 739, 701 cm-1; MS (ESI) m/z 225 (Mþ
þ
H); HRMS calcd for C15H17N2 (Mþ þ H) 225.1391, found
225.1401.
entry
1/4/6
2
3/5/7
yield,b %
7,12b-Dimethyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-c]quino-
xaline, 3b: 69% yield; thick pale yellow oil; Rf 0.60 (hexane/
EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.12 (d, J=8.3
Hz, 2H), 6.83 (d, J=7.9 Hz, 1H), 6.58-6.48 (m, 1H), 6.26 (t, J=
3.2 Hz, 1H), 5.89 (br s, 1H), 3.40-3.27 (m, 2H), 2.32 (s, 3H),
2.31-2.07 (m, 4H), 1.09 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
125.4, 115.0, 114.1, 113.8, 113.5, 110.1, 110.0, 101.3,101.1, 96.2,
44.7, 36.8, 29.7, 22.7, 21.7, 21.0; IR (film) νmax 2961, 2922, 2856,
1618, 1516, 1480, 1362, 1332, 1170, 802, 704 cm-1; MS (ESI) m/z
239 (Mþ þ H); HRMS calcd for C16H19N2 (Mþ þ H) 239.1548,
found 239.1552.
1
2
3
4
5
1a
1a
4e
4e
6a
2a
2b
2a
2b
2a
3a
3a
5e
5e
7a
62
70
75
64
70
aA solution of the aminoaromatics 1a/4e/6a (0.6 mmol), alkynols
2a/2b (0.6 mmol), and PtCl4 (5 mol %) in methanol (2 mL) was subjected
to microwave irradiation at 150 °C (P = 40-50 W) for 15 min (Biotage,
Initiator Eight, single-mode reactor). bIsolated yield.
P=40-50 W) afforded 3a in 62% and 70% yields, respec-
tively (Table 5, entries 1 and 2). Similarly, 2a and 2b reacted
smoothly with 4e to give 5e in 75% and 64% yield, respec-
tively (entries 3 and 4). Product 7a was generated in 70%
yield when 6a was reacted with 2a (entry 5). To know whether
the reaction is thermally driven, we performed the reaction
between 1a and 2a, in a preheated oil bath, at 150 °C for
15 min. However, 3a was obtained in only 20% yield.
5,12b-Dimethyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-c]quino-
xaline, 3c: 60% yield; thick pale yellow oil; Rf 0.61 (hexane/
EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.20-7.09 (m,
1H), 6.92 (t, J=7.5 Hz, 1H), 6.68-6.35 (m, 2H), 6.20 (t, J=3.0
Hz, 1H), 5.85 (s, 1H), 3.41-3.20 (m, 2H), 2.63 (s, 3H), 2.42-2.09
(m, 4H), 1.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 137.8,
137.1, 125.4, 124.7, 121.6, 118.4, 114.1, 111.9, 108.8, 99.6, 44.5,
36.8, 29.7, 21.7, 21.3, 20.7; (film) νmax 2942, 2928, 2841, 1622,
1518, 1456, 1368, 1332, 1180, 810, 715 cm-1; MS (ESI) m/z 239
(Mþ þ H); HRMS calcd for C16H19N2 (Mþ þ H) 239.1548,
found 239.1542.
Conclusion
12b-Methyl-3,12b-dihydro-10H-spiro[cyclopentane-1,2-dipyr-
rolo[1,2-a:2,1-c]quinoxaline], 3d. 65% yield; thick blackish oil;
Rf 0.63 (hexane/EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ
7.28 (dd, J=7.9, 1.7 Hz, 1H), 7.07-7.03 (m, 1H), 6.97 (t, J=7.7
Hz, 1H), 6.74 (t, J=7.5 Hz, 1H), 6.53 (d, J=7.1 Hz, 1H), 6.20 (t,
J=3.2 Hz, 1H), 5.84-5.77 (m, 1H), 3.24 (s, 2H), 2.32 (ABq, J=
12.2 Hz, 2H), 1.89-1.48 (m, 8H) 1.16 (s, 3H); 13C NMR (75
MHz, CDCl3) δ 124.7, 124.4, 117.4, 114.1, 113.9, 113.7, 109.9,
100.7, 99.2, 60.3, 58.4, 50.7, 41.6, 29.6, 24.4, 24.2, 23.9, 20.9; IR
(film) νmax 2942, 2860, 2812, 1622, 1570, 1465, 1364, 1315, 1298,
1109, 740, 708 cm-1; MS (ESI) m/z 279 (Mþ þ H); HRMS calcd
for C19H23N2 (Mþ þ H) 279.1861, found 279.1858.
In summary, we developed a PtCl4-catalyzed hydroamina-
tion-triggered cyclization strategy for the synthesis of multi-
substituted fused pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]-
quinoxalines, and indolo[3,2-c]quinolines. The mechanism
of the reaction, as described, involves multiple catalytic cycles
and each of them is catalyzed by PtCl4. Furthermore, a one-
pot cascade process for the synthesis of fused indolo[3,2-c]-
quinolines starting from symmetrical 2-[2-(2-aminophenyl)-
1-ethynyl]anilines and alkynols was demonstrated. We have
also noticed a significant enhancement of reaction rate under
microwave conditions. Due to the importance of these com-
pounds in medicinal chemistry, the present reaction may
prove to be an efficient means for library construction.
Further extension of this chemistry toward the synthesis of
other heterocycles via design of a related cascade process can
be easily envisioned, and currently is being explored in our
laboratory.
12b-Methyl-3,12b-dihydro-10H-spiro[cyclohexane-1,2-dipyr-
rolo[1,2-a:2,1-c]quinoxaline], 3e: 59% yield; pale yellow oil;
Rf 0.62 (hexane/EtOAc=90/10); 1H NMR (300 MHz, CDCl3)
δ 7.30 (d, J=7.9 Hz, 1H), 7.11-7.06 (m, 1H), 7.02 (t, J=7.5 Hz,
1H), 6.77 (t, J=7.1 Hz, 1H), 6.60 (d, J=7.3 Hz, 1H), 6.26 (t, J=
3.0 Hz, 1H), 5.86 (br s, 1H), 3.20 (ABq, J=9.4 Hz, 2H), 2.20
(ABq, J=12.4 Hz, 2H), 1.74-1.35 (m, 10H), 1.11 (s, 3H); 13
C
NMR (75 MHz, CDCl3) δ 124.7, 117.4, 117.3, 114.1, 113.9,
113.6, 110.0, 109.8, 100.7, 96.0, 56.9, 50.2, 41.4, 39.1, 38.6, 29.6,
25.6, 24.2, 24.0, 23.5; IR (film) νmax 2924, 2851, 2809, 1610,
1512, 1473, 1364, 1332, 1293, 1177, 740 cm-1; MS (ESI) m/z 293
(Mþ þ H); HRMS calcd for C20H25N2 (Mþ þ H) 293.2017,
found 293 0.2010.
Experimental Section
General Procedure for PtCl4-Catalyzed Hydroamination-
Triggered Cyclization (Table 1, entry 4 and Tables 2-4). To a
mixture of aminoaromatics 1-(2-aminophenyl)pyrroles 1/N-(2-
aminophenyl)indoles 4/2-(2-aminophenyl)indoles 6 (0.6 mmol),
alkynols 2 (0.6 mmol), and PtCl4 (5 mol %) in a screw cap vial
was added methanol (2 mL) under argon atmosphere and the
mixture was stirred at 100 °C for 48 h. The reaction mixture was
passed through a pad of silica gel with ethyl acetate as an eluent.
After solvents were removed in vacuo, the residue was purified
by flash column chromatography with hexane/EtOAc as eluent to
give fused pyrrolo[1,2-a]quinoxalines 3/indolo[1,2-a]quinoxalines
5/indolo[3,2-c]quinolines 7.
12b-Methyl-2-phenyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-c]-
quinoxaline, 3f: 55% yield; yellow oil; Rf 0.62 (hexane/EtOAc=
90/10); 1H NMR (300 MHz, CDCl3) δ 7.37-7.26 (m, 5H),
7.22-7.20 (m, 1H), 7.13 (dd, J=2.8, 1.5 Hz, 1H), 7.03 (t, J=7.5
Hz, 1H), 6.78 (t, J=7.5 Hz, 1H), 6.62-6.56 (m, 1H), 6.30 (t, J=
3.0 Hz, 1H), 5.97-5.88 (m, 1H), 3.88 (dd, J=13.7, 9.2 Hz, 1H),
3.82-3.72 (m, 1H), 3.40 (dd, J=9.0, 3.3 Hz, 1H), 2.75-2.63 (m,
1H), 2.49 (t, J=11.0 Hz, 1H), 1.25 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 128.6, 127.5, 127.3, 126.7, 126.6, 125.0, 124.9, 118.3,
117.3, 115.9, 114.3, 114.1, 113.8, 113.5, 110.2, 110.1, 103.6,
101.3, 100.6, 53.1, 46.9, 45.8, 42.9, 41.9, 29.7, 29.3, 26.5, 23.6,
22.7; IR (film) νmax 2980, 2868, 2808, 1621, 1590, 1450, 1315,
12b-Methyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-c]quinoxa-
line, 3a: 78% yield; white solid; mp 55-57 °C; Rf 0.60 (hexane/
EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.28 (d, J=8.3
J. Org. Chem. Vol. 75, No. 10, 2010 3377

Patil et al.
JOCArticle
1290, 1107, 1019, 780, 706 cm-1; MS (ESI) m/z 301 (Mþ þ H);
HRMS calcd for C21H21N2 (Mþ þ H) 301.1705, found
300.1713.
2.34-2.16 (m, 2H), 2.11 (t, J=7.5 Hz, 2H), 1.14-1.02 (m, 10H),
0.79 (t, J=7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 135.5,
132.9, 125.5, 124.8, 116.6, 113.8, 113.6, 113.4, 109.9, 102.8, 62.8,
45.6, 36.8, 35.0, 31.7, 29.5, 25.0, 22.6, 22.1, 14.0; IR (film) νmax
Methyl 12a-methyl-10,11,12,12a-tetrahydrodipyrrolo[1,2-a:2,1-c]-
quinoxaline-6-carboxylate, 3g: 72% yield; white solid; mp 89-
92 °C; Rf 0.60 (hexane/EtOAc=90/10); H NMR (300 MHz,
2927, 2854, 1609, 1514, 1469, 1368, 1120, 1007, 732, 702 cm-1
;
MS (ESI) m/z 295 (Mþ þ H); HRMS calcd for C20H27N2 (Mþ þ
1
CDCl3) δ 7.96 (d, J=1.5 Hz, 1H), 7.70 (dd, J=8.3, 2.2 Hz, 1H),
7.17 (dd, J=3.0, 1.5 Hz, 1H), 6.53 (d, J=8.3 Hz, 1H), 6.25 (t, J=
3.0 Hz, 1H), 5.88-5.84 (m, 1H), 3.88 (s, 3H), 3.56-3.39 (m, 2H),
2.35-2.16 (m, 4H), 1.18 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
166.7, 138.7, 134.2, 127.2, 124.4, 115.1, 114.1, 112.0, 110.6,
101.7, 60.0, 51.7, 44.6, 37.0, 29.6, 24.6, 21.7; IR (KBr) νmax
2964, 2856, 1699, 1520, 1483, 1378, 1336, 1251, 1189, 1116, 759,
720 cm-1; MS (ESI) m/z 283 (Mþ þ H); HRMS calcd for
C17H19N2O2 (Mþ þ H) 283.1446, found 283.1440.
H) 295.2174, found 295.2176.
13a-Methyl-11,12,13,13a-tetrahydro-10H-pyrido[1,2-a]pyr-
rolo[2,1-c]quinoxaline, 3m: 71% yield; thick yellow oil; Rf 0.61
(hexane/EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.26 (d,
J=7.7 Hz, 1H), 7.06-6.93 (m, 2H), 6.80 (t, J=7.3 Hz, 1H), 6.73
(d, J=7.9 Hz, 1H), 6.20 (t, J=3.0 Hz, 1H), 5.85 (dd, J=3.0, 2.0
Hz, 1H), 3.42-3.29 (m, 1H), 2.91-2.77 (m, 1H), 2.28-1.60 (m,
6H), 1.12 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 124.7, 118.9,
114.3, 113.9, 113.0, 110.4, 110.1, 103.2, 101.3, 96.2, 42.6, 35.5,
30.7, 29.8, 25.6, 19.6; IR (film) νmax 2960, 2940, 2860, 1622,
1560, 1473, 1360, 1170, 742, 710 cm-1; MS (ESI) m/z 239 (Mþ þ
H); HRMS calcd for C16H19N2 (Mþ þ H) 239.1548, found
239.1537.
12b-Methyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-c]quino-
xalin-6-yl methyl ether, 3h: 76% yield; thick pale yellow oil;
Rf 0.65 (hexane/EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ
7.18 (d, J=8.4 Hz, 1H), 7.03-6.97 (m, 1H), 6.25 (d, J=8.4 Hz,
1H), 6.21 (t, J=3.0 Hz, 1H), 6.12 (br s, 1H), 5.83 (d, J=2.0 Hz,
1H), 3.78 (s, 3H), 3.35 (t, J=6.7 Hz, 2H), 2.35-2.10 (m, 4H),
1.11 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 157.3, 136.2, 134.6,
120.0, 114.5, 113.3, 109.4, 100.8, 100.6, 100.1, 55.2, 44.2, 36.8,
29.6, 22.9, 21.5; IR (film) νmax 2948, 2912, 2855, 1560, 1510,
1470, 1367, 1270, 1109, 1090, 990, 753 cm-1; MS (ESI) m/z 255
(Mþ þ H); HRMS calcd for C16H19N2O (Mþ þ H) 255.1497,
found 255.1494.
14b-Methyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyrrolo[2,1-c]quino-
xaline, 5a: 65% yield; white solid; mp 76-78 °C; Rf 0.72
(hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ 7.94
1
(d, J=8.3 Hz, 1H), 7.86 (dd, J=8.3, 1.5 Hz, 1H), 7.54 (d, J=6.7
Hz, 1H), 7.22-7.01 (m, 3H), 6.91 (t, J=7.5 Hz, 1H), 6.67 (br s,
1H), 6.24 (s, 1H), 3.54-3.26 (m, 2H), 2.48-2.12 (m, 4H), 1.26 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 143.9, 136.2, 133.7, 127.2,
124.2, 122.0, 120.8, 120.6, 117.8, 116.2, 114.0, 111.6, 95.2, 60.0,
43.8, 36.6, 29.6, 20.6; IR (KBr) νmax 3050, 3009, 2967, 2922,
2847, 1586, 1505, 1455, 1359, 1302, 1242, 1192, 1117, 1048, 747,
684 cm-1; MS (ESI) m/z 275 (Mþ þ H); HRMS calcd for
C19H19N2 (Mþ þ H) 275.1548, found 275.1550.
7-Chloro-12b-methyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-
c]quinoxaline, 3i: 75% yield; pale yellow oil; Rf 0.64 (hexane/
EtOAc = 90/10); 1H NMR (300 MHz, CDCl3) δ 7.18 (d,
J=8.3 Hz, 1H), 7.02-6.96 (m, 1H), 6.66 (dd, J=8.3, 2.0 Hz,
1H), 6.49 (d, J = 2.0 Hz, 1H), 6.22 (t, J = 3.0 Hz, 1H),
5.85-5.81 (m, 1H), 3.36 (t, J=6.9 Hz, 2H), 2.31-2.12 (m,
4H), 1.11 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 136.0, 134.8,
129.9, 124.2, 116.5, 114.8, 113.7, 113.1, 110.4, 101.4, 44.4,
36.8, 29.6, 23.4, 21.6; IR (film) νmax 2980, 2915, 2808, 1602,
1560, 1448, 1218, 1106, 760, 718 cm-1; MS (ESI) m/z 259
(Mþ þ H); HRMS calcd for C15H16N2Cl (Mþ þ H) 259.1002,
found 259.0996
6,8-Dichloro-12b-methyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-
a:2,1-c]quinoxaline, 3j: 67% yield; thick pale yellow oil; Rf
0.65 (hexane/EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ
7.86-7.83 (m, 1H), 6.82 (d, J=2.0 Hz, 1H), 6.47 (d, J=2.0 Hz,
1H), 6.28 (t, J=3.2 Hz, 1H), 5.91-5.87 (m, 1H), 3.28-3.26
(m, 2H), 2.37-2.12 (m, 4H), 1.09 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 136.7, 129.8, 119.2, 118.8, 112.2, 109.7, 109.5,
100.5, 59.4, 44.7, 36.9, 29.7, 21.9; IR (film) νmax 2968, 2925,
2853, 1595, 1492, 1438, 1215, 1163, 758, 709 cm-1; MS (ESI)
m/z 293 (Mþ þ H); HRMS calcd for C15H15Cl2N2 (Mþ þ H)
293.0612, found 293.0601.
12b-Ethyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-c]quinoxa-
line, 3k: 68% yield; thick brownoil; Rf 0.60 (hexane/EtOAc=90/
10); 1H NMR (300 MHz, CDCl3) δ 7.32 (ABq, J=1.5 Hz, 1H),
7.14 (dd, J=3.0, 1.5 Hz, 1H), 7.04 (t, J=7.5 Hz, 1H), 6.81-6.55
(m, 2H), 6.32 (t, J = 3.0 Hz, 1H), 5.93 (d, J = 1.5 Hz, 1H),
3.56-3.31 (m, 2H), 2.38-2.09 (m, 4H), 1.47 (q, J=12.0, 7.5 Hz,
2H), 0.70 (t, J=7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
124.8, 116.7, 116.6, 113.8, 113.6, 113.4, 109.9, 103.2, 103.1, 45.7,
34.5, 29.6, 22.6, 22.0, 9.3; IR (film) νmax 2964, 2923, 2850, 1608,
1513, 1468, 1367, 1332, 1297, 751, 701 cm-1; MS (ESI) m/z 239
(Mþ þ H); HRMS calcd for C16H19N2 (Mþ þ H) 239.1548,
found 239.1546.
12b-Hexyl-1,2,3,12b-tetrahydrodipyrrolo[1,2-a:2,1-c]quinoxa-
line, 3l: 74% yield; thick yellow oil; Rf 0.65 (hexane/EtOAc=90/
10); 1H NMR (500 MHz, CDCl3) δ 7.25 (t, J=7.5 Hz, 1H), 7.05
(br s, 1H), 6.96 (t, J=7.5 Hz, 1H), 6.69 (t, J=7.5 Hz, 1H), 6.55
(br s, 1H), 6.22 (t, J=3.3 Hz, 1H), 5.81 (d, J=1.6 Hz, 1H), 3.47
(dd, J = 14.2, 6.7 Hz, 1H), 3.35 (dd, J = 15.9, 7.5 Hz, 1H),
7,14b-Dimethyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyrrolo[2,1-
c]quinoxaline, 5b: 60% yield; thick pale yellow oil; Rf 0.61
1
(hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ 8.03
(d, J = 8.3 Hz, 1H), 7.74 (s, 1H), 7.60 (d, J = 7.5 Hz, 1H),
7.26-7.11 (m, 2H), 6.90 (d, J=7.5 Hz, 1H), 6.68-6.56 (m, 1H),
6.28 (s, 1H), 3.36-3.18 (m, 2H), 2.41 (s, 3H), 2.38-2.31 (m, 4H),
1.08 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 133.8, 129.9, 127.5,
127.3, 124.6, 121.9 120.8, 120.6, 117.1, 114.3, 114.1, 111.6, 95.2,
44.1, 36.5, 29.6, 21.5, 21.1, 20.3; IR (film) νmax 3050, 2960, 2867,
1592, 1510, 1460, 1368, 1267, 1160, 1059, 781 cm-1; MS (ESI) m/
z 289 (Mþþ H); HRMS calcd for C20H21N2 (Mþ þ H) 289.1705,
found 289.1701.
14,14b-Dimethyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyrrolo-
[2,1-c]quinoxaline, 5c: 70% yield; thick pale yellow oil; Rf 0.67
(hexane/EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.90 (d,
J=8.3 Hz, 1H), 7.85 (dd, J=9.0, 1.5 Hz, 1H), 7.51 (d, J=7.5 Hz,
1H), 7.22-7.08 (m, 2H), 7.05-6.98 (m, 1H), 6.89 (t, J=7.5 Hz,
1H), 6.73-6.60 (m, 1H), 3.45-3.21 (m, 2H), 2.57-2.40 (m, 2H),
2.36 (s, 3H), 2.28-2.14 (m, 2H), 1.13 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 139.4, 135.9, 132.8, 130.8, 127.2, 123.7, 122.1, 120.1,
118.6, 117.9, 115.8, 113.7, 111.6, 110.5, 60.9, 43.0, 36.9, 21.3, 19.6,
8.8; IR (film) νmax 2962, 2920, 2816, 1615, 1517, 1467, 1373, 1310,
1166, 1120, 1042, 798, 740 cm-1; MS (ESI) m/z 289 (Mþ þ H);
HRMS calcd for C20H21N2 (Mþ þ H) 289.1705, found 289.1714.
Methyl 14b-methyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyrrolo-
[2,1-c]quinoxaline-7-carboxylate, 5d: 69% yield; yellow solid;
mp 90-92 °C; Rf 0.55 (hexane/EtOAc=90/10); 1H NMR (300
MHz, CDCl3) δ 8.57 (d, J=1.5 Hz, 1H), 8.03 (d, J=8.3 Hz, 1H),
7.77 (dd J=8.3, 1.7 Hz, 1H), 7.55 (d, J=7.5 Hz, 1H), 7.30-7.22
(m, 1H), 7.13 (t, J=7.7 Hz, 1H), 6.70 (d, J=8.3 Hz, 1H), 6.27 (s,
1H), 3.94 (s, 3H), 3.58-3.38 (m, 2H), 2.51-2.15 (m, 4H), 1.21 (s,
3H); 13C NMR (75 MHz, CDCl3) δ 167.3, 142.7, 139.8, 133.8,
130.0, 126.6, 126.0, 122.5, 121.0, 120.9, 118.6, 117.2, 112.5,
111.8, 95.9, 60.2, 51.8, 44.2, 36.8, 29.7, 21.6; IR (KBr) νmax
2941, 2860, 1690, 1622, 1542, 1460, 1340, 1286, 1260, 1103, 770,
741 cm-1; MS (ESI) m/z 333 (Mþ þ H); HRMS calcd for
C21H21N2O2 (Mþ þ H) 333.1603, found. 333.1595.
3378 J. Org. Chem. Vol. 75, No. 10, 2010

Patil et al.
13-Methoxy-14b-methyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyr-
rolo[2,1-c]quinoxaline, 5e: 59% yield; thick yellow oil; Rf 0.65
JOCArticle
118.6, 115.5, 115.3, 114.9, 112.2, 111.0, 62.4, 44.9, 37.5, 25.0,
21.3; IR (KBr) νmax 3402, 3055, 2956, 2852, 1607, 1510, 1461,
1357, 1296, 1194, 1161, 1048, 744, 625 cm-1; MS (ESI) m/z 275
(Mþ þ H); HRMS calcd for C19H19N2 (Mþ þ H) 275.1548,
found 275.1546.
7,12,13c-Trimethyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]pyr-
rolo[1,2-a]quinoline, 7b: 83% yield; thick pale yellow oil; Rf 0.48
(hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ 8.03
(br s, D2O exchangeable, 1H), 7.22-6.80 (m, 6H), 6.35 (s, 1H),
3.60-3.14 (m, 2H), 2.59-2.46 (m, 2H), 2.41 (s, 3H), 2.37-2.26
(m, 2H), 2.22 (s, 3H), 1.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
140.4, 135.6, 130.0, 128.9, 125.5, 124.5, 123.2, 120.4, 118.4,
115.3, 115.1, 112.2, 110.6, 62.3, 45.1, 37.5, 29.7, 24.7, 21.4,
20.6; IR (KBr) νmax 3409, 2965, 2915, 2860, 1622, 1541, 1470,
1360, 1307, 1155, 1120, 1070, 780, 740 cm-1; MS (ESI) m/z 303
(Mþ þ H); HRMS calcd for C21H23N2 (Mþ þ H) 303.1861,
found 303.1867.
1
(hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ 7.88
(d, J=7.9 Hz, 1H), 7.62 (d, J=8.4 Hz, 1H), 7.20-7.04 (m, 2H),
6.92 (t, J=6.9 Hz, 1H), 6.74-6.64 (m, 1H), 6.59 (d, J=7.7 Hz,
1H), 6.42 (s, 1H), 3.94 (s, 3H), 3.44-3.20 (m, 2H), 2.46-2.11 (m,
4H), 1.10 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 153.2, 136.3,
135.0, 127.3, 124.3, 122.8, 120.2, 117.8, 116.4, 114.0, 107.3,
105.2, 100.9, 92.3, 55.3, 44.0, 36.7, 29.7, 21.5, 20.8; IR (film)
1
ν
max 2961, 2925, 2841, 1567, 1505, 1462, 1437, 1361, 1256, 1181,
1083, 753 cm-1; MS (ESI) m/z 305 (Mþ þ H); HRMS calcd for
C20H21N2O (Mþ þ H) 305.1654, found 305.1661.
7-Chloro-14b-methyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyr-
rolo[2,1-c]quinoxaline, 5f: 67% yield; thick yellow oil; Rf 0.62
(hexane/EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.91 (d,
J=8.3 Hz, 1H), 7.85 (d, J=2.0 Hz, 1H), 7.55 (d, J=7.5 Hz, 1H),
7.27-7.19 (m, 1H), 7.13 (t, J=7.4 Hz, 1H), 7.03 (dd, J=8.4, 2.2
Hz, 1H), 6.70-6.60 (m, 1H), 6.27 (s, 1H), 3.34 (t, J=6.9 Hz, 2H),
2.48-2.10 (m, 4H), 1.16 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
143.6, 134.9, 133.6, 130.0, 127.8, 123.8, 122.6, 122.4, 121.1,
121.0, 116.3, 114.5, 111.4, 95.9, 60.0, 44.0, 36.6, 21.5, 20.8; IR
(film) νmax 3051, 2967, 1584, 1504, 1454, 1364, 1264, 1189, 791,
743 cm-1; MS (ESI) m/z 309 (Mþ þ H); HRMS calcd for
C19H18ClN2 (Mþ þ H) 309.1159, found. 309.1149.
12,13c-Dimethyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]pyr-
rolo[1,2-a]quinoline, 7c: 85% yield; thick pale yellow oil; Rf 0.55
(hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ 7.93
1
(br s, D2O exchangeable, 1H), 7.22-7.14 (m, 3H), 7.04 (t,
J=7.7 Hz, 1H), 6.90 (d, J=7.9 Hz, 1H), 6.66-6.54 (m, 1H),
6.50-6.38 (m, 1H), 3.59-3.25 (m, 2H), 2.65-2.53 (m, 1H), 2.43
(s, 3H), 2.39-2.10 (m, 3H), 1.29 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 142.5, 135.7, 129.0, 128.4, 123.3, 120.4, 119.8, 118.5,
115.5, 115.1, 112.1, 110.7, 45.0, 37.6, 29.7, 25.0, 21.5, 21.4; IR
(KBr) νmax 3429, 2959, 2917, 2853, 1607, 1507, 1461, 1365, 1303,
14b-Ethyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyrrolo[2,1-c]quino-
xaline, 5g: 61% yield; thick pale yellow oil; Rf 0.65 (hexane/
EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.97 (d, J=8.3
Hz, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.54 (d, J = 7.5 Hz, 1H),
7.20-6.97 (m, 3H), 6.88 (t, J=7.5 Hz, 1H), 6.78-6.52 (m, 1H),
6.23 (s, 1H), 3.48-3.20 (m, 2H), 2.45-2.06 (m, 4H), 1.50-1.20
(m, 2H), 0.76 (t, J=7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ
133.8, 129.8, 127.2, 124.2, 121.9, 120.7, 120.5, 117.5, 116.2,
114.0, 111.6, 100.4, 97.5, 44.8, 33.4, 29.6, 26.1, 21.9, 9.4; IR
(film) νmax 2930, 2860, 1612, 1523, 1460, 1363, 1327, 1187, 1070,
745, 692 cm-1; MS (ESI) m/z 289 (Mþ þ H); HRMS calcd for
C20H21N2 (Mþ þ H) 289.1705, found 289.1711.
1166, 1125, 1040, 799, 741 cm-1; MS (ESI) m/z 289 (Mþ
þ
H); HRMS calcd for C20H21N2 (Mþ þ H) 289.1705, found
289.1711.
12-Chloro-13c-methyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]-
pyrrolo[1,2-a]quinoline, 7d: 81% yield; yellow solid; mp 64-
1
66 °C; Rf 0.45 (hexane/EtOAc=90/10); H NMR (500 MHz,
CDCl3) δ 8.06 (br s, D2O exchangeable, 1H), 7.37 (d, J=1.9 Hz,
1H), 7.22-7.15 (m, 2H), 7.10-7.01 (m, 2H), 6.62 (t, J=6.8 Hz,
1H), 6.47 (br s, 1H), 3.56-3.30 (m, 2H), 2.59-2.08 (m, 4H), 1.28
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 142.5, 135.6, 131.3, 129.1,
126.3, 125.4, 128.8, 120.1, 118.0, 115.6, 114.8, 114.4, 112.4,
111.9, 62.2, 45.0, 37.4, 25.0, 21.3; IR (KBr) νmax 3368, 2960,
2912, 2860, 1615, 1515, 1470, 1367, 1290, 1192, 1109, 810, 753
cm-1; MS (ESI) m/z 309 (Mþ þ H); HRMS calcd for
C19H18ClN2 (Mþ þ H), 309.1159, found 309.1153.
14b-Hexyl-1,2,3,14b-tetrahydroindolo[1,2-a]pyrrolo[2,1-c]quino-
xaline, 5h: 59% yield; thick pale yellow oil; Rf 0.70 (hexane/
EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.98 (d, J=8.3
Hz, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.55 (d, J = 7.3 Hz, 1H),
7.20-7.00 (m, 3H), 6.95-6.60 (m, 2H), 6.23 (s, 1H), 3.48-3.29
(m, 2H), 2.48-2.09 (m, 4H), 1.48-0.95 (m, 10H), 0.78 (t, J=6.7
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 141.7, 136.3, 133.8,
129.9, 127.2, 124.2, 121.9, 120.7, 120.5, 117.5, 116.3, 114.0,
111.6, 97.4, 63.3, 44.7, 34.1, 33.3, 31.7, 29.5, 25.2, 22.5, 21.9,
14.0; IR (film) νmax 2927, 2855, 1609, 1506, 1456, 1361, 1310,
1195, 740, 692 cm-1; MS (ESI) m/z 345 (Mþ þ H); HRMS calcd
for C24H29N2 (Mþ þ H) 345.2331, found 345.2328.
7-Chloro-13c-methyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]pyr-
rolo[1,2-a]quinoline, 7e: 63% yield; yellow solid; mp 185-
187 °C; Rf 0.60 (hexane/EtOAc=90/10); 1H NMR (500 MHz,
CDCl3) δ 8.13 (br s, D2O exchangeable, 1H), 7.46 (d, J=8.7 Hz,
1H), 7.33 (d, J=8.7 Hz, 1H), 7.25-7.19 (m, 1H), 7.14 (t, J=7.8
Hz, 1H), 7.06 (t, J = 7.8 Hz, 1H), 7.02 (d, J = 7.8 Hz, 1H),
6.54-6.36 (m, 1H), 3.61-3.49 (m, 1H), 3.38-3.27 (m, 1H), 2.60
(t, J=9.7 Hz, 1H), 2.53-2.37 (m, 1H), 2.32-2.06 (m, 2H), 1.29
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 137.5, 128.6, 127.9, 125.0,
122.3, 120.1, 119.6, 118.9, 116.3, 113.2, 111.2, 45.1, 37.4, 29.7,
25.0, 21.3; IR (KBr) νmax 3432, 2962, 2921, 2848, 1601, 1511,
1462, 1364, 1285, 1191, 1107, 802, 746 cm-1; MS (ESI) m/z 309
(Mþ þ H); HRMS calcd for C19H18ClN2 (Mþ þ H) 309.1159,
found 309.1164.
15b-Methyl-1,3,4,15b-tetrahydro-2H-indolo[1,2-a]pyrido[2,1-
c]quinoxaline, 5i: 62% yield; pale yellow oil; Rf 0.62 (hexane/
EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 7.98 (d, J=8.3
Hz, 1H), 7.90 (d, J=8.3, Hz, 1H), 7.62 (d, J= 6.7 Hz, 1H),
7.27-7.09 (m, 3H), 7.02 (t, J=8.3 Hz, 1H), 6.91 (d, J=7.5 Hz,
1H), 6.33 (s, 1H), 3.40-3.31 (m, 1H), 2.91-2.82 (m, 1H),
2.38-1.60 (m, 6H), 1.14 (s, 3H); 13C NMR (75 MHz, CDCl3)
δ 138.9, 129.9, 125.3, 124.2, 121.9, 120.7, 120.8, 119.6, 116.2,
114.9, 111.8, 95.7, 43.5, 35.9, 29.6, 25.4, 19.4, 17.9; IR (film) νmax
3015, 2960, 1610, 1516, 1470, 1377, 1267, 1160, 1060, 780, 740
cm-1; MS (ESI) m/z 289 (Mþ þ H); HRMS calcd for C20H21N2
(Mþ þ H) 289.1705, found 289.1709.
7,12-Dichloro-13c-methyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]-
pyrrolo[1,2-a]quinoline, 7f: 71% yield; thick pale yellow; Rf 0.67
(hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ 8.32
1
13c-Methyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]pyrrolo-
[1,2-a]quinoline, 7a: 81% yield; white solid; mp 162-164 °C; Rf
(br s, D2O exchangeable, 1H), 7.41 (s, 1H), 7.24 (d, J=8.3 Hz,
2H), 7.10-7.02 (m, 2H), 6.59-6.21 (m, 1H), 3.60-3.10 (m, 2H),
2.63-2.08 (m, 4H), 1.24 (s, 3H); 13C NMR (75 MHz, CDCl3) δ
135.8, 130.1, 128.4, 126.0, 125.6, 122.4, 119.9, 118.2, 115.6,
113.4, 112.0, 45.1, 37.3, 29.7, 25.0, 21.3; IR (film) νmax 3411,
2967, 2918, 2859, 1607, 1522, 1476, 1360, 1280, 1190, 1102, 802,
760 cm-1; MS (ESI) m/z 343 (Mþ þ H); HRMS calcd for
C19H17N2Cl2 (Mþ þ H) 343.0769, found 343.0777.
1
0.55 (hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ
7.96 (br s, D2O exchangeable, 1H), 7.43 (d, J=7.5 Hz, 1H), 7.27
(d, J=7.9 Hz, 1H), 7.15 (d, J=7.3 Hz, 1H), 7.12-6.99 (m, 3H),
6.61 (t, J=7.3 Hz, 1H), 6.44 (d, J=8.1 Hz, 1H), 3.58-3.32 (m,
2H), 2.60-2.10 (m, 4H), 1.29 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 142.5, 137.3, 129.7, 128.6, 125.2, 121.7, 120.0, 119.8,
J. Org. Chem. Vol. 75, No. 10, 2010 3379

Patil et al.
JOCArticle
12-Chloro-7,13c-dimethyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]-
pyrrolo[1,2-a]quinoline, 7g: 67% yield; thick yellow oil; Rf 0.53
(hexane/EtOAc=90/10); H NMR (300 MHz, CDCl3) δ 8.08
740, 690 cm-1; MS (ESI) m/z 345 (Mþ þ H); HRMS calcd for
C24H29N2 (Mþ þ H) 345.2331, found 345.2328.
1
13c-Ethyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]pyrrolo[1,2-a]-
quinoline, 7k: 77% yield; thick pale yellow oil; Rf 0.67 (hexane/
EtOAc=90/10); 1H NMR (300 MHz, CDCl3) δ 8.07 (br s, D2O
exchangeable, 1H), 7.35 (d, J=1.7 Hz, 1H), 7.22-7.11 (m, 2H),
7.09-6.92 (m, 3H), 6.71 (t, J=6.9 Hz, 1H), 6.51-6.38 (m, 1H),
3.57-3.21 (m, 2H), 2.60-2.09 (m, 6H), 1.21 (t, J=7.5 Hz, 3H);
13C NMR (75 MHz, CDCl3) δ 142.5, 135.6, 131.3, 129.0, 126.2,
125.3, 121.7, 120.2, 117.9, 115.6, 114.4, 114.3, 112.4, 111.9, 62.2,
44.9, 37.4, 29.7, 24.9, 21.3; IR (film) νmax 3435, 2960, 2918, 2860,
1611, 1525, 1470, 1367, 1290, 1187, 1108, 802, 760 cm-1; MS
(ESI) m/z 289 (Mþ þ H); HRMS calcd for C20H21N2 (Mþ þ H)
289.1705, found 289.1706.
(br s, D2O exchangeable, 1H), 7.37 (s, 1H), 7.23-7.14 (m, 1H),
7.03 (d, J=8.1 Hz, 2H), 6.88 (d, J=7.9 Hz, 1H), 6.45-6.30 (m,
1H), 3.60-3.22 (m, 2H), 2.59-2.14 (m, 7H), 1.23 (s, 3H); 13C
NMR (75 MHz, CDCl3) δ 140.5, 135.6, 131.4, 129.6, 126.3,
125.3, 124.7, 121.7, 120.7, 118.0, 115.0, 114.4, 112.5, 111.8, 62.0,
45.1, 37.4, 29.7, 24.6, 21.4; IR (KBr) νmax 3388, 2920, 2852, 1617,
1507, 1462, 1361, 1286, 1158, 1059, 860, 787, 706 cm-1; MS
(ESI) m/z 323 (Mþ þ H); HRMS calcd for C20H20ClN2 (Mþ þ
H) 323.1315, found 323.1318.
Methyl 13c-methyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]pyr-
rolo[1,2-a]quinoline-12-carboxylate, 7h: 59% yield; thick pale
yellow oil; Rf 0.40 (hexane/EtOAc = 90/10); 1H NMR (300
MHz, CDCl3) δ 8.72 (br s, D2O exchangeable, 1H), 8.16 (s, 1H),
7.80 (dd, J=8.4,1.3 Hz, 1H), 7.32-7.22 (m, 2H), 7.06 (t, J=7.5
Hz, 1H), 6.60 (t, J=7.1 Hz, 1H), 6.50-6.37 (m, 1H), 3.94 (s, 3H),
3.56-3.24 (m, 2H), 2.67-2.56 (m, 1H), 2.43-2.28 (m, 3H), 1.28
(s, 3H); 13C NMR (75 MHz, CDCl3) δ 165.3, 143.9, 136.2, 127.2,
124.2, 121.9, 120.6, 117.8, 116.2, 113.9, 111.6, 95.2, 59.9, 43.8,
36.6, 29.6, 20.6 ; IR (film) νmax 3396, 2916, 2860, 2812, 1693,
1622, 1514, 1473, 1338, 1272, 1250, 1108, 770, 743 cm-1; MS
(ESI) m/z 333 (Mþ þ H); HRMS calcd for C21H21N2O2 (Mþ þ
H) 333.1603, found 333.1613.
General Procedure for Ph3PAuOTf-Catalyzed One-Pot
Synthesis of Fused Indolo[1,2-a]quinoxalines from 8 and 2a
(Scheme 1). To a mixture of diamine 8 (0.6 mmol) and
4-pentyn-1-ol 2a (0.6 mmol) in toluene (2 mL) were added
Ph3PAuCl (5 mol %) and AgOTf (5 mol %) in a screw cap vial
under argon atmosphere. The mixture was stirred at 100 °C for
48 h. The reaction mixture was passed through a pad of silica
gel with ethyl acetate as an eluent. After solvents were removed
in vacuo, the residue was purified by flash column chromato-
graphy with hexane/EtOAc as eluent to give indolo[3,2-c]-
quinolines 7.
13c-Methyl-1,3,9,13c-tetrahydrospiro[cyclopentane-1,2-indolo-
[3,2-c]pyrrolo[1,2-a]quinoline], 7i: 65% yield; thick pale yellow
oil; Rf 0.60 (hexane/EtOAc = 90/10); 1H NMR (300 MHz,
CDCl3) δ 8.18 (br s, D2O exchangeable, 1H), 7.46 (d, J=7.5
Hz, 1H), 7.30 (d, J = 6.7 Hz, 1H), 7.21 (d, J = 6.7 Hz, 1H),
7.13-7.03 (m, 3H), 6.65 (t, J=6.7 Hz, 1H), 6.46 (d, J=7.5 Hz,
1H), 3.40-3.23 (m, 2H), 2.72-2.40 (m, 2H), 1.93-1.38 (m,
10H), 1.32 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 142.4, 137.2,
129.5, 128.4, 125.1, 121.7, 120.0, 119.7, 118.6, 116.6, 115.9,
115.4, 112.8, 111.0, 62.9, 58.8, 51.2, 48.0, 41.9, 40.1, 25.9, 24.5,
23.9; IR (film) νmax 3412, 3259, 2952, 2862, 1610, 1511,
1461, 1359, 1322, 1213, 1160, 745 cm-1; MS (ESI) m/z 329
(Mþ þ H); HRMS calcd for C23H25N2 (Mþ þ H) 329.2018,
found 329.2012.
Typical Procedure for PtCl4-Catalyzed Hydroamination-Trig-
gered Cyclization under Microwave-Assisted Conditions. A
sealed 10 mL glass tube containing a solution of the aminoaro-
matics 1, 4, or 6 (0.6 mmol), alkynols 2 (0.6 mmol), and PtCl4 (5
mol %) in methanol (2 mL) was kept in the cavity of a
microwave reactor (Biotage, initiator 8, single-mode reactor).
The mixture was subjected to microwave irradiation under
stirring at 150 °C (P = 40-50 W) for 15 min. The reaction
mixture was passed through a pad of silica gel with ethyl acetate
as an eluent. After solvents were removed in vacuo, the residue
was purified by flash column chromatography with hexane/
EtOAc as eluent to give pyrrolo[1,2-a]quinoxalines 3/indolo-
[1,2-a]quinoxalines 5/indolo[3,2-c]quinolines 7.
13c-Hexyl-2,3,9,13c-tetrahydro-1H-indolo[3,2-c]pyrrolo[1,2-a]-
quinoline, 7j: 69% yield; thick pale yellow oil; Rf 0.65 (hexane/
EtOAc=90/10); 1H NMR (400 MHz, CDCl3) δ 8.05 (br s, D2O
exchangeable, 1H), 7.42 (d, J=7.2 Hz, 1H), 7.28 (d, J=7.2 Hz,
1H), 7.15 (d, J=7.2 Hz, 1H), 7.09-6.94 (m, 3H), 6.63-6.53 (m,
1H), 6.43 (d, J=7.2 Hz, 1H), 3.62-3.32 (m, 2H), 2.67-2.60 (m,
1H), 2.48-1.96 (m, 4H), 1.69-1.54 (m, 2H), 1.24-1.00 (m, 7H),
0.74 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 144.0,
128.6, 121.7, 119.8, 119.7, 119.1, 115.2, 114.9, 112.4, 111.7,
110.9, 60.4, 46.1, 36.6, 32.6, 29.7, 29.4, 29.3, 21.4, 14.1, 9.1; IR
(film) νmax 3233, 2930, 2860, 1615, 1512, 1460, 1370, 1312, 1190,
Acknowledgment. We gratefully acknowledge financial
support from the Council of Scientific and Industrial Re-
search, India. N.T.P. is grateful to Dr. J. S. Yadav, Director,
IICT and Dr. V. V. N. Reddy, Head, Org-II Division for
their support and encouragement.
Supporting Information Available: All experimental proce-
dures, analytical data, and copies of 1H and 13C NMR spectra of
all newly synthesized products. This material is available free of
charge via the Internet at http://pubs.acs.org.
3380 J. Org. Chem. Vol. 75, No. 10, 2010