Palladium-catalyzed synthesis of 1,2-dihydro-4(3H)-carbazolones. Formal total synthesis of murrayaquinone A

Article abstract of DOI:10.1016/S0040-4020(03)00976-1

Two sequential palladium-catalyzed reactions are the key steps in a novel synthetic route to 1,2-dihydro-4(3H)-carbazolones. The steps are an intermolecular Stille cross-coupling followed by a reductive N-heteroannulation. A formal total synthesis of murrayaquinone A, employing this sequence, is reported.

Full text of DOI:10.1016/S0040-4020(03)00976-1

Tetrahedron 59 (2003) 6323–6332
Palladium-catalyzed synthesis of 1,2-dihydro-4(3H)-carbazolones.
Formal total synthesis of murrayaquinone A
*
¨ ¨
Tricia L. Scott and Bjorn C. G. Soderberg
Department of Chemistry, West Virginia University, P.O. Box 6045, Morgantown, WV 26506-6045, USA
Received 25 March 2003; revised 11 June 2003; accepted 19 June 2003
Abstract—Two sequential palladium-catalyzed reactions are the key steps in a novel synthetic route to 1,2-dihydro-4(3H)-carbazolones.
The steps are an intermolecular Stille cross-coupling followed by a reductive N-heteroannulation. A formal total synthesis of
murrayaquinone A, employing this sequence, is reported.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
prepared by reaction of the unsaturated bromoketal 5 with
2 equiv. of tert-butyllithium followed by addition of tri-n-
butyltin chloride. The crude reaction mixture was stirred
with hydrochloric acid affording the deprotected ketone 6 in
high overall yield (Scheme 2). Palladium-catalyzed cross-
coupling of 6 with 2-iodo-1-nitrobenzene gave the expected
cross coupling product 3 in 71% yield.
We have recently described a mild and very efficient
palladium-catalyzed route to substituted indoles via a
palladium-catalyzed reductive N-heteroannulation of func-
tionalized 2-nitrostyrenes.1–6 This annulation reaction has
been used as the key step to prepare a variety of tricyclic
3,4-fused indoles7 in addition to some naturally occurring
mushroom metabolites.8
Carbazolones have been used as intermediates in total
synthesis of a variety of naturally occurring carbazole
alkaloids for example, pyrayaquinones A and B, murraya-
quinone A, koeniginequinone A,12 and murrayafoline A.13
A variety of methods have been utilized to prepare
carbazolones. One of the most common methods used is
the Fischer indole synthesis. For example, the parent ring-
system, 1,2-dihydro-4(3H)-carbazolone (4), was prepared in
51% yield by reaction of phenylhydrazine with 1,3-
cyclohexanedione followed by treatment of the obtained
hydrazone with sulfuric acid.14 Drawbacks of this method-
ology are the highly acidic reaction conditions and the
formation of regioisomeric products when unsymmetrical
substrates are used. The synthetic relay seen in Scheme 1 is
As an extension of this work, we have communicated a
related relatively mild and efficient palladium-catalyzed
route to substituted 1,2-dihydro-4(3H)-carbazolones.9 The
annulation precursors were prepared by intermolecular
Stille cross-couplings.10 In our initial synthetic sequence,
2-(tri-n-butylstannyl)-1-nitrobenzene (1) was reacted with
2-iodo-2-cyclohexenone (2) in the presence of bis(benzo-
nitrile)palladium dichloride (PdCl2(PhCN)2, 5 mol%),
triphenylarsine (AsPh3, 10 mol%), and copper iodide
(10 mol%) in N-methylpyrrolidinone (NMP) to give the
expected coupling product 3 in good isolated yield.
Palladium-catalyzed N-heteroannulation of 3 using palla-
dium bis(dibenzylideneacetone) (Pd(dba)2, 6 mol%),
1,3-bis(diphenylphosphino)propane (dppp, 6 mol%),
1,10-phenanthroline (12 mol%), and CO (6 atm) in
dimethylformamide (DMF) at 808C, furnished the
expected 1,2-dihydro-4(3H)-carbazolone 4 (Scheme 1).11
The polarity of the cross-coupling reagents can readily be
switched, i.e. using 2-iodo-1-nitrobenzene and 2-tri-n-butyl-
2-cyclohexene-1-one (6). The required tin reagent was
Keywords: palladium-catalyzed reactions; murrayaquinone A; cross-
coupling.
*
Corresponding author. Tel.: þ1-3042933435; fax: þ1-3042934904;
e-mail: bjorn.soderberg@mail.wvu.edu
Scheme 1.
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00976-1

¨
T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6324
Scheme 4.
(,10%) of homo-coupling products of the0tin reagents 1 and
6, namely 2,20-dinitrobiphenyl16 and 2,2 -bis-(2-cyclohex-
ene-1-one),17,18 were isolated as byproducts in most
coupling reactions.
Scheme 2.
The conditions of the N-heteroannulation warrant some
comment. The results of a brief study of the influence of
catalyst, ligand(s), temperature, solvent, and CO pressure
are summarized in Table 1. Initial attempts to cyclize 3 to 4
using palladium diacetate (6 mol%), triphenylphosphine
(24 mol%), and carbon monoxide (4 atm) in acetonitrile at
708C, reaction conditions previously employed for the
preparation of a large variety of indoles,1 surprisingly, gave
only recovered starting material (entry 1, Table 1). A
moderate yield of product was observed at upon elevating
the temperature and CO pressure, however a fair amount of
starting material still remained (entry 2, Table 1). Changing
the solvent to DMF produced a similar yield of 4 with
complete disappearance of 3 (entry 3, Table 1). Combi-
nations of Pd(OAc)2-dppp, Pd(OAc)2-1,10-phenanthroline,
Pd(dba)2-dppp, and Pd(dba)2-1,10-phenathroline resulted in
the formation of the expected product with somewhat better
results using Pd(dba)2 (entries 4–7, Table 1). Finally, a
combination of the two bidentate ligands dppp (12 mol%)
and 1,10-phenanthroline (12 mol%), in the presence of
Pd(dba)2, under 6 atm of CO in (DMF) at 808C gave the
expected 1,2-dihydro-4(3H)-carbazolone 4 in 74% yield
(entry 8, Table 1). It should be noted that palladium-
phenanthroline complexes have been shown to be particu-
larly active catalysts for the reductive carbonylation of
nitrobenzenes to give isocyanates.19 The reason for the
increased efficiency of the annulation in the presence of two
different bidentate ligands is presently unclear.
inherently regioselective and tolerates a wide range of
functional groups. Herein is reported the full scope of the
two-step reaction relay to 1,2-dihydro-4(3H)-carbazolones
and an application thereof in a formal total synthesis of the
carbazole alkaloid murrayaquinone A.
2. Results and discussion
In order to examine the scope and limitation of sequence
seen in Scheme 1, a number of cycloalkenones and
nitroaromatic compounds were required as starting
materials for the cross-coupling reaction. Most of the
compounds were commercially available or prepared as
previously described in the literature. 2-Iodo-5-methyl-2-
cyclohexenone (8) was prepared by base mediated iodina-
tion of the corresponding cycloalkenone according to
Johnson et al. (Scheme 3).15
3-Iodo-2-nitrotoluene (13) and 4-bromo-2-iodo-1-nitro-
benzene (15) were prepared by modified literature
procedures from the corresponding anilines 17–18
(Schemes 4 and 5).
With the starting materials in hand, a variety of substituted
2-(2-nitrophenyl)-2-cycloalkenones (19–27) were prepared
by a palladium-catalyzed Stille type cross-coupling of 1 or 6
with 2-iodo-2-cycloalkenones or aryl halides, respectively.
The results are summarized in Table 2. The Stille cross-
couplings proceeded uneventfully; however, lower yields of
product were observed for the more sterically congested aryl
bromides (12 and 14) and for vinyl bromide 10. Some
modifications of the reaction conditions were required for
the synthesis of compounds 24 and 26. Although still
moderate, the best yield of 26 was obtained by replacing
AsPh3 with 1,10-bis-(diphenylphosphino)ferrocene (dppf) as
the ligand. In addition to the expected coupling product 26,
transfer of one of the n-butyl groups from 1 to 14 was also
observed in some reactions. Compound 24 was prepared
using PdCl2(PPh3)2 as the catalyst in DMF (1108C) without
added ligand. It should be noted that minor amounts
Using the above conditions, palladium-catalyzed N-hetero-
annulation of 19–27 gave the expected 2,3-fused indoles
31–39 in 52–89% isolated yield (Table 2). The mono-
hydrate of 1,10-phenanthroline was used in all reactions
with no apparent detrimental effect compared to our initial
reaction seen in Scheme 1. The reactions were monitored by
TLC until all starting material had been consumed, and most
of the reductive cyclizations were complete in 1–3 days.
However, substrate 27 required an extended period of 8 days
to go to completion. The yield of the 6-bromocarbazolone
39 was also significantly lower compared to the other
cyclizations. A 5-bromo substituent has previously been
problematic in this type of reaction. For example, attempted
cyclization of 5-bromo-2-nitrostyrene yielded only recov-
ered starting material.15 It is interesting to note that no
Scheme 3.
Scheme 5.

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T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6325
Table 1. Catalysts for transformation of 3 to 4
Entrya
Catalyst
Ligand(s)
PPh3
PPh3
PPh3
dppp
1,10-Phen
dppp
1,10-Phen
dppp/1,10-Phen
Solvent
pCO (atm)
Temperature (8C)
3 (%)
4 (%)
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(dba)2
Pd(dba)2
Pd(dba)2
MeCN
MeCN
DMF
DMF
DMF
DMF
DMF
DMF
4
6
6
6
6
6
6
6
70
80
80
80
80
80
80
80
43
50
n.o
45
43
35
43
58
52
74
n.o
n.o
n.o
n.o
39
n.o
a
All reactions were performed on a 0.5 mmol scale for 20 h. 1,10-Phen¼1,10-Phenanthroline; DPPP¼bis(diphenylphosphino)propane; n.o¼not observed.
formal condensation with the ketone functionality occurred.
This type of annulation was observed by Watanabe et al.
upon palladium-catalyzed N-heteroannulation of 28 afford-
ing both the expected indole 29 and a significant amount of
quinoline 30 (Scheme 6).3 Related nitrogen–carbonyl
carbon reactions of N-(2-nitrobenzoyl)amides have also
been reported.20
prepared by aromatic nucleophilic substitution employing
2-iodo-1-nitrobenzene and 1,3-cyclohexanedione, and
methylation of 41 with dimethylsulfate gave the annulation
precursor 42 (Scheme 8). N-heteroannulation of dienone 41
and enol ether 42 produced carbazolone 4 in acceptable
yields under the standard reaction conditions. However,
longer reaction times (90–96 h) were required for the
cyclizations to go to completion.
Five- to seven-membered rings were readily fused to the
indole skeleton (entries 1–3). The annulation reaction
appears to be relatively unaffected by electron-withdrawing
or electron-donating substituents on the aromatic ring. As
can be seen in entries 5 and 8, both methoxy and methyl
ester functionalized benzene rings work well. Substituents
adjacent to the alkene or the nitro group of the aromatic ring
also do not appear to affect the yield of the reaction (entries
6–7). Similar results were obtained in our previous studies
of the formation of indoles by reductive N-heteroannula-
tion.9
We decided to examine a potentially general route to
carbazoloquinone alkaloids. Murrayaquinone A was
selected as the initial target molecule (Scheme 8).12,23,24,25
In the event, iodination of 6-methyl-2-cyclohexenone (43)
gave 2-iodo-6-methyl-2-cyclohexenone (44). Stille cross-
coupling of 44 with arylstannane 1 gave annulation
precursor 45 in high isolated yield. The reductive cycliza-
tion of 45 also proceeded uneventfully affording carbazo-
lone 46 in an excellent yield (97%). Dehydrogenation of
carbazolone 46 using 10% Pd/C in a mixture of diphenyl
ether and 1,2,4-trimethylbenzene at 2308C furnished 3-
methyl-4-hydroxycarbazole 47. As was previously shown
by Bringmann et al. addition of a small amount of 1,2,4-
trimethylbenzene was crucial for the dehydrogenation to
occur.26 A number of carbazolequinone alkaloids have been
efficiently synthesized via oxidation of 1- or 4-hydroxy-
carbazoles. For example, oxidation of 4-hydroxy-3-methyl-
carbazole (47), using Fremy’s salt ((KSO3)2NO) to
Nitropyridines can also be used as precursor. Palladium-
catalyzed cross-coupling of 2-chloro-3-nitropyridine with
a-tin substituted alkenone 6 gave a low yield of impure
coupling product after workup and chromatographic
purification (Scheme 7). The coupling product was found
to be unstable and readily decomposed into a myriad of
intractable products upon attempted further purification on
silica gel or alumina. However, annulation of the crude
reaction mixture furnished the expected 5-aza-carbazolone
40 in 54% yield over two steps. This compares very
favorably with the only previous synthesis, starting from
3-amino-2-chloropyridine, affording 40 in 23% yield over
two steps.21
In addition to the cross-coupling products 19–27, two
additional 2-(2-nitrophenyl)-2-cyclohexenones were pre-
pared according to literature procedures.22 The dione 41 was
Scheme 7.
Scheme 6.
Scheme 8.

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T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6326
Table 2. Stille cross-coupling and N-heteroannulation forming carbazolones
Entry Nitrobenzene Alkenone
Coupling Producta,b
Carbazolonea,b
1
2
3
4
5
6
7
8
9
a
See Section 3 for detailed procedures.
Isolated yields in parenthesis.
b

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T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6327
cedures have been footnoted the first time used; all other
reagents were obtained from commercial sources and used
as received. All reactions were performed under an argon
atmosphere in oven-dried glassware unless otherwise stated.
Solvents were removed from reaction mixtures and products
on a rotary evaporator at water aspirator pressure. Elemental
Analyses were performed by Atlantic Microlab, Inc.,
Norcross, GA. High Resolution Mass Spectra (HRMS)
were performed at University of California Riverside Mass
Spectrometry Center.
3.1.1. 2-(tri-n-Butylstannyl)-2-cyclohexen-1-one (6).29
tert-Butyllithium (34.5 mL, 1.7 M in hexanes, 58.7 mmol)
was added dropwise to a solution of 6-bromo-1,4-dioxas-
piro[4,5]dec-6-ene (5)30 (6.00 g, 27.4 mmol) in diethyl ether
(480 mL) cooled to 2788C. After 30 min, tri-n-butyltin
chloride (8.2 mL, 30.2 mmol) was added slowly, and the
reaction mixture stirred an additional 30 min at 2788C. The
reaction mixture was allowed to warm to ambient
temperature followed by slow addition of HCl (10%, aq.,
200 mL). The resulting reaction mixture was stirred for 3 h.
After dilution with diethyl ether (500 mL), the reaction
mixture was washed successively with water (500 mL),
NH4OH (10%, aq., 500 mL), and water (500 mL). The
organic phase was dried (MgSO4), filtered, and the solvent
was removed at reduced pressure. The crude product was
purified by chromatography (hexanes/EtOAc, 95:5) to give
6 (8.38 g, 21.8 mmol, 79%) as a clear, colorless oil.
Scheme 9.
murrayaquinone A in good yield has been reported in the
literature (Scheme 9).27,28 The presented synthesis of the
murrayaquinone A precursor 47 was completed in only four
steps from 6-methyl-2-cyclohexen-1-one with an overall
yield of 38%. As a comparison, the previous synthesis of 47
by Miki et al.26 was achieved in nine steps from dimethyl
indole-2,3-dicarboxylate with an overall of yield of less than
16%.
3.1.2. 2-Iodo-5-methyl-2-cyclohexen-1-one (8). To a
solution of 5-methyl-2-cyclohexen-1-one (16)31 (502 mg,
4.55 mmol) in 20 mL of 1:1 CCl4/pyridine cooled to 08C
was added dropwise, a solution of iodine (2.30 g,
9.04 mmol) in 20 mL of 1:1 CCl4/pyridine. The reaction
mixture was allowed to warm to ambient temperature
overnight. The reaction mixture was diluted with ether
(100 mL) and washed successively with water (40 mL), HCl
(5%, aq., 2£40 mL), water (40 mL), and Na2S2O3 (20%,
aq., 40 mL). The organic phase was dried (MgSO4), filtered,
and the solvent was removed at reduced pressure.
Purification of the crude product by chromatography
(hexanes/EtOAc, 9:1) gave 8 (911 mg, 3.86 mmol, 85%)
as a pale yellow solid. Mp 39–408C; IR 2955, 1682,
1590 cm21; 1H NMR d 1.08 (d, J¼5.9 Hz, 3H), 2.11–2.53
(m, 4H), 2.69–2.83 (m, 1H), 7.72 (dd, J¼5.9, 2.9 Hz, 1H);
13C NMR d 20.6 (2), 30.4 (2), 37.9 (þ), 45.0 (þ), 103.5
(þ), 158.6 (2), 192.5 (þ); CG-MS (EI) m/z 236 (Mþ);
HRMS (EI) calcd for C7H9IO (Mþ) 235.9698, found
235.9703.
In summary, a novel route to tricyclic substituted 2,3-fused
indoles in general and carbazolones in particular has been
developed. The route was applied to a formal total synthesis
of murrayaquinone A. Further applications in total synthesis
are presently being pursued in our laboratories.
3. Experimental
3.1. General procedures
All NMR spectra were determined in CDCl3 at 270 MHz
(1H NMR) and 67.5 MHz (13C NMR). The chemical shifts
are expressed in d values relative to Me4Si (0.0 ppm, 1H and
3.1.3. 2-Iodo-6-methyl-2-cyclohexen-1-one (44). To a
solution of 6-methyl-2-cyclohexen-1-one (43)31 (441 mg,
4.00 mmol) in 20 mL of 1:1 CCl4/pyridine cooled to 08C
1
13C) or CDCl3 (77.0 ppm, 13C) internal standards. H–1H
was added dropwise
a solution of iodine (2.09 g,
coupling constants are reported as calculated from spectra;
thus a slight difference between Ja,b and Jb,a is usually
obtained. Results of APT (attached proton test)–13C NMR
experiments are shown in parentheses where, relative to
CDCl3, (þ) denotes CH3 or CH and (2) denotes CH2 or C.
8.23 mmol) dissolved in 20 mL of 1:1 CCl4/pyridine with
stirring. The reaction was allowed to warm to ambient
temperature overnight. The reaction mixture was diluted
with ether (100 mL) and washed successively with water
(40 mL), HCl (5%, aq., 2£40 mL), water (40 mL), and
Na2S2O3 (20%, aq., 40 mL). The organic phase was dried
(MgSO4), filtered, and the solvent was removed at reduced
pressure. The crude product was purified by chromato-
graphy (hexanes/EtOAc, 9:1) to give 44 (675 mg,
Benzene and diethyl ether were distilled from sodium
benzophenone ketyl prior to use. Hexanes, dichloro-
methane, and ethyl acetate were distilled from calcium
hydride. Chemicals prepared according to literature pro-

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T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6328
2.86 mmol, 71%) as a pale yellow oil; IR 2929, 1682, 1594,
1454 cm21; 1H NMR d 1.21 (d, J¼6.7 Hz, 3H), 1.75–1.91
(m, 1H), 2.06–2.18 (m, 1H), 2.35–2.68 (m, 3H), 7.68–7.73
(m, 1H); 13C NMR d 15.2 (2), 29.0 (þ), 29.9 (þ), 40.7 (2),
102.8 (þ), 158.3 (2), 193.9 (þ); GC-MS (Mþ) m/z 236
(Mþ); HRMS (EI) calcd for C7H9IO (Mþ) 235.9698, found
235.9688.
Compound 3 was also prepared in a similar fashion
described above using 2-(tri-n-butylstannyl)-2-cyclohexe-
none (6) (931 mg, 2.42 mmol), 1-iodo-2-nitrobenzene
(502 mg,
2.01 mmol),
PdCl2(PhCN)2
(38.5 mg,
0.10 mmol), Ph3As (70.1 mg, 0.22 mmol), CuI (41.9 mg,
0.22 mmol), and NMP (4 mL) to give 3 (309 mg,
1.42 mmol, 71%) after purification.
3.1.4. 3-Iodo-2-nitrotoluene (13).32 To a mixture of 3-
methyl-2-nitroaniline (17)16 (502 mg, 3.30 mmol), ice-
water (4 mL), and H2SO4 (conc., 0.2 mL), cooled in an
ice bath, was added a solution of NaNO2 (251 mg,
3.64 mmol) in water (1 mL) very slowly (,1 drop/min).
After the addition, the reaction mixture was stirred for
20 min and additional H2SO4 (conc., ,0.07 mL) was added.
The reaction mixture was poured slowly into an ice-cold
solution of KI (656 mg, 3.95 mL) in water (1 mL). After a
few minutes, copper powder (4 mg, 0.06 mmol) was added,
and the reaction mixture was heated slowly to 808C over
30 min. The mixture was allowed to cool to ambient
temperature, extracted with CH2Cl2 (3£50 mL), washed
with Na2S2O3 (20%, aq., 50 mL), dried (MgSO4), filtered,
and concentrated under reduced pressure. The crude product
was purified by chromatography (hexanes/EtOAc, 8:2) to
give 13 (764 mg, 2.90 mmol, 88%) as a yellow-orange
solid.
3.1.7. 2-(2-Nitrophenyl)-2-cyclopenten-1-one (19).22 As
described for 3, reaction of 2-iodo-2-cyclopenten-1-one
(7)35 (290 mg, 1.40 mmol) with 1-(tri-n-butylstannyl)-2-
nitrobenzene (1) (643 mg, 1.56 mmol), PdCl2(PhCN)2
(26.7 mg, 0.07 mmol), Ph3As (43.7 mg, 0.14 mmol), CuI
(29.2 mg, 0.15 mmol), and NMP (2.8 mL) for 20 h gave,
after chromatography (EtOAc/hexanes, 2:8), 19 (183 mg,
0.90 mmol, 65%) as a pale yellow solid. Mp 94.5–96.58C;
IR 1697, 1518, 1349 cm21; 1H NMR d 2.56–2.60 (m, 2H),
2.78–2.83 (m, 2H), 7.32 (dd, J¼7.5, 1.6 Hz, 1H), 7.49 (td,
J¼7.5, 1.4 Hz, 1H), 7.61 (td, J¼7.5, 1.4 Hz, 1H), 7.69 (t,
J¼2.8 Hz, 1H), 8.02 (dd, J¼8.1, 2.6 Hz, 1H); 13C NMR d
27.0 (þ), 34.5 (þ), 124.3 (2), 127.1 (þ), 129.1 (2), 131.2
(2), 133.0 (2), 143.7 (þ), 148.2 (þ), 159.0 (2), 205.3 (þ);
Anal. calcd for C11H9NO3: C, 65.02; H, 4.46, found: C,
65.15; H, 4.46.
3.1.8. 5-Methyl-2-(2-nitrophenyl)-2-cyclohexen-1-one
(20). As described for 3, reaction of 2-iodo-5-methyl-2-
cyclohexen-1-one (8) (241 mg, 1.02 mmol) with 1-(tri-n-
butylstannyl)-2-nitrobenzene (1) (455 mg, 1.10 mmol),
PdCl2(PhCN)2 (20.6 mg, 0.05 mmol), Ph3As (31.6 mg,
0.10 mmol), CuI (19.1 mg, 0.10 mmol), and NMP (1 mL)
for 24 h gave, after chromatography (EtOAc/hexanes, 1:9
followed by 2:8), 20 (175 mg, 0.75 mmol, 74%) as a pale
yellow solid. Mp 107–1098C; IR 1672, 1517, 1340 cm21; 1H
NMR d 1.03 (d, J¼8.1 Hz, 3H), 2.10–2.35 (m, 3H), 2.44–
2.59 (m, 2H), 6.90 (dd, J¼5.5, 2.8 Hz, 1H), 7.16 (dd, J¼7.5,
1.6 Hz, 1H), 7.35 (td, J¼6.4, 1.6 Hz, 1H), 7.49 (td, J¼7.3,
1.2 Hz, 1H), 7.88 (dd, J¼8.1, 1.2 Hz, 1H); 13C NMR d 20.9
(2), 29.9 (2), 34.3 (þ), 46.1 (þ), 123.9 (2), 128.6 (2), 131.5
(2), 131.7 (þ), 133.2 (2), 138.8 (þ), 146.0 (2), 148.4 (þ),
196.5 (þ); GC-MS (EI) m/z 185 (Mþ2NO2); HRMS (DEI)
calcd for C13H13NO3 (MHþ) 232.0974, found 232.0965.
3.1.5. 4-Bromo-2-iodo-1-nitrobenzene (15).33 To a mix-
ture of 5-bromo-2-nitroaniline (18)34 (198 mg, 0.91 mmol),
ice-water (5 mL), and H2SO4 (conc., 0.2 mL) cooled to 08C
was added a solution of NaNO2 (70.2 mg, 1.02 mL) very
slowly (,1 drop/min). The reaction mixture was stirred for
1.5 h at ambient temperature, and was then added very
slowly to an ice-cold solution of KI (190 mg, 1.14 mmol) in
water (1 mL). After a few minutes copper powder (2 mg,
0.03 mmol) was added, and the reaction mixture was heated
slowly to 808C over 20 min. The reaction mixture was
allowed to cool to ambient temperature and was extracted
with CH2Cl2 (3£50 mL). The combined organic phases
were washed with Na2S2O3 (10%, aq., 50 mL), dried
(MgSO4), filtered, and concentrated under reduced pressure.
The crude product was purified by chromatography
(hexanes/EtOAc, 9:1) to give 15 (182 mg, 0.55 mmol,
61%) as a yellow solid. Mp 77–798C; IR 1563, 1518,
3.1.9. 2-(2-Nitrophenyl)-2-cyclohepten-1-one (21). As
described for 3, reaction of 2-iodo-2-cyclohepten-1-one
(9)37 (389 mg, 1.65 mmol) with 1-(tri-n-butylstannyl)-2-
nitrobenzene (1) (820 mg, 1.99 mmol), PdCl2(PhCN)2
(31.9 mg, 0.08 mmol), Ph3As (51.7 mg, 0.16 mmol), CuI
(31.2 mg, 0.16 mmol), and NMP (1.6 mL) for 72 h gave,
after chromatography (benzene/CH2Cl2, 19:1), 21 (259 mg,
1.12 mmol, 68%) as a pale yellow solid. Mp 83–858C; IR
1
1335 cm21; H NMR d (dd, J¼8.5, 2.0 Hz, 1H), 7.77 (d,
J¼8.5 Hz, 1H), 8.22 (d, J¼2.0 Hz, 1H); 13C NMR d 87.4
(þ), 126.4(2), 127.7 (þ), 132.2 (2), 144.1 (2), 151.7 (þ).
3.1.6. 2-(2-Nitrophenyl)-2-cyclohexen-1-one (3).22 To a
solution of 2-iodo-2-cyclohexen-1-one (2)35 (808 mg,
3.64 mmol) and 2-(tri-n-butylstannyl)-1-nitrobenzene (1)36
(1.80 g, 4.34 mmol) in N-methylpyrrolidinone (NMP,
4 mL) was added PdCl2(PhCN)2 (77.5 mg, 0.20 mmol),
Ph3As (117 mg, 0.40 mmol), and CuI (77.2 mg,
0.40 mmol). The reaction mixture was heated at 808C for
20 h. The reaction mixture was diluted with EtOAc
(100 mL) and washed successively with NH4OH (10%,
aq., 3£30 mL) and H2O (2£30 mL). The aqueous portions
were combined and extracted with EtOAc (50 mL). The
organic phases were combined, dried (MgSO4), filtered, and
concentrated under reduced pressure. Purification of the
crude product by chromatography (hexanes/EtOAc, 9:1)
gave 3 (603 mg, 2.77 mmol, 76%) as a pale yellow solid.
1
1665, 1517, 1340 cm21; H NMR d 1.81–1.99 (m, 4H),
2.53–2.61 (m, 2H), 2.74–2.80 (m, 2H), 6.74 (t, J¼6.5 Hz,
1H), 7.28 (dd, J¼7.5, 1.6 Hz, 1H), 7.43 (td, J¼8.1, 1.6 Hz,
1H), 7.58 (td, J¼7.5, 1.6 Hz, 1H) 8.00 (dd, J¼8.1, 1.2 Hz,
1H); 13C NMR d 21.0 (þ), 25.0 (þ), 27.8 (þ), 42.4 (þ),
124.2 (2), 128.5 (2), 132.6 (2), 133.5 (2), 135.1 (þ),
142.9 (þ), 143.1 (2), 147.2 (þ), 202.5 (þ); GC-MS (EI) m/
z 186 (Mþ2NO2þH); HRMS (EI) calcd for C13H13NO3
(Mþ) 231.0895, found 231.0895.
3.1.10. 8,9-Dihydro-5H-6-(2-nitrophenyl)-benzocyclo-
hepten-5-one (22). As described for 3, reaction of

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T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6329
6-bromo-8,9-dihydro-5H-benzocyclohepten-5-one (10)38
(250 mg, 1.06 mmol) with 1-(tri-n-butylstannyl)-2-nitro-
benzene (1) (496 mg, 1.20 mmol), PdCl2(PhCN)2
(21.5 mg, 0.06 mmol), Ph3As (34.1 mg, 0.11 mmol), CuI
(21.0 mg, 0.11 mmol), and NMP (1 mL) for 40 h gave, after
chromatography (EtOAc/hexanes, 1:9 followed by 2:8), 22
(183 mg, 0.90 mmol, 65%) as an orange oil; IR 3408, 2941,
1665, 1517, 1340 cm21; 1H NMR d 2.78 (q, J¼5.1 Hz, 2H),
3.14 (t, J¼5.1 Hz, 2H), 6.81 (t, J¼5.1 Hz, 1H), 7.19–7.70
(m, 7H), 8.07 (dd, J¼8.1, 2.9 Hz, 1H); 13C NMR d 30.6 (þ),
33.7 (þ), 124.3 (2), 127.0 (2), 128.2 (2), 128.6 (2), 129.9
(2), 132.1 (2), 132.5 (2), 133.4 (2), 136.2 (þ), 139.1 (þ),
140.9 (þ), 141.5 (þ), 144.2 (2), 148.1 (þ), 194.2 (þ); GC-
MS (Mþ) m/z 233 (Mþ2NO2); HRMS (DEI) calcd for
C14H15NO4 (MHþ) 280.0974, found 280.0964.
(2), 22.5 (þ), 26.3 (þ), 38.3 (þ), 128.9 (2), 130.4 (2),
130.6 (þ), 130.7 (þ), 131.2 (2), 137.8 (þ), 148.6 (2),
150.3 (þ), 196.5 (þ); GC-MS (EI) m/z 231 (Mþ), 185
(Mþ2NO2); HRMS (EI) calcd for C13H13NO3 (Mþ)
231.0895, found 231.0898.
3.1.14. 2-(6-Carbomethoxy-2-nitrophenyl)-2-cyclo-
hexen-1-one (26). As described for 3, reaction of 2-(tri-n-
butylstannyl)-2-cyclohexen-1-one (6) (887 mg, 2.30 mmol)
with 1-carbomethoxy-2-bromo-3-nitrobenzene
(501 mg, 1.92 mmol), PdCl2(PhCN)2
(14)16
(38.2 mg,
0.10 mmol), Ph3As (59.8 mg, 0.20 mmol), CuI (39.7 mg,
0.20 mmol), and NMP (4 mL) for 96 h gave, after
chromatography (EtOAc/hexanes, 2:8), 26 (233 mg,
0.84 mmol, 44%) as a yellow-orange solid. Mp 86.5–
1
88.58C; IR 1730, 1681, 1531, 1357, 1294, 1273 cm21; H
3.1.11. 2-(4-Methoxy-2-nitrophenyl)-2-cyclohexen-1-one
(23). As described for 3, reaction of 2-(tri-n-butylstannyl)-2-
cyclohexen-1-one (6) (183 mg, 0.48 mmol) with 1-bromo-
2-nitro-4-methoxybenzene (11)39 (103 mg, 0.44 mmol),
PdCl2(PhCN)2 (8.2 mg, 0.02 mmol), 1,10-bis(diphenylphos-
pino)ferrocene (24.1 mg, 0.04 mmol), CuI (8.9 mg,
0.04 mmol), and NMP (1 mL) for 3 days gave, after
chromatography (EtOAc/hexanes, 2:8 followed by 3:7), 23
(73.4 mg, 0.30 mmol, 67%) as a yellow-orange solid. Mp
63–658C; IR 1682, 1531, 1357, 1234 cm21; 1H NMR d 2.14
(pentet, J¼5.9 Hz, 2H), 2.52–2.60 (m, 4H), 3.85 (s, 3H),
6.96 (t, J¼4.1 Hz, 1H), 7.1–7.16 (m, 2H), 7.55 (d,
J¼3.9 Hz, 1H); 13C NMR d 22.6 (þ), 26.2 (þ), 38.3 (þ),
55.8 (2), 109.1 (2), 119.5 (2), 124.1 (þ), 132.4 (2), 139.0
(þ), 146.2 (2), 149.0 (þ), 159.5 (þ), 196.8 (þ); GC-MS
(EI) m/z 247 (Mþ), 201 (Mþ2NO2); HRMS (EI) calcd for
C13H13NO3 (Mþ) 247.0845, found 247.0849.
NMR d 2.15 (pentet, J¼6.3 Hz, 2H), 2.47 (q, J¼5.3 Hz,
2H), 2.63 (t, J¼6.3 Hz, 2H), 6.66 (t, J¼4.1 Hz, 1H), 7.53 (t,
J¼7.9 Hz, 1H), 7.99 (d, J¼8.1 Hz, 1H), 8.12 (d, J¼7.9 Hz,
1H); 13C NMR d 22.2 (þ), 26.0 (þ), 38.0 (þ), 52.3 (2),
126.9 (2), 128.5 (2), 132.5 (þ), 132.7 (þ), 133.8 (2),
136.9 (þ), 144.6 (2), 150.3 (þ), 165.4 (þ), 196.3 (þ); GC-
MS (EI) m/z 275 (Mþ), 229 (Mþ2NO2); HRMS (EI) calcd
for C14H15NO4 (Mþ) 275.0794, found 275.0804.
This reaction was performed a number of times and methyl
2-butyl-3-nitrobenzoate (tentatively assigned) was usually
obtained as an inseparable byproduct. Partial spectral data
for the byproduct: 1H NMR d 0.91 (t, J¼7.3 Hz, 3H), 1.25–
1.42 (m, 4H), 1.64 (pentet, J¼6.9 Hz, 2H), 3.63 (s, 3H), 7.68
(t, J¼7.9 Hz, 1H), 8.28 (m, 1H). Partial 13C NMR d 13.4
(2), 17.4 (þ), 26.6 (þ), 27.6 (þ), 52.4 (2), 127.7 (2),
128.8 (2), 134.7 (2).
3.1.12. 2-(6-Methyl-2-nitrophenyl)-2-cyclohexen-1-one
(24). As described for 3, reaction of 2-(tri-n-butylstannyl)-
2-cyclohexen-1-one (6) (351 mg, 0.91 mmol) with 2-
bromo-3-nitrotoluene (12) (177 mg, 0.82 mmol), PdCl2(-
PPh3)2 (27.7 mg, 0.04 mmol), and DMF (5 mL) at 1108C for
26 h gave, after chromatography (EtOAc/hexanes, 2:8), 24
(58.2 mg, 0.25 mmol, 31%) as a pale yellow solid. Mp 79–
808C; IR 1671, 1520, 1356 cm21; 1H NMR d 2.09–2.20 (m,
2H), 2.22 (s, 3H), 2.51 (q, J¼5.7 Hz, 2H), 2.57–2.74 (m,
2H), 6.72 (t, J¼4.2 Hz, 1H), 7.33 (t, J¼7.8 Hz, 1H), 7.46 (d,
J¼7.5 Hz, 1H), 7.78 (d, J¼8.1 Hz, 1H); 13C NMR d 20.0
(2), 22.5 (þ), 26.0 (þ), 38.2 (þ), 121.6 (2), 127.9 (2),
131.4 (þ), 134.4 (2), 137.2 (þ), 138.3 (þ), 146.8 (2),
149.4 (þ), 196.8 (þ); GC-MS (EI) m/z 231 (Mþ), 185
(Mþ2NO2); HRMS (EI) calcd for C13H13NO3 (Mþ)
231.0895, found 231.0902.
3.1.15. 2-(5-Bromo-2-nitrophenyl)-2-cyclohexen-1-one
(27). As described for3, reaction of 2-(tri-n-butylstannyl)-
2-cyclohexen-1-one (6) (459 mg, 1.19 mmol) with 4-
bromo-2-iodo-1-nitrobenzene (15) (318 mg, 0.97 mmol),
PdCl2(PhCN)2 (18.9 mg, 0.05 mmol), Ph3As (30.5 mg,
0.10 mmol), CuI (18.2 mg, 0.10 mmol), and NMP (3 mL)
for 2 days gave, after chromatography (EtOAc/hexanes,
1:9), 27 (160 mg, 0.54 mmol, 56%) as a yellow-orange
solid. Mp 168–1698C; IR 2948, 1668, 1520, 1557, 1520,
1348 cm21; 1H NMR d 2.14 (p, J¼5.8 Hz, 2H), 2.52–2.61
(m, 4H), 7.02 (t, J¼3.2 Hz, 1H), 7.41 (d, J¼3.5 Hz, 1H),
7.59 (dd, J¼8.9, 3.4 Hz, 1H), 7.90 (d, J¼8.7 Hz, 1H); 13C
NMR d 22.4 (þ), 26.2 (þ), 38.1 (þ), 125.7 (2), 127.9 (þ),
131.7 (2), 133.9 (þ), 134.4 (2), 134.5 (þ), 138.4 (þ),
147.3 (2), 196.1 (þ); GC-MS (EI) m/z 251 (Mþ2NO2),
249 (Mþ2NO2); HRMS (DEI) calcd for C12H10BrNO3
(Mþ) 295.9923, found 295.9915.
3.1.13. 2-(3-Methyl-2-nitrophenyl)-2-cyclohexen-1-one
(25). As described for 3, reaction of 2-(tri-n-butylstannyl)-
2-cyclohexen-1-one (6) (385 mg, 1.00 mmol) with 3-iodo-
2-nitrotoluene (13) (215 mg, 0.82 mmol), PdCl2(PhCN)2
(15.7 mg, 0.04 mmol), Ph3As (25.3 mg, 0.08 mmol), CuI
(16.1 mg, 0.08 mmol), and NMP (2.5 mL) for 2 days gave,
after chromatography (EtOAc/hexanes, 1:9 followed by
2:8), 25 (117 mg, 0.51 mmol, 62%) as a pale yellow solid.
3.1.16. 1,2-Dihydrocarbazol-4(3H)-one (4).9 2-(2-Nitro-
phenyl)-2-cyclohexen-1-one (3) (285 mg, 1.31 mmol),
Pd(dba)2 (45.3 mg, 0.08 mmol), dppp (32.5 mg,
0.08 mmol), 1,10-phenanthroline monohydrate (31.2 mg,
0.16 mmol), and DMF (5 mL) were placed in an ACE Glass
pressure tube fitted with a pressure head. The tube was
pressurized-depressurized with CO to 6 atm 3 times, and the
reaction was heated at 808C under CO (6 atm) for 24 h. The
reaction mixture was filtered through a Celite pad, the pad
was washed with CH2Cl2, and the filtrate was concentrated
under high vacuum. The crude product was purified by
1
Mp 129–1318C; IR 1677, 1523, 1362 cm21; H NMR d
2.10 (pentet, J¼6.2 Hz, 2H), 2.39 (s, 3H), 2.48–2.58 (m,
4H), 6.99 (t, J¼4.3 Hz, 1H), 7.07 (d, J¼7.6 Hz, 1H), 7.26
(d, J¼7.8 Hz, 1H), 7.37 (t, J¼7.5 Hz, 1H); 13C NMR d 18.5

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T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6330
chromatography (EtOAc/hexanes, 3:7) to give 4 (180 mg,
0.97 mmol, 74%) as a white powder.
nitrophenyl)-2-cyclohexen-1-one
(23)
(43.5 mg,
0.18 mmol) with Pd(dba)2 (6.3 mg, 0.01 mmol), dppp
(4.6 mg, 0.01 mmol), 1,10-phenanthroline monohydrate
(4.5 mg, 0.02 mmol), and DMF (5 mL) for 22 h gave,
after chromatography (EtOAc/hexanes, 3:7 followed by
EtOAc), 35 (33.8 mg, 0.16 mmol, 89%) as a white powder.
Compound 4 was also prepared using the above procedure
except that a mixture of 2-(2-nitrophenyl)-1,3-cyclohex-
anedione21 (41) (202 mg, 0.87 mmol), Pd(dba)2 (29.7 mg,
0.05 mmol), dppp (22.5 mg, 0.05 mmol), 1,10-phenanthro-
line monohydrate (23.5 mg, 0.12 mmol), and DMF (5 mL)
was heated at 1008C for 90 h to give 4 (133 mg, 0.72 mmol,
83%) after chromatography.
3.1.22. 5-Methyl-1,2-dihydrocarbazol-4(3H)-one (36). As
described for 4, reaction of 2-(6-methyl-2-nitrophenyl)-2-
cyclohexen-1-one (24) (117 mg, 0.51 mmol) with Pd(dba)2
(17.5 mg, 0.03 mmol), dppp (12.7 mg, 0.03 mmol), 1,10-
phenanthroline monohydrate (12.4 mg, 0.06 mmol), and
DMF (5 mL) for 36 h gave, after chromatography (EtOAc/
hexanes, 3:7), 36 (79.5 mg, 0.40 mmol, 79%) as a white
powder. Mp 234–2358C; IR (Nujol) 1711, 1620,
Compound 4 was also prepared using the above procedure
except that a mixture of 3-methoxy-2-(2-nitrophenyl)-2-
cyclohexen-1-one21 (42) (141 mg, 0.57 mmol), Pd(dba)2
(20.6 mg, 0.04 mmol), dppp (16.3 mg, 0.04 mmol), 1,10-
phenanthroline monohydrate (15.4 mg, 0.08 mmol), and
DMF (5 mL) was heated at 1208C for 96 h to give 4
(64.5 mg, 0.35 mmol, 61%) after chromatography.
1
1575 cm21; H NMR (CDCl3þDMSO-d6) d 2.16 (pentet,
J¼5.9 Hz, 2H), 2.50 (t, J¼5.9 Hz, 2H), 2.86 (s, 3H), 2.97 (t,
J¼5.9 Hz, 2H), 6.88 (d, J¼7.2 Hz, 1H), 7.03 (t, J¼7.4 Hz,
1H), 7.15 (d, J¼8.2 Hz, 1H), 11.47 (s, 1H); 13C NMR
(CDCl3þDMSO-d6) d 23.3 (2), 23.6 (þ), 23.9 (þ), 38.9
(þ), 109.4 (2), 113.5 (þ), 123.2 (2), 123.7 (2), 124.6 (þ),
131.7 (þ), 137.0 (þ), 153.0 (þ), 192.1 (þ); GC-MS (EI)
m/z 199 (Mþ); HRMS (EI) calcd for C13H13NO (Mþ)
199.0997, found 199.0997.
3.1.17. 3,4-Dihydrocyclopent[b]indol-1(2H)-one (31).40
As described for 4, reaction of 2-(2-nitrophenyl)-2-cyclo-
penten-1-one (19) (125 mg, 0.61 mmol) with Pd(dba)2
(21.2 mg, 0.04 mmol), dppp (15.7 mg, 0.04 mmol), 1,10-
phenanthroline monohydrate (14.8 mg, 0.07 mmol), and
DMF (5 mL) for 3 days gave, after chromatography
(EtOAc/hexanes, 1:1 followed by EtOAc), 31 (90.4 mg,
0.53 mmol, 86%) as a white powder.
3.1.23. 8-Methyl-1,2-dihydrocarbazol-4(3H)-one (37).45
As described for 4, reaction of 2-(3-methyl-2-nitrophenyl)-
2-cyclohexen-1-one (25) (108 mg, 0.47 mmol) with
Pd(dba)2 (16.5 mg, 0.03 mmol), dppp (11.9 mg,
0.03 mmol), 1,10-phenanthroline monohydrate (11.4 mg,
0.06 mmol), and DMF (5 mL) for 144 h gave, after
chromatography (EtOAc/hexanes, 3:7 followed by 7:3), 37
(69.8 mg, 0.35 mmol, 75%) as a white powder.
3.1.18. 2-Methyl-1,2-dihydrocarbazol-4(3H)-one (32). As
described for 4, reaction of 5-methyl-2-(2-nitrophenyl)-2-
cyclohexenone (20) (98.3 mg, 0.42 mmol) with Pd(dba)2
(14.7 mg, 0.03 mmol), dppp (10.5 mg, 0.03 mmol), 1,10-
phenanthroline monohydrate (10.2 mg, 0.05 mmol), and
DMF (5 mL) for 36 h gave, after chromatography (EtOAc/
hexanes, 3:7), 32 (75.1 mg, 0.38 mmol, ,89%)40 as a white
powder. Mp 260–2618C; IR (Nujol) 2925, 1630, 1583,
1458, 1376 cm21; 1H NMR (CDCl3þDMSO-d6) d 1.19 (d,
J¼6.2 Hz, 3H), 2.22–2.71 (m, 4H), 2.98–3.11 (m, 1H),
7.11–7.21 (m, 2H), 7.32–7.40 (m, 1H), 8.04–8.12 (m, 1H),
11.25 (s, 1H); 13C NMR (CDCl3þDMSO-d6) d 20.3 (2),
30.4 (þ), 30.7 (2), 45.6 (þ), 110.5 (2), 111.1 (þ), 119.7
(2), 120.7 (2), 121.6 (2), 123.7 (þ), 135.4 (þ), 150.8 (þ),
192.4 (2).
3.1.24. Methyl 1,2-dihydrocarbazol-4(3H)-one-5-carbox-
ylate (38).46 As described for 4, reaction of 2-(6-
carbomethoxy-2-nitrophenyl)-2-cyclohexen-1-one
(158 mg, 0.57 mmol), with Pd(dba)2
0.03 mmol), dppp (14.2 mg, 0.03 mmol), 1,10-phenanthro-
line monohydrate (13.6 mg, 0.07 mmol), and DMF (5 mL)
for 96 h gave, after chromatography (EtOAc/hexanes, 3:7
followed by EtOAc), 38 (105 mg, 0.43 mmol, 75%) as a
white powder.
(26)
(19.7 mg,
3.1.19. 6,7,8,9-Tetrahydrocyclohept[b]indol-10(5H)-one
(33).41 As described for 4, reaction of 2-(2-nitrophenyl)-2-
cycloheptenone (21) (136 mg, 0.59 mmol) with Pd(dba)2
(20.4 mg, 0.04 mmol), dppp (14.5 mg, 0.04 mmol), 1,10-
phenanthroline monohydrate (14.7 mg, 0.07 mmol), and
DMF (5 mL) for 48 h gave, after chromatography (EtOAc/
hexanes, 3:7), 33 (77.9 mg, 0.39 mmol, 66%) as a white
powder.
3.1.25. 6-Bromo-1,2,3,9-tetrahydro-4H-carbazol-4-one
(39).47 As described for 4, reaction of 2-(5-bromo-2-
nitrophenyl)-2-cyclohexen-1-one
(27)
(123 mg,
0.42 mmol) with Pd(dba)2 (14.3 mg, 0.025 mmol), dppp
(10.4 mg, 0.025 mmol), 1,10-phenanthroline monohydrate
(9.9 mg, 0.050 mmol), and DMF (5 mL) for 8 days gave,
after chromatography (EtOAc/hexanes, 3:7 followed by
7:3), 39 (56.9 mg, 0.22 mmol, 52%) as a white powder.
3.1.20. 6,7-Dihydrobenzo[4,5]cyclohept-[1,2-b]indol-
12(5H)-one (34).42 As described for 4, reaction of 22
(31.5 mg, 0.11 mmol) with Pd(dba)2 (5.1 mg, 0.009 mmol),
dppp (3.5 mg, 0.009 mmol), 1,10-phenanthroline monohy-
drate (3.4 mg, 0.017 mmol), and DMF (3 mL) for 30 h gave,
after chromatography (EtOAc/hexanes, 3:7), 34 (24.1 mg,
0.098 mmol, 86%) as a white powder.
3.1.26. 6,7,8,9-Tetrahydro-5H-pyrido[3,2-b]indol-9-one
(40).21 A mixture of 2-(tri-n-butylstannyl)-2-cyclohexen-
1-one (6) (621 mg, 1.61 mmol), 2-chloro-3-nitropyridine16
(201 mg, 1.26 mmol), Pd(dba)2 (22.1 mg, 0.038 mmol),
Ph3As (47.1 mg, 0.15 mmol), and toluene (5 mL) was
heated at reflux for 20 h. The reaction was diluted with
benzene (100 mL) and washed with NH4OH (10%, aq.,
3£50 mL) and H2O (2£50 mL). The organic phase was
dried (MgSO4), filtered, and concentrated under reduced
pressure. As described for 4, the crude product was reacted
3.1.21. 7-Methoxy-1,2-dihydrocarbazol-4(3H)-one
(35).43,44 As described for 4, reaction of 2-(4-methoxy-2-

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T. L. Scott, B. C. G. Soderberg / Tetrahedron 59 (2003) 6323–6332
6331
4. Tollari, S.; Cenini, S.; Crotti, C.; Gianella, E. J. Mol. Catal.
1994, 87, 203–214.
without purification with Pd(dba)2 (43.6 mg, 0.075 mmol),
dppp (31.2 mg, 0.076 mmol), 1,10-phenanthroline mono-
hydrate (30.1 mg, 0.152 mmol), and DMF (5 mL) for 24 h
to give, after chromatography (CHCl3 to CHCl3/MeOH,
9:1), 40 (128 mg, 0.685 mmol, 54%) as a tan solid.
5. Crotti, C.; Cenini, R.; Todeschini, R.; Tollari, S. J. Chem. Soc.,
Faraday Trans. 1991, 2811–2820.
6. Crotti, C.; Cenini, S.; Rindone, B.; Tollari, S.; Demartin, F.
J. Chem. Soc., Chem. Commun. 1986, 784–786.
¨
7. Soderberg, B. C.; Rector, S. R.; O’Neil, S. N. Tetrahedron
3.1.27. 6-Methyl-2-(2-nitrophenyl)-2-cyclohexen-1-one
(45) and 1-nitro-2-(2-nitrophenyl)benzene. As described
for 3, reaction of 2-iodo-6-methyl-2-cyclohexen-1-one (44)
(305 mg, 1.29 mmol) with1-(tri-n-butylstannyl)-2-nitroben-
zene (1) (412 mg, 1.53 mmol), PdCl2(PhCN)2 (65 mg,
0.13 mmol), Ph3As (306 mg, 0.127 mmol), CuI (190.5 mg,
0.129 mmol), and NMP (2.5 mL) for 48 h gave, after
chromatography (EtOAc/hexanes, 1:9), an inseparable
Lett. 1999, 40, 3657–3660.
¨
8. Soderberg, B. C.; Chisnell, A. C.; O’Neil, S. N.; Shriver, J. A.
J. Org. Chem. 1999, 64, 9731–9734.
¨
9. Scott, T. L.; Soderberg, B. C. G. Tetrahedron Lett. 2002, 43,
1621–1624.
10. For an excellent review, see Farina, V.; Krishnamurthy, V.;
Scott, V. J. Organic Reactions; Wiley: New York, 1967; vol.
50. pp 1–652.
1
mixture (288 mg, ca. 9:1 ratio as determined by H NMR)
of 45 (ca. 87%) and 1-nitro-2-(2-nitrophenyl)benzene17,48
(ca. 15%) as a pale yellow oil. Spectral data of 45 from the
mixture: IR 2931, 1679, 1524, 1349 cm21; 1H NMR d 1.19
(d, J¼6.7 Hz, 3H), 1.82–1.98 (m, 1H), 2.12–2.23 (m, 1H),
2.50–2.67 (m, 3H), 6.96 (td, J¼3.6, 2.0 Hz, 1H), 7.26 (dd,
J¼8.3, 1.6 Hz, 1H), 7.47 (td, J¼7.5, 1.6 Hz, 1H), 7.59 (td,
J¼7.7, 1.6 Hz, 1H), 8.02 (dd, J¼8.1, 1.4 Hz, 1H); 13C NMR
d 14.7 (2), 25.5 (þ), 30.3 (þ), 41.5 (2), 123.9 (2), 128.5
(2), 131.6 (2), 132.1 (þ), 133.2 (2), 138.6 (þ), 146.0 (2),
148.3 (þ), 198.9 (þ); GC-MS (EI) m/z 231 (Mþ), 185
(Mþ2NO2); HRMS (DEI) calcd for C13H13NO3 (MHþ)
232.0974, found 232.0968.
11. Palladium–phenanthroline complexes have been shown to be
particularly active catalysts for the reductive carbonylation of
nitrobenzenes to give isocyanates, see: Gallo, E.; Ragaini, S.;
Cenini, S.; Demartin, F. J. Organomet. Chem. 1999, 586,
190–195, and references therein.
12. For a review, see: Bouaziz, Z.; Nebois, P.; Poumaroux, A.;
Fillion, H. Heterocycles 2000, 52, 977–1000.
13. Chakraborty, D. P.; Chowdhury, B. K. J. Org. Chem. 1968, 33,
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16. Commercially available.
3.1.28. 1,2,3,9-Tetrahydro-3-methyl-4H-carbazol-4-one
(46).49 As described for 4, reaction of 208 mg of the
mixture obtained in the previous experiment with Pd(dba)2
(31.0 mg, 0.054 mmol), dppp (22.2 mg, 0.053 mmol), 1,10-
phenanthroline monohydrate (21.4 mg, 0.108 mmol), and
DMF (5 mL) for 48 h gave, after chromatography (EtOAc/
hexanes, 3:7 followed by 7:3), 46 (156 mg, 0.78 mmol, 84%
based on 44) as a white powder.
17. Lin, G.-Q.; Hong, R. J. Org. Chem. 2001, 66, 2877–2880.
18. Prasad, A. S. B.; Knochel, P. Tetrahedron 1997, 53,
16711–16720.
19. Gallo, E.; Ragaini, S.; Cenini, S.; Demartin, F. J. Organomet.
Chem. 1999, 586, 190. and references therein.
20. Akazome, M.; Kondo, T.; Watanabe, Y. J. Org. Chem. 1993,
58, 310–312.
3.1.29. 4-Hydroxy-3-methyl-9H-carbazol (47).50 A mix-
ture of 3-methyl-1,2-dihydrocarbazol-4(3H)-one (46)
(159 mg, 0.80 mmol), 10% Pd/C (108 mg), diphenyl ether
(6 mL), and 1,2,4-trimethylbenzene (0.75 mL) was
degassed by bubbling argon through the mixture for
10 min. The reaction mixture was heated at 2308C for
20 h. The reaction was filtered through a short column of
silica gel using petroleum ether followed by CH2Cl2/formic
acid (99.9:0.1) to give 47 (99 mg, 0.50 mmol, 63%) as a
white solid.
21. Blache, Y.; Sinibaldi-Troin, M.-E.; Voldoire, A.; Chavignon,
O.; Gramain, J.-C.; Teulade, J.-C.; Chapat, J.-P. J. Org. Chem.
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This work was supported by a research grant from the
National Institutes of Health (R01 GM57416).
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