Efficient photochemical synthesis of tricyclic keto-indoles

Article abstract of DOI:10.1002/jhet.5570390517

Tricyclic keto-indoles were synthesized by photocyclization of easily obtained enaminones in an electrocyclic photochemical reaction. The three methods reported were chosen according to the enaminone structure. The most general procedure using one-step synthesis was carried out in a benzene-methanol solution in the presence of sodium methylate. In the case of base sensitive substrates, the best method was photocyclization followed by oxidation. Besides, N-unsubstituted indoles with a five-membered ring were prepared by a photolysis reaction. All three methods are efficient and easy to perform.

Full text of DOI:10.1002/jhet.5570390517

Sep-Oct 2002
Efficient Photochemical Synthesis of Tricyclic Keto-Indoles
965
Christèle Tietcheu, Christophe Garcia, Daniel Gardette,
Denise Dugat and Jean-Claude Gramain
Synthèse et Etude de Systèmes à Intérêt Biologique (SEESIB), UMR CNRS 6504,
Université Blaise Pascal de Clermont-Ferrand, 63177 Aubière, France
Received February 11, 2002
Tricyclic keto-indoles were synthesized by photocyclization of easily obtained enaminones in an electro-
cyclic photochemical reaction. The three methods reported were chosen according to the enaminone struc-
ture. The most general procedure using one-step synthesis was carried out in a benzene-methanol solution in
the presence of sodium methylate. In the case of base sensitive substrates, the best method was photocy-
clization followed by oxidation. Besides, N-unsubstituted indoles with a five-membered ring were prepared
by a photolysis reaction. All three methods are efficient and easy to perform.
J. Heterocyclic Chem., 39, 965(2002).
Tricyclic indoles 1 are biologically important com-
Attemps were soon made to develop experimental con-
ditions that would direct this reaction towards an oxidative
photocyclization leading straight to indole derivatives.
Although oxidative products were obtained as by-products
when the solution was not thoroughly degassed [6a], pio-
neering attempts to prepare these compounds in good
yields met little success and gave mixtures of compounds
owing to incomplete reaction [9, 11].
pounds [1] because of their specific pharmacological
activities and their presence in the structures of various
active alkaloids (e.g., aristoteline, yuehchukene). The cor-
responding keto-compounds 2 are key intermediates in the
building of tetra and pentacyclic alkaloid skeletons [2,3].
Here we describe two preparative photochemical
processes (methods A and B) to synthesize, in good to
excellent yield, substituted tricyclic keto-indoles 5, with a
five or six-membered C ring, from N-arylenaminones 3 by
an oxidative cyclization reaction. Photocyclizations were
Since the discovery of the Fischer indole synthesis [4]
numerous strategies have been developed for the indole
ring formation [5a] such as base-initiated cyclization of
halogenated imines/enamines [5b], transition metal cat-
alyzed reactions [5c-5e] and radical initiated reactions [5f].
However, the search for new approaches is still a topic of
current interest.
We previously described the non-oxidative photocy-
clization of N-arylenaminones 3 leading to trans-hexahy-
drocarbazolones 4 [6], which were intermediates in the
synthesis of dihydroindolic Aspidosperma alkaloids [7].
The reaction mechanism is similar to that proposed by
Grellmann [8] and Chapman [9] for the photocyclization
of N-arylenamines, which gave trans compounds in agree-
ment with the Woodward-Hoffmann rules [10]. It probably
involves the n, p* triplet excited state [11].
®
performed using a 400 W medium pressure Pyrex -jack-
eted immersion lamp (> 300 nm).
In method A, irradiation was conducted in non-degassed
neutral medium and the crude mixture (mixture of com-
pounds 4 and 5) was oxidized in the presence of 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or man-
ganese (III) acetate dihydrate [12].
In method B we first investigated the oxidative photocy-
clization of N-arylenaminones 3 in the presence of iodine
or oxygen [9]. These reactions gave indoles 5 in low yield.
In contrast, good to excellent yields of indoles 5 were
obtained when irradiation of N-arylenaminones 3 was
performed in the presence of sodium methoxide. The use

966
C. Tietcheu, C. Garcia, D. Gardette, D. Dugat and J.-C. Gramain
Vol. 39
oxidation of ketones in basic medium [14,15] as related in
the Büchi vindoline synthesis [16]. The reaction certainly
proceeds by oxidation of the thermodynamic enolate of the
saturated ketone followed by aromatization. After opti-
mization of experimental conditions, the photocyclization
of compounds 3 was carried out in the presence of sodium
(3 equivalents) in a benzene/methanol (1:1) solution.
Enaminones 3a [17], 3h-m were prepared following the
reaction pathway of Scheme 4 and enaminones 3b-g were
obtained by alkylation of 3a as previously described [17,18].
These thirteen compounds were photocyclized to lead to the
expected indoles 5a-m. The results are collected in the Table.
of a strong base was suggested by the oxidation of hexa-
hydrocarbazolones 4 into indoles 5 during alkylation
attempts of 4 in strongly basic medium [13]. The same
transformation was observed on treatment of 4 with
sodium in methanol. These experiments call to mind the
Table
Experimental Conditions and Results of Enaminone Photocyclization by Different Methods
Enaminone
Solvents
Method A
Method B
t (h)
Indole
t (h)
%
%
3a
3b
3c
C H
1.2
1.0
0.7
-
0.5
2.5
0.5
0.5
-
3.0
1.0
1.5
1.5
4.0
-
49
75 [a]
95 [b]
-
65 [b]
72 [b]
68
66 [b]
-
40
36
56
63
78 [a,c]
-
-
3.0
-
3.2
-
4.0
-
-
2.5
3.0
2.0
4.0
4.0
4.0
7.0
-
-
80
-
81
-
63
-
-
42
traces
traces
traces
54
56[c]
91
-
30
35
5a
5b
5c
6
6
C H + MeOH
6
6
C H
6
6
C H + MeOH
6
6
C H
6
6
C H + MeOH
6
6
3d
3e
C H
5d
5e
6
6
C H
6
6
C H + MeOH
6
6
3f
3g
3h
3i
3j
3k
3l
C H + MeOH
5f
5g
5h
5i
5j
5k
5l
6
6
C H + MeOH
6
6
C H + MeOH
6
6
C H + MeOH
6
6
C H + MeOH
6
6
C H + MeOH
6
6
C H
76.0
-
-
50 [d]
-
-
6
6
C H + MeOH
48.0
48.0
6
6
3m
C H + MeOH
5m
6
6
[a] Photocyclization followed by oxidative treatment with Mn(OAc) (1.1 eq) in dichloromethane + acetic acid at 70°C for 3h;
3
[b] Photocyclization followed by oxidative treatment with DDQ (0.6 eq) in benzene at 80°C for 6h; [c] Formation of two indoles
5j (5-OMe) and 5j' (7-OMe), ratio 65:35; [d] Yield relative to converted enaminone 3l; conversion 25%, real yield 12%.

Sep-Oct 2002
Efficient Photochemical Synthesis of Tricyclic Keto-Indoles
967
on a Reichert hot-stage microscope and are uncorrected. Infrared
spectra were run on a Perkin Elmer 377 or 881 spectrophotome-
ter. H nmr spectra were recorded on Jeol C60H, Bruker MSL
300 or Bruker AC 400 instrument and 13C nmr spectra on Jeol
FX 60, Bruker MSL 300 or Bruker AC 400 spectrometer (d val-
ues are given in ppm and J-values in Hz). Mass spectra were
measured on a Varian CH-5 or a Varian VG 30F apparatus.
Elemental combustion analysis were obtained from CNRS,
Service Central d'Analyse, Vernaison, France.
Indoles 5a-k, prepared from six-membered ring enam-
inones 3a-k, were obtained in good yields using either
method A or B. Method B offered the great advantage of
being an one-pot synthesis, but could not be used for base-
sensitive compounds 3d-h bearing a chloroalkyl group or
ester function. Also, method A gave the best yields in ben-
zene/methanol solution, although the reaction was faster in
benzene. Photocyclization of enaminone 3j afforded two
regioisomers 5j (5-OMe) and 5j' (7-OMe) in 65:35 ratio as
already observed for non-oxidative photocyclization [19].
In contrast, indoles 5l,m, prepared from five-membered
ring substrates 3l,m, were generated in moderate yields by
methods A or B. These disappointing results are certainly
due to the high ring strain in the corresponding indoles
5l,m. N-Unsubstituted compound 5n, with a five-mem-
bered C-ring, could, however, be synthesized in good yield
by a third approach, namely free radical photocyclization
of 2'-bromoaryl enaminone 3n, according to Kibayashi's
method [20] (Scheme 5). The best result (63% yield) was
obtained when the photolysis was carried out for 1.5 hour
in a methanol solution, in the presence of triethylamine,
using a quartz insert.
1
Preparation of Aromatic Amides 7i-k.
General Procedure.
To a solution of aromatic amine 6, triethylamine (1.2 eq) and
4-(dimethylamino)-pyridine (DMAP) (catalytic amount) in
dichloromethane (3 ml/mmole) was added dropwise, at 0° and
under nitrogen, a solution of benzoyl chloride (1.2 eq) in
dichloromethane (4 ml/mmole). The solution was allowed to
warm up to room temperature, stirred for 6 hours and washed
with brine (1 ml/mmole). The organic layer was dried on magne-
sium sulfate, filtered and evaporated under reduced pressure.
Crystallization of the crude material afforded the pure amide.
N-(4-Methylphenyl)-benzamide (7i).
This compound was prepared from p-toluidine (6i) (3.92 g,
36.7 mmoles), triethylamine (4.44 g, 6.10 ml, 44.0 mmoles),
DMAP (3 mg) and benzoyl chloride (6.18 g, 5.10 ml, 44.0
mmoles). The work-up afforded a residue which was crystallized
from ethanol as a white solid, 7.43 g (35.2 mmoles, 96%), mp
1
156° (lit. [21] 154°); ir and H nmr spectroscopic data of 7i have
been already reported [21]; 13C nmr (15 MHz, methanol-d4): d
20.9 (CH3), 122.4 (C-2, C-6), 128.7 (C-2', C-6'), 129.6 (C-3', C-
5'), 130.3 (C-3, C-5), 132.9 (C-4'), 135.2 (C-4), 136.2 (C-1'),
137.4 (C-1), 168.4 (CO).
N-(3-Methoxyphenyl)-benzamide (7j).
In conclusion, we describe versatile and efficient photo-
chemical methods to obtain tricyclic keto-indoles from
readily available enaminones. N-substituted indoles 5 with
a six-membered C-ring were easily obtained from N-aryl-
enaminones using an electrocyclic photochemical reac-
tion. Experimental conditions depend on the enaminone
stucture. Photocyclization in the presence of sodium in a
benzene/methanol solution (method B) has proved to be a
general and useful one-step synthesis to access to indoles
5. However, photocyclization followed by oxidation
(method A) is shown to be more efficient for base-sensi-
tive substrates. N-unsubstituted indoles 5n with a five-
membered C ring were prepared by a photolysis reaction.
The three methods described require inexpensive reagents,
are complementary, easy to perform and compare favorably
with other methods recently reported in the literature.
This compound was prepared from meta-anisidine (6j) (4.92 g,
4.50 ml, 40.0 mmoles), triethylamine (4.85 g, 6.66 ml, 48.0
mmoles), DMAP (3 mg) and benzoyl chloride (6.75 g, 5.57 ml,
48.0 mmoles). The work-up afforded a residue which was crys-
tallized from ethanol as a white solid, 8.63 g (38.0 mmoles,
95%), mp 175°; ir (chloroform): 1675 (CO) cm-1; H nmr (60
1
MHz, deuteriochloroform): d 3.70 (s, 3H, OCH3), 6.50-8.50 (m,
10H, phenyl protons + NH); 13C nmr (100 MHz, methanol-d4): d
55.3 (OCH3), 106.0 (C-2), 110.5 (C-4), 112.6 (C-6), 127.1 (C-5),
128.7 (C-2', C-6'), 129.7 (C-4'), 131.8 (C-3', C-5'), 134.8 (C-1'),
139.2 (C-1), 160.1 (C-3), 171.4 (CO).
N-(3,5-Dimethylphenyl)-benzamide (7k).
This compound was prepared from 3,5-dimethylaniline (6k)
(4.44 g, 4.57 ml, 36.7 mmoles), triethylamine (4.44 g, 6.10 ml,
44.0 mmoles), DMAP (3 mg) and benzoyl chloride (6.18 g, 5.10
ml, 44.0 mmoles). The work-up afforded a residue which was
crystallized from ethanol as a white solid, 8.09g (35.9 mmoles,
98%), mp 144-147°; ir (chloroform): 1670 (CO) cm-1; H nmr
1
EXPERIMENTAL
General Methods.
(60 MHz, methanol-d4): d 2.20 (s, 6H, 2CH3), 4.90 (s, 1H, NH),
6.85 (m, 1H, H-4), 7.30-7.70 (m, 5H, phenyl protons), 8.15 (m,
2H, H-2, H-6); 13C nmr (15 MHz, methanol-d4): d 22.9 (CH3),
120.1 (C-2, C-6), 120.5 (C-4), 128.9 (C-2', C-5'), 129.8 (C-3', C-
5'), 132.8 (C-4'), 136.3 (C-1'), 139.3 (C-1), 141.5 (C-3, C-5),
167.3 (CO).
Thin layer chromatography was performed with Merck silica
gel 60 F254 and flash column chromatography was carried out
with Merck silica gel 0.040-0.063 mm. Melting points were taken

968
C. Tietcheu, C. Garcia, D. Gardette, D. Dugat and J.-C. Gramain
Vol. 39
Preparation of Aromatic Amines 8i-k.
(400 MHz, deuteriochloroform) [24]: d 2.47-2.70 (m, 4H, 2H-4,
2H-6), 3.02 (m, 1H, H-5), 3.74 (s, 3H, OCH3), 4.85 (s, 2H,
CH2Ph), 5.47 (s, 1H, H-2), 7.10-7.42 (m, 10H, phenyl protons);
13C nmr (100 MHz, deuteriochloroform) [24]: d 30.4 (C-4),
37.5 (C-6), 39.1 (C-5), 52.1 (OCH3), 57.2 (CH2Ph), 100.8
(C-2), 127.1 (C-4'), 127.7 (C-4'', C-2', C-6'), 128.1 (C-2'', C-6''),
128.8 (C-3'', C-5''), 129.9 (C-3', C-5'), 135.7 (C-1''), 143.9
(C-1'), 164.4 (C-3), 176.4 (CO ester), 195.7 (CO ketone) .
Anal. Calcd. for C21H21NO3: C, 75.20; H, 6.31; N, 4.18.
Found: C, 75.11; H, 6.20; N, 4.32.
General Procedure.
To a suspension of lithium aluminium hydride (LiAlH4) (2 eq)
in THF (1 ml/mmole) was added dropwise, at 0° and under nitro-
gen, a solution of aromatic amide 7 (1 eq) in THF (5 ml/mmole).
After refluxing for 2 hours the excess of hydride was destroyed
by addition of H2O (0.1 ml/mmole) and a 15% solution of NaOH
(0.1 ml/mmole). After filtration, the residue was washed with
ethyl acetate (2 x 5 ml/mmole). The organic solution was dried
on magnesium sulfate and filtered. Evaporation of the solvant
afforded the expected aromatic amine with a satisfying purity.
3-[Benzyl-(4-methylphenyl)-amino]-cyclohex-2-enone (3i).
This compound was prepared from cyclohexane-1,3-dione
(2.24 g, 20.0 mmoles), N-benzyl-p-methylaniline (8i) (4.30 g,
22.0 mmoles), and PTSA (100 mg) in toluene (200 ml).
Chromatography with ethyl acetate afforded enaminone 3i, 4.00
g (14.0 mmol, 70%); ir (carbon tetrachloride): 1635 (CO) cm-1;
1H nmr (400 MHz, deuteriochloroform): d 1.86 (quint., 2H,
2H-5, J = 6.3 Hz), 2.24-2.34 (m, 4H, 2H-4, 2H-6), 2.27 (s, 3H,
CH3), 4.76 (s, 2H, CH2Ph), 5.34 (s, 1H, H-2), 6.90-7.35 (m, 9H,
phenyl protons); 13C nmr (100 MHz, deuteriochloroform):d 21.2
(CH3), 22.4 (C-5), 28.4 (C-4), 35.9 (C-6), 56.0 (CH2Ph), 101.4
(C-2), 126.8 (C-2', C-6'), 127.0 (C-2'', C6''), 127.2 (C-4''), 128.5
(C-3'', C-5''), 129.9 (C-3', C-5'), 136.3 (C-1''), 136.9 (C-4'), 144.2
(C-1'), 165.1 (C-3), 197.3 (CO).
N-Benzyl-N-(4-methylphenyl)amine (8i).
This compound was prepared from amide 7i (10.97 g, 52.0
mmoles) and LiAlH4 (3.95 g, 104.0 mmoles) and isolated as an
oil, 7.80 g (39.5 mmoles, 76%); ir (carbon tetrachloride): 3430
(NH) cm-1; nmr spectroscopic data of 8i have been already
reported [22].
N-Benzyl-N-(3-methoxyphenyl)amine (8j).
This compound was prepared from amide 7j (16.09 g, 70.9
mmoles) and LiAlH4 (5.39 g, 141.8 mmoles) and isolated as an oil,
13.43 g (63.1 mmoles, 89%); ir (carbon tetrachloride): 3440 (NH)
cm-1; 1H nmr (60 MHz, deuteriochloroform): d 3.85 (s, 3H, OCH3),
4.40 (s, 2H, CH2Ph), 6.27 (br. s, 1H, NH), 6.25-6.45 (m, 2H, phenyl
protons), 7.15-7.50 (m, 7H, phenyl protons); 13C nmr (100 MHz,
deuteriochloroform): d 48.2 (NCH2Ph), 55.0 (OCH3), 98.8 (C-2),
102.6 (C-4), 105.9 (C-6), 127.2 (C-4'), 127.5 (C-2', C-6'), 128.6 (C-
3', C-5'), 130.3 (C-5), 139.3 (C-1'), 149.5 (C-1), 160.8 (C-3).
Anal. Calcd. for C20H21NO: C, 82.44; H, 7.26; N, 4.81. Found:
C, 82.11; H, 7.02; N, 4.63.
3-[Benzyl-(3-methoxyphenyl)-amino]-cyclohex-2-enone (3j).
This compound was prepared from cyclohexane-1,3-dione (3.05
g, 27.2 mmoles), N-(methoxyphenyl)benzylamine 8j (6.38 g, 30.0
mmoles) and PTSA (136 mg) in toluene (270 ml).
Chromatography with ethyl acetate:methanol (95:5, v/v) afforded
enaminone 3j, 7.26 g (23.7 mmoles, 87%); ir (carbon tetrachlo-
N-Benzyl-N-(3,5-dimethylphenyl)amine (8k).
This compound was prepared from amide 7k (10.37 g, 46.1
mmoles) and LiAlH4 (3.50 g, 92.2 mmoles) and isolated as an oil
(9.03 g, 42.8 mmoles, 93%); ir (carbon tetrachloride): 3420 (NH)
cm-1; 1H nmr (60 MHz, deuteriochloroform): d 2.18 (s, 6H,
2 CH3), 3.65 (s, 1H, NH), 4.10 (s, 2H, CH2Ph), 6.13 (s, 2H, H-2,
H-6), 6.37 (s, 1H, H-4), 7.45 (s, 5H, phenyl protons); 13C nmr (15
MHz, deuteriochloroform): d 21.4 (2 CH3), 48.3 (NCH2Ph),
110.8 (C-2, C-6), 119.6 (C-4), 127.1 (C-4'), 127.5 (C-2', C-6'),
128.6 (C-3', C-5'), 138.8 (C-3, C-5), 139.7 (C-1'), 148.3 (C-1).
-1 1
ride): 1635 (CO) cm ; H nmr (400 MHz, deuteriochloroform): d
1.93 (quint., 2H, 2H-5, J = 6.2 Hz), 2.40 (m, 4H, 2H-4, 2H-6), 3.79
(s, 3H, OCH3), 4.84 (s, 2H, CH2Ph), 5.40 (s, 1H, H-2), 6.65-7.45
(m, 9H, phenyl protons); 13C nmr (100 MHz, deuteriochloroform):
d 22.3 (C-5), 28.4 (C-4), 35.8 (C-6), 55.2 (OCH3), 56.4 (CH2Ph,),
101.2 (C-2), 112.7 (C-2'), 113.5 (C-4'), 119.7 (C-6'), 126.7 (C-2'',
C-6''), 127.2 (C-4''), 128.5 (C-3'', C-5''), 130.1 (C-5'), 136.1 (C-1''),
145.2 (C-1'), 160.2 (C-3'), 164.8 (C-3), 197.5 (CO).
Preparation of Enaminones 3.
Anal. Calcd. for C20H21NO2: C, 78.15; H, 6.89; N, 4.56.
Found: C, 77.85; H, 7.16; N, 4.70.
General Procedure.
To a suspension of diketone (1 eq) in toluene (10 ml/mmole)
was added para-toluenesulfonic acid (PTSA) (5 mg/mmole) and
aromatic amine 8 (1.1 eq). The mixture was refluxed overnight in
a Dean-Stark apparatus, neutralized with potassium carbonate,
filtered and evaporated under reduced pressure. The residual
semisolid was purified on a silica gel column.
3-[Benzyl-(3,5-dimethylphenyl)-amino]-cyclohex-2-enone (3k).
This compound was prepared from cyclohexane-1,3-dione (440
mg, 3.93 mmoles), N-benzyl-3,5-dimethylaniline 8k (910 mg, 4.32
mmoles), and PTSA (20 mg) in toluene (40 ml). Chromatography
with ethyl acetate:hexane (50:50, v/v) afforded enaminone 3k, 1.08
g (3.54 mmoles, 90%); crystals (Et2O), mp 70-71°; ir (carbon tetra-
Compounds 3a [17], 3b [17], 3c [18], 3d [18], 3e [17], 3f [18],
and 3g [18] have been already described.
1
chloride): 1640 (CO) cm-1; H nmr (400 MHz, deuteriochloro-
form): d 1.97 (quint., 2H, 2H-5, J = 6.3 Hz), 2.34 (s, 6H, 2 CH3),
2.37 (m, 4H, 2H-4, 2H-6), 4.87 (s, 2H, CH2Ph), 5.40 (s, 1H, H-2),
6.80 (s, 2H, H-2', H-6'), 6.97 (s, 1H, H-4'), 7.25-7.40 (m, 5H,
phenyl protons); 13C nmr (100 MHz, deuteriochloroform): d 21.1
(2CH3), 22.5 (C-5), 28.6 (C-4), 36.0 (C-6), 56.7 (CH2Ph), 101.3
(C-2), 125.1 (C-2', C-6'), 126.7 (C-2'', C-6''), 127.2 (C-4''), 128.6
(C-3'', C-5''), 129.1 (C-4'), 136.4 (C-1''), 139.3 (C-3', C-5'), 144.4
3-(Benzylphenylamino)-5-oxo-cyclohex-3-ene Carboxylic Acid
Methyl Ester (3h).
This compound was prepared from methyl 3,5-dioxocyclo-
hexylformiate [23] (1.84 g, 10.8 mmoles), N-benzylamine (2.17
g, 11.9 mmoles), and PTSA (54 mg) in toluene (110 ml).
Chromatography with ethyl acetate:hexane (70:30, v/v)
afforded enaminone 3h, 2.88 g (8.60 mmoles, 80%); ir (carbon
tetrachloride): 1740 (CO ester), 1640 (CO ketone) cm-1; 1H nmr
.
(C-1'), 165.0 (C-3), 197.5 (CO); ms: m/z 305 (17, M+ ), 249 (11),
234 (5), 186 (3), 134 (4), 91 (100), 65 (12), 28 (25).

Sep-Oct 2002
Efficient Photochemical Synthesis of Tricyclic Keto-Indoles
969
Anal. Calcd. for C21H23NO: C, 82.58; H, 7.59; N, 4.59. Found:
C, 82.63; H, 7.67; N, 4.95.
solvents: i) the residue was dissolved in toluene (100 ml/mmole)
and refluxed for 5 hours in presence of 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone (DDQ) (0.5 eq); after removal of part of the
solvent (2/3) and filtration of the DDQ reduced form, the solution
was concentrated; the crude material was then purified by chro-
matography; ii) the residue was dissolved in dichloromethane (3
ml/mmole) and the solution added dropwise to a suspension of
manganese (III) acetate dihydrate (1.1 eq) in acetic acid (5
ml/mmole); the mixture was warmed at 70° for 3 hours, cooled
and filtered; the organic layer was washed successively with sat-
urated solutions of sodium hydrogen carbonate (2 x 20 ml) and
brine (2 x 10 ml), dried on magnesium sulfateand concentrated;
the crude material then was purified by chromatography.
3-(Benzylphenylamino)-cyclopent-2-enone (3l).
This compound was prepared from cyclopentane-1,3-dione
(0.50 g, 5.10 mmoles), N-benzylaniline (1.02 g, 5.60 mmoles,
and PTSA (25 mg) in toluene (50 ml). Chromatography with
ethyl acetate afforded enaminone 3n, 1.30 g (4.94 mmoles, 97%);
1
ir (carbon tetrachloride): 1705 (CO), 1675 (N-C=C) cm-1; H
nmr (400 MHz, deuteriochloroform): d 2.20 (m, 2H, 2H-5), 2.40
(m, 2H, 2H-4), 4.70 (s, 2H, NCH2Ph), 5.20 (s, 1H, H-2), 7.00-
7.25 (m, 10H, phenyl protons); 13C nmr (100 MHz, deuteriochlo-
roform): d 28.0 (C-4), 33.8 (C-5), 57.3 (NCH2Ph), 102.5 (C-2),
126.6 (C-2', C-6', C-2'', C-6''), 126.8 (C-4'), 127.2 (C-4''), 128.2
(C-3'', C-5''), 129.1 (C-3', C-5'), 135.7 (C-1''), 143.2 (C-1'), 176.7
(C-3), 203.7 (CO).
Method B.
A solution of enaminone (0.72 to 1.08 mmole) in
benzene:methanol (1:1, v/v) (150 ml) was irradiated at ambient
air and in presence of sodium (3 eq). After evaporation of the sol-
vents, the residue was dissolved in ethyl acetate (50 ml/mmole).
The solution was washed with brine (2 x 10 ml) and the aqueous
phase extracted a last time with dichloromethane (10 ml). The
combined organic layers were dried on magnesium sulfate and
concentrated. The residue was purified by chromatography on a
silica gel column.
Anal. Calcd. for C18H17NO: C, 82.10; H, 6.51; N, 5.32. Found:
C, 82.30; H, 6.38; N, 5.16.
3-[Benzyl-(3,5-dimethylphenyl)-amino]-cyclopent-2-enone
(3m).
This compound was prepared from cyclopentane-1,3-dione (353
mg, 3.60 mmoles), N-benzyl-3,5-dimethylaniline (836 mg, 3.96
mmoles), and PTSA (18 mg) in toluene (40 ml). Chromatography
with ethyl acetate afforded enaminone 3m, 922 mg (3.17 mmoles,
88%); ir (carbon tetrachloride): 1695 (CO), 1675 (N-C=C) cm-1;
1H nmr (400 MHz, deuteriochloroform): d 2.30 (s, 6H, 2CH3),
2.35-2.47 (m, 2H, 2H-5), 2.50-2.65 (m, 2H, 2H-4), 4.72 (s, 2H,
NCH2Ph), 5.22 (s, 1H, H-2), 6.77 (s, 2H, H-2', H-6'), 6.95 (s, 1H,
H-4'), 7.20-7.38 (m, 5H, phenyl protons); 13C nmr (100 MHz, deu-
teriochloroform): d 21.6 (2 CH3), 29.7 (C-4), 35.3 (C-5), 59.2
(NCH2Ph), 102.9 (C-2), 125.9 (C-4'), 128.9 (C-4''), 129.0 (C-2'', C-
6''), 130.0 (C-2', C-6'), 130.8 (C-3'', C-5''), 137.7 (C-3', C-5'), 140.9
(C-1''), 144.9 (C-1'), 181.2 (C-3), 207.2 (CO).
9-Benzyl-1,2,3,9-tetrahydrocarbazol-4-one (5a).
This compound was prepared either by method A (solvent: i)
benzene ii) benzene-methanol (1:1, v/v) or by method B.
Method A: i) Irradiation of 3a (300 mg, 1.08 mmole) was real-
ized in benzene (150 ml, c = 7.22 x 10-3 M) for 1.2 hour.
Chromatography with ethyl acetate:hexane (50:50, v/v) as eluent
afforded 5a (145 mg, 0.53 mmole, 49%); ii) irradiation of 3a
(500 mg, 1.80 mmole) in benzene-methanol 1:1 (150 ml, c = 12.0
x 10-3 M) for 1 hour was followed by treatment with a suspension
of manganese (III) acetate dihydrate (536 mg, 2.00 mmoles) in
acetic acid (9 ml). Chromatography with ethyl acetate:hexane
(40:60, v/v) as eluent afforded 5a, 370 mg (1.35 mmole, 75%).
Method B: Irradiation of 3a (300 mg, 1.08 mmole) in benzene-
methanol 1:1 (150 ml, c = 7.22 x 10-3 M) was performed in pres-
ence of sodium (75 mg, 3.24 mmoles) for 3 hours.
Chromatography with ethyl acetate:hexane (40:60, v/v) as eluent
afforded 5a, 240 mg (0.87 mmole, 80%).
Anal. Calcd. for C20H21NO: C, 82.44; H, 7.26; N, 4.81. Found:
C, 82.72; H, 7.35; N, 4.62.
3-(2-Bromophenylamino)-cyclopent-2-enone (3n).
This compound was prepared from cyclopentane-1,3-dione
(0.98 g, 10.0 mmoles), o-bromoaniline (1.80 g, 10.5 mmoles),
and PTSA (50 mg) in toluene (100 ml). Chromatography with
ethyl acetate afforded enaminone 3n, 2.49 g (9.9 mmoles, 99%);
yellow crystals (Et2O), mp 161-163°; ir (carbon tetrachloride):
1695 (CO) cm-1; 1H nmr (400 MHz, deuteriochloroform): d 2.40
(m, 2H, 2H-5), 2.80 (m, 2H, 2H-4), 5.55 (s, 1H, H-2), 7.10 (m,
1H, phenyl proton), 7.25-7.62 (m, 3H, phenyl protons); 13C nmr
(100 MHz, deuteriochloroform): d 29.1 (C-4), 33.5 (C-5), 103.7
(C-2), 116.2 (C-2'), 122.7 (C-6'), 126.1 (C-4'), 128.5 (C-5'), 133.2
(C-3'), 137.5 (C-1'), 171.9 (C-3), 205.9 (CO); ms: m/z 253 [40,
Compound 5a was obtained as white crystals (ethyl acetate),
mp 160-161°; ir (chloroform): 1640 (CO) cm-1; 1H nmr (400
MHz, deuteriochloroform): d 2.25 (quint, 2H, 2H-2, J = 6.4 Hz),
2.60 (t, 2H, 2H-3, J = 6.4 Hz,), 2.90 (t, 2H, 2H-1, J = 6.2 Hz),
5.37 (s, 2H, NCH2Ph), 7.05 (dd, 2H, H-2', H-6', J = 7.6, 1.2 Hz),
7.21-7.34 (m, 6H, phenyl protons), 8.31 (dt, 1H, H-5, J = 7.4, 1.2
Hz); 13C NMR (100 MHz, deuteriochloroform): d 22.1 (C-2),
23.3 (C-1), 37.8 (C-3), 46.9 (NCH2Ph), 109.7 (C-8), 112.9 (C-
4a), 121.5 (C-5), 122.9 (C-6), 123.1 (C-7), 124.8 (C-4b), 126.0
(C-2', C-6'), 127.8 (C-4'), 128.9 (C-3', C-5') , 136.0 (C-1'), 137.0
.
.
M+ 81Br)], 251 [41, M+ 79Br)], 224 (11), 222 (12), 196 (4),
( (
172 (100), 157 (5), 89 (12), 28 (49), 27 (12).
Anal. Calcd. for C11H10BrNO: C, 52.40; H, 4.00; N, 5.56.
Found: C, 52.72; H, 3.78; N, 5.48.
.
(C-9a), 151.9 (C-8a), 193.9 (CO); ms: m/z 275 (80, M+ ), 247
(30), 218 (18), 156 (8), 128 (13), 91 (100), 65 (12).
Anal. Calcd. for C19H17NO: C, 82.88; H, 6.22; N, 5.09. Found:
C, 82.49; H, 6.38; N, 5.14.
Preparation of Indoles 5. General Procedure.
Method A.
A solution of enaminone 3 (0.23 to 1.80 mmole) in benzene
(150 ml) or benzene:methanol (1:1, v/v) (150 ml) was irradiated
at ambient air. When formation of tetrahydrocarbazolone 5 was
accompanied by small amounts of hexahydrocarbazolone 4, two
alternative processes were followed after evaporation of the
9-Benzyl-3-ethyl-1,2,3,9-tetrahydrocarbazol-4-one (5b).
This compound was prepared either by method A or method B.
Method A: Irradiation of 3b (160 mg, 0.52 mmole) in benzene
(150 ml, c = 3.5 x 10-3 M) for 0.7 hour was followed by treat-

970
C. Tietcheu, C. Garcia, D. Gardette, D. Dugat and J.-C. Gramain
Vol. 39
ment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (60 mg,
0.26 mmole, 0.5 eq) in toluene (52 ml). Chromatography with
ethyl acetate:cyclohexane (20:80, v/v) as eluent afforded 5b, 151
mg (0.50 mmole, 95%).
Method B: irradiation of 3b (160 mg, 0.52 mmole) in ben-
zene:methanol (1:1, v/v) (150 ml, c = 3.5 x10-3 M) was per-
formed in presence of sodium (36 mg, 1.57 mmole, 3 eq) for 3.2
hours. Chromatography with ethyl acetate:cyclohexane (20:80,
v/v) as eluent afforded 5b, 129 mg (0.42 mmole, 81%).
9-Benzyl-3-(3-chloropropyl)-1,2,3,9-tetrahydrocarbazol-4-one
(5d).
This compound was prepared according to the procedure of
method A. Irradiation of 3d (185 mg, 0.52 mmole) in benzene
(150 ml, c = 3.5 x 10-3 M) for 0.5 hour was followed by treatment
with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (60 mg, 0.26
mmole, 0.5 eq) in toluene (52 ml). Chromatography with ethyl
acetate:cyclohexane (15:85, v/v) afforded 5d, 114 mg (0.32
mmole, 62%); white solid (ethyl acetate), mp 118-119°; ir (car-
Compound 5b was obtained as white crystals (ethyl acetate),
mp 135-137°; ir (carbon tetrachloride): 1660 (CO) cm-1; 1H nmr
(400 MHz, deuteriochloroform): d 1.04 (t, 3H, CH3, J = 7.5 Hz),
1.58 (ddq, 1H, CHB-Me,J = 15.0, 7.5, 7.5 Hz), 1.97-2.09 (m, 2H,
CHA-Me, H-2ax), 2.32 (dddd, 1H, H-2eq, J = 13.3, 5.0, 5.0, 5.0
Hz), 2.42 (dddd, 1H, H-3, J = 9.5, 7.5, 7.5, 5.0 Hz), 2.85 (ddd,
1H, H-1ax, J = 17.0, 8.5, 5.0 Hz), 2.96 (ddd, 1H, H-1eq,J = 17.0,
5.0, 5.0 Hz), 5.30 (s, 2H, NCH2Ph), 7.04 (dd, 2H, H-2', H-6', J =
7.2, 1.8 Hz), 7.20-7.34 (m, 6H, phenyl protons), 8.32 (dt, 1H, H-
5, J = 7.8, 1.0 Hz); 13C nmr (100 MHz, deuteriochloroform): d
12.0 (CH3), 21.2 (C-1), 22.5 (CH2Me), 27.8 (C-2), 47.0
(NCH2Ph), 47.8 (C-3), 109.7 (C-8), 112.8 (C-4a), 121.8 (C-5),
122.7 (C-6), 123.2 (C-7), 125.2 (C-4b), 126.1 (C-2', C-6'), 127.9
(C-4'), 129.1 (C-3', C-5'), 136.2 (C-1'), 137.4 (C-9a), 151.1 (C-
1
bon tetrachloride): 1660 (CO) cm-1; H nmr (400 MHz, deuteri-
ochloroform): d 1.71 (dddd, 1H, CHB-C2H5Cl, J = 14.0, 7.0, 7.0,
7.0 Hz), 1.91-2.15 (m, 4H, CHA-C2H5Cl, CH2-CH2Cl, H-2ax),
2.30 (dddd, 1H, H-2eq, J = 13.0, 5.0, 5.0, 5.0 Hz), 2.50 (dddd,
1H, H-3, J = 9.0, 7.0, 5.0, 5.0 Hz), 2.84 (ddd, 1H, H-1ax,J = 17.0,
9.0, 5.0 Hz), 2.95 (ddd, 1H, H-1eq, J = 17.0, 5.0, 5.0 Hz), 3.60
(m, 2H, CH2Cl), 5.30 (s, 2H, NCH2Ph), 7.03 (dd, 2H, H-2', H-6',
J = 7.0, 1.7 Hz), 7.21-7.34 (m, 6H, phenyl protons), 8.30 (d, 1H,
H-5, J = 7.7 Hz); 13C nmr (100 MHz, deuteriochloroform): d 21.3
(C-1), 27.2 (CH2-C2H5Cl), 28.7 (C-2), 30.5 (CH2-CH2Cl), 45.3
(CH2Cl), 45.6 (C-3), 46.9 (NCH2Ph), 109.7 (C-8), 112.5 (C-4a),
121.6 (C-5), 122.7 (C-6), 123.2 (C-7), 125.1 (C-4b), 126.1 (C-2',
C-6'), 127.9 (C-4'), 129.1 (C-3', C-5'), 136.0 (C-1'), 137.3 (C-9a),
.
151.0 (C-8a), 195.5 (CO); ms: m/z 353 [4, M+ (37Cl)], 351 [12,
.
.
M+
(
35Cl)], 316 (64), 288 (11), 275 (36), 246 (10), 218 (15), 167
8a), 196.3 (CO); ms: m/z 303 (38, M+ ), 275 (100), 246 (18), 218
(7), 128 (15), 91 (100), 65 (21).
Anal. Calcd. for C22H22NOCl: C, 75.09; H, 6.30; N, 3.98; Cl,
10.07. Found: C, 74.80; H, 6.28; N; 4.04; Cl, 9.72.
(26), 184 (7), 156 (8), 128 (19), 115 (6), 91 (83), 77(6), 65 (19);
hrms calcd. for C21H21NO: 303.1623, found 303.1620.
Anal. Calcd. for C21H21NO: C, 83.13; H, 6.98; N, 4.62. Found:
C, 82.67; H, 6.95; N, 4.69.
9-Benzyl-3-(3-chloropropyl)-3-ethyl-1,2,3,9-tetrahydrocarbazol-
4-one (5e).
9-Benzyl-3,3-dimethyl-1,2,3,9-tetrahydrocarbazol-4-one (5c).
This compound was prepared either by method A or method B.
Method A: Irradiation of 3e (200 mg, 0.52 mmole) in benzene
(150 ml, c = 3.5 x 10-3 M) for 0.5 hour was followed by treatment
with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (60 mg, 0.26
mmole, 0.5 eq) in toluene (52 ml). Chromatography with ethyl
acetate/cyclohexane (10:90, v/v) afforded 5e, 132 mg (0.35
mmole, 66%) as a foam.
Method B: Irradiation of 3e (200 mg, 0.52 mmole) in benzene
(150 ml, c = 3.5 x 10-3 M) was performed in presence of sodium
(36 mg, 1.57 mmole, 3 eq) for 2.5 hours. The aqueous phase was
extracted with dichloromethane (2 x 5 ml). Chromatography with
ethyl acetate:cyclohexane (10:90, v/v) afforded 5e, 83 mg (0.22
mmole, 42%).
This compound was prepared either by method Aor method B.
Method A: Irradiation of 3c (160 mg, 0.52 mmole) in benzene
(150 ml, c = 3.5 x 10-3 M) for 0.5 hour or benzene:methanol (1:1,
v/v) (150 ml, c = 3.5 x 10-3 M) for 2.5 hours was followed by
treatment with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (60
mg, 0.26 mmole, 0.5 eq) in toluene (52 ml). Chromatography
with ethyl acetate:cyclohexane (10:90, v/v) afforded 5c, 103 mg
(0.34 mmole, 65%) (irradiation in benzene) or 115 mg (0.38
mmole, 72%) (irradiation in benzene:methanol).
Method B: Irradiation of 3c (160 mg, 0.52 mmole) in ben-
zene:methanol (1:1, v/v) (150 ml, c = 3.5 x 10-3 M) was per-
formed in presence of sodium (36 mg, 1.57 mmole, 3 eq) for 4
hours. Chromatography with ethyl acetate:cyclohexane (10:90,
v/v) afforded 5c, 101 mg (0.33 mmole, 63%).
Compound 5e was obtained as beige foam; ir (carbon tetra-
1
chloride): 1650 (CO) cm-1; H nmr (400 MHz, deuteriochloro-
Compound 5c was obtained as white crystals (ethyl acetate),
mp 171-172°; ir (carbon tetrachloride): 1640 (CO) cm-1; 1H
nmr (400 MHz, deuteriochloroform): d 1.25 (s, 6H, 2CH3), 2.08
(t, 2H, 2H-2, J = 6.3 Hz), 2.90 (t, 2H, 2H-1, J = 6.3 Hz), 5.33 (s,
2H, NCH2Ph), 7.03 (dd, 2H, H-2', H-6', J = 6.4, 1.7 Hz), 7.20-
form): d 0.93 (t, 3H, CH3, J = 7.5 Hz), 1.62-1.91 (m, 6H, CH2Me,
CH2-CH2-CH2Cl), 2.13 (t, 2H, 2H-2, J = 6.3 Hz), 2.91 (t, 2H,
2H-1, J = 6.3 Hz,), 3.53 (m, 2H, CH2Cl), 5.32 (s, 2H, NCH2Ph),
7.03 (dd, 2H, H-2', H-6', J = 7.8, 1.6 Hz), 7.19-7.34 (m, 6H,
phenyl protons), 8.33 (d, 1H, H-5, J = 7.6 Hz); 13C nmr (100
MHz, deuteriochloroform): d 8.6 (CH3), 19.2 (C-1), 27.5
(CH2Me), 27.6 (CH2-CH2Cl), 31.3 (C-2), 31.8 (CH2-C2H4Cl),
45.9 (CH2Cl), 46.8 (NCH2Ph), 47.5 (C-3), 109.7 (C-8), 112.0 (C-
4a), 121.8 (C-5), 122.6 (C-6), 123.2 (C-7), 125.4 (C-4b), 126.0
7.35 (m, 6H, phenyl protons), 8.34 (d, 1H, H-5, J = 7.8 Hz); 13
C
nmr (100 MHz, deuteriochloroform): d 19.7 (C-1), 24.5
(2 CH3), 37.1 (C-2), 41.6 (C-3), 46.8 (NCH2Ph), 109.6 (C-8),
111.3 (C-4a), 121.7 (C-5), 122.6 (C-6), 123.1 (C-7), 125.5 (C-
4b), 126.0 (C-2', C-6'), 127.9 (C-4'), 129.1 (C-3', C-5'), 127.9
(C-4'), 136.1 (C-1'), 137.5 (C-9a), 150.3 (C-8a), 199.2 (CO);
(C-2', C-6'), 127.9 (C-4'), 129.1 (C-3', C-5'), 136.0 (C-1'), 137.4
.
(C-9a), 149.9 (C-8a), 197.7 (CO); ms: m/z 381 [14, M+
(
37Cl)],
.
ms: m/z 303 (100, M+ ), 232 (7), 218 (24), 128 (13), 101 (6), 91
.
379 [42, M+
(
35Cl)], 351 (25), 344 (69), 303 (47), 288 (14), 247
(70), 77 (4), 65 (24), 56 (10), 41 (16), 29 (8); hrms calcd. for
C21H21NO: 303.1623, found 303.1630.
Anal. Calcd. for C21H21NO: C, 83.13; H, 6.98; N, 4.62. Found:
C, 83.50; H, 6.97; N, 4.53.
(28), 218 (17), 128 (11), 91 (100), 65 (14), 40 (42), 36 (22), 29
(28); hrms calcd. for C24H26NOCl: 379.1697, found 379.1693.
Anal. Calcd. for C24H26NOCl: C, 75.87; H, 6.90; N, 3.69; Cl,
9.33. Found: C, 75.77; H, 7.12; N, 3.39; Cl, 8.98.

Sep-Oct 2002
Efficient Photochemical Synthesis of Tricyclic Keto-Indoles
971
9-Benzyl-3-methoxycarbonyl-1,2,3,9-tetrahydrocarbazol-4-one
(5f).
(NCH2Ph), 52.3 (OCH3), 109.8 (C-8), 112.6 (C-4a), 121.6 (C-5),
122.8 (C-6), 123.4 (C-7), 124.5 (C-4b), 126.1 (C-2', C-6'), 127.9
(C-4'), 129.0 (C-3', C-5'), 135.6 (C-1'), 137.3 (C-9a), 149.5 (C-
8a), 173.2 (CO ester), 190.6 (C-4).
Anal. Calcd. for C21H19NO3: C, 75.65; H, 5.74; N, 4.20.
Found: C, 75.51; H, 5.85; N, 3.95.
This compound was prepared according to the procedure of
method A.Irradiation of 3f (500 mg, 1.49 mmole) was performed
in benzene (150 ml, c = 10.6 x 10-3 M) for 3 hours.
Chromatography with ethyl acetate afforded 5f, 200 mg (0.60
mmole, 40 %); ir (carbon tetrachloride): 1735 (CO ester), 1665
9-Benzyl-6-methyl-1,2,3,9-tetrahydrocarbazol-4-one (5i).
1
(CO enaminone) cm-1; H nmr (400 MHz, deuteriochloroform):
This compound was prepared either by method Aor method B.
Method A: Irradiation of 3i (400 mg, 1.37 mmole) was per-
formed in benzene:methanol (1:1, v/v) (150 ml, c = 9.1 x 10-3 M)
for 1.5 hour. Chromatography with ethyl acetate afforded 5i, 250
mg (0.86 mmole, 63%).
Method B: Irradiation of 3i (300 mg, 1.03 mmoles) in ben-
zene:methanol (1:1, v/v) (150 ml, c = 6.9 x 10-3 M) was per-
formed in presence of sodium (71 mg, 3.09 mmoles, 3 eq) for 4
hours. Chromatography with ethyl acetate afforded 5i, 160 mg
(0.55 mmole, 54%).
d 2.35 (m, 1H, H-2ax), 2.52 (ddd, 1H, H-1ax, J = 13.0, 9.0, 5.4
Hz), 2.76 (m, 1H, H-2eq), 3.00 (ddd, 1H, H-1eq, J = 13.0, 5.4, 5.4
Hz), 3.55 (dd, 1H, H-3, J = 10.0, 5.4 Hz), 3.75 (s, 3H, OCH3),
5.20 (s, 2H, CH2Ph), 7.00 (d, 2H, H-2', H-6', J = 6.8 Hz,), 7.20-
7.30 (m, 6H, phenyl protons), 8.27 (d, 1H, H-5, J = 7.6 Hz); 13
C
nmr (100 MHz, deuteriochloroform): d 20.5 (C-1), 26.2 (C-2),
46.9 (NCH2Ph), 52.2 (OCH3), 53.0 (C-3), 109.8 (C-8), 111.9 (C-
4a), 121.5 (C-5), 122.9 (C-6), 123.5 (C-7), 124.8 (C-4b), 126.0
(C-2', C-6'), 127.8 (C-4'), 128.9 (C-3', C-5'), 135.6 (C-1'), 137.2
(C-9a), 151.6 (C-8a), 171.1 (CO ester), 187.9 (C-4).
Compound 5i was obtained as white crystals; mp 146-148°
(acetone); ir (carbon tetrachloride): 1660 (CO) cm-1; 1H nmr
(400 MHz, deuteriochloroform): d 2.20 (quint, 2H, 2H-2, J = 6.4
Hz), 2.46 (s, 3H, CH3), 2.56 (t, 2H, 2H-3, J= 6.4 Hz), 2.83 (t, 2H,
2H-1, J = 6.4 Hz), 5.25 (s, 2H, NCH2Ph), 7.04 (d, 2H, H-2', H-6',
J = 7.2 Hz), 7.19-7.34 (m, 5H, phenyl protons), 8.15 (s, 1H, H-5);
13C nmr (100 MHz, deuteriochloroform): d 21.4 (CH3), 22.2 (C-
2), 23.3 (C-1), 37.8 (C-3), 47.0 (NCH2Ph), 109.3 (C-8), 112.6 (C-
4a), 121.6 (C-5), 123.5 (C-7), 124.5 (C-4b), 126.1 (C-2', C-6'),
127.8 (C-4'), 129.0 (C-3', C-5'), 132.3 (C-6), 135.4 (C-9a), 136.1
(C-1'), 151.8 (C-8a), 194.0 (CO).
Anal. Calcd. for C21H19NO3: C, 75.65; H, 5.74; N, 4.20.
Found: C, 75.90; H, 5.65; N, 4.40.
9-Benzyl-1-methoxycarbonyl-1,2,3,9-tetrahydrocarbazol-4-one
(5g).
This compound was prepared according to the procedure of
method A. Irradiation of 3g (170 mg, 0.51 mmole) was per-
formed in benzene:methanol (1:1, v/v) (150 ml, c = 3.4 x 10-3 M)
for 1 hour. Chromatography with ethyl acetate:hexane (30:70,
v/v) afforded 5g, 60 mg (0.18 mmole, 36%); white crystals (ethyl
acetate), mp 133-135°; ir (carbon tetrachloride): 1735 (CO ester),
1670 (CO enaminone) cm-1; 1H nmr (400 MHz, deuteriochloro-
form): d 2.42 (dddd, 1H, H-2ax, J = 14.0, 14.0, 5.5, 4.5 Hz), 2.57
(ddd, 1H, H-3eq, J = 17.0, 4.5, 2.5 Hz), 2.62 (dddd, 1H, H-2eq, J
= 14.0, 5.0, 2.5, 2.5 Hz), 2.89 (ddd, 1H, J= 17.0, 14.0, 5.0 Hz, H-
3ax), 3.55 (s, 3H, OCH3), 4.02 (dd, 1H, J = 5.5, 2.5 Hz, H-1eq),
5.45 (s, 2H, CH2Ph), 7.00 (dd, 2H, H-2', H-6', J = 7.0, 1.5 Hz),
7.25-7.35 (m, 6H, phenyl protons), 8.37 (d, 1H, H-5, J = 8.0 Hz);
13C nmr (100 MHz, deuteriochloroform): d 27.4 (C-2), 34.9 (C-
3), 38.3 (C-1), 47.3 (NCH2Ph), 52.6 (OCH3), 110.2 (C-8), 113.5
(C-4a), 122.1 (C-5), 123.0 (C-6), 123.8 (C-7), 124.5 (C-4b),
125.9 (C-2', C-6'), 127.8 (C-4'), 128.9 (C-3', C-5'), 135.8 (C-1'),
137.4 (C-9a), 146.6 (C-8a), 170.4 (CO ester), 193.5 (C-4); ms:
Anal. Calcd. for C20H19NO: C, 83.01; H, 6.62; N, 4.84. Found:
C, 82.90; H, 6.75; N, 4.68.
9-Benzyl-5-methoxy-1,2,3,9-tetrahydrocarbazol-4-one (5j) and
9-Benzyl-7-methoxy-1,2,3,9-tetrahydrocarbazol-4-one (5j').
These compounds were prepared either by method A or
method B.
Method A: Irradiation of 3j (200 mg, 0.65 mmole) in ben-
zene:methanol (1:1, v/v) (150 ml, c = 4.33 x 10-3 M) for 4 hours
was followed by treatment with a suspension of manganese (III)
acetate dihydrate (193 mg, 0.72 mmole) in acetic acid (3.3 ml).
Chromatography with ethyl acetate:hexane (40:60, v/v) as eluent
afforded 5j, 101 mg (0.33 mmole, 51%,) and 5j', 54 mg (0.18
mmole, 27%).
Method B: Irradiation of 3j (252 mg, 0.82 mmole) in ben-
zene:methanol (1:1, v/v) (150 ml, c = 5.5 x 10-3 M) was per-
formed in presence of sodium (57 mg, 2.46 mmole) for 4 hours.
Chromatography with ethyl acetate:hexane (40:60, v/v) as eluent
afforded 5j, 90 mg (0.30 mmole, 36%) and 5j', 50 mg (0.16
mmole, 20%).
.
m/z 333 (34, M+ ), 305 (10), 274 (19), 246 (11), 154 (8), 127 (5),
91 (100), 65 (27), 59 (27), 39 (11), 29 (11) 15 (45).
Anal. Calcd. for C21H19NO3: C, 75.65; H, 5.74; N, 4.20.
Found: C, 75.95; H, 5.90; N, 4.38.
9-Benzyl-2-methoxycarbonyl-1,2,3,9-tetrahydrocarbazol-4-one
(5h).
This compound was prepared according to the procedure of
method A. Irradiation of 3h (231 mg, 0.69 mmole) was per-
formed in benzene:methanol (1:1, v/v) (150 ml, c = 4.6 x 10-3 M)
for 1.5 hour. Chromatography with ethyl acetate:hexane (50:50,
v/v) afforded 5h, 128 mg (0.39 mmole, 56 %); ir (carbon tetra-
chloride): 1735 (CO ester), 1665 (CO enaminone) cm-1; 1H nmr
(400 MHz, deuteriochloroform): d 2.81 (ABX spectrum, AB
part, 2H, 2H-3, J= 16.6, 8.9, 5.8Hz), 3.12 (A'B'X spectrum, A'B'
part, 2H, 2H-1, J = 16.8, 8.0, 6.2 Hz,), 3.28 (ABX+A'B'X spec-
trum, X part, 1H, H-2), 3.68 (s, 3H, OCH3), 5.30 (s, 2H, CH2Ph),
7.05 (d, 2H, H-2', H-6', J = 7.0 Hz,), 7.20-7.30 (m, 6H, phenyl
protons), 8.28 (d, 1H, H-5, J = 8.0 Hz); 13C nmr (100 MHz, deu-
teriochloroform): d 24.5 (C-1), 39.7 (C-3), 40.5 (C-2), 47.0
Compound 5j was obtained as white crystals (acetone), mp
1
167-168°C; ir (carbon tetrachloride): 1670 (CO) cm-1; H nmr
(300 MHz, deuteriochloroform): d 2.21 (quint, 2H, 2H-2, J = 6.0
Hz), 2.65 (t, 2H, 2H-3, J= 6.0 Hz), 2.87 (t, 2H, 2H-1, J= 6.0 Hz),
4.05 (s, 3H, OCH3), 5.32 (s, 2H, NCH2Ph), 6.75 (d, 1H, H-8, J =
8.2 Hz), 6.90 (d, 1H, H-6, J = 8.2 Hz), 7.05 (dd, 2H, H-2', H-6', J
= 8.2, 2.0 Hz), 7.20 (t, 1H, H-7, J = 8.0 Hz), 7.30 (m, 3H, H-3', H-
4', H-5'); 13C nmr (75 MHz, deuteriochloroform): d 22.7 (C-2),
22.9 (C-1), 38.9 (C-3), 47.1 (NCH2Ph), 56.1 (OCH3), 102.9 (C-
8), 104.8 (C-6), 113.7 (C-4b), 114.5 (C-4a), 124.5 (C-7), 125.9
(C-2', C-6'), 127.8 (C-4'), 129.0 (C-3', C-5'), 135.9 (C-1'), 139.3
(C-9a), 151.2 (C-8a), 154.5. (C-5), 191.9 (CO); ms: m/z 305

972
C. Tietcheu, C. Garcia, D. Gardette, D. Dugat and J.-C. Gramain
Vol. 39
(100, M+.), 248 (19), 218 (11), 186 (20), 171 (11), 128 (13), 115
(11), 103 (10), 91 (75), 65 (17), 27 (29).
(C-4'), 129.0 (C-3', C-5'), 135.5 (C-1'), 142.6 (C-3a), 168.1 (C-
.
4a), 195.3 (CO); ms: m/z 261 (89, M+ ), 170 (38), 120 (21), 116
Anal. Calcd. for C20H19NO2: C, 78.66; H, 6.27; N, 4.59.
Found: C, 78.61; H, 6.20; N, 4.41.
(10), 91 (100), 65 (13), 28 (100).
Anal. Calcd. for C18H15NO: C, 82.73; H, 5.79; N, 5.36. Found:
C, 82.46; H, 5.92; N, 5.18.
Compound 5j' was obtained as white crystals (ethyl
acetate:hexane), mp 137-138°; ir (carbon tetrachloride): 1650
(CO) cm-1; 1H nmr (300 MHz, deuteriochloroform): d 2.22
(quint, 2H, 2H-2, J = 6.0 Hz), 2.57 (t, 2H, 2H-3, J = 6.0 Hz), 2.85
(t, 2H, 2H-1, J = 6.0 Hz), 3.82 (s, 3H, OCH3), 5.27 (s, 2H,
NCH2Ph), 6.75 (d, 1H, H-8, J = 2.0 Hz), 6.94 (dd, 1H, H-6, J =
8.0, 2.0 Hz), 7.05 (dd, 2H, H-2', H-6', J = 8.0, 1.0 Hz), 7.30 (m,
3H, H-3', H-4', H-5'), 8.20 (d, 1H, H-5, J = 8.0 Hz); 13C nmr (75
MHz, deuteriochloroform): d 22.3 (C-2), 23.5 (C-1), 37.8 (C-3),
47.0 (NCH2Ph), 55.7 (OCH3), 94.4 (C-8), 110.9 (C-6), 113.1 (C-
4a), 118.9 (C-4b), 122.3 (C-5), 126.1 (C-2', C-6'), 127.9 (C-4'),
129.0 (C-3', C-5'), 136.0 (C-1'), 137.9 (C-9a), 151.3 (C-8a),
157.1 (C-7), 193.9 (CO); ms: m/z 305 (100, M+.), 290 (17), 277
(16), 248 (15), 214 (13), 186 ( 27), 158 (15), 91 (65), 65 (12).
Anal. Calcd. for C20H19NO2: C, 78.66; H, 6.27; N, 4.59.
Found: C, 78.31; H, 6.20; N, 4.23.
4-Benzyl-6,8-dimethyl-3,4-dihydro-2H-cyclopenta[b]indol-1-
one (5m).
This compound was prepared by method B. Irradiation of 3m
(291 mg, 1.00 mmole) in benzene:methanol (1:1, v/v) (150 ml, c
= 6.7 x 10-3 M) was performed in presence of sodium (69 mg,
3.00 mmoles) for 48 hours. Chromatography with ethyl
acetate:hexane (50:50, v/v) afforded 5m, 100 mg (0.35 mmole,
35%); ir (carbon tetrachloride): 1665 (CO) cm-1; 1H nmr (400
MHz, deuteriochloroform): d 2.40 (s, 3H, CH3), 2.85 (s, 3H,
CH3), 2.88 (m, 2H, 2H-2), 2.92 (m, 2H, 2H-3), 5.23 (s, 2H,
NCH2Ph), 6.90 (d, 2H, H-2', H-6', J = 7.3 Hz), 7.15-7.40 (m, 5H,
phenyl protons); 13C nmr (100 MHz, deuteriochloroform):d 20.7
(C-3), 20.8 (CH3), 21.8 (CH3), 40.8 (C-2), 47.9 (NCH2Ph), 107.7
(C-5), 123.5 (C-2', C-6'), 124.9 (C-8b), 126.7 (C-4'), 127.0 (C-7),
128.1 (C-8a), 129.0 (C-3', C-5'), 132.4 (C-8), 134.0 (C-6), 135.8
(C-1'), 142.6 (C-3a), 167.5 (C-4a), 194.6 (CO).
9-Benzyl-5,7-dimethyl-1,2,3,9-tetrahydrocarbazol-4-one (5k).
Anal. Calcd. for C20H19NO: C, 83.01; H, 6.62; N, 4.84. Found:
C, 83.22; H, 6.48; N, 4.65.
This compound was prepared by method B. Irradiation of 3k
(300 mg, 0.98 mmole) in benzene:methanol (1:1, v/v) (150 ml,
c = 6.6 x 10-3 M) was performed in presence of sodium (68 mg,
2.95 mmoles, 3 eq) for 7 hours. Chromatography with ethyl
acetate afforded 5k, 270 mg (0.89 mmole, 91%); white crystals
(acetone), mp 145-146°; ir (carbon tetrachloride): 1665 (CO)
cm-1; 1H nmr (400 MHz, deuteriochloroform): d 2.18 (quint., 2H,
2H-2, J = 6.4 Hz), 2.39 (s, 3H, CH3), 2.59 (t, 2H, 2H-3, J = 6.4
Hz), 2.84 (t, 2H, 2H-1, J = 6.4 Hz), 2.97 (s, 3H, CH3), 5.30 (s,
2H, NCH2Ph), 6.88 (s, 1H, H-8), 6.90 (s, 1H, H-6), 7.02 (dd, 2H,
H-2', H-6', J = 6.6, 1.5 Hz,), 7.26-7.35 (m, 5H, phenyl protons);
13C nmr (100 MHz, deuteriochloroform): d 21.4 (CH3), 22.6
(C-2), 22.8 (C-1), 23.0 (CH3), 38.9 (C-3), 46.6 (NCH2Ph), 107.0
(C-8), 114.1 (C-4a), 122.1 (C-4b), 125.8 (C-2', C-6'), 126.2
(C-6), 127.6 (C-4'), 128.9 (C-3', C-5'), 132.6 (C-5), 133.2 (C-7),
136.0 (C-1'), 138.1 (C-9a), 151.7 (C-8a), 192.6 (CO).
3,4-Dihydro-2H-cyclopenta[b]indol-1-one (5n).
A solution of bromo-enaminone 3n (251 mg, 1.0 mmole) and
triethylamine (101 mg, 140 ml, 1.0 mmole) was irradiated for 1.5
hour in methanol (150 ml, c = 6.7 x 10-3 M) in a quartz apparatus.
After evaporation of the solvent, addition of water and extraction
with dichloromethane, the crude mixture was purified by chro-
matography. Elution with ethyl acetate gave compound 5n, 107
mg (0.63 mmole; 63%); crystals (ethanol), mp 250° (lit. [25] 247-
1
248°); ir (carbon tetrachloride): 1675 (CO) cm-1; H nmr (400
MHz, deuteriochloroform): d 2.99 (m, 2H, 2H-3), 3.09 (m, 2H,
2H-2), 7.10-7.45 (m, 3H, 3 Ar-H), 7.92 (dd, 1H, J = 6.7, 2.3 Hz,
H-8), 9.20 (br.s, 1H, NH); 13C nmr (100 MHz, deuteriochloro-
form): d 21.7 (C-3), 41.1 (C-2), 111.9 (C-5), 121.1 (C-8), 122.6
(C-7), 123.9 (C-6), 130.0 (C-8b), 141.0 (C-8a), 154.9 (C-3a),
166.6 (C-4a), 196.0 (CO).
Anal. Calcd. for C21H21NO: C, 83.13; H, 6.98; N, 4.62. Found:
C, 83.40; H, 7.12; N, 4.55.
Anal. Calcd. for C11H9NO: C, 77.17; H, 5.30; N, 8.18. Found:
C, 76.90; H, 5.42; N, 8.31.
4-Benzyl-3,4-dihydro-2H-cyclopenta[b]indol-1-one (5l).
This compound was prepared either by method A or method B.
Method A: Irradiation of 3l (526 mg, 2.00 mmole) in benzene
(150 ml, c = 13.3 x 10-3 M) was performed for 4 days.
Chromatography with ethyl acetate:hexane (50:50, v/v) as eluent
afforded 5l, 65 mg (0.25 mmole, 12%, 50% yield based on con-
sumed product).
Method B: Irradiation of 3l (263 mg, 1.0 mmole) in ben-
zene:methanol (1:1, v/v) (150 ml, c = 6.7 x 10-3 M) was per-
formed in presence of sodium (69 mg, 3.0 mmoles) for 48 hours.
Chromatography with ethyl acetate:hexane (50:50, v/v) as eluent
afforded 5l, 79 mg (0.30 mmole, 30%).
REFERENCES AND NOTES
*
To whom correspondence should be addressed: E-mail:
gardette@chisg1.univ-bpclermont.fr; Fax +(33) 04 73 40 77 17.
[1] R. J. Sunberg, Indoles, Academic Press, London, 1996 and
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(1994).
Compound 5l was obtained as crystals (ethyl acetate:hexane),
mp 140-142°; ir (carbon tetrachloride): 1695 (CO) cm-1; 1H nmr
(400 MHz, deuteriochloroform): d 2.80-2.90 (m, 4H, 2H-2, 2H-
3), 5.25 (s, 2H, NCH2Ph), 7.12 (d, 2H, H-2', H-6', J = 7.5 Hz,),
7.18-7.35 (m, 6H, phenyl protons), 7.95 (d, 1H, H-8, J = 7.0 Hz);
13C nmr (100 MHz, deuteriochloroform): d 20.8 (C-3), 40.8
(C-2), 48.1 (NCH2Ph), 110.6 (C-5), 120.9 (C-8), 121.5 (C-8b),
122.4 (C-7), 123.5 (C-6), 123.7 (C-8a), 126.7 (C-2', C-6'), 128.1
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according to the general numerotation of enaminones as indicated in
scheme 3, in an homogeneity purpose.
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