Novel applications of hypervalent iodine: PIFA mediated synthesis of benzo[c]phenanthiridines and benzo[c]phenanthridinones

Article abstract of DOI:10.1016/S0040-4020(01)00459-8

A short and efficient access to benzo[c]phenanthridines and phenanthridinones is achieved by the action of phenyliodine(III)-bis(trifluoroacetate) (PIFA) on properly substituted benzylnaphthylamines and naphthylbenzamides, respectively. This reagent promotes a non-phenolic oxidative biaryl coupling process, the key step of the synthesis. A study of the electronic and steric requirements of the substrates is carried out since, in some cases, dimerization processes prevail over intramolecular cyclization. A mechanistic proposal is also included.

Full text of DOI:10.1016/S0040-4020(01)00459-8

TETRAHEDRON
Pergamon
Tetrahedron 57 -2001) 5403±5411
Novel applications of hypervalent iodine: PIFA mediated
synthesis of benzo[c]phenanthiridines and
benzo[c]phenanthridinones
p
 Â
 Â
Isabel Moreno, Imanol Tellitu, Jesus Etayo, Raul SanMartõn and Esther Domõnguez
  Â
Departamento de Quõmica Organica II, Facultad de Ciencias, Universidad del Paõs Vasco, P.O. Box 644-48080 Bilbao, Spain
Received 3 February 2001; revised 21 March 2001; accepted 24 April 2001
AbstractÐA short and ef®cient access to benzo[c]phenanthridines and phenanthridinones is achieved by the action of phenyliodine-III)-
bis-tri¯uoroacetate) -PIFA) on properly substituted benzylnaphthylamines and naphthylbenzamides, respectively. This reagent promotes a
non-phenolic oxidative biaryl coupling process, the key step of the synthesis. A study of the electronic and steric requirements of the
substrates is carried out since, in some cases, dimerization processes prevail over intramolecular cyclization. A mechanistic proposal is also
included. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
latter case, radical,5 photochemical6 and benzyne-
mediated5c,7 syntheses of the benzophenanthridine skeleton
have been reported. Despite of the success of these
approaches several steps are needed to prepare such
elaborated precursors, and in many cases the overall yields
are synthetically unattractive.
Benzo[c]phenanthridines 1 are among the most biologically
active isoquinoline derivatives.1 However, the high toxicity
associated with some of the most active members of this
family of alkaloids2 has encouraged the scienti®c com-
munity to persue the preparation of analogs, along with
the search for novel, short and ef®cient synthetic routes.3
Towards this end, two main strategies have been commonly
employed, as depicted in Fig. 1, both of them featuring the
construction of ring C in the ®nal step of the synthesis: -i)
reductive amination of 2-aryltetralones 2 and subsequent
heterocyclization,4 and -ii) the intramolecular biaryl
coupling of benzylnaphthylamines of type 3 bearing the
adequate functional group -FG) in the benzyl ring. In the
During the last years, considerable attention has been
devoted to the chemistry of hypervalent iodine reagents as
a powerful tool for organic synthetic chemists.8 Among
them, easily handling PIFA and PIDA -phenyliodine-III)-
diacetate) have been frequently used as radical promoters8b
to generate alkoxy,9 aminyl10 and azidyl11 radicals starting
from the corresponding alcohols, amines and azides, respec-
tively. They have been also used for the generation of arylic
radical-cations via a SET mechanism12 showing the same
reactivity than other oxidants as, for example, Tl-III), V-V),
Ru-IV) and Fe-III) salts, but with disminished toxicity.
Following this strategy a series of nucleophiles -azides,12,13
acetates,12 dicarbonyl compounds,12 thiophenolates14 and
thiocyanates14b) has been introduced onto electron-rich
benzene rings. In the particular case of using an aryl ring
as nucleophile, this methodology would give rise to a new
biarylic connection in an elegant and simple way -see Fig.
2).15 In fact, several reports on hypervalent iodine mediated
syntheses of different biologically active compounds
containing the biarylic moiety have appeared in the litera-
ture,16 an approach that, to our minds, is far to be deeply
extended.
Figure 1.
Therefore, in this paper we want to show new applications
of the PIFA reagent for the synthesis of the already
mentioned heterocycles of type 1 starting from properly
substituted benzylamines and benzamides.
Keywords: hypervalent iodine; PIFA; biaryl coupling; benzo[c]phenanthri-
dines; benzo[c]phenanthridinones.
Corresponding author. Tel.: 134-94-601-2577; fax: 134-94-4648500;
p
e-mail: qopdopee@lg.ehu.es
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020-01)00459-8

5404
I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
Scheme 2.
Figure 2.
2. Results and discussion
According to the general mechanistic proposal shown in
Fig. 2, the success of the synthesis will probably rely on
the nucleophilic character of one of the rings involved in the
coupling step, and on the ease of formation of the radical
cation intermediate located on the other ring. In the absence
of such nucleophilic aromatic ring, dimerization processes
may result -vide infra). Thus, we ®rst checked this assump-
tion studying the behaviour of amines 9a,b and amides
12a,b under oxidative cyclization conditions in the eventual
formation of the corresponding phenanthridines and
phenanthridinones.
Scheme 3.
8c -which would eventually lead to substrates with a high
nucleophilic ring), and submitted to the typical cyclization
conditions. However, in this case, dimerization instead of
intramolecular biaryl bond formation was the only process
observed even under variable temperature conditions -220
to 1408C). These results can be explained in terms of stabi-
lization of amides 12 in a trans conformation which hinders
the proximity of both rings needed for the desired intra-
molecular coupling -Schemes 2 and 3).17
Amines 9a,b were easily prepared by reductive amination of
veratraldehyde using aniline 8a and m-anisidine 8b, respec-
tively -94, 97% yield). In a typical procedure, treatment of
9a,b with 1.2 equiv. of PIFA, 2.4 equiv. of BF3´Oet2 in
CH2Cl2 at 2208C produced, after 20 min, a crude material
which was puri®ed by column chromatography -SiO2)
giving rise to phenanthridines 10a,b. These results showed,
®rstly, that a spontaneous aromatization process accompanied
the formation of the biaryl bond, as can be deduced by inspec-
tion of their 1H NMR spectra -dH-6<9.1 ppm). And, secondly,
that the presence of the less activated N-aryl ring in substrate
9a can explain the lower yield obtained in this case with
respect to 9b -63 vs 67%) -Scheme 1).
In order to circumvent this obstacle, amide 12a was trans-
formed into the corresponding N-methyl derivative 14
-NaH, MeI, THF) to ensure the required conformation. As
planned, when oxidative conditions were applied, the
expected phenanthridinone 15 was obtained in very good
yield -83%) -Scheme 4).
Analogously, amides 12a,b were prepared from the corre-
sponding benzoyl chloride 11a,b and 3,4-dimethoxyaniline
Scheme 1.
Scheme 4.

I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
5405
Scheme 6.
hydronaphthylamine 19 was benzoylated with a series of
substituted benzoyl chlorides 11a±c, and the resulting
amides 23a±c were submitted to the cyclization conditions
affording the results enlisted in Table 2. Amides 23a and
23c afforded nicely -69 and 63% yield) the corresponding
tetracycle 24a and 24c, respectively, provided the reaction
temperature was rised to dichloromethane re¯ux. Other-
wise, the starting materials were recovered completely
unchanged. These results can be explained considering
that, conversely to amides 12, the energetic barrier between
both rotamers in amides 23a and 23c can be easily over-
come at high temperature -408C). On the other hand, amide
23b resulted in a complex mixture of unidenti®ed products.
Related reports also show the lability of the methylendioxy
group under similar oxidative reaction conditions.20 To the
view of these results, the reason of the successful transfor-
mation of the methylendioxy substituted amine 21b into
phenanthridine 22b is unclear -Schemes 7 and 8).
Scheme 5.
We next moved to our second objective, namely, the forma-
tion of benzo[c]phenanthridines, benzo[c]phenanthridi-
nones and partially hydrogenated derivatives by using the
expressed methodology. Therefore, amine 17a was prepared
as shown in Scheme 5 using naphthylamine 16 and veratral-
dehyde 20a, and then N-alkylated to render amine 17b.
When both substrates were submitted to our PIFA mediated
cyclization conditions, dimers 18a,b were the only products
identi®ed -87 and 64% yield, respectively), even when the
experiments were run under high dilution conditions. The
higher nucleophilicity of the 3,4-dimethoxybenzene ring
over the naphthalene system can be argued to explain the
more favoured intermolecular dimerization reaction.
Partially hydrogenated precursors, which eventually would
give rise to a more nucleophilic pattern, were prepared using
5,6,7,8-tetrahydronaphthylamine 19 and several aromatic
aldehydes 20a±e, and the resulting amines 21a±e were
treated with PIFA under the typical conditions. As expected,
in all cases under study, the corresponding tetrahydro-
benzo[c]phenanthridines 22a±d were obtained in very
good overall yields -see Table 1) except for 21e. This is in
agreement with previous results from our group indicating
that, at least, two methoxy groups are needed for a radical
cation to be formed.18 It should be emphasized that yields
are not affected by steric crowding, as could be expected in
entry 4 due to the presence of a bulky methoxy group ortho
to the coupling position -Scheme 6).19
Finally, amides 25a,b were also tested under the same
Table 2. Series of benzophenanthridinones 24a±c prepared from amides
23a±c
Entry
Substrate
Product
R1
R2
R3
Yield -%)
69a
1
2
3
23a
23b
23c
24a
24b
24c
OMe
OCH2O
OMe
OMe
OMe
H
H
OMe
b
±
63c
a
Yield for crystallized product -Et2O).
Complex mixture of unidenti®ed products.
Yield for crystallized product -hexanes).
b
c
In order to accomplish the synthesis of partially hydro-
genated benzo[c]phenanthridinones of type 24 5,6,7,8-tetra-
Table 1. Series of benzophenanthridines 22a±e prepared from amines
21a±e
Entry Substrate Product
R1
R2
R3
R4
Yield -%)a
1
2
3
4
5
21a
21b
21c
21d
21e
22a
22b
22c
22d
22e
H
H
OMe OMe
OCH2O
OMe OMe OMe
H
H
H
77
60
74
73
H
H
OMe OMe Ome
OMe
H
H
,5b
a
Yield for crystallized product -Et2O).
Not isolated, detected by GC±MS.
b
Scheme 7.

5406
I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
and acetic acid -0.05 mL) was added to the solution. After
1 h, NaBH3CN -5 mmol) was added at 08C and the mixture
was stirred at rt until complete conversion of the starting
material -TLC, 12±18 h). Then, EtOAc -15 mL) was added
and the mixture was washed with water -3£15 mL). The
organic layer was dried -Na2SO4) and concentrated in
vacuo. The residue was crystallized from diethyl ether
yielding the corresponding benzylamines.
4.1.1. N-Phenyl-3,4-dimethoxybenzylamine 29a). -94%)
Mp 69±718C -Et2O); 1H NMR -CDCl3) 3.88 -s, 3H,
OCH3), 3.89 -s, 3H, OCH3), 3.98 -br s, 1H, NH), 4.26 -s,
2H, NCH2), 6.65 -d, Jˆ8.7 Hz, 1H, Harom), 6.71±6.76 -m,
2H, Harom), 6.82±6.94 -m, 3H, Harom), 7.16±7.23 -m, 2H,
Harom); 13C NMR -CDCl3) 48.2, 55.8, 55.9, 110.6, 111.0,
112.8, 117.5, 119.2, 131.8, 148.1, 149.0; IR -KBr) n
3366, 2935, 1602, 1515 cm21; MS -EI) m/z -rel. intensity)
243 -M1, 21), 151 -100); Anal. Calcd for C15H17NO2: C:
74.05, H: 7.04, N: 5.76. Found C: 74.02, H: 7.01, N: 5.79.
Scheme 8.
4.1.2. N-23-Methoxyphenyl)-3,4-dimethoxybenzylamine
29b). -97%) Mp 78±808C -Et2O); H NMR -CDCl3) 3.76
1
cyclization conditions. Amide 25a was prepared by
benzoylation of 1-naphthylamine, and then N-methylated
to ensure, if necessary, that the resulting derivative 25b
will adopt the required conformation for the projected intra-
molecular cyclization. In both cases, when oxidative condi-
tions were applied at solvent re¯ux temperature, the
corresponding benzo[c]phenanthridinones 26a,b were
obtained in moderate yield -42±40%). Unlike amines 17,
no dimers were detected in this ®nal experiment, which can
be explained considering that the carbonyl group in amides
25 deactivates the ring and prevents it from an inter-
molecular nucleophilic attack, favouring the target hetero-
cyclization.21
-s, 3H, OCH3), 3.88 -s, 6H, 2£OCH3), 3.97 -br s, 1H, NH),
4.24 -s, 2H, NCH2), 6.21±6.31 -m, 3H, Harom), 6.81±6.90
-m, 3H, Harom), 7.06±7.12 -m, 1H, Harom); 13C NMR
-CDCl3) 48.1, 55.0, 55.7, 55.8, 98.7, 102.5, 105.9, 110.6,
111.0, 119.6, 129.9, 131.6, 148.1, 149.0, 149.5, 160.7
-Carom) IR -KBr) n 3377, 2936, 1609, 1512 cm21; MS -EI)
m/z -rel. intensity) 243 -21), 151 -100); Anal. Calcd for
C16H19NO3: C: 70.31, H: 7.01, N: 5.12. Found C: 70.32,
H: 6.98, N: 5.14.
4.1.3. N-21-Naphthyl)-3,4-dimethoxybenzylamine 217a).
-89%) Mp 124±1268C -Et2O); H NMR -CDCl3) 3.89 -s,
1
3H, OCH3), 3.90 -s, 3H, OCH3), 4.43 -s, 2H, NCH2), 4.63
-br s, 1H, NH), 6.65 -d, Jˆ7.5 Hz, 1H, Harom), 6.87 -d,
Jˆ8.5 Hz, 1H, Harom), 6.96±7.06 -m, 2H, Harom), 7.28±
7.50 -m, 4H, Harom), 7.77±7.84 -m, 2H, Harom); 13C NMR
-CDCl3) 48.4, 55.6, 104.5, 110.3, 110.8, 111.0, 112.8, 117.5,
119.8, 124.6, 125.6, 126.5, 128.6, 131,4, 134.1, 143.2,
148.2, 149.0; IR -KBr) n 3044, 2932, 1580, 1513, 1463,
1408 cm21; MS -EI) m/z -rel. intensity) 293 -M1, 21), 152
-11), 151 -100); Anal. Calcd for C19H19NO2: C: 77.79, H:
6.53, N: 4.77. Found C: 77.76, H: 6.54, N: 4.75.
3. Conclusion
Novel applications of hypervalent iodine chemistry have
been described. The formation of the benzo[c]phenanthri-
dine skeleton by ®nal closure of ring C has been accom-
plished in very few steps and with good overall yields. The
reaction takes place under mild conditions through the
formation of a radical cation intermediate which is trapped
by an arylic nucleophile in an internal fashion. Conversely,
low nucleophilic aryl rings do not react and dimers are
formed.
4.1.4. N-[1-25,6,7,8-Tetrahydronaphthyl)]-3,4-dimethoxy-
benzylamine 221a). -77%) Mp 93±968C -Et2O); H NMR
1
-CDCl3) 1.74±1.90 -m, 4H, 2£CH2), 2.43 -t, Jˆ5.9 Hz, 2H,
CH2), 2.77 -t, Jˆ5.9 Hz, 2H, CH2), 3.89 -s, 6H, 2£OCH3),
4.29 -s, 2H, NCH2), 6.48±6.56 -m, 2H, Harom), 6.80±7.07
-m, 4H, Harom); 13C NMR -CDCl3) 22.6, 23.0, 23.8, 30.0,
48.3, 55.7, 55.8, 107.1, 110.7, 111.0, 118.4, 119.6, 112.1,
121.0, 125.9, 131.9, 137.4, 145.5, 148.0; IR -KBr) n 3424,
1590, 1512 cm21; MS -EI) m/z -rel. intensity) 297 -M1, 24),
151 -100); Anal. Calcd for C19H23NO2: C: 76.73, H: 7.80, N:
4.71. Found C: 76.69, H: 7.82, N: 4.70.
For the construction of the benzo[c]phenanthridinone
derivatives higher -rt or solvent re¯ux) temperatures are
required to ensure the proper cis conformation of the
rotamers in the starting amides. However, for the prepara-
tion of simple phenanthridinone, as in 15, N-methylated
precursors are required.
4. Experimental22
4.1.5. N-[1-25,6,7,8-Tetrahydronaphthyl)]-3,4-methyl-
endioxybenzylamine 221b). -73%) Mp 47±498C -Et2O);
1H NMR -CDCl3) 1.75±1.91 -m, 4H, 2£CH2), 2.44 -t,
Jˆ5.9 Hz, 2H, CH2), 2.77 -t, Jˆ5.9 Hz, 2H, CH2), 3.81
-br s, 1H, NH), 4.27 -s, 2H, NCH2), 5.96 -s, 2H, OCH2O),
6.46 -d, Jˆ7.8 Hz, 1H, Harom), 6.54 -d, Jˆ7.5 Hz, 1H,
4.1. General procedure for the synthesis of benzylamines
9, 17 and 21
A mixture of the aromatic amine -1.2 mmol) and the corre-
sponding aldehyde -1 mmol) was dissolved in DMF-5 mL)

I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
5407
Harom), 6.78±6.90 -m, 3H, Harom), 7.03 -dd, Jˆ7.9, 7.5 Hz,
1H, Harom); 13C NMR -CDCl3) 22.6, 23.0, 23.8, 30.0, 48.1,
100.9, 107.1, 108.2, 118.4, 120.6, 121.0, 133.4, 137.6,
146.6, 147.8; IR -KBr) n 3432, 2922, 1590 cm21; MS -EI)
m/z -rel. intensity) 281-M1, 30), 250 -12), 135 -100); Anal.
Calcd for C18H19NO2: C: 76.84, H: 6.81, N: 4.98. Found C:
76.81, H: 6.84, N: 4.97.
55.6, 60.7, 110.5, 111.0, 115.5, 120.1, 122.9, 123.5, 125.1,
128.2, 128.9, 130.9, 134.6, 147.7, 148.6, 149.7; IR -neat) n
2948, 2831, 1576, 1512, 1460, 1395 cm21; MS -EI) m/z -rel.
intensity) 307 -M1, 17), 151 -100).
4.2. General procedure for the synthesis of benzamides
12, 23and 25a
4.1.6. N-[1-25,6,7,8-Tetrahydronaphthyl)]-2,3,4-trimethoxy-
benzylamine 221c). -71%) Mp 54±568C -Et2O); H NMR
Thionyl chloride -20 mmol) was added to a solution of the
corresponding aromatic carboxylic acid -10 mmol) in
CH2Cl2 -20 mL). The mixture was heated at re¯ux for 4 h.
Removal of solvent in vacuo gave the corresponding aroyl
chlorides 11 as a residue which, without isolation, was
dissolved again in CH2Cl2 -20 mL). To this solution, the
corresponding amine -10 mmol) and pyridine -5 mL) were
added at 08C and the mixture was stirred at rt until the
conversion was complete -TLC, 10±14 h). Then, the solu-
tion was washed with saturated CuSO4, the organic layer
was dried -Na2SO4) and concentrated in vacuo. The residue
was puri®ed by crystallization to yield the following
amides.
1
-CDCl3) 1.77±1.90 -m, 4H, 2£CH2), 2.45 -dd, Jˆ6.3,
5.9 Hz, 2H, CH2), 2.79 -dd, Jˆ5.9, 5.5 Hz, 2H, CH2), 3.88
-s, 3H, OCH3), 3.93 -s, 3H, OCH3), 3.97 -s, 3H, OCH3), 4.33
-s, 2H, NCH2), 6.55 -d, Jˆ7.9 Hz, 2H, Harom), 6.66 -d,
Jˆ8.3 Hz, 1H, Harom), 7.02±7.10 -m, 2H, Harom); 13C
NMR -CDCl3) 22.3, 22.7, 23.3, 29.7, 42.7, 55.3, 60.2,
60.6, 106.6, 106.8, 117.8, 120.5, 124.7, 125.5, 136.8,
141.7, 154.4, 151.4, 152.6 -Carom); IR -KBr) n 3466, 2932,
1588, 1507, 1454, 1326 cm21; MS -EI) m/z -rel. intensity)
327 -M1, 31), 296 -3), 181 -100), 166 -39); Anal. Calcd for
C20H25NO3: C: 73.37, H: 7.70, N: 4.28. Found C: 73.38, H:
7.73, N: 4.30.
4.2.1. N-23,4-Dimethoxyphenyl)-3,4-dimethoxybenzamide
212a). -97%) Mp 179±1828C -Et2O); 1H NMR -CDCl3) 3.88
-s, 3H, OCH3), 3.92 -s, 3H, OCH3), 3.95 -s, 3H, OCH3), 3.96
-s, 3H, OCH3), 6.83±6.97 -m, 3H, Harom), 7.38 -d, Jˆ8.3 Hz,
2H, Harom), 7.51 -d, Jˆ2.3 Hz, 1H, Harom), 7.72 -br s, 1H,
NH); 13C NMR -CDCl3) 55.8, 55.9, 61.5, 62.0, 104.7, 111.1,
111.6, 115.4, 122.5, 124.6, 124.7, 126.6, 131.9, 145.5,
146.9, 152.4, 162.6; IR -KBr) n 3325, 2937, 2834, 1663,
1605, 1513, 1473 cm21; MS -EI) m/z -rel. intensity) 317
-M1, 31), 165 -100), 122 -14); Anal. Calcd for
C17H19NO5: C: 64.34, H: 6.03, N: 4.41. Found C: 64.32,
H: 6.07, N: 4.40.
4.1.7. N-[1-25,6,7,8-Tetrahydronaphthyl)]-3,4,5-trimethoxy-
benzylamine 221d). -67%) Mp 109±1118C -Et2O); 1H
NMR -CDCl3) 1.76±1.89 -m, 4H, 2£CH2), 2.44 -dd,
Jˆ6.3, 5.9 Hz, 2H, CH2), 2.76 -t, Jˆ5.9 Hz, 2H, CH2),
3.85 -s, 3H, OCH3), 3.86 -s, 6H, OCH3), 4.27 -s, 2H,
NCH2), 6.48 -d, Jˆ8.3 Hz, 1H, Harom), 6.55 -d, Jˆ7.5 Hz,
1H, Harom), 6.64 -s, 2H, Harom), 7.00±7.04 -m, 1H, Harom);
13C NMR -CDCl3) 22.6, 23.0, 23.8, 30.0, 48.9, 55.0, 60.6,
104.3, 107.1, 118.5, 121.0, 126.0, 135.3, 136.8, 137.5,
145.7, 153.3; IR -KBr) n 3427, 2930, 1589, 1503, 1461,
1419, 1329 cm21; MS -EI) m/z -rel. intensity) 327 -21),
312 -1), 181 -100); Anal. Calcd for C20H25NO3: C: 73.37,
H: 7.70, N: 4.28. Found C: 73.33, H: 7.68, N: 4.25.
4.2.2. N-23,4-Dimethoxyphenyl)benzamide 212b). -94%)
Mp 170±1728C -Et2O); H NMR -CDCl3) 3.87 -s, 3H,
1
4.1.8. N-[1-25,6,7,8-Tetrahydronaphthyl)]-3-methoxy-
benzylamine 221e). -63%) H NMR -CDCl3) 1.77±1.90
OCH3), 3.89 -s, 3H, OCH3), 6.83 -d, Jˆ8.7 Hz, 1H,
Harom), 6.99 -dd, Jˆ8.7, 2.3 Hz, 1H, Harom), 7.43±7.54 -m,
3H, Harom), 7.84±7.88 -m, 3H, Harom); 13C NMR -CDCl3)
55.7, 55.9, 105.1, 111.1, 112.2, 126.9, 128.6, 131.5, 131.6,
134.8, 145.8, 148.9, 165.7; IR -KBr) n 3354, 1649, 1513,
1449 cm21; MS -EI) m/z -rel. intensity) 257 -M1, 49), 242
-2), 105 -100); Anal. Calcd for C15H15NO3: C: 70.02, H:
5.88, N: 5.44. Found C: 69.99, H: 5.89, N: 5.47.
1
-m, 4H, 2£CH2), 2.44 -t, Jˆ6.3, 5.9 Hz, 2H, CH2), 2.76 -t,
Jˆ6.3, 5.9 Hz, 2H, CH2), 3.81 -s, 3H, OCH3), 4.30 -s, 2H,
NCH2), 6.46 -d, Jˆ7.8 Hz, 1H, Harom), 6.53 -d, Jˆ7.5 Hz,
1H, Harom), 6.84 -dd, Jˆ8.5, 2.0 Hz, 1H, Harom), 6.95±7.04
-m, 3H, Harom), 7.24±7.30 -m, 1H, Harom); 13C NMR
-CDCl3) 22.6, 23.0, 23.7, 30.0, 48.2, 55.0, 107.1, 112.0,
118.3, 119.6, 120.9, 125.9, 129.5, 137.4, 141.2, 145.6,
159.7; IR -neat) n 3435, 1588, 1489, 1465, 1314 cm21
;
4.2.3. N-[1-25,6,7,8-Tetrahydronaphthyl)]-3,4-dimethoxy-
benzamide 223a). -91%) Mp 163±1658C -Et2O); H NMR
MS -EI) m/z -rel. intensity) 267 -M1, 100), 252 -5), 236
-22), 146 -73), 121 -84).
1
-CDCl3) 1.80±1.87 -m, 4H, 2£CH2), 2.68 -t, Jˆ5.8 Hz, 2H,
CH2), 2.81 -t, Jˆ5.8 Hz, 2H, CH2), 3.95 -s, 3H, OCH3), 3.96
-s, 3H, OCH3), 6.90±6.97 -m, 2H, Harom), 7.17 -t, Jˆ7.9 Hz,
1H, Harom), 7.39 -d, Jˆ8.3 Hz, 1H, Harom), 7.52 -s, 1H,
Harom), 7.60 -br s, 1H, NH), 7.77 -d, Jˆ7.5, 1H, Harom);
13C NMR -CDCl3) 22.4, 22.8, 24.5, 29.7, 55.9, 110.2,
110.7, 119.2, 120.5, 125.8, 126.3, 127.6, 128.5, 135.4,
138.0, 149.1, 151.9, 165.2; IR -KBr) n 3312, 1561,
1501 cm21; MS -EI) m/z -rel. intensity) 311 -M1, 16), 165
-100), 146 -19); Anal. Calcd for C19H21NO3: C: 73.29, H:
6.80, N: 4.50. Found C: 73.33, H: 6.82, N: 4.48.
4.1.9. N-Methyl-N-21-naphthyl)-3,4-dimethoxybenzyl-
amine 217b). HCHO -aq. 37%, 2 mmol) was added to a
solution of amine 17a in MeCN -15 mL) and, after stirring
for 30 min, NaBH3CN -5 mmol) was added at 08C. Then,
the mixture was stirred at rt for 12 h, water -15 mL) was
added and extracted with CH2Cl2 -3£15 mL). The combined
extracts were dried -Na2SO4) and evaporated. The residue
was chromatographed -Hex:EtOAc, 1:1) yielding pure
1
amine 17b as an oil -78%). H NMR -CDCl3) 2.84 -s, 3H,
NCH3), 3.87 -s, 3H, OCH3), 3.91 -s, 3H, OCH3), 4.29 -s, 2H,
NCH2), 6.86±7.08 -m, 3H, Harom), 7.12 -d, Jˆ7.5 Hz, 1H,
Harom), 7.41±7.76 -m, 4H, Harom), 7.88±7.1 -m, 1H, Harom),
8.44±8,47 -m, 1H, Harom); 13C NMR -CDCl3) 41.3, 55.5,
4.2.4. N-[1-25,6,7,8-Tetrahydronaphthyl)]-3,4-methyl-
endioxybenzamide 223b). -90%) Mp 182±1848C -Et2O);
1H NMR -CDCl3) 1.73±1.86 -m, 4H, 2£CH2), 2.65 -t,

5408
I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
Jˆ5.9 Hz, 2H, CH2), 2.80 -t, Jˆ5.9 Hz, 2H, CH2), 6.05 -s,
2H, OCH2O), 6.87 -d, Jˆ7.9 Hz, 1H, Harom), 6.93 -d,
Jˆ8.0 Hz, 1H, Harom), 7.15 -dd, Jˆ7.5, 7.0 Hz, 1H, Harom),
7.36±7.42 -m, 2H, Harom), 7.54 -br s, 1H, NH), 7.74 -d,
Jˆ7.9 Hz, 1H, Harom); 13C NMR -DMSO-d6) 22.4, 22.7,
24.5, 29.4, 102.0, 107.8, 108.1, 122.8, 124.5, 125.3, 127.1,
128.6, 133.2, 136.3, 137.7, 147.6, 150.1, 164.6; IR -KBr) n
3268, 1920, 1647, 1481 cm21; MS -EI) m/z -rel. intensity)
295 -M1, 16), 149 -100), 146 -47), 121 -21); Anal. Calcd for
C18H17NO3: C: 73.20, H: 5.80, N: 4.74. Found C: 73.21, H:
5.79, N: 4.73.
6.85 -dd, Jˆ8.3, 1.6 Hz, 1H, Harom), 6.97 -d, Jˆ6.7, 1H,
Harom), 7.15 -t, Jˆ7.7 Hz, 1H, Harom), 7.37±7.54 -m, 2H,
Harom), 7.59 -d, Jˆ 8.3 Hz, 1H, Harom), 7.75 -d, Jˆ7.9 Hz,
1H, Harom), 7.98 -d, Jˆ8.3 Hz, 1H, Harom); 13C NMR
-CDCl3) 32.2, 54.7, 55.1, 109.4, 110.8, 121.3, 122.3,
125.4, 125.8, 126.1, 127.0, 127.4, 127.5, 128.3, 129.6,
134.1, 141.4, 147.1, 148.6, 170.8 -C); IR -KBr) n 3055,
3000, 2933, 2834, 1637, 1581, 1513, 1418, 1355 cm21
;
MS -EI) m/z -rel. intensity) 321 -M1, 21), 165 -100);
Anal. Calcd for C20H19NO3: C: 74.75, H: 5.96, N: 4.36.
Found C: 74.71, H: 5.94, N: 4.39.
4.2.5. N-[1-25,6,7,8-Tetrahydronaphthyl)]-3,4,5-trimethoxy-
benzamide 223c). -94%) Mp 174±1768C -Et2O); H NMR
4.4. General procedure for the oxidative coupling
1
-CDCl3) 1.73±1.85 -m, 4H, 2£CH2), 2.65 -t, Jˆ5.9 Hz, 2H,
CH2), 2.79 -t, Jˆ5.9 Hz, 2H, CH2), 3.90 -s, 9H, 3£OCH3),
6.95 -d, Jˆ 7.5 Hz, 1H, Harom), 7.08 -s, 2H, Harom), 7.11±
7.18 -m, 1H, Harom), 7.63±7.67 -m, 2H, Harom, NH); 13C
NMR -CDCl3) 22.4, 22.8, 24.5, 29.7, 56.2, 60.9, 104.4,
120.7, 125.8, 126.5, 128.8, 130.5, 135.2, 138.1, 141.0,
153.2, 165.4; IR -KBr) n 3272, 1643, 1584 cm21; MS -EI)
m/z -rel. intensity) 341 -M1, 15), 195 -100), 146 -19); Anal.
Calcd for C20H23NO4: C: 70.36, H: 6.79, N: 4.10. Found C:
70.40, H: 6.77, N: 4.12.
A solution of PIFA -1.2 mmol) and BF3´OEt2 -2.4 mmol) in
CH2Cl2 -10 mL) was added to a solution of the correspond-
ing substrate -1 mmol) in CH2Cl2 -15 mL) -at 2208C for
amines 9, 21 and amide 14, and at solvent re¯ux for amides
12, 23 and 25). After 20 min, at the same temperature, the
crude was allowed to rise rt, and the solvent was removed in
vacuo. The residue was subjected to ¯ash chromatography
yielding the corresponding product.
4.4.1. 8,9-Dimethoxyphenanthridine 210a).23 -63%) 1H
NMR -CDCl3) 4.08 -s, 3H, OCH3), 4.15 -s, 3H, OCH3),
7.38 -s, 1H, Harom), 7.65±7.72 -m, 2H, Harom), 7.89 -s, 1H,
Harom), 8.17 -d, Jˆ7.4 Hz, 1H, Harom), 8.45 -dd, Jˆ8.9,
7.4 Hz, 1H, Harom), 9.18 -s, 1H, Harom); 13C NMR -CDCl3)
56.0, 56.1, 101.6, 107.7, 121.5, 121.6, 121.7, 126.6, 127.8,
128.2, 129.7, 149.9, 151.4, 153.0; IR -neat) n 2923,
1504 cm21; MS -EI) m/z -rel. intensity) 239 -M1, 100),
224 -17), 196 -39).
4.2.6. N-21-Naphthyl)-3,4-dimethoxybenzamide 225a).
-89%) Mp 143±1468C -Et2O); H NMR -CDCl3) 3.95 -s,
1
3H, OCH3), 3.96 -s, 3H, OCH3), 6.93 -d, Jˆ8.3 Hz, 1H,
Harom), 7.47±7.57 -m, 5H, Harom), 7.73±7.92 -m, 3H,
Harom), 7.97 -d, Jˆ7.9 Hz, 1H, Harom), 8.21 -s, 1H, NH);
13C NMR -CDCl3) 56.0, 110.2, 110.8, 119.5, 120.8, 121.3,
125.7, 126.3, 127.3, 127.6, 128.7, 132.5, 134.1, 149.1,
152.0, 165.9; IR -neat) n 3295, 3053, 2932, 1642, 1597,
1402 cm21; MS -EI) m/z -rel. intensity) 307 -M1, 20), 165
-100), 137 -10); Anal. Calcd for C19H17NO3: C: 74.25, H:
5.58, N: 4.56. Found C: 74.21, H: 5.55, N: 4.53.
1
4.4.2. 3,8,9-Trimethoxyphenanthridine 210b). -69%) H
NMR -CDCl3) 3.97 -s, 3H, OCH3), 4.04 -s, 3H, OCH3),
4.11 -s, 3H, OCH3), 7.24±7.30 -m, 2H, Harom), 7.54 -d,
Jˆ2.3 Hz, 1H, Harom), 7.75 -s, 1H, Harom), 8.30 -d,
Jˆ9.1 Hz, 1H, Harom), 9.09 -s, 1H, Harom); 13C NMR
-CDCl3) 55.5, 56.0, 56.1, 101.2, 107.6, 109.4, 117.9,
122.9, 149.2, 127.3, 128.6, 130.9, 145.3, 151.9, 153.1,
159.4; IR -neat) n 2924, 1616, 1501 cm21; MS -EI) m/z
-rel. intensity) 269 -M1, 100), 254 -36), 226 -22).
4.3. General procedure for the N-methylation of amides
MeI -8 mmol) was added to a solution of the corresponding
amide in THF-20 mL). This mixture was added to a cooled
-08C) suspension of NaH -2.5 mmol) in THF-5 mL) and
stirred at room temperature during 20 min until total
consumption of the starting material -TLC). Then, water
-20 mL) was added slowly, the organic phase was separated,
and the aqueous phase was extracted with EtOAc
-3£25 mL). The combined extracts were dried -Na2SO4)
and evaporated yielding the corresponding N-methylamide.
4.4.3. 2,20-Bis-[4,5-dimethoxy-N-23,4-dimethoxybenzoyl)]-
aniline 213a). -92%) Mp 244±2468C -Et2O); 1H NMR
-CDCl3) 3.83 -s, 6H, 2£OCH3), 3.86 -s, 12H, 4£OCH3),
4.00 -s, 6H, 2£OCH3), 6.78 -d, Jˆ8.3 Hz, 2H, Harom), 6.81
-s, 2H, Harom), 7.01 -dd, Jˆ8.3, 1.8 Hz, 2H, Harom), 7.15 -d,
Jˆ1.8 Hz, 2H, Harom), 7.78 -s, 2H, 2£NH), 8.23 -s, 2H,
Harom); 13C NMR -CDCl3) 55.7, 55.9, 56.0, 105.3, 109.6,
111.4, 112.7, 118.7, 119.4, 126.5, 129.8, 145.7, 148.9,
152.0, 164.8; Anal. Calcd for C34H36N2O10: C: 64.55, H:
5.74, N: 4.43. Found C: 65.59, H: 5.71, N: 4.39.
4.3.1. N-23,4-Dimethoxyphenyl)-N-methyl-3,4-dimethoxyl-
benzamide 214). -77%) H NMR -CDCl3) 3.31 -s, 3H,
1
NCH3), 3.55 -s, 3H, OCH3), 3.58 -s, 3H, OCH3), 3.66 -s,
3H, OCH3), 3.68 -s, 3H, OCH3), 6.51 -m, 4H, Harom), 6.76
-m, 2H, Harom); 13C NMR -CDCl3) 38.4, 55.2, 55.3, 55.5,
109.4, 110.1, 110.6, 11.7, 118.5, 122.0, 127.6, 138.1, 147.0,
147.4, 148.7, 149.5, 169.6; IR -neat) n 2936, 2834, 1642,
1598, 1510 cm21; MS -EI) m/z -rel. intensity) 331 -M1, 31),
165 -100).
4.4.4. 2,20-Bis-24,5-dimethoxy-N-benzoyl)aniline 213b).
-67%) Mp 135±1378C -Et2O); H NMR -CDCl3) 3.82 -s,
1
6H, 2£OCH3), 3.96 -s, 6H, 2£OCH3), 6.78 -s, 2H, Harom),
7.32±7.72 -m, 10H, Harom), 7.91 -br s, 2H, 2£NH), 8.05 -s,
2H, Harom); 13C NMR -CDCl3) 56.0, 56.1, 106.4, 112.6,
126.7, 128.7, 129.4, 131.8, 134.1, 146.1, 149.1, 165.6; IR
-KBr) n 3311, 2934, 1648, 1517 cm21. Anal. Calcd for
C30H28N2O6: C: 76.30, H: 5.51, N: 5.47. Found C: 76.28,
H: 5.48, N: 5.50.
4.3.2. N-Methyl-N-21-naphthyl)-3,4-dimethoxybenzamide
225b). -87%) Mp 104±1068C -Et2O); 1H NMR -CDCl3) 3.15
-s, 3H, NCH3), 3.42 -s, 3H, OCH3), 3.53 -s, 3H, OCH3), 6.34
-d, Jˆ8.3 Hz, 1H, Harom), 6.66 -d, Jˆ1.6 Hz, 1H, Harom),

I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
5409
4.4.5. 5-Methyl-2,3,8,9-tetramethoxyphenanthridin-6-one
215). -83%) Mp 189±1918C -Et2O); 1H NMR -CDCl3) 3.77
-s, 3H, NCH3), 4.01 -s, 9H, 3£OCH3), 4.07 -s, 3H, OCH3),
6.78 -s, 1H, Harom), 7.29, -s, 1H, Harom), 7.41 -s, 1H, Harom),
7.83 -s, 1H, Harom); 13C NMR -CDCl3) 30.1, 56.0, 56.1, 56.5,
98.4, 101.7, 104.9, 108.9, 111.7, 118.5, 128.1, 132.3, 144.9,
148.9, 150.0, 153.0, 161.3; IR -KBr) n 2916, 1614, 1580,
1505 cm21; MS -EI) m/z -rel. intensity) 329 -M1, 100), 314
-44), 286 -46); Anal. Calcd for C18H19NO5: C: 65.64, H:
5.81, N: 4.25. Found C: 65.66, H: 5.79, N: 4.22.
CH2), 3.41 -t, Jˆ5.5 Hz, 2H, CH2), 4.01 -s, 3H, OCH3), 4.11
-s, 3H, OCH3), 4.13 -s, 3H, OCH3), 7.36 -d, Jˆ8.5 Hz, 1H,
Harom), 7.66 -s, 1H, Harom), 8.20 -d, Jˆ8.5 Hz, 1H, Harom),
9.52 -s, 1H, Harom); 13C NMR -CDCl3) 22.9, 23.1, 25.4, 30.1,
56.1, 61.3, 62.1, 97.6, 118.9, 128.3, 116.0, 120.9, 130.7,
135.5, 137.5, 140.7, 146.0, 150.2 156.8; IR -neat) n 2923,
2849, 1602, 1474, 1369, 1260 cm21; MS -EI) m/z -rel. inten-
sity) 323 -M1, 100), 208 -19); Anal. Calcd for C20H21NO3:
C: 74.28, H: 6.55, N: 4.33. Found C: 74.30, H: 6.56, N: 4.31.
4.4.11. 8,9,10-Trimethoxy-1,2,3,4-tetrahydrobenzo[c]-
phenanthridine 222d). -73%) Mp 137±1408C -Et2O); H
1
4.4.6.
2,20-Bis-[4,5-dimethoxy-N-21-naphthyl)]benzyl-
amine 218a). -87%) 1H NMR -CDCl3) 3.92 -s, 12H,
4£OCH3), 4.49 -s, 4H, 2£NCH2), 4.71 -br s, 2H, 2£NH),
6.78 -d, Jˆ7.5 Hz, 2H, Harom), 6.91 -d, Jˆ8.7 Hz, 2H,
Harom), 7.05±7.07 -m, 4H, Harom), 7.23±7.49 -m, 8H,
Harom), 7.91 -d, Jˆ8.3 Hz, 2H, Harom); 13C NMR -CDCl3)
48.7, 55.9, 56.2, 104.4, 111.0, 111.1, 119.9, 120.0, 123.2,
124.5, 125.6, 127.6, 128.5, 128.9, 131.6, 142.7, 148.3,
NMR -CDCl3) 1.91±1.99 -m, 4H, 2£CH2), 2.99 -t,
Jˆ5.9 Hz, 2H, CH2), 3.40 -t, Jˆ5.9 Hz, 2H, CH2), 4.01 -s,
3H, OCH3), 4.06 -s, 3H, OCH3), 4.08 -s, 3H, OCH3), 7.25 -s,
1H, Harom), 7.40 -d, Jˆ8.9 Hz, 1H, Harom), 9.11 -d,
Jˆ8.9 Hz, 1H, Harom), 9.19 -s, 1H, Harom); 13C NMR
-CDCl3) 22.9, 23.2, 25.6, 30.0, 56.1, 60.4, 61.3, 105.0,
122.2, 128.9, 121.2, 123.0, 123.5, 134.7, 136.9, 142.0,
146.4, 150.7, 151.2, 152.9; IR -neat) n 2929, 2852, 1605,
1595, 1482, 1466, 1397 cm21; MS -EI) m/z -rel. intensity)
323 -M1, 100), 208 -25); Anal. Calcd for C20H21NO3: C:
74.28, H: 6.55, N: 4.33.Found C: 74.32, H: 6.52, N: 4.30.
149.1; IR -neat) n 3411, 2931, 1676, 1586, 1512 cm21
;
MS -EI) m/z -rel. intensity) 584 -M1, 35), 433 -11), 151
-100).
4.4.7. 2,20-Bis-[4,5-dimethoxy-N-methyl-N-21-naphthyl)]-
benzylamine 218b). -64%) H NMR -CDCl3) 3.37 -s, 6H,
1
4.4.12. 8,9-Dimethoxy-1,2,3,4-tetrahydrobenzo[c]phe-
nanthridin-6-one 224a). -69%) Mp 171±1738C -Et2O); H
1
2£NCH3), 3.65 -s, 6H, 2£OCH3), 3.71 -s, 6H, 2£OCH3),
4.75 -s, 2£NCH2), 6.55 -d, Jˆ8.5 Hz, 2H, Harom), 6.70±6.73
-m, 4H, Harom), 7.37±7.57 -m, 8H, Harom), 7.73±7.82 -m, 2H,
Harom), 8.33 -d, Jˆ7.5 Hz, 2H, Harom); 13C NMR -CDCl3)
42.3, 55.5, 55.7, 62.6, 110.5, 113.0, 121.4, 122.9, 123.4,
124.7, 126.7, 126.9, 127.7, 128.9, 134.4, 148.5, 149.5; IR
-neat) n 2926, 1593, 1571 cm21
NMR -CDCl3) 1.82±2.17 -m, 4H, 2£CH2), 2.74 -t,
Jˆ6.0 Hz, 2H, CH2), 2.88 -t, Jˆ6.0 Hz, 2H, CH2), 4.04 -s,
3H, OCH3), 4.10 -s, 3H, OCH3), 7.03 -d, Jˆ 8.3 Hz, 1H,
Harom), 7.59 -s, 1H, Harom), 7.86 -s, 1H, Harom), 7.88 -d,
Jˆ8.3 Hz, 1H, Harom), 8.60 -br s, 1H, NH); 13C NMR
-DMSO-d6) 21.9, 22.5, 23.4, 24.6, 55.7, 55.8, 93.6, 109.3,
112.0, 119.7, 121.1, 129.0, 132.8, 148.3, 149.1, 151.3,
4.4.8. 8,9-Dimethoxy-1,2,3,4-tetrahydrobenzo[c]phenan-
thridine 222a). -77%) Mp 149±1518C -Et2O); H NMR
153.5, 159.9; IR -KBr) n 3170, 2918, 1636, 1604 cm21
;
MS -EI) m/z -rel. intensity) 309 -M1, 100), 294 -32);
Anal. Calcd for C19H19NO3: C: 73.77, H: 6.19, N: 4.53.
Found C: 73.70, H: 6.23, N: 4.50.
1
-CDCl3) 1.90±1.99 -m, 4H, 2£CH2), 2.97 -t, Jˆ5.8 Hz,
2H, CH2), 3.40 -t, Jˆ5.9 Hz, 2H, CH2), 4.06 -s, 3H,
OCH3), 4.13 -s, 3H, OCH3), 7.32 -s, 1H, Harom), 7.33 -d,
Jˆ8.5 Hz, 1H, Harom), 7.84 -s, 1H, Harom), 8.19 -d,
Jˆ8.5 Hz, 1H, Harom), 9.14 -s, 1H, Harom); 13C NMR
-CDCl3) 22.9, 23.1, 25.3, 30.1, 55.9, 56.0, 101.5, 107.3,
118.5, 128.3, 121.2, 121.3, 128.5, 135.3, 136.6, 142.3,
4.4.13. 8,9,10-Trimethoxy-1,2,3,4-tetrahydrobenzo[c]-
phenanthridin-6-one 224c). -63%) Mp 220±2228C
-Hexanes); H NMR -CDCl3) 1.82±1.88 -m, 2H, CH2),
1
1.96±2.08 -m, 2H, CH2), 2.76 -t, Jˆ6.1 Hz, 2H, CH2),
2.88 -t, Jˆ6.1 Hz, 2H, CH2), 3.94 -s, 3H, OCH3), 4.02 -s,
3H, OCH3), 4.04 -s, 3H, OCH3), 7.03 -d, Jˆ8.7 Hz, 1H,
Harom), 7.86 -s, 1H, Harom), 8.61 -br s, 1H, NH), 8.84 -d,
Jˆ8.7 Hz, 1H, Harom); 13C NMR -CDCl3) 22.2, 22.7, 23.7,
29.9, 56.1, 60.4, 61.2, 105.3, 107.2, 116.0, 122.1, 122.6,
124.1, 125.2, 138.4, 148.3, 151.5, 153.0, 162.2; IR -neat)
n 2925, 1652, 1598 cm21; MS -EI) m/z -rel. intensity) 339
-M1, 100), 324 -54), 212 -38); Anal. Calcd for C20H21NO4:
C: 70.78, H: 6.24, N: 4.13. Found C: 70.81, H: 6.19, N: 4.52.
149.9, 150.0, 152.6; IR -neat) n 2930, 1613, 1444 cm21
;
MS -EI) m/z -rel. intensity) 293 -M1, 100), 278 -33);
Anal. Calcd for C19H19NO2: C: 77.79, H: 6.53, N: 4.77.
Found C: 77.82, H: 6.50, N: 4.74.
4.4.9.
8,9-Methylendioxy-1,2,3,4-tetrahydrobenzo[c]-
1
phenanthridine 222b). -60%) Mp 127±1298C -Et2O); H
NMR -CDCl3) 1.91±1.95 -m, 4H, 2£CH2), 2.97 -t,
Jˆ5.6 Hz, 2H, CH2), 3.39 -t, Jˆ5.6 Hz, 2H, CH2), 6.15 -s,
2H, OCH2O), 7.32 -s, 1H, Harom), 7.36 -d, Jˆ8.5 Hz, 1H,
Harom), 7.89 -s, 1H, Harom), 8.14 -d, Jˆ8.5 Hz, 1H, Harom),
9.10 -s, 1H, Harom); 13C NMR -CDCl3) 22.9, 25.4, 29.7, 30.1,
99.8, 101.7, 105.2, 107.1, 108.3, 118.9, 122.5, 128.5, 135.5,
147.7, 150.2, 151.3; IR -neat) n 2918, 1465, 1438,
1390 cm21; MS -EI) m/z -rel. intensity) 377 -M1, 100),
262 -47); Anal. Calcd for C18H15NO2: C: 77.96, H: 5.45,
N: 5.05. Found C: 77.98, H: 5.41, N: 5.09.
4.4.14. 8,9-Dimethoxybenzo[c]phenanthridin-6-one 226a).
-42%) Mp .3008C -Hexanes) 1H NMR -CDCl3) 4.00 -s, 3H,
OCH3), 4.09 -s, 3H, OCH3), 7.04 -d, Jˆ8.5 Hz, 1H, Harom),
7.35 -m, 1H, Harom), 7.48 -d, Jˆ8.5 Hz, 1H, Harom), 7.65 -m,
1H, Harom), 7.83 -s, 1H, Harom), 7.91 -s, 1H, Harom), 7.97 -dd,
Jˆ8.3, 2.0 Hz, 1H, Harom), 8.72 -dd, Jˆ8.3, 0.6 Hz, 1H,
Harom); 13C NMR -CDCl3) 56.0, 56.1, 109.9, 111.0, 112.2,
120.1, 120.9, 122.5, 125.5, 126.3, 126.9, 127.5, 130.9,
135.9, 137.7, 147.3, 149.2, 151.7, 162.8; IR -KBr) n 2954,
1667, 1496 cm21; MS -EI) m/z -rel. intensity) 305 -M1, 100),
290 -11), 262 -29), 152 -12), 115 -15). Anal. Calcd for
4.4.10. 7,8,9-Trimethoxy-1,2,3,4-tetrahydrobenzo[c]phe-
nanthridine 222c). -74%) Mp 143±1458C -Et2O); 1H NMR
-CDCl3) 1.94±1.96 -m, 4H, 2£CH2), 2.98 -t, Jˆ5.5 Hz, 2H,

5410
I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
6. -a) Kessar, S. V.; Gupta, Y. P.; Dhingra, K.; Sharma, G. S.;
Narula, S. Tetrahedron Lett. 1977, 17, 1459±1462.
-b) Smidrkal J. Collect. Czech., Chem. Commun. 1984, 49,
1412±1430.
Â
7. -a) Castedo, L.; Guitian, E. Isoquinoline alkaloid synthesis via
Arynes. In Natural Product Chemistry, Atta-ur-Rahman, A.,
Ed.; Springer: Berlin, 1998.
C19H15NO3: C: 74.74, H: 4.95, N: 4.59. Found C: 74.76, H:
4.92, N: 4.55.
4.4.15. 5-Methyl-9,10-dimethoxybenzo[c]phenanthridin-
6-one 226b). -40%) Mp .3008C -Hexanes) 1H NMR
-CDCl3) 3.99 -s, 3H, NCH3), 4.07 -s, 3H, OCH3), 4.18 -s,
3H, OCH3), 7.26±7.60 -m, 5H, Harom), 8.00 -s, 1H, Harom),
8.23 -s, 1H, Harom), 8.49 -d, Jˆ8.7 Hz, 1H, Harom); 13C NMR
-CDCl3) 41.5, 56.3, 102.8, 108.6, 116.6, 119.7, 122.0, 124.7,
125.0, 125.7, 126.5, 127.2, 128.2, 133.6, 134.0, 135.8,
150.0, 153.6, 164.1; IR -KBr) n 2943, 1629, 1607,
1508 cm21; Anal. Calcd for C20H17NO3: C: 75.22, H:
5.37, N: 4.39. Found C: 75.19, H: 5.34, N: 4.42.
8. -a) Varvoglis, A. Hypervalent Iodine in Organic Synthesis,
Academic: New York, 1997. -b) Muraki, T.; Togo, H.;
Yokoyama, M. Rev. Heteroatoms Chem. 1997, 17, 213±243.
-c) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271±1287.
9. -a) Ellwood, C. W.; Pattenden, N. G. Tetrahedron Lett. 1991,
32, 1591±1594. -b) Mowbray, C. E.; Pattenden, N. G.
Tetrahedron Lett. 1993, 34, 127±130. -c) Marchand, A. P.;
Rajadopal, D.; Burrit, A.; Bott, S.; Watson, W. H.; Sun, D.
Tetrahedron 1995, 51, 11673±11680. -d) Togo, H.; Muraki,
T.; Hoshina, Y.; Yamaguchi, K.; Yokoyama, M. J. Chem.
Soc., Perkin Trans. 1 1997, 787±793.
Acknowledgements
Financial support from the University of the Basque
Country -Project UPV 170.310-G37/98), Basque Govern-
ment -PI 96/53) and MEC -PB97-0600) is gratefully
acknowledged. One of us -I. M.) acknowledges the
10. Rawal, V. H.; Iwasa, S. Tetrahedron Lett. 1996, 37, 2441±
2444.
11. Magnus, P.; Lacour, J.; Evans, P. A.; Roe, M. B.; Hulme, C.
J. Am. Chem. Soc. 1996, 118, 3406±3418.
Â
Ministerio de Educacion y Cultura -Spain) for a grant.
12. -a) Kita, Y.; Tohma, H.; Hatanaka, K.; Takada, T.; Fujita, S.;
Mitoh, S.; Sakurai, H.; Oka, S. J. Am. Chem. Soc. 1994, 116,
3684±3691. -b) Kita, Y.; Takada, T.; Ibaraki, M.; Gyoten, M.;
Mihara, S.; Fujita, S.; Tohma, H. J. Org. Chem. 1996, 61,
223±227. -c) Arisawa, M.; Ramesh, N. G.; Nakajima, M.;
Tohma, H.; Kita, Y. J. Org. Chem. 2001, 66, 59±56.
13. -a) Kita, Y.; Tohma, H.; Inagaki, M.; Hatanaka, K.; Kikuchi,
K.; Yakura, T. Tetrahedron Lett. 1991, 32, 4321±4324.
-b) Kita, Y.; Tohma, H.; Takada, T.; Mitoh, S.; Fujita, S.;
Gyoten, M. Synlett 1994, 427±428.
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21. The dif®culties encountered in the preparation of some of the

I. Moreno et al. / Tetrahedron 57 02001) 5403±5411
5411
 Â
example, Gonzalez, C.; Guitian, E.; Castedo, L. Tetrahedron
tetracycles mentioned in this paper can, in principle, be over-
come considering the synthetic relationship between phenan-
thridines and phenanthridinones. Thus, for the transformation
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 Â
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Â
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Á
V.; Chiacchio, U.; Pistara, V.; Resci®na, A. Tetrahedron
1998, 54, 9187±9194; and for the transformation of 6-
methoxyphenanthridines into phenanthridinones see, for