One-pot synthesis of benzo[a]phenanthridin-5-ones by photoinduced cycloaddition of 3-chloroisoquinolin-1-ones with styrenes

Article abstract of DOI:10.1016/j.tetlet.2010.05.037

One-pot synthesis of benzo[a]phenanthridin-5-ones and benzo[k] phenanthridin-6-ones in fairly good yields was achieved by the photocycloaddition reactions of 3-chloroisoquinolin-1-ones and 3-chloroquinolin-2-ones with styrenes. The reactions were proceeded via photoinduced dechlorinative coupling of 3-chloroisoquinolin-1-ones and 3-chloroquinolin-2-ones with styrenes and subsequent photocyclization, oxidative aromatization.

Full text of DOI:10.1016/j.tetlet.2010.05.037

Tetrahedron Letters 51 (2010) 3748–3751
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
One-pot synthesis of benzo[a]phenanthridin-5-ones by photoinduced
cycloaddition of 3-chloroisoquinolin-1-ones with styrenes
*
Bing Li, Bing Han, Zong-jun Shi, Yu-wei Ren, Shen-ci Lu, Wei Zhang
State Key Laboratory of Applied Organic Chemistry and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 March 2010
Revised 9 May 2010
Accepted 11 May 2010
Available online 31 May 2010
One-pot synthesis of benzo[a]phenanthridin-5-ones and benzo[k]phenanthridin-6-ones in fairly good
yields was achieved by the photocycloaddition reactions of 3-chloroisoquinolin-1-ones and 3-chloro-
quinolin-2-ones with styrenes. The reactions were proceeded via photoinduced dechlorinative coupling
of 3-chloroisoquinolin-1-ones and 3-chloroquinolin-2-ones with styrenes and subsequent photocycliza-
tion, oxidative aromatization.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
One-pot synthesis
Photocycloaddition
Benzo[a]phenanthridin-5-one
Benzo[k]phenanthridin-6-one
3-Chloroisoquinolin-1-one
3-Chloroquinolin-2-one
The photochemistry of aryl halides has long received great
attention due to their values in the organic synthesis and the reac-
tion mechanistic investigation.1 Photoinduced addition reactions
of aryl halogens to alkenes and arenes have become useful tools
for the synthesis of aryl-substituted alkylamines, alkanols, ketones,
and biaryls.2 In this strategy, photochemistry could offer a conve-
nient access to the formation of aryl-C bonds under mild condi-
tions, via fragmentation of an Ar–X bond in aromatic derivatives
to give a trappable intermediate (e.g., an aryl radical or cation).
Recently, Albini and co-workers were engaged in the extensive re-
search on the inter- and intramolecular photoaddition reactions of
amino- and alkoxy-substituted aryl halogens to electron-rich al-
kenes, alkynes, and arenes.2a–e We have focused on inter- or intra-
molecular reactions of halogenated heterocycles with alkenes as
they hold promise for a tin-free route to polycyclic heterocycles.3
Although the photoreactions of halogenated heterocycles such as
5-halofurfural and 5-halothaphene with styrenes were investi-
gated by others,4 only stilbene-like coupling products were pro-
duced. We found that high yields of polycyclic aromatic
heterocycles benzo[a]phenanthridin-5-ones and benzo[k]phenan-
thridin-6-ones could be obtained in the photoreactions of 3-chlo-
roisoquinolin-1-ones and 3-chloroquinolin-2-ones with styrenes
(Schemes 1 and 2).
have similar skeletons to the benzophenanthridine alkaloids and
have many pharmacological properties5a–c and some applications
in material sciences.5d,e A variety of methods was reported for
the synthesis of benzo[a]phenanthridines and benzo[k]phenan-
thridines, such as photocyclization of N-(2-iodiophenyl)-2-naph-
R2
hv
Cl
R2
C5H5N
+
+
N
CH2Cl2
R1
Ph
N
N
R1
R1
O
O
O
2a R2 = H
2b R2 = Me
2c R2 = Ph
1a R1 = H
1b R1 = Me
1c R1 = Ph
3a-i
4a-c
Scheme 1. Reactions of 3-chloroisoquinolin-1-ones with styrenes.
R
hv
Cl
R
C5H5N
+
CH2Cl2
N
O
Ph
N
O
CH3
CH3
Procedures for the synthesis of benzo[a]phenanthridines and
benzo[k]phenanthridines are of interest since these compounds
6a-c
5a
2a R = H
2b R = Me
2c R = Ph
* Corresponding author. Tel.: +86 931 358 8553; fax: +86 931 891 2582.
E-mail address: zhangwei6275@lzu.edu.cn (W. Zhang).
Scheme 2. Reactions of 3-chloro-1-methylquinolin-2-one with styrenes.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.05.037

B. Li et al. / Tetrahedron Letters 51 (2010) 3748–3751
3749
Table 1
Photoreaction of 3-chloroisoquinolin-1-one (1a) and styrene (2a) under different conditions
Entry
Solvent
k >300 nm
k >200 nm
b
b
Time (h)
Convna (%)
Yield (%)
Time (h)
Convna (%)
Yield (%)
1
2
3
4
5
CH2Cl2
32
30
30
—
77
86
84
—
52
61
28
—
25
25
25
25
25
88
95
93
92
95
65
69
35
30
28
CH2Cl2/C5H5N
CH3COCH3
CH3OH
C6H6
—
—
—
a
Conversion was calculated on the basis of 1a.
Yield of isolated product based on consumed 1a.
b
thalenecarboxamide ions via SRN1 reactions;6a Bu3SnH-mediated
radical cyclization of 3-(2-iodiophenylethenyl)quinoline;6b SmI2-
mediated radical cyclization of N-(2-iodiophenyl)-2-naphthalene-
carboxamide;6c cyclocondensation of lithiated N,N-diethyl-2-tol-
uamides with benzaldimines and subsequent bromination and
AgBF4-catalyzed rearrangements of spirodihydroisoquinolones6d
and photocyclization of 3-(2-phenylethenyl)quinolin-2-ones.6e De-
spite of these developments, to the best of our knowledge, there
has been no procedure for a direct synthesis of benzo[a]phenan-
thridines and benzo[k]phenanthridines by the photocycloaddition
of isoquinolin-1-one and quinolin-2-one with olefins. Herein we
report the first one-pot synthesis of benzo[a]phenanthridin-5-ones
and benzo[k]phenanthridin-6-ones by the photochemical annula-
tion of readily available 3-chloroisoquinolin-1-one and 3-chloro-
quinolin-2-one with styrenes (Schemes 1 and 2).
We surveyed the effects of reaction conditions on the photore-
action of 3-chloroisoquinolin-1-one (1a) with styrene (2a). No
great difference was found for the photoreaction of 1a and 2a un-
der oxygen or air in solutions, but the photoreaction was greatly af-
fected by the solvents as shown in Table 1. Mixtures were
produced in all selected solvents in short time, but the yield of
3a in dichloromethane was increased after the irradiation was con-
tinued for a longer time. Solvent-mediated reaction products were
detected in methanol and benzene, which resulted in the decrease
of the yield of 3a. The conversion of 1a and the yield of 3a were in-
creased a little with the addition of base such as pyridine. More-
over the conversion of 1a and the yield of 3a were also
influenced by the reaction vessels as indicated in Table 1. A mix-
ture was produced in dichloromethane in Pyrex tubes under irradi-
ation of a medium-pressure mercury lamp (500 W), but 3a was
obtained as a main product when quartz tubes were used. Thus
irradiation in dichloromethane in quartz tubes with the addition
of pyridine was selected as the standard condition for the photore-
actions of all substrates.
Figure 1. X-ray crystal structure of 3h.
Table 3
Photoreaction of 3-chloroquinolin-2-one (5a) and styrenes (2a–c)
Entry
Reactant
R1
Product Time (h) Convna (%) Yieldb (%)
R2
H
1
2
3
5a Me 2a
5a Me 2b Me 6b
5a Me 2c Ph 6c
6a
18
20
20
98
97
97
57
65
68
a
Conversion was calculated on the basis of 5a.
Yield of isolated product based on consumed 5a.
b
A spectrum of 3-chloroisoquinolin-1-ones (1a–c) and styrenes
(2a–c) was first examined to explore the generality of this new
one-pot photochemical cycloaddition reaction. The photoreactions
were conducted under above-mentioned reaction conditions for
18–40 h and the expected benzo[a]phenanthridin-5-ones 3a–i
were obtained as major products in all cases (Table 2). The prod-
ucts were fully identified by 1H NMR, 13C NMR, and MS,7 and the
structure of 3h was further confirmed by the X-ray analysis as de-
picted in Figure 1.8 It was noticed that the conversion of 1a–c and
the yields of 3a–i were increased when the time of irradiation was
prolonged. Intermediates were produced during the reactions of
1a–c with 2a–c and these intermediates could be converted to
3a–i after prolonged irradiation except the intermediates 4a–c
which were produced in the reactions of 1a–c with 2b and led to
the great decrease of the yields of 3b, 3e, and 3h. The presence
of substituents (R1 = Me, Ph) in 1b and 1c retarded the photoreac-
tions, but substituents (R2 = Me, Ph) in 2b and 2c favored the con-
version of 1a–c.
Table 2
Photoreaction of 3-chloroisoquinolin-1-ones (1a–c) and styrenes (2a–c)
Entry
Reactant
R1
Product Time (h) Convna (%) Yieldb (%)
R2
H
1
2
3
4
5
6
7
8
9
1a
1a
1a
H
H
H
2a
3a
25
18
25
25
28
36
40
35
35
95
93
96
85
90
96
80
85
90
69
2b Me 3b + 4a
2c Ph
25 + 50
71
3c
1b Me 2a
1b Me 2b Me 3e + 4b
1b Me 2c Ph
H
3d
60
23 + 46
82
3f
1c Ph
1c Ph
1c Ph
2a
H
3g
50
2b Me 3h + 4c
2c Ph 3i
22 + 44
63
To expand the scope of this one-pot photochemical synthesis of
polycyclic compounds, we next examined the reactions of another
reactant 3-chloroquinolin-2-one (5a) with 2a–c under similar con-
ditions (Scheme 2). As shown in Table 3, the results were very sim-
a
Conversion was calculated on the basis of 1a–c.
Yield of isolated product based on consumed 1a–c.
b

3750
B. Li et al. / Tetrahedron Letters 51 (2010) 3748–3751
Cl
H
Ph
hv
. . Cl
PhCH=CH
2
.
.
N
N
N
Cl
2a
H
H
O
O
N
O
1a
hv
Ph
OH
Ph
N
Cl
+
H
H
MeCOMe-H2
O
O
O
8
9
Ph
Ph
C H N
5
5
ET
-
N
Cl
N
-HCl
H
H
O
O
10
Ph
O
2
H
hv
hv
H
-H O
2
2
N
N
H
N
H
H
O
O
O
3a
Scheme 3. Proposal mechanism for the photoreaction 3-chloroisoquinolin-1-one with styrene.
ilar to those obtained from 3-chloroisoquinolin-1-one (1a–c) that
the photoreactions of 5 with 2a–c afforded benzo[k]phenanthri-
din-6-ones (6a–c) as the main products from dechlorinative cou-
pling, cyclization, and oxidative aromatization. All products were
fully identified by 1H NMR, 13C NMR, and MS.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.05.037.
A plausible mechanism for the formation of benzo[a]phenan-
thridin-5-one (3a) via the photoreaction of 1a with 2a is shown
in Scheme 3. The coupling of 1a with 2a was initiated by the
photoinduced C–Cl bond cleavage in 1a and subsequent addition
of the produced 3-isoquinolinyl radical to double bond of sty-
rene (2a). The homolysis of C–Cl bond to produce 3-isoquinolinyl
radical could be confirmed from the formation of the coupling
product 3-phenylisoquinolin-1-one while the photoreaction of
1a with 2a was conducted in benzene. The adduct 3-(2-chloro-
2-phenylethyl)isoquinolin-1-one (8) could be converted to cou-
pling product 3-(2-phenylethenyl)isoquinolin-1-one (10) upon
prolonged irradiation via homolysis of C–Cl bond and subsequent
electron transfer and deprotonation. Photoisomerization, photo-
cyclization, and oxidation aromatization of 10 afforded the prod-
uct 3a. It was supposed that the light of k <300 nm would be
helpful to the homolysis of 8 because the yield of 3a was higher
in quartz tube than that in Pyrex tube. In fact benzyl cation
could be easily produced from photolysis of benzyl chloride un-
der 254 nm irradiation in polar solvents and transformed to stil-
bene as observed by Sket9 and the cation-trapping product 9
was also separable when the photoreaction of 1a and 2a was
conducted in acetone–water.
References and notes
1. (a) Fagnoni, M.; Albini, A. Acc. Chem. Res. 2005, 38, 713; (b) Rossi, R. A.; Pierini, A.
B.; Penenory, A. B. Chem. Rev. 2003, 103, 71; (c) Dichiarante, V.; Fagnoni, M.
Synlett 2008, 787; (d) Fagnoni, M. Heterocycles 2003, 60, 1921; (e) D0Auria, M.
Trends Photochem. Photobiol. 1994, 3, 1; (f) Grimshaw, J.; De Silva, A. P. Chem. Soc.
Rev. 1981, 10, 181.
2. (a) Dichiarante, V.; Fagnoni, M.; Albini, A. Angew. Chem., Int. Ed. 2007, 46, 6495;
(b) Protti, S.; Fagnoni, M.; Albini, A. J. Am. Chem. Soc. 2006, 128, 10670; (c)
Dichiarante, V.; Fagnoni, M.; Mella, M.; Albini, A. Chem. Eur. J. 2006, 12, 3905; (d)
Protti, S.; Fagnoni, M.; Albini, A. Angew. Chem., Int. Ed. 2005, 44, 5675; (e) Protti,
S.; Fagnoni, M.; Mella, M.; Albini, A. J. Org. Chem. 2004, 69, 3465; (f) Fraboni, A.;
Fagnoni, M.; Albini, A. J. Org. Chem. 2003, 68, 4886; (g) Clyne, M. A.; Aldabbagh, F.
Org. Biomol. Chem. 2006, 4, 268; (h) Barolo, S. M.; Teng, X.; Cuny, G. D.; Rossi, R.
A. J. Org. Chem. 2006, 71, 8493; (i) Ho, T. I.; Ku, C. K.; LIu, R. S. H. Tetrahedron Lett.
2001, 42, 715.
3. (a) Wang, C.; Zhang, W.; Lu, S.; Wu, J.; Shi, Z. Chem. Commun. 2008, 5176; (b) Lu,
S.; Duan, X.; Shi, Z.; Li, B.; Zhang, W. Org. Lett. 2009, 11, 3902.
4. D’Auria, M.; Piancatelli, G.; Ferri, T. J. Org. Chem. 1990, 55, 4019.
5. (a) Knoerzer, T. A.; Watts, V. J.; Nichols, D. E.; Mailman, R. B. J. Med. Chem. 1995,
38, 3062; (b) Brewster, W. K.; Nichols, D. E.; Riggs, R. M.; Mottola, D. M.;
Lovenberg, T. W.; Lewis, M. H.; Mailman, R. B. J. Med. Chem. 1990, 33, 1756; (c)
Izumi, S.; Yamamoto, H. JP 2004203813 A, 2004.; (d) Demeter, A.; Berces, T.;
Hinderberger, J.; Timari, G. Photochem. Photobiol. Sci. 2003, 2, 273; (e) Breyne, O.
US 6379591, 2002.
6. (a) Bude0n, M. E.; Rossi, R. A. Tetrahedron Lett. 2007, 48, 8739; (b) Harrowven, D.
C.; Sutton, B. J.; Coulton, S. Tetrahedron 2002, 58, 3387; (c) Iwasaki, H.; Eguchi, T.;
Tsutsui, N.; Ohno, H.; Tanaka, T. J. Org. Chem. 2008, 73, 7145; (d) Jahangir, L. E.;
Fisher, R. D.; Clark, J. M. J. Org. Chem. 1989, 54, 2992; (e) Arisvaran, V.; Ramesh,
M.; Rajendran, S. P.; Shanmugam, P. Synthesis 1981, 821.
7. General procedure for the photochemical reactions: To 100 mL dry
dichloromethane were added 2.0 mmol 1a, 2.5 mmol 2a, and a drop of dry
pyridine. The solution was distributed in five 25 mL quartz tubes and irradiated
with a medium-pressure mercury lamp (500 W) at ambient temperature for
appropriate time. The progress of the reaction was monitored by TLC at regular
intervals. After 1a and other intermediates were disappeared, the solvent was
washed with water, dried on anhydrous sodium sulfate, and removed in vacuo.
The residual was separated by silica gel column chromatography eluted with
hexane/acetone 10:1(v/v) to afford 3a. The solid was further purified by
recrystallization from ethanol to give pure 3a.
In summary, an efficient one-pot synthesis of benzo[a]phe-
nanthridin-5-one and benzo[k]phenanthridin-6-one derivatives
by the photoreactions of 3-chloroisoquinolin-1-ones and 3-chlo-
roquinolin-2-ones with styrenes has been developed. To the best
of our knowledge, this is the first report on the synthesis of
these compounds via photoinduced dechlorinative annulation
of 3-chloroisoquinolin-1-ones and 3-chloroquinolin-2-ones with
styrenes.
Benzo[a]phenanthridin-8-one (3a): white solid; mp: 240–244 °C. 1H NMR
(DMSO-d6) d 7.51–7.57 (m, 2H), 7.67–7.71 (m, 2H), 7.92 (dt, J = 7.6, 1.6 Hz,
1H), 8.02 (d, J = 8.4 Hz, 2H), 8.45 (dd, J = 8.0, 1.2 Hz, 1H), 8.80 (t, J = 8.4 Hz, 2H),
12.00 (s, 1H, NH); 13C NMR (DMSO-d6) d 110.3, 116.5, 123.9, 124.3, 126.2, 126.3,
126.6, 127.1, 127.2, 128.7, 128.9, .129.8, 130.2, 131.9, 134.1,135.2, 160.3. MS m/e
(relative intensity) 245 (M+, 100), 217 (151), 216 (16), 189 (15); ESI-HRMS: m/z
calcd for C17H11NO + H+: 246.0915, found 246.0921.
Acknowledgment
We thank the National Natural Science Foundation of China
(Grant Nos. 20872056 and J0730425) for financial support.

B. Li et al. / Tetrahedron Letters 51 (2010) 3748–3751
3751
6,8-Diphenylbenzo[a]phenanthridin-5-one (3i): Pale yellow solid; mp: 222–
224 °C; 1H NMR (400 MHz, CDCl3): d = 8.90 (d, 1H, J = 8.4 Hz, ArH), 8.76 (d, 1H,
J = 8.4 Hz, ArH), 8.65 (dd, 1H, J = 8.0 Hz, 1.6 Hz, ArH), 7.91–7.84 (m, 2H, ArH),
7.67–7.63 (m, 2H, ArH), 7.60 (d, 2H, J = 7.2 Hz, ArH), 7.52–7.50 (m, 1H, ArH),
7.44–7.39 (m, 4H, ArH), 7.37–7.34 (m, 4H, ArH), 6.68 (s, 1H, ArH); 13C NMR
(100 MHz, CDCl3): d = 161.9, 141.6, 139.7, 138.2, 136.7, 134.2, 132.0, 130.3,
130.2, 129.2, 129.1, 128.9, 128.8, 128.3, 127.7, 127.3, 127.2, 127.1, 127.0, 126.9,
126.3, 124.9, 117.4, 113.2; MS (EI-m/z): 397 (M+, 34), 320 (12), 290 (6), 259 (21),
237 (4), 165 (12), 77 (100), 51 (53); ESI-HRMS: m/z calcd for C29H19NO + H+:
398.1539, found 398.1535.
J = 7.6 Hz, ArH), 3.86 (s, 3H, CH3); 13C NMR (100 MHz, CDCl3): d = 161.8, 140.4,
139.9, 138.5, 134.7, 132.0, 130.0, 130.0, 129.0, 128.8, 128.4, 128.4, 128.2, 128.0,
127.8, 127.6, 126.9, 126.4, 124.4, 123.8, 121.9, 119.3, 114.8, 30.40; MS (EI-m/z):
335 (M+, 89), 319 (2), 307 (3), 291 (10), 276 (7), 167 (100), 152 (20), 144 (10);
ESI-HRMS: m/z calcd for C24H17NO + H+: 336.1383, found 336.1378.
8. Crystal data for compound 3h (recrystallized from acetone–hexane). C24H17NO,
Mr = 335.39. Monoclinic, a = 11.7093(19) Å, b = 17.477(3) Å, c = 9.2337(15) Å,
b = 109.781(2), V = 1778.1(5) Å3, colorless plates,
space group P2 (1)/c, Z = 4,
q
= 1.253 g cmꢀ3, T = 296(2) K,
l (Mo Ka
) = 0.71073 mmꢀ1, 2hmax = 51.0°, 3298
reflections measured, 2223 unique (Rint = 0.0729) which were used in all
calculation. the final wR(F2) was 0.1191 (for all data), R1 = 0.0431. CCDC file
No. 763203.
5-Methyl-8-phenylbenzo[k]phenanthridin-6-one (6c): Pale yellow solid; mp 116–
118 °C. 1H NMR (400 MHz, CDCl3): d = 8.91 (d, 1H, J = 8.4 Hz, ArH), 8.63 (d, 1H,
J = 8.4 Hz, ArH), 8.46 (s, 1H, CH), 8.07 (d, 1H, J = 8.0 Hz, ArH), 7.65 (t, 1H,
J = 7.2 Hz, ArH), 7.61–7.50 (m, 7H, ArH), 7.47 (d, 1H, J = 7.2 Hz, ArH), 7.37 (t, 1H,
9. (a) Kosmrlj, B.; Sket, B. J. Org. Chem. 2000, 65, 6890; (b) Cristol, S. J.; Greenwald,
B. E. Tetrahedron Lett. 1976, 25, 2105.