Photoinduced tandem reactions of isoquinoline-1,3,4-trione with alkynes to build Aza-polycycles

Article abstract of DOI:10.1021/jo100218w

Photoinduced tandem reactions of isoquinoline-1,3,4-triones (3) with azaaryl substituted acetylenes (4a-4o) are described as an efficient method to build novel aza-polycycles. Most of the reactions proceeded via the tandem reaction sequence of photoinduce

Full text of DOI:10.1021/jo100218w

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Photoinduced Tandem Reactions of Isoquinoline-1,3,4-trione
with Alkynes To Build Aza-polycycles
Haitao Yu,† Jinbo Li,† Zhuangfei Kou,† Xuewen Du,† Yi Wei,† Hoong-Kun Fun,‡
Jianhua Xu,† and Yan Zhang*,†
†School of Chemistry and Chemical Engineering, Key Lab of Analytical Chemistry for Life Science,
Ministry of Education of China, Nanjing University, Nanjing, 210093, P. R. China, and
‡X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800 USM Penang, Malaysia
njuzy@nju.edu.cn
Received February 8, 2010
Photoinduced tandem reactions of isoquinoline-1,3,4-triones (3) with azaaryl substituted acetylenes
(4a-4o) are described as an efficient method to build novel aza-polycycles. Most of the reactions
proceeded via the tandem reaction sequence of photoinduced [2 þ 2] cycloaddition (the Paterno-
€
Buchi reaction)-oxetene electrocyclic ring opening-hexatriene to phenanthrene type electrocyclization-
oxidative dehydrogenation. Using these photo tandem reactions of isoquinolinetrione with acetylenes
substituted by different azaaryl rings including pyridine, pyrimidine, pyrazine, and quinoline, we were
able to obtain diverse aza-polycyclic frameworks with isoquinolinedione fused with naphthalene,
quinoline or isoquinoline, quinazoline, quinoxaline, and phenanthridine, respectively, with yields up to
85%. Regioselectivity of the [2 þ 2] photocycloadditions and the electrocyclization reactions in the
reaction sequence that leads to the formation of different aza-polycyclic ring systems is discussed.
Changing the other substitution group on the azaaryl substituted acetylenes from benzene to pyridine
or cyclopropane resulted in acetylenes with different photoreactivities with isoquinolinetrione and
improved regioselectivity to form single aza-polycyclic products.
Introduction
wise difficult to make.1 Photocycloaddition along with sub-
sequent cascade reactions has provided an expeditious way
to construct various structures1,2 including polycyclic com-
pounds such as alkaloids,1,3 polycyclic terpenoid,4 and poly-
cyclic heterocycles.1,5 Synthesis of aza-polycyclic aromatic
Photoinduced organic reactions have played important
roles in building diverse organic frameworks that are other-
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(b) Griesbeck, A. G.; Hoffmann, N.; Warzecha, K.. Acc. Chem. Res. 2007,
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DOI: 10.1021/jo100218w
r
Published on Web 03/30/2010
J. Org. Chem. 2010, 75, 2989–3001 2989
2010 American Chemical Society

Yu et al.
SCHEME 1. Bioactive Isoquinolinedione-Fused Polycyclic
Compounds
JOCArticle
compounds with diversified structure is of current research
interest6 because aza-polycycles and their ring-substituted
derivatives are important heterocycles with pharmocological
and biological activities.7 Aza-polycycles with isoquinoline-
fused ring systems have been reported to have DNA binding
and cleavage abilities.8 Aza-polycyclic analogues of amona-
fide and azonafide, such as 5,6-dihydro-4H-dibenz[de,g]-
isoquinoline-4,6-dione (1) or 5,6-dihydro-4H-quinolino-
[7,6,5-de]isoquinoline-4,6-dione (2) derivatives (Scheme 1),
have been found to have antitumor activities.9,10 It is there-
fore interesting to develop convenient methods to build aza-
polycycles with isoquinolinedione-fused moieties. Photo-
induced cascade reactions that could lead to the formation
of isoquinolinedione-fused polycyclic compounds from
readily available materials such as carbonyl compounds
and acetylenes could serve well for this purpose.
been explored extensively so far14 compared with alkenes. It
€
is known that Paterno-Buchi reactions of carbonyl com-
pounds with alkynes usually give quinone methides as the
result of rearrangements of the labile oxetenes formed by the
[2 þ 2] cycloaddition.15 In our previous work on photoin-
duced electron transfer reactions between o-diones and
€
The Paterno-Buchi reaction is the photoinduced [2 þ 2]
diverse electron donors,16,17 we found that Paterno-Buchi
cycloaddition between an nπ* excited carbonyl compound
€
and alkenes or alkynes.11 Paterno-Buchi reactions of car-
€
reactions between o-diones and acetylenes followed by sub-
sequent spontaneous thermal and photochemical transfor-
mations of the oxetene primary product may result in the
formation of complex polycyclic heterocycles.17 For exam-
ple, the photoreactions between N-acetylisatin and terminal
acetylenes were found to give novel final products such as
dispiro[oxindole[3,20]furan[30,300]oxindole]s as a result of the
tandem reactions with quinone methide formation as the
initial step.17a,b The versatile roles played by quinone methides
as intermediates in the photo tandem reactions indicated that
it is important to choose the right combination of carbonyl
compounds and acetylenes to induce desired tandem reac-
tions via quinone methide intermediates.
Isoquinoline-1,3,4-trione and its derivatives have been
known as redox mediators of photosystems I and also have
been used as herbicides.18 Recently it was reported that
isoquinoline-1,3,4-trione derivatives are potent caspase-3
inhibiotors19 and can attenuate β-amyloid-induced apopto-
sis of neuronal cells.20 As an important o-dione species,
isoquinolinetrione has been used as building block in the
bonyl compounds and alkenes have been widely investigated
both in synthetic and mechanistic aspects,12 and the regio-
selectivity and stereoselectivity of these reactions have been
of much current research interest.13 However, photocyclo-
additions of carbonyl compounds with alkynes have not
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Yu et al.
SCHEME 2. Proposed Pathway for the Photoinduced Tandem Reaction between Isoquinolinetrione and 2-(Phenylethynyl)pyridine
JOCArticle
synthesis of benzo[c]phenanthridine alkaloids.21 The C4
carbonyl group in isoquinoline-1,3,4- trione provides an
ideal photoreactive site for photoinduced reactions that
may result in diverse isoquinoline-related heterocycles. How-
ever, its photoreaction has rarely been studied. In our
preliminary study on photoreactions between isoquinoline-
trione and diphenylacetylenes,17c we observed an photo-
induced sequential reaction that provided an efficient one-pot
method to prepare dibenz[de,g]-(2H)-isoquinoline-4,6-dione
derivatives. To explore further on the applications of similar
sequential reactions to form different azaaryl-fused isoqui-
nolinedione derivative, we synthesized a series of azaaryl
substituted acetylenes and investigated their photoreactions
with 1,3,4-isoquinolinetrione 3. The reactions proceeded via
a sequential photocycloaddition-oxetene rearrangement-
cyclization-dehydrogenation sequence and resulted in the forma-
tion of novel isoquinoline-fused aza-polycyclic derivatives.
acetylenes with isoquinolinetriones. Solvent for the photo-
reactions was optimized, and reactions in acetonitrile gave
the highest conversion rate of 1,3,4-isoquinolinetrione 3
compared with reactions in benzene, acetone, and dichloro-
methane. For acetylenes with two different substitution groups,
their photoinduced tandem reactions with isoquinolinetrione
are proposed to proceed via different quinone methide inter-
mediates whose structure determines the framework of the
polycycles in the final products. For example, photolysis of
N-methyl-1,3,4-isoquinolinetrione 3 and 2-(phenylethynyl)-
pyridine 4a in acetonitrile resulted in the formation of a
quinoline fused isoquinolinedione 5a (55%) and a naphthelene
fused isoquinolinedione 6a (36%). The regioselectivity of the
initial photocycloaddition step plays a decisive role in the ratio
of naphthalene-fused isoquinolinedione derivative to other
isoquinolinedione-fused aza-polycycles in the final products.
To get accurate information on the regioselectivity involved in
the photoreactions, the reaction mixtures were analyzed by
HPLC to give the relative ratio of different products.
Results and Discussion
The photoinduced tandem reaction was proposed to pro-
ceed via the pathway shown in Scheme 2. Photoinduced
Photoreactions of Isoquinolinetrione (3) with 1-Phenyl-
2-azaarylethynes 4a-4e.
€
[2 þ 2] cycloaddition (Paterno-Buchi reaction) between the
acetylene 4a and isoquinolinetrione 3 led to formation of the
unstable spirooxetene (SOE) intermediates. Triplet state of
isoquinolinetrione 33* was confirmed to be the reactive excited
state since the presense of quencher such as styrene or quinoline
quenched the reaction effectively as we described before.17c The
€
Paterno-Buchi reaction between the excited 3 and 4a proceeded
via the two oxetene intermediates SOE1 and SOE2 with regio-
selectivity. Rearrangement of SOE1 gave the quinone methide
QM1, while SOE2 gave QM2 correspondingly. Although qui-
€
none methides were the final products for most Paterno-Buchi
reactions between quinone and alkynes,17a,22d QM1 and QM2
formed here were further involved in a spontaneous electro-
cyclization and subsequent oxidative dehydrogenation reaction,
A series of 2-azaaryl substituted phenylacetylene (4a-4e)
in which the azaaryl is pyridine, pyrimidine, pyrazine, or
quinoline were prepared, and their photoreactions with
N-methyl 1,3,4-isoquinolinetrione 3 were investigated. For-
mation of various isoquinoline-fused aza-polycyclic com-
pounds was observed in the photoreactions of these different
(22) For reviews, see: (a) Mallory, F. B.; Mallory, C. W. Org. React. 1984,
30, 1. (b) Laarhoven, W. H. In Organic Photochemistry; Padwa, A., Ed.; Marcel
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Chem. Rev. 1993, 93 (1), 3. (d) Hewlins, M. J. E.; Salter, R. Synthesis 2007, 14,
2164. (e) Abbott, B. M.; Ferrari, F. D.; Harnor, S. J.; Barnes, J. C.; Marquez, R.
Tetrahedron 2008, 64 (22), 5072. (f) Lewis, F. D.; Kalgutkar, R. S.; Yang,
J.-S. J. Am. Chem. Soc. 2001, 123 (17), 3878.
(21) (a) Pollers-Wieers, C.; Vekemans, J.; Toppet, S.; Hoornaert, G.
Tetrahedron 1981, 37, 4321. (b) Malamas, M. S.; Hohman, T. C.; Millen, J.
J. Med. Chem. 1994, 37 (13), 2043.
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Yu et al.
JOCArticle
SCHEME 3. Quinone Methide Intermediates and Aza-polycyclic Products Formed in the Photoreaction between isoquinolinetrione 3 and
3-(Phenylethynyl)pyridine 4b
and the reaction ended with the formation of the aza polycyclic
products 5a and 6a.
through the same quinone methide intermediate QM3, 7b was
from the other quinone methide isomer QM4. The relative ratio
of the product in the reaction mixture showed that the two
quinone methide intermediates QM3 and QM4 were also formed
with little regioselectivity. However, the cyclization of the inter-
mediate QM3 is highly regioselective, with the R-C of the N atom
on the pyridine ring being the predominant site of electrocycliza-
tion and dehydrogentation to give 5b as the major product, while
cyclization at the alternative site (C4 in the pyridine ring)
contributes only slightly to give 6b as a minor product. It
therefore indicates that the electron-negative N atom made its
adjacent position more labile for electrocyclization.
Other than phenyl pyridinyl acetylenes, 3-(phenylethynyl)
pyrimidine 4c and 2-(phenylethynyl) pyrazine 4d were also
used in the photoreactions with isoquinolinetrione 3. Final
products isolated from the reaction mixture and their corres-
ponding quinone methide precursors are shown in scheme 4.
The photoreaction between 3 and 4c proceeded smoothly
and within 48 h of irradiation all of the starting material 3
could be converted to give two major products 5c and 6c
(41% and 47%, respectively). Again the similar yields of the
quinazoline fused isoquinolinedione 5c and the naphthalene
The transformation of the quinone methides QM1 and
QM2 to 5a and 6a is similar to the stilbene-phenanthrene
phototransformation.22 It is noteworthy that the tandem
reaction could happen even if the reaction was performed
under Ar atmosphere. Since alkenes such as cyclohexene has
been found to act as an oxidant for a similar dehydrogena-
tion reaction,23 we questioned whether the CdC bond in the
quinone methide intermediates QM1 and QM2 could be the
oxidant for the dehydrogenation step. However, the absence
of hydrogenated quinone methides in the final products as
the corresponding reduced species was against this possibi-
lity. Therefore, we believe that a trace amount of oxygen in
the reaction mixture should have played an essential role in
the oxidation leading to the final aza-polycyclic compounds.
The favorable geometry in QM1 and QM2 made the follow-
ing transformation to 5a and 6a spontaneous under the
reaction conditions with trace amount of O2 as oxidant.
The regioselectivity of the initial photocycloaddition step
could be attributed to the relative stability of the correspond-
ing diradical intermediates DR1 and DR2 (Figure 1 in Suppor-
ting Information). SOE1 was formed by radical recombination
of the diradical intermediate DR1 with one radical adjacent to
the 2-pyridinyl group, while SOE2 was formed from DR2 with
one radical adjacent to the phenyl group. A DFT calculation on
the triplet 1,4-diradicals DR1 and DR2 at the UB3LYP/6-31G
level showed no distinct difference on their energy level. It is in
accord with the poor regioselectivity of the initial photocyclo-
addition reaction as shown in Scheme 2 that finally leads to the
similar yields of 5a and 6a (55% and 36% respectively) in the
final products.
SCHEME 4. Photoinduced Cascade Reactions between Isoqui-
nolinetrione 3 with 4c and with 4d
Photolysis of N-methyl-1,3,4-isoquinolinetrione 3 and
3-(phenylethynyl)pyridine 4b resulted in a quinoline fused
isoquinolinedione 5b (34%), an isoquinoline fused isoquino-
linedione 6b (6%), and a naphthelene fused isoquinoline-
dione 7b (54%) (Scheme 3). While 5b and 6b were formed
(23) Talele, H. R.; Gohil, M. J.; Bedekar, A. V. Bull. Chem. Soc. Jpn.
2009, 82, 1182.
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JOCArticle
SCHEME 5. Regioselective Photocycloaddition and Regiospecific Electrocyclization Involved in the Photo Tandem Reaction Sequence
of 3 with 4e
TABLE 1. Results of the Photoreactions of N-Methyl-1,3,4-isoquinoline-
trione 3 with Pyridinyl Aza-arynyl Acetylenes
phenanthridine fused isoquinolinedione 5e formed from the
intermediate QM5, and no acridine fused product was iso-
lated. The C4 position in the quinoline ring is preferred for
further cyclization, leading to a highly regioselective cycliza-
tion of the quinone methide QM5.
irradiation conversion
(%)
entry alkyne time (h)
products and yielda
1
2
3
4f
4g
4h
48
48
48
72
100
100
5f (13%), 6f (61%), 7f (23%)
5g (30%), 6g (64%)
5h (33%), 6h (18%),
7h (30%), 8h (9%)
5i (88%), 6i (8%)
5j (80%)
Photoreactions of Isoquinolinetrione with Pyridinyl Aza-arynyl
Acetylenes.
4
5
6
4i
4j
4k
48
60
60
45
30
28
5k (85%)
aisolated yield based on consumed isoquinolinetrione 3
fused isoquinolinedione 6c indicated poor regioselectivity in
the photocycloaddition step. On the other side, when
2-(phenylethynyl) pyrazine 4d was irradiated together with
isoquinolinetrione 3, the quinoxaline fused isoquinoline-
dione 5d was formed in a yield of 14% while its isomer 6d
accounted for 60% of the products. This indicates that the
initial photocyclization is more regioselective. It is also
noteworthy that the pyrazine substitution on the acetylene
seemed to be an unfavorable factor on the reactivity since
only 85% of 3 was consumed after 48 h of irradiation.
As a representative example of photoreaction between
isoquinolinetrione with quinoline substituted acetylene, the
reaction between 3 with 3-(phenylethynyl)quinoline 4e was
also investigated. The absorption wavelength of 4e is longer
than that of 4a-4d, and the partial overlap of its absorption
spectrum with that of isoquinolinetrione resulted in compe-
titive absorption with 3. Therefore, slower reaction of 4e
with 3 was observed compared with 4a-4d. Upon 60 h of
irradiation at 400 nm, a maximum of 70% conversion of 3
could be achieved, and prolonged irradiation did not inc-
rease the conversion significantly. Based on the converted
isoquinolinetrione, the yields of 5e and 6e were 55% and
20%, respectively, indicating a moderate regioselectivity of
the initial photocycloaddition reaction. It is noteworthy that
only two isomers were detected in the final products instead
of three possible isomers as shown in Scheme 5. Only the
To further explore whether the regioselectivity of the photo-
induced tandem reaction is controllable through proper
combinations of different substitution groups at the two
ends of the acetylene, we synthesized acetylenes with pyri-
dine at one end and another aza-aryl group at the other
(4f-4k) and investigated their photoreactions with isoqui-
nolinetrione 3. We observed that pyridine substituted at C2
and C3 contributed differently to the regioselectivity as well
as the reactivity of the acetylenes in their photoreactions with
isoquinolinetrione. The 1,2-di(pyridin-2-yl)ethyne with two
2-pyridinyl substituents showed very low reactivity with
isoquinolinetrione 3. When one of the 2-pyridinyl groups
was replaced by the 3-pyridinyl group as in 4f, it could
convert 72% isoquinolinetrione 3 into the tetracyclic pro-
ducts after 48 h of irradiation (Table 1). The regioselectivity
in the photocycloaddition and electrocyclization steps in
the tandem reaction of 3 with 4f is shown in Scheme 6.
The amount of the products 6f and 7f with the original
3-pyridinyl ring cyclized with the isoquinolinedione was
almost 6 times more than that of 5f, which derived from
J. Org. Chem. Vol. 75, No. 9, 2010 2993

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FIGURE 1. Structures of diradical intermediates DR3 and DR4.
SCHEME 6. Regioselectivity in the Photocycloaddition and Electrocyclization Steps in the Reaction Sequence of 3 with 4f
the cyclization of the original 2-pyridinyl ring with the
isoquinolinedione.
and 174° in DR4) as shown in Figure 1, with the spin bearing
carbon atom having an sp hybridization so that the pyridinyl
π system is orthogonal with the vinyl CdC π orbital but is
parallel with the singly occupied p-orbital at the sp-hybridized
carbon atom, resulting in unpaired electron delocalization to
the pyridinyl. The DFT calculation on the relative energy
We envision that this regioselectivity results from the rela-
tive stability of the 1,4-diradical intermediate in the Paterno-
Buchi-type reaction24 and suggests a greater thermodynamic
stability of the 1,4-diradical intermetidates DR4 than the
corresponding regioisomeric diradicals DR3 (Scheme 6). We
carried out a DFT calculation on the structures of the triplet
1,4-diradicals DR3 and DR4 at the UB3LYP/6-31G level,
and it turns out that the R-pyridinyl vinyl radical center has a
linear structure (pyridinyl to CdC bond angle: 173° in DR3
showed that the diradical DR4 was 2.0 kcal mol-1 lower than
3
DR3, which could have contributed to the regioselectivity of
the photocycloaddition as shown in Scheme 6.
The regioselectivity in the electrocyclization of the 3-pyri-
dinyl with the isoquinolinedione in the quinone methide
intermediate showed an obvious preference on the R-posi-
tion of pyridine N over the other available site. The relative
ratio of 5b/6b in Scheme 3 and 6f/7f in Scheme 6 consistently
showed the tendency. Therefore it is not surprising that
reaction of 3 with the symmetrically substituted acetylene
(24) (a) Freilich, S. C.; Peters, K. S. J. Am. Chem. Soc. 1981, 103 (20),
6255. (b) Schepp, N. P.; Johnston, L. J. J. Am. Chem. Soc. 1996, 118 (12),
2872. (c) Peters, K. S. Adv. Electron. Trans. Chem. 1994, 4, 27. (d) Eckert, G.;
Goez, M. J. Am. Chem. Soc. 1994, 116 (26), 11999. (e) Friedrich, L. E.;
Bower, J. D. J. Am. Chem. Soc. 1973, 95 (20), 6869.
2994 J. Org. Chem. Vol. 75, No. 9, 2010

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SCHEME 7. Chemical Structure of Products from the Photoreactions of 3 with 4g, 4i, 4j, and 4k, Respectively
SCHEME 8. Primary and Secondary Products Formed in the Photoreaction between 3 and 4h
4g gave 5g and 6g (Scheme 7) with a ratio of 1:2 (Table 1).
Moreover, it is interesting that we found an overconjugated
product 8h in the reaction between 3 and 4h (Scheme 8). The
product 8h was formed from the primary product 7h through
further electrocyclization of the 3-pyridinyl with the quina-
zoline-fused isoquinolinedione. The primary product 7h was
also isolated from the reaction mixture, and its structure has
been confirmed by X-ray single crystallagraphic analysis
(Supporting Information). Transformation from 7h to 8h
was observed by irradiating the solution containing 7h with
>400 nm light. The highly conjugated product 8h showed
poor solubility but strong fluorescent emission around 430 nm
even in diluted solutions (Supporting Information). The
isoquinoline-fused isoquinolinedione 6h, whose structure
has also been confirmed by X-ray single crystallagraphic
analysis (Supporting Information), could not undergo
further electrocyclization to form overconjugated systems
like 8h under similar reaction conditions.
Products of the photoreactions between isoquinolinetrione 3
and 4i, 4j, and 4k, respectively, are shown in Scheme 7. High
regioselectivity was found in the reaction of isoquinoline-
trione 3 with the quinoline pyridine substituted acetylenes 4j
and 4k. The yields of different products as well as the
conversion rate of the isoquinolinetrione 3 are listed in
Table 1. Compared with other acetylenes, lower reactivity was
observed in the acetylenes 4i,4j,and4k with isoquinolinetrione 3.
Less than 50% 3could be converted into aza-polycyles even after
prolonged photo irradiation. The relatively low reactivity of 4i
might be attributed to the less stabilizing effect of 2-pyridinyl or
2-pyrazinyl group on the diradical intermediates. The competi-
tive absorption of 4j and 4k might be one reason for the low
conversion rate of isoquinolinetrione 3 in its photoreactions with
these acetylenes. On the other side, the scattered distribution of
the precipitated final product in the reaction mixture might also
lead to the low conversion of the reactants because light to excite
the isoquinolinetrione for photoreaction was blocked or scat-
tered. However, it is worth mentioning that it was very con-
venient to get the pure product 5j or 5k from the reaction mixture
of 3 with 4j or 4k because the sole product just precipitated out
along with the photoirradiation. Pure 5j or 5k could be isolated
simply by collecting the precipitate.
Photoreactions of Isoquinolinetrione with Alkyl Arynyl
Acetylenes. The photoinduced tandem reaction was then
extended to acetylenes with only one aryl substitution group
since it might lead to quinone methides products which may
serve as evidence for our proposed mechanism for these
photo cascade reactions. It turned out that terminal acetyl-
enes with only one aryl substituent had very poor reactivity
with isoquinolinetrione. No aza-polycyclic compounds
could be obtained in the photoreactions of isoquinoline-
trione with 2-pyridinyl acetylene or 3-pyridinyl acetylene.
Electron withdrawing group such as ester group linked to the
acetylene also made the alkyne unreactive toward 3. How-
ever, acetylenes with an azazryl substituent on one end and
an alkyl group on the other end showed reasonable reactivity
in the photoreactions with isoquinolinetriones 3 (Table 2).
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TABLE 2. Results of the Photoreactions of Isoquinolinetrione 3 with Alkyl Arynyl Acetylenes
entry
1
alkyne
atmosphere
irradiation Time (h)
conversion (%)
products and yielda
4l
Ar
O2
Ar
O2
Ar
O2
Ar
O2
12
12
12
12
48
12
12
12
71
80
90
93
nrc
46
45
57
5l (38%), 6l (31%), 9l (10%), 10l (8%)b
5l (41%), 6l (31%),9l (9%), 10l (7%)b
5m (62%), 9m (21%)b
2
3
4
4m
4n
4o
5m (69%), 9m (18%)b
5n (59%)
5o (69%)
5o (88%)
aYield based on consumed isoquinolinetrione. bExact ratio quantified by HPLC. cNo reaction.
SCHEME 9. Products Isolated from the Photo Tandem
Reactions between 3 and Acetylenes 4l-4o
showed similar or higher conversion of 3 to the aza-poly-
cyclic products than the ones proceeded under Ar atmo-
sphere (Table 2). Among all the aza-aryl substituted acetyl-
enes, 2-(cyclopropylethynyl)pyrazine 4n showed the most
obvious dependence on the amount of O2 in the reaction
mixture. Reaction between 3 and 4n could hardly happen
under Ar atmosphere even after 48 h irradiation, while under
O2 atmosphere a conversion of 46% could be achieved with
the formation of quinoxaline-fused isoquinolinedione deri-
vative 5n. The reaction between 3-(cyclopropylethynyl) qui-
noline 4o and 3 was also facilitated under O2 atmosphere. A
conversion of 57% could be achieved under O2 atmosphere
after 12 h of irradiation, whereas the one under Ar was 45%.
And the yield of the phenanthridine-fused isoquinolinedione
derivative 5o based on converted 3 was obviously higher under
O2 atmosphere (88%) than under Ar atmosphere (69%). It
further confirmed our assumption that the dehydrogenation
step in the tandem reaction was facilitated by trace amount of
O2 remained in the reaction mixture.
Conclusions
Therefore several aza-aryl cyclopropyl acetylenes 4l-4o
were synthesized from ethynylcyclopropane and the corres-
ponding azaaryl bromides (see Experimental Section for
detail). The photoreactions of these azaaryl cyclopropyl
acetylenes with isoquinolinetrione 3 were then investigated.
In summary, we have developed the photoinduced tandem
reactions of isoquinoline-1,3,4-trione with various azaaryl sub-
stituted acetylenes to provide a convenient one-pot synthesis
of a diversity of aryl and azaaryl fused isoquinolinedione
derivatives. Initiated by the photoinduced [2þ2] cycloaddi-
tion between the carbonyl group on isoquinolinetrione and
the acetylene, most of the reactions proceeded via the se-
quential photocycloaddition-oxetene rearrangement-elec-
trocyclization-dehydrogenation sequence. Regioselectivity
in the [2þ2] cycloaddition and in the electrocyclization reac-
tion determines the framework of the final aza-polycyclic
products. Since both the photocyclization and the elec-
trocyclization reactions are found to be regioselective by
adjusting the combination of substitution groups on the
alkynes, it is possible to use these tandem photoreactions
to build specific aryl or azaaryl fused isoquinolinediones as
novel aza-polycycles with potential applications. Detailed
biological studies on the application of these compounds for
photoinduced DNA cleavage and as microRNA inhibitors
are underway in our group.
Reaction between 3 and 4l gave four compounds in the
final products. Except for the polycyclic products 5l and 6l,
two quinone methide products 9l and 10l were also isolated
from the reaction mixture as expected (Scheme 9). The
cyclopropyl group linked to the CdC bond in the quinone
methide moiety made it impossible for further electrocycli-
zation. The presence of 9l and 10l in the final product serves
as solid evidence for the proposed sequences of the photo-
initiated cascade reaction via quinone methide intermediates
as shown in Scheme 2. Similar reaction pattern was found
between 3 and 4 m, leading to the products including quino-
zaline-fused isoquinolinedione derivative 5m and quinone
methide products 9m as a mixture of its (E)-/(Z)- conformers.
It is noteworthy that the photoreactions between 3 and
alkyl arynyl acetylenes proceeded under O2 atmosphere
Experimental Section
Synthesis of Substituted Acetylenes. Acetylenes 4a-4e were
prepared from phenylacetylene and corresponding bromo-
substituted heterocycles according to reported procedure,20
and 4f and 4g were prepared by the Sonagashira coupling of
3-ethynylpyridine with 2-bromopyridine and 3-bromopyridine
respectively according to a reported method. For acetylenes
including 4h-4o, which have not been reported before, detailed
2996 J. Org. Chem. Vol. 75, No. 9, 2010

Yu et al.
JOCArticle
information on their synthesis and characterization was given
below.
under an nitrogen atmosphere followed by addition of cyclo-
propyl acetylene (1.18 g, 18 mmol) and CuI (30 mg). The mixture
was stirred under an nitrogen atmosphere at 40 °C overnight.
The reaction mixture was cooled to room temperature and then
concentrated under vacuum. The residue diluted with diethyl
ether (50 mL) and filtered through a filter paper. The mixture
was washed with water (20 mL ꢀ 3). The ether layer was sepa-
rated, dried over anhydrous sodium sulfate, and concentrated to
give the crude product. The product was then purified by flash
column chromatography on silica gel (petroleum ether/ethyl
acetate 4:1) to give pale yellow liquid (1.2 g, 70%); 1H NMR (300
MHz; CDCl3) δ 8.60(d, 1H, J=2.1), 8.47(dd, 1H, J=1.8, 4.8),
7.66(td, 1H, J=1.8, 7.8), 7.20(dd, 1H, J=4.8, 7.8), 1.47(m, 1H),
0.91(m, 2H), 0.84(m, 2H); 13C NMR (75 MHz; CDCl3) δ 0.2,
8.7, 72.5, 97.1, 121.1, 122.8, 138.4, 147.8, 152.3; MS m/z (%
base) 143(Mþ, 100), 142(62), 141(6), 117(6), 116(5), 115(27),
86(11), 84(18), 49(46), 44(22). Anal. Calcd for C10H9N: C, 83.88;
H, 6.34; N, 9.78. Found: C, 83.81; H, 6.34; N, 9.80.
5-(Pyridin-3-ylethynyl)pyrimidine (4h). A solution of 5-bromo
pyrimidine (1.4 g, 9 mmol) and Et3N (9 mL) in THF (20 mL)
was purged with nitrogen for 10 min at room temperature.
3-Ethynylpyridine (1.1 g, 10.8 mmol) was added to the solution
at room temperature under an nitrogen atmosphere, followed
by addition of Pd(PPh3)4 (1.08 g, 0.76 mmol). The mixture was
stirred under an nitrogen atmosphere at 50 °C for 8 h. The reac-
tion mixture was cooled to room temperature and then concen-
trated under vacuum. The residue was diluted with diethyl ether
(50 mL), and filtered through a filter paper to get rid of the
catalyst. The filtrate was washed with water (20 mLꢀ3) and the
ether layer was separated, dried over anhydrous sodium sulfate,
and concentrated. The crude product was purified by flash
column chromatography on silica gel (petroleum ether/ethyl
1
acetate 2:1) as a brown solid (1.3 g, 80%), mp 76-78 °C; H
NMR (300 MHz; CDCl 3) δ 9.12(s, 1H), 8.83(s, 2H), 8.75(s, 1H),
8.57(d, 1H, J=5.1), 7.79(d, 1H, J=7.8), 7.27(dd, 1H, J=5.4,
7.5); 13C NMR (75 MHz; CDCl3) δ 85.6, 92.8, 119.2, 123.2,
128.5, 132.0, 138.7, 149.7, 152.4, 157.2, 158.8; MS m/z (% base)
182(1), 181(Mþ, 100), 127(25), 100(1), 86(2), 84(6), 49(8). Anal.
Calcd for C11H7N3: C, 72.92; H, 3.89; N, 23.19. Found: C, 72.87;
H, 3.80; N, 23.29.
5-(Cyclopropylethynyl)pyrimidine (4m). Similar to the proce-
dure to make 4l as discribed above, 4m was prepared from
cyclopropyl acetylene (1.18 g, 18 mmol) and 5-bromo pyrimi-
dine (1.4 g, 9 mmol). The purified 4m after flash column
1
chromatographyappeared as yellow oil (1 g, 77%); H NMR
(300 MHz; CDCl3) δ 9.04(s, 1H), 8.66(s, 2H), 1.46(m, 1H),
0.91(m, 4H); 13C NMR (75 MHz; CDCl3) δ 0.24,8.9, 69.1, 101.1,
120.5, 156.0, 158.7; MS m/z (% base) 144(Mþ, 100), 143(27),
117(9), 116(9), 90(60), 89(72), 62(17). Anal. Calcd for C9H8N2:
C, 74.98; H, 5.59; N, 19.43. Found: C, 74.92; H, 5.60; N, 19.42.
2-(Cyclopropylethynyl)pyrazine (4n). Similar to the procedure
to make 4l as discribed above, 4n was prepared from cyclopropyl
acetylene (1.18 g, 18 mmol) and 2-chloro pyrazine (1 g, 9 mmol).
Further purification by flash column chromatography on silica gel
(petroleum ether/ethyl acetate 4:1) gave 4n as pale yellow oil (0.8 g,
61%); 1H NMR (300 MHz; CDCl3) δ 8.51(d, 1H, J=1.5), 8.40(d,
1H, J= 2.4), 8.34(d, 1H, J= 2.7), 1.44(m, 1H), 0.86(m, 4H); 13C
NMR (75 MHz; CDCl3) δ 0.2, 9.0, 72.98, 98.8, 140.7, 142.2, 144.1,
147.6; MS m/z (% base) 144(Mþ, 100), 143(25), 118(33), 91(22),
86(6), 84(10), 64(8), 49(13). Anal. Calcd for C9H8N2: C, 74.98; H,
5.59; N, 19.43. Found: C, 74.99; H, 5.52; N, 19.40.
2-(Pyridin-2-ylethynyl)pyrazine (4i). Similar to the procedure
to make 4h as discribed above, 4i was prepared from 2-chloro-
pyrazine (1.0 g, 9 mmol) and 2-ethynylpyridine (1.1 g,10.8
mmol) and purified by flash column chromatography on silica
gel (petroleum ether/ethyl acetate 3:1) to give a yellow solid (1.4 g,
87%), mp 42-44 °C; 1H NMR (300 MHz; CDCl3) δ 8.83(d, 1H,
J = 1.5), 8.65(qd, 1H, J = 0.9, 5.1), 8.59(dd, 1H, J = 1.8, 2.7),
8.52(t, 1H, J=2.7), 7.72(dt, 1H, J=2.1, 7.8), 7.62(td, 1H, J=
1.2, 8.1) 7.31(m, 1H); 13C NMR (75 MHz; CDCl3) δ 84.8, 91.5,
123.8, 127.9, 136.3, 139.5, 141.9, 143.4, 144.5, 148.1, 150.3; MS
m/z (% base) 182(1.5), 181(Mþ, 100), 180(2), 129(37), 128(12),
101(2), 84(3), 44(7). Anal. Calcd for C11H7N3: C, 72.92; H, 3.89;
N, 23.19. Found: C, 72.91; H, 3.89; N, 23.20.
3-(Pyridin-3-ylethynyl)quinoline (4j). Similar to the procedure
to make 4h as discribed above, 4j was prepared from 3-ethynyl-
pyridine(1.1 g, 10.8 mmol) and 3-bromo quinoline (1.8 g, 9 mmol)
and purified by flash column chromatography on silica gel
(mobile phase petroleum ether/ethyl acetate 1:1) as a white solid
(1.6 g, 80%), mp 88-90 °C; 1H NMR (300 MHz; CDCl3) δ 9.0
(d, 1H, J=2.1), 8.83(d, 1H, J=1.8), 8.59(dd, 1H, J=1.2, 4.8),
8.33(d, 1H, J = 1.8), 8.10(d, 1H, J = 8.4), 7.87(td,1H, J = 1.8,
8.1), 7.86(d, 1H, J=7.8), 7.78(dt, 1H, J=1.8, 7.2), 7.57(t, 1H,
6.9), 7.30(dd, 1H, 4.8, 8.4); 13C NMR (75 MHz; CDCl3) δ 89.3,
90.0, 116.8, 120.0, 123.3, 127.3, 127.6, 127.8, 129.6, 130.6, 138.7,
138.8, 147.2, 149.2, 152.0, 152.5; MS m/z (% base) 231(1),
230(Mþ, 100), 229(8). Anal. Calcd for C16H 10N2: C, 83.46; H,
4.38; N, 12.17. Found: C, 83.44; H, 4.37; N, 12.18.
3-(Pyridin-2-ylethynyl)quinoline (4k). Similar to the proce-
dure to make 4h as discribed above, 4k was prepared from
2-ethynylpyridine (1.1 g, 10.8 mmol) and 3-bromo quinoline (1.8 g,
9 mmol) and purified by flash column chromatography on silica
gel (mobile phase petroleum ether/ethyl acetate 2:1) as a pale
yellow crystal(1.5 g, 75%), mp 91-93 °C; 1H NMR (300 MHz;
CDCl3) δ 8.98(d, 1H, J = 2.1), 8.57(d, 1H, J = 3.9), 8.28(d, 1H,
J=2.1), 8.03d, 1H, J=8.1), 7.70(d, 1H, 8.1), 7.63(m, 2H), 7.50(m,
2H), 7.17(dd, 1H, J=2.8, 7.5); 13C NMR (75 MHz; CDCl3) δ 86.2,
91.6, 116.4, 123.2, 127.3, 127.7, 128.5, 129.4, 130.4, 132.1, 136.2,
139.1, 142.8, 147.0, 150.2, 152.0; MS m/ z (% base) 231(1), 230(Mþ,
100), 229(45), 128(2). Anal. Calcd for C16H10N2: C, 83.46; H, 4.38;
N, 12.17. Found: C, 83.46; H, 4.35; N, 12.20.
3-(Cyclopropylethynyl)quinoline (4o). Similar to the proce-
dure to make 4l as discribed above, 4o was prepared from
cyclopropyl acetylene (1.18 g, 18 mmol) and 3-bromo qunino-
line (1.8 g, 9 mmol) was obtained overnight, the crude product
was purified by using column chromatography on silica gel to
give 4o as a dark yellow oil (1.1 g, 63%); 1H NMR (300 MHz;
CDCl3) δ 8.84(d, 1H, J=1.8), 8.11(s, 1H), 8.04(d, 1H, J=8.4),
7.65(m, 2H), 7.50(t, 1H, J=7.5), 1.50(m, 1H), 0.89(m, 4H); 13
C
NMR (75 MHz; CDCl3) δ 0.4, 8.9, 73.2, 97.2, 118.2, 127.1,
127.4, 127.3, 129.3, 129.6, 138.0, 146.5, 152.5; MS m/z (% base)
194(1), 193(Mþ, 100), 192(62), 191(17), 167(3), 165(7). Anal.
Calcd for C14H11N: C, 87.01; H, 5.74; N, 7.25. Found: C, 87.09;
H, 5.72; N, 7.25.
General Procedures for the Preparative Photolysis of Isoqui-
nolinetrione with Acetylenes. The light source was a medium-
pressure mercury lamp (500 W) in a cooling water jacket that
was further surrounded by a layer of filter solution (1 cm thick,
20% aqueous sodium nitrite) to cut off light of wavelength
shorter than 400 nm. The solution of isoquinolinetrione and an
excess amount of acetylenes in anhydrous acetonitrile was
purged with dry argon for 10 min and then irradiated under
continuous argon purging. The reaction course was monitored
by TLC. At the end of the reaction, the solvent was removed
under reduced pressure, and the residue was separated by flash
chromatography on a silica gel column.
3-(Cyclopropylethynyl)pyridine (4l). A solution of Pd(PPh3)4-
(1.08 g, 0.76 mmol) and Et3N (9 mL) in THF (20 mL) was pur-
ged with nitrogen for 10 min at room temperature. 3-Bromo-
pyridine (1.4 g, 9 mmol) was then added at room temperature
Photolysis of 3 with 4a. A solution of 3 (378 mg, 2 mmol) and
4a (716 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a complete
conversion of isoquinolinetrione. Workup as described above
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Yu et al.
JOCArticle
gave the products 5a and 6a as a mixture. The ratio of the two
products was determined by HPLC with acetonitrile and water
gradient eluting. Flash column chromatagraph with chloroform
as eluents afforded pure analytic samples of 5a and 6a.
7-Benzoyl-5-methyl-4H-isoquinolino[5,4-fg]quinoline-4,6(5H)-
dione (5a). Yellow powder; 1H NMR (300 MHz; CDCl3) δ
9.05(dd, 1H, J = 8.7, 1.8), 9.00(m, 2H), 8.78(dd, 1H, J = 7.5,
0.9), 8.04(t, 1H, J=7.8), 7.88(dd, 2H, J=8.1), 7.74(q, 1H, J=4.5),
7.55(tt, 1H, J = 7.2, 2.1), 7.43(t, 2H, J = 7.5), 3.48(s, 1H); 13C
NMR (75 MHz; d6-DMSO) δ 27.3, 121.4, 123.6, 125.3, 125.8,
128.0, 128.8, 129.0, 129.1, 129.8, 130.8, 132.6, 133.3, 137.7, 144.8,
145.7, 151.9, 163.3, 163.8, 195.8; MS m/z (% base) 367(3),
366(Mþ, 45), 337(100), 323(10), 289(10), 253(11), 105(2), 77(9).
Anal. Calcd for C23H14N2O3: C, 75.41; H, 3.82; N, 7.65. Found: C,
75.19; H, 4.03; N, 7.75.
gave the products 5c and 6c as a mixture. The ratio of the two
products was determined by HPLC with acetonitrile and water
gradient eluting. Flash column chromatagraph with chloroform
as eluent afforded pure analytic samples of 5c and 6c.
7-Benzoyl-5-methyl-4H-isoquinolino[4,5-gh]quinazoline-4,6(5H)-
1
dione (5c). Pale yellow powder; H NMR (300 MHz; CDCl3) δ
9.64(dd, 1H, J=8.4, 0.9), 9.62(s, 1H), 9.28(s, 1H), 8.92(dd, 1H, J=
7.5, 1.5), 8.13(t, 1H, J=7.8), 7.86(d, 2H, J=7.2), 7.63(t, 1H, J=
7.5), 7.48(t, 2H, J=7.5), 3.48(s, 3H); 13C NMR (75 MHz; CDCl3)
δ 27.5, 121.4, 123.3, 128.9, 129.0, 129.4, 129.2, 131.1, 134.3, 134.5,
136.7, 143.1, 151.5, 158.0, 159.0, 162.9, 163.6, 195.2; MS m/z (%
base), 367(Mþ, 100), 338(13), 290(35), 105(51), 77(28). Anal.
Calcd for C22H13N3O3: C, 71.93; H, 3.54; N, 11.44. Found: C,
71.81; H, 3.72; N, 11.03.
5-Methyl-7-(pyrimidine-5-carbonyl)-5,6-dihydro-4H-dibenz[de,g]-
isoquinoline-4,6(5H)-dione (6c). Pale yellow powder; 1HNMR(300
MHz; CDCl3) δ 9.36(s, 1H), 9.10(s, 2H), 9.05(d, 1H, J = 7.8),
8.84(d, 1H, J=8.4), 8.73(d, 1H, J=7.2), 8.0(t, 1H, J=7.8), 7.93(t,
1H, J=7.2), 7.7(m, 2H), 3.45(s, 3H); 13C NMR (75 MHz; CDCl3)
δ 27.4, 118.6, 123.4, 123.8, 125.5, 128.0, 128.3, 128.7, 128.9, 129.2,
129.6, 130.5, 131.0, 131.3, 132.4, 142.5, 156.9, 161.4, 164.0, 194.6;
MS m/z (% base), 367(Mþ, 79), 338(5), 288(100). Anal. Calcd for
C22H13N3O3: C, 71.93; H, 3.54; N, 11.44. Found: C, 71.93; H, 3.58;
N, 11.31.
5-Methyl-7-picolinoyl-5,6-dihydro-4H-dibenz[de,g]isoquinoline-
1
4,6-dione (6a). White powder; H NMR (300 MHz; CDCl3) δ
9.02(d, 1H, J = 7.5), 8.7(d, 1H, J = 7.8), 8.67(d, 1H, J = 7.5),
8.52(d, 1H, J=7.8), 8.42(d, 1H, J=4.8), 8.01(td, 1H, J=7.5, 1.8),
7.94(t, 1H, J=7.8), 7.84(td, 1H, J=7.2, 1.2), 7.77(d, 1H, J=8.1),
7.60(m, 1H), 7.45(m, 1H), 3.43(s, 3H); 13C NMR (75 MHz;
CDCl3) δ 27.1, 122.1, 123.1, 123.3, 125.9, 127.2, 127.8, 128.2,
128.4, 128.5, 129.2, 130.3, 130.4, 132.0, 137.3, 146.8, 149.3, 154.3,
164.2, 164.3, 198.1; MS m/z (% base), 366(Mþ, 1), 337(49),
288(100). Anal. Calcd for C23H14N2O3: C, 75.41; H, 3.82; N,
7.65. Found: C, 75.27; H, 4.21; N, 7.69.
Photolysis of 3 with 4d. A solution of 3 (378 mg, 2 mmol) and
4d (720 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a 85% conversion
of isoquinolinetrione. Workup as described above gave the
products 5d and 6d as a mixture. The ratio of the three products
was determined by HPLC with acetonitrile and water gra-
dient eluting. Flash column chromatagraph with chloroform/
methanol as eluents afforded pure analytic samples of 5d and 6d.
7-Benzoyl-5-methyl-4H-isoquinolino[5,4-fg]quinoxaline-4,6(5H)-
Photolysis of 3 with 4b. A solution of 3 (378 mg, 2 mmol) and
4b (716 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a complete
conversion of isoquinolinetrione. Workup as described above
gave the products 5b, 6b, and 7b as a mixture. The ratio of the
three products was determined by HPLC with acetonitrile and
water gradient eluting. Flash column chromatagraph with
chloroform/methanol as eluents afforded pure analytic samples
of 6b and 7b. Crude 5b was further purified by flash column
chromatagraph with petroleum ether/ethyl acetate as eluents.
7-Benzoyl-5-methyl-4H-isoquinolino[4,5-gh]quinoline-4,6(5H)-
1
dione (5d). Pale yellow powder; H NMR (300 MHz; CDCl3) δ
9.57(dd, 1H, J=8.1, 1.2), 9.08(d, 1H, J=1.8), 8.96(d, 1H, J=1.8),
8.86(dd, 1H, J=7.5, 1.2), 8.11(t, 1H, J=8.4), 7.86(d, 2H, J=8.4),
7.58(tt, 1H, J=7.5, 1.8), 7.44(t, 2H, J=7.8), 3.49(s, 3H); 13C NMR
(75 MHz; CDCl3) δ 27.5, 121.8, 123.2, 127.5, 128.8, 129.0, 129.2,
130.1, 130.6, 132.8, 133.6, 137.2, 141.2 142.9, 145.2, 146.2 146.5,
163.1, 163.8, 195.8; MS m/z(%base),368(6),367(Mþ, 100), 338(25),
290(40), 254(39), 105(10), 77(17). Anal. Calcd for C22H13N3O3: C,
71.93; H, 3.54; N, 11.44. Found: C, 71.66; H, 3.76; N, 11.12.
5-Methyl-7-(pyrazine-2-carbonyl)-5,6-dihydro-4H-dibenz[de,g]-
isoquinoline-4,6(5H)-dione (6d). White powder; 1H NMR (300
MHz; CDCl3) δ 9.69(s, 1H), 9.03(d, 1H, J = 8.1), 8.81(d, 1H,
J = 8.1), 8.75(d, 1H, J = 2.7), 8.70(d, 1H, J = 7.5), 8.38(s, 1H),
7.97(t, 1H, J = 8.1), 7.89(t, 1H, 7.2), 7.78(d, 1H, J= 7.8), 7.66(t,
1H, J = 7.5), 3.43(s, 3H); 13C NMR (75 MHz; CDCl3) δ 27.3,
118.7, 123.3, 123.6, 125.8, 128.3, 129.0, 129.5, 130.7, 130.8, 132.2,
143.8, 144.2, 145.1, 147.9, 148.9, 164.3, 164.4, 197.2; MS m/z
(% base), 367(Mþ, 2), 339(0.9), 288(100). Anal. Calcd for C22H13-
N3O3: C, 71.93; H, 3.54; N, 11.44. Found: C, 71.73; H, 3.84; N,
11.21.
Photolysis of 3 with 4e. A solution of 3 (378 mg, 2 mmol) and
4e (916 mg, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a 70% conversion
of isoquinolinetrione. Workup as described above gave the
products 5e and 6e as a mixture. Flash column chromatagraph
with chloroform/methanol as eluents afforded pure analytic
samples of 5e (55%) and 6e (20%).
7-Benzoyl-5-methyl-4H-isoquinolino[4,5-jk]phenanthridine-
4,6(5H)-dione (5e). Yellow powder; 1HNMR(300MHz;CDCl3) δ
9.47(d, 1H, J=8.4), 9.21(s, 1H), 9.00(d, 1H, J=8.1), 8.91(dd, 1H,
J=7.2, 1.2), 8.38(d, 1H, J=7.8), 8.11(t, 1H, J=7.5), 7.97(t, 1H,
J=7.2), 7.87(m, 2H), 7.58(tt, 1H, J=6, 1.5), 7.44(t, 1H, J=7.5),
3.49(s, 3H); MS m/z (% base), 416(Mþ, 100), 387(30), 339(34),
105(18), 77(21). Anal. Calcd for C27H16N2O3: C, 77.87; H, 3.87; N,
6.73. Found: C, 77.71; H, 3.98; N, 6.72.
1
dione (5b). Pale yellow crystal; H NMR (300 MHz; CDCl3) δ
9.58(dd, 1H, J=8.1, 0.9), 9.12(dd, 1H, J=4.2, 1.8), 8.73(dd, 1H,
J=7.2, 1.2), 8.09(dd, 1H, J=8.4, 1.8), 7.99(t, 1H, J=8.1), 7.85(d,
2H, J=7.2), 7.5(m, 2H), 7.41(t, 2H, J = 7.8), 3.42(s, 3H); 13C
NMR (75 MHz; CDCl3) δ 27.1, 118.2, 122.5, 123.2, 123.9, 127.0,
128.4, 128.6, 128.9, 130.1, 130.5, 131.9, 133.7, 135.7, 136.7, 144.2,
147.1, 152.3, 163.2, 163.8, 196.3; MS m/z (% base) 367(4), 366(Mþ,
18), 337(12), 289(100), 105(15), 77(9). Anal. Calcd for C23H14-
N2O3: C, 75.41; H, 3.82; N, 7.65. Found: C, 75.49; H, 3.87; N, 7.64.
7-Benzoyl-5-methyl-4H-Benzo[de]pyrido[4,3-g]isoquinoline-
4,6(5H)-dione (6b). Pale yellow powder; 1H NMR (300 MHz;
CDCl3) δ 9.17(s, 1H), 9.05(dd, 1H, J=8.4, 1.2), 8.95(d, 1H, J=6),
8.84(dd, 1H, J=7.5, 1.2), 8.54(d, 1H, J=5.4), 8.06(t, 1H, J=8.1),
7.87(d, 2H, J=7.2), 7.61(tt, 1H, J=7.5, 1.2), 7.46(t, 2H, J=7.8),
3.46(s, 3H); MS m/z (ESI, % base) 389(MþNaþ, 20%), 755(2Mþ
Naþ, 100%). Anal. Calcd for C23H14N2O3: C,75.41; H, 3.82; N,
7.65. Found: C, 75.12; H, 4.00; N, 6.91.
5-methyl-7-nicotinoyl-5,6-dihydro-4H-dibenz[de,g]isoquinoline-
4,6(5H)-dione (7b). White powder; 1H NMR (300 MHz; CDCl3) δ
9.05(d, 1H, J=8.1), 8.78(m,4H), 8.42(d,1H, J=7.8), 8.01(t, 1H,
J=7.8), 7.91(t, 1H, J=7.5), 7.78(d, 1H, J=8.4), 7.67(t, 1H, J=
7.5), 7.52(m, 1H), 3.45(s, 3H); 13C NMR (75 MHz; CDCl3) δ 27.3,
118.4, 123.5, 123.6, 124.2, 125.8, 128.5, 128.6, 128.8, 128.9, 129.5,
130.9, 131.0, 132.4, 133.1, 135.9, 144.0, 150.2, 153.6, 163.9, 164.1,
196.1; MS m/z (% base) 367(10), 366(Mþ, 48), 337(14), 289(10),
288(100), 106(11), 78(20). Anal. Calcd for C23H14N2O3: C, 75.41;
H, 3.82; N, 7.65. Found: C, 75.27; H, 3.91; N, 7.78.
Photolysis of 3 with 4c. A solution of 3 (378 mg, 2 mmol) and
4c (720 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a complete
conversion of isoquinolinetrione. Workup as described above
2998 J. Org. Chem. Vol. 75, No. 9, 2010

Yu et al.
5-Methyl-7-(quinoline-3-carbonyl)-5,6-dihydro-4H-dibenz[de,g]-
JOCArticle
5-Methyl-7-nicotinoyl-4H-isoquinolino[4,5-gh]quinoline-4,6(5H)-
dione (6g). Colorless crystal; 1H NMR (300 MHz; CDCl3) δ
9.65(dd, 1H, J = 8.1, 1.2), 9.18(dd, 1H, J = 4.2, 1.5), 8.81(m,
3H),8.23(d, 1H, J = 4.2), 8.08(m, 2H), 7.59(q, 1H, J = 4.2),
7.47(dd, 1H, J = 8.1, 4.8), 3.44(s, 3H); 13C NMR (75 MHz;
CDCl3) δ 27.4, 119.0, 122.9, 123.7, 123.8, 124.3, 127.2, 129.1,
130.6, 131.0, 132.4, 132.7, 135.5, 135.9, 142.8, 147.6, 150.2, 152.8,
154.0, 163.7, 164.0, 195.3; MS m/z (% base), 368(4), 367(Mþ, 52),
338(10), 289(100), 106(4), 78(10). Anal. Calcd for C22H13N3O3: C,
71.93; H, 3.54; N, 11.44. Found: C, 71.66; H, 3.71; N, 11.21.
Photolysis of 3 with 4h. A solution of 3 (378 mg, 2 mmol) and
4h (724 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a complete
conversion of isoquinolinetrione. Workup as described above
gave the products 5h, 6h, 7h, and 8h as a mixture. The ratio of the
four products was determined by HPLC with acetonitrile and
water gradient eluting. Flash column chromatagraph with
chloroform/methanol as eluents afforded pure analytic samples
of 5 h, 6h, 7h, and 8h.
5-Methyl-7-(pyrimidine-5-carbonyl)-4H-isoquinolino[4,5-gh]-
quinoline-4,6(5H)-dione (5h). Pale yellow powder; 1H NMR (300
MHz; CDCl3) δ 9.69(dd, 1H, J = 8.1, 1.2), 9.37(s, 1H), 9.22(dd,
1H, J = 4.5, 1.8), 9.09(s, 2H), 8.83(dd, 1H, J =7.5, 1.2), 8.10(m,
2H), 7.65(q, 1H, J = 4.2), 3.46(s, 3H); 13C NMR (75 MHz; d6-
DMSO) δ 27.3, 119.7, 123.3, 123.5, 124.6, 127.3, 129.5, 130.1,
130.2, 130.3, 131.7, 135.8, 140.9, 147.1, 153.4, 157.4, 161.8, 163.9,
194.2; MS m/z (% base), 368(Mþ, 100), 289(80), 176(3), 107(4),
79(3). Anal. Calcd for C21H12N4O3: C, 68.48; H, 3.28; N, 15.21.
Found: C, 68.37; H, 3.49; N, 15.21,
isoquinoline-4,6(5H)-dione (6e). Pale yellow powder; 1H NMR
(300 MHz; CDCl3) δ 9.41(s, 1H), 9.05(d, 1H, J = 8.4), 8.83(d,
1H, J=8.4), 8.71(d, 1H, J=7.5), 8.54(s, 1H), 8.17(d, 1H, J=8.4),
7.97(t, 1H, J=8.4), 7.79-7.92(m, 4H), 7.64(t, 1H, J=7.1), 7.56(t,
1H, J=7.2), 3.41(s, 3H);MSm/z(%base), 416(Mþ, 100), 387(32),
288(95), 128(10). Anal. Calcd for C27H16N2O3: C, 77.87; H, 3.87;
N, 6.73. Found: C, 77.81; H, 3.88; N, 6.66.
Photolysis of 3 with 4f. A solution of 3 (378 mg, 2 mmol) and 4f
(720 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a 72% conversion
of isoquinolinetrione. Workup as described above gave the
products 5f, 6f ,and 7f as a mixture. The ratio of the three
products was determined by HPLC with acetonitrile and water
gradient eluting. Flash column chromatagraph with chloroform
as eluents afforded pure analytic sample 6f and the mixture of 7f
and 5f. Then flash column chromatagraph with ethyl ether/
petroleum ether afforded a few pure analytic samples 5f and 7f.
5-Methyl-7-nicotinoyl-4H-isoquinolino[5,4-fg]quinoline-4,6(5H)-
dione (5f). White powder; 1H NMR (300 MHz; CDCl3) δ 9.07(dd,
1H, J = 1.8, 8.4), 8.99(dt, 1H, J = 0.9, 4.8), 8.98(s, 1H), 8.77(m,
3H), 8.42(td, 1H, J= 2.1, 8.1), 8.06(dd, 1H, J= 7.5, 8.4), 7.77(q,
1H, J = 4.5), 7.49(m, 1H), 3.47(s, 3H); 13C NMR (75 MHz;
CDCl3) δ27.4, 121.5, 123.7, 124.0, 124.7, 125.8, 128.0, 128.5, 129.0,
129.1, 131.2, 131.5, 133.1, 135.8, 144.5, 146.1, 150.5, 151.7, 153.2,
163.5, 163.8, 195.5; MS m/z (% base), 368(4), 367(Mþ, 48),
338(29), 324(20), 310(100), 289(30), 282(32), 254(30), 78(10). Anal.
Calcd for C22H13N3O3: C, 71.93; H, 3.54; N, 11.44. Found: C,
71.78; H, 3.61; N, 11.47,
5-Methyl-7-picolinoyl-4H-isoquinolino[4,5-gh]quinoline-4,6(5H)-
dione (6f). white powder; 1H NMR (300 MHz; CDCl3) δ 9.65(dd,
1H, J=8.4, 0.6), 9.16(dd, 1H, J=4.5, 1.8), 8.76(dd, 1H, J=7.5,
1.2), 8.51(d, 1H, J=7.5), 8.4(d, 1H, J=3.9), 8.09(dd, 1H, J=8.1,
1.2), 8.02(t, 2H, J=7.8), 7.59(q, 1H, J=4.5), 7.46(m, 1H), 3.43(s,
3H); 13C NMR (75 MHz; CDCl3) δ27.3, 118.9, 122.4, 122.7, 123.3,
124.5, 127.6, 128.5, 130.4, 130.9, 132.1, 136.0, 136.3, 137.6, 145.8,
147.4, 149.4, 152.2, 154.2, 164.0, 164.3, 197.3; MS m/z (% base),
367(Mþ, 3), 339(83), 338(50), 310(5), 290(9), 289(100), 78(8). Anal.
Calcd for C22H13N3O3: C, 71.93; H, 3.54; N, 11.44. Found: C,
71.65; H, 3.65; N, 11.56.
5-Methyl-7-picolinoyl-4H-benzo[de]pyrido[4,3-g]isoquinoline-
4,6(5H)-dione (7f). White powder; 1H NMR (300 MHz; CDCl3)
δ 9.13(s, 1H), 9.05(dd, 1H, J = 0.9, 8.1), 8.94(d, 1H, J = 6),
8.84(dd, 1H, J=1.2, 7.5), 8.58(d, 1H, J=5.1), 8.56(dt, 1H, J=
1.2, 7.8), 8.41(d, 1H, J=4.8), 8.04(m, 2H), 7.49(m, 1H), 3.45(s,
3H); MS m/z (% base), 367(Mþ, 48), 338(30), 310(100), 289(30),
78(10). Anal. Calcd for C22H13N3O3: C, 71.93; H, 3.54; N, 11.44.
Found: C, 71.81; H, 3.57; N, 11.39.
Photolysis of 3 with 4g. A solution of 3 (378 mg, 2 mmol) and
4g (720 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a complete
conversion of isoquinolinetrione. Workup as described above
gave the products 5g and 6g as a mixture. The ratio of the three
products was determined by HPLC with acetonitrile and water
gradient eluting. Flash column chromatagraph with chloro-
form/methanol as eluents afforded pure analytic samples of 5g
and 6g.
5-Methyl-7-(pyrimidine-5-carbonyl)-4H-benzo[de]pyrido[4,3-g]-
isoquinoline-4,6(5H)-dione (6h). Pale yellow powder; 1H NMR
(300 MHz; CDCl3) δ 9.35(s, 1H), 9.11(s, 1H), 9.09(s, 2H),
9.03(d, 1H, J = 7.5), 8.97(d, 1H, J = 6), 8.79(dd, 1H, J = 7.5,
0.9), 8.55(d, 1H, J = 6.3), 8.07(t, 1H, J = 8.1), 3.42(s, 3H); 13C
NMR (75 MHz; CDCl3) δ 27.5, 116.7, 119.6, 123.8, 127.1, 127.9,
129.2, 129.6, 130.3, 133.2, 136.8, 149.0, 151.1, 156.9, 161.8, 163.4,
193.3; MS m/z (% base), 368(Mþ, 100), 339(10), 289(47), 176(3),
107(4), 79(3). Anal. Calcd for C21H12N4O3: C, 68.47; H, 3.26; N,
15.21. Found: C, 68.70; H, 3.51; N, 15.14.
5-Methyl-7-nicotinoyl-4H-isoquinolino[4,5-gh]quinazoline-
4,6(5H)-dione (7h). Pale yellow crystal; 1H NMR (300 MHz;
CDCl3) δ 9.57(s, 1H), 9.54(dd, 1H, J = 8.1, 1.2), 9.21(s, 1H),
8.80(m, 3H), 8.32(dt, 1H, J=8.1, 1.2), 8.07(t, 1H, J=8.4), 7.49(m,
1H), 3.4(s, 3H); 13C NMR (75 MHz; CDCl3) δ 27.5, 120.1, 121.0,
123.2, 124.4, 128.8, 129.1, 129.8, 131.1, 132.5, 134.4, 135.8, 141.3,
150.2, 151.5, 154.4, 158.3, 158.7, 163.0, 163.4, 193.9; MS m/z (%
base), 368(Mþ, 100), 339(20), 290(57), 178(11), 106(10), 78(15).
Anal. Calcd for C21H12N4O3: C, 68.47; H, 3.26; N, 15.21. Found:
C, 68.45; H, 3.46; N, 14.91.
10-(Methylcarbamoyl)-8-oxo-8H-benzo[e]pyrido[3,2-j]perimidine-
9-carboxylic Acid (8h). Pale yellow powder; 1H NMR (300 MHz;
d6-DMSO) δ 12.99(s, 1H), 9.30(d, 1H, J=8.1), 8.87(s, 1H), 8.72(d,
1H, J = 7.5), 8.69(dd, 1H, J = 1.5, 4.5), 8.58(d, 1H, J = 3.3),
8.12(m, 2H), 7.48(dd, 1H, J = 5.1, 8.1), 3.23(s, 3H); MS m/z
(% base), 384(Mþ, 0.9), 356(2.5), 341(3.3), 327(97), 306(100),
106(2.7), 78(14). Anal. Calcd for C21H12N4O4: C, 65.62; H, 3.15;
N, 14.58. Found: C, 65.45; H, 3.40; N, 14.62.
5-Methyl-7-nicotinoyl-4H-benzo[de]pyrido[4,3-g]isoquinoline-
4,6(5H)-dione (5g). Pale yellow crystal; H NMR (300 MHz;
Photolysis of 3 with 4i. A solution of 3 (378 mg, 2 mmol) and 4i
(724 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h to reach a 45% conversion
of isoquinolinetrione. Workup as described above gave the
products 5i and 6i as a mixture. The ratio of the three products
was determined by HPLC with acetonitrile and water gradient
eluting. Flash column chromatagraph with petroleum ether/
ethyl acetate as eluents afforded pure analytic samples of 5i
and 6i.
1
CDCl3) δ 9.08(s, 1H), 9.0(d, 1H, J=8.1), 8.94(d, 1H, J=5.1),
8.78(d, 3H, J= 7.2), 8.50(d, 1H, J = 5.7), 8.33(dt, 1H, J =8.1,
1.8), 8.03(t, 1H, J=7.8), 7.47(dd, 1H, J=7.8, 5.1), 3.40(s, 3H);
13C NMR (75 MHz; CDCl3) δ 27.4, 116.5, 119.6, 123.6, 124.0,
124.4, 127.2, 127.7, 129.1, 129.3, 132.7, 132.9, 135.8, 136.6,
142.9, 148.8, 150.3, 151.5, 154.1, 163.3, 163.5, 194.8; MS m/z
(% base), 368(7), 367(Mþ, 100), 338(22), 289(95), 106(18),
78(20). Anal. Calcd for C22H13N3O3: C, 71.93; H, 3.54; N,
11.44. Found: C, 71.74; H, 3.84; N, 11.37.
5-Methyl-7-(pyrazine-2-carbonyl)-4H-isoquinolino[5,4-fg]-
quinoline-4,6(5H)-dione (5i). White powder; 1H NMR (300 MHz;
J. Org. Chem. Vol. 75, No. 9, 2010 2999

Yu et al.
JOCArticle
CDCl3) δ 9.70(s, 1H), 9.03(d, 1H, J = 8.4), 8.94(m, 2H), 8.74(m,
2H), 8.36(s, 1H), 8.02 (t, 1H, J=7.5), 7.72(m, 1H), 3.46(s, 3H); MS
m/z (% base), 368(Mþ, 28), 340(10), 289(100). Anal. Calcd for
C21H12N4O3: C, 68.47; H, 3.26; N, 15.21. Found: C, 68.50; H, 3.31;
N, 15.24.
24), 302(89), 289(100), 272(8), 246(16), 218(9). Anal. Calcd for
C20H14N2O3: C, 72.72; H, 4.27; N, 8.48. Found: C, 72.70; H,
4.28; N, 8.44.
(E)-4-(1-Cyclopropyl-2-oxo-2-(pyridin-3-yl)ethylidene)-2-methyl-
isoquinoline-1,3(2H,4H)-dione (9l). Yellow powder; 1H NMR
(300 MHz; CDCl3) δ 9.0(d, 1H, J = 2.1), 8.78(dd, 1H, J =5.4,
1.8), 8.34(dd, 1H, J=7.8, 1.2), 8.24-8.29(m, 2H), 7.72(td, 1H,
J=7.5, 1.5), 7.57(td, 1H, J=7.8, 0.9), 7.47(qd, 1H, J=5.4, 0.9),
3.19(s, 3H), 2.28(m, 1H), 1.30(m, 1H), 1.16(m, 1H), 1.0(m, 1H),
0.73(m, 1H); 13C NMR (75 MHz; CDCl3) δ 9.9, 10.2, 15.6, 27.3,
124.0, 125.2, 126.3, 127.6, 129.1, 129.7, 131.6, 132.0, 133.0,
135.3, 149.7, 153.5, 156.8, 164.1, 164.6, 192.8; MS m/z (% base),
332(Mþ, 33), 304(100), 275(7), 169(11), 106(77), 78(54). Anal.
Calcd for C20H16N2O3: C, 72.28; H, 4.85; N, 8.43. Found: C,
72.30; H, 4.81; N, 8.41.
5-Methyl-7-picolinoyl-4H-isoquinolino[5,4-fg]quinoxaline-
4,6(5H)-dione (6i). Pale yellow powder; H NMR (300 MHz;
1
CDCl3) δ 9.55(dd, 1H, J=8.1, 1.2), 9.06(d, 1H, J=2.1), 8.91(d,
1H, J = 1.8), 8.83(dd, 1H, J = 7.5, 1.5), 8.56(d, 1H, J = 7.5),
8.43(d, 1H, J=4.2), 8.08(m, 2H), 7.50(m, 1H), 3.47(s, 3H); MS
m/z (% base), 368(Mþ, 21), 340(100), 325(8), 290(30), 177(4),
78(3). Anal. Calcd for C21H12N4O3: C, 68.47; H, 3.26; N, 15.21.
Found: C, 68.40; H, 3.41; N, 15.24.
Photolysis of 3 with 4j. A solution of 3 (378 mg, 2 mmol) and 4j
(924 mg, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 60 h to reach a 30% conversion
of isoquinolinetrione. The yellow solid precipitated from the
solution was filtrated and rinsed with acetonitrile to give the
pure product 5j (80%).
(Z)-4-(1-Cyclopropyl-2-oxo-2-(pyridin-3-yl)ethylidene)-2-methyl-
isoquinoline-1,3(2H,4H)-dione (10l). Yellow powder; H NMR
1
(300 MHz; CDCl3) δ 8.89(d, 1H, J=2.1), 8.65(dd, 1H, J=4.5,
1.5), 8.06(m, 1H), 8.23(td, 1H, J=1.8, 8.1), 8.14(dd, 1H, J=1.2,
7.8), 7.81(dt, 1H, J=1.5, 7.2), 7.63(dt, 1H, J=1.2, 7.5), 7.98(dt,
1H, J = 8.1, 1.8), 7.25(m, 4H), 3.46(s, 3H), 3.07(m, 1H),
0.43-1.28(m, 4H); 13C NMR (75 MHz; CDCl3) δ 8.5, 9.4,
14.0, 27.5, 123.9, 125.1, 125.7, 126.7, 128.9, 129.2, 130.6,
132.8, 132.9, 136.0, 150.5, 154.4, 155.0, 164.4, 166.0, 195.0;
MS m/z (% base), 332(Mþ, 24), 304(100), 275(7), 169(7),
106(52), 78(34). Anal. Calcd for C20H16N2O3: C, 72.28; H,
4.85; N, 8.43. Found: C, 72.29; H, 4.88; N, 8.38.
Photolysis of 3 with 4m. A solution of 3 (378 mg, 2 mmol) and
4m (576 m g, 4 mmol) in acetonitrile (100 mL) was irradiated
with light of wavelength >400 nm for 24 h to reach a 96%
conversion of isoquinolinetrione. Workup as described above
gave the products 5m and 9m. Flash column chromatagraph
with chloroform/methanol as eluents afforded pure analytic
samples of 5m and 9m.
5-Methyl-7-nicotinoyl-4H-isoquinolino[4,5-jk]phenanthridine-
4,6(5H)-dione (5j). Yellow powder; 1H NMR (300 MHz; CDCl3)
δ 9.48(d, 1H, J=8.4), 9.18(s, 1H), 9.01(d, 1H, J=8.4), 8.92(d,
1H, J=7.5), 8.81(bs, 2H), 8.48(d, 1H, J=8.1), 8.37(d, 1H, J=
7.2), 8.14(t, 1H J=7.8), 7.98(t, 1H, J=7.2), 7.89(t, 1H, J=6.9),
7.57(t, 1H, J = 4.8), 3.49(s, 3H); MS m/z (% base), 417(Mþ,
100), 388(31), 339(40), 78(10). Anal. Calcd for C26H15N3O3: C,
74.81; H, 3.62; N, 10.07. Found: C, 74.77; H, 3.70; N, 10.12,
Photolysis of 3 with 4k. A solution of 3 (378 mg, 2 mmol) and
4k (924 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 60 h to reach a 28% conversion
of isoquinolinetrione. Dark yellow solid precipitated from the
reaction solution was filtrated and rinsed with acetonitrile to
give the pure product 5k(85%).
5-Methyl-7-picolinoyl-4H-isoquinolino[4,5-jk]phenanthridine-
4,6(5H)-dione (5k). Dark yellow powder; 1H NMR (300 MHz;
CDCl3) δ 9.45(d, 1H, J=8.4), 9.17(s, 1H), 9.01(d, 1H, J=7.8),
8.88(dd, 1H, J = 7.5, 0.9), 8.57(d, 1H, J = 7.8), 8.38-8.44(m,
2H), 8.02-8.11(m, 2H), 7.96(t, 1H, J = 6.9), 7.88(t, 1H, J =
7.2),7.46-7.50(m, 1H), 3.47(s, 3H); MS m/z (% base), 417(Mþ,
90), 388(100), 339(25), 78(4). Anal. Calcd for C26H15N3O3: C,
74.81; H, 3.62; N, 10.07. Found: C, 74.90; H, 3.60; N, 10.11,
Photolysis of 3 with 4l. A solution of 3 (378 mg, 2 mmol) and 4l
(572 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h. Workup as described
above gave the products 5l, 6l and 9l, 10l as a mixture. The ratio
of the four products was determined by HPLC with acetonitrile
and water gradient eluting. Flash column chromatagraph with
chloroform as eluents afforded pure analytic samples of 5l, 6l
and 9l, 10l.
7-(Cyclopropanecarbonyl)-5-methyl-4H-isoquinolino[4,5-gh]-
quinazoline-4,6(5H)-dione (5m). White powder; H NMR (300
1
MHz; CDCl3) δ 9.60(s, 1H), 9.54(dd, 1H, J = 8.1, 1.2), 9.38(s,
1H), 8.84(dd, 1H, J=7.8, 1.5), 8.05(t, 1H, J=7.5), 3.56(s, 3H),
2.37(m, 1H), 1.89(m, 1H), 1.22-1.46(m, 3H); 13C NMR (75 MHz;
CDCl3) δ 12.6, 14.8, 24.3, 27.6, 118.0, 120.1, 123.2, 128.8, 129.1,
129.3, 131.0, 134.2, 145.6, 151.7, 158.1, 159.1, 163.3, 163.7, 205.1;
MS m/z (% base), 331(Mþ, 5), 303(100), 290(35), 276(16),
273(7), 178(15). Anal. Calcd for C19H13N3O3: C, 68.88; H,
3.95; N, 12.68. Found: C, 68.86; H, 3.97; N, 12.70.
(E)-4-(1-Cyclopropyl-2-oxo-2-(pyrimidin-5-yl)ethylidene)-
2-methylisoquinoline-1,3(2H,4H)-dione (9m). Yellow powder;
1H NMR (300 MHz; CDCl3) δ 9.36(s, 1H), 9.16(s, 2H),
8.34(dd, 1H, J = 8.1, 1.2), 8.26(d, 1H, J = 8.1), 7.73(td, 1H,
J=7.5, 1.5), 7.59(td, 1H, J=8.1, 1.2), 3.20(s, 3H), 2.28(m, 1H),
1.35(m, 1H), 1.16(m, 1H), 1.10(m, 1H), 0.71(m, 1H); 13C NMR
(75 MHz; CDCl3) δ 10.0, 10.2, 15.3, 27.4, 125.5, 126.2, 127.6,
129.2, 129.5, 129.8, 131.6, 133.2, 155.5, 156.5, 161.2, 163.9,
164.6, 190.9; MS m/z (% base), 333(Mþ, 7), 305(100), 169(15),
107(40). Anal. Calcd for C19H15N3O3: C, 68.46; H, 4.54; N,
12.61. Found: C, 68.47; H, 4.50; N, 12.69.
7-(Cyclopropanecarbonyl)-5-methyl-4H-isoquinolino[4,5-gh]-
quinoline-4,6(5H)-dione (5l). White powder; 1H NMR (300 MHz;
CDCl3) δ 9.58(dd, 1H, J = 8.4, 1.5), 9.17(dd, 1H, J = 4.5, 1.8),
8.75(dd, 1H, J=4.5, 1.2), 8.24(dd, 1H, J=8.4, 1.5), 7.99(t, 1H, J=
7.5), 7.68(q, 1H, J = 4.2), 3.57(s, 3H), 2.34(m, 1H), 1.83(m, 1H),
1.16-1.42(m, 3H); 13C NMR (75 MHz; CDCl3) δ 12.2, 14.1, 23.9,
27.4, 116.8, 122.7, 122.8, 123.4,127.3, 128.5, 130.1, 130.7, 132.1,
135.9, 147.1, 147.7, 152.4, 163.8, 164.1, 206.5; MS m/z (% base),
330(Mþ, 20), 302(100), 289(86), 246(18), 247(20), 218(7). Anal.
Calcd for C20H14N2O3: C, 72.72; H, 4.27; N, 8.48. Found: C, 72.68;
H, 4.25; N, 8.51.
Photolysis of 3 with 4n. A solution of 3 (378 mg, 2 mmol) and
4n (576 m g, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 12 h in oxygen atmosphere.
Workup as described above gave the product 5n. Flash column
chromatagraph with chloroform/methanol as eluents afforded
pure analytic samples of 5n (21%).
7-(Cyclopropanecarbonyl)-5-methyl-4H-benzo[de]pyrido[4,3-g]-
isoquinoline-4,6(5H)-dione (6l). Pale yellow powder; H NMR
1
7-(Cyclopropanecarbonyl)-5-methyl-4H-isoquinolino[5,4-fg]-
quinoxaline-4,6(5H)-dione (5n). White powder; H NMR (300
1
(300 MHz; CDCl3) δ 9.33(s, 1H), 8.98(m, 2H), 8.80(d, 1H, J =
6.3), 8.51(d, 1H, J = 5.4), 8.01(t, 1H, J = 7.5), 3.57(s, 3H),
MHz; CDCl3) δ 9.48(dd, 1H, J=7.8, 1.2), 9.07(s, 2H), 8.78(dd,
1H, J=7.5, 1.2), 8.03(t, 1H, J=7.8), 3.58(s, 3H), 2.35(m, 1H),
1.80(m, 1H), 1.54(m, 1H), 1.13-1.26(m, 2H); 13C NMR (75
MHz; CDCl3) δ 11.4, 13.4, 23.7, 27.4, 119.9, 122.9, 127.2, 128.8,
129.6, 130.3, 132.5, 140.0, 142.8, 146.0, 146.1, 147.2, 163.1,
2.39(m, 1H), 1.90(m, 1H), 1.52(m, 1H), 1.20-1.40(m, 2H); 13
C
NMR (75 MHz; CDCl3) δ 12.7, 14.7, 24.2, 27.5, 116.3, 117.5,
123.1, 123.5, 127.3, 127.4, 128.7, 128.9, 132.6, 136.7, 147.2,
148.5, 151.9, 163.4, 163.7, 206.1; MS m/z (% base), 330(Mþ,
3000 J. Org. Chem. Vol. 75, No. 9, 2010

Yu et al.
JOCArticle
163.7, 205.2; MS m/z (% base), 331(Mþ, 1), 304(2), 303(100),
290(65), 288(6), 273(4), 177(2). Anal. Calcd for C19H13N3O3: C,
68.88; H, 3.95; N, 12.68. Found: C, 68.81; H, 3.99; N, 12.69.
Photolysis of 3 with 4o. A solution of 3 (378 mg, 2 mmol) and
4o (772 mg, 4 mmol) in acetonitrile (100 mL) was irradiated with
light of wavelength >400 nm for 48 h. Workup as described above
gave the product 5o. Flash column chromatagraph with chloro-
form/methanol as eluents afforded pure analytic samples of 5o.
7-(Cyclopropanecarbonyl)-5-methyl-4H-isoquinolino[4,5-jk]-
phenanthridine-4,6(5H)-dione (5o). Pale yellow powder; 1H
NMR (300 MHz; CDCl3) δ 9.37(d, 1H, J = 8.4), 9.36(s, 1H),
8.90(d, 1H, J=8.1), 8.83(dd, 1H, J=1.2, 7.5), 8.35(dd, 1H, J=
1.2, 8.1), 8.03(t, 1H, J=8.1), 7.93(dt, 1H, J=1.5, 7.2), 7.83(dt,
1H, J=1.5, 7.2), 3.59(s, 3H), 2.43(m, 1H), 1.92(m, 1H), 1.55(m,
1H), 1.24-1.38(m, 2H); 13C NMR (75 MHz; CDCl3) δ 12.8,
14.9, 24.6, 27.5, 117.5, 121.1, 123.2, 123.3, 127.5, 127.9,128.2,
128.3, 128.7, 130.6, 130.9, 132.4, 134.2, 135.3, 146.6, 147.3,
150.0, 163.4, 163.9, 206.4; MS m/z (% base), 381(1), 380(Mþ,
35), 352(100), 339(54), 337(4), 322(3), 296(6), 44(2). Anal. Calcd
for C24H16N2O3: C, 75.78; H, 4.24; N, 7.36. Found: C, 75.78; H,
4.23; N, 7.40.
Acknowledgment. The authors would like to acknowledge
financial support from the National Natural Science Foun-
dation of China (20702024, 20972067, 90813035) and the
Ministry of Science and Technology on the Austria-China
Cooperation project (2007DFA41590).
Supporting Information Available: General experimental
information; structure and DFT calculation on the diradical
intermediates DR1 and DR2; ORTEP drawing of compound 6h
and 7h; CIF files of 6h and 7h; UV absorption and fluorescent
emission of representative aza-polycyclic products; copies of 1H
and 13C NMR spectra for new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 9, 2010 3001