Photoinduced reactions of 1,3,4(2H)-isoquinolinetriones with diphenylacetylenes - An efficient one pot syntheses of dibenz[de,g]-(2H)-isoquinoline-4, 6-dione derivatives

Article abstract of DOI:10.1016/S0040-4039(00)01430-1

Photoinduced reactions of 1,3,4(2H)-isoquinolinetriones with diphenylacetylenes afforded the corresponding dibenz[de,g]-(2H)-isoquinoline-4,6-dione derivatives in moderate to high yields via a reaction sequence involving [2+2] photocycloaddition, ring opening rearrangement of the oxetene intermediate and dehydrogenative cyclization in one pot. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01430-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8141–8145
Photoinduced reactions of 1,3,4(2H)-isoquinolinetriones with
diphenylacetylenes—an efficient one pot syntheses of
dibenz[de,g]-(2H)-isoquinoline-4,6-dione derivatives
Yan Zhang,a Su-Ping Qian,b Hoong-Kun Func and Jian-Hua Xua,*
aDepartment of Chemistry, Nanjing University, Nanjing 210093, PR China
bShanghai Institute of Nuclear Research, Chinese Academy, Shanghai 201800, PR China
cX-Ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, 11800, USM, Penang, Malaysia
Received 8 May 2000; revised 1 August 2000; accepted 23 August 2000
Abstract
Photoinduced reactions of 1,3,4(2H)-isoquinolinetriones with diphenylacetylenes afforded the corre-
sponding dibenz[de,g]-(2H)-isoquinoline-4,6-dione derivatives in moderate to high yields via a reaction
sequence involving [2+2] photocycloaddition, ring opening rearrangement of the oxetene intermediate and
dehydrogenative cyclization in one pot. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: photochemistry; isoquinolines; alkynes; polycyclic heterocyclic compounds.
Reactions of triplet excited quinones1 and aromatic ketones2 with diphenylacetylenes are
known to give quinone methides and a,b-unsaturated ketones, respectively, via an oxetene
intermediate3 formed by [2+2] cycloaddition of the carbonyl group with the alkyne CꢀC bond.
The scope of these reactions, however, has not been extensively explored. 1,3,4(2H)-Isoquino-
linetrione derivatives have a variety of biological activities and are synthetic precursors for many
naturally occurring alkaloids.4 Therefore, investigations on structural elaborations of isoquino-
linetriones have been attracting much research interest recently.5 To explore further the scope of
the photoinduced reactions of carbonyl compounds with alkynes and their synthetic applica-
tions, we report here photoinduced reactions between 1,3,4(2H)-isoquinolinetriones 1a–c and
diphenylacetylenes 2a–c, which gave the dibenz[de,g]-(2H)–isoquinoline-4,6-dione derivatives
3a–g via sequential reactions in one pot.
* Corresponding author. Tel: 086-025-3592709; fax: 086-025-3317761; e-mail: xujh@nju.edu.cn
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01430-1

8142
Irradiation of a solution of 1a (0.05 mol dm−3) and 2a (0.1 mol dm−3) in MeCN with light of
u>400 nm under an argon atmosphere led to the formation of the tetracyclic product 3a (82%
yield) and a mixture of two diastereoisomeric hydrogenated 4-[benzoylphenylmethylene]-iso-
1
quinoline-1,3-diones 4a and 4b in a ratio of ꢀ2.8:1 in a total yield of 8%. In the H NMR
spectrum of 3a, the protons in the ‘bay’ area (H9 and H10) which are deshielded by all the three
phenyl rings of the phenanthrene framework, and H7 which is deshielded by the nearby carbonyl
group resonate at the lowest field (l 8.7–9.1 ppm). The MS spectrum is characterized by a strong
molecular ion peak at m/z 365. This dibenz[de,g]-(2H)-isoquinoline-4,6-dione structure was
further unambiguously proved by an X-ray crystallographic analysis of product 3f (vide infra)
as shown in Fig. 1. The structure of 4a was also established by an X-ray crystallographic
analysis as shown in Fig. 2.
Figure 1. ORTEP drawing of compound 3f
Figure 2. ORTEP drawing of compound 4a

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Table 1
Photoinduced reactions of 1,3,4(2H)-isoquinolinetriones 1 with alkynes 2a
Products and yieldd
red
ox
c
1
E1/2
2
E1/2
DGET (kcal
Irrad. time
(h)
Conversion
(%)
(V)b
(V)b
mol−1
)
1a
1b
1c
1a
−1.24
−0.99
−1.18
−1.24
2a
2a
2a
2b
1.81
1.81
1.81
1.97
6.0
0.2
4.5
9.6
48
48
48
60
100
81
84
3a (82%), 4a (6%), 4b (2%)
3b (83%), 5a, 6a (7.5%)
3c (68%), 7 (2%), 5b, 6b (5%)
3d (50%), 3e (40%). 5c, 5d,
6c, 6d (7%)
51
1a
−1.24
2c
1.48
8.5
60
30
3f (44%), 3g (4%), 5e, 5f, 6e,
6f (2%), 8 (40%)
a All the reactions were conducted in MeCN except for the photoreaction of 1a with 2c, which was carried out in
benzene. The concentration of 1 was 0.05 mol dm−3, and 2 was 0.1 mol dm−3
.
b Measured by cyclic voltammetry in MeCN with tetrabutylammonium perchlorate (0.1 M) as supporting
electrolyte and platinum as working and auxiliary electrodes versus a saturated calomel electrode (SCE).
c Estimated by the Weller Equation.8
d Yields of isolated products based on consumed 1. The ratios of the stereoisomers were determined from H NMR
1
spectra of the product mixtures.
Similar irradiation of 1b and 1c with 2a, respectively, in MeCN gave the corresponding
tetracyclic products (3b, 3c) and a mixture of E- and Z-4-[benzoylphenylmethylene]-1,3-iso-
quinolinediones (5a, 6a and 5b, 6b), respectively (Table 1). A small amount (2% yield) of 7 was
also obtained as a by-product in the reactions of 1c with 2a. The isomers 5a and 6a, as well as
5b and 6b are inseparable by flash chromatography on a silica gel column and the ratio of the
1
two isomers was determined by H NMR measurement of the product mixture.
The structure of the products 3 and the isolation of the 4-methylene-1,3-isoquinolinedione
products 5 and 6 suggest that a reaction sequence shown in Scheme 1 is involved in the
3
formation of the products. [2+2] Cycloaddition of 1* with diphenylacetylene via a diradical
intermediate may give an unstable spirooxetene, which rearranges to the E- and Z-4-methylene-
Scheme 1.

8144
1,3-isoquinolinediones. The E-isomer could be photoisomerized to the Z-isomer which is then
irreversibly transformed to product 3 by cyclization and oxidative dehydrogenation, which is a
further example of the much investigated stilbene–phenanthrene photo-transformation6 in the
presence of a trace amount of oxygen in the solution.
That the triplet np* state7 of 1 is the reactive excited state was proved by quenching
experiments in which the reactions were found to be fully quenched by such quenchers as styrene
(ET 61.7 kcal mol−1) and quinoline (ET 62.8 kcal mol−1). The intermediacy of 5 and 6 in the
formation of 3 by electrocyclic reactions was supported by a control experiment where
independent irradiation of a pure sample of 5a in MeCN under conditions as mentioned above
afforded 3b quantitatively.
Photoinduced reactions of 1a with the monosubstituted diphenylacetylenes 2b and 2c were
also investigated. Photolysis of 1a with 2b in acetonitrile gave two tetracyclic products 3d (50%
yield) and 3e (40% yield) as well as all the four possible 4-methylene-1,3-isoquinolinedione
isomers 5c, 5d, 6c and 6d in a total yield of 7%. The two tetracyclic products 3d and 3e were
obtained in a ratio of 5/4, indicating that the two isomeric oxetene intermediates are formed
with low regioselectivity. On the contrary, photocycloaddition of 1a with 2c proceeded with high
regioselectivity to afford the corresponding tetracyclic products 3f and 3g (total yield 48%) in a
ratio of 11:1, together with a small amount (2%) of a mixture the isomeric 4-methylene-1,3-iso-
quinolinediones. In this case, serious hydrolysis of 1a accompanied the reaction and the acid 8
was obtained in 40% yield. The structure of 3f9 was established by an X-ray crystallographic
analysis as shown in Fig. 1.
3
To assess the possibility of single electron transfer (SET) interaction between 1* and the
alkynes, free enthalpies for SET (DGET) in MeCN have been estimated by the Weller equation.8
Although the DGETs are slightly positive in most cases, the following facts suggest that an
electron transfer (charge transfer) interaction between 31* and the alkyne may play an important
role in these reactions: (1) compounds 1a–c could hardly take part in photocoupling reactions
with electron deficient alkynes such as ethyl phenylpropiolate and 1,3-diphenyl-2-propyn-1-one,
and irradiation under the same conditions as mentioned above resulted in a very sluggish
reaction. (2) Photo reactions of 1a with 2c in MeCN, where the DGET is −1.6 kcal mol−1, are
extremely slow, while reactions in benzene (DGET 8.5 kcal mol−1) proceed substantially faster. In
MeCN, further dissociation of the triplet solvent separated ion radical pair (SSIP) prevails,
leading to a much diminished reaction efficiency.
In summary, photoinduced reactions of 1a–c with diphenylacetylenes 2a–c, respectively,
resulted in the efficient formation of the dibenz[de,g]-(2H)-isoquinoline-4,6-diones 3a–g via a
reaction sequence of photoinduced [2+2] cycloaddition-ring opening rearrangement—E-, Z-iso-
merization of the 4-methylene-1,3-isoquinolinedione-electrocyclic cyclization-dehydrogenative
aromatization, with all these reactions accomplished in one pot. These dibenz[de,g]-(2H)-iso-
quinoline-4,6-diones are interesting targets for biological activity investigation in view of their
structural similarity with the wide range of dibenzoannelated isoquinoline alkaloids (e.g.
apomorphine etc.).10 The mechanistic details of these reactions are being further investigated.
Acknowledgements
Project supported by the National Natural Science Foundation of China (29772016).

8145
References
1. (a) Zimmerman, H. E.; Craft, L. Tetrahedron Lett. 1964, 2131; (b) Bryce-Smith, D.; Fray, G. I.; Gilbert, A.
Tetrahedron Lett. 1964, 2137; (c) Bryce-Smith, D.; Gilbert, A.; Johnson, M. G. Tetrahedron Lett. 1968, 2863; (d)
Farid, S.; Kothe, W.; Pfundt, G. Tetrahedron Lett. 1968, 4147; (e) Pappas, S. P.; Portnoy, N. A.; J. Org. Chem.
1968, 33, 2200; (f) Bardamova, M. I.; Berus, E. I.; Vlasov, A. A.; Kotlyarevskii, I. L.; Izv. Akad. Nauk SSSR,
Ser. Khim. (Russ) 1977, 912; (g) Bosch, E.; Hubig, S. M.; Kochi, J. K. J. Am. Chem. Soc. 1998, 120, 386.
2. Polman, H.; Mosterd, A.; Bos, H. J. T. Rec. Trav. Chim. 1973, 92, 845 and references cited therein.
3. (a) Friedrich, L. E.; Lam, P. Y. J. Org. Chem. 1981, 46, 306. (b) Friedrich, L. E.; Schuster, G. B. J. Am. Chem.
Soc. 1971, 93, 4602.
4. See, for example: (a) Malamas, M. S.; Hohman, T. C.; Millen, J. J. Med. Chem. 1994, 37, 2043; (b) Hall, I. H.;
Chapman, J. M.; Wong, O. T. Anticancer Drugs 1994, 5, 75.
5. See, for example: (a) Ling, K. Q.; Cai, H.; Ye, J. H.; Xu, J. H. Tetrahedron 1999, 55, 1707; (b) Cornforth, J.; Du,
M. H. J. Chem. Soc., Perkin Trans. 1 1990, 5, 1463.
6. For reviews, see, (a) Mallory, F. B.; Mallory, C. W. Organic Reactions 1984, 30, 1 (b) Laarhoven, W. H., In
Organic Photochemistry, Padwa, A. Ed. Marcel Dekker: New York, 1983; Vol. 6, p. 1.
7. (a) Suau, R.; De Innstrosa Villatoro, E. P. Tetrahedron 1994, 50, 4987. (b) Suau, R.; De Innstrosa Villatoro, E.
P. Tetrahedron 1995, 51, 6293.
8. Weller, A. Z. Phys. Chem. (Wiesbaden) 1982, 133, 193.
9. Spectral data of Compound 3f: colorless crystals from chloroform, mp 296–298°C IR(KBr): 3050, 2950, 1680,
1
1650, 1610, 1580, 1520, 1360, 790, 760, 740, 700 cm−1. H NMR (CDCl3, 300 MHz, H–H COSY): 3.47 (3H, s,
NꢁCH3), 4.08 (3H, s, OꢁCH3), 7.25 (1H, d, J=9.2, H1), 7.45 (2H, t, J=7.3, 7.3, H13, H16), 7.59 (1H, t, J=7.3,
H12), 7.75 (1H, d, J=9.2, H2), 7.89 (2H, d, J=7.3, H14, H15), 7.95 (1H, dd, J=7.3, 8.2, H8), 8.12 (1H, s, H10),
8.73 (1H, d, J=7.3, H7), 8.97 (1H, d, J=8.2, H9) m/z (EI): 395 (M+, 55), 366 (23), 318 (100), 275 (11), 190 (6),
105 (32), 77 (38) (found: C, 75.81, H, 4.44, N, 3.55%. C25H17O4N requires C, 75.95; H, 4.30; N, 3.54%). Crystal
,
structure of 3f: triclinic, space group P-1 with a=8.4046(4), b=11.4204(5), c=12.4969(6) A, h=77.150(2),
3
i=89.217(1), k=83.092(2)°, V=1160.86(9) A , Z=2, Dc=1.473 g cm−3. Absorption coefficient 0.430 mm−1
,
,
F(000)=528. A crystal of 0.28×0.12×0.04 mm was used. Data were collected on an Siemens SMART CCD area
detector diffractometer equipped with graphite-monochromated Mo Ka radiation in the range of q 1.67–28.31°.
The structure was solved by direct method (SHELXL-97) and refined on F2 by full-matrix least-squares method.
A total of 8008 independent reflections [R(int)=0.0515] were used in the refinement which converged with
R=0.0706 and wR=0.1720.
10. Shamma, M. In Chemistry of the Alkaloids; Pelletier S. W. Ed. Van Nostrand Reinhold: New York, 1970;
Chapter 3, p. 31.
.