LETTER
Polymer-Assisted Strategy towards Fused [2,1-b]Quinazolinones
2611
Table 2 Products and Yields for the Preparation of Optically Active
Vasicinones
(3) (a) Amin, A. H.; Mehta, D. R. Nature 1959, 183, 1317.
(b) Mehta, D. R.; Naravane, J. S.; Desai, R. M. J. Org. Chem.
1963, 28, 445. (c) Jain, M. P.; Koul, S. K.; Dhar, K. L.; Atal,
C. K. Phytochemistry 1980, 19, 1880.
Substrate
PS-Reagent
Product,a Yield (%)b
(4) (a) Kamal, A.; Ramana, K. V.; Rao, M. V. J. Org. Chem.
2001, 66, 997. (b) Mhaske, S. B.; Argade, N. P. J. Org.
Chem. 2001, 66, 9098. (c) Kamal, A.; Ramana, A. V.;
Reddy, K. S.; Ramana, K. V.; Babu, A. H.; Prasad, B. R.
Tetrahedron Lett. 2004, 45, 8187.
(5) (a) Al-Shamma, A.; Drake, S.; Flynn, D. L.; Mitscher, L. A.;
Park, Y. H.; Rao, G. S. R.; Simpson, A.; Swayze, J. K.;
Veysoglu, T.; Wu, S. T. S. J. Nat. Prod. 1981, 44, 745.
(b) Koizumi, M.; Matsuura, I.; Murakami, Y. Japan Kokai
7,777,093, 1977; Chem. Abstr. 1978, 88, 6930.
(6) (a) Duan, J.; Zhou, R.; Zhao, S.; Wang, M.; Che, C.
Zhongguo Yaoke Daxue Xuebao 1998, 29, 21. (b) Fan, Z.;
Yao, X.; Gu, L.; Wang, J.; Wang, J.; He, A.; Zhang, B.;
Wang, X.; Wang, H. Shenyang Yaoxueyuan Xuebao 1993,
10, 136. (c) Rahman, A. U.; Sultana, N.; Akhter, F.; Nighat,
F.; Choudhary, M. I. Nat. Prod. Lett. 1997, 10, 249. (d) D'
Cruz, J. L.; Nimbkar, A. Y.; Kokate, C. K. Indian Drugs
1980, 17, 99. (e) Bhide, M. B.; Mahajani, S. S. Bull.
Haffkine Inst. 1975, 3, 128. (f) Choudhury, M. K.
6a–c
C
9a (>99)
9b (98)
9c (99)
9a–c
D+E
F
10a (95)
10b (86)
10c (89)
10a–c
11a–c
11a–c
11a (92)
11b (90)
11c (87)
H
(10S)a (93)
(10S)b (90)
(10S)c (90)
G
(10R)a (95)
(10R)b (91)
(10R)c (90)
Naturwissenschaften 1979, 66, 205.
a Characterized by 1H NMR and EI mass spectra.
b Isolated yields.
(7) (a) Kamal, A.; Reddy, K. L.; Devaiah, V.; Shankaraiah, N.
Synlett 2004, 2533. (b) Kamal, A.; Devaiah, V.; Reddy, K.
L.; Shankaraiah, N. Adv. Synth. Catal. 2006, 348, 249.
(8) (a) Weinshenker, N. M.; Shen, C. M.; Wong, J. Y. Org.
Synth., Coll. Vol. VI; John Wiley & Sons: London, 1988,
951. (b) Wolman, Y.; Kivity, S.; Frankel, M. J. Chem. Soc.,
Chem. Commun. 1967, 629. (c) Grieder, A.; Thomas, A. W.
Synthesis 2003, 1707. (d) Ploypradith, P.; Kagan, R. K.;
Ruchirawat, S. J. Org. Chem. 2005, 70, 5119. (e) Choi, J.;
Yoon, N. M. Synth. Commun. 1995, 25, 2655. (f)Frechet,J.
M. J.; Darling, P.; Farrall, M. J. J. Org. Chem. 1981, 46,
1728. (g) Hu, J.-B.; Zhao, G.; Ding, Z.-D. Angew. Chem. Int.
Ed. 2001, 40, 1109.
(9) Typical Procedure: Preparation of Compound 3a.
N-Cyclohexylcarbodiimide N-methyl polystyrene A (1.32
mmol, 1.30 mmol/g) was added to a dry reaction vessel.
Compound 1a (163 mg, 1.0 mmol) in CH2Cl2 (10 mL) was
added to the dry resin and the resulting mixture was stirred
at r.t. for 5 min before the corresponding lactam 2 (56 mg,
0.66 mmol) in CH2Cl2 (2 mL) was added and the stirring
continued at r.t. for 10 h. The resin was removed by filtration
and washed with CH2Cl2. Evaporation of the filtrate
provided 3a in 97% yield. Mp 81–83 °C; IR (KBr): 2150,
1750, 1680 cm–1; 1H NMR (200 MHz, CDCl3): d = 2.19 (q,
J = 6.8 Hz, 2 H), 2.62 (t, J = 7.5 Hz, 2 H), 4.0 (t, J = 7.5 Hz,
2 H), 7.2 (m, 3 H), 7.5 (t, J = 7.5 Hz, 1 H); MS (EI): m/z =
230 [M+].
(10) Typical Procedure: Preparation of Compound 6a.
Triphenylphosphine-impregnated polystyrene B (3.2 mmol,
3 mmol/g) was suspended in anhydrous CH2Cl2 (10 mL) and
the 2-azidobenzoyl lactam 3a (150 mg, 0.65 mmol) was
added and the suspension was stirred for 5 h at r.t. The resin
was removed by filtration and washed with CH2Cl2 and
evaporation of the filtrate afforded 6a in 98% yield. Mp 104–
106 °C; IR (KBr): 1675 cm–1; 1H NMR (200 MHz, CDCl3):
d = 2.32 (q, J = 7.5 and 8.0 Hz, 2 H), 3.22 (t, J = 8.0 Hz, 2
H), 4.19 (t, J = 7.5 Hz, 2 H), 7.5 (t, J = 7.4 Hz, 1 H), 7.6–7.8
(m, 2 H), 8.31 (d, J = 8.0 Hz, 1 H); MS (EI): m/z = 186 [M+].
(11) Typical Procedure: Preparation of Compound 9a. To a
stirred solution of compound 6a (115 mg, 0.61 mmol) in dry
THF was added the Br3– form of Amberlyst A-26 C (515 mg,
0.65 mmol, 1.26 mmol/g). The mixture was allowed to stir at
r.t. for 18–20 h. After completion of the reaction as indicated
In conclusion, a clean preparation of fused [2,1-
b]quinazolinones and enantioselective preparations of
(d)- and (l)-vasicinone has been developed by employing
polymer-supported reagents. This synthetic strategy is
readily amenable for designing and preparing a combina-
torial library. It is noteworthy that in the entire process,
the work-up has been simplified to filtration and evapora-
tion for all the steps and all the reagents could be reused,
thus addressing the problems of environmental and
economical sustainability.
Acknowledgment
The authors VD, NS and KLR are grateful to CSIR, New Delhi for
the award of Research fellowships.
References and Notes
(1) For recent reviews, see: (a) Kirschning, A.; Monenschein,
H.; Wittenberg, R. Angew. Chem. Int. Ed. 2001, 40, 650.
(b) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P.
S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.;
Storer, R. I.; Taylor, S. J. J. Chem. Soc., Perkin Trans. 1
2000, 3815. (c) Storer, R. I.; Takemoto, T.; Jackson, P. S.;
Ley, S. V. Angew. Chem. Int. Ed. 2003, 42, 2521.
(d) Jaunzems, J.; Hofer, E.; Jesberger, M.; Sourkouni-
Argirusi, G.; Kirschning, A. Angew. Chem. Int. Ed. 2003, 42,
1166. (e) Storer, P. I.; Takemoto, T.; Jackson, P. S.; Brown,
D. S.; Baxendale, I. R.; Ley, S. V. Chem. Eur. J. 2004, 10,
2529. (f) Wang, Y.; Sauer, D. R. Org. Lett. 2004, 6, 2793.
(g) Siu, J.; Baxendale, I. R.; Lewthwaite, R. A.; Ley, S. V.
Org. Biomol. Chem. 2005, 3, 3140.
(2) (a) Johne, S.; Groger, D. Pharmazie 1970, 25, 22.
(b) Coppola, M. Synthesis 1980, 505. (c) Johne, S. Prog.
Drug Res. 1982, 26, 259. (d) Johne, S. Prog. Chem. Org.
Nat. Prod. 1984, 46, 159. (e) Michael, J. P. Nat. Prod. Rep.
2000, 17, 603; and references cited therein.
Synlett 2006, No. 16, 2609–2612 © Thieme Stuttgart · New York