ORGANIC LETTERS
Lewis Acid-Promoted Annulation of o-Quinonediimines by Allylstannane: A Facile Synthesis of Quinoxaline Derivatives†
2004 Vol. 6, No. 25 4743-4745
Vijay Nair,*,‡ R. Dhanya,‡ C. Rajesh,‡ Mohan M. Bhadbhade,§ and K. Manoj§ Organic Chemistry DiVision, Regional Research Laboratory (CSIR), TriVandrum, India, and National Chemical Laboratory, Pune, India
[email protected] Received September 30, 2004
ABSTRACT
Lewis acid-promoted addition of allyltri-n-butylstannane to o-quinonediimines afforded tetrahydroquinoxaline derivatives or allylated amides depending on the nature of the substituent on imine nitrogen.
The chemistry of o-benzoquinones, especially their involvement in cycloadditions, has been the subject of extensive investigations in recent years.1,2 In contrast, their aza analogues, viz.,o-quinonediimines, have received only scant attention,3 the available information on their cycloaddition being mainly concerned with their participation in DielsAlder reaction with alkenes4 and fulvenes.5 In the context of our general interest in the dipolar cycloaddition of quinonoids,6 and in view of the reported proclivity of allylstannane to manifest dipolar reactivity,7 we have examined the reaction of allyltri-n-butyltin with o-quinonediimines, in anticipation of a dihydroindole synthesis. No dipolar cycloaddition occurred, but the reaction led to a facile
synthesis of tetrahydroquinoxaline derivatives. It is noteworthy that tetrahydroquinoxaline derivatives are important from a therapeutic point of view since promising anti HIV agents,8 glucogen receptor antagonists9 and angiotensin receptor antagonists10 possess this ring system. The results of our preliminary investigations are presented in this letter. The present studies were initiated by exposing a solution of 4-chloro-o-quinonedibenzenesulfonimide11 1a to allyltrin-butyltin 2a in the presence of ZnCl2. A facile reaction occurred, and the reaction mixture on usual processing12 afforded the tetrahydroquinoxaline derivative 3a, instead of the expected dihydroindole derivative 3a′, as a colorless crystalline solid in 98% yield (Scheme 1).
† Dedicated with best wishes to Professor Minoru Isobe on the occasion of his 60th birthday. ‡ Regional Research Laboratory. § National Chemical Laboratory. (1) For a review on the chemistry of quinones, see: The Chemistry of Quinonoid Compounds; Patai, S., Rappoport, Z., Eds.; John Wiley and Sons: New York, 1988; Vol. 2, Parts 1 and 2. (2) (a) Nair, V.; Kumar, S. Synlett 1996, 1035. (b) Nair, V.; Kumar, S. J. Chem. Soc., Chem. Commun. 1994, 1341. (c) Nair, V.; Kumar, S. J. Chem. Soc., Perkin Trans. 1 1996, 443. (3) Friedrichsen, W.; Bottcher, A. Heterocycles 1981, 16, 1009 and references therein. (4) Friedrichsen, W.; Schmidt, R. Liebigs Ann. Chem. 1978, 1129. (5) (a) Friedrichsen, W.; Oeser, H. G. Liebigs Ann. Chem. 1978, 1139. (b) Friedrichsen, W.; Oeser, H. G. Liebigs Ann. Chem. 1978, 1146. (c) Friedrichsen, W.; Oeser, H. G. Liebigs Ann. Chem. 1978, 1161.
(6) (a) Nair, V.; Rajesh, C.; Dhanya, R.; Vinod, A. U. Tetrahedron Lett. 2001, 42, 2045. (b) Nair, V.; Rajesh, C.; Dhanya, R.; Rath, N. P. Tetrahedron Lett. 2002, 43, 5349. (c) Nair, V.; Rajesh, C.; Dhanya, R.; Rath, N. P. Org. Lett. 2002, 4, 953. 39, 5627. (7) (a) Herndon, J. W. J. Am. Chem. Soc. 1987, 109, 3165. (b) Herndon, J. W.; Wu, C.; Harp, J. J.; Kreutzer, K. A. Synlet 1991, 1. (c) Herndon, J. W.; Wu, C. Tetrahedron Lett. 1989, 30, 5745. (8) Patel, M.; Mc Hugh, R. J., Jr.; Cordova, B. C.; Klabe, R. M.; Erickson-Vitanen, S.; Trainor, G. L.; Rodgers, J. D. Bioorg. Med. Chem Lett. 2000, 10, 1729. (9) Guillon, J.; Dallemagne, P.; Pfeiffer, B.; Renard, P.; Manechez, D. Kervran, A.; Rault, S. Eur. J. Med. Chem. 1998, 33, 293. (10) Kim, K. S.; Qian, L.; Bird, J. E.; Dickinson, K. E. J.; Moreland, S.; Schaeffer, T. R.; Waldron, T. L.; Delaney, C. L.; Weller, H. N.; Miller, A. V. J. Med. Chem. 1993, 36, 2335. (11) Adams, R.; Winnick, C. N. J. Am. Chem. Soc. 1951, 73, 5687.
10.1021/ol048004m CCC: $27.50 Published on Web 11/11/2004
© 2004 American Chemical Society
Scheme 1
Table 2.
Similar reactivity was displayed with other substituted o-quinonedibenzenesulfonimides, and the results are summarized in Table 1.
Table 1.
entry
subsrate
yield (%)
1 2 3 4 5
1a, ) Cl, )H 1b, R1 ) Br, R2 ) H 1c, R1 ) CH3, R2 ) H 1d, R1 ) Cl, R2 ) Cl 1e, R1 ) Me, R2 ) Me
98 72 72 82 44
R1
R2
The tetrahydroquinoxaline structure of 3a was assigned on the basis of spectroscopic analysis. In 1H NMR, the C-2 proton was discernible as a multiplet at δ 4.64. The C-3 protons afforded two separate signals: one at δ 3.75 (dd, J ) 12.4 Hz, 3.4 Hz) and the other at δ 3.01 (dd, J ) 12.4 Hz, 4.0 Hz). The C-11 protons and the protons of the n-butyl group were discernible as a multiplet between δ 1.51-0.87. In the 13C NMR, the two carbons adjacent to nitrogen were seen at δ 53.7 and 50.7. The exocyclic carbon was discernible at δ 13.3. Conclusive evidence for the structure of 3a was obtained by single-crystal X-ray analysis (Figure 1).
entry
Lewis acid
yield (%)
1 2 3 4 5 6
0 AlCl3 Me2AlCl BF3‚OEt2 TiCl4 ZnCl2
