Synthesis of 4-, 5- and 6-Benzoylated 7-Azaindoles

Abstract

Efficient syntheses of 4-, 5- and 6-benzoyl-7-azaindoles are described. Two strategies were developed: i) formation of 4-lithio and 5-lithio-7-azaindole and reaction with aldehydes and ii) organomagnesium addition to 6-cyano-7-azaindole. Both methods should allow the introduction of a diverse range of acyl substituents.

Key words

7-azaindole - acylation - 6-cyano-7-azaindole - fused-ring system - lithium-halogen exchange

References

• 1 Mérour J.-Y. Joseph B. Curr. Org. Chem.  2001,  5:  471 ; and references cited therein
• 2 Popowycz F. Routier S. Joseph B. Mérour J.-Y. Tetrahedron  2007,  63:  1031 
• 3 Zhang Z. Yang Z. Wong H. Zhu J. Meanwell NA. Kadow JF. Wang T. J. Org. Chem.  2002,  6226 
• 4 Thibault C. L’Heureux A. Bhide RS. Ruel R. Org. Lett.  2003,  5:  5023 
• 5 Minakata S. Komatsu M. Ohshiro Y. Synthesis  1992,  661 
• 6 During the referee process, an alternative syntheses of 6-cyano-7-azaindole(4) was reported, see: Storz T. Bartberger M. Sukit S. Wilde C. Soukup T. Synthesis  2008,  201 
• 7 An Minakata S. Hamada T. Komatsu M. J. Agric. Food Chem.  1997,  45:  2345 
• 8 Benoît S, Gringas S, and Soundara N. inventors; PCT Int. Appl. WO  2003082289.  ; Chem. Abstr. 2003, 139, 307795
• 9 Fife WK. J. Org. Chem.  1983,  48:  1375 
• 10 Vorbrüggen H. Krolikiewicz K. Synthesis  1983,  316 
• 12a Guillaumet G, Savelon L, Viaud MC, Pavli P, Renard P, Pfeiffer B, Caignard DH, and Bizo-Espiard JG. inventors; Eur. Pat. Appl. EP  691339.  ; Chem. Abstr. 1996, 124, 261019p
• 12b Mazéas D. Guillaumet G. Viaud MC. Heterocycles  1999,  50:  1065 
• 13 Estel L. Marsais F. Quéguiner G. J. Org. Chem.  1988,  53:  2740 
• 14a Leusink AJ. Budding HA. Drenth W. J. Organomet. Chem.  1968,  11:  541 
• 14b Wollenberg RH. Albizati KF. Peries R. J. Am. Chem. Soc.  1977,  99:  7365 
• 15 Sakamoto T. Satoh C. Kondo Y. Yamanaka H. Heterocycles  1992,  34:  2379 
• 16 Moyer M. Shiurba JF. Rapoport H. J. Org. Chem.  1986,  51:  5106 
• 17 Brière J.-F. Dupas G. Quéguiner G. Bourguignon J. Heterocycles  2000,  52:  1371 
• 18 N’Ait Ajjou A. Muzart J. Savelon L. Guillaumet G. Synthesis  1993,  539 
• 19 L’Heureux A. Thibault C. Ruel R. Tetrahedron Lett.  2004,  45:  2317 
• 20 Bourguignon G. Quéguiner G. J. Heterocycl. Chem.  1989,  26:  1029 
• 21 Bhupathy M. Conlon D. Wells K. Nelson J. Reider P. Rossen K. Sager J. Volante R. Dorsey B. Hoffman J. Joseph S. McDaniel S. J. Heterocycl. Chem.  1995,  32:  1283 

11

It is noteworthy that using Et₃N stored on KOH, the reaction did not work.