A New Route to Acridines: Pauson-Khand Reaction on Quinoline-Bearing 1-En-7-ynes Leading to Novel Tetrahydrocyclopenta[c]acridine-2,5-diones

Abstract

Efficient Pauson-Khand reactions on quinolines bearing 1-en-7-ynes features gave tetrahydrocyclopenta[c]acridine derivatives. The quinoline intermediates were obtained in two steps: a Sonogashira reaction with functionalized alkynes (TMS, Bu, Ph, CHB₂OTHP) followed by a Grignard reaction with allylmagnesium bromide. The sequence provides new acridine structures in four high yielding steps from commercially available quinolines.

Key words

quinoline - acridine - enynes - intramolecular Pauson-Khand reaction - cyclopenta[c]acridine

References

• 2a Demeunynck M. Exp. Opin. Ther. Patents  2004,  14:  55 
• 2b Demeunynck M. Charmantray F. Martelli A. Curr. Pharm. Design  2001,  7:  1703 
• 3a Carlier PR. Chow ES.-H. Han Y. Liu J. El Yazal J. Pang Y.-P. J. Med. Chem.  1999,  42:  4225 
• 3b Lee HH. Wilson WR. Ferry DM. van Zijl P. Pullen SM. Denny WA. J. Med. Chem.  1996,  39:  2508 
• 4 Belmont P. Andrez J.-C. Allan CSM. Tetrahedron Lett.  2004,  45:  2783 
• 6 Acheson RM. The Chemistry of Heterocyclic Compounds: Acridines   Vol. 9 2nd ed.:  Interscience Publishers; New York: 1973. ; and references therein
• 7 Atwell GJ. Rewcastle GW. Baguley BC. Denny WA. J. Med. Chem.  1987,  30:  664 
• 8 Sourdon V. Mazoyer S. Pique V. Galy J.-P. Molecules  2001,  6:  673 
• 9 Bernthsen A. Bender F. Chem. Ber.  1883,  16:  1802 
• 10a Gamage SA. Spicer JA. Rewcastle GW. Denny WA. Tetrahedron Lett.  1997,  38:  699 
• 10b Rosevear J. Wilshire JFK. Aust. J. Chem.  1981,  34:  839 
• 10c Albert A. Heterocyclic Compounds   Vol. 4:  Elderfield RC. J. Wiley and Sons, Inc.; New York, N.Y.: 1952. 
• 11 Smolders RR. Waefelaer A. Coomans R. Francart D. Hanuise J. Voglet N. Bull. Soc. Chim. Belg.  1982,  91:  33 
• 12a Khand IU. Knox GR. Pauson PL. Watts WE. J. Chem. Soc. D  1971,  36 
• 12b Foreman MI. J. Chem. Soc., Perkin Trans. 1  1973,  977 
• Intramolecular version of the reaction and an accepted mechanism can be found in:
• 13a Schore NE. Croudace MC. J. Org. Chem.  1981,  46:  5436 
• 13b Exon C. Magnus P. J. Am. Chem. Soc.  1983,  105:  2477 
• 13c Magnus P. Príncipe L.-M. Tetrahedron Lett.  1985,  26:  4851 
• 14a Blanco-Urgoiti J. Añorbe L. Pérez-Serrano L. Domínguez G. Pérez-Castells J. Chem. Soc. Rev.  2004,  33:  32 
• 14b Brummond KM. Kent JL. Tetrahedron  2000,  56:  3263 
• 15 Gibson SE. Stevenazzi A. Angew. Chem. Int. Ed.  2003,  42:  1800 
• 16a Pérez-Serrano L. Domínguez G. Pérez-Castells J. J. Org. Chem.  2004,  69:  5413 
• 16b Pérez-Serrano L. Blanco-Urgoiti J. Casarrubios L. Domínguez G. Pérez-Castells J. J. Org. Chem.  2000,  65:  3513 
• 17 Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  16:  4467 
• 18a Sonogashira reactions on chlorinated quinolines have already been reported, but it was not applicable on 2-chloro-3-quinoline carboxaldehyde: Ciufolini MA. Mitchell JW. Roschangar F. Tetrahedron Lett.  1996,  37:  8281 
• 18b The methodology has been applied recently on this substrate with only(trimethylsilyl)acetylene: Toyota M. Komori C. Ihara M. J. Org. Chem.  2000,  65:  7110 ; here we extended the methodology to other alkyne species
• 19 Blanco-Urgoiti J. Casarrubios L. Domínguez G. Pérez-Castells J. Tetrahedron Lett.  2001,  42:  3315 
• 22 Krafft ME. Scott IL. Romero RH. Feilbelmann S. Van Pelt CE. J. Am. Chem. Soc.  1993,  115:  7199 
• 23 Dess PB. Martin JC. J. Am. Chem. Soc.  1991,  113:  7277 
• 24 Ley SV. Normant J. Griffith WP. Marsden SP. Synthesis  1994,  639 

1

Albert A.; The Acridines; Edward Arnold Publishers Ltd.: London, 1966; 2^nd ed.:

5

Diphenylamine derivatives are constructed via the Ullman reaction.

20

Observation made by the analysis of the ¹NMR spectra, showing only one diastereomer (trans/cis ratio > 95:5).

21

These results were correlated with other studies from the literature, see ref. 16a, 19.