Synthesis of isocryptolepine via a Pd-catalyzed 'amination-arylation' approach

Synlett

Volumn , Issue 5, 2003, Pages 615-618

  Jonckers, Tim H M ^a   Maes, Bert U W ^a   Lemière, Guy L F ^a   Rombouts, Geert ^a   Pieters, Luc ^a   Haemers, Achiel ^a   Dommisse, Roger A ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Buchwald Hartwig amination; Intramolecular arylation; Isocryptolepine; Malaria; Palladium

Indexed keywords

2 CHLOROANILINE; 4 CHLOROQUINOLINE; 5 METHYL 5H INDOLO[3,2 C]QUINOLINE; ANILINE DERIVATIVE; ANTIMALARIAL AGENT; CRYPTOLEPINE DERIVATIVE; PALLADIUM; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; ARYLATION; CATALYSIS; CHEMICAL BOND; CYTOTOXICITY; DRUG ACTIVITY; DRUG SYNTHESIS; STRUCTURE ACTIVITY RELATION;

EID: 0037263604     PISSN: 09365214     EISSN: None     Source Type: Journal    
DOI: 10.1055/s-2003-38364     Document Type: Article

References (45)

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8. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
9. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
10. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
11. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
12. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
13. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
14. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
15. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
16. For the synthesis of 11H-indolo[3,2-c]quinolines see: (a) Arcadi, A.; Cacchi, S.; Cassetta, A.; Fabrizi, G.; Parisi, L. M. Synlett 2001, 1605. (b) Mouaddib, A.; Joseph, B.; Hasnaoui, A.; Mérour, J.-Y. Synthesis 2000, 549. (c) Cacchi, S.; Fabrizi, G.; Pace, P.; Marinelli, F. Synlett 1999, 620. (d) Go, M.-L.; Ngiam, T.-L.; Tan, A. L.-C.; Kuaha, K.; Wilairat, P. Eur. J. Pharm. Sci. 1998, 6, 19. (e) Molina, A.; Vaquero, J. J.; Garcia-Navio, J. L.; Alvarez-Builla, J.; Pascual-Teresa, B.; Gago; F.; Rodrigo, M. M.; Ballesteros, M. J. Org. Chem. 1996, 61, 5587. (f) Trécourt, F.; Mongin, F.; Mallet, M.; Quéguiner, G. Synth. Commun. 1995, 25, 4011. (g) Go, M. L.; Ngiam, T. L.; Phillipson, J. D.; Kirby, G. C.; O'Neill, M. J.; Warhurst, D. C. Eur. J. Med. Chem. 1992, 27, 301. (h) Molina, P.; Alajarin, M.; Vidal, A. Tetrahedron 1990, 46, 1063. (i) Dave, V.; Warnhoff, E. W. Tetrahedron 1975, 31, 1255.
17. For recent reviews on the Buchwald-Hartwig reaction see: (a) Barañano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (b) Frost, C. G.; Mendonça, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615. (c) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046. (d) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131.
18. For recent reviews on the Buchwald-Hartwig reaction see: (a) Barañano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (b) Frost, C. G.; Mendonça, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615. (c) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046. (d) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131.
19. For recent reviews on the Buchwald-Hartwig reaction see: (a) Barañano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (b) Frost, C. G.; Mendonça, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615. (c) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046. (d) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131.
20. For recent reviews on the Buchwald-Hartwig reaction see: (a) Barañano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (b) Frost, C. G.; Mendonça, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615. (c) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046. (d) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131.
21. For examples on intramolecular Pd-catalyzed arylation of N-(o-bromoazaheteroaryl)anilines and N-azaheteroaryl-2-bromoanilines see: (a) Ames, D. E.; Bull, D. Tetrahedron 1982, 38, 383. (b) Iwaki, T.; Yasuhara, A.; Sakamoto, T. J. Chem. Soc., Perkin Trans. 1 1999, 1505.
22. For examples on intramolecular Pd-catalyzed arylation of N-(o-bromoazaheteroaryl)anilines and N-azaheteroaryl-2-bromoanilines see: (a) Ames, D. E.; Bull, D. Tetrahedron 1982, 38, 383. (b) Iwaki, T.; Yasuhara, A.; Sakamoto, T. J. Chem. Soc., Perkin Trans. 1 1999, 1505.
23. Just before submitting this manuscript an article appeared dealing with intramolecular Pd-catalyzed arylation of N-(2-chloroaryl)-N-methylanilines and N-benzyl-N-(2-chloroaryl)-anilines: Bedford, R. B.; Cazin, C. S. J. Chem. Commun. 2002, 2310.
24. Several examples of the beneficial effect of the use of large excesses of inorganic bases in Pd-catalyzed aminations using Pd(BINAP) catalyst have already been reported by our research group: (a) Košmrlj, J.; Maes, B. U. W.; Lemière, G. L. F.; Haemers, A. Synlett 2000, 1581. (b) Jonckers, T. H. M.; Maes, B. U. W.; Lemière, G. L. F.; Dommisse, R. Tetrahedron 2001, 57, 7027. (c) Maes, B. U. W.; Loones, K. T. J.; Jonckers, T. H. M.; Lemière, G. L. F.; Dommisse, R. A.; Haemers, A. Synlett 2002, 1995.
25. Several examples of the beneficial effect of the use of large excesses of inorganic bases in Pd-catalyzed aminations using Pd(BINAP) catalyst have already been reported by our research group: (a) Košmrlj, J.; Maes, B. U. W.; Lemière, G. L. F.; Haemers, A. Synlett 2000, 1581. (b) Jonckers, T. H. M.; Maes, B. U. W.; Lemière, G. L. F.; Dommisse, R. Tetrahedron 2001, 57, 7027. (c) Maes, B. U. W.; Loones, K. T. J.; Jonckers, T. H. M.; Lemière, G. L. F.; Dommisse, R. A.; Haemers, A. Synlett 2002, 1995.
26. Several examples of the beneficial effect of the use of large excesses of inorganic bases in Pd-catalyzed aminations using Pd(BINAP) catalyst have already been reported by our research group: (a) Košmrlj, J.; Maes, B. U. W.; Lemière, G. L. F.; Haemers, A. Synlett 2000, 1581. (b) Jonckers, T. H. M.; Maes, B. U. W.; Lemière, G. L. F.; Dommisse, R. Tetrahedron 2001, 57, 7027. (c) Maes, B. U. W.; Loones, K. T. J.; Jonckers, T. H. M.; Lemière, G. L. F.; Dommisse, R. A.; Haemers, A. Synlett 2002, 1995.
27. 3 were performed.
28. For the Pd-catalyzed amination of 2-chloroquinoline with ethyl 2-amino-4-phenyl-1,3-thiazole-5-carboxylate see: Yin, J.; Zhao, M. M.; Huffman, M. A.: McNamara, J. M. Org. Lett. 2002, 4, 3481.
29. For the Ni-catalyzed amination of 2-chloroquinoline see: Desmarets, C.; Schneider, R.; Fort, Y. J. Org. Chem. 2002, 67, 3029.
30. NAr model of oxidative addition see: Fitton, P.; Rick, E. A. J. Organomet. Chem. 1971, 28, 287.
31. 2-(Dicyclohexylphosphino)biphenyl, 2-(di-t-butyl-phosphino)biphenyl and tri-t-butylphosphine are commercially available from Strem Chemicals.
32. Tripotassium phosphate (minimum 98%) was obtained from Sigma (catalogue number: P-5629). The pellets were finely grinded in a mortar.
33. Tri-t-butylphosphine has already been used as an effective ligand in intermolecular Heck reactions of non-activated aryl chlorides with alkenes: (a) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10. (b) Ehrentraut, A.; Zapf, A.; Beller, M. Synlett 2000, 1589. (c) N,N-Dicyclohexyl-methylamine was found to be a superior base for intermolecular Heck reactions of non-activated aryl chloride substrates in comparison with inorganic bases: Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989. Attempts to use 1.1 equiv of this amine in our intramolecular Pd-catalyzed arylation reaction on 10 gave no better result since starting material remained after 36 h heating.
34. Tri-t-butylphosphine has already been used as an effective ligand in intermolecular Heck reactions of non-activated aryl chlorides with alkenes: (a) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10. (b) Ehrentraut, A.; Zapf, A.; Beller, M. Synlett 2000, 1589. (c) N,N-Dicyclohexyl-methylamine was found to be a superior base for intermolecular Heck reactions of non-activated aryl chloride substrates in comparison with inorganic bases: Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989. Attempts to use 1.1 equiv of this amine in our intramolecular Pd-catalyzed arylation reaction on 10 gave no better result since starting material remained after 36 h heating.
35. Tri-t-butylphosphine has already been used as an effective ligand in intermolecular Heck reactions of non-activated aryl chlorides with alkenes: (a) Littke, A. F.; Fu, G. C. J. Org. Chem. 1999, 64, 10. (b) Ehrentraut, A.; Zapf, A.; Beller, M. Synlett 2000, 1589. (c) N,N-Dicyclohexyl-methylamine was found to be a superior base for intermolecular Heck reactions of non-activated aryl chloride substrates in comparison with inorganic bases: Littke, A. F.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 6989. Attempts to use 1.1 equiv of this amine in our intramolecular Pd-catalyzed arylation reaction on 10 gave no better result since starting material remained after 36 h heating.
36. Most probably an interphase mechanism is acting since the large excess of base used in the Pd-catalyzed reaction does not dissolve in the solvent used. The insoluble excess speeds up these Pd-catalyzed reactions by supplying a higher surface area.
37. 4 for the cyclodehydrohalogenation of 10 gave similar results as with 10 equiv while the cyclization of 6 gave a significant rate decrease in comparison with the reference experiment where 10 equiv of base were used.
38. Dubovitskii, S. V.; Radchenko, O. S.; Novikov, V. L. Russ. Chem. Bull. 1996, 45, 2657.
39. Timári, G.; Soós, T.; Hajós, G. Synlett 1997, 1067.
40. (a) Fresneda, P. M.; Molina, P.; Delgado, S. Tetrahedron Lett. 1999, 40, 7275.
41. (b) Fresneda, P. M.; Molina, P.; Delgado, S. Tetrahedron 2001, 57, 6197.
42. While our work was in progress an article appeared dealing with a photochemical synthesis of isocryptolepine: Kumar, R. N.; Suresh, T.; Mohan, P. S. Tetrahedron Lett. 2002, 43, 3327.
43. 3): δ = 103.8, 119.8, 120.5, 121.4, 124.3, 125.7, 125.8, 127.6, 129.5, 130.2, 130.3, 137.2, 145.9, 149.3, 150.8. LRMS (DCI): 255.
44. 18
45. 1b