Selective Amination of Polyhalopyridines Catalyzed by a Palladium-Xantphos Complex

Organic Letters

Volumn 5, Issue 24, 2003, Pages 4611-4614

  Ji, Jianguo ^a   Li, Tao ^a   Bunnelle, William H ^a  

^a ABBOTT LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 5 BROMOPYRIDINE; 2,5 DIBROMOPYRIDINE; 5 BROMO 2 CHLOROPYRIDINE; PALLADIUM; POLYHALO DERIVATIVE; PYRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; CATALYSIS; COMPLEX FORMATION; STEREOCHEMISTRY;

EID: 0347411081     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0357696     Document Type: Article

References (57)

1. (a) Quintela, J. M.; Peinador, C.; González, L.; Iglesias, R.; Paramá, A.; Alvarez, F.; Sanmartín, M. L.; Riguera, R. Eur. J. Med. Chem. 2003, 38, 265.
2. (b) O'Hagan, D. Nat. Prod. Rep. 2000, 17, 435.
3. (c) van Rhee, A. M.; Jiang, J.; Melman, N.; Olah, M. E.; Stiles, G. L.; Jacobson, K. A. J. Med. Chem. 1996, 39, 2980.
4. (d) Bever, C. T., Jr. CNS Drug Rev. 1995, 1, 261.
5. Balboni, G.; Marastoni, M.; Merighi, S.; Borea, P. A.; Tomatis, R. Eur. J. Med. Chem. 2000, 35, 979.
6. Chen, B.-C.; Hynes, J. Jr.; Pandit, C. R.; Zhao, R. Heterocycles 2001, 55, 951.
7. Gfesser, G. A.; Bayburt, E. K.; Cowart, M.; DiDomenico, S.; Gomtsyan, A. ; Lee, C.-H.; Stewart, A. O.; Jarvis, M. F.; Kowaluk, E. A.; Bhagwat, S. S. Eur. J. Med. Chem. 2003, 38, 245.
8. Brodbeck, B.; Püllmann, B.; Schmitt, S.; Nettekoven, M. Tetrahedron Lett. 2003, 44, 1675.
9. Guram, A. S.; Rennels, R. A.; Buchwald, S. L. Angew. Chem., Int. Ed. Engl. 1995, 34, 1348.
10. Louie, J.; Hartiwig, J. F. Tetrahedron Lett. 1995, 36, 3609.
11. For recent reviews, see: (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131. (b) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046. (c) Baranano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (d) Frost, C. G.; Mendonca, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615.
12. For recent reviews, see: (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131. (b) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046. (c) Baranano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (d) Frost, C. G.; Mendonca, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615.
13. For recent reviews, see: (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131. (b) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046. (c) Baranano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (d) Frost, C. G.; Mendonca, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615.
14. For recent reviews, see: (a) Muci, A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131. (b) Hartwig, J. F. Angew. Chem., Int. Ed. 1998, 37, 2046. (c) Baranano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem. 1997, 1, 287. (d) Frost, C. G.; Mendonca, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615.
15. (a) Maes, B. U. W.; Loones, K. T. J.; Jonckers, T. H. M.; Lemière, G. L. F.; Dommisse, R. A.; Haemers, A. Synlett 2002, 1995.
16. (b) Jonckers, T. H. M.; Maes, B. U. W.; Lemière, G. L. F.; Dommisse, R. Tetrahedron 2001, 57, 7027.
17. Some recent examples of Pd-catalyzed N-arylation with aminopyridines: (a) Yin, J.; Zhao, M. M.; Huffman, M. A.; McNamara, J. M. Org. Lett. 2002, 4, 3481. (b) Yang, J.-S.; Lin, Y.-H.; Yang, C.-S. Org. Lett. 2002, 4, 777. (c) Arterburn, J. B.; Pannala, M.; Gonzalez, A. M. Tetrahedron Lett. 2001, 42, 1475. (d) Khan, M. M.; Ali, H.; van Lier, J. E. Tetrahedron Lett. 2001, 42, 1615.
18. Some recent examples of Pd-catalyzed N-arylation with aminopyridines: (a) Yin, J.; Zhao, M. M.; Huffman, M. A.; McNamara, J. M. Org. Lett. 2002, 4, 3481. (b) Yang, J.-S.; Lin, Y.-H.; Yang, C.-S. Org. Lett. 2002, 4, 777. (c) Arterburn, J. B.; Pannala, M.; Gonzalez, A. M. Tetrahedron Lett. 2001, 42, 1475. (d) Khan, M. M.; Ali, H.; van Lier, J. E. Tetrahedron Lett. 2001, 42, 1615.
19. Some recent examples of Pd-catalyzed N-arylation with aminopyridines: (a) Yin, J.; Zhao, M. M.; Huffman, M. A.; McNamara, J. M. Org. Lett. 2002, 4, 3481. (b) Yang, J.-S.; Lin, Y.-H.; Yang, C.-S. Org. Lett. 2002, 4, 777. (c) Arterburn, J. B.; Pannala, M.; Gonzalez, A. M. Tetrahedron Lett. 2001, 42, 1475. (d) Khan, M. M.; Ali, H.; van Lier, J. E. Tetrahedron Lett. 2001, 42, 1615.
20. Some recent examples of Pd-catalyzed N-arylation with aminopyridines: (a) Yin, J.; Zhao, M. M.; Huffman, M. A.; McNamara, J. M. Org. Lett. 2002, 4, 3481. (b) Yang, J.-S.; Lin, Y.-H.; Yang, C.-S. Org. Lett. 2002, 4, 777. (c) Arterburn, J. B.; Pannala, M.; Gonzalez, A. M. Tetrahedron Lett. 2001, 42, 1475. (d) Khan, M. M.; Ali, H.; van Lier, J. E. Tetrahedron Lett. 2001, 42, 1615.
21. Trudell et al. reported a palladium-catalyzed amination of 2-chloro-5-iodopyridine with 7-azabicyclo[2.2.1]heptane. Chen, J.; Trudell, M. L. Org. Lett. 2001, 3, 1371.
22. For systematic studies of Pd-ligand combination in the amination of aryl halides, see: (a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694. (b) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144. (c) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158. (d) Harris, M. C.; Geis, O.; Buchwald, S. L. J. Org. Chem. 1999, 64, 6019.
23. For systematic studies of Pd-ligand combination in the amination of aryl halides, see: (a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694. (b) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144. (c) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158. (d) Harris, M. C.; Geis, O.; Buchwald, S. L. J. Org. Chem. 1999, 64, 6019.
24. For systematic studies of Pd-ligand combination in the amination of aryl halides, see: (a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694. (b) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144. (c) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158. (d) Harris, M. C.; Geis, O.; Buchwald, S. L. J. Org. Chem. 1999, 64, 6019.
25. For systematic studies of Pd-ligand combination in the amination of aryl halides, see: (a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 3694. (b) Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1144. (c) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 1158. (d) Harris, M. C.; Geis, O.; Buchwald, S. L. J. Org. Chem. 1999, 64, 6019.
26. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
27. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
28. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
29. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
30. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
31. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
32. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
33. Xantphos was first developed by van Leeuwen and co-workers: (a) Kraneburg, M.; van der Burgt, Y. E. M.; Kamper, P. C. J.; van Leeuwen, P. W. N. M. Organometallics, 1995, 14, 3081. For excellent reviews on Xantphos ligands in transition-metal complexes and catalysis, see: (b) van Leeuwen, P. W. N. M.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes, P. Chem. Rev. 2000, 100, 2741. (c) Kamer, P. C. J.; van Leeuwen, P. W. N. M.; Reek, J. N. H. Acc. Chem. Res. 2001, 34, 895. For recent examples using palladium-Xantphos in N-arylations, see: refs 9, 10a, 12, and: (d) Yin, J.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 6043. (e) Guari, Y.; van Strijdonck, G. P. F.; Boele, M. D. K.; Reek, J. N. H.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem. Eur. J. 2001, 7, 475. (f) Sergeev, A. G.; Artamkina, G. A.; Beletskaya, I. P. Tetrahedron Lett. 2003, 44, 4719. (g) Browning, R. G.; Mahmud, H.; Badarinarayana, V.; Lovely, C. J. Tetrahedron Lett. 2001, 42, 7155. Examples using palladium-Xantphos in C-S bond formation: Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Org. Lett. 2002, 4, 4719.
34. Old, D. W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120, 9722 and ref 12(d).
35. 3P in N-arylation: (a) Prashad, M.; Mak, X. Y.; Liu, Y.; Repic, O. J. Org. Chem. 2003, 68, 1163. (b) Lee, M.; Jørgensen, J.; Hartwig, J. F. Org. Lett. 2001, 3, 2729. (c) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39, 2367.
36. 3P in N-arylation: (a) Prashad, M.; Mak, X. Y.; Liu, Y.; Repic, O. J. Org. Chem. 2003, 68, 1163. (b) Lee, M.; Jørgensen, J.; Hartwig, J. F. Org. Lett. 2001, 3, 2729. (c) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39, 2367.
37. 3P in N-arylation: (a) Prashad, M.; Mak, X. Y.; Liu, Y.; Repic, O. J. Org. Chem. 2003, 68, 1163. (b) Lee, M.; Jørgensen, J.; Hartwig, J. F. Org. Lett. 2001, 3, 2729. (c) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39, 2367.
38. 3P in N-arylation: (a) Prashad, M.; Mak, X. Y.; Liu, Y.; Repic, O. J. Org. Chem. 2003, 68, 1163. (b) Lee, M.; Jørgensen, J.; Hartwig, J. F. Org. Lett. 2001, 3, 2729. (c) Yamamoto, T.; Nishiyama, M.; Koie, Y. Tetrahedron Lett. 1998, 39, 2367.
39. (a) Arduengo, A. J., III Acc. Chem. Res. 1999, 32, 913.
40. Examples using heterocyclic carbene ligands in AT-arylation: (b) Huang, J.; Grasa, G.; Nolan, S. P. Org. Lett. 1999, 1, 1307.
41. (c) Stauffer, S. R.; Lee, S.; Stambuli, J. P.; Hauck, S. I.; Hartwig, J. F. Org. Lett. 2000, 2, 1423.
42. By using Pd-bisimidazolium (a modified IPr·HCl ligand by Trudell) complex, the reaction of 2-chloro-5-iodopyridine with 7-azabicyclo[2.2.1]- heptane was reported to give predominantly 7-(5-iodo-2-pyridinyl)-7- azabicyclo[2.2.1]heptane. See ref 11.
43. Repetition of the experiment of entry 3 (Table 1) in absence of amine 2a produced 6 as the major product in 56% isolated yield.
44. (a) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805.
45. (b) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852.
46. (a) Paul, F.; Patt, J.; Hartwig, J. F. Organometallics 1995, 14, 3030.
47. (b) Hartwig, J. F.; Paul, F. J. Am. Chem. Soc. 1995, 117, 5373.
48. (a) Hartwig, J. F. Synlett 1997, 329.
49. (b) Widenhoefer, R. A.; Buchwald, S. L. Organometallics 1996, 15, 2755.
50. Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1997, 119, 8232.
51. tBuONa (2.5 mmol) in toluene at 100°C for 3 h, 5a was obtained in 96% yield.
52. Under the standard conditions summarized in the Table 2, animation of 2a with 4-bromo-2-chloropyridine (7) and 3-bromo-2-chloropyridine (8) provided the corresponding 1-N-Boc-4-(2-chloropyridin-4-yl)-piperazine (9) and 1-N-Boc-4-(2-chloropyridin-3-yl)-piperazine (10) in 91% and 87% isolated yields, respectively (eq 4). (Matrix presented).
53. 3 as base led to a much slower reaction (18 h) but greatly improved yield of 3j (91%) owing to diminished conversion to the bis(arylated) byproduct (7%). Bis(arylation) is not an issue with the secondary amines N-methylaniline and N-methylbenzylamine, which furnished 3k and 31 in excellent yields under the standard conditions. Benzamide reacts smoothly to provide the monoarylated product 3m. (Matrix presented).
54. tBuONa (2.5 mmol) in toluene at 100°C for 3 h affording 5a in 54% isolated yield.
55. Amination of 2,5-dibromopyridine using palladium catalysts: (a) Gomtsyan, A.; Didomenico, S.; Lee, C.; Matulenko, M. A.; Kim, K.; Kowaluk, E. A.; Wismer, C. T.; Mikusa, J.; Yu, H.; Kohlhaas, K.; Jarvis, M. F.; Bhagwat, S. S. J. Med. Chem. 2002, 45, 3639. (b) Madar, D.; Kopecka, H.; Pireh, D.; Pease, J.; Pliushchev, M.; Sciotti, R. J.; Wiedeman, P. E.; Djuric, S. W. Tetrahedron Lett. 2001, 42, 3681. Amination of 2,5-dibromopyridine using copper catalysts: (c) Lang, F.; Zewge, D.; Houpis, I. N.; Volante, R. P. Tetrahedron Lett. 2001, 42, 3251.
56. Amination of 2,5-dibromopyridine using palladium catalysts: (a) Gomtsyan, A.; Didomenico, S.; Lee, C.; Matulenko, M. A.; Kim, K.; Kowaluk, E. A.; Wismer, C. T.; Mikusa, J.; Yu, H.; Kohlhaas, K.; Jarvis, M. F.; Bhagwat, S. S. J. Med. Chem. 2002, 45, 3639. (b) Madar, D.; Kopecka, H.; Pireh, D.; Pease, J.; Pliushchev, M.; Sciotti, R. J.; Wiedeman, P. E.; Djuric, S. W. Tetrahedron Lett. 2001, 42, 3681. Amination of 2,5-dibromopyridine using copper catalysts: (c) Lang, F.; Zewge, D.; Houpis, I. N.; Volante, R. P. Tetrahedron Lett. 2001, 42, 3251.
57. Amination of 2,5-dibromopyridine using palladium catalysts: (a) Gomtsyan, A.; Didomenico, S.; Lee, C.; Matulenko, M. A.; Kim, K.; Kowaluk, E. A.; Wismer, C. T.; Mikusa, J.; Yu, H.; Kohlhaas, K.; Jarvis, M. F.; Bhagwat, S. S. J. Med. Chem. 2002, 45, 3639. (b) Madar, D.; Kopecka, H.; Pireh, D.; Pease, J.; Pliushchev, M.; Sciotti, R. J.; Wiedeman, P. E.; Djuric, S. W. Tetrahedron Lett. 2001, 42, 3681. Amination of 2,5-dibromopyridine using copper catalysts: (c) Lang, F.; Zewge, D.; Houpis, I. N.; Volante, R. P. Tetrahedron Lett. 2001, 42, 3251.