Chiral amine synthesis-strategies, examples, and limitations

Process Chemistry in the Pharmaceutical Industry, Volume 2: Challenges in an Ever Changing Climate

Volumn , Issue , 2007, Pages 137-156

  Nugent, Thomas C ^a  

^a JACOBS UNIVERSITY BREMEN   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84985030383     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/9781420008357     Document Type: Chapter

References (105)

1. The author worked as a process research chemist for three years with Catalytica/DSM (Mountain View, CA) and then 2 years with Pharmacia/Pfizer (South San Francisco, CA) before joining Jacobs University (Bremen, Germany) as an assistant professor of organic chemistry in October 2003. Email address: t.nugent@jacobs-university.de.
2. Chen, B.; Dingerdissen, U.; Krauter, J. G. E.; Rotgerink, H. G. J. L; Möbus, K.; Ostgard, D. J.; Panster, P.; Riermeier, T. H.; Seebald, S.; Tacke, T.; Trauthwein, H. Appl. Catal. A: General 2005, 280, 17-46;
3. Vilaivan, T.; Bhanthumnavin, W.; Sritana-Anant, Y. Curr. Org. Chem. 2005, 9, 1315-1392;
4. Breuer, M.; Ditrich, K.; Habicher, T.; Hauer, B.; Keßeler, M.; Stürmer, R.; Zelinski, T. Angew. Chem. 2004, 116, 806-843;
5. Angew. Chem., Int. Ed. 2004, 43, 788-824;
6. Spindler, F.; Blaser, H.-U. Enantioselective reduction of C=N bonds and enamines with hydrogen. In Transition Metals for Organic Synthesis, 2nd Edition (Ed.: Beller, M.; Bolm, C.), Wiley-VCH, Weinheim, 2004, pp. 113-123;
7. Kukula, P.; Prins, R. Topics in Catalysis 2003, 25, 29-42;
8. Besson, M.; Pinel, C. Topics in Catalysis 2003, 25, 43-61;
9. Blaser, H.-U.; Malan, C.; Pugin, B.; Spindler, F.; Steiner, H.; Studer, M. Adv. Synth. Catal. 2003, 345, 103-151;
10. Juaristi, E.; León-Romo, J. L.; Reyes, A.; Escalante, J. Tetrahedron: Asymmetry 1999, 10, 2441-2495;
11. Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069-1094.
12. Unfunctionalized amines here implies the exclusion of substrates requiring functional groups that are intimately involved in the transition state for production formation, e.g., ester chelation to a metal center.
13. The term ‘chiral amine’ is used in the title, but refers to an α-chiral amine, i.e., an α-carbon stereocenter adjacent to a nitrogen atom.
14. The time honored adage, especially in sophomore organic chemistry courses, of teaching students that over alkylation of amines makes their substitution chemistry unfit for consideration is outdated; though limited the strategy should not be ignored for the mono-alkylation of amines, see, for example, Hayler, J. D.; Howie, S. L. B.; Giles, R. G.; Negus, A.; Oxley, P. W.; Walsgrove, T. C.; Whiter, M. Org. Process. Res. Dev. 1998, 2, 3-9.
15. Kim, M.; Mulcahy, J. V.; Espino, C. G.; Du Bois, J. Org. Lett. 2006, 8, 1073-1076;
16. Wehn, P. M.; Du Bois, J. Org. Lett. 2005, 7, 4685-4688;
17. Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. J. Am. Chem. Soc. 2004, 126, 15378-15379.
18. Blaser, H.-U.; Eissen, M.; Fauquex, P. F.; HungerBühler, K.; Schmidt, E.; Sedelmeier, G.; Studer, M. Comparison of Four Technical Syntheses of Ethyl (R)-2-Hydroxy-4-Phenylbutyrate. In Asymmetric Catalysis on Industrial Scale: Challenges, Approaches, and Solutions; Blaser, H.-U.; Schmidt, E. Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2004, pp 91-103;
19. Blaser, H.-U.; Burkhardt, S.; Kirner, H. J.; Mössner, T.; Studer, M. Synthesis 2003, 1679-1682.
20. Similar examples of ketone reduction, followed by alcohol activation, and nucleophilic displacement thereof by an amine, have been demonstrated for other drug classes, see Reference 5 and Noyori, R.; Ohkuma, T. Angew. Chem. 2001, 113, 40-75;
21. Angew. Chem., Int. Ed. 2001, 40, 40-73.
22. Huffman, M. A.; Reider, P. J. Tetrahedron Lett. 1999, 40, 831-834;
23. Huffman, M. A.; Reider, P. J.; Leblond, C.; Sun, Y.; Merck & Co., Ltd. Patent number US6025500, 2000.
24. Note that very specialized syntheses, i.e., specialized for one substrate in particular, are not considered here.
25. Bunlaksananusorn, T.; Rampf, F. Synlett 2005, 17, 2682-2684;
26. Ikemoto, N.; Tellers, D. M.; Dreher, S. D.; Liu, J.; Huang, A.; Rivera, N. R.; Njolito, E.; Hsiao, Y.; McWilliams, J. C.; Williams, J. M.; Armstrong, J. D.; Sun, Y.; Mathre, D. J.; Grabowski, E. J. J.; Tillyer, R. D. J. Am. Chem. Soc. 2004, 126, 3048-3049;
27. Hsiao, Y.; Rivera, N. R.; Rosner, T.; Krska, S. W.; Njolito, E.; Wang, F.; Sun, Y.; Armstrong, J. D.; Grabowski, E. J. J.; Tillyer, R. D.; Spindler, F.; Malan, C. J. Am. Chem. Soc. 2004, 126, 9918-9919.
28. Hu, X.-P.; Zheng, Z. Org. Lett. 2005, 7, 419-422;
29. Zhang, Y. J.; Kim, K. Y.; Park, J. H.; Song, C. E.; Lee, K.; Lah, M. S.; Lee, S.-G. Adv. Synth. Catal. 2005, 347, 563-570;
30. You, J.; Drexler, H.-J.; Zhang, S.; Fischer, C.; Heller, D. Angew. Chem. 2003, 115, 942-945;
31. Angew. Chem., Int. Ed. 2003, 42, 913-916.
32. Phua, P. H., de Vries, J. G.; Hiia, K. K. Adv. Synth. Catal. 2005, 347, 1775-1780.
33. Kadyrov, R.; Riermeier, T. H.; Dingerdissen, U.; Tararov, V. I.; Börner, A. J. Org. Chem. 2003, 68, 4067-4070.
34. Menzel, A.; Werner, H.; Altenbuchner, J.; Groeger, H. Eng. in Life Sci. 2004, 4, 573-576;
35. See references cited within: Côté, A.; Charette, A. B. J. Org. Chem. 2005, 70, 10864-10867.
36. Qin, H.; Yamagiwa, N.; Matsunaga, S.; Shibasaki, M. J. Am. Chem. Soc. 2006, 128, 1611-1614;
37. Karshtedt, D.; Bell, A. T.; Tilley, T. D. J. Am. Chem. Soc. 2005, 127, 12640-12646;
38. Zulys, A.; Dochnahl, M.; Hollmann, D.; Loehnwitz, K.; Herrmann, J.-S.; Roesky, P. W.; Blechert, S. Angew. Chem. 2005, 117, 7972-7976;
39. Angew. Chem. Int. Ed. 2005, 44, 7794-7798.
40. McMahon, J. P.; Ellman, J. A. Org. Lett. 2004, 6, 1645-1647;
41. J. A. Ellman, Pure Appl. Chem. 2003, 75, 39-46;
42. Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984-995.
43. Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 1278-1284;
44. Cogan, D. A.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J. A. J. Am. Chem. Soc. 1998, 120, 8011-8019.
45. Cogan, D. A.; Liu, G.; Ellman, J. Tetrahedron 1999, 55, 8883-8904;
46. Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1999, 121, 268-269.
47. Shaw, A. W.; deSolms, S. J. Tetrahedron Lett. 2001, 42, 7173-7176.
48. Akullian, L. C.; Snapper, M. L.; Hoveyda, A. H. Angew. Chem. 2003, 115, 4376-4379;
49. Angew. Chem. Int. Ed. 2003, 42, 4244-4247;
50. Akullian, L. C.; Porter, J. R.; Traverse, J. F.; Snapper, M. L.; Hoveyda, A. H. Adv. Synth. Catal. 2005, 347, 417-425.
51. Porter, J. R.; Traverse, J. F.; Hoveyda, A. H.; Snapper, M. L. J. Am. Chem. Soc. 2001, 123, 10409-10410
52. For further N-aryl oxidative cleavage protocols, see: Kobayashi, S.; Ueno, M.; Suzuki, R.; Ishitani, H.; Kim, H.-S.; Wataya, Y. J. Org. Chem. 1999, 64, 6833-6841.
53. No experimental description could be found.
54. See the Supporting Information section of Ref. 15b.
55. McLaughlin, M.; Rubio, S. G.; Tilstam, U.; Antunes, O. A. C.; Laird, T.; Yadav, G. D.; Andrei Zlota, A. Org. Process Res. Dev. 2006, 10, 168-183. See specifically pages 169-170.
56. Côté, A.; Boezio, A. A.; Charette, A. B. Angew. Chem. 2004, 116, 6687-6690;
57. Angew. Chem. Int. Ed. 2004, 43, 6525-6528;
58. Boezio, A. A.; Pytkowicz, J.; Côté, A.; Charette, A. B. J. Am. Chem. Soc. 2003, 125, 14260-14261;
59. Boezio, A. A.; Charette, A. B. J. Am. Chem. Soc. 2003, 125, 1692-1693.
60. Côté, A.; Boezio, A. A.; Charette, A. B. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5405-5410.
61. Wakchaure, V. N.; Mohanty, R. R.; Shaikh, J. A.; Nugent, T. C. Eur. J. Org. Chem. 2007, 959-964.
62. Bandini, M.; Cozzi, P. G.; Umani-Ronchi, A.; Villa, M. Tetrahedron 1999, 55, 8103-8110;
63. Alvaro, G.; Savioa, D. Valentinetti, M. R. Tetrahedron 1996, 52, 12571-12586.
64. Weix, D. J.; Shi, Y.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 1092-1093.
65. Blacker, J.; Martin, J. Scaleup Studies in Asymmetric Transfer Hydrogenation. In Asymmetric Catalysis on Industrial Scale: Challenges, Approaches, and Solutions; Blaser, H.-U.; Schmidt, E. Eds.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2004, pp 201-216.
66. Transfer hydrogenation process. Martin, J.; Campbell; L. A.; Avecia Limited, Great Britain. Patent publication number WO0112574, 2001;
67. Transfer hydrogenation process. Martin, J.; Campbell, L. A.; Avecia Limited, Great Britain. Patent publication number US6696608, 2004.
68. Spindler, F.; Blaser, H.-U. Enantioselective reduction of C=N bonds and enamines with hydrogen. In Transition Metals for Organic Synthesis, 2nd Edition (Ed.: M. Beller, C. Bolm), Wiley-VCH, Weinheim, 2004, pp. 113-123;
69. Spindler, F.; Blaser, H.-U. Adv. Synth. Catal. 2001, 343, 68-70.
70. Willoughby, C. A.; Buchwald S. L. J. Am. Chem. Soc. 1994, 116, 8952-8965;
71. Willoughby, C. A.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 11703-11714.
72. Verdaguer, X.; Lange, U. E. W.; Reding, M. T.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 6784-6785;
73. Reding, M. T.; Buchwald, S. L. J. Org. Chem. 1998, 63, 6344-6347;
74. Hansen, M. C.; Buchwald, S. L. Org. Lett. 2000, 2, 713-715;
75. Yun, J.; Buchwald, S. L. J. Org. Chem. 2000, 65, 767-774.
76. Blaser, H.-U. Adv. Synth. Catal. 2002, 344, 17-31.
77. Kadyrov, R.; Riermeier, T. H. Angew. Chem. 2003, 115, 5630-5632;
78. Angew. Chem., Int. Ed. 2003, 42, 5472-5474.
79. Method for the production of amines by reductive amination of carbonyl compounds under transferhydrogenation conditions. Börner, A.; Dingerdissen, U.; Kadyrov, R.; Riermeier, T. H.; Tararov, V.; Degussa AG, Germany. Patent publication number US2004267051, 2004.
80. Method for producing amines by homogeneously catalyzed reductive amination of carbonyl compounds. T. Riermeier, K.-J. Haack, U. Dingerdissen, A. Boerner, V. Tararov, R. Kadyrov; Degussa AG, Germany. Patent publication number US6884887, 2005.
81. Emerson, W. S. Org. React. 1948, 4, 174-255;
82. Moore, M. L. Org. React. 1949, 5, 301-330.
83. Reetz, M. T. Organotitanium Reagents in Organic Synthesis; Reetz, M. T. Ed.; Springer-Verlag:Berlin, 1986; specifically see p 107;
84. Reetz, M. T.; Westermann, J.; Steinbach, R.; Wenderoth, B.; Peter, R.; Ostarek, R.; Maus, S. Chem. Ber. 1985, 118, 1421-1440.
85. Mattson, R. J.; Pham, K. M.; Leuck, D. J.; Cowen, K. A. J. Org. Chem. 1990, 55, 2552-2554.
86. Miriyala, B.; Bhattacharyya, S.; Williamson, J. S. Tetrahedron 2004, 60, 1463-1471;
87. Bhattacharyya, S.; Kumpaty, H. J. Synthesis 2005, 2205-2209.
88. Nugent, T. C.; Seemayer, R. Org. Process. Res. Dev. 2006, 10, 142-148 and references cited therein for earlier work regarding the use of hydrides for Lewis acid based reductive amination;
89. Process for the Preparation of (S, S)-cis-2-Benzhydryl-3-benzylaminoquinuclidine; Nugent, T. C.; Seemayer, R. (Pfizer Products, Inc. and DSM Pharmaceuticals, Inc.), publication number:WO2004035575, 29 April 2004.
90. Nugent, T. C.; Wakchaure, V. N.; Ghosh, A. K.; Mohanty, R. R. Org. Lett. 2005, 7, 4967-4970.
91. Nugent, T. C.; Ghosh, A. K.; Wakchaure, V. N.; Mohanty, R. R. Adv. Synth. Catal. 2006, 348, 1289-1299.
92. We recently became aware of Pd-C catalysts specifically for debenzylations and suppression of racemization, see: V. Farina, K. Grozinger, H. Müller-Bötticher, G. P. Roth, Ontazolast: The Evolution of a Process. In Process Chemistry in the Pharmaceutical Industry; K. G. Gadamasetti, Ed.; Marcel Dekker, Inc.: New York, 1999, pp 107-124.
93. 3.
94. Nugent, T. C., El-Shazly, M.; Wakchaure, V. N. submitted for publication in 2007.
95. For a brief overview regarding imine formation, see page 1291 of Ref. 46.
96. Zhang, Z.; Zhu, G.; Jiang, Q.; Xiao, D.; Zhang, X. J. Org. Chem. 1999, 64, 1774-1775.
97. Burk, M. J.; Casy, G.; Johnson, N. B. J. Org. Chem. 1998, 63, 6084-6085.
98. Bernsmann, H.; Van den Berg, M.; Hoen, R.; Minnaard, J. A.; Mehler, G.; Reetz, M. T.; De Vries, J. G.; Feringa, B. L. J. Org. Chem. 2005, 70, 943-951;
99. Hoen, R.; Van den Berg, M.; Bernsmann, H.; Minnaard, A. J.; De Vries, J. G.; Feringa, B. L. Org. Lett. 2004, 6, 1433-1436.
100. Chi, Y.; Tang, W.; Zhang, X. Rhodium-Catalyzed Asymmetric Hydrogenation. In Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A. Ed.; Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2005, pp 1-31.
101. Li, W.; Zhang, X. J. Org. Chem. 2000, 65, 5871-5874.
102. Xiao, D.; Zhang, Z.; Zhang, X. Org. Lett. 1999, 1, 1679-1681.
103. Zhu, G.; Zhang, X. J. Org. Chem. 1998, 63, 9590-9593.
104. Tang, W.; Chi, Y.; Zhang, X. Org. Lett. 2002, 4, 1695-1698.
105. Huang, H.; Liu, X.; Chen, H.; Zheng, Z. Tetrahedron: Asymmetry 2005, 16, 693-697.