Strategy-level separations in organic synthesis: From planning to practice

Angewandte Chemie - International Edition

Volumn 37, Issue 9, 1998, Pages 1174-1196

  Curran, Dennis P ^a  

^a UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

Combinatorial chemistry; Fluorous synthesis; Solid phase synthesis; Synthesis design

Indexed keywords

EID: 0032543080     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1521-3773(19980518)37:9<1174::AID-ANIE1174>3.0.CO;2-P     Document Type: Review

References (115)

1. a) E. J. Corey, X.-M. Cheng, The Logic of Chemical Synthesis, Wiley, New York, 1989;
2. b) K. C. Nicoloau, E. J. Sorenson, Classics in Total Synthesis, VCH, Weinheim, 1995.
3. a) Combinatorial Peptide and Non Peptide Libraries (Ed.: G. Jung), VCH, Weinheim. 1996;
4. b) F. Balkenhohl, C. von dem Büssche-Hünnefeld, A. Lansky, C. Zechel, Angew. Chem. 1996, 108, 2436; Angew. Chem. Int. Ed. Engl. 1996, 35, 2288;
5. b) F. Balkenhohl, C. von dem Büssche-Hünnefeld, A. Lansky, C. Zechel, Angew. Chem. 1996, 108, 2436; Angew. Chem. Int. Ed. Engl. 1996, 35, 2288;
6. M. Rinnova, M. Lebl, Collect. Czech. Chem. Commun. 1996, 61, 171;
7. J. S. Früchtel, G. Jung, Angew. Chem. 1996, 109, 19; Angew. Chem. Int. Ed. Engl. 1996, 35, 17.
8. J. S. Früchtel, G. Jung, Angew. Chem. 1996, 109, 19; Angew. Chem. Int. Ed. Engl. 1996, 35, 17.
9. a) P. H. H. Hermkens, H. C. J. Ottenheijm, D. Rees, Tetrahedron 1996, 52, 4527;
10. b) ibid. 1997, 53, 5643;
11. L. A. Thompson, J. A. Ellman, Chem. Rev. 1996, 96, 555.
12. The terms in Scheme 1 are used with an eye towards combinatorial applications. In a combinatorial synthesis, "substrates" are combined with "reactants" in the presence of "reagents" and/or "catalysts" (or "additives") to give "products" and "by-products". The "substrates" and "products" are the compounds used further in the synthesis, whereas "by-products" are undesired products from any source and must be separated from the products. "Catalysts" and "reagents" differ in their stoichiometry and provide either no atoms to the product library or provide a constant atom or group to all products. In other words, they are required for the reaction but do not contribute to the diversity of the products. Multiple "reactants" are used in a combinatorial synthesis and these provide variable groups of atoms to the product library when allowed to react with single or multiple substrates. The collective term "reaction components" is used to describe all of these classifications.
13. a) T. Lard, Chem. Brit. 1996, 32/8, 43;
14. b) Applied Homogeneous Catalysis with Organonmetallic Compounds, Vol. 2 (Eds.: B. Cornils, W. A. Herrmann), VCH, Weinheim, 1996, chap. 3.1.1, p. 575.
15. a) P. A. Wender, B. L. Miller in Organic Synthesis: Theory and Applications, Vol. 2 (Ed.: T. Hudlicky), Jai Press, Greenwich, 1993, p. 27;
16. b) P. A. Wender, Chem. Rev. 1996, 96, 1 (this short article introduces a special issue of Chem. Rev. on "Frontiers in Organic Synthesis");
17. P. A. Wender, S. T. Handy, D. L Wright, Chem. Ind. 1997, 765.
18. An alternative term to "phase labeling" is "phase tagging". These terms should not be confused with chemical, laser, or radiofrequency labeling or tagging methods used in solid-phase synthesis to identify beads.
19. a) I. T. Horváth, J. Rábai, Science 1994, 266, 72;
20. b) recent developments in flourous biphasic catalysis: B. Cornils, Angew. Chem. 1997, 109, 2147; Angew. Chem. Int. Ed. Engl. 1997, 36, 2057.
21. b) recent developments in flourous biphasic catalysis: B. Cornils, Angew. Chem. 1997, 109, 2147; Angew. Chem. Int. Ed. Engl. 1997, 36, 2057.
22. a) R. L. Scott, J. Am. Chem. Soc. 1948, 70, 4090;
23. b) J. H. Hildebrand, D. F. R. Cochran, ibid. 1949, 71, 22;
24. M. Hudlicky, Chemistry of Organic Fluorine Compounds, Ellis Horwood, New York, 1992.
25. D.-W. Zhu, Synthesis 1993, 953.
26. D. P. Curran, Chemtracts: Org. Chem. 1996, 9, 75.
27. a) T. Carell, E. A. Wintner, A. J. Sutherland, J. Rebek, Jr., Y. M. Dunayevskiy, P. Vouros, Chem. Biol. 1995, 2, 171;
28. b) T. Carell, E. A. Wintner, J. Rebek, Jr., Angew. Chem. 1994, 106, 2162; Angew. Chem. Int. Ed. Engl. 1994, 33, 2061;
29. b) T. Carell, E. A. Wintner, J. Rebek, Jr., Angew. Chem. 1994, 106, 2162; Angew. Chem. Int. Ed. Engl. 1994, 33, 2061;
30. T. Carell, E. A. Wintner, A. Bashir-Hashemi, J. Rebek, Jr., ibid. 1994, 106, 2159 and 1994, 33, 2059.
31. T. Carell, E. A. Wintner, A. Bashir-Hashemi, J. Rebek, Jr., ibid. 1994, 106, 2159 and 1994, 33, 2059.
32. The chromatography of aggregate mixtures was recently reported: a) H. An, L. L. Cummins, R. H. Griffey, R. Bharadwaj, B. D. Haly, A. S. Fraser, L. Wilson-Lingardo, L. M. Risen, J. R. Wyatt, P. D. Cook, J. Am. Chem. Soc. 1997, 119, 3696;
33. b) H. An, P. D. Cook, Tetrahedron Lett. 1996, 37, 7233.
34. a) K. S. Lam, M. Lebl, V. Krchnak, Chem. Rev. 1997, 97, 411;
35. b) in ref. [14c], p. 173;
36. A. Furka in ref. [14c], p. 111;
37. Combinatorial Peptide and Nonpeptide Libraries (Ed.: G. Jung), VCH, Weinheim, 1996.
38. J. Rebek, Jr., Tetrahedron 1979, 35, 723.
39. a) J. J. Parlow, Tetrahedron Lett. 1995, 36, 1395;
40. b) B. J. Cohen, M. A. Kraus, A. Patchornik, J. Am. Chem. Soc. 1981, 103, 7620.
41. A. J. Kirby, Adv. Phys. Org. Chem. 1980, 17, 183.
42. This can be done either by conducting a suitable copolymerization or by grafting the reagent to a preformed polymer backbone.
43. B. M. Kim, K. B. Sharpless, Tetrahedron Lett. 1990, 31, 3003.
44. W.-S. Huang, Q.-S. Hu, X.-F. Zheng, J. Anderson, L. Pu, J. Am. Chem. Soc. 1997, 119, 4313.
45. J. C. Sheehan, P. Preston, P. A. Cruickshank, J. Am. Chem. Soc. 1965, 87, 2942.
46. a) C. G. Overberger, K. N. Sannes, Angew. Chem. 1974, 86, 139; Angew. Chem. Int. Ed. Engl. 1974, 13, 99;
47. a) C. G. Overberger, K. N. Sannes, Angew. Chem. 1974, 86, 139; Angew. Chem. Int. Ed. Engl. 1974, 13, 99;
48. b) G. Manecke, W. Storck, ibid. 1978, 90, 657 and
49. 1978, 17, 657;
50. A. Akelah, Synthesis 1981, 413;
51. C. W. Pittman in Comprehensive Organometallic Chemistry, Vol. 8 (Eds.: G. Wilkinson, F. G. A. Stone, E. Abel), Pergamon, Oxford, 1982, p. 553;
52. e) D. C. Sherrington, P. Hodge, Syntheses and Separations Using Functional Polymers, Wiley, New York, 1988;
53. f) P. Hodge in ref. [22e], p. 108;
54. g) D. E. Bergbreiter, CHEMTECH 1987, 686.
55. D. J. Gravert, K. D. Janda, Chem. Rev. 1997, 97, 489.
56. a) H. Han, K. D. Janda, J. Am. Chem. Soc. 1996, 118, 7632;
57. b) H. S. Han, K. D. Janda, Tetrahedron Lett. 1997, 38, 1527;
58. C. Bolm, A. Gerlach, Angew. Chem. 1997, 109, 773: Angew. Chem. Int. Ed. Engl. 1997, 36, 741.
59. C. Bolm, A. Gerlach, Angew. Chem. 1997, 109, 773: Angew. Chem. Int. Ed. Engl. 1997, 36, 741.
60. a) J. W. J. Knapen, A. W. Vandermade, J. C. Dewilde, P. W. N. M. van Leeuwen, P. Wijkens, D. M. Grove, G. van Koten, Nature 1994, 372, 659;
61. b) M. T. Reetz, G. Lohmer, R. Schwickardi, Angew. Chem. 1997, 109, 1559; Angew. Chem. Int. Ed. Engl. 1997, 36, 1526.
62. b) M. T. Reetz, G. Lohmer, R. Schwickardi, Angew. Chem. 1997, 109, 1559; Angew. Chem. Int. Ed. Engl. 1997, 36, 1526.
63. a) S. G. DiMagno, P. H. Dussault, J. A. Schultz, J. Am. Chem. Soc. 1996, 118, 5312. H. V. R. Dias, H. J. Kim, Organametallics 1996, 15, 5374;
64. a) S. G. DiMagno, P. H. Dussault, J. A. Schultz, J. Am. Chem. Soc. 1996, 118, 5312. H. V. R. Dias, H. J. Kim, Organametallics 1996, 15, 5374;
65. b) G. Pozzi, F. Montanari, S. Quici, Chem. Commun. 1997, 69; R. P. Hughes, H. A. Trujillo, Orgammielallics 1996, 15, 286;
66. b) G. Pozzi, F. Montanari, S. Quici, Chem. Commun. 1997, 69; R. P. Hughes, H. A. Trujillo, Orgammielallics 1996, 15, 286;
67. G. Pozzi, I. Colombani, M. Miglioli, F. Montanari, S. Quici, Tetrahedron 1997, 53, 6145;
68. I. Klement, H. Lütjens, P. Knochel, Angew. Chem. Int. Ed. Engl. 1997, 36, 1454;
69. e) J. J. J. Juliette, I. T. Horváth, J. A. Gladysz, Angew. Chem. 1997, 109, 1682; Angew. Chem. Int. Ed. Engl. 1997, 36, 1610;
70. e) J. J. J. Juliette, I. T. Horváth, J. A. Gladysz, Angew. Chem. 1997, 109, 1682; Angew. Chem. Int. Ed. Engl. 1997, 36, 1610;
71. f) M.-A. Guillevic, A. M. Arif, I. T. Horváth, J. A. Gladysz, ibid. 1997, 36, 1612 and 1997, 36, 1612.
72. f) M.-A. Guillevic, A. M. Arif, I. T. Horváth, J. A. Gladysz, ibid. 1997, 36, 1612 and 1997, 36, 1612.
73. a) D. P. Curran, S. Hadida, J. Am. Chem. Soc. 1996, 118, 2531;
74. b) J. H. Horner, F. N. Martinez, M. Newcomb, S. Hadida, D. P. Curran, Tetrahedron Lett. 1997, 38, 2783;
75. A. Ogawa, D. P. Curran, J. Org. Chem. 1997, 62, 450;
76. I. Ryu, T. Niguma, S. Minakata, M. Komatsu, S. Hadida, D. P. Curran, Tetrahedron Lett. 1997, 45, 7883.
77. a) D. P. Curran, M. Hoshino, J. Org. Chem. 1996, 61, 6480;
78. b) D. P. Curran, M. Hoshino, P. Degenkolb, ibid. 1997, 62, 8341;
79. for the synthesis and use of a fluorous tin-Cp reagent, see N. Spetseris, S. Hadida, D. P. Curran, T. Y. Meyer, Organometallics, in press.
80. M. Larhed, M. Hoshino, S. Hadida, D. P. Curran, A. Hallberg, J. Org. Chem. 1997, 62, 5583.
81. D. P. Curran, S. Hadida, M. He, J. Org. Chem. 1997, 62, 6714.
82. N. D. Danielson, L. G. Beaver, J. Wangsa, J. Chromat. 1991, 544, 187.
83. V. J. Nilsson, E. Fournier, O. Hindsgaul, Bioorg. Med. Chem. Lett., in press. I thank Prof. Hindsgaul for a preprint of this paper.
84. K. C. Nicolaou, N. Wissinger, J. Pastor, S. Ninkovic, F. Sarabia, Y. He, D. Vourloumis, Z. Yang, T. Li, P. Giannakakou, E. Hamel, Nature 1997, 387, 268.
85. R. M. Kim, M. Manna, S. M. Hutchins, P. R. Griffin, N. A. Yates, A. M. Bernick, K. T. Chapman, Proc. Natl. Acad. Sci. USA 1996, 93, 10012.
86. a) D. A. Tomalia, Aldrichimica Acta 1993, 26, 91;
87. b) J. Issberner, R. Moors, F. Vogtle, Angew. Chem. 1994, 106, 2507; Angew. Chem. Int. Ed. Engl. 1994, 33, 2413.
88. b) J. Issberner, R. Moors, F. Vogtle, Angew. Chem. 1994, 106, 2507; Angew. Chem. Int. Ed. Engl. 1994, 33, 2413.
89. This is only true if each substrate produces a single product. If, for example, a chiral substrate produces a chiral product with no selectivity, the resulting "racemic" small molecules combine to produce diastereomeric dendrimers.
90. a) A. Studer, S. Hadida, R. Ferritto, S. Y. Kim, P. Jeger, P. Wipf, D. P. Curran, Science 1997, 275, 823;
91. b) A. Studer, D. P. Curran, Tetrahedron 1997, 53, 6681;
92. A. Studer, P. Jeger, P. Wipf, D. P. Curran, J. Org. Chem. 1997, 62, 2917.
93. C.-H. Wong, G. M. Whitesides, Enzymes in Synthetic Organic Chemistry, Pergamon, Oxford, 1994.
94. a) A. Gutman, Manuf. Chemist. 1995, 66, 23;
95. b) S. C. Stinson, Chem. Eng. News 1997, 75(20), 34.
96. a) D. L. Boger, C. M. Tarby, P. L. Myers, L. H. Caporale, J. Am. Chem. Soc. 1996, 118, 2109;
97. b) S. Cheng, D. D. Comer, J. P. Williams, P. L. Myers, D. L. Boger, ibid. 1996, 118, 2567;
98. J. P. Whitten, Y. F. Xie, P. E. Erickson, T. R. Webb, E. B. DeSouza, D. E. Grigoriadis, J. R. McCarthy, J. Med. Chem. 1996, 39, 4354;
99. C. Chen, R. Dagnino, Jr., E. B. DeSouza, D. E. Grigoriadis, C. Q. Huang, K.-I. Kim, Z. Liu, T. Moran, T. R. Webb, J. P. Whitten, Y. F. Xie, J. R. McCarthy, ibid. 1996, 39, 4358.
100. M. G. Siegel, P. J. Hahn, B. A. Dressman, J. E. Fritz, J. R. Grunwell, S. W. Kaldor, Tetrahedron Lett. 1997, 38, 3357.
101. L. M. Gayo, M. J. Suto, Tetrahedron Lett. 1997, 38, 513.
102. D. L. Flynn, J. Z. Crich, R. V. Devraj, S. L. Hockerman, J. J. Parlow, M. S. South, S. Woodard, J. Am. Chem. Soc. 1997, 119, 4874.
103. R. M. Lawrence, S. A. Biller, O. M. Fryszman, M. A. Poss, Synthesis 1997, 553.
104. A. Chucholowski, T. Masquelin, D. Obrecht, J. Stadlwieser, J. M. Villalgordo, Chimia 1996, 50, 525.
105. T. L. Deegan, O. W. Gooding, S. Baudant, J. A. Porco, Jr., Tetrahedron Lett. 1997, 38, 4973.
106. S. V. McKinley, J. W. Rakshys, J. Chem. Soc. Chem. Commun. 1972, 134.
107. a) T. A. Keating, R. W. Armstrong, J. Am. Chem. Soc. 1996, 118, 2574;
108. b) R. W. Armstrong, A. P. Combs, P. A. Tempest, S. D. Brown, T. A. Keating, Acc. Chem. Res. 1996, 29, 123;
109. S. D. Brown, R. W. Armstrong, J. Am. Chem. Soc. 1996, 118, 6331.
110. S. H. DeWitt, A. W. Czarnik, Acc. Chem. Res. 1996, 29, 114.
111. a) A. R. Brown, D. C. Rees, Z. Rankovic, J. R. Morphy, J. Am. Chem. Soc. 1997, 119, 3288;
112. b) Y. Ito, T. Ogawa, ibid. 1997, 119, 5562.
113. R. J. Booth, J. C. Hodges, J. Am. Chem. Soc. 1997, 119, 4882.
114. S.-Y. Kim, University of Pittsburgh, unpublished results.
115. A. R. Brown, S. L. Irving, R. Ramage, G. Raphy, Tetrahedron 1995, 51, 11815.