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Substitution Reactions

  • Manfred T. Reetz
Part of the Reactivity and Structure: Concepts in Organic Chemistry book series (REACTIVITY, volume 24)

Abstract

One of the prime virtues of carbanion chemistry is the diversity of reactions possible: Grignard-type, aldol and Michael additions, oxidative dimerization as well as substitution processes at sp3 and sp2 hybridized C-atoms [1], In case of the latter reactions, “resonance-stabilized” species such as ester and ketone enolates (and the nitrogen analogs), lithiated sulfones, sulfoxides, nitriles, etc. as well as hetero-atom-substituted reagents undergo smooth SN2 reactions with primary and some secondary alkyl halides and tosylates. A synthetic gap becomes apparent upon attempting to perform these reactions with tertiary alkyl halides and certain base sensitive secondary analogs, because they are not SN2 active. A similar situation arises in case of carbon nucleophiles lacking additional functionality. For example, (CH3)2CuLi and higher order cuprates undergo smooth substitution reactions with primary and most secondary alkyl halides, but not with tertiary analogs. It turns out that in many cases these problems can be solved using titanium chemistry (Section 7.1). Certain titanium reagents also allow for the combination of two processes in a one-pot sequence, namely addition to carbonyl compounds followed by SNl-type substitution of the oxygen function (Section 7.2.1). Conversely, titanium reagents are generally not nucleophilic enough to undergo SN2-reactions with primary alkyl halides.

Keywords

Substitution Reaction Alkyl Halide Oxidative Dimerization Titanium Reagent Carbanion Chemistry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1. a)
    Stowell, J. C.: “Carbanions in Organic Chemistry”, Wiley, N. Y. 1979;Google Scholar
  2. 1. b)
    Bates, R. B., Ogle, C. A.: “Carbanion Chemistry”, Springer-Verlag, Berlin 1983;Google Scholar
  3. 1. c)
    Caine, D.: in “Carbon—Carbon Bond Fomation”, (Augustine, R. L., editor), Vol. I., Marcel Dekker, N.Y. 1979.Google Scholar
  4. 2.
    Reetz, M. T., Maier, W. F.: Angew. Chem. 90, 50 (1978); Reetz, M. T., Maier, W. F. Angew. Chem., Int. Ed. Engl. 17, 48 (1978); Reetz, M. T., Chatziisosifidis, I., Löwe, U., Maier, W. F.: Tetrahedron Lett. 20, 1427 (1979).Google Scholar
  5. 3. a)
    Reetz, M. T., Maier, W. F., Heimbach, H., Giannis, A., Anastassiou, G.: Chem. Ber. 113, 3734 (1980);CrossRefGoogle Scholar
  6. 3. b)
    Reetz, M. T., Maier, W. F., Chatziiosifídis, I., Giannis, H., Heimbach, H., Löwe, U.: Chem. Ber. 113, 3741 (1980);CrossRefGoogle Scholar
  7. 3. c)
    Reetz, M. T., Chatziiosifídis, I., Hübner, F., Heimbach, H.: Org. Synth. 62, 95 (1984).Google Scholar
  8. 4. a)
    Review of α-alkylation of carbonyl compounds using SN1-active alkylating agents: Reetz, M. T.: Angew. Chem. 94, 91 (1982); Reetz, M. T. Angew. Chem., Int. Ed. Engl. 21, 96 (1982);Google Scholar
  9. 4. b)
    see also Fleming, I.: Chimia 34, 265 (1980);Google Scholar
  10. 4. c)
    Brown-bridge, P.: Synthesis 1983, 1, 85.CrossRefGoogle Scholar
  11. 5. a)
    Heimbach, H.: Diplomarbeit, Univ. Bonn 1980;Google Scholar
  12. 5. b)
    Reetz, M. T.: Nachr. Chem. Techn. Lab. 29, 165 (1981);CrossRefGoogle Scholar
  13. 5. c)
    Reetz, M. T.: “30 Jahre Fonds der Chemischen Industrie”, Verband der Chemischen Industrie, Frankfurt, p. 29, 1980.Google Scholar
  14. 6.
    Nakamura, E., Kuwajima, I.: Tetrahedron Lett. 24, 3347 (1983).CrossRefGoogle Scholar
  15. 7. a)
    Maier, W. F.: Dissertation, Univ. Marburg 1978;Google Scholar
  16. 7. b)
    Chan, T. H., Paterson, I., Pinsonnault, J.: Tetrahedron Lett. 18, 4183 (1977);CrossRefGoogle Scholar
  17. 7. c)
    See also lit. [3a].Google Scholar
  18. 8.
    Schwellnus, K.: Dissertation, Univ. Marburg 1981.Google Scholar
  19. 9. a)
    Reetz, M. T., Schwellnus, K.: Tetrahedron Lett. 19,1455 (1978); Reetz, M. T., Schwellnus, K., Hübner, F., Massa, W., Schmidt, R. E.: Chem. Ber. 116, 3708 (1983).Google Scholar
  20. 10. a)
    Reetz, M. T., Hüttenhain, S. H., Walz, P., Löwe, U.: Tetrahedron Lett. 20, 4971 (1979);CrossRefGoogle Scholar
  21. 10. b)
    Reetz, M. T., Walz, P., Hübner, F., Hüttenhain, S. H., Heimbach, H., Schwellnus, K.: Chem. Ber. 117, 322 (1984).CrossRefGoogle Scholar
  22. 11. a)
    Paterson, I.: Tetrahedron Lett. 20, 1519 (1979);CrossRefGoogle Scholar
  23. 11. b)
    Fleming, I., Goldhill, J., Paterson, I.: Tetrahedron Lett. 20, 3209 (1979);CrossRefGoogle Scholar
  24. 11. c)
    Trost, B. M., Fray, M. J.: Tetrahedron Lett. 25, 4605 (1984).CrossRefGoogle Scholar
  25. 12.
    Reetz, M. T., Sauerwald, M., Walz, P.: Tetrahedron Lett. 22, 1101 (1981).CrossRefGoogle Scholar
  26. 13.
    Mukaiyama, T.: Angew. Chem. 89, 858 (1977); Mukaiyama, T. Angew. Chem., Int. Ed. Engl. 16, 817 (1977).Google Scholar
  27. 14.
    Reetz, M. T., Peter, R.: Tetrahedron Lett. 22, 4691 (1981).CrossRefGoogle Scholar
  28. 15.
    Peter, R.: Dissertation, Univ. Marburg 1983.Google Scholar
  29. 16.
    In other cases the more reactive allylacetate does in fact undergo Pd(PPh3)4 catalyzed C—C bond formation [15].Google Scholar
  30. 17. a)
    Seebach, D., Weller, T., Protschuk, G., Beck, A. K., Hoekstra, M. S.: Helv. Chim. Acta 64, 716 (1981);CrossRefGoogle Scholar
  31. 17. b)
    Tirpak, R. E., Rathke, M. W.: J. Org. Chem. 47, 5099 (1982).CrossRefGoogle Scholar
  32. 18. a)
    This reaction is general for other Li-enolates [15] and is thus simpler than alternative methods for preparing α-iodo ketones: Rubottom, G. M., Mott, R. C.: J. Org. Chem. 44, 1731 (1979);CrossRefGoogle Scholar
  33. 18. b)
    D’Ascoli, R., D’Auria, M., Nucciarelli, L., Piancatelli, G., Scettri, A.: Tetrahedron Lett. 21, 4521 (1980) and lit. cited therein.CrossRefGoogle Scholar
  34. 19. a)
    Posner, G. H.: Org. React. 19,1 (1972);Google Scholar
  35. 19. b)
    Lipshutz, B. H., Wilhelm, R. S., Kozlowski, J. A.: Tetrahedron 40, 5005 (1984).CrossRefGoogle Scholar
  36. 20.
    Whitesides, G. M., Fischer, W. F., San Filippo, J., Bashe, R. W., House, H. O.: J. Am. Chem. Soc. 91, 4871 (1969).Google Scholar
  37. 21. a)
    Asinger, F., Vogel, H. H,: in Houben-Weyl-Müller, „Methoden der Organischen Chemie”, Vol. 5/la, p. 347, Thieme-Verlag, Stuttgart 1970;Google Scholar
  38. 21. b)
    Buck, R. F.: J. Int. Petrol. 34, 339 (1948).Google Scholar
  39. 22. a)
    Kennedy, J. P., Desai, W., Sivaram, S.: J. Am. Chem. Soc. 95, 6386 (1973);CrossRefGoogle Scholar
  40. 22. b)
    Beckhaus, H. D., Hellmann, G., Rüchardt, C.: Chem. Ber. 111, 72 (1978).CrossRefGoogle Scholar
  41. 23. a)
    Westermann, J.: Diplomarbeit, Univ. Bonn, 1980;Google Scholar
  42. 23. b)
    Westermann, J.: Dissertation, Univ. Marburg 1982;Google Scholar
  43. 23. c)
    Steinbach, R.: Diplomarbeit, Univ. Bonn 1980;Google Scholar
  44. 23. d)
    Steinbach, R.; Dissertation, Univ. Marburg 1982.Google Scholar
  45. 24.
    Nützel, K.: in Houben-Weyl-Müller, „Methoden der Organischen Chemie”, Vol. 13/2a, p. 47, Thieme-Verlag, Stuttgart 1973.Google Scholar
  46. 25.
    Reetz, M. T., Westermann, J., Steinbach, R.: Angew. Chem. 92, 931 (1980);CrossRefGoogle Scholar
  47. 25.
    Reetz, M. T., Westermann, J., Steinbach, R Angew. Chem., Int. Ed. Engl. 19, 900 (1980).CrossRefGoogle Scholar
  48. 26.
    Reetz, M. T., Westermann, J., Steinbach, R.: Angew. Chem. 92, 933 (1980);CrossRefGoogle Scholar
  49. 26.
    Reetz, M. T., Westermann, J., Steinbach, R. Angew. Chem., Int. Ed. Engl. 19, 901 (1980).CrossRefGoogle Scholar
  50. 27.
    Review of synthesis of compounds having quaternary C-atoms: Martin, S. F.: Tetrahedron 36,419 (1980).CrossRefGoogle Scholar
  51. 28.
    Reetz, M. T., Wenderoth, B., Peter, R., Steinbach, R., Westermann, J.: J. Chem. Soc., Chem. Commun. 1980, 1202.Google Scholar
  52. 29.
    Becker, K. B., Grob, C.A.: Synthesis 1973, 789.Google Scholar
  53. 30. a)
    Reetz, M. T., Stephan, W.: Angew. Chem. 89, 46 (1977);Google Scholar
  54. 30.
    Reetz, M. T., Stephan, W. Angew. Chem., Int. Ed. Engl. 16, 44 (1977);Google Scholar
  55. 30. b)
    Reetz, M. T., Weis, C.: Synthesis 1977, 135;Google Scholar
  56. 30. c)
    Reetz, M. T., Stephan, W.: Liebigs Ann. Chem. 1980, 171.Google Scholar
  57. 31. a)
    Reetz, M. T., Stephan, W.: Tetrahedron Lett. 18,2693 (1977);CrossRefGoogle Scholar
  58. 31. b)
    Reetz, M. T., Stephan, W.: J. Chem. Res. (S) 1981, 44;Google Scholar
  59. 31. b)
    Reetz, M. T., Stephan, W. J. Chem. Res. (M) 1981, 583.Google Scholar
  60. 32. a)
    Sasaki, T., Usuki, A., Ohno, M.: J. Org. Chem. 45, 3559 (1980); reviews of TiCl4 mediated allylsilane reactions:CrossRefGoogle Scholar
  61. 32. b)
    Fleming, I., Paterson, I.: Synthesis 1979, 446 (1979);Google Scholar
  62. 32. c)
    Parnes, Z. N., Bolestova, G. I.: Synthesis 1984, 991.Google Scholar
  63. 32. d)
    Reetz, M. T., Jung, A.: unpublished.Google Scholar
  64. 33.
    Peter, R.: Diplomarbeit, Univ. Marburg 1980.Google Scholar
  65. 34.
    Negishi, E., Baba, S.: J. Am. Chem. Soc. 97, 7385 (1975).CrossRefGoogle Scholar
  66. 35.
    Reetz, M. T., Steinbach, R., Wenderoth, B.: Synth. Commun. 11, 261 (1981).CrossRefGoogle Scholar
  67. 36.
    Reetz, M. T. et al.: unpublished.Google Scholar
  68. 37.
    Reetz, M. T., Westermann, J., Steinbach, R.: J. Chem. Soc., Chem. Commun. 1981, 237.Google Scholar
  69. 38.
    Meisters, A., Mole, T.: Aust. J. Chem. 27, 1655, 2569 (1974).CrossRefGoogle Scholar
  70. 39.
    In lit. [37] one equivalent of (CH3)2Zn is erroneously reported. Full experimental details are available in ref. [23 d].Google Scholar
  71. 40.
    Uemura, M., Isobe, K., Hayashi, Y.: Tetrahedron Lett. 26, 767 (1985).CrossRefGoogle Scholar
  72. 41.
    Reetz, M. T., Sauerwald, M.: Tetrahedron Lett. 24, 2387 (1983).CrossRefGoogle Scholar
  73. 42.
    Reetz, M. T., Westermann, J., Kyung, S. H.: Chem. Ber. 118, 1050 (1985).CrossRefGoogle Scholar
  74. 43.
    Posner, G. H., Koga, T. P.: J. Chem. Soc., Chem. Commun. 1983, 1481.Google Scholar
  75. 44.
    Reetz, M. T., Westermann, J.: J. Org. Chem. 48, 254 (1983).CrossRefGoogle Scholar
  76. 45.
    Brown-Wensley, K. A., Buchwald, S. L., Cannizzo, L., Clawson, L., Ho, S., Meinhardt, D., Stille, J. R., Straus, D., Grubbs, R. H.: Pure Appl. Chem. 55,1733 (1983).CrossRefGoogle Scholar
  77. 46.
    Ishikawa, H., Mukaiyama, T., Ikeda, S.: Bull. Chem. Soc. Jap. 54, 776 (1981).CrossRefGoogle Scholar
  78. 47.
    Barbot, F., Miginiac, P.: J. Organomet. Chem. 170, 1 (1979).CrossRefGoogle Scholar
  79. 48.
    Ghribi, A., Alexakis, A., Normant, J. F.: Tetrahedron Lett. 25, 3075 (1984).CrossRefGoogle Scholar
  80. 49. a)
    Hosomi, A., Endo, M., Sakurai, H.: Chem. Lett. 1976, 941;Google Scholar
  81. 49. b)
    Ojima, I., Kumagai, M., Miyazawa, Y.: Tetrahedron Lett. 18, 1385 (1977);CrossRefGoogle Scholar
  82. 49. c)
    Tsunoda, T., Suzuki, M., Noyori, R.: Tetrahedron Lett. 21, 71 (1980).CrossRefGoogle Scholar
  83. 50. a)
    Casara, P., Metealf, B. W.: Tetrahedron Lett. 19, 1581 (1978);CrossRefGoogle Scholar
  84. 50. b)
    Schmid, R., Huermann, P. L., Johnson, W. S.: J. Am. Chem. Soc. 102, 5122 (1980).CrossRefGoogle Scholar
  85. 51. a)
    Utimoto, K., Wakabayashi, Y., Horiie, T., Inoue, M., Shishiyama, Y., Obayashi, M., Nozaki, H.: Tetrahedron 39, 967 (1983);CrossRefGoogle Scholar
  86. 51. b)
    Reetz, M. T., Chatziiosifldis, I., Künzer, H., Müller-Starke, H.: Tetrahedron 39, 961 (1983).CrossRefGoogle Scholar
  87. 52.
    McNamara, J. M., Kishi, Y.: J. Am. Chem. Soc. 104, 7371 (1982).CrossRefGoogle Scholar
  88. 53.
    Bartlett, P. A., Johnson, W. S., Elliott, J. D.: J. Am. Chem. Soc. 105, 2088 (1983).CrossRefGoogle Scholar
  89. 54. a)
    Hoffmann, R. W., Herold, T.: Chem. Ber. 114, 375 (1981);CrossRefGoogle Scholar
  90. 54. b)
    Brown, H. C., Jadhav, P. K.: J. Org. Chem. 49, 4089 (1984); and lit. cited therein.CrossRefGoogle Scholar
  91. 55.
    Choi, V. M. F., Elliot, J. D., Johnson, W. S.: Tetrahedron Lett. 25, 591 (1984).CrossRefGoogle Scholar
  92. 56.
    Johnson, W. S., Crackett, P. H., Elliott, J. D., Jagodzinski, J. J., Lindell, S. D., Natarajan, S.: Tetrahedron Lett. 25, 3951 (1984).CrossRefGoogle Scholar
  93. 57.
    Johnson, W. S., Elliott, R., Elliott, J. D.: J. Am. Chem. Soc. 105, 2904 (1983).CrossRefGoogle Scholar
  94. 58.
    Lindell, S. D., Elliott, J. D., Johnson, W. S.: Tetrahedron Lett. 25, 3947 (1984).CrossRefGoogle Scholar
  95. 59. a)
    See for example: Mukaiyama, T., Soai, K., Sato, T., Shimizu, H., Suzuki, K.: J. Am. Chem. Soc. 101, 1455 (1979);CrossRefGoogle Scholar
  96. 59. b)
    Mazaleyrat, J. P., Cram, D. J.: J. Am. Chem. Soc. 103, 4585 (1981);CrossRefGoogle Scholar
  97. 59. c)
    Eleveid, M. B., Hogeveen, H.: Tetrahedron Lett. 25, 5187 (1984);CrossRefGoogle Scholar
  98. 59. d)
    Meyers, A. I., Harre, M., Garland, R.: J. Am. Chem. Soc. 106,1146 (1984);CrossRefGoogle Scholar
  99. 59. e)
    Mori, A., Fujiwara, J., Maruoka, K., Yamamoto, H.: Tetrahedron Lett. 24, 4581 (1983);CrossRefGoogle Scholar
  100. 59. f)
    Midland, M. M., Kazubski, A.: J. Org. Chem. 47, 2495 (1982);CrossRefGoogle Scholar
  101. 59. g)
    Noyori, R., Tomino, I., Tanimoto, Y.: J. Am. Chem. Soc. 101, 3129 (1979).CrossRefGoogle Scholar
  102. 60.
    Mashraqui, S. H., Kellogg, R. M.: J. Org. Chem. 49, 2513 (1984).CrossRefGoogle Scholar
  103. 61.
    Mori, A., Maruoka, K., Yamamoto, H.: Tetrahedron Lett. 25, 4421 (1984).CrossRefGoogle Scholar
  104. 62.
    Ghribi, A., Alexakis, A., Normant, J. F.: Tetrahedron Lett. 25, 3082 (1984).Google Scholar
  105. 63. a)
    .Seebach, D., Beck, A. K., Schiess, M., Widler, L., Wonnacot, A.: Pure Appl. Chem. 55, 1807 (1983);CrossRefGoogle Scholar
  106. 63. b)
    Seebach, D., Betschart, C., Schiess, M.: Helv. Chim. Acta 67, 1593 (1984).CrossRefGoogle Scholar
  107. 64. a)
    Comins, D. L., Brown, J. D.: Tetrahedron Lett. 22, 4213 (1981);CrossRefGoogle Scholar
  108. 63. b)
    Comins, D. L., Brown, J. D., Mantlo, N. B.: Tetrahedron Lett. 23, 3979 (1982).CrossRefGoogle Scholar
  109. 65.
    Reetz, M. T., Wenderoth, B., Peter, R.: J. Chem. Soc., Chem. Commun. 1983,406.Google Scholar
  110. 66.
    Wenderoth, B.: Dissertation, Univ. Marburg 1983.Google Scholar
  111. 67.
    Reetz, M. T.: Top. Curr. Chem. 106, 1 (1982).Google Scholar
  112. 68. a)
    Abenhaim, D., Henry-Basch, E., Freon, P.: Bull. Soc. Chim. Fr. 1970, 179;Google Scholar
  113. 68. b)
    Courtois, G., Miginiac, L.: J. Organomet. Chem. 69, 1 (1974).CrossRefGoogle Scholar
  114. 69.
    If carbonyl compounds are added, olefination sets in: M. T. Reetz, et al., unpublished.Google Scholar
  115. 70. a)
    Plevyak, J. E., Heck, R. F.: J. Org. Chem. 43, 2454 (1978);CrossRefGoogle Scholar
  116. 70. b)
    Heck, R. F.: Pure Appl. Chem. 50, 691 (1978).CrossRefGoogle Scholar
  117. 71.
    Barber, J. J., Willis, C., Whitesides, G. M.: J. Org. Chem. 44, 3603 (1979).CrossRefGoogle Scholar
  118. 72.
    Schlosser, M., Fujita, K.: Angew. Chem. 94, 320 (1982);CrossRefGoogle Scholar
  119. 72.
    Schlosser, M., Fujita, K. Angew. Chem., Int. Ed. Engl. 21, 309 (1982);CrossRefGoogle Scholar
  120. 72.
    Schlosser, M., Fujita, K. Angew. Chem. Supplement 1982, 646.Google Scholar
  121. 73.a)
    Youngblood, A. V., Nichols, S. A., Coleman, R. A., Thompson, D. W.: J. Organomet. Chem. 146,221 (1978);CrossRefGoogle Scholar
  122. 73. b)
    Schultz, F. W., Ferguson, G. S., Thompson, D. W.: J. Org. Chem. 49,1736 (1984);CrossRefGoogle Scholar
  123. 73. c)
    Brown, D. C., Nichols, S. A., Gilpin, A. B., Thompson, D. W.: J. Org. Chem. 44, 3457 (1979);CrossRefGoogle Scholar
  124. 73. d)
    Sato, F., Tomuro, Y., Ishikawa, H., Sato, M.: Chem. Lett. 1980, 99;Google Scholar
  125. 73. e)
    Negishi, E.: Pure Appl. Chem. 53, 2333 (1981);CrossRefGoogle Scholar
  126. 73. f)
    Hayami, H., Oshima, K., Nozaki, H.: Tetrahedron Lett. 25, 4433 (1984);CrossRefGoogle Scholar
  127. 73. g)
    Richey, H. G., Jr., Moses, L. M., Hangeland, J. J.: Organometallics 2, 1545 (1983) and lit. cited therein.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • Manfred T. Reetz
    • 1
  1. 1.Fachbereich Chemie der Universität MarburgMarburgGermany

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