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.
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References
Stowell, J. C.: “Carbanions in Organic Chemistry”, Wiley, N. Y. 1979;
Bates, R. B., Ogle, C. A.: “Carbanion Chemistry”, Springer-Verlag, Berlin 1983;
Caine, D.: in “Carbon—Carbon Bond Fomation”, (Augustine, R. L., editor), Vol. I., Marcel Dekker, N.Y. 1979.
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).
Reetz, M. T., Maier, W. F., Heimbach, H., Giannis, A., Anastassiou, G.: Chem. Ber. 113, 3734 (1980);
Reetz, M. T., Maier, W. F., Chatziiosifídis, I., Giannis, H., Heimbach, H., Löwe, U.: Chem. Ber. 113, 3741 (1980);
Reetz, M. T., Chatziiosifídis, I., Hübner, F., Heimbach, H.: Org. Synth. 62, 95 (1984).
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);
see also Fleming, I.: Chimia 34, 265 (1980);
Brown-bridge, P.: Synthesis 1983, 1, 85.
Heimbach, H.: Diplomarbeit, Univ. Bonn 1980;
Reetz, M. T.: Nachr. Chem. Techn. Lab. 29, 165 (1981);
Reetz, M. T.: “30 Jahre Fonds der Chemischen Industrie”, Verband der Chemischen Industrie, Frankfurt, p. 29, 1980.
Nakamura, E., Kuwajima, I.: Tetrahedron Lett. 24, 3347 (1983).
Maier, W. F.: Dissertation, Univ. Marburg 1978;
Chan, T. H., Paterson, I., Pinsonnault, J.: Tetrahedron Lett. 18, 4183 (1977);
See also lit. [3a].
Schwellnus, K.: Dissertation, Univ. Marburg 1981.
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).
Reetz, M. T., Hüttenhain, S. H., Walz, P., Löwe, U.: Tetrahedron Lett. 20, 4971 (1979);
Reetz, M. T., Walz, P., Hübner, F., Hüttenhain, S. H., Heimbach, H., Schwellnus, K.: Chem. Ber. 117, 322 (1984).
Paterson, I.: Tetrahedron Lett. 20, 1519 (1979);
Fleming, I., Goldhill, J., Paterson, I.: Tetrahedron Lett. 20, 3209 (1979);
Trost, B. M., Fray, M. J.: Tetrahedron Lett. 25, 4605 (1984).
Reetz, M. T., Sauerwald, M., Walz, P.: Tetrahedron Lett. 22, 1101 (1981).
Mukaiyama, T.: Angew. Chem. 89, 858 (1977); Mukaiyama, T. Angew. Chem., Int. Ed. Engl. 16, 817 (1977).
Reetz, M. T., Peter, R.: Tetrahedron Lett. 22, 4691 (1981).
Peter, R.: Dissertation, Univ. Marburg 1983.
In other cases the more reactive allylacetate does in fact undergo Pd(PPh3)4 catalyzed C—C bond formation [15].
Seebach, D., Weller, T., Protschuk, G., Beck, A. K., Hoekstra, M. S.: Helv. Chim. Acta 64, 716 (1981);
Tirpak, R. E., Rathke, M. W.: J. Org. Chem. 47, 5099 (1982).
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);
D’Ascoli, R., D’Auria, M., Nucciarelli, L., Piancatelli, G., Scettri, A.: Tetrahedron Lett. 21, 4521 (1980) and lit. cited therein.
Posner, G. H.: Org. React. 19,1 (1972);
Lipshutz, B. H., Wilhelm, R. S., Kozlowski, J. A.: Tetrahedron 40, 5005 (1984).
Whitesides, G. M., Fischer, W. F., San Filippo, J., Bashe, R. W., House, H. O.: J. Am. Chem. Soc. 91, 4871 (1969).
Asinger, F., Vogel, H. H,: in Houben-Weyl-Müller, „Methoden der Organischen Chemie”, Vol. 5/la, p. 347, Thieme-Verlag, Stuttgart 1970;
Buck, R. F.: J. Int. Petrol. 34, 339 (1948).
Kennedy, J. P., Desai, W., Sivaram, S.: J. Am. Chem. Soc. 95, 6386 (1973);
Beckhaus, H. D., Hellmann, G., Rüchardt, C.: Chem. Ber. 111, 72 (1978).
Westermann, J.: Diplomarbeit, Univ. Bonn, 1980;
Westermann, J.: Dissertation, Univ. Marburg 1982;
Steinbach, R.: Diplomarbeit, Univ. Bonn 1980;
Steinbach, R.; Dissertation, Univ. Marburg 1982.
Nützel, K.: in Houben-Weyl-Müller, „Methoden der Organischen Chemie”, Vol. 13/2a, p. 47, Thieme-Verlag, Stuttgart 1973.
Reetz, M. T., Westermann, J., Steinbach, R.: Angew. Chem. 92, 931 (1980);
Reetz, M. T., Westermann, J., Steinbach, R Angew. Chem., Int. Ed. Engl. 19, 900 (1980).
Reetz, M. T., Westermann, J., Steinbach, R.: Angew. Chem. 92, 933 (1980);
Reetz, M. T., Westermann, J., Steinbach, R. Angew. Chem., Int. Ed. Engl. 19, 901 (1980).
Review of synthesis of compounds having quaternary C-atoms: Martin, S. F.: Tetrahedron 36,419 (1980).
Reetz, M. T., Wenderoth, B., Peter, R., Steinbach, R., Westermann, J.: J. Chem. Soc., Chem. Commun. 1980, 1202.
Becker, K. B., Grob, C.A.: Synthesis 1973, 789.
Reetz, M. T., Stephan, W.: Angew. Chem. 89, 46 (1977);
Reetz, M. T., Stephan, W. Angew. Chem., Int. Ed. Engl. 16, 44 (1977);
Reetz, M. T., Weis, C.: Synthesis 1977, 135;
Reetz, M. T., Stephan, W.: Liebigs Ann. Chem. 1980, 171.
Reetz, M. T., Stephan, W.: Tetrahedron Lett. 18,2693 (1977);
Reetz, M. T., Stephan, W.: J. Chem. Res. (S) 1981, 44;
Reetz, M. T., Stephan, W. J. Chem. Res. (M) 1981, 583.
Sasaki, T., Usuki, A., Ohno, M.: J. Org. Chem. 45, 3559 (1980); reviews of TiCl4 mediated allylsilane reactions:
Fleming, I., Paterson, I.: Synthesis 1979, 446 (1979);
Parnes, Z. N., Bolestova, G. I.: Synthesis 1984, 991.
Reetz, M. T., Jung, A.: unpublished.
Peter, R.: Diplomarbeit, Univ. Marburg 1980.
Negishi, E., Baba, S.: J. Am. Chem. Soc. 97, 7385 (1975).
Reetz, M. T., Steinbach, R., Wenderoth, B.: Synth. Commun. 11, 261 (1981).
Reetz, M. T. et al.: unpublished.
Reetz, M. T., Westermann, J., Steinbach, R.: J. Chem. Soc., Chem. Commun. 1981, 237.
Meisters, A., Mole, T.: Aust. J. Chem. 27, 1655, 2569 (1974).
In lit. [37] one equivalent of (CH3)2Zn is erroneously reported. Full experimental details are available in ref. [23 d].
Uemura, M., Isobe, K., Hayashi, Y.: Tetrahedron Lett. 26, 767 (1985).
Reetz, M. T., Sauerwald, M.: Tetrahedron Lett. 24, 2387 (1983).
Reetz, M. T., Westermann, J., Kyung, S. H.: Chem. Ber. 118, 1050 (1985).
Posner, G. H., Koga, T. P.: J. Chem. Soc., Chem. Commun. 1983, 1481.
Reetz, M. T., Westermann, J.: J. Org. Chem. 48, 254 (1983).
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).
Ishikawa, H., Mukaiyama, T., Ikeda, S.: Bull. Chem. Soc. Jap. 54, 776 (1981).
Barbot, F., Miginiac, P.: J. Organomet. Chem. 170, 1 (1979).
Ghribi, A., Alexakis, A., Normant, J. F.: Tetrahedron Lett. 25, 3075 (1984).
Hosomi, A., Endo, M., Sakurai, H.: Chem. Lett. 1976, 941;
Ojima, I., Kumagai, M., Miyazawa, Y.: Tetrahedron Lett. 18, 1385 (1977);
Tsunoda, T., Suzuki, M., Noyori, R.: Tetrahedron Lett. 21, 71 (1980).
Casara, P., Metealf, B. W.: Tetrahedron Lett. 19, 1581 (1978);
Schmid, R., Huermann, P. L., Johnson, W. S.: J. Am. Chem. Soc. 102, 5122 (1980).
Utimoto, K., Wakabayashi, Y., Horiie, T., Inoue, M., Shishiyama, Y., Obayashi, M., Nozaki, H.: Tetrahedron 39, 967 (1983);
Reetz, M. T., Chatziiosifldis, I., Künzer, H., Müller-Starke, H.: Tetrahedron 39, 961 (1983).
McNamara, J. M., Kishi, Y.: J. Am. Chem. Soc. 104, 7371 (1982).
Bartlett, P. A., Johnson, W. S., Elliott, J. D.: J. Am. Chem. Soc. 105, 2088 (1983).
Hoffmann, R. W., Herold, T.: Chem. Ber. 114, 375 (1981);
Brown, H. C., Jadhav, P. K.: J. Org. Chem. 49, 4089 (1984); and lit. cited therein.
Choi, V. M. F., Elliot, J. D., Johnson, W. S.: Tetrahedron Lett. 25, 591 (1984).
Johnson, W. S., Crackett, P. H., Elliott, J. D., Jagodzinski, J. J., Lindell, S. D., Natarajan, S.: Tetrahedron Lett. 25, 3951 (1984).
Johnson, W. S., Elliott, R., Elliott, J. D.: J. Am. Chem. Soc. 105, 2904 (1983).
Lindell, S. D., Elliott, J. D., Johnson, W. S.: Tetrahedron Lett. 25, 3947 (1984).
See for example: Mukaiyama, T., Soai, K., Sato, T., Shimizu, H., Suzuki, K.: J. Am. Chem. Soc. 101, 1455 (1979);
Mazaleyrat, J. P., Cram, D. J.: J. Am. Chem. Soc. 103, 4585 (1981);
Eleveid, M. B., Hogeveen, H.: Tetrahedron Lett. 25, 5187 (1984);
Meyers, A. I., Harre, M., Garland, R.: J. Am. Chem. Soc. 106,1146 (1984);
Mori, A., Fujiwara, J., Maruoka, K., Yamamoto, H.: Tetrahedron Lett. 24, 4581 (1983);
Midland, M. M., Kazubski, A.: J. Org. Chem. 47, 2495 (1982);
Noyori, R., Tomino, I., Tanimoto, Y.: J. Am. Chem. Soc. 101, 3129 (1979).
Mashraqui, S. H., Kellogg, R. M.: J. Org. Chem. 49, 2513 (1984).
Mori, A., Maruoka, K., Yamamoto, H.: Tetrahedron Lett. 25, 4421 (1984).
Ghribi, A., Alexakis, A., Normant, J. F.: Tetrahedron Lett. 25, 3082 (1984).
.Seebach, D., Beck, A. K., Schiess, M., Widler, L., Wonnacot, A.: Pure Appl. Chem. 55, 1807 (1983);
Seebach, D., Betschart, C., Schiess, M.: Helv. Chim. Acta 67, 1593 (1984).
Comins, D. L., Brown, J. D.: Tetrahedron Lett. 22, 4213 (1981);
Comins, D. L., Brown, J. D., Mantlo, N. B.: Tetrahedron Lett. 23, 3979 (1982).
Reetz, M. T., Wenderoth, B., Peter, R.: J. Chem. Soc., Chem. Commun. 1983,406.
Wenderoth, B.: Dissertation, Univ. Marburg 1983.
Reetz, M. T.: Top. Curr. Chem. 106, 1 (1982).
Abenhaim, D., Henry-Basch, E., Freon, P.: Bull. Soc. Chim. Fr. 1970, 179;
Courtois, G., Miginiac, L.: J. Organomet. Chem. 69, 1 (1974).
If carbonyl compounds are added, olefination sets in: M. T. Reetz, et al., unpublished.
Plevyak, J. E., Heck, R. F.: J. Org. Chem. 43, 2454 (1978);
Heck, R. F.: Pure Appl. Chem. 50, 691 (1978).
Barber, J. J., Willis, C., Whitesides, G. M.: J. Org. Chem. 44, 3603 (1979).
Schlosser, M., Fujita, K.: Angew. Chem. 94, 320 (1982);
Schlosser, M., Fujita, K. Angew. Chem., Int. Ed. Engl. 21, 309 (1982);
Schlosser, M., Fujita, K. Angew. Chem. Supplement 1982, 646.
Youngblood, A. V., Nichols, S. A., Coleman, R. A., Thompson, D. W.: J. Organomet. Chem. 146,221 (1978);
Schultz, F. W., Ferguson, G. S., Thompson, D. W.: J. Org. Chem. 49,1736 (1984);
Brown, D. C., Nichols, S. A., Gilpin, A. B., Thompson, D. W.: J. Org. Chem. 44, 3457 (1979);
Sato, F., Tomuro, Y., Ishikawa, H., Sato, M.: Chem. Lett. 1980, 99;
Negishi, E.: Pure Appl. Chem. 53, 2333 (1981);
Hayami, H., Oshima, K., Nozaki, H.: Tetrahedron Lett. 25, 4433 (1984);
Richey, H. G., Jr., Moses, L. M., Hangeland, J. J.: Organometallics 2, 1545 (1983) and lit. cited therein.
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Reetz, M.T. (1986). Substitution Reactions. In: Organotitanium Reagents in Organic Synthesis. Reactivity and Structure: Concepts in Organic Chemistry, vol 24. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-70704-9_7
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DOI: https://doi.org/10.1007/978-3-642-70704-9_7
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