Facile preparation of N-methyl secondary amines by titanium(IV) isopropoxide-mediated reductive amination of carbonyl compounds

Abstract

A simple, mild and efficient procedure for obtaining N-methyl secondary amines from aldehydes and ketones is reported. Treatment of carbonyl compounds with methylamine hydrochloride, triethylamine and titanium(IV) isopropoxide, followed by in situ sodium borohydride reduction and straightforward aqueous work-up, affords clean products in good to excellent yields.

References

1. (a) For some leading references, see: J. Kirschbaum, in Analytical Profiles of Drug Substances, ed. K. Florey, Academic Press, New York, 1983, vol. 12, p. 1; (b) K. T. Shaw, J. R. Luly and H. Rapoport, J. Org. Chem., 1985, 50, 4515; (c) W. R. Roush, J. A. Staub and R. J. Brown, J. Org. Chem., 1987, 52, 5127; (d) J. T. Welch, Tetrahedron, 1987, 43, 3123; (e) I. Ojima, K. Kato, K. Nakahashi, T. Fuchikami and M. Fujita, J. Org. Chem., 1989, 54, 4511; (f) P. S. Manchand, R. L. Cerruti, J. A. MArtin, C. H. Hill, J. H. Merrett, E. Keech, R. B. Belshe, E. V. Connell and I. S. Sim, J. Med. Chem., 1990, 33, 1992; (g) D. Askin, M. A. Wallace, J. P. Vacca, R. A. Reamer, R. P. Volante and I. Shinkai, J. Org. Chem., 1992, 57, 2771; (h) V. P. Kukhar, N. Yu Svistunova, V. A. Soloshonok and V. A. Solodenko, Russ. Chem. Rev. (Engl. Transl.), 1993, 62, 284; (i) B. G. Main and H. Tucker, in Medicinal Chemistry, eds. C. R. Genellin and S. M. Roberts, Academic Press, New York, 2nd edn., 1993, p. 187; (j) R. R. Goehring, Tetrahedron Lett., 1994, 35, 8145; (k) T. Tsunoda, F. Ozaki, N. Shirakata, Y. Tamaoka, H. Yamamato and S. Ito, Tetrahedron Lett., 1996, 37, 2463.
2. For recent reviews, see: (a) M. A. Gallop, R. W. Barrett, W. J. Dower, S. P. A. Fodor and E. M. Gordon, J. Med. Chem., 1994, 37, 1233; (b) E. M. Gordon, R. W. Barrett, W. J. Dower, S. P. A. Fodor and M. A. Gallop, J. Med. Chem., 1994, 37, 1385; (c) J. S. Fruchtel and G. Jung, Angew. Chem., Int. Ed. Engl., 1996, 35, 17; (d) P. H. H. Hermkens, H. C. J. Ottenheijm and D. Rees, Tetrahedron, 1996, 52, 4527.
3. For some recent publications, see: (a) K. Kaljuste and A. Unden, Tetrahedron Lett., 1995, 36, 9211; (b) S. V. Ley, D. M. Mynett and W.-J. Koot, Synlett, 1995, 1017; (c) G. C. Look, M. M. Murphy, D. A. Campbell and M. A. Gallop, Tetrahedron Lett., 1995, 36, 2937; (d) W. C. Chan and S. L. Mellor, J. Chem. Soc., Chem. Commun., 1995, 1475; (e) A. K. Szardenings, T. S. Burkoth, G. C. Look and D. A. Campbell, J. Org. Chem., 1996, 61, 6720; (f) I. A. Nash, B. W. Bycroft and W. C. Chan, Tetrahedron Lett., 1996, 37, 2625; (g) B. Ruhland, A. Bhandari, E. M. Gordon and M. A. Gallop, J. Am. Chem. Soc., 1996, 118, 253; (h) C. Y. Ho and M. J. Kukla, Tetrahedron Lett., 1997, 38, 2799; (i) L. Yang and K. Chiu, Tetrahedron Lett., 1997, 38, 7307.
4. See, for example: (a) B. E. Rossiter and M. Eguchi, Tetrahedron Lett., 1990, 31, 965; (b) M. S. McQueney, S. Lee, W. H. Swartz, H. L. Ammon, P. S. Mariano and D. D. Mariano, J. Org. Chem., 1991, 56, 7121; (c) M. Swamura and Y. Ito, Chem. Rev., 1992, 92, 857; (d) A. Togni and L. M. Venanzi, Angew. Chem., Int. Ed. Engl., 1994, 33, 497; (e) C. A. Jones, I. G. Jones, M. North and C. R. Pool, Tetrahedron Lett., 1995, 36, 7885; (f) M. Swamura, Y. Nakayama, T. Kato and Y. Ito, J. Org. Chem., 1995, 60, 1727.
5. (a) C. Sango and E. Zimmerson, J. Liq. Chromatogr., 1980, 3, 971; (b) L. H. Kormos, R. L. Sandrige and J. Keller, Anal. Chem., 1981, 53, 1122.
6. K. G. Wahlund and A. Sokolowski, J. Chromatogr., 1978, 151, 299.
7. (a) H. Hidaka, M. Inagaki, S. Kawamoto and Y. Sasaki, Biochemistry, 1984, 23, 5036; (b) R. J. Guajardo, J. D. Tan and P. K. Mascharak, Inorg. Chem., 1994, 33, 2838; (c) C. H. Hsieh and W. G. Wu, Biophys. J., 1995, 69, 2521.
8. (a) S. R. Sandler and W. Karo, Organic Functional Group Preparations, Academic Press, New York, 2nd edn., 1983, vol. 12-I, pp. 378–429; (b) J. March, Advanced Organic Chemistry, Wiley, New York, 1992, p. 411.
9. For reviews on reductive aminations see: (a) W. S. Emerson, Org. React. (N.Y.), 1948, 4, 174; (b) M. L. Moore, Org. React. (N.Y.), 1949, 5, 301; (c) C. F. Lane, Synthesis, 1975, 135; (d) R. O. Hutchins and N. Natale, Org. Prep. Proced. Int., 1979, 11, 201; (e) G. W. Gribble and C. F. Nutaitis, Org. Prep. Proced. Int., 1985, 17, 317; (f) J. K. Whitesell, in Comprehensive Organic Synthesis, eds. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol. 6, p. 724; (g) R. O. Hutchins and M. K. Hutchins, in Comprehensive Organic Synthesis, eds. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol. 8, p. 25.
10. (a) C. L. Barney, E. W. Huber and J. R. McCarthy, Tetrahedron Lett., 1990, 31, 5547; (b) I. V. Micovic, M. D. Ivanovic, D. M. Piatek and V. Dj. Bojic, Synthesis, 1991, 1043 and references cited therein.
11. (a) R. F. Borch and H. D. Durst, J. Am. Chem. Soc., 1969, 91, 3996; (b) R. F. Borch, M. D. Bernstein and H. D. Durst, J. Am. Chem. Soc., 1971, 93, 2897; (c) R. F. Borch, Org. Synth., 1988, Coll. Vol. 6, 499; (d) R. J. Mattson, K. M. Pham, D. J. Leuck and K. A. Cowen, J. Org. Chem., 1990, 55, 2552.
12. The Sigma-Aldrich Library of Chemical Safety Data, ed. R. E. Lenga, Sigma–Aldrich Corp., Milwaukee, 1st edn., 1985, p. 1609.
13. (a) A. E. Moormann, Synth. Commun., 1993, 23, 789; (b) A. F. Abdel-Magid and C. A. Maryanoff, in Reductions in Organic Synthesis, ACS Symposium Series 641, ed. A. F. Abdel-Magid, Americal Chemical Society, Washington, DC, 1996, p. 202.
14. (a) G. W. Gribble, P. D. Lord, J. Skotnicki, S. E. Dietz, J. T. Eaton and J. L. Johnson, J. Am. Chem. Soc., 1974, 96, 7812; (b) G. W. Gribble, J. M. Jasinski, J. T. Pellicone and J. A. Panetta, Synthesis, 1978, 766; (c) G. W. Gribble and C. F. Nutaitis, Synthesis, 1987, 709; (d) A. F. Abdel-Magid, C. A. Maryanoff and K. G. Carson, Tetrahedron Lett., 1990, 31, 5595; (e) A. F. Abdel-Magid and C. A. Maryanoff, Synlett, 1990, 537; (f) A. F. Abdel-Magid, K. G. Carson, B. D. Harris, C. A. Maryanoff and R. D. Shah, J. Org. Chem., 1996, 61, 3849.
15. (a) A. G. Giumanini, G. Chiavari, M. M. Musiani and P. Rossi, Synthesis, 1980, 743; (b) G. Verado, A. G. Giumanini, P. Strazzolini and M. Poina, Synthesis, 1993, 121 and references cited therein.
16. (a) A. Pelter, R. M. Rosser and S. J. Mills, J. Chem. Soc., Perkin Trans. 1, 1984, 717; (b) M. D. Bomann, I. C. Guch and M. Dimare, J. Org. Chem., 1995, 60, 5995.
17. S. Bhattacharyya, Tetrahedron Lett., 1994, 35, 2401.
18. (a) S. Bhattacharyya, Synlett, 1994, 1029; (b) S. Bhattacharyya, A. Chatterjee and J. S. Williamson, Synlett, 1995, 1079; (c) S. Bhattacharyya, J. Org. Chem., 1995, 60, 4928.
19. D. Seebach, E. Hungerbuhler, R. Naef, P. Schnurrenberger, B. Weidmann and M. Zueger, Synthesis, 1982, 138.
20. (a) M. T. Reetz, J. Westermann, R. Steinbach, B. Wenderoth, R. Peter, R. Ostarek and S. Maus, Chem. Ber., 1985, 118, 1421; (b) R. Imwinkelried and D. Seebach, Helv. Chim. Acta, 1984, 67, 1496.
21. H. Takahashi, T. Tsubuki and K. Higashiyama, Synthesis, 1988, 238 and references cited therein.