Alkylation of chiral 2-(aminomethyl)oxazolines 

Abstract

Chiral 2-(aminomethyl)oxazolines 3 and 7, in which the heterocycle is derived from (R)-phenylglycinol, are synthesized and studied in alkylation reactions involving strong base and alkyl halides. The tertiary amine derivative 3 is alkylated efficiently at the α-carbon centre with no stereochemical induction, while the tertiary carbamate 7 is alkylated in moderate yield and reasonable diastereomeric excess. The stereochemical control observed in the latter case can be explained by the preferred formation of an E-enolate during the deprotonation step by prior complexation of the carbamate carbonyl group to the base.

References

1. K. A. Lutomski and A. I. Meyers, in Asymmetric Synthesis, ed., J. D. Morrison, Academic Press, New York, 1984, vol. 3, pp. 213–274.
2. T. G. Gant and A. I. Meyers, Tetrahedron, 1994, 50, 2297.
3. For recent examples of the diversity of applications, see: (a) A. I. Meyers and K. A. Novachek, Tetrahedron Lett., 1996, 37, 1747; (b) M. Shimano and A. I. Meyers, J. Org. Chem., 1995, 60, 7445; (c) D. Amurrio, K. Khan and E. P. Kundig, J. Org. Chem., 1996, 61, 2258; (d) N. Dahuron and N. Langlois, Synlett, 1996, 51; (e) C. M. Shafer and T. F. Molinski, J. Org. Chem., 1996, 61, 2044; (f) T. Sammakia and H. A. Latham, J. Org. Chem., 1996, 61, 1629.
4. A. I. Meyers, G. Knaus and P. M. Kendall, Tetrahedron Lett., 1974, 3495.
5. T. R. Kelly and A. Arvanitis, Tetrahedron Lett., 1984, 25, 39.
6. J. C. Clinet and G. Balavoine, Tetrahedron Lett., 1987, 28, 5509.
7. Y. Langlois and A. Pouilhes, Tetrahedron: Asymmetry, 1991, 2, 1223.
8. J.-C. Combret, J. Tekin and D. Postaire, Bull. Soc. Chim. Fr., 1984, 371.
9. S. Florio, V. Capriati and R. Luisi, Tetrahedron Lett., 1996, 37, 4781.
10. P. Breton, PhD Thesis, Université Paris-Sud (Orsay), 1992.
11. P. Breton, C. André-Barrès and Y. Langlois, Synth. Commun., 1992, 22, 2543.
12. Professor J. Liebscher's group (Humboldt-Universität zu Berlin) has studied the alkylation of chiral 2-(sulfonamidomethyl)oxazolines and a manuscript concerning this work has been accepted for publication in Synthesis; we thank Prof. Liebscher for this information. The alkylation of 2-(ω-aminoalkyl)oxazolines has also been studied: A. Rottman and J. Liebscher, Tetrahedron Lett., 1996, 37, 359.
13. The expected products of such reactions, 2-(α-aminoalkyl)-oxazolines, are usually prepared by cyclization of appropriate peptide precursors; for recent examples, see: (a) C. D. J. Boden and G. Pattenden, Tetrahedron Lett., 1995, 36, 6153; (b) E. Aguilar and A. I. Meyers, Tetrahedron Lett., 1994, 35, 2477; (c) P. Wipf and C. P. Miller, J. Org. Chem., 1993, 58, 1575 An interesting alternative approach, involving the reaction of an α-amino-electrophile and a metallated 2-methyloxazoline, has been described: T. Shono, N. Kise, F. Sanda, S. Ohi and K. Tsubata, Tetrahedron Lett., 1988, 29, 231.
14. G. Grangier, D. J. Aitken, D. Guillaume, A. Tomas, B. Viossat and H.-P. Husson, J. Heterocyclic Chem., 1994, 31, 1707.
15. D. Guillaume, M. Brum-Bousquet, D. J. Aitken and H.-P. Husson, Bull. Soc. Chim. Fr., 1994, 131, 391.
16. (a) D. J. Aitken, F. Vergne, A. S. Phimmanao, D. Guillaume and H.-P. Husson, Synlett, 1993, 599; (b) D. Guillaume, D. J. Aitken and H.-P. Husson, Synlett, 1991, 747.
17. F. Vergne, D. J. Aitken and H.-P. Husson, J. Org. Chem., 1992, 57, 6071.
18. The synthons described in this manuscript may be considered as chiral glycine equivalents; for leading references on the use of such species in the asymmetric synthesis of amino acids, see: (a) R. M. Williams, Synthesis of Optically Active α-Amino Acids, Pergammon, Oxford, 1989; (b) R. O. Duthaler, Tetrahedron, 1994, 50, 1539.
19. (a) H.-P. Husson and J. Royer, in Advances in the Use of Synthons in Organic Chemistry, ed., A. Dondoni, JAI Press, Greenwich, 1995, vol. 2, pp. 1–68; (b) H.-P. Husson, in New Aspects of Organic Chemistry II, eds., Z. Yoshida and Y. Ohshiro, VCH, Basel, 1992, pp. 87–103.
20. A short communication of this work was read at the 11th International Conference on Organic Chemistry (ICOS-11), Amsterdam, July 1996(Paper OC-38).
21. L. Velluz, G. Amirad and R. Heymès, Bull. Soc. Chim. Fr., 1954, 1012.
22. M. Bodanszky, Principles of Peptide Synthesis, Springer-Verlag, Berlin, 2nd edn., 1993.
23. (a) P. Wipf and P. C. Fritch, Tetrahedron Lett., 1994, 35, 5397; (b) B. A. Savatote and A. B. Smith III, Tetrahedron Lett., 1994, 35, 1329; (c) P. Wipf and S. Venkatraman, Tetrahedron Lett., 1996, 37, 4659; (d) P. Wipf and S. Venkatraman, J. Org. Chem., 1995, 60, 7224.
24. For other examples of the use of these conditions for oxazoline formation, see: (a) N. Galéotti, C. Montagne, J. Poncet and P. Jouin, Tetrahedron Lett., 1992, 33, 2807; (b) P. Wipf and C. P. Miller, Tetrahedron Lett., 1992, 33, 6267.
25. Literature preparations of N,N-dialkylglycine amides generally avoid this approach, employing instead a strategy involving condensation of an α-chloroacetamide with a dialkylamine; for examples, see: Beilstein, E IV, 4, pp. 2368–2383.
26. A. N. Baksheev and N. I. Gavrilov, J. Gen. Chem. USSR, 1952, 22, 2077.
27. M. A. Hoobler, D. E. Bergbreitner and M. Newcomb, J. Am. Chem. Soc., 1978, 100, 8182.
28. A. I. Meyers, E. S. Snyder and J. J. H. Ackerman, J. Am. Chem. Soc., 1978, 100, 8186.
29. J. Suffert, J. Org. Chem., 1989, 54, 509.
30. W. G. Kofron and L. M. Baclawski, J. Org. Chem., 1976, 41, 1879.
31. L. D. Arnold, J. C. G. Drover and J. C. Vederas, J. Am. Chem. Soc., 1987, 109, 4649.