The enantiospecific synthesis of functionalised pipecolic acids as constrained analogues of lysine

Tetrahedron Letters

Volumn 37, Issue 11, 1996, Pages 1875-1878

  Murray, Peter John ^a   Starkey, Ian D ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

PIPECOLIC ACID DERIVATIVE;

ARTICLE; DRUG SYNTHESIS; ENANTIOMER; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029887905     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)00140-2     Document Type: Article

References (37)

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2. (b) Williams, R.M. In 'Synthesis of Optically Active α-Amino Acids'; Organic Chemistry Series, Eds. Baldwin, J.E. and Magnus, P.D.: Pergamon Press, Oxford, 1989, Vol 7;
3. (c) Bailey, P.D.; Clayson, J.; Boa, A.N. Contemporary Organic Synthesis, 1995, 173.
4. (a) Christie, B.D; Rappoport, H. J.Org. Chem., 1985, 50, 1239;
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23. All new compounds were fully characterized and gave spectroscopic and analytical data consistent with assigned structures.
24. 1H NMR (DMSO, 400MHz) enol tautomer δ: 2.51 (1H, dm, J=16.5 Hz), 2.71 (1H, dd, J=16.5, 11.8 Hz), 4.03 (1H, m), 4.48 (2H, m), 5.01 (1H, s), 11.45 (1H, s br).
25. Hermitage, S.A.; Maloney, M. Tetrahedron: Asymmetry, 1994, 5, 1463.
26. Addition of the enolate to a stirred solution of benzyl bromide (5 equiv.) gave a separable mixture of cis and trans alkylation products in 46% isolated yield.
27. Pedregal, C.; Ezquerra, J.; Escribano, A.; Carreno, M.C.; Ruano, J.L.G. Tetrahedron Lett., 1994, 35, 2053.
28. 2O/ hexane 2:1); 7: 0.23, 8a: 0.28, 8b: 0.21. The corresponding methyl esters were more difficult to separate.
29. 1H NMR (DMSO, 400 MHz, 100°C) 9a: δ: 1.04 (1H, m), 1.19 (3H, t, J=7 Hz), 1.40 (9H, s), 1.65-1.80 (3H, m), 2.14 (1H, m), 2.40-2.52 (2H, m), 2.62, (1H, dd, J=12.5, 12 Hz), 3.96 (1H, dd, J=12.5, 5 Hz), 4.15 (2H, q, J=7 Hz), 4.66 (1H, dd, J=6, 1.5 Hz); 9b: δ: 1.21 (3H, t, J=7 Hz), 1.40 (9H, s), 1.51 (1H, m), 1.60 (1H, m), 1.84-1.91 (2H, m), 2.10 (1H, m), 2.48 (1H, dd, J=17.5, 7.5 Hz), 2.54 (1H, dd, J=17.5, 8.5 Hz), 3.20 (1H, dd, J=13.5, 4 Hz), 3.69 (1H, dd, J=13.5, 3.5 Hz), 4.14 (2H, q, J=7 Hz), 4.55 (1H, dd, J=5.0, 5.0 Hz).
30. 3, 400 MHz, 30°C) 10a: δ: 1.21 (3H, t, J=7 Hz), 1.47 (1H, m), 1.79 (1H, m), 1.87 (1H, m) 1.92 (1H, m), 2.00 (1H, m), 2.37-2.42 (2H, m), 2.39 (1H, dd, J=12, 7.5 Hz), 2.94 (1H, dd, J=12, 3.5 Hz), 4.08-4.20 (2H, m); 10b: δ: 1.21 (3H, t, J=7 Hz), 1.27 (1H, m), 1.46 (1H, dddd, J=13, 13, 11, 4 Hz), 1.78 (1H, m), 1.96 (1H, m), 2.03 (1H, dq, J=13, 3 Hz), 2.18 (1H, m), 2.23 (1H, m), 2.39 (1H, dd, J=12, 11 Hz), 3.17 (1H, ddd, J=12, 4, 2 Hz), 3.21 (1H, dd, J=11, 3 Hz), 4.12 (2H, q, J=7 Hz).
31. 1H NMR (DMSO, 400 MHz, 100°C) δ: 1.30-1.54 (4H, m), 1.68-1.88 (3H, m), 3.0 (2H, m), 3.13 (1H, dd, J=13, 3 Hz), 3.60 (1H, d, J=13 Hz), 4.24 (1H, dd, J=6, 6 Hz,), 4.32-4.42 (2H, ddd, J=20, 10, 6 Hz), 4.50 (1H, dd, J=6, 4 Hz), 5.01 (2H, s), 6.74 (1H, s br), 7.20-7.40 (9H, m), 7.60 (2H, d, J=7 Hz), 7.90 (2H, d, J=7 Hz).
32. 3N (95: 4.95: 0.05), 1ml/min at 40°C; 15b: Chiralcel OJ column eluted with heptane/ EtOH, (95:5) 1ml/min at 25°C. matrix presented
33. 1H NMR.
34. (a) Jouin, P.; Castro, B.; Nisato, D. J. Chem. Soc., Perkin Trans. 1. 1987, 1177;
35. (b) Tohdo, K.; Hamada, Y.; Shioiri, T. Syn. Lett., 1994, 105.
36. 3,400 MHz) keto tautomer δ: 1.49 (9H, s), 2.84 (1H, dd, J=18, 7 Hz), 3.07 (1H, dd, J=18, 2 Hz), 3.33 (1H, d, J=19 Hz), 3.47 (1H, J=19 Hz), 5.20 (2H, s), 5.26 (1H, dd, J=7, 2 Hz), 7.25-7.40 (5H, m).
37. 3, 400 MHz) δ: 1.48 (9H, s), 2.78 (1H, m), 2.88 (1H, ddd, J=17.5, 6, 1.7 Hz), 5.09 (1H, m), 5.12 (1H, d, J=13 Hz), 5.23 (1H, d, J=13 Hz), 5.95 (1H, dd, J=10, 2.5 Hz), 6.58 (1H, m), 7.32 (5H, m).