P. Karoyan, G. Chassaing / Tetrahedron Letters 43 (2002) 253–255
255
22.9, 19.2. Anal. calcd for C22H24N2O2: C, 75.86; H, 6.89;
N, 8.04. Found: C, 75.71; H, 7.05; N, 8.04.
12. Carpes, M. J.; Miranda, P. C. M.; Correia, C. R. D.
Tetrahedron Lett. 1997, 38, 1872.
3-Cyanomethyl-1(1-phenyl-ethyl)-pyrrolidine-2-carboxylic-
acid-methyl ester 7.
13. Langlois, N.; Andriamialisoa, R. Z. Tetrahedron Lett.
1991, 32, 3057.
Same protocol from amine 8 yielding after purification
(flash chromatography, cyclohexane/ethylacetate, 9/1)
and crystallisation (ether/pentane) colourless needles:
14. Karoyan, Ph.; Chassaing, G. Tetrahedron Lett. 1997, 38,
85.
15. Karoyan, P.; Chassaing, G. Tetrahedron: Asymmetry
1997, 8, 2025.
16. Lorthiois, E.; Marek, I.; Normant, J.-F. Tetrahedron
Lett. 1997, 38, 89.
17. Vaupel, A.; Knochel, P. J. Org. Chem. 1996, 61, 5743.
18. Klement, I.; Lennick, K.; Tucker, C. E.; Knochel, P.
Tetrahedron Lett. 1993, 34, 4623.
1
[h]2D5 76 (c 1, CHCl3); H NMR (250 MHz CDCl3): l 7.3
(m, 5H), 3.98 (q, 1H), 3.69 (s, 3H), 3.48 (d, 1H, J3=7.8
Hz), 3.1 (m, 1H), 2.96 (m, 1H), 2.45–2.17 (m, 3H), 1.8 (m,
1H), 1.39 (d, 3H, J3=6.5 Hz), 1.23–1.16 (tr, 3H). 13C
NMR (62.5 MHz, CDCl3): l 172.5, 143.5, 128, 127, 118,
65.4, 61, 51.5, 49, 38, 29.5, 22.4, 19. Anal. calcd for
C16H20N2O2: C, 70.58; H, 7.35; N, 10.29. Found: C,
70.69; H, 7.69; N, 9.95.
19. Experimental part: All compounds had the expected ana-
lytical and spectroscopic properties.
(2S,3S)-3-Prolinoglutamic acid 5: 3-carboxymethyl-pyrrol-
idine-2-carboxylic acid.
3-Cyanomethyl-1(-1-phenyl-ethyl)-pyrrolidine-2-carboxylic-
acid–benzyl ester 4.
White powder after ion-exchange chromatography and
According to general procedure for the cyclisation–
transmetalation reaction.14,15 From amine 1 (3.23 g, 10
mmol), THF (25 ml), LDA (6 ml, 12 mmol), ZnBr2 (1.6
M, 19 ml), CuCN/2LiCl (1 M, 20 ml), yielding after
purification by flash chromatography (cyclohexane/ethyl-
acetate, 9/1), and crystallisation from cold ether/pentane
pale yellow crystals (2.37 g, 68%). Mp: 51–53°C; [h]2D5 −70
1
lyophilisation. H NMR (250 MHz, D2O): l 4.33 (d, 1H,
J3=8.25 Hz), 3.73–3.65 (m, 1H), 3.53–3.42 (m, 1H),
3.1–3.06 (m, 1H), 2.71–2.60 (m, 1H), 2.42–2.30 (m, 2H),
2.00–1.92 (m, 1H). 13C NMR (62.5 MHz, D2O): l 178.5,
172, 63.7, 44, 36.8, 36, 28.8. [h]2D5−32 (c 1, H2O). MH+:
calcd: 174 (obtained: 174).
(2S,3R)-3-Prolinoglutamic acid 9: 3-Carboxymethyl-pyrrol-
idine-2-carboxylic acid.
1
(c 1, CHCl3); H NMR (400 MHz, CDCl3): l 7.29–7.24
1
(m, 5H), 7.15–7.14 (m, 3H), 7.07–7.05 (m, 2H), 5.05–4.97
(AB, 2H), 3.66–3.63 (q, 1H), 3.37–3.35 (d, 1H, J3=8 Hz),
3–3.05 (m, 1H), 2.93–2.83 (m, 1H), 2.71–2.6 (m, 1H),
2.2–2 (m, 3H), 1.75–1.6 (m, 1H), 1.25–1.24 (d, 3H). 13C
NMR (100 MHz, CDCl3): l 172.1, 144, 135.8, 129.3–
129–128.8–127.7, 118.6, 66.7, 65.7, 61.2, 49.4, 38.6, 29.7,
White crystals from ethanol. H NMR (250 MHz, D2O):
l 3.79 (d, 1H, J3=7.5 Hz), 3.44–3.36 (m, 2H), 2.85 (m,
1H), 2.7 (m, 1H), 2.55 (m, 1H), 2.3 (m, 1H), 1.8 (m, 1H).
13C NMR (62.5 MHz, D2O): l 178, 173.5, 64.9, 44.7,
39.8, 39.2, 29.7. [h]D25 20 (c 0.1, H2O). Mp: 242–244°C.
MH+: calcd: 174 (obtained: 174).