F. Lamaty et al.
(S)-tert-Butyl-2-(diphenylmethyleneamino)pent-4-enoate (8) [119244–22–
3]:[20] Yield: 97.3 mg (97%); colorless oil; [a]D20 =À40 (c=2, CHCl3); ee=
75% (HPLC analysis of the Marfey derivative: tr =7.6 (S), 7.9 min (R)];
1H NMR (300 MHz, CDCl3): d=1.36 (s, 9H), 2.51–2.59 (m, 2H), 3.93
(dd, J=5.5, 7.5 Hz, 1H), 4.93 (d, J=10.2 Hz, 1H), 5.00 (d, J=18.2 Hz,
1H), 5.56–5.72 (m, 1H), 7.04–7.14 (m, 2H), 7.19–7.33 (m, 2H), 7.35–7.48
(m, 3H), 7.57 (d, J=7.8 Hz, 2H), 7.73 ppm (d, J=7.0 Hz, 1H); 13C NMR
(300 MHz, CDCl3): d=28.8, 38.8, 66.5, 81.7, 118.0, 128.6, 128.7, 129.0,
129.1, 129.2, 129.5, 130.8, 130.9, 133.1, 135.4, 138.3, 140.4, 170.8,
171.6 ppm; MS (ESI): m/z: 336.3 [M+H]+, 280.2.
CHCl3); ee=42% (HPLC analysis of the Marfey derivative: tr =8.8 (S),
9.1 min (R)); H NMR (300 MHz, CDCl3): d=1.47 (s, 9H), 2.18–2.31 (m,
1
2H), 2.46–2.53 (m, 2H), 4.08 (dd, J=4.7, 7.7 Hz, 1H), 7.19–7.25 (m, 2H),
7.32–7.43 (m, 3H), 7.48–7.52 (m, 3H), 7.69 ppm (d, J=7.8 Hz, 2H);
13C NMR (300 MHz, CDCl3): d=28.1, 45.6, 63.9, 81.6, 119.7, 128.0, 128.3,
128.7, 128.9, 130.2, 136.2, 139.7, 170.1, 171.4 ppm; MS (ESI): m/z: 349.1
[M+H]+, 293.3.
(S)-tert-Butyl-2-(diphenylmethyleneamino)-3-(2-iodophenyl)propanoate
(16): Yield: 139 mg (91%); colorless oil; [a]2D0 =À149 (c=2, CHCl3); ee=
59% (HPLC analysis of the Marfey derivative: tr =8.9 (S), 9.2 min (R));
1H NMR (300 MHz, CDCl3): d=1.50 (s, 9H), 3.18–3.50 (m, 2H), 4.39
(dd, J=3.9, 9.8 Hz, 1H), 6.59 (d, J=6.7 Hz, 2H), 6.87 (dd, J=0.9, 1.1 Hz,
1H), 7.18–7.22 (m, 2H), 7.26–7.42 (m, 6H), 7.64 (d, J=8.0 Hz, 2H),
7.79 ppm (d, J=7.6 Hz, 1H); 13C NMR (300 MHz, CDCl3): d=28.1, 43.9,
65.2, 81.2, 101.4, 127.7, 127.8, 128.0, 128.2, 1283, 128.8, 130.1, 130.2, 132.1,
136.2, 139.2, 139.4, 140.7, 170.6, 170.8 ppm; MS (ESI): m/z: 511.9
[M+H]+, 456.1; HRMS: m/z: calcd for C26H27NO2I: 512.1087; found:
512.1091.
ACHTUNGTRENNUNG(S,E)-tert-Butyl-2-(diphenylmethyleneamino)hex-4-enoate (9) [486406–38–
6]:[21] Yield: 96 mg (92%); colorless oil; [a]D20 =À20 (c=1, CHCl3); ee=
66% (HPLC analysis of the Marfey derivative: tr =8.1 (S), 8.4 min (R));
1H NMR (300 MHz, CDCl3): d=1.36 (s, 9H), 1.53 (d, J=6.3 Hz, 3H),
2.32–2.54 (m, 2H), 3.88 (dd, J=5.6, 7.6 Hz, 1H), 5.13–5.29 (m, 1H),
5.31–5.47 (m, 1H), 7.02–7.11 (m, 2H), 7.16–7.36 (m, 6H), 7.56 ppm (d,
J=6.9 Hz, 2H); 13C NMR (300 MHz, CDCl3): d=17.8, 27.9, 36.8, 66.2,
80.7, 126.9, 127.6, 127.8, 127.9, 128.2, 128.6, 129.9, 136.6, 139.7, 169.7,
170.9 ppm; MS (ESI): m/z: 350.3 [M+H]+, 294.3.
(S)-tert-Butyl-3-(2-bromo-5-fluorophenyl)-2-(diphenylmethyleneamino)-
propanoate (17): Yield: 138 mg (96%); colorless oil; [a]2D0 =À102 (c=1,
CHCl3); ee=53% (HPLC analysis of the Marfey derivative: tr =8.8 (S),
9.1 min (R)); 1H NMR (300 MHz, CDCl3): d=1.49 (s, 9H), 3.27 (dd, J=
9.3, 13.4 Hz, 1H), 3.45 (dd, J=4.4, 13.4 Hz, 1H), 4.38 (dd, J=4.4, 9.3 Hz,
1H), 6.72–6.85 (m, 3H), 7.00 (dd, J=3.0, 9.4 Hz, 1H), 7.29–7.47 (m, 7H),
7.59–7.68 ppm (m, 2H); 13C NMR (300 MHz, CDCl3): d=28.0, 39.7, 65.0,
81.4, 115.2 (d, J=21.9 Hz), 119.4 (d, J=22.6 Hz), 127.7, 128.0, 128.2,
128.5, 128.8, 133.5 (d, J=7.5 Hz), 136.1, 139.3, 139.8 (d, J=7.5 Hz), 159.8,
163.1, 170.3, 171.0 ppm; MS (ESI): m/z: 482.2 [M+H]+, 484.2 [M+H]+;
HRMS: m/z: calcd. for C26H26NO2BrF: 482.1131; found: 482.1129.
(S)-tert-Butyl-2-(diphenylmethyleneamino)-4-methylpent-4-enoate
(10)
[200132–62–3]:[22] Yield: 97 mg (93%); colorless oil; [a]2D0 =À33 (c=1,
CHCl3); ee=61% (HPLC analysis of the Marfey derivative: tr =8.0 (S),
8.3 min (R)); 1H NMR (300 MHz, CDCl3): d=1.36 (s, 9H), 1.43 (s, 3H),
2.48–2.55 (m, 2H), 4.00 (dd, J=5.3, 8.1 Hz, 1H), 4.64 (d, J=6.0 Hz, 1H),
7.06–7.11 (m, 2H), 7.16–7.36 (m, 6H), 7.55 ppm (d, J=6.7 Hz, 2H);
13C NMR (300 MHz, CDCl3): d=20.3, 25.8, 39.6, 62.5, 78.5, 111.1, 125.7,
125.8, 126.0, 126.2, 126.5, 127.8, 134.2, 137.5, 139.6, 167.6, 168.9 ppm; MS
(ESI): m/z: 350.3 [M+H]+, 294.3.
(S)-tert-Butyl-4-bromo-2-(diphenylmethylene amino)pent-4-enoate (11)
[583827–73–6]: Yield: 117 mg (95%); colorless oil; [a]2D0 =À113 (c=1,
CHCl3); ee=71% (HPLC analysis of the Marfey derivative: tr =7.9 (S),
(S)-tert-Butyl 2-(diphenylmethyleneamino)-4-(2-methoxyethoxy)butanoate
(18): Yield: 110 mg (93%); colorless oil; [a]2D0 =À26 (c=1, CHCl3); ee=
36% (HPLC analysis of the Marfey derivative: tr =7.0 (S), 7.2 min (R));
1H NMR (300 MHz, CDCl3): d=1.45 (s, 9H), 2.17–2.32 (m, 2H), 3.35 (s,
3H), 3.43–3.55 (m, 6 Hz), 4.13 (dd, J=4.7, 8.3 Hz, 1H), 7.17–7.23 (m,
2H), 7.28–7.55 (m, 9H), 7.65 (d, J=6.9 Hz, 2H), 7.83 ppm (d, J=9.0 Hz,
1H); 13C NMR (300 MHz, CDCl3): d=27.6, 33.0, 58.6, 62.5, 67.5, 69.6,
71.4, 80.6, 127.5, 127.6, 127.9, 128.1, 128.4, 129.7, 129.8, 132.0, 136.2,
139.3, 170.2, 170.8 ppm; MS (ESI): m/z: 398.1 [M+H]+, 183.1; HRMS:
m/z: calcd for C24H32NO4: 398.2331; found: 398.2328.
1
8.3 min (R)); H NMR (300 MHz, CDCl3): d=1.49 (s, 9H), 3.05–3.12 (m,
2H), 4.30 (dd, J=5.1, 8.0 Hz, 1H), 5.46 (s, 1H), 5.73 (s, 1H), 7.25–7.30
(m, 2H), 7.32–7.44 (m, 3H), 7.47–7.52 (m, 3H), 7.66 ppm (d, J=6.0 Hz,
1H); 13C NMR (300 MHz, CDCl3): d=28.1, 45.6, 63.9, 81.6, 119.7, 128.0,
128.2, 128.3, 128.7, 128.9, 130.2, 136.2, 139.7, 170.1, 171.4 ppm; MS (ESI):
m/z: 416.1 [M+H]+, 414.1 [M+H]+, 360.1, 358.1; HRMS: m/z: calcd for
C22H25NO2Br: 414.1069; found: 414.1072.
(S)-tert-Butyl-2-(diphenylmethyleneamino)-3-phenylpropanoate
(12)
[119244–23–4]:[20] Yield: 110 mg (96%); [a]D20 =À113 (c=2, CHCl3); ee=
59% (HPLC analysis of the Marfey derivative: tr =8.4 (S), 8.7 min (R));
1H NMR (300 MHz, CDCl3): d=1.35 (s, 9H), 3.02–3.20 (m, 2H), 4.03
(dd, J=4.5, 9.0 Hz, 1H), 6.51 (d, J=6.7 Hz, 1H), 6.90–6.99 (m, 3H),
7.03–7.09 (m, 3H), 7.15–7.27 (m, 6H), 7.49 ppm (d, J=6.7 Hz, 2H);
13C NMR (300 MHz, CDCl3): d=28.6, 40.1, 68.5, 81.6, 126.7, 128.2, 128.4,
128.5, 128.6, 128.7, 129.2, 130.4, 130.6, 136.9, 138.9, 140.1, 170.8,
171.3 ppm; MS (ESI): m/z: 386.0 [M+H]+, 330.2.
General procedure for the derivatization with Marfeyꢂs reagent: The al-
kylated products 3–13 were dissolved in Et2O (2 mL) and an aqueous so-
lution of 1N HCl (2 mL) was added. The mixture was stirred magnetical-
ly at RT overnight, the aqueous layer was washed with Et2O (2ꢄ2 mL)
and evaporated to obtain the amino acid hydrochloride as a solid. Four
solutions were then prepared: Solution 1 [amino acid (10 mg) in water
(1.3 mL], Solution 2 [Marfeyꢀs reagent (50 mg) in acetone (5 mL)], Solu-
tion 3 (aqueous solution of 1m NaHCO3), and Solution 4 (1N HCl). So-
lution 2 (200 mL) and Solution 3 (60 mL) were then added to Solution 1
(100 mL) and the mixture was stirred for 1 h at 408C, cooled to RT and
then Solution 4 (60 mL) was added. The resulting mixture was analyzed at
340 nm using a Symmetry Shield column, with a linear gradient of aceto-
nitrile in water, from 0 to 100% in 20 min.
(S)-tert-Butyl-2-(diphenylmethyleneamino)-3-(naphthalen-2-yl)propanoate
(13) [119244–29–0]:[20] Yield: 124 mg (95%); pale-yellow oil; [a]2D0 =À58
(c=1, CHCl3); ee=75% (HPLC analysis of the Marfey derivative: tr =
9.9 (S), 10.3 min (R)); 1H NMR (300 MHz, CDCl3): d=1.36 (s, 9H),
3.20–3.35 (m, 2H), 4.16 (dd, J=4.4, 9.0 Hz, 1H), 7.01–7.13 (m, 3H),
7.18–7.27 (m, 4H), 7.29–7.52 (m, 6H), 7.58 (d, J=7.9 Hz, 2H), 7.62–
7.78 ppm (m, 2H); 13C NMR (300 MHz, CDCl3): d=28.1, 39.8, 67.9, 81.2,
125.3, 125.8, 127.5, 127.6, 127.7, 128.0, 128.1, 128.3, 128.4, 128.8, 130.2,
132.2, 133.5, 136.0, 136.3, 139.6, 170.5, 170.9 ppm; MS (ESI): m/z: 436.0
[M+H]+.
Acknowledgements
(S)-tert-Butyl-2-(diphenylmethyleneamino)pent-4-ynoate (14) [326667–
54–3]:[20] Yield: 92 mg (92%); colorless oil; [a]D20 =À30 (c=2, CHCl3);
ee=70% (HPLC analysis of the Marfey derivative: tr =7.2 (S), 7.4 min
(R)); 1H NMR (300 MHz, CDCl3): d=1.36 (s, 9H), 1.86 (t, J=2.6 Hz,
1H), 2.65–2.73 (m, 2H), 4.10 (dd, J=5.3, 8.5 Hz, 1H), 7.12–7.45 (m, 6H),
7.59 (m, 2H), 7.72 ppm (m, 2H); 13C NMR (300 MHz, CDCl3): d=23.4,
28.0, 64.8, 70.1, 81.2, 81.6, 128.0, 128.2, 128.3, 128.4, 128.7, 129.0, 130.0,
130.4, 132.4, 136.3, 137.6, 139.6, 169.6, 171.4 ppm; MS (ESI): m/z: 334.3
[M+H]+, 278.2.
We thank the CNRS and the MENRT for financial support. P. N. thanks
The Fondation d’Entreprise EADS for a fellowship. Technical support
from Retsch Gmbh is also acknowledged.
[1] V. A. Soloshonok, K. Izawa, Asymmetric Synthesis and Application
of alpha-Amino Acids, ACS Symposium Series, 2009.
[2] M. J. OꢀDonnell, J. M. Boniece, S. E. Earp, Tetrahedron Lett. 1978,
2641.
(S)-tert-Butyl-4-cyano-2-(diphenylmethyleneamino)butanoate
(15)
[3] M. J. OꢀDonnell, W. D. Bennett, S. Wu, J. Am. Chem. Soc. 1989, 111,
2353.
[271601–28–6]:[23] Yield: 98 mg (94%); yellow oil; [a]2D0 =À29 (c=1,
3778
ꢃ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2012, 18, 3773 – 3779