PAPER
Resolution of Amino Acids
1017
13C NMR (75 MHz, CDCl3): d = 206.0, 173.0, 170.1, 87.8, 82.2,
The iron carbonyl appendage offers a great advantage due
to the large difference in polarity of the yellow com-
pounds obtained; this polarity difference considerably fa-
cilitates product separation. This successful resolution
procedure is suitable for preparative purposes and appli-
cable to a large panel of amino acids.
58.5, 52.2, 50.5, 49.0, 41.7, 24.9, 22.9, 21.7, 19.2.
(2S)-Tricarbonyl{h4-N-[(R)-1-(methoxycarbonyl)-3-methylbu-
tyl]hexa-2,4-dienamide}iron (7)
Yield: 49%; mp 130 °C.
[a]D20 +116 (c 1.0, CHCl3).
IR (CCl4): 2058, 1995, 1980, 1743, 1670, 2960, 2930 cm–1.
Reactions were carried out under a positive pressure of argon with
magnetic stirring and by using degassed solvents in oven-dried
glassware. Et2O and THF were distilled from Na/benzophenone,
CH2Cl2 was distilled over P2O5, MeOH was distilled over Mg and
stored over 3Å MS. TLC was carried out on silica gel plates Merck
60F254 and the spots were visualized under a UV lamp (254 or 365
nm) and/or sprayed with a soln of vanillin (25 g) in EtOH–H2SO4
(98:2, 1 L) or with phosphomolybdic acid followed by heating on a
hot plate. For column chromatography, silica gel (Merck, Si60, 40–
60 mm) was used. Melting points were measured on a hot stage Stu-
art Scientific SMP 3 apparatus. IR spectra were recorded as CCl4
1H NMR (300 MHz, CDCl3): d = 5.91 (d large, J = 8.2 Hz, 1 H),
5.80 (dd, J = 7.7, 5.1 Hz, 1 H), 5.18 (dd, J = 8.4, 5.0 Hz, 1 H), 4.65
(td, J = 9.9, 4.6 Hz, 1 H), 3.71 (s, 3 H), 1.47–1.65 (m, 3 H), 1.45 (d,
J = 6.2 Hz, 3 H), 1.30–1.38 (m, 1 H), 0.95 (d, J = 3.3 Hz, 3 H), 0.93
(d, J = 3.3 Hz, 3 H), 0.89 (d, J = 7.8 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 206.0, 173.0, 170.1, 87.8, 82.2,
58.5, 52.2, 50.5, 49.0, 41.7, 24.9, 22.9, 21.7, 19.2.
(2S)-Tricarbonyl{h4-N-[(S)-1-(methoxycarbonyl)-2-phenyleth-
yl]hexa-2,4-dienamide}iron (8)
Yield: 45%; mp 147 °C.
solns. 1H NMR spectra were recorded at 200 or 300 MHz and 13
C
NMR spectra at 75 or 125 MHz on a Bruker AC-300 or ARX-500
using the signal of the residual nondeuterated solvent as the internal
reference. The ratios of compounds indicated below were calculated
from NMR integration. IR spectra were recorded as CCl4 solns on a
Perkin Elmer IR-881 and on a Bruker Alpha spectrophotometer.
Microanalysis were carried out by the Service Commun d’Analyses
du CNRS, Institut de Chimie-Strasbourg.
[a]D20 –6 (c 1.0 CHCl3).
IR (CCl4): 2060, 1997, 1981, 1747, 1669, 2955, 2921 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.18–7.38 (m, 3 H), 7.08 (d,
J = 7.0 Hz, 2 H), 5.81 (dd, J = 7.3, 4.4 Hz, 1 H), 5.81 (s large, 1 H),
5.19 (dd, J = 8.5, 5.0 Hz, 1 H), 4.83 (dd, J = 13.4, 5.9 Hz, 1 H), 3.74
(s, 3 H), 3.12 (ABX, JAB = 13.9 Hz, Dn = 28.4 Hz, JAX = 5.7 Hz,
JBX = 5.9 Hz, dA = 3.17, dB = 3.08, 2 H), 1.44 (d, J = 6.0 Hz, 3 H),
1.20–1.40 (m, 1 H), 0.81 (d, J = 7.9 Hz, 1 H).
(h4-dienecarboxamide)–Fe(CO)3 Complexes 3, 4, 7–11; General
Procedure
13C NMR (75 MHz, CDCl3): d = 210.4, 172.0, 170.5, 136.2, 129.4,
128.6, 127.1, 87.9, 82.2, 58.5, 53.6, 52.4, 49.1, 37.8, 19.2.
To a suspension of (h4-dienecarboxylic acid)Fe(CO)3 complex 1 (1
equiv) in anhyd CH2Cl2 (10 mL), amino ester hydrochloride (1.2
equiv) in anhyd CH2Cl2 (10 mL/mmol), DMAP (3 equiv), and
EDC·HCl were added sequentially. The mixture was stirred at 20 °C
for 2 h, hydrolyzed with 1 M HCl (10 mL/mmol), washed with sat.
aq NaHCO3 (20 mL), and extracted with CH2Cl2 (20 mL) and Et2O
(2 × 20 mL). The combined organic layers were washed with brine,
dried (MgSO4), and filtered and the solvent was removed under re-
duced pressure (40 °C/20 mbar).The residue was purified by chro-
matography (silica gel, hexane–EtOAc, 9:1).
(2S)-Tricarbonyl{h4-N-[(R)-1-(methoxycarbonyl)-2-phenyleth-
yl]hexa-2,4-dienamide}iron (9)
Yield: 45%; mp 38 °C.
[a]D20 +104 (c 1.0 CHCl3).
IR (CCl4): 2056, 1998, 1980, 1746, 1667, 2955, 2921 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.20–7.42 (m, 3 H), 7.12 (d,
J = 6.8 Hz, 2 H), 5.96 (d large, J = 7.3 Hz, 1 H), 5.81 (dd, J = 7.5,
5.1 Hz, 1 H), 5.19 (dd, J = 8.7, 5.0 Hz, 1 H), 4.93 (dd, J = 12.3, 6.7
Hz, 1 H), 3.73(s, 3 H), 3.09 (ABX, JAB = 13.9 Hz, Dn = 29.3 Hz,
JAX = 5.2 Hz, JBX = 5.8 Hz, dA = 3.14, dB = 3.04, 2 H), 1.44 (d,
J = 6.2 Hz, 3 H), 1.19–1.48 (m, 1 H), 0.86 (d, J = 7.9 Hz, 1 H).
(2S)-Tricarbonyl{h4-N-[(S)-1-(methoxycarbonyl)-3-methylbu-
tyl]hexa-2,4-dienamide}iron (3)
Yield: 47%; mp 117 °C.
[a]D20 +94 (c 1.0, CHCl3).
IR(CCl4): 2060, 1995, 1980, 1745, 1672, 2957, 2930 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.81 (dd, J = 7.5, 5.1 Hz, 1 H),
5.65 (d large, J = 8.2 Hz, 1 H), 5.19 (dd, J = 8.4, 4.9 Hz, 1 H), 4.58
(td, J = 8.9, 4.8 Hz, 1 H), 3.73 (s, 3 H), 1.40–1.65 (m, 3 H), 1.45 (d,
J = 6.0 Hz, 3 H), 1.27–1.38 (m, 1 H), 0.92 (d, J = 3.3 Hz, 6 H), 0.86
(d, J = 7.9 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 211.0, 173.3, 170.6, 87.6, 81.9,
58.3, 52.3, 50.0, 49.1, 41.5, 24.8, 22.8, 21.9, 19.2.
13C NMR (75 MHz, CDCl3): d = 210.7, 172.3, 170.1, 135.9, 129.4,
128.8, 127.2, 88.0, 82.4, 58.8, 53.0, 52.4, 49.1, 38.2, 19.3.
(2S)-Tricarbonyl{h4-N-[(S)-2-(4-fluorophenyl)-1-(methoxycar-
bonyl)ethyl]hexa-2,4-dienamide}iron (10)
Yield: 46%; mp 166 °C.
[a]D20 +112 (c 1.0 CHCl3).
IR (CCl4): 2060, 1997, 1982, 1746, 1668, 2960, 2929 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.03 (td, J = 5.9, 2.4 Hz, 2 H),
6.95 (t, J = 8.7 Hz, 2 H), 5.79 (dd, J = 7.1, 5.4 Hz, 1 H), 5.79 (s
large, 1 H), 5.19 (dd, J = 8.5, 5.0 Hz, 1 H), 4.80 (dd, J = 13.4, 5.7
Hz, 1 H), 3.73 (s, 3 H), 3.09 (ABX, JAB = 14.1 Hz, Dn = 31.4 Hz,
JAX = 5.8 Hz, JBX = 5.7 Hz, dA = 2.14, dB = 3.04, 2 H), 1.44 (d,
J = 6.0 Hz, 3 H), 1.27–1.38 (m, 1 H), 0.80 (d, J = 7.9 Hz, 1 H).
(2R)-Tricarbonyl{h4-N-[(S)-1-(methoxycarbonyl)-3-methylbu-
tyl]hexa-2,4-dienamide}iron (4)
Yield: 47%; mp 130 °C.
[a]D20 –115 (c 1.0, CHCl3).
IR (CCl4): 2058, 1995, 1980, 1743, 1670, 2960, 2930 cm–1.
1H NMR (300 MHz, CDCl3): d = 5.91 (d large, J = 8.2 Hz, 1 H),
5.80 (dd, J = 7.7, 5.1 Hz, 1 H), 5.18 (dd, J = 8.4, 5.0 Hz, 1 H), 4.65
(td, J = 9.9, 4.6 Hz, 1 H), 3.71 (s, 3 H), 1.47–1.65 (m, 3 H), 1.45 (d,
J = 6.2 Hz, 3 H), 1.30–1.38 (m, 1 H), 0.95 (d, J = 3.3 Hz, 3 H), 0.93
(d, J = 3.3 Hz, 3 H), 0.89 (d, J = 7.8 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 210.0, 171.8, 170.4, 161.9, 131.7,
130.7, 115.4, 87.8, 82.0, 58.5, 53.5, 52.4, 48.8, 36.9, 19.1.
(2S)-Tricarbonyl{h4-N-[(R)-2-(4-fluorophenyl)-1-(methoxycar-
bonyl)ethyl]hexa-2,4-dienamide}iron (11)
Yield: 46%; mp 137 °C.
Synthesis 2009, No. 6, 1014–1020 © Thieme Stuttgart · New York