M. Fitz et al. / Tetrahedron: Asymmetry 17 (2006) 1129–1134
1133
1
Anal. Calcd for C H N O : C, 62.24; H, 9.50; N 13.02.
1.0, MeOH); H NMR (400 MHz, DMSO-d ): d 0.81
1
1
20
2
2
6
Found: C, 61.95; H, 9.31; N, 12.73.
(3H, t, J = 7.2 Hz, CH ), 1.04–1.75 (8H, om, 4 · CH ),
3
2
1
.46 (2H, m, CH CH CH ), 1.95 (2H, t, J = 7.14 Hz,
3 2 2
4.3. Gram-scale resolution of trans-2-aminocyclopentane-
carboxamide, rac-3
CH CH CH ), 2.09 (1H, m, CHCONH ), 3.71 (1H, m,
2 2 3 2
CHNHCOPr), 6.70 (1H, s, NH ), 6.93 (1H, s, NH ), 7.49
2
2
13
(
1H, d, J = 8.4 Hz, NHCOPr) ppm;
C
NMR
Compound rac-3 (0.098 mg, 0.76 mmol) was dissolved in a
mixture (15.4 mL) of TBME and TAA (1:1), after which
CAL-B (0.765 g, 50 mg/mL) was added. The reaction was
initiated by the addition of 2,2,2-trifluoroethyl butanoate
(100 MHz, DMSO-d ): d 13.9 (CH ), 19.3 (CH CH CH ),
25.0 (C4), 29.6 (C6), 33.1 (C5), 39.4 (C3), 40.0
6 3 2 2 3
(CH CH CH ), 49.2 (C2), 49.6 (C1), 171.3 (NHCO),
2
2
3
175.8 (CONH ) ppm. Anal. Calcd for C H N O :
2
11 20
2
2
(
0.23 mL, 1.52 mmol). The mixture was shaken at 45 ꢁC.
C, 62.24; H, 9.50; N 13.02. Found: C, 62.13; H, 9.27; N,
13.46.
After 10 h, the enzyme was filtered off, at 50% conversion
(
(
1S,2S)-3
(1R,2R)-7
ee
= 99%, ee
>99%). The substrate and the
product were separated as described above.
4.5. Absolute configuration of (1R,2S)-2
Compound (1S,2S)-3 (0.023mg, 0.18 mmol) was obtained
Compound (1R,2S)-2 (30 mg) was reduced with lithium
20
as white crystals: mp 123–124 ꢁC, ee = 98%, ½aꢂ ¼ þ38:0
aluminium hydride, to yield the corresponding diamine
D
1
20
(
c 0.25, MeOH); H NMR (400 MHz, DMSO-d ): d 0.95–
(17 mg) as a light-yellow oil: ee = 97%, ½aꢂ ¼ þ16:8 (c
6
D
1
1
.90 (6H, om, 3 · CH ), 1.65 (2H, s, CHNH ), 2.63 (2H,
0.5, EtOH); H NMR (400 MHz, CDCl ): d 1.22–2.05
2
2
3
m, H-1 and H-2), 6.67 (1H, s, CONH ), 7.28 (1H, s,
(9H, om, H-2-6), 1.43 (2H, s, CH NH ), 2.27 (2H,
2
2
2
CONH ) ppm. Anal. Calcd for C H N O: C, 56.23; H,
s, CH NH ), 3.70 (1H, m, H-1), 5.00 (2H, s, CHNH )
2
6
12
2
2
2
2
9
.44; N 21.86. Found: C, 55.97; H, 9.21; N, 21.79.
ppm. Rotation data correspond to the literature
value for (1S,2S)-(+)-2-aminomethylcyclohexylamine
2
D
0
Compound (1R,2R)-7 (0.031 mg, 0.16 mmol) was obtained
{½aꢂ ¼ þ21:8 (c 2.18, EtOH) and +20.5 (c 1.0,
20
11,22
as white crystals: mp 174–175 ꢁC, ee >99%, ½aꢂ ¼ ꢁ22 (c
EtOH)}.
(1R,2S) absolute configuration.
The less reactive enantiomer thus has the
D
1
0
.25, MeOH); H NMR (400 MHz, DMSO-d ): d 0.84
6
(
1
3H, t, J = 7.37 Hz, CH ), 1.25–1.90 (6H, om, 3 · CH ),
3
2
.45 (2H, m, CH CH CH ), 2.01 (2H, t, J = 7.30 Hz,
3 2 2
CH CH CH ), 2.74 (1H, m, CHCONH ), 4.10 (1H, m,
2
2
3
2
Acknowledgements
CHNHCOPr), 6.72 (1H, s, NH ), 7.28 (1H, s, NH ), 7.78
2
2
(
1H, d, J = 7.28 Hz, NH) ppm. Anal. Calcd for
M.F. is grateful for a grant from the Centre for Interna-
tional Mobility (CIMO) in Finland. The authors also
acknowledge the receipt of Hungarian Research Founda-
tion (OTKA) grant T 049407 and the Academy of Finland
grant to L.K. (grant 210263).
C H N O : C, 60.58; H, 9.15; N 14.13. Found: C,
6
1
0
18
2
2
0.14; H, 8.79; N, 14.00.
4.4. Gram-scale resolution of trans-2-aminocyclohexane-
carboxamide, rac-4
Compound rac-4 (0.4 g, 2.82 mmol) was dissolved in a mix-
ture (56 mL) of TBME and TAA (1:1), after which CAL-B
References
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2.8 g, 50 mg/mL) was added. The reaction was initiated by
1
. F u¨ l o¨ p, F. Chem. Rev. 2001, 101, 2181–2204.
the addition of 2,2,2-trifluoroethyl butanoate (0.85 mL,
2. F u¨ l o¨ p, F.; Martinek, T. A.; T o´ th, G. K. Chem. Soc. Rev.
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5
.64 mmol). The mixture was shaken at 45 ꢁC. The reaction
(1S,2S)-4
was stopped after 21 h, at 50% conversion (ee
9
=
(1R,2R)-8
8% and ee
>99%) by filtering off the enzyme. After
4
5
6
. Konishi, M.; Nishio, M.; Saitoh, K.; Miyaki, T.; Oki, T.;
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tography, using CH Cl /MeOH (1:1).
2
2
Compound (1S,2S)-4 (0.170 g, 1.2 mmol) was obtained as
20
white crystals: mp 125–126.5 ꢁC, ee = 98% ½aꢂ ¼ þ47:2
D
2
2
(
c 0.1, MeOH), in accordance with the literature value
1
3, 433–436.
given for (1S,2S)-(+)-2-aminocyclohexanecarboxamide
7. Kanerva, L. T.; Csom o´ s, P.; Sundholm, O.; Bern a´ th, G.;
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hedron: Asymmetry 1996, 7, 1789–1796.
20
1
(
½aꢂ ¼ þ70:1 (c 0.107, MeOH)); H NMR (400 MHz,
D
CDCl ): d 0.98–1.83 (8H, om, 4 · CH ), 1.64 (2H, s,
CHNH ), 2.60–2.65 (2H, om, H-1 and H-2), 6.68 (1H, s,
CONH ), 7.29 (1H, s, CONH ); C NMR (100 MHz,
3
2
2
1
3
9. K a´ m a´ n, J.; Forr o´ , E.; F u¨ l o¨ p, F. Tetrahedron: Asymmetry
2
2
2
000, 11, 1593–1600.
CDCl ): d 24.8 (C4), 25.1 (C6), 29.0 (C5), 34.9 (C3),
3
1
1
0. Forr o´ , E.; F u¨ l o¨ p, F. Org. Lett. 2003, 5, 1209–1212.
1. Fitz, M.; Lundell, K.; Londroos, M.; F u¨ l o¨ p, F.; Kanerva,
L. T. Tetrahedron: Asymmetry 2005, 16, 3690–3697.
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H.; Garcia-Echeverria, C.; Gay, B.; Irving, E.; Press, N. J.;
Rahuel, J.; Schoepfer, J.; Walker, C. V. Bioorg. Med. Chem.
Lett. 2000, 10, 2337–2341.
5
1.26 (C2), 52.8 (C1), 176.6 (CONH ) ppm. Anal. Calcd
2
for C H N O: C, 59.13; H, 9.92; N 19.70. Found: C,
7
14
2
5
9.07; H, 9.60; N, 19.51.
1
Compound (1R,2R)-8 (0.219 g; 1.04 mmol) was obtained as
20
white crystals: mp 274–276 ꢁC, ee >99% ½aꢂD ¼ ꢁ12:0 (c