1
706
S. Bastin et al. / Tetrahedron: Asymmetry 14 (2003) 1701–1708
1
3
J=6.0 Hz, 1H), 7.18–7.39 (m, 10H). C (75 MHz,
4.4.6.
(1R,2S)-2-(N,N-Dibenzylamino)-1-ferrocenyl-3-
CDCl ): l=9.2, 54.0, 54.5, 57.9, 65.6, 67.5, 67.6, 68.3,
9.6, 71.4, 92.6, 126.8, 128.1, 128.7, 139.8. MS (FAB):
m/z 462 (M +Na), 440 (M +H), 420. HRMS (C.I.):
calcd for C H FeNO m/z 440.1677, found m/z
methyl-1-butanol 5c. Purification of 5c by column chro-
matography is not possible, diastereomer 5c is obtained
3
6
+ +
1
as a mixture with ferrocene and 4c. H NMR (300
MHz, CDCl +D O): l=0.70 (d, J=7.0 Hz, 3H), 0.86
(d, J=7.0 Hz, 3H), 1.80–1.91 (m, 1H), 2.38 (dd, J=3.5
and 8.5 Hz, 1H), 3.66 (d, J=12.5 Hz, 2H), 3.70 (d,
J=12.5 Hz, 2H), 3.90–4.26 (m, 4H), 4.27 (s, 5H), 4.55
(d, J=8.5 Hz, 1H), 7.22–7.38 (m, 10H).
2
7
30
3
2
440.1678.
4
.4.2. (1R,2S)-2-(N,N-Dibenzylamino)-1-ferrocenyl-1-
propanol 5a. Yellow crystals (56 mg, 5%). Mp 163°C,
20
D 3
1
[
h] =−20 (c 0.92, CHCl ). H NMR (300 MHz,
CDCl +D O): l=0.91 (d, J=6.5 Hz, 3H), 2.52 (qd,
4.5. (1S,2S)-2-Amino-1-ferrocenyl-1-propanol 6
3
2
J=6.5 and 9.5 Hz, 1H), 3.32 (d, J=13.5 Hz, 2H), 3.86
(
(
7
d, J=13.5 Hz, 2H), 4.00 (m, 1H), 4.03 (m, 2H), 4.10
A mixture of ferrocenyl amino alcohol 4a (400 mg, 0.91
mmol), Pd/C 5% (800 mg) and ammonium formate in
MeOH (20 mL) was stirred under reflux for 15 min
under nitrogen. The reaction was monitored by thin-
layer chromatography (eluent diethyl ether). Pd/C was
removed by filtration through a pad of Celite 545, the
filtrate was washed with water (20 mL) and extracted
with CH Cl (3×20 mL). The combined organic layers
m, 1H), 4.15 (d, J=9.5 Hz, 1H), 4.18 (s, 5H), 7.23–
+
+
.32 (m, 10H). MS (FAB): m/z 478 (M +K), 462 (M +
+ 13
Na), 440 (M +H), 420. C (75 MHz, CDCl ): l=8.2,
3
5
1
3.3, 60.5, 65.0, 66.9, 67.4, 68.2, 68.6, 70.1, 90.2, 127.2,
28.5, 129.0, 138.8. HRMS (C.I.): calcd for
C H FeNO m/z 440.1677, found m/z 440.1672.
27
30
2
2
were dried over Na SO and the solvent was removed
2
4
4
.4.3.
(1S,2S)-2-(N,N-Dibenzylamino)-1-ferrocenyl-4-
in vacuo to afford the amino alcohol 6 as a yellow–
methyl-1-pentanol 4b. Yellow crystals for 4b (334 mg,
20
orange powder (188 mg, 80%). Mp 94°C, [h] =+74 (c
D
2
0
1
4
4%). Mp 118°C, [h] =−141 (c 1.74, CHCl ).
H
1
D
3
1
0
1
.04, CHCl ). H NMR (300 MHz, CDCl +D O): l=
.98 (d, J=6.5 Hz, 3H), 2.97 (qd, J=4.8 and 6.5 Hz,
H), 4.15–4.22 (m, 4H), 4.22 (s, 5H), 4.27 (m, 1H).
3
3
2
NMR (300 MHz, CDCl +D O): l=0.72 (d, J=6.5 Hz,
3
3
2
H), 0.88 (d, J=6.5 Hz, 3H), 1.28–1.37 (m, 1H), 1.50
13
C
(
m, 1H), 1.73 (m, 1H), 2.79 (ddd, J=4, 6.5 and 6.5 Hz,
(
75 MHz, CDCl ): l=51.2, 65.0, 67.9, 68.0, 68.4, 68.7,
4.5, 90.0. l MS (FAB): m/z 298 (M +K), 282 (M +
3
1
2
5
H), 3.48 (d, J=13.5 Hz, 2H), 3.56 (d, J=13.5 Hz,
H), 4.04 (m, 1H), 4.09 (m, 1H), 4.13 (m, 1H), 4.17 (s,
H), 4.31 (m, 1H), 4.61 (d, J=4.0 Hz, 1H), 7.23–7.31
+
+
7
+
Na), 259 (M ). HRMS (C.I.): calcd for C H FeNO
13
17
m/z 259.0660, found m/z 259.0661.
1
3
(
m, 10H). C NMR (75 MHz, CDCl ): l=22.9, 24.7,
3
3
1
4.0, 54.8, 59.6, 66.1, 67.2, 67.3, 67.9, 68.6, 91.8, 127.0,
28.3, 129.0, 140.0. HRMS (C.I.): calcd for
4
.6. (1S,2S)-2-(N,N-Dimethylamino)-1-ferrocenyl-1-
propanol 7
C H FeNO m/z 482.2147, found m/z 482.2146.
30
36
A mixture of ferrocenyl amino alcohol 6 (336 mg, 1.29
mmol) and 37% aqueous solution of formaldehyde (971
mL) in MeOH (20 mL) was stirred under reflux for 30
min. The reaction mixture was allowed to cool down to
4
.4.4.
(1R,2S)-2-(N,N-Dibenzylamino)-1-ferrocenyl-4-
20
methyl-1-pentanol 5b. Yellow oil (84 mg, 11%). [h] =
D
1
3 3
−
120 (c 0.75, CHCl ). H NMR (300 MHz, CDCl +
2
rt and NaBH (73 mg, 1.93 mmol) was slowly added.
4
D O): l=0.58 (d, J=6.5 Hz, 3H), 0.69 (d, J=6.5 Hz,
The reaction was run at rt for 1 h, treated with H O (20
2
3
4
H), 0.98–1.13 (m, 2H), 1.39 (m, 1H), 2.43 (ddd, J=
.5, 6 and 9 Hz, 1H), 3.45 (d, J=13.5 Hz, 2H), 3.87 (d,
mL) and extracted with CH Cl (3×20 mL). The com-
2
2
bined organic layers were dried over Na SO and the
2
4
J=13.5 Hz, 2H), 4.05 (m, 3H), 4.13 (m, 1H), 4.16 (d,
13
solvent was removed in vacuo. The residue was purified
on silica gel chromatography (petroleum ether/diethyl
ether/triethylamine gradient) giving the amino alcohol 7
as a yellow powder (214 mg, 57%). Mp 48–50°C,
J=9.0 Hz, 1H), 4.21 (s, 5H), 7.21–7.39 (m, 10H).
75 MHz, CDCl ): l=22.7, 22.9, 25.8, 35.5, 51.8, 62.9,
C
(
6
1
3
5.1, 66.8, 67.7, 68.5, 70.7, 90.9, 127.0, 128.4, 129.1,
39.4. MS (FAB): m/z 482 (M +H). HRMS (C.I.):
+
2
0
1
[
h] =+7 (c 0.45, CHCl ). H NMR (300 MHz,
D 3
calcd for C H FeNO m/z 482.2147, found m/z
3
0
36
CDCl +D O): l=0.88 (d, J=7 Hz, 3H), 2.26 (s, 6H),
.44 (qd, J=4 and 7 Hz, 1H), 4.12 (m, 3H), 4.19 (s,
H), 4.31 (m, 1H), 4.58 (d, J=4 Hz, 1H). C NMR (75
3
2
482.2142.
2
5
13
4
.4.5.
(1S,2S)-2-(N,N-Dibenzylamino)-1-ferrocenyl-3-
MHz, CDCl ): l=9.2, 42.6, 64.8, 66.0, 66.9, 67.2, 67.6,
3
methyl-1-butanol 4c. Yellow oil for 4c (342 mg, 46%).
68.6, 70.5, 91.2. HRMS (C.I.): calcd for C H FeNO
15
21
2
0
1
[
h] =−11 (c 1.04, CHCl ). H NMR (300 MHz,
m/z 287.0973, found m/z 287.0978.
D
3
CDCl +D O): l=1.00 (d, J=6.5 Hz, 3H), 1.16 (d,
3
2
J=6.5 Hz, 3H), 2.16–2.23 (m, 1H), 2.52 (dd, J=5.2
and 7.7 Hz, 1H), 3.57 (d, J=13.5 Hz, 2H), 3.64 (d,
J=13.5 Hz, 2H), 4.04 (m, 1H), 4.13 (m, 1H), 4.16 (s,
4.7. (1S,2S)-2-(N,N-Dibutylamino)-1-ferrocenyl-1-
propanol 8
5
1
2
6
1
4
H), 4.21 (m, 1H), 4.32 (m, 1H), 4.72 (d, J=5.2 Hz,
The ferrocenyl amino alcohol 6 (100 mg, 0.386 mmol)
and butyraldehyde (250 mL, 1.54 mmol) were dissolved
in ethanol (20 mL) in the presence of molecular sieves 3
1
3
H), 7.19–7.31 (m, 10H). C (75 MHz, CDCl ): l=
3
1.4, 21.5, 27.6, 55.4, 66.7, 67.1, 67.2, 67.3, 67.5, 67.9,
8.2, 68.6, 69.7, 92.8, 126.9, 128.1, 128.2, 129.0, 129.1,
39.9. HRMS (C.I.): calcd for C H FeNO m/z
A
,
(3g). The reaction mixture was stirred for 30 min at
rt. NaBH (147 mg, 3.86 mmol) was added slowly. The
2
9
34
4
68.4421, found m/z 468.4416.
reaction was run for 1 h at rt, treated with H O (20
2