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4.4.4.
(S)-2-(Piperidine-1-carbonyl)-pyrrolidine-1-car-
4.5.3. (S)-2-(1-Benzylmethyl)pyrrolidine, 1c. Colorless
oil (770 mg, 80%), kugelrohr distillation, bp: 120°C/
baldehyde, 9b. (60% yield). In the same way as for 9a,
9b was obtained by reacting 6 (2 mmol, 489 mg) with
pyrrolidine (2 mmol, 200 ml) in ethanol 10 min at rt.
1
5×10−2 mmHg. [h]2D0=+15.6 (c 1.01, EtOH). H NMR
(400 MHz, CDCl3) l ppm: 1.33 (m, 1H), 1.70 (m,
2H), 1.86 (m, 1H), 1.90 (bs, 2H, NH), 2.50–2.66 (AB
system, 2H), 2.89 (m, 2H), 3.25 (m, 1H), 7.24–7.33
(m, 5H, arom.). 13C NMR (100 MHz, CDCl3) l ppm:
140.64, 128.45, 128.22, 126.95, 58.45, 54.80, 54.32,
46.65, 30.46, 29.83, 25.88. GC–MS, m/z: 191 (M+).
1
[h]2D1=−69.5 (c 1.05, EtOH). H NMR (CDCl3/TMS),
(400 MHz) l ppm: 1.55 (m, 4H), 1.68 (m, 2H), 1.90
(m, 2H), 2.08 (m, 1H), 2.22 (m, 1H), 3.48 (m, 3H),
3.70 (m, 3H), 4.64–4.84 (dd, 1H), 8.27 (s, 1H). 13C
NMR (100 MHz, CDCl3) l ppm: 169.20, 160.50,
60.74, 54.20, 46.75, 43.44, 29.52, 26.49, 25.60, 24.61,
24.47. GC–MS m/z: 211 (M+).
4.5.4. (S)-2-((1R)-Phenylethylmethyl)pyrrolidine, 1d.
Colorless oil (795 mg, 80%), kugelrohr distillation,
bp: 113°C/7.6 10−2 mmHg. [h]2D0=+54.4 (c 1.02,
4.4.5.
(S)-2-(N-Methyl-1-carbonyl)-pyrrolidine-1-car-
1
baldehyde, 9c. (63% yield). In the same way as for 9a,
9c was obtained by reacting 6 (2 mmol, 489 mg) with
ethylamine 33%/EtOH (2 mmol, 250 ml) in acetonitrile
10 min at rt. 1H NMR (400 MHz, CDCl3) l ppm:
1.85–2.10 (m, 3H), 2.50 (m, 1H), 2.78 (d, 3H), 3.58
(m, 2H), 4.50 (dd, 1H), 8.28 (s, 1H). 13C NMR (100
MHz, CDCl3) l ppm: 171.22, 162.36, 61.47, 57.93,
47.11, 27.50, 24.30.
EtOH). H NMR (400 MHz, CDCl3) l ppm: 1.28 (m,
1H), 1.37 (d, 3H, J=6.7 Hz), 1.68 (m, 2H), 1.82 (m,
1H), 2.00 (bs, 2H, NH), 2.31 (dd, 1H), 2.54 (dd, 1H),
2.86 (t, 2H, J=7.21 Hz), 3.21 (m, 1H, J=7.10 Hz),
3.77 (q, 1H, J=6.78 Hz), 7.23–7.33 (m, 5H, arom.).
13C NMR (100 MHz, CDCl3) l ppm: 146.01, 128.53,
126.92, 126.67, 58.50, 52.79, 46.52, 30.48, 29.77,
25.78, 24.64. GC–MS, m/z: 205 (M+).
4.5. General procedure for preparation of diamines 1
and 5 from 4 and 9
4.5.5. (S)-N-Methyl-2-(1-pyrrolidinomethyl)pyrrolidine,
5a. Colorless oil (638 mg, 77%) bp: 50°C/0.7 mmHg.
[h]2D0=−83.6 (c 0.63, EtOH) (lit.13 [h]D=−84.5 (c 0.5,
1
Preparation of 1b from 4b illustrates a typical proce-
dure: LiAlH4 (1.140 g, 30 mmol) in dry THF (10 ml)
at 20°C was stirred for few minutes under a nitrogen
atmosphere. The mixture was cooled to 0°C and 4b
(980 mg, 5 mmol) in dry THF (20 ml) was added
dropwise over 30 min. The mixture was heated under
reflux for 4 h and then cooled in an ice bath.
Aqueous NaOH (2 M) was added dropwise until a
white precipitate of inorganic salts had formed. The
inorganic salts were removed by filtration and washed
with (3×30 ml) of THF. The filtrate was dried
(Na2SO4) and concentrated under reduced pressure.
Distillation of the residue under reduced pressure
gave 1b as a colorless oil (740 mg, 88%). Amines
1a–1d and 5a, 5b were prepared analogously.
EtOH)). H NMR (CDCl3/TMS), (400 MHz) l ppm:
1.58 (m, 1H), 1.60–1.76 (m, 6H), 2.00 (m, 1H), 2.13
(m, 1H), 2.23 (m, 1H), 2.32 (m, 1H), 3.37 (s, 3H),
2.45–2.51 (m, 4H), 2.64 (dd, 1H), 3.03 (t, 1H). 13C
NMR (100 MHz, CDCl3) l ppm: 64.96, 61.71, 57.65,
55.04, 41.45, 31.14, 23.52, 22.64. GC–MS, m/z: 169
(M+).
4.5.6. (S)-N-Methyl-2-(1-piperidinylmethyl)pyrrolidine,
5b. Colorless oil (630 mg, 70%) bp: 55°C/0.6 mmHg.
[h]2D0=−65.1 (c 0.55, EtOH) (lit. [h]2D0=−65.6 (c 0.56,
1
EtOH). H NMR (CDCl3/TMS), (400 MHz) l ppm:
1.39 (m, 2H), 1.50–1.55 (m, 4H), 1.66–1.78 (m, 4H),
1.96 (m, 1H), 2.10–2.20 (m, 2H), 2.27 (m, 1H), 2.35
(m, 2H), 3.38 (s, 3H), 2.47 (dd, 1H), 3.02 (t, 1H). 13C
NMR (100 MHz, CDCl3) l ppm: 65.07, 63.12, 57.92,
55.52, 41.64, 31.43, 26.19, 24.63, 22.83. GC–MS, m/z:
183 (M+).
4.5.1. (S)-(1-Pyrrolidinylmethyl)pyrrolidine, 1a. Color-
less oil (693 mg, 90%), bp: 30°C/7.6×10−2 mmHg.
[h]D20=+8.9 (c 2.4, EtOH) (lit.2 [h]2D0=8.2, (c 2.4,
EtOH)). 1H NMR (400 MHz, CDCl3) l ppm: 1.34
(m, 1H), 1.65–1.80 (m, 6H), 1.87 (m, 1H), 2.05 (bs,
1H), 2.33 (dd, 1H), 2.45–2.60 (m, 5H), 2.85 (m, 1H),
2.97 (m, 1H), 3.20 (m, 1H). 13C NMR (100 MHz,
CDCl3) l ppm: 62.33, 57.59, 54.78, 46.30, 30.33,
25.24, 23.62. GC–MS, m/z: 155 (M+).
4.6. General procedure for determination of enantio-
meric composition of diamines 1
To a 50 ml two-necked round bottomed flask under a
nitrogen atmosphere containing a solution of
L-
ephedrine (0.83 g, 5 mmol) in dry toluene (20 ml)
was added dropwise tris(diethylamino)phosphine (1.24
g, 5 mmol). The mixture was then heated under
reflux and monitored by 31P NMR spectroscopy.
After 1 h, 1 ml (0.25 mmol) was reacted in a 2 ml
round flask under a nitrogen atmosphere with 1
equiv. of the desired racemic or chiral diamine 1 at
70°C for 30 min. The solvent was then removed
under vaccum. The residue was transferred under
nitrogen into a 5 mm NMR tube and CDCl3 was
added.
4.5.2. (S)-2-(1-Piperidinylmethyl)pyrrolidine, 1b. Color-
less oil (740 mg, 88%), kugelrohr distillation, 110°C/
7.6 mmHg. [h]2D1=+15 (c 7.75, EtOH) (lit.2 [h]2D5=+14,
c 10, EtOH). 1H NMR (400 MHz, CDCl3) l ppm:
1.28 (m, 1H), 1.42 (m, 2H), 1.58 (m, 4H), 1.72 (m,
2H), 1.86 (m, 1H), 2.24–2.36 (m, 6H), 2.83 (m, 1H),
2.99 (m, 1H), 3.26 (m, 1H). 13C NMR (100 MHz,
CDCl3) l ppm: 65.23, 55.50, 51.51, 46.09, 30.46,
26.20, 25.30, 24.44. GC–MS, m/z: 17 (M++1).