PhSeX-Induced Cyclization of Secondary Homoallylamines
FULL PAPER
trans-1-Benzyl-4-chloro-2-ethylpyrrolidine (4c): Oil. 0.410 g, 61%
H, 4-H), 7.18Ϫ7.35 (m, 5 H, Ph). 13C NMR: δ ϭ 15.7 (Me), 20.0
yield. H NMR: δ ϭ 0.92 (t, J ϭ 7.4 Hz, 3 H, Me), 1.37 (m, 1 H, (Me), 28.6 (CHMe2), 37.0 (C-3), 44.8 (C-4), 58.7 (CH2Ph), 63.4 (C-
CH2Me), 1.76 (m, 1 H, CH2Me), 2.06 (m, 1 H, 3-H), 2.16 (m, 1 5), 68.1 (C-2), 127.3, 128.5, 128.7, 138.6. C14H20BrN: calcd. C
H, 3-H), 2. 48 (dd, J ϭ 6.4, 10.5 Hz, 1 H, 5-H), 2.78 (m, 1 H, 2- 59.56, H 7.14, N 4.96; found C 59.27, H6.94, N 5.12.
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H), 3.31 (d, 1 H, JAB ϭ 13.1 Hz, Bn), 3.37 (dd, J ϭ 6.4, 10.5 Hz,
1 H, 5-H), 4.05 (d, 1 H, JAB ϭ 13.1 Hz, Bn), 4.26 (m, 1 H, 4-H),
trans-1-Benzyl-4-bromo-2-tert-butylpyrrolidine (5e): Oil. 0.486 g,
55% yield. H NMR: δ ϭ 0.96 (s, 9 H, tBu), 2.08Ϫ2.24 (m, 2 H,
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7.20Ϫ7.35 (m, 5 H, Ph). 13C NMR: δ ϭ 9.8 (Me), 25.7 (CH2Me),
3-H), 2.77 (dd, J ϭ 4.2, 11.9 Hz, 1 H, 5-H), 3.03 (m, 1 H, 2-H),
41.1 (C-3), 54.5 (C-4), 57.9 (CH2Ph), 63.0 (C-5), 63.7 (C-2), 126.7,
3.21 (dd, J ϭ 4.4, 11.9 Hz, 1 H, 5-H), 3.98 (d, 1 H, JAB ϭ 14.2 Hz,
128.0, 128.4, 138.7. C13H18ClN: calcd. C 69.78, H 8.11, N 6.26;
Bn), 4.13 (d, 1 H, JAB ϭ 14.2 Hz, Bn), 4.33 (m, 1 H, 4-H),
found C 70.12, H 8.22, N 6.35.
7.20Ϫ7.35 (m, 5 H, Ph). 13C NMR: δ ϭ 26.7 (Me), 42.4 (C-3), 44.3
(C-4), 57.7 (CH2Ph), 62.9 (C-5), 65.1 (C-2), 127.8, 128.8, 129.3,
138.7. C15H22BrN: calcd. C 60.81, H 7.48, N 4.73; found C 60.75,
H 7.38, N 4.68.
trans-1-Benzyl-4-chloro-2-isopropylpyrrolidine (4d): Oil. 0.484 g,
68% yield. 1H NMR: δ ϭ 0.91(dd, 6 H, J ϭ 1.9, 6.9 Hz, Me), 1.95
(m, 2 H, 3-H and CHMe2), 2.14 (m, 1 H, 3-H), 2.48 (dd, 1 H, J ϭ
6.6, 10.2 Hz, 5-H), 2.83 (m, 1 H, 2-H), 3.26Ϫ3.40 (m, 2 H, 5-H
and CH2Ph), 4.04 (d, 1 H, JAB ϭ 13.2 Hz, CH2Ph), 4.21 (m, 1 H,
4-H), 7.18Ϫ7.34 (m, 5 H, Ph). 13C NMR: δ ϭ 20.0 (Me), 28.4
(CHMe2), 36.6 (C-3), 55.0 (C-4), 58.9 (CH2Ph), 62.5 (C-5), 68.0
(C-2), 127.3, 128.3, 128.8, 138.7. C14H20ClN: calcd. C 70.72, H
8.48, N 5.89; found C 7068, H 8.37, N 5.92.
trans-1-Benzyl-4-bromo-2-phenylpyrrolidine (5f): Oil. 0.583 g, 62%
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yield. H NMR: δ ϭ 2.35Ϫ2.68 (m, 2 H, 3-H), 2.86 (dd, J ϭ 6.3,
10.8 Hz, 1 H, 5-H), 3.27 (d, 1 H, JAB ϭ 13.0 Hz, Bn), 3.73 (dd,
J ϭ 6.6, 10.8 Hz, 1 H, 5-H), 3.94 (d, 1 H, JAB ϭ 13.0 Hz, Bn), 3.94
(m, 1 H, 2-H), 4.45 (m, 1 H, 4-H), 7.25Ϫ7.60 (m, 10 H, Ph). 13C
NMR: δ ϭ 44.4 (C-4), 46.9 (C-3), 57.6 (CH2Ph), 63.3 (C-5), 67.7
(C-2), 127.2, 127.6, 128.4, 128.7, 128.8, 129.1, 138.9, 141.9.
C17H18BrN: calcd. C 64.56, H 5.74, N 4.43; found C 64.18, H 5.65,
N 4.73.
trans-1-Benzyl-2-tert-butyl-4-chloropyrrolidine (4e): Oil. 0.540 g,
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71% yield. H NMR: δ ϭ 0.90 (s, 9 H, tBu), 2.13Ϫ2.35 (m, 2 H,
3-H), 2.65 (dd, J ϭ 6.4, 10.5 Hz, 1 H, 5-H), 3.01 (m,1 H, 2-H), 3.95
(d, 1 H, JAB ϭ 13.2 Hz, Bn), 4.03 (dd, J ϭ 6.1, 10.5 Hz, 1 H, 5-
H), 4.08 (d,1 H, JAB ϭ 13.2 Hz, Bn), 4.29 (m, 1 H, 4-H), 7.18Ϫ7.30
(m, 5 H, Ph). 13C NMR: δ ϭ 26.0 (Me), 41.30 (C-3), 54.7 (C-4),
59.8 (CH2Ph), 62.8 (C-5), 69.6 (C-2), 127.4, 128.3, 128.9, 138.7.
C15H22ClN: calcd. C 71.55, H 8.81, N 5.56; found C 71.48, H 8.64,
N 5.89.
Method A2. General Procedure (for Amines 1g to 1k): A solution of
PhSeX (X ϭ Cl or Br, 3 mmol) in anhydrous CH3CN (10 mL) was
slowly added to amine 1 (1g to 1k, 1 mmol) dissolved in the same
solvent (5 mL). The mixture was heated at reflux for 18 h. After
this had cooled, sodium carbonate (0.2 g) and water (15 mL) were
added. The aqueous phase was extracted with CH2Cl2 (3 ϫ 20 mL)
and the organic layers were dried and concentrated under reduced
pressure. The oily residue was chromatographed on silica gel. After
elimination of PhSeSePh, the halopyrrolidine 4 (or 5) was eluted
with a 80:20 mixture of cyclohexane/CH2Cl2.
trans-1-Benzyl-4-chloro-2-phenylpyrrolidine (4f): Oil. 0.524 g, 65%
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yield. H NMR: δ ϭ 2.20Ϫ2.48 (m, 2 H, 3-H), 2.59 (dd, J ϭ 5.8,
10.6 Hz, 1 H, 5-H), 3.20 (d, 1 H, JAB ϭ 13.1 Hz, CH2Ph), 3.60 (dd,
J ϭ 6.6, 10.6 Hz, 1 H, 5-H), 3.82Ϫ3.90 (m, 2 H, 2-H and CH2Ph),
4.40 (m, 1 H, 4-H), 7.20Ϫ7.60 (m, 10 H, Ph). 13C NMR: δ ϭ 46.4
(C-3), 54.9 (C-4), 57.6 (CH2Ph), 62.8 (C-5), 67.3 (C-2), 127.5, 128.3,
128.5, 138.8. C17H18ClN: calcd. C 75.12, H 6.75, N 5.15; found C
75.38, H 6.81, N 4.95.
The simple halopyrrolidines 4a[20] and 5a[18,19] (R1 ϭ R2 ϭ H) were
formed without heating. Their instability, especially during silica
gel chromatography, prevented their isolation in pure form.
1-Benzyl-3-chloropyrrolidine (4a):[20] 1H NMR: δ ϭ 1.99Ϫ2.15 (m,
1 H, 4-H), 2.32Ϫ2.52 (m, 1 H, 4-H), 2.60Ϫ2.84 (m, 3 H, 2-H and
trans-1-Benzyl-4-bromo-2-methylpyrrolidine (5b): Oil. 0.440 g, 58%
yield. 1H NMR: δ ϭ 1.18 (d, J ϭ 6.0 Hz, 3 H, Me), 2.08Ϫ2.37 (m,
2 H, 3-H), 2.65 (dd, J ϭ 6.5, 10.7 Hz, 1 H, 5-H), 2.89 (m, 1 H, 2-
H), 3.28 (d, 1 H, JAB ϭ 12.9 Hz, Bn), 3.46 (dd, J ϭ 6.8, 10.7 Hz,
1 H, 5-H), 4.05 (d, 1 H, JAB ϭ 12.9 Hz, Bn), 4.28 (m, 1 H, 4-H),
7.18Ϫ7.35 (m, 5 H, Ph). 13C NMR: δ ϭ 18.6 (Me), 43.9 (C-4), 44.6
(C-3), 57.5 (C-2), 57.9 (CH2Ph), 63.6 (C-5), 126.8, 128.0, 128.5,
138.7. C12 H16 BrN: calcd. C 56.69, H 6.34, N 5.51; found C 56.80,
H 6.26, N 5.93.
5-H), 3.11 (dd, J ϭ 6.3, 10.7 Hz, 1 H, 2-H), 3.65 (d, 1 H, JAB
ϭ
12.9 Hz, Bn), 3.73 (d, 1 H, JAB ϭ 12.9 Hz, Bn), 4.38 (m, 1 H, 3-
H), 7.25Ϫ7.36 (m, 5 H, Ph). 13C NMR: δ ϭ 35.8 (C-4), 52.4 (C-
5), 56.2 (C-3), 59.9 (CH2Ph), 63.1 (C-2), 127.1, 128.3, 128.7, 131.4.
1-Benzyl-4-chloro-2,2-dimethylpyrrolidine (4g): Oil. 0.128 g, 58%
yield. 1H NMR: δ ϭ 1.14 (s, 3 H, Me), 1.26 (s, 3 H, Me), 2.06 (dd,
J ϭ 4.8, 13.8 Hz, 1 H, 3-H), 2.35 (dd, J ϭ 8.6, 13.8 Hz, 1 H, 3-H),
2.86 (dd, J ϭ 5.0, 10.6 Hz, 1 H, 5-H), 3.14 (dd, J ϭ 7.3, 10.6 Hz,
1 H, 5-H), 3.58 (s, 2 H, Bn), 4.32 (m, 1 H, 4-H), 7.16Ϫ7.40 (m, 5
H, Ph). 13C NMR: δ ϭ 23.9 (Me), 24.5 (Me), 51.5 (CH2Ph), 52.3
(C-3), 54.4 (C-4), 60.7 (C-5), 127.2, 128.6. C13H18ClN: calcd. C
69.78, H 8.11, N 6.26; found C 69.86, H 8.48, N 5.97.
trans-1-Benzyl-4-bromo-2-ethylpyrrolidine (5c): Oil. 0.442 g, 55%
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yield. H NMR: δ ϭ 0.91 (t, J ϭ 7.4 Hz, 3 H, Me), 1.28Ϫ1.50 (m,
1 H, CH2Me), 1.65Ϫ1.85 (m, 1 H, CH2Me), 2.07Ϫ2.36 (m, 2 H,
3-H), 2.65 (dd, J ϭ 6.8, 10.6 Hz, 1 H, 5-H), 2.80 (m, 1 H, 2-H),
3.31 (d, 1 H, JAB ϭ 13.1 Hz, Bn), 3.44 (dd, J ϭ 6.3, 10.6 Hz, 1 H,
5-H), 4.05 (d, 1 H, JAB ϭ 13.1 Hz, Bn), 4.25 (m, 1 H, 4-H),
7.18Ϫ7.35 (m, 5 H, Ph). 13C NMR: δ ϭ 10.0 (Me), 25.8 (CH2Me),
41.7 (C-3), 44.1 (C-4), 58.0 (CH2Ph), 63.4 (C-5), 64.2 (C-2), 127.0,
128.2, 128.6, 138.4. C13H18BrN: calcd. C 58.21, H 6.76, N 5.22;
found C 58.28, H 6.93, N 5.62.
1-Benzyl-4-chloro-2-methyl-2-phenylpyrrolidine (4h): Oil. 0.186 g,
65% yield. Mixture of cis and trans isomers (55:45). cis isomer:
stereochemistry assigned by NOESY (Me and Cl trans). 1H NMR:
δ ϭ 1.45 (s, 3 H, Me), 2.42 (dd, J ϭ 5.1, 14.1 Hz, 1 H, 3-H), 2.54
(dd, J ϭ 7.7, 14.1 Hz, 1 H, 3-H), 3.05 (dd, J ϭ 6.6, 11.5 Hz, 1 H,
5-H), 3.25 (m, 2 H, 5-H and CH2Ph), 3.63 (d, 1 H, JAB ϭ 13.5 Hz,
CH2Ph), 4.50 (m, 1 H, 4-H), 7.27Ϫ7.45 (m, 8 H), 7.75Ϫ7.82 (m, 2
trans-1-Benzyl-4-bromo-2-isopropylpyrrolidine (5d): Oil. 0.521 g,
61% yield. H NMR: δ ϭ 0.92 (d, J ϭ 6.9 Hz, 6 H, Me), 1.97 (m, H). 13C NMR: δ ϭ 16.5 (Me), 51.0 (C-3), 53.3 (CH2Ph), 54.5 (C-
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1 H, CHMe2), 2.00Ϫ2.30 (m, 2 H, 3-H), 2.64 (dd, J ϭ 7.1, 10.4 Hz,
4), 58.2 (C-5), 65.2 (C-2), 125.2, 125.5, 125.7, 126.9, 127.2, 127.4,
1 H, 5-H), 2.84 (m, 1 H, 2-H), 3.34 (d, 1 H, JAB ϭ 13.2 Hz, Bn), 127.8, 138.6. C18H20ClN: calcd. C 75.64, H 7.05, N 4.90; found C
3.39 (m, 1 H, 5-H), 4.05 (d, 1 H, JAB ϭ 13.2 Hz, Bn), 4.20 (m, 1 75.32, H 7.01, N 5.10.
Eur. J. Org. Chem. 2002, 1007Ϫ1014
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