PRACTICAL SYNTHETIC PROCEDURES
Chloroaminations
555
Major Isomer
Rf 0.32 (P–EtOAc–MeOH, 80:15:5); mp 115 °C.
MS (EI, 70 eV): m/z (%) = 201 (20, [M+]), 166 (100, [M+ – Cl]), 136
(85), 110 (78).
IR (KBr): 3054 (s), 2987 (s), 1712 (w), 1422 (m), 1261 (s), 896 (m),
749 cm–1 (s).
HRMS: m/z calcd for C10H16ClNO: 201.09204; found: 201.08981.
1H NMR (360 MHz, CDCl3): d = 1.10–1.49 (m, 5 H), 1.55–1.80 (m,
6 H), 1.81–1.91 (m, 1 H), 2.19–2.33 (m, 1 H), 2.35–2.48 (m, 2 H),
3.66 (dd, 3J = 8.2 Hz, 3J = 3.4 Hz, 1 H), 3.96 (pseudo q, 3J ≈ 7.4 Hz,
1 H), 5.87 (br s, 1 H).
Acknowledgment
Support of this work by the Fonds der Chemischen Industrie and by
the Deutsche Forschungsgemeinschaft is gratefully acknowledged.
13C NMR (90.6 MHz, CDCl3): d = 25.3 (t), 25.8 (t), 26.0 (t), 26.1
(t), 26.9 (t), 30.5 (t), 31.0 (t), 40.2 (d), 57.0 (d), 73.2 (d), 176.9 (s).
References
MS (EI, 70 eV): m/z (%) = 215 (100, [M+]), 179 (70, [M+ – HCl]),
136 (30), 132 (24, [M+ – C6H11]), 108 (15).
(1) Present address: Degussa (China) Co., Ltd., 55 Chundong
Road, Xinzhuang Industry Park, Shanghai 201108, P.R.
China.
Anal. Calcd for C11H18ClNO (215.72): C, 61.25; H, 8.41. Found: C,
61.60; H, 8.47.
(2) Present address: LANXESS Fine Chemicals, LXS-FCH-
RD-LP2, Geb. Q18, R 304, 51369 Leverkusen, Germany.
(3) Reviews: (a) Kemp, J. E. G. In Comprehensive Organic
Synthesis, Vol. 7; Trost, B. M.; Fleming, I., Eds.; Pergamon:
Oxford, 1991, 469. (b) Mackiewicz, P.; Furstoss, R.
Tetrahedron 1978, 34, 3241. (c) Minisci, F. Acc. Chem. Res.
1975, 8, 165. (d) Kovacic, P.; Lowery, M. K.; Field, K. W.
Chem. Rev. 1970, 70, 639.
( )-(RS)-5-[(RS)-1-Chlorohexyl]pyrrolidin-2-one (7d)
The product was a mixture of the threo- and the erythro-isomer
(dr = 60:40). The analytical data are provided for the major isomer.
Major Isomer
Rf 0.49 [CHCl3–P–MeOH–NH3(aq), 60:30:10:0.5]; mp 97 °C.
(4) Reviews: (a) Stella, L. In Radicals in Organic Synthesis,
Vol. 2; Renaud, P.; Sibi, M. P., Eds.; Wiley-VCH:
IR (KBr): 3054 (m), 2957 (s), 1694 (s), 1421 (m), 1264 (s), 747
cm–1 (s).
Weinheim, 2001, 407. (b) Fallis, A. G.; Brinza, I. M.
Tetrahedron 1997, 53, 17543. (c) Esker, J. L.; Newcomb,
M. Adv. Heterocycl. Chem. 1993, 58, 1. (d) Cardilllo, G.;
Orena, M. Tetrahedron 1990, 46, 3321. (e) Stella, L.
Angew. Chem., Int. Ed. Engl. 1983, 22, 337.
1H NMR (360 MHz, CDCl3): d = 0.90 (pseudo t, J ≈ 6.7 Hz, 3 H),
1.19–1.45 (m, 6 H), 1.55–1.90 (m, 3 H), 2.22–2.47 (m, 3 H), 3.72–
3.89 (m, 2 H), 6.54 (br s, 1 H).
13C NMR (90.6 MHz, CDCl3): d = 14.0 (q), 23.1 (t), 24.9 (t), 25.8
(t), 31.1 (t), 31.1 (t), 33.6 (t), 59.5 (d), 67.2 (d), 176.4 (s).
MS (EI, 70 eV): m/z (%) = 203 (100, [M+]), 168 (50, [M+ – Cl]), 152
(15), 136 (10), 124 (29), 110 (87).
(5) Examples: (a) Kuehne, M. E.; Horne, D. A. J. Org. Chem.
1975, 40, 1287. (b) Mackiewicz, P.; Furstoss, R.; Waegell,
B.; Cote, R.; Lessard, J. J. Org. Chem. 1978, 43, 3746.
(c) Chow, Y. L.; Perry, R. A. Can. J. Chem. 1985, 63, 2203.
(d) Daoust, B.; Lessard, J. Tetrahedron 1999, 55, 3495.
(e) Sjöholm, Å.; Hemmerling, M.; Pradeille, N.; Somfai, P.
J. Chem. Soc., Perkin Trans. 1 2001, 891. (f) Noack, M.;
Kalsow, S.; Göttlich, R. Synlett 2004, 1110.
Anal. Calcd for C10H18ClNO (203.11): C, 58.96; H, 8.91. Found: C,
58.98; H, 8.71.
( )-(4RS)-5-[(RS)-Chlorophenylmethyl]-4-methylpyrrolidin-2-
one (trans-7e)
(6) Examples: (a) Foglia, T. A.; Swern, D. J. Org. Chem. 1966,
31, 3625. (b) Schrage, K. Tetrahedron 1967, 23, 3033.
(c) Schrage, K. Tetrahedron 1967, 23, 3039. (d) Daniher, F.
A.; Butler, P. E. J. Org. Chem. 1968, 33, 2637. (e) Neale,
R. S. Synthesis 1971, 1. (f) Touchard, D.; Lessard, J.
Tetrahedron Lett. 1971, 4425. (g) Barlow, M. G.; Fleming,
G. L.; Haszeldine, R. N.; Tipping, A. E. J. Chem. Soc. C
1971, 2744. (h) Akasaka, T.; Furukawa, N.; Oae, S. J. Chem.
Soc., Perkin Trans. 1 1980, 1257. (i) Lessard, J.; Mondon,
M.; Touchard, D. Can. J. Chem. 1981, 59, 431. (j) Carpino,
L. A.; Lee, S.-N. J. Org. Chem. 1983, 48, 746. (k) Orlek, B.
S.; Stemp, G. Tetrahedron Lett. 1991, 32, 4045. (l) Nagao,
Y.; Katagiri, S. Chem. Lett. 1992, 2379. (m) Tsuritani, T.;
Shinokubo, H.; Oshima, K. J. Org. Chem. 2003, 68, 3246.
(7) Examples: (a) Minisci, F. Synthesis 1973, 1. (b) Driguez,
H.; Lessard, J. Can J. Chem. 1977, 55, 720. (c) Borch, R.
F.; Evans, A. J.; Wade, J. J. J. Am. Chem. Soc. 1977, 99,
1612. (d) Lessard, J.; Cote, R.; Mackiewicz, P.; Furstoss, R.;
Waegell, B. J. Org. Chem. 1978, 43, 3750. (e) Stella, L.;
Raynier, B.; Surzur, J. M. Tetrahedron 1981, 37, 2843.
(f) Bougeois, J.-L.; Stella, L.; Surzur, J.-M. Tetrahedron
Lett. 1981, 22, 61. (g) Göttlich, R. Synthesis 2000, 1561.
(h) Wei, H.-X.; Kim, S. H.; Li, G. Tetrahedron 2001, 57,
3869. (i) Chen, D.; Timmons, C.; Chao, S.; Li, G. Eur. J.
Org. Chem. 2004, 3097. (j) Manzoni, M. R.; Zabawa, T. P.;
Kasi, D.; Chemler, S. R. Organometallics 2004, 23, 5618.
(8) CAUTION! BocN3 is potentially explosive upon heating,
see: (a) Koppel, H. C. Chem. Eng. News 1976, 54 (39), 5.
(b) Feyen, P. Angew. Chem., Int. Ed. Engl. 1977, 16, 115.
The product was obtained as a mixture of the threo- and the erythro-
isomer (dr = 59:41). The analytical data are provided for the major
isomer.
Major Isomer
Rf 0.48 (P–EtOAc–MeOH, 60:35:5); mp 95 °C.
IR (KBr): 3200 (br), 2970 (s), 1701 (s), 1265 cm–1 (m).
3
1H NMR (360 MHz, CDCl3): d = 0.76 (d, J = 6.8 Hz, 3 H), 1.97
(dd, 2J = 17.2 Hz, 3J = 6.0 Hz, 1 H), 2.12–2.23 (m, 1 H), 2.57 (dd,
2J = 17.2 Hz, 3J = 9.0 Hz, 1 H), 3.68 (dd, 3J = 8.4 Hz, 3J = 4.5 Hz, 1
H), 4.71 (d, 3J = 8.4 Hz, 1 H), 6.30 (br s, 1 H), 7.31–7.45 (m, 5 H).
13C NMR (90.6 MHz, CDCl3): d = 20.2 (q), 32.6 (d), 38.6 (t), 67.1
(d), 67.8 (d), 127.6 (d), 129.0 (d), 129.2 (d), 137.3 (s), 176.4 (s).
MS (EI, 70 eV): m/z (%) = 223 (9, [M+]), 188 (32, [M+ – Cl]), 144
(18), 131 (88), 125 (95, [PhCHCl+]), 117 (56), 107 (100).
HRMS: m/z calcd for C12H14ClNO: 223.0764; found: 223.0761.
( )-5-(1-Chlorocyclohexyl)pyrrolidin-2-one (7f)
Rf 0.32 (P–EtOAc–MeOH, 60:35:5), mp 103 °C.
1H NMR (360 MHz, CDCl3): d = 0.98–1.14 (m, 1 H), 1.27–1.47 (m,
2 H), 1.50–1.70 (m, 5 H), 1.73–1.83 (m, 2 H), 1.96–2.05 (m, 1 H),
2.06–2.15 (m, 1 H), 2.18–2.26 (m, 1 H), 2.28–2.38 (m, 1 H), 3.67
(dd, 3J = 8.2 Hz, 3J = 5.0 Hz, 1 H), 6.35 (br s, 1 H).
13C NMR (90.6 MHz, CDCl3): d = 21.4 (t), 22.1 (t), 25.2 (t), 30.1
(t), 34.6 (t), 35.4 (t), 64.5 (d), 178.8 (s).
Synthesis 2006, No. 3, 551–556 © Thieme Stuttgart · New York