1604
J. J. Caldwell et al.
LETTER
under reduced pressure. Chromatographic purification
(2) Sulphones in Organic Synthesis; Simpkins, N. S., Ed.;
Pergamon: Oxford, 1993.
(SiO2; 30% EtOAc-petrol) of the crude product gave
[2S,3R,5R]-2-benzyl-3-phenylsulfonyl-5-nonylpyrrolidine4
(360 mg, 0.842 mmol, 78%) as a clear oil; [ ]D20 –9.6 (c
4.16, CHCl3); max(film) 3336, 3084, 3066, 3032, 3003,
2981, 2954, 2924, 2848, 2731, 2669, 1603, 1585, 1495,
(3) Najera, C.; Yus, M. Tetrahedron 1999, 55, 10547.
(4) (a) Schartz, R. E.; Liesch, J.; Hensens, O.; Zitano, L.;
Honeycutt, S.; Garrity, G.; Fromtling, R. A.; Onishi, J.;
Monaghan, R. J. Antibiot. 1988, 1744. (b) Johnson, J. H.;
Phillipson, D. W.; Kahle, A. D. J. Antibiot. 1989, 1184.
(5) (a) Pak, C. S.; Lee, G. H. J. Org. Chem. 1991, 56, 1128.
(b) Shimazaki, M.; Okazaki, F.; Nakajima, F.; Ishikawa, T.;
Ohta, A. Heterocycles 1993, 36, 1823. (c) McGrane, P. L.;
Livinghouse, T. J. Am. Chem. Soc. 1993, 115, 11485.
(d) Overhand, M.; Hecht, S. M. J. Org. Chem. 1994, 59,
4721. (e) Deng, W.; Overman, L. E. J. Am. Chem. Soc. 1994,
116, 11241. (f) Yoda, H.; Yamazaki, H.; Takabe, K.
Tetrahedron: Asymmetry 1996, 7, 373. (g) Beier, C.;
Schaumann, E. Synthesis 1997, 1296. (h) deArmas, P.;
Garcia-Tellado, F.; Marrero-Tellado, J. J.; Robles, J.
Tetrahedron Lett. 1998, 39, 131. (i) Kanazawa, A.; Gillet,
S.; Delair, P.; Greene, A. E. J. Org. Chem. 1998, 63, 4660.
(j) Bach, T; Brummerhop H. Angew. Chem. Int. Ed. 1998,
37, 3400. (k) Verma, R.; Ghosh, S. K. J. Chem. Soc., Perkin
Trans. 1 1999, 265. (l) Veeresa, G.; Datta, A. Tetrahedron
1998, 54, 15673. (m) Lee, K.-Y.; Kim, Y.-H.; Oh, C.-Y.;
Ham, W.-H. Org. Lett. 2000, 4041. (n) Okue, M.;
Watanabe, H.; Kitahara, T. Tetrahedron 2001, 57, 4107.
(6) Craig, D.; East, S. P. unpublished observations.
(7) Maurer, P. J.; Takahata, H.; Rapoport, H. J. Am. Chem. Soc.
1984, 106, 1095 ; all yields reported herein refer to isolated,
pure materials which had 1H and 13C NMR, IR and high-
resolution MS characteristics in accord with the proposed
structures.
1446, 1406, 1377, 1304, 1176, 1145, 1086, 1028 cm–1;
H
(300 MHz) 7.97–7.91 (2 H, m, Ar), 7.73–7.57 (3 H, m, Ar),
7.32–7.10 (5 H, m, Ar), 3.76 (1 H, ddd, J 9.0, 7.0, 3.5 Hz, H-
2), 3.36 (1 H, ddd, J 10.5, 7.0, 3.5 Hz, H-3), 3.08 (1 H, dq, J
10.0, 6.5 Hz, H-5), 2.82 (1 H, dd, J 13.5, 3.5 Hz, CHHPh),
2.64 (1 H, dd, J 13.5, 9.0 Hz, CHHPh), 2.40 (1 H, ddd, J
13.5, 6.5, 3.5 Hz, H-4), 1.88 (1 H, br s, N-H), 1.57 (1 H, dt,
J 13.5, 10.0 Hz, H-4), 1.49–1.15 (16 H, m, (CH2)8), 0.89 (3
H, t, J 6.5 Hz, CH3); C (75 MHz) 139.0, 138.4, 134.0, 129.6,
129.4, 128.8, 128.7, 126.8, 67.3, 60.7, 58.4, 41.8, 35.9, 34.3,
32.0, 29.9, 29.7 (2 C), 29.5, 27.2, 22.8, 14.3; m/z (CI) 428
[MH]+ (Found: [MH]+, 428.2615; C26H37NO2S requires
[MH]+, 428.2623).
Preparation of 3.
To a stirred solution of sulfone 14 (164 mg, 0.371 mmol) in
THF (2 mL) at –78 °C under nitrogen was added n-BuLi
(165 L of a 2.7 M solution in hexanes, 0.446 mmol, 1.2
equiv) to give a pale yellow solution. After 15 min a solution
of TMSOOTMS (86 mg, 0.483 mmol, 1.3 equiv) in THF
(0.5 mL) was added via syringe. The solution was allowed to
attain r.t. over 2 h, and then stirred at r.t. for a further 15 h.
After quenching with saturated aqueous NaHCO3 (15 mL)
the mixture was extracted with EtOAc (3 10 mL). The
combined organic layers were dried (MgSO4) and
concentrated under reduced pressure. The resulting crude
product was purified by chromatography (SiO2; 20%
EtOAc-petrol) to give recovered starting material 14 (55 mg,
34%) and [2S,5R]-2-benzyl-1-methyl-5-nonyl-3-oxo-
pyrrolidine 3 (57 mg, 49%, 74% based on recovered 14) as a
(8) Hofmann, K.; Jöhl, A.; Furlenmeier, A. E.; Kappeler, H. J.
Am. Chem. Soc.; 1956, 79, 1636.
(9) The method used was an adaptation of a procedure for N-
Boc aziridination using Boc2O–KOH in Et2O:Wessig, P.;
Schwarz, J. Synlett 1997, 893.
(10) Weinreb, S. M.; Demko, D. M.; Lessen, T. A.; Demers, J. P.
Tetrahedron Lett. 1986, 27, 2099.
(11) Pyne, S. G.; David, D. M.; Dong, Z. Tetrahedron Lett. 1998,
39, 8499.
pale yellow oil; [ 20 –97.9 (c 1.43, CHCl3); max(film)
D
3055, 2956, 2927, 2856, 1751, 1411, 1379, 1265, 1151,
1115, 1082 cm–1; H (300 MHz) 7.32–7.15 (5 H, m, Ph), 3.08
(1 H, dd, J 14.0, 4.5 Hz, CHHPh), 2.87 (1 H, dd, J 14.0, 5.0
Hz, CHHPh), 2.78 (1 H, distorted t, H-2), 2.55-2.44 (1 H, m,
H-5), 2.41 (1 H, dd, J 17.5, 6.0 Hz, H-4), 2.33 (3 H, s, NMe),
1.79 (1 H, dd, J 18.0, 10.5 Hz, H-4), 1.40–1.10 (16 H, m,
(CH2)8), 0.91 (3 H, t, J 6.5 Hz, CH2CH3); C (75 MHz) 215.0,
138.7, 129.9, 128.2, 126.3, 74.5, 62.6, 42.9, 39.4, 36.1, 33.1,
32.1, 30.0, 29.7 (2C), 29.5, 25.8, 22.9, 14.3; m/z (CI) 306
[MH]+ (Found: [MH]+, 316.2637; C21H33NO requires
[MH]+, 316.2640).
(12) Hwu, J. R. J. Org. Chem. 1983, 48, 4433.
(13) Preparation of 4.
A solution of 12 (640 mg, 1.08 mmol) in TBAF (16.22 mL
of a 1 M solution in THF, 16.22 mmol, 15 equiv) was heated
under reflux under nitrogen for 38 h. MeOH (5 mL) was
added to the cooled solution followed by water (50 mL). The
mixture was extracted with EtOAc (2 50 mL) and the
combined organic layers dried (MgSO4), and concentrated
Synlett 2001, No. 10, 1602–1604 ISSN 0936-5214 © Thieme Stuttgart · New York