I. Alfonso et al. / Tetrahedron: Asymmetry 10 (1999) 2515–2522
2521
3.5. (S,S)-N,N0-(Cyclohexane-1,2-diyl)bis-[3-(p-toluenesulphonylamino)propyl methanesulphonate]
(S,S)-8
The title compound was obtained from (S,S)-1 as described for its enantiomer (R,R)-8.9 42% Yield: mp
20
138–140°C; [α]D +20.4 (c 0.25, CHCl3). The spectral data are in accordance with literature values.9
3.6. (1S,7S,12S,18S)-2,6,13,17-Tetrakis(p-toluenesulphonyl)-2,6,13,17-tetraazatricyclo[16.4.0.07,12 ]-
docosane (S,S,S,S)-9
Dry acetonitrile (45 mL) was added to a flask containing (S,S)-5 (633 mg, 1.5 mmol) and cesium
carbonate (4.89 g, 15.0 mmol) under a nitrogen atmosphere. The mixture was refluxed for 30 min and
then a solution of (S,S)-8 (1044 mg, 1.5 mmol) in dry acetonitrile (30 mL) was added dropwise. The
reaction mixture was kept at reflux for 5 days; after this time the solvent was removed and the residue
was subjected to column chromatography (ethyl acetate:hexane 2:3) to yield (S,S,S,S)-9 (875 mg, 64%)
20
1
as a foamy solid which was precipitated in hexane, mp 152–154°C; [α]D +28.5 (c 0.52, CHCl3). H
NMR (CDCl3, 300 MHz) δ 0.70–1.70 (several m, 14H), 1.80–2.20 (several m, 6H), 2.40 (m, 12H),
2.75–3.90 (several m, 12H), 7.41 (m, 8H), 7.73 (m, 8H). MS (FAB+, NBA matrix) m/z (rel. intensity):
947 [(M+Na)+, 25], 925 [(M+1)+, 13], 769 [(M−Ts)+, 18].
3.7. (1S,7S,12S,18S)-2,6,13,17-Tetraazatricyclo[16.4.0.07,12 ]docosane tetrahydrobromide
(S,S,S,S)-4·4HBr
Compound (S,S,S,S)-9 (750 mg, 0.81 mmol) and phenol (0.90 mL, 10.1 mmol) were dissolved in
aqueous 48% HBr (11 mL), and the solution was heated at reflux for 4 days. Water and dichloromethane
were then added and the aqueous phase was repeatedly washed with dichloromethane. The organic layer
was discarded and the aqueous one was evaporated under reduced pressure. Recrystallization of the
residue from EtOH–48% aq. HBr yielded (S,S,S,S)-4·4HBr (272 mg, 72%) as a white solid, which was
dried under vacuum. Decomposition of the compound was observed when heated at 160°C. [α]D20 +18.1
1
(c 0.53, H2O). H NMR (D2O, 300 MHz) δ 1.00 (bm, 4H), 1.22 (bm, 4H), 1.40 (bm, 4H), 1.70–2.10
(bm, 8H), 2.60–3.50 (bm, 12H). MS (FAB+, NBA matrix) m/z (rel. intensity): 309 [(M+1)+, 55], 389
[(M+1+H79Br)+, 12], 391 [(M+1+H81Br)+, 12]. 13C NMR of the free amine (S,S,S,S)-4 (DMSO-d6, 75
MHz, 373 K) δ 24.2 (CH2), 24.4 (CH2), 30.7 (CH2), 44.3 (CH2), 60.6 (CH).
Acknowledgements
This work was supported by the CICYT (BIO-98-0770). I.A. thanks the Ministerio de Educación y
Ciencia for a predoctoral fellowship.
References
1. (a) Kimura, E.; Wada, S.; Shionoya, M.; Takahashi, T.; Iitaka, Y. J. Chem. Soc., Chem. Commun. 1990, 397–398. (b)
Collman, J. P.; Zang, X.; Herrmann, P. C.; Uffelman, E. S.; Boitrel, B.; Straumanis, A.; Brauman, J. I. J. Am. Chem. Soc.
1994, 116, 2681–2682. (c) Collman, J. P.; Herrmann, P. C.; Fu, L.; Eberspacher, T. A.; Eubanks, M.; Boitrel, B.; Hayoz,
P.; Zang, X.; Brauman, J. I.; Day, V. W. J. Am. Chem. Soc. 1997, 119, 3481–3489.
2. (a) Lauffer, R. B. Chem. Rev. 1987, 87, 901–927. (b) Takenouchi, K.; Watanabe, K.; Kato, Y.; Koike, T.; Kimura, E. J.
Org. Chem. 1993, 58, 1955–1958.