2 T. Kusaka, H. Yamamoto, M. Shibata, M. Muroi, T. Kishi and K.
Mizuno, J. Antibiot., 1968, 255; M. Arita, K. Adachi, H. Sawai and M.
Ohno, Nucleic Acids Res. Symp. Ser., 1983, 12, 25.
3 E. L. White, W. B. Parker, L. J. Macy, S. C. Shaddix, G. McCaleb, J. A.
Secrist III, R. Vince and W. M. Shannon, Biochem. Biophys. Res.
Commun., 1989, 161, 393; R. Vince, M. Hua, J. Brownell, S. Daluge, F.
Lee, W. M. Shannon, G. C. Lavelle, J. Qualls, O. S. Weislow, R. Kiser,
P. G. Canonico, R. H. Schultz, V. L. Narayanan, J. G. Mayo, R. H.
Showmaker and M. R. Boyd, Biochem. Biophys. Res. Commun., 1988,
156, 1046.
4 Other related biologically active compounds. Neplanocin A: M. Arita, K.
Adachi, H. Sawai and M. Ohno, Nucleic Acids Res. Symp. Ser., 1983, 12,
25; M.-I. Lim, J. D. Moyer, R. L. Cysyk and V. E. Marquez, J. Med.
Chem., 1984, 27, 1536; M.-I. Lim and V. E. Marquez, Tetrahedron Lett.,
1983, 24, 5559. Guanine derivatives: A. B. Reitz, M. G. Goodman, B. L.
Pope, D. C. Argentieri, S. C. Bell, L. E. Burr, E. Chourmouzis, J. Come,
J. H. Goodman, D. H. Klaubert, B. E. Maryanoff, M. E. McDonnell,
M. S. Rampulla, M. R. Schott and R. Chen, J. Med. Chem., 1994, 37,
3561. Adenosine analogues: Y. F. Shealy and J. D. Clayton, J. Am. Chem.
Soc., 1966, 88, 3885. Tubercidin analogues: J. A. Montgomery and K.
Hewson, J. Med. Chem., 1967, 10, 665. Noraristeromycin: S. M. Siddiqi,
F. P. Oertel, X. Chen and S. W. Schneller, J. Chem. Soc., Chem.
Commun., 1993, 708. Adenosine deaminase inhibitors: H. J. Schaeffer,
D. D. Godse and G. Liu, J. Pharm. Sci., 1964, 53, 1510. g-Aminobutyric
acid analogue: M. J. Milewska and T. Polonski, Tetrahedron: Asym-
metry, 1994, 5, 359. Carboxylic sugars and nucleosides: S. Ranganathan
and K. S. George, Tetrahedron, 1997, 53, 3347; M. J. Mulvihill, M. D.
Surman and M. J. Miller, J. Org. Chem., 1998, 63, 4874.
5 (a) M. J. So¨dergren and P. G. Andersson, Tetrahedron Lett., 1996, 37,
7577; (b) D. A. Alonso, D. Guijarro, P. Pinho, O. Temme and P. G.
Andersson, J. Org. Chem., 1998, 63, 2749; (c) D. Guijarro, P. Pinho and
P. G. Andersson, J. Org. Chem., 1998, 63, 2530; (d) P. Pinho, D. Guijarro
and P. G. Andersson, Tetrahedron, 1998, 54, 7897; (e) M. J. So¨dergren
and P. G. Andersson, J. Am. Chem. Soc., 1998, 120, 10760; (f) D. A.
Alonso, S. K. Bertilsson, S. Y. Johnsson, S. J. M. Nordin, M. So¨dergren
and P. G. Andersson, J. Org. Chem., 1999, in the press.
6 L. Stella, H. Abraham, J. Feneu-Dupont, B. Tinant and J. P. Declercq,
Tetrahedron Lett., 1990, 31, 2603; H. Abraham and L. Stella,
Tetrahedron, 1992, 48, 9707.
7 The absolute configuration of the aza-Diels–Alder adduct has been
determined by means of X-ray analysis of a derivative, see: H. Nakano,
N. Kumagai, C. Kabuto, H. Matsuzaki and H. Hongo, Tetrahedron:
Asymmetry, 1995, 6, 1233.
8 For interesting compounds containing this structure unit, see for example:
G. E. Keck and S. A. Fleming, Tetrahedron Lett., 1978, 48, 4763; T.
Hudlicky and H. F. Olivo, Tetrahedron Lett., 1991, 32, 6077; F. Chretien,
S. I. Ahmed, A. Masion and Y. Chapleur, Tetrahedron, 1993, 49, 7463;
S. Grabowski, J. Armbruster and H. Prinzbach, Tetrahedron Lett., 1997,
38, 5485; H. Noguchi, T. Aoyama and T. Shioiri, Tetrahedron Lett.,
1997, 38, 2883.
Scheme 2 Reagents and conditions: (i) (MeO)2C(CH3)2, TsOH, warm
MeOH, 15 min, 87%; (ii) ammonium formate, Pd/C (10%), EtOH, reflux,
1 h, 99%; (iii) TsCl, Et3N, CH2Cl2, rt, overnight, 90%; (iv) LiAlH4, THF,
rt, 2 h, 92%; (v) CBr4, Ph3P, CH2Cl2, rt, 24 h, 59%; (vi) Mg, BrCH2CH2Br,
THF, reflux, 32 h, 89%.
reflux in the presence of Pd/C (10%) to afford the corresponding
free amino ester, and then submitted to the same synthetic
sequence as described for 1 to yield the corresponding bromide
7. Compound 7 ring opened to give product 8 under the
conditions described for 3, albeit in a slightly slower reaction.
By simply using cyclohexa-1,3-diene in the aza-Diels–Alder
reaction, a bicyclic [2.2.2] structure was obtained.6 Dihydrox-
ylation of the purified adduct under the conditions described
earlier yielded compound 9 (Scheme 3) which, when submitted
to the same synthetic sequence as 5, yielded the ring opened
product 10.8 The yields for the transformation of 9 into 10 were
similar to those obtained in the transformation of 5 into 8.9
9 Representative spectroscopic and analytical data. (1R,3S)-1-Tosylamino-
3-vinylcyclopentane (4). Magnesium metal (3.0 g, 123 mmol) was placed
in a 50 mL two-neck round-bottom flask loaded with a magnetic bar. To
one neck a condenser was adapted and to the other a septum. The system
was evacuated and placed under argon, after which the magnesium was
suspended in dry THF (3 mL). The stirring suspension was then set to
reflux and a solution of compound 3 (6.0 g, 17 mmol) in dry THF (20 mL)
was added in one portion via syringe. After stirring for 15 min a small
amount of 1,2-dibromoethane was added to activate the magnesium and
the mixture was heated at reflux for 24 h. The reaction was then cooled
to 0 °C and quenched by addition of saturated NH4Cl solution. After
separation of the phases and extraction of the water phase with CH2Cl2,
the combined organic layers were dried with magnesium sulfate. Solvent
evaporation afforded a residue that was purified by flash chromatography
to yield compound 4 (4.1 g, 15 mmol, 90%) as a white solid; mp
65–66 °C; Rf 0.11 (silica gel, pentane–ether: 80:20); [a]24 = 28.9 (c =
1.0, CH2Cl2); n(CH2Cl2)/cm21 3623, 3369, 2870, 164D1, 1599, 1345,
1092, and 1047; dH(CDCl3, 400 MHz) 1.14–1.24 (1H, m), 1.38–1.45
(2H, m), 1.62–1.79 (1H, m), 1.80–1.90 (1H, m), 1.99–2.10 (1H, m),
2.34–2.42 (1H, m), 2.41 (3H, s), 3.57–3.63 (1H, m), 4.83–4.94 (2H, m),
5.65–5.75 (1H, m), 7.28 (2H, app. d, J 8.0), and 7.76 (2H, app. d, J 8.0);
dC(CDCl3, 100 MHz) 21.5, 29.9, 32.6, 40.2, 41.8, 54.5, 113.1, 127.1,
129.6, 137.8, 141.9, and 143.2; m/z (EI) (rel. intensity) 264 (M+, < 1%),
236 (25), 210 (13), 172 (14), 155 (62), 133 (44), 132 (36), 110 (41), 106
(17), 97 (12), 96 (43), 94 (13), 93 (25), 92 (35), 91 (100), 80 (21), 79 (17),
and 65 (20) (Anal. Calcd. for C14H19NO2S: C, 63.37; H, 7.22; N, 5.28.
Found: C, 63.10; H, 7.07; N, 5.20%). The relative stereochemistry of this
compound was determined by means of NOESY experiments.
Scheme 3 Reagents and conditions: (i) (MeO)2C(CH3)2, TsOH, warm
MeOH, 15 min, 87%; (ii) ammonium formate, Pd/C (10%), EtOH, reflux,
1 h, 99%; (iii) TsCl, Et3N, CH2Cl2, rt, overnight, 91%; (iv) LiAlH4, THF,
rt, 2 h, 94%; (v) CBr4, Ph3P, CH2Cl2, rt, 24 h, 62%; (vi) Mg, BrCH2CH2Br,
THF, reflux, 32 h, 85%.
This work opens up a new route to cyclopentyl- and
cyclohexyl-amines via a novel ring opening reaction of [2.2.1]
and [2.2.2] azabicyclic structures. The fact that the [2.2.2]
structure ring opens without increased difficulty indicates that
the reaction is not only a consequence of ring strain on the
[2.2.1] system.
We thank the Swedish Natural Research Council (NFR), The
Swedish Foundation for Strategic Research (SSF), The Swedish
Research Council for Engineering Sciences (TFR) and Astra
Arcus for generous financial support.
Notes and references
1 S.-Y. Sung and A. W. Frahm, Arch. Pharm. Pharm. Med. Chem., 1996,
329, 291; S. Nakamura, K. Karasawa, N. Tanaka, H. Yonehara and H.
Umezawa, J. Antibiot., Ser. A, 1960, 392; H. Nagata T. Taniguchi and K.
Ogasawara, Tetrahedron: Asymmetry, 1997, 8, 2679.
Communication 9/01073D
598
Chem. Commun., 1999, 597–598