34
LETTERS
SYNLETT
designing beticolin 2 and cycloheptanyl analogs. Related studies are in
progress and will be reported later.
Acknowledgment. We are indebted to Jacqueline MAHUTEAU
(Faculté de Pharmacie, Chatenay-Malabry) and Claude MERIENNE
(Université Paris XI, Orsay) for NMR experiments and their
interpretation.
References and Notes
(1) Milat, M-L.; Prange, T.; Ducrot, P-H.; Tabet, J-C.; Einhorn, J.;
Blein, J-P.; Lallemand, J-Y. J. Am. Chem. Soc. 1992, 114, 1478.
(2) Jalal, M.A.F.; Hossain, M.B.; Robesson, D.J.; van der Helm, D.
1992,
J. Am. Chem. Soc.
(3) Giese, B.; Kopping, B.; Göbel, T.; Dickhaut, J.; Thoma, G.;
Kulicke, K.J.; Trach, F.
1997, , 301.
114, 5967.
14
The compound 6 substitued at the α-alkene center with methyl group
gave only the product 7 by intramolecular addition to the double bond
(Scheme 5).
Org. React.
48
Brown, C.D.S.; Dishington, A.P.; Shiskin, O.; Simpkins, N.S.
1995, 943.
Synlett
Destabel, C.; Kilburn, J.D., Knight, J. Tetrahedron 1994, 50, 11267.
Destabel, C.; Kilburn, J.D., Knight, J. Tetrahedron 1994, 50, 11289.
Wu, S.H.; Journet, M.; Malacria, M. Tetrahedron Lett. 1994, 35,
8601.
Baldwin, J.E. J. Chem. Soc., Chem. Commun. 1976, 734.
(4) Jasperse, C.P.; Curran, D.P.; Fevig, T.L. Chem. Rev. 1991, 91,
1237.
(5) Neumann, W.P. Synthesis 1987, 665.
(6) Cason, J. Org. Syn. 1955, 3, 169.
(7) Carpenter, A.J.; Chadwick, D.J. Tetrahedron Lett. 1985, 26, 1777.
(8) Yoon, N.M.; Young, Y.S.G. J. Org. Chem. 1985, 50, 2443.
(9) Knight, D.W.; Nott, A.P. J. Chem. Soc., Perkin Trans. 1 1981,
Scheme 5
1125.
(10) Tanabe, M.; Crowe, D.F. J. Chem. Soc., Chem. Commun. 1973,
The coupling of (R)-(-)-carvone with 1a led to the precursor 8 in 30%
yield. The radical cyclisation afforded only product 9 (Scheme 6).
564.
(11) Ueno, Y.; Chino, K.; Okawara, M. Tetrahedron Lett. 1982, 23,
2575.
(12) Beckwith, A.L.J.; Schiesser, C.H. Tetrahedron 1985, 41, 3925.
(13) Typical experimental procedure : To a stirred and refluxing solution
of 2 (2 mmol) containing azoisobutyronitrile (AIBN) (0.2 equiv.) in
dry benzene (6 ml), tributyltin hydride (2 equiv.) was added
dropwise over 2 h. The reaction mixture was continued at this
temperature for 4 h, then cooled to 0°C and quenched with H2O (10
ml). The residue was extracted with dichloromethane, washed with
H2SO4 (1N), NaHCO3 sat. and NaCl sat. solutions. The organic
phase was dried over MgSO4, filtered and evaporated under
vacuum. The residue was subsequently purified by flash column
chromatography on silica gel with CH2Cl2 as eluent and HPLC
using a Nucleosil 5 C18 column eluted with CH3CN/TFA (1%) to
give 3 and 4.
Selected data : e.g. 3d ; 13C NMR (75.5 MHz, CDCl3) : 207.54
(CO), 190.22 (CO), 136.27 (C quat.), 129.25 (C quat.), 128.44
(CH), 126.47 (CH), 50.67 (CH), 33.13 (CH2), 25.64 (CH2), 24.51
(CH2), 17.27 (CH). MS : m/z (EI) : 206 (M+., 100), 178 (18), 163
(8), 150 (39), 135 (22), 121 (14), 109 (15), 96 (14), 77 (13), 65 (28),
55 (18), 45 (39). 4a ; 13C NMR : 206.13 (CO), 146.85 (C quat.),
139.76 (C quat.), 130.81 (CH), 129.57 (CH), 128.45 (CH), 119.27
(CH), 46.56 (CH), 41.30 (CH2), 35.55 (CH), 27.93 (CH2), 24.90
(CH2), 23.11 (CH2). MS : m/z (EI) : 186 (M+., 82), 185 (25), 158
(47), 130 (98), 115 (100), 102 (8), 89 (13), 77 (15), 63 (17), 51 (9).
Scheme 6
In the first case, the radical has been closed only by the 7-endo-trig
process, it should be helpful for the subsequent introduction at this
position of the keto group necessary for beticolin synthesis. The second
case gave the 6-exo-trig mode (thermodynamically more stable
product), indeed the presence of double bonds has made the system
more complex.
(14) Shimazaki, M.; Huang, Z-H; Goto, M.; Suzuki, N.; Ohta, A.
In summary, we have succeeded in the synthesis of seven-membered
ring radical-mediated cyclisations. These results should be useful for
1990, 677.
Synthesis