A. Fernaꢀndez-Mateos et al. / Tetrahedron 62 (2006) 7809–7816
7815
dropwise with stirring to a solution of 18 (6 g, 21.89 mmol)
in acetone (253 mL) at 0 ꢀC. The resulting mixture was
stirred at this temperature for an additional 30 min. Then,
isopropilic alcohol was added. The solvent was evaporated
under reduced pressure to afford a residue, which was dis-
solved in water and extracted with ether. The extracts were
washed with brine, dried and evaporated to afford the epoxy-
ketone 16 (5.5 g, 93%).
ketone 20 (41 mg, 0.16 mmol) in CH2Cl2 (1 mL) at
ꢁ10 ꢀC under argon, were added catalytic Na2CO3 and
m-CPBA (28 mg, 0.16 mmol). The reaction mixture was
gradually warmed to room temperature, and stirred for 3 h
at room temperature. Then, a 5% solution of Na2S2O3 was
added and the resulting heterogeneous mixture was stirred
for 15 min. The organic layer was separated, and the aque-
ous phase was extracted with CH2Cl2. The combined organic
extracts were washed with saturated NaHCO3, water and
brine, and then dried (Na2SO4). Evaporation of the solvent
afforded the epoxyketone 21 (30 mg, 85%) as a colourless
solid: mp 97–100 ꢀC; IR 2924, 1711, 1458 cmꢁ1; 1H NMR
d: 0.94 (3H, s), 1.01 (3H, s), 1.35 (3H, s), 1.93 (2H, m),
2.11 (1H, m), 2.21 (1H, m), 2.46 (1H, m), 2.61 (1H, m),
3.44 (1H, dd, J¼7 Hz, J0¼11.4 Hz), 3.57 (1H, br s), 7.1–
7.4 (5H, m) ppm; 13C NMR d: 17.8 (CH3), 26.5 (CH3),
27.6 (CH3), 30.7 (CH2), 32.7 (C), 36.6 (CH2), 36.7 (CH2),
42.3 (CH), 56.1 (C), 56.7 (CH), 74.1 (C), 126.3 (CH),
127.7 (2CH), 130.4 (2CH), 138.6 (C), 213.2 (C) ppm;
Anal. Calcd for C16H22O2: C, 79.30; H, 7.49. Found: C,
79.69; H, 7.78; MS m/z (relative intensity) 255 (25,
M+ꢁ15), 197 (100), 156 (66), 115 (46), 91 (67), 77 (46),
55 (52); HRMS (ESI): 271.1690 (M++H, C18H23O2), calcd
271.1693.
3.1.19. Cyclization of the epoxyketone 16 with n-Bu3SnH.
A solution of tributyltin hydride (2.8 mL, 10.5 mmol) in benz-
ene (300 mL) was added via a dropping funnel (4.3 mmol/h)
to a refluxing solution of the epoxyketone 16 (9.5 g,
34.9 mmol) and AIBN (1.7 mmol) in benzene (700 mL)
under argon. The reaction mixture was refluxed for 8 h.
Removal of the solvent afforded a crude residue, which
was purified by chromatography. Eluting with hexane–ethyl
acetate (9:1) furnished epoxyketone 16 (4.7 g, 50%), as a
colourless oil. Eluting with hexane–ethyl acetate (8:2)
furnished enone 13 (625 mg, 14%), as a colourless oil.
Eluting with hexane–ethyl acetate (8:2) furnished 7a-
hydroxy-3a,7,7-trimethyl-3-phenyl-octahydro-inden-4-one
19 (709 mg, 16%), as a colourless oil: IR 3518, 2965,
1
1694 cmꢁ1; H NMR d: 0.76 (3H, s), 1.06 (6H, s), 1.7–2.2
(6H, m), 2.61 (2H, m), 3.67 (1H, dd, J¼6.8 Hz, J0¼11.3 Hz),
7.1–7.3 (5H, m) ppm; 13C NMR d: 17.5 (CH3), 22.4 (CH3),
25.9 (CH3), 28.4 (CH2), 32.6 (CH2), 34.2 (CH2), 36.1 (CH2),
37.6 (C), 51.0 (CH), 62.5 (C), 87.6 (C), 126.3 (CH), 127.8
(2CH), 129.5 (2CH), 141.0 (C), 214.5 (C) ppm; MS m/z (rel-
ative intensity) 254 (53, M+ꢁ18), 198 (60), 173 (64), 159
(100), 115 (56), 91 (83), 70 (48), 55 (90); HRMS (ESI):
273.1858 (M++H, C18H25O2), calcd 273.1849. Eluting
with ethyl acetate furnished 2-methyl-1,3-cyclohexanodione
14 (1.8 g, 69%), as a white solid identified by comparison
with a standard.
Acknowledgements
Financial support for this work from the Ministerio de Cien-
´
cia y Tecnologıa of Spain (PPQ2002-00290) and the Junta de
Castilla y Leon (SA027/03) is gratefully acknowledged.
´
References and notes
1. (a) Taylor, D. A. H. Prog. Chem. Org. Nat. Prod. 1984, 45, 1;
(b) Champagne, D. E.; Koul, O.; Isman, M. B.; Scudder,
G. G. E.; Towers, G. H. N. Phytochemistry 1992, 31, 377; (c)
Akhila, A.; Rani, K. Prog. Chem. Org. Nat. Prod. 1999, 78, 48.
3.1.20. 3a,7,7-Trimethyl-3-phenyl-2,3,3a,5,6,7-hexa-
hydro-inden-4-one 20. To a solution of the hydroxyketone
19 (200 mg, 0.7 mmol) in dry CH2Cl2 (3.5 mL) at 0 ꢀC
under argon were gradually added pyridine (0.2 mL) and
SOCl2 (0.1 mL, 1.5 mmol). The mixture was stirred at
0 ꢀC for 2 h and then poured into ice water. The organic layer
was separated, and the aqueous phase was extracted with
CH2Cl2. The combined extracts were washed with NaHCO3
(5%) and brine, and then dried (Na2SO4). Evaporation of the
solvent left a crude, which was purified by flash chromato-
graphy. Elution with hexane–ethyl acetate (93:7) afforded
unsaturated ketone 20 (516 mg, 74%), as a white solid, mp
ꢀ
2. (a) Fernandez-Mateos, A.; de la Fuente Blanco, J. A. J. Org.
Chem. 1990, 55, 1349; (b) Fernandez-Mateos, A.; Lopez
´
ꢀ
Barba, A. J. Org. Chem. 1995, 60, 3580; (c) de la Fuente
ꢀ
Blanco, J. A.; Marugan, J. J.; Cross, S. S.; Fernandez-Mateos,
A.; Garcıa, S.; Menendez, A. Bioorg. Med. Chem. Lett. 1995,
ꢀ
´
´
ꢀ
5, 1471; (d) Fernandez-Mateos, A.; Pascual Coca, G.; Rubio
Gonzalez, R.; Tapia Hernandez, C. Tetrahedron 1996, 52,
ꢀ
ꢀ
´
4817; (e) Fernandez Mateos, A.; Pascual Coca, G.; Perez
Alonso, J. J.; Rubio Gonzalez, R. Synlett 1996, 1134; (f)
ꢀ
ꢀ
ꢀ
ꢀ
Fernandez-Mateos, A.; Pascual Coca, G.; Rubio Gonzalez,
R.; Tapia Hernandez, C. J. Org. Chem. 1996, 61, 9097; (g)
1
70–71 ꢀC; IR 2926, 1717, 1458, 1377 cmꢁ1; H NMR d:
ꢀ
ꢀ
´
Fernandez Mateos, A.; Pascual Coca, G.; Perez Alonso, J. J.;
1.03 (3H, s), 1.23 (3H, s), 1.31 (3H, s), 1.65 (1H, m), 1.90
(1H, m), 2.32 (1H, m), 2.50 (1H, m), 2.72 (2H, m), 3.80
(1H, dd, J¼8.4 Hz, J0¼10.8 Hz), 5.63 (1H, dd, J¼1.6 Hz,
J0¼3.2 Hz), 7.1–7.6 (5H, m) ppm; 13C NMR d: 21.0
(CH3), 29.4 (CH3), 30.2 (CH3), 33.6 (C), 34.5 (CH2), 36.2
(CH2), 38.3 (CH2), 50.5 (CH), 61.6 (C), 122.7 (CH), 126.2
(CH), 127.7 (2CH), 130.2 (2CH), 140.5 (C), 154.5 (C),
215.1 (C) ppm; MS m/z (relative intensity) 254 (30, M+),
239 (12), 198 (100), 183 (40), 115 (45), 91 (84), 77 (53),
65 (24), 55 (63); HRMS (ESI): 255.1741 (M++H,
C18H23O), calcd 255.1744.
ꢀ
Rubio Gonzalez, R.; Simmonds, M. S. J.; Blaney, W. M.
Tetrahedron 1998, 54, 14989; (h) Fernandez-Mateos, A.;
ꢀ
´
Lopez Barba, A.; Pascual Coca, G.; Rubio Gonzalez, R.;
Tapia Hernandez, C. Synlett 1995, 409; (i) Fernandez-
ꢀ
ꢀ
ꢀ
´
Mateos, A.; Lopez Barba, A.; Pascual Coca, G.; Rubio
Gonzalez, R.; Tapia Hernandez, C. Synthesis 1997, 1381; (j)
ꢀ
ꢀ
ꢀ
´
Fernandez Mateos, A.; Martın de la Nava, E. M.; Pascual
Coca, G.; Rubio Gonzalez, R.; Ramos Silvo, A. I.;
ꢀ
Simmonds, M. S. J.; Blaney, W. M. J. Org. Chem. 1998, 63,
ꢀ
´
9440; (k) Fernandez-Mateos, A.; Martın de la Nava, E. M.;
Rubio Gonzalez, R. Synthesis 2002, 1728; (l) Fernandez-
ꢀ
ꢀ
´ ´
Mateos, A.; Mateos Buron, L.; Martın de la Nava, E. M.;
ꢀ
Rubio Gonzalez, R. J. Org. Chem. 2003, 68, 3585; (m)
3.1.21. 3a,7,7-Trimethyl-3-phenyl-hexahydro-1-oxa-
cyclopropa[c]inden-4-one 21. To a stirred solution of