E. Kaasalainen et al. / Tetrahedron Letters 47 (2006) 5669–5672
5671
8. Bull, J. R.; de Koning, P. D. Synthesis 2000, 1761–1765;
Bull, J. R.; Thomson, R. I. J. Chem. Soc., Perkin Trans. 1
1990, 241–251.
O
Ha
Me
Ha
Ar
Ar
Me
9. Reviews: Gibson, S. E.; Stevenazzi, A. Angew. Chem. Int.
Ed. 2003, 42, 1800–1810; Brummond, K. M.; Kent, J. L.
Tetrahedron 2000, 56, 3263–3283.
O
Hb
Hb
a
b
10. Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.;
Foreman, M. I. J. Chem. Soc., Perkin Trans. 1 1973, 977.
11. Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.
J. Chem. Soc., Perkin Trans. 1 1973, 975.
12. La Belle, B. E.; Knudsen, M. J.; Olmstead, M. M.; Hope,
H.; Yanuck, M. D.; Schore, N. E. J. Org. Chem. 1985, 50,
5215; MacWhorter, S. E.; Sampath, V.; Olmstead, M. M.;
Schore, N. E. J. Org. Chem. 1988, 53, 203–205; Schore, N.
E.; Najdi, S. D. J. Am. Chem. Soc. 1990, 112, 442–444;
Kowalczyk, B. A.; Smith, T. C.; Dauben, W. G. J. Org.
Chem. 1998, 63, 1379–1389; Mayo, P.; Tam, W. Tetra-
hedron 2001, 57, 5943–5952.
13. Shapiro, R. H.; Heath, M. J. J. Am. Chem. Soc. 1967, 89,
5734–5735.
14. Davies, M. W.; Maskell, L.; Shipman, M.; Slawin, A. M.
Z.; Vidot, S. M. E.; Whatmore, J. C. Org. Lett. 2004, 6,
3909–3912.
Scheme 3. Observed ROE correlations.
to depend not only on through-bond inductive effects of
the remote substituents but also to be controlled by
through-space orbital interactions.21 The only examples
of the formation of unsymmetrical rings have been with
bridged alkenes, such as norbornyl- or 8-oxabicy-
clo[3.2.1]oct-6-ene derivatives or strained cyclobut-
enes.12 Due to the insertion of the less hindered face of
the alkene p-bond into a less substituted C–Co–bond
in the cobalt–alkyne complex, the intermolecular PK
reaction commonly yields exo-fused products with the
larger alkyne substrate in the a-position with respect
to the carbonyl. Large allylic substituents on the alkene
tend to align themselves ‘anti’ to the carbonyl group.
15. Sadek, S. A.; Shaw, S. M.; Kessler, W. V.; Wolf, G. C. J.
Org. Chem. 1981, 3259–3262.
The ratios of regioisomers a and b in adducts 8–11 indi-
cate (Scheme 2) that electronic effects exerted by alkyne
substituents have no significant influence on the regiose-
lectivity. However, the fact that the sterically less bulky
phenylacetylene 4 leads to adduct 8a as the major isomer
while regioisomers 9–11b dominate with substituted
phenyl alkynes 5–7, implies that even distant steric ef-
fects, i.e. smaller substitution of 4, may affect the
regioselectivity.
16. Anderson, A.; Boyd, A. C.; Clark, J. K.; Fielding, L.;
Gemmell, D. K.; Hamilton, N. M.; Maidment, M. S.;
May, V.; McGuire, R.; McPhail, P.; Sansbury, F. H.;
Sundaram, H.; Taylor, R. J. Med. Chem. 2000, 43, 4118–
4125.
17. Representative experimental procedure: Phenylacetylene
(0.05 ml, 0.46 mmol) and cobalt octacarbonyl (157 mg,
0.46 mmol) were stirred in DCM (14 ml) under argon for
30 min. Alkene 3 (170 mg, 0.633 mmol) dissolved in 3 ml
of DCM was added to the dark red solution. The reaction
mixture was stirred for 20 min prior to the addition of
t-BuSMe (0.14 ml, 1.110 mmol). The reaction mixture
was stirred for 15 min at rt and then refluxed for three
days. The reaction mixture was adsorbed on silica and
purified by column chromatography (hexane–ethyl acetate
80:1 ! 1:1) yielding 81 mg (55%) of the desired cyclo-
To conclude, 2-phenylcyclopentenone was introduced to
the estrone D-ring via an intermolecular PK reaction
yielding E-ring extended estrone derivatives. Our cur-
rent efforts are aimed at broadening the scope of this
reaction.
pentenone
8 as a white solid. Rf = 0.59 (hexane–
EtOAc = 3:1). ESI HRMS [M+H]+ 399.2327 calculated
399.2324 D = 0.8 ppm.
Acknowledgements
1
18. The H and 13C NMR spectra were recorded at 400 and
100 MHz, respectively in CDCl3 (8a); dH: 7.74 (2H), 7.71
(1H, d, J = 3.2 Hz), 7.39 (2H), 7.33 (1H), 7.19 (1H), 6.70
(1H), 6.61 (1H), 3.76 (s, 3H, CH3O–), 3.42 (1H, s,
@CHCH), 2.82 (2H), 2.61 (1H, d, J = 5.5 Hz, COCH),
2.35 (1H, m), 2.20–2.01 (2H, m), 1.86 (1H, m), 1.77 (2H,
m), 1.65–1.44 (2H, m), 1.42–1.14 (3H, m), 1.00 (3H, s,
CH3C); 13C NMR (100 MHz, CDCl3) (8a); dC: 207.7,
161.6, 157.5, 143.9, 137.7, 132.5, 131.5, 128.5, 128.4, 126.3,
113.8, 111.4, 61.8, 55.2, 49.6, 48.2, 44.6, 43.4, 41.6, 38.4,
34.3, 29.8, 29.6, 27.9, 26.3, 20.9 (8b); dH: 7.81 (1H, CH@),
7.76 (2H, Ph), 7.39 (3H, Ph), 7.17 (1H), 6.70 (1H), 6.61
(1H), 3.76 (s, 3H, CH3O–), 3.01 (2H, m ), 2.82 (2H, m),
2.33 (1H, m), 2.15–1.96 (2H, m), 1.89–1.70 (3H, m), 1.63–
1.38 (3H, m), 1.36–1.09 (2H, m), 0.98 (3H, s, CH3C) (8b);
dC: 210.7, 159.2, 157.5, 145.1, 137.9, 132.2, 131.6, 128.5,
128.4, 127.1, 126.2, 113.7, 111.5, 55.2, 54.9, 49.4, 47.8,
43.4, 42.8, 38.3, 35.1, 30.4, 29.7, 27.8 26.4, 20.6.
The authors kindly acknowledge the Academy of
Finland for financial support (JH, Project No. 205770
and KR, 205729).
References and notes
1. Bull, J. R.; Mountford, P. G. J. Chem. Soc., Perkin Trans.
1 1999, 1581–1587.
2. Bydal, P.; Auger, S.; Poirier, D. Steroids 2004, 69, 325–
342.
3. Fischer, D. S.; Allan, G. M.; Bubert, C.; Vicker, N.;
Smith, A.; Tutill, H. J.; Purohi, A.; Wood, L.; Packham,
G.; Mahon, F.; Reed, M. J.; Potter, B. V. L. J. Med.
Chem. 2005, 48, 5749–5770.
4. Vicker, N.; Lawrence, H. R. R.; Allan, G. M.; Bubert, C.;
Fischer, D. S. M.; Purohit, A.; Reed, M. J.; Potter, B. V.
L. Patent WO 2004085457, CAN 141:332361.
5. Wolfling, J.; Frank, E.; Schneider, G.; Tietze, L. F. Eur. J.
Org. Chem. 1999, 11, 3013–3020.
1
19. (a) All new compounds were characterised by H and 13C
NMR spectroscopic techniques (400 and 100 MHz,
respectively) and by high resolution mass spectroscopy
(ESI MS); (b) Crystal data for 8a: C28H30O2, FW =
398.54, monoclinic P21, a = 11.677(2) b = 6.534(1),
6. Takasu, K.; Ueno, M.; Inanaga, K.; Ihara, M. J. Org.
Chem. 2004, 64, 517–521.
7. Loozen, H. J. J.; Patent WO 0200682, CAN 136:70001.
3
˚
c = 14.350(3) A, b = 100.03(3)°, dc = 1.221 g/cm , Reflec-
tions collected 2922 of which 1875 (Rint = 0.0449)