4636
S. K. Bagal et al. / Tetrahedron Letters 46 (2005) 4633–4637
tropic shift from 38 and 43, respectively). Moreover,
our studies have shown that the ÔCcÕ derived dimers
are stable at room temperature in benzene for 24 h. In-
stead, therefore, we favour products 36, 37, 41 and 42
formation via radicaloid dimerisation from either the
ÔCaÕ or ÔCcÕ positions of 35 and 40, in which individual
product forming pathways are subject to steric consider-
ations and under kinetic control.
Conclusion: A general method for the preparation of bis-
butenolides from butenolides via the dimerisation of
captodative stabilised radicaloids generated using
CoCl(PPh3)3 has been developed. The regioselectivity
of the dimerisation process can be controlled to some
extent by the substituent appended adjacent to the car-
bonyl moiety (Cc) of the chlorolactone precursor.
Figure 4. X-ray crystal structure of ( )-41b.
References and notes
1. (a) Huang, B. S.; Sun, J. S.; Chen, Z. L. Zhiwu Xuebao
1992, 34, 614; (b) Endo, K.; Taguchi, T.; Taguchi, F.;
Hikino, H.; Fujimura, H.; Yamahara, J. Chem. Pharm.
Bull. 1979, 27, 2954; (c) Wang, Y. S.; Chang, J. C.; Li, K.
K.; Wu, C. H.; Tin, K.; Liu, Y. H. Shaanxi Xinyiyao 1980,
9, 47.
Figure 5. X-ray crystal structure of ( )-meso 46.
2. Takeda, K.; Horibe, I.; Minato, H. J. Chem. Soc. (C)
1968, 5, 569.
3. Zhang, C. F.; Nakamura, N.; Tewtrakul, S.; Hattori, M.;
Sun, Q. S.; Wang, Z. T.; Fujiwara, T. Chem. Pharm. Bull.
2002, 50, 1195.
.
β
O
α
O
γ
Figure 6.
4. Peng, J.; Franzblau, S. G.; Zhang, F.; Hamann, M. T.
Tetrahedron Lett. 2002, 43, 9699.
5. (a) Lin, Y.; Jin, T.; Wu, X.; Huang, Z.; Fan, J. J. Nat.
Prod. 1997, 60, 27; (b) Huang, Z.; Lin, Y.; Liu, S.; Chan,
W. Indian J. Chem. 1999, 38B, 106; (c) Pu, H. L.; Wang, Z.
L.; Huang, Q. J.; Xu, S. B.; Lin, Y. C.; Wu, X. Y.
Zhongguo Yaolixue Tongbao 2000, 16, 60.
6. Wang, B. D.; Yu, Y. H.; Teng, N. N.; Jiang, S. H.; Zhu,
D. Y. Huaxue Xuebao 1999, 57, 1022.
7. Kouno, I.; Hirai, A.; Jiang, Z. H.; Tanaka, T. Phyto-
chemistry 1997, 46, 1283.
8. Bagal, S. K.; Adlington, R. M.; Marquez, R.; Baldwin,
J. E.; Cowley, A. R. Tetrahedron Lett. 2003, 44, 4993.
9. Bagal, S. K.; Adlington, R. M.; Marquez, R.; Baldwin,
J. E.; Cowley, A. Org. Lett. 2003, 5, 3049.
10. Bagal, S. K.; Adlington, R. M.; Marquez, R.; Baldwin,
J. E. J. Org. Chem. 2004, 69, 9100.
11. Tiecco, M.; Testaferri, L.; Tingoli, M.; Bartoli, D.
Tetrahedron 1990, 46, 7139.
12. Yao, Z. J.; Wu, Y. L. J. Org. Chem. 1995, 60, 1170.
13. Stoilov, I.; Kolaczkowska, E.; Watt, D. S. J. Org. Chem.
1993, 58, 3444.
14. (a) Aresta, M.; Rossi, M.; Sacco, A. Inorg. Chim. Acta
1969, 3, 227; (b) Yamada, Y.; Momose, D.; Iguchi, K.;
Sugiyama, T. Tetrahedron Lett. 1983, 24, 921; (c) Yamada,
Y.; Momose, D. Chem. Lett. 1981, 1277.
15. Janousek, Z.; Merenyi, R.; Viehe, H. G. Acc. Chem. Res.
1985, 18, 148.
16. The atomic coordinates for 30a (Deposition number
CCDC 201013), 8 (Deposition number CCDC 207880),
9 (Deposition number CCDC 207879), 33 (Deposition
number CCDC 254587), 36a (Deposition number CCDC
267716), 41a (Deposition number CCDC 267717), 41b
(Deposition number CCDC 267718) and 46 (Deposition
number CCDC 261268), are available on request from the
Cambridge Crystallographic Data Centre, University
Chemical Laboratory, Lensfield Road, Cambridge CB2
were isolated, that is, 30, and biatractylolide 8, biepias-
terolide 9, 33 and 46, respectively. However, if hydrogen
was appended at the ÔCcÕ site, as in the case of chloro-
butenolides 34 and 39, products generated by dimerisa-
tion of radicals via the ÔCcÕ position were obtained, that
is, 36, 37 and incrustoporin analogue 41,17 and 42,
respectively. In these cases, no ÔCa–Ca0Õ linked adducts,
38 and 43, respectively, were isolated from the product
mixture.
Mechanistically, the formation of the ÔCc–Cc0Õ dimer 36
could most simply be explained by a faster rate of cou-
pling between the less hindered ÔCcÕ centres followed by
tautomerisation. A similar explanation is given for the
formation of dimer 41. ÔCa–Cc0Õ coupled products, that
is, 37 and 42, probably arise again by the result of steric
factors on the rate of formation of the C–C bond. By
this method the dimerisation of chlorolactones to bis-
butenolides with CoCl(PPh3)3 can be performed with
some degree of regiocontrol: the ÔCcÕ position should
be functionalised with methyl or alkyl substituents if
the ÔCa–Ca0Õ dimer product is required (e.g., 30, 8, 9,
33 and 46); however, if the ÔCcÕ derived dimer products
are desired, only hydrogen should be appended at ÔCcÕ
(e.g., 36, 37, 41 and 42). It should be noted that the for-
mation of dimers 36 and 41 could also be postulated to
be derived from intermediate forms of 38 and 43, respec-
tively, via a [3,3] sigmatropic shift,18 possibly catalysed
by cobalt ion complexation.19 However, analogous peri-
cyclic proposals seem unlikely as explanations for the
formation of dimers 37 and 42 (formally a [1,3] sigma-