1022
G. Bose, P. Langer
LETTER
O
A second, alternative formal synthesis of lucidone was
developed. We have recently reported the synthesis of
E-configured butenolide 7a by Me3SiOTf-catalyzed cy-
clization of 1,3-bis-silyl enol ether 1a with oxalyl chloride
(Scheme 2).12a Methylation of 7a gave 8a and subsequent
silylation (Me3SiOTf/Et3N) afforded the g-(2-silyloxy-
propenylidene)butenolide 9a. The TiCl4-mediated con-
densation of 9a with benzaldehyde afforded the aldol 10a,
which was transformed into 6a by treatment with TFA.
O
Me3SiO
OSiMe3
OMe
O
i
82%
HO
OMe
1b
7b
ii
92%
O
Me3SiO
O
O
O
O
iii
O
Me3SiO
OSiMe3
O
MeO
MeO
i
93%
OMe
OMe
57%
O
HO
8b
9b
1a
7a
O
62%
iv
ii
66%
Ph
H
O
O
O
MeO
O
O
O
O
O
O
O
Ph
Ph
iii
v
O
HO
MeO
95%
94%
MeO
MeO
Me3SiO
OMe
OMe
10b
8a
9a
6b
O
vi
ref.6
iv
79%
O
O
MeO
MeO
Ph
H
OH
O
O
v
O
Ph
6a
OH
74%
linderone
MeO
Ph
10a
Scheme 3 Formal synthesis of linderone by method 2: i, oxalyl
chloride, Me3SiOTf (0.5 equiv), CH2Cl2, –78 °C to 20 °C; ii, Me2SO4,
K2CO3, acetone, 20 °C; iii, Me3SiOTf, Et3N, Et2O, 0 °C to 20 °C; iv,
TiCl4 (1.0 equiv), CH2Cl2, –78 °C to 20 °C; v, TFA, CH2Cl2, 20 °C
(ref.6).
Scheme 2 Formal synthesis of lucidone by method 2: i, oxalyl chlo-
ride, Me3SiOTf (0.5 equiv), CH2Cl2, –78 °C to 20 °C; ii, Me2SO4,
K2CO3, acetone, 20 °C; iii, Me3SiOTf, Et3N, Et2O, 0 °C to 20 °C; iv,
TiCl4 (1.0 equiv), CH2Cl2, –78 °C to 20 °C; v, TFA, CH2Cl2, 20 °C.
We have reported earlier the synthesis of Z-configured
g-alkylidenebutenolide 7b by cyclization of 1,3-bis-silyl
enol ether 1b with oxalyl chloride (Scheme 3).12a
Butenolide 7b was transformed into g-(2-silyloxypro-
penylidene)butenolide 9b by methylation and subsequent
silylation. The reaction of 9b with benzaldehyde and sub-
sequent treatment with TFA afforded 6b – a known direct
precursor of linderone.6,8a The configuration of 6b was
established by comparison of the spectroscopic data with
those reported in the literature.6
Acknowledgment
Financial support from the Deutsche Forschungsgemeinschaft is
gratefully acknowledged.
References
(1) Kiang, A. K.; Lee, H. H.; Sim, K. Y. J. Chem. Soc. 1962,
4338.
(2) Lee, H. H. Tetrahedron Lett. 1968, 4243.
(3) (a) Takai, M.; Liu, S. Y.; Ogihara, Y.; Iitaka, Y. Chem.
Pharm. Bull. 1977, 25, 1404. (b) Leong, Y.-W.; Harrison,
L. J.; Bennett, G. J.; Kadir, A. A.; Connolly, J. D.
Phytochemistry 1998, 47, 891.
(4) Li, X.-C.; Ferreira, D.; Jacob, M. R.; Zhang, Q.; Khan, S. I.;
ElSohly, H. N.; Nagle, D. G.; Smillie, T. J.; Khan, I. A.;
Walker, L. A.; Clark, A. M. J. Am. Chem. Soc. 2004, 126,
6872.
(5) Aoyama, Y.; Konoike, T.; Kanda, A.; Naya, N.; Nakajima,
M. Bioorg. Med. Chem. Lett. 2001, 11, 1695.
(6) Clemo, N. G.; Gedge, D. R.; Pattenden, G. J. Chem. Soc.,
Perkin Trans. 1 1981, 1448.
(7) Birch, A. J.; Elliot, P. Aust. J. Chem. 1956, 9, 95.
(8) For the synthesis of linderones from phloroglucinols, see:
(a) Lee, H.-H.; Tan, C. H. J. Chem. Soc. 1967, 1583.
(b) For lucidones, see: Lee, H.-H.; Que, Y.-T. J. Chem. Soc.,
Perkin Trans. 1 1985, 453.
The synthetic precursor 6a of lucidone was prepared from
1a via 4a in 4 steps in 25% overall yield (method 1,
Scheme 1). The synthesis of 6a from 1a via 7a was carried
out in 5 steps in 21% overall yield (method 2, Scheme 2).
The synthetic precursor 6b of linderone was prepared
from 1b via 7b in 5 steps in 41% overall yield (method 2,
Scheme 3). Both approaches compare well with known
syntheses of lucidone and linderone.6,8
The synthetic methods reported herein are currently being
employed in the synthesis of other natural products and
natural product analogues.
Synlett 2005, No. 6, 1021–1023 © Thieme Stuttgart · New York