822
R. M. Adlington et al.
LETTER
The natural product 2, substituted by alkenyl and carboxy-
ethyl groups, has been isolated from three different fun-
gi.3,8,17 This compound can also be prepared using our
methodology, thus iodide 15 was prepared by conjugate
addition to the acetylenic ester followed by quench of the
copper enolate with iodine. Coupling of 15 with borole 16
under modified Suzuki conditions18 gave a mixture of es-
ters, which were subjected to acetal hydrolysis, oxidation,
ester hydrolysis and anhydride formation to yield the
natural product 2 in 45% overall yield (Scheme 7).
Acknowledgement
We thank the EPSRC for a studentship (to R. J. C.).
References
(1) New address: R. J. Cox, Department of Chemistry, Colorado
State University, Fort Collins, Colorado 80523, USA.
(2) Weidenmüller, H.-L.; Cavagna, F.; Fehlhaber, H.-W.; Präve,
P. Tetrahedron Lett. 1972, 13, 3519.
(3) Jabbar, A.; Hasnat, A.; Bhuiyan, S. A.; Rashid, M. A.; Reza,
S. Pharmazie 1995, 50, 706.
(4) (a) Nikawa, M.; Adachi, T.; Hirai, Y.; Tagawa, M. Jap P 10
316 510/1998, 1998; Chem. Abstr. 1999, 130, 80430f.
(b) Hirata, H.; Nakatani, S.; Kato, A.; Aiba, T.; Oohashi, Y.;
Goto, M. Jap P 5 294 952/1993, 1993; Chem. Abstr. 1994,
120, 296789w.
O
MeO2C
MeO2C
I
i
O
15
O
Br
O
(5) Weber, W.; Semar, M.; Anke, T.; Bross, M.; Steglich, W.
Planta Med. 1992, 58, 56.
(6) Mondal, G.; Dureja, P.; Sen, B. Indian J. Exp. Biol. 2000, 38,
84.
O
O
ii
16
B
(7) Singh, S. B.; Zink, D. L.; Liesch, J. M.; Goetz, M. A.;
Jenkins, R. G.; Nallin-Omstead, M.; Silverman, K. C.; Bills,
G. F.; Mosley, R. T.; Gibbs, J. B.; Albers-Schonberg, G.;
Lingham, R. B. Tetrahedron 1993, 49, 5917.
(8) Aldridge, D. C.; Carman, R. C.; Moore, R. B. J. Chem. Soc.,
Perkin Trans. 1 1980, 2134.
(9) (a) Baldwin, J. E.; Barton, D. H. R.; Bloomer, J. L.;
Jackman, L. M.; Rodriguez-Hahn, L.; Sutherland, J. K.
Experientia 1962, 18, 345. (b) Barton, D. H. R.; Godinho, L.
D. S.; Sutherland, J. K. J. Chem. Soc. (C) 1965, 1779.
(10) Isaka, M.; Tanticharoen, M.; Thebtaranonth, Y. Tetrahedron
Lett. 2000, 41, 1657.
RO2C
RO2C
iii - v
2
O
O
R = Me or Et
Scheme 7 Reagents and conditions: i, Mg, THF, I2 (cat.) then bro-
mide added, 25 ºC, 1.5 h then added to CuBr SMe2, THF, –40 ºC, 1 h
then MeO2CC CCO2Me, THF, –60 ºC, 1.75 h then I2, THF, –70 ºC,
2.5 h, 86%; ii, 16, Pd(OAc)2 (cat.), Ph3P (cat.), K2CO3, EtOH, reflux,
3 h; iii, 5% aq HCl, THF, 30 ºC, 36 h; iv, Na2Cr2O7 2H2O, H2SO4,
H2O, Et2O, 0 ºC, 2 h; v, 1 M aq NaOH, r.t., 19 h then 6 M aq HCl, 52%
(4 steps).
(11) Ratemi, E. S.; Dolence, J. M.; Poulter, C. D.; Vederas, J. C.
J. Org. Chem. 1996, 61, 6296.
(12) Baldwin, J. E.; Beyeler, A.; Cox, R. J.; Keats, C.; Pritchard,
G. J.; Adlington, R. M.; Watkin, D. J. Tetrahedron 1999, 55,
7363.
(13) Jabri, N.; Alexakis, A.; Normant, J. F. Tetrahedron Lett.
1981, 22, 959.
(14) All new compounds described in this communication have
been fully characterised by 1H and 13C NMR, IR, mass
spectroscopy and HRMS.
(15) Almassi, F.; Ghisalberti, E. L.; Rowland, C. Y. J. Nat. Prod.
1994, 57, 833.
(16) Itoh, S.; Esaki, N.; Masaki, K.; Blank, W.; Soda, K. J.
Ferment. Bioeng. 1994, 77, 513.
(17) Yamanishi, R.; Okada, K.; Tamugi, N.; Iwashima, M.;
Iguchi, K. Bull. Chem. Soc. Jpn. 2000, 73, 2087.
(18) Yanagi, T.; Oh-e, T.; Miyaura, N.; Suzuki, A. Bull. Chem.
Soc. Jpn. 1989, 62, 3892.
In summary, we have demonstrated the addition of alkyl-
and allylcopper reagents to dimethyl acetylenedicarboxy-
late, followed by reaction of the copper enolate with a
variety of reagents. These conditions provide a maleic
diester substituted by an allyl or alkenyl substituent in one
-position and either iodine, an allyl bromide, or an alke-
nyl iodide at the other -position. This diester is then sub-
jected to selective oxidation and hydrolysis reactions to
give a disubstituted maleic anhydride. This general and
facile route provides an excellent method to make this
class of compounds.
Synlett 2002, No. 5, 820–822 ISSN 0936-5214 © Thieme Stuttgart · New York