Scheme 3
noacetaldehyde in the presence of an acidic catalyst and
to furnish cis alkene 24. Removal of the trityl residue from
24 followed by oxidation of the resultant alcohol 25 gave
an aldehyde, which upon Takai-Utimoto reaction22 with
iodoform led to iodoalkene 26.23 The silyl ether was cleaved
from 26 to yield alcohol 27 as the coupling partner for 20.
The reaction of 27 with 20 under Nozaki-Hiyama-Hishi
conditions24 led to a mixture of two alcohols in the ratio
3.5:1. The major R alcohol 28 is the result of Felkin-Anh
attack at the si face of aldehyde 20 and its NMR spectra
matched precisely those of natural3 and synthetic7 solan-
delactone E. Similarly, the spectral data for the minor â
alcohol 29 were identical with those reported for solandelac-
tone F.3 The proportion of 28 to 29 corresponds closely to
the ratio of constanolactones A (9R OH) and B (9â OH)
obtained from an analogous Nozaki-Hiyama-Kishi cou-
pling of a trans iodoalkene with a cyclopropanecarboxalde-
hyde.5
In summary, we have confirmed through synthesis the
revised structure of solandelactone E put forward by Martin7
and we have firmly established the stereostructure of
solandelactone F.
However, uncertainty remains regarding configurational
assignments made to other solandelactones.3 Our strategy
invoking Nagao asymmetric aldol methodology for establish-
ing configuration at C7, directed cyclopropanation, Claisen
rearrangement for octalactone construction, and Nozaki-
Hiyama-Kishi coupling for linking two major fragments at
C11,12 offers an effective means for determining the absolute
stereochemistry of other members of the solandelactone
series.
effect in situ Claisen rearrangement of the ketene acetal
derived from oxidative elimination of selenium as previously
described15-17 led to an inseparable mixture of products
which contained <30% of lactone 19. In an alternative move
to reach this target,18 16 was first converted to cyclic
carbonate 17 with triphosgene and 17 was then reacted with
Petasis’ reagent.19 Ketene acetal 18 underwent in situ Claisen
rearrangement in hot toluene to produce lactone 19 in 64%
yield from 17. Cleavage of the silyl ether from 19 followed
by oxidation of the resultant alcohol gave aldehyde 20.
Synthesis of the acyclic segment of the solandelactones
for coupling with 20 commenced from dihydroxy ester 21,
prepared from dimethyl (S)-(+)-malate.20 Diol 21 was
advanced to its protected derivative 22 and then to alcohol
23 by reduction of the ester (Scheme 3). Subsequent
oxidation yielded an unstable aldehyde21 that underwent
Wittig olefination with hexyltriphenylphosphonium bromide
(8) White, J. D.; Lincoln, C. M.; Yokochi, A. F. T. Chem. Commun.
2004, 2846.
(9) Pappo, R.; Alen, D. S., Jr.; Lemieux, R. U.; Johnson, W. S. J. Org.
Chem. 1956, 21, 478.
(10) Phillips, A. J.; Guz, N. R. Org. Lett. 2002, 4, 2253.
(11) Evans, D. A.; Starr, J. T. Angew. Chem., Int. Ed. 2002, 41, 1787.
(12) Nagao, Y.; Hagiwara, Y.; Kumagai, T.; Ochiai, M.; Inoue, T.;
Hashimoto, K.; Fujita, E. J. Org. Chem. 1986, 51, 2391.
(13) Charette, A. B.; Lebel, H. J. Org. Chem. 1995, 60, 2966.
(14) Smith, A. B. III; Simov, V. Org. Lett. 2006, 8, 3315.
(15) (a) Carling, R. W.; Holmes, A. B. J. Chem. Soc., Chem. Commun.
1986, 325. (b) Robinson, R. A.; Clark, J. S.; Holmes, A. B. J. Am. Chem.
Soc. 1993, 115, 10400. (c) Burton, J. W.; Clark, J. S.; Derrer, S.; Stork, T.
C.; Bendall, J. G.; Holmes, A. B. J. Am. Chem. Soc. 1997, 119, 7483.
(16) Paterson, I.; Florence, G. J.; Gerlach, K.; Scott, J. P.; Sereinig, N.
J. Am. Chem. Soc. 2001, 123, 9535.
(17) Baudat, R.; Petrzilka, M. HelV. Chim. Acta 1979, 62, 1406.
(18) Anderson, E. A.; Davidson, J. E. P.; Harrison, J. R.; O’Sullivan, P.
T.; Burton, J. W.; Collins, I.; Holmes, A. B. Tetrahedron 2002, 58, 1943.
(19) Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc. 1990, 112, 6392.
(20) Saito, S.; Hasegawa, T.; Inaba, M.; Nishida, R.; Fujii, T.; Nomizu,
S.; Moriwake, T. Chem. Lett. 1984, 1389.
(21) (a) Solladie´, G.; Hamdouchi, C.; Ziani-Che´rif, C. Tetrahedron:
Asymmetry 1991, 2, 457. (b) Chattopadhyay, A. J. Org. Chem. 1996, 61,
6104.
Acknowledgment. We are grateful to David B. Chan,
Oregon State University, for experimental assistance. Finan-
cial support for this work was provided by the National
Science Foundation (0413994-CHE).
Supporting Information Available: Experimental pro-
cedures and NMR spectra of new compounds. This material
(22) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.;
Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048.
(23) Pietruszka, J.; Wilhelm, T. Synlett 2003, 1698.
(24) Kishi, Y. Tetrahedron 2002, 58, 6239.
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