described the only synthesis of a tricyclic framework of
vinigrol (1).6f,g,o Recently, we reported the formation of the
cis-decalin and bicyclo[5.3.1]undecenone vinigrol subunits
2 and 4 using tandem pericyclic reactions (Scheme 1).6a,b
Scheme 2. Proposed Retrosynthesis
Scheme 1. Previous Approaches
copper(I)-mediated coupling between iodide 15 and alcohol
169 in the presence tetramethylphenantroline and cesium
Scheme 3
However, these initial approaches were plagued by an
incapacity to form the final eight-membered or six-membered
rings via various ring-closing reactions. From our approaches
and those reported by the others groups, we learned that the
formation of two of the three rings of vinigrol can be
achieved without posing serious problems. However, the
formation of the third ring, especially the eight-membered
ring, via alkylation-type reactions or ring-closing metathesis,
remains problematic.6a,e,h We suggest that the preferential
conformation and the compact nature of the substrate are
the responsible factors that inhibit the desired cyclization.
On the basis of these results, we contemplated the
generation of two rings in one step. Thus, we envisaged the
synthesis of tricycle 7 via an intramolecular Diels-Alder
reaction of triene 8 (Scheme 2). The latter could be formed
from an enyne metathesis reaction of alkyne 9 which could
be derived from readily available aldehyde 10.7
carbonate at 90 °C led to the desired enol ether 13 in 83%
yield along with aldehyde 18 in 13% yield as a mixture of
epimer at C2.10 This reaction was particularly sensitive to
Scheme 4
A close inspection of the intramolecular Diels-Alder of
diene 11 reveals that two endo cycloadducts 12 and 13 could
be formed (Scheme 3). At first glance, one might propose
that electronic and steric factors should favor the formation
of 12 over 13. In order to validate this approach, we
investigated the synthesis of a Diels-Alder precursor of
triene 11.
The synthesis began by a Takai olefination of aldehyde
14 to give iodide 15 in 72% yield (Scheme 4).8 Buchwald’s
(6) (a) Barriault, L.; Morency, L. J. Org. Chem. 2005, 70, 8841. (b)
Barriault, L.; Morency, L. Tetrahedron Lett. 2004, 45, 6105. (c) Paquette,
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Y. J. Org. Chem. 1997, 62, 5062. (k) Kito, M.; Sakai, T.; Shirahama, H.;
Miyashita, M.; Matsuda, F. Synlett 1997, 219. (l) Kito, M.; Sakai, T.; Haruta,
N.; Shirahama, H.; Matsuda, F. Synlett 1996, 1057. (m) Mehta, G.; Reddy,
K. S. Synlett 1996, 625. (n) Devaux, J.-F.; Hanna, I.; Fraisse, P.; Lallemand,
J.-Y. Tetrahedron Lett. 1995, 36, 9471. (o) Devaux, J.-F.; Hanna, I.;
Lallemand, J.-Y. J. Org. Chem. 1993, 58, 2349.
the thermal conditions as a slight increase of the temperature
above 90 °C led to a significant increase in the amount of
the Claisen rearrangement product 18. Owing to the facile
epimerization of the resulting aldehyde 18, we turned our
attention toward the use of a Lewis acid that will catalyze
the sigmatropic rearrangement and at the same time reduce
(8) Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986, 108, 7408.
(9) Parziale, P. A.; Berson, J. A. J. Am. Chem. Soc. 1991, 113, 4595.
(10) Nordmann, G.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 4978.
(7) Pattenden, G.; Smithies, A. J.; Tapolczay, D.; Walter, D. S. J. Chem.
Soc., Perkin Trans. 1 1996, 7.
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