similar to that of doubly activated compounds.6 The impor-
tance of this transformation is further stressed by the fact
that intramolecular allylation of ester and ketone enolates
can be a surprisingly difficult reaction. In the whole chemical
literature we were able to find only four examples of
intramolecular allylations of ester,7 ketone,8 or amide eno-
lates.9 In the course of a project directed toward the total
synthesis of the antibiotic abyssomicin,10 we needed a method
for the efficient vinylcyclohexane ring-closure from the
corresponding proenolate. Several attempts to accomplish this
transformation under conventional experimental conditions,
as delineated in Scheme 1, (KHMDS, THF, with or without
ing enamine separately, which would be inconvenient and
of limited synthetic value, we designed a catalytic cycle, as
represented in Scheme 2, which would create in situ the
Scheme 2. Mechanism of the [Pd]/Amine Cocatalyzed
Cyclization
Scheme 1. Attempted Intramolecular Allylation of Esters
required reactive intermediates. The salient feature of this
concept is the combination of organocatalysis13 and organo-
transition metal catalysis. The issue of our concern was the
fact that both catalysts (Pd and amine) must operate on the
same molecule; given the reversible nature of all steps and
substoichiometric quantities of the catalysts, the question was
whether the active intermediate 3senamine of the π-allyl
palladium complexswould be present in sufficiently high
concentration to secure an efficient synthetic transformation.
The feasibility of the envisaged protocol was tested in the
reaction of 4 with catalytic amounts of Pd(PPh3)4, pyrrolidine,
and one equivalent of triethylamine, in THF as a solvent, at
rt (conditions A). Much to our delight, a rapid reaction took
place, giving rise to 2-vinyl-cyclopentanecarbaldehyde 12,
which was isolated in 72% yield (Table 1, entry 1). The
cyclization was stereoselective, with the ratio of diastereo-
isomers trans:cis ) 11:1. No reaction took place in the
absence of any of the two catalysts, thus confirming the
proposed mechanism. While this research was underway,
Cordova reported a similar approach to the intermolecular
allylation of carbonyl compounds, using allyl acetate as the
electrophile, in DMSO as a solvent.14 We found these
conditions also suitable for cyclizations, which occurred with
comparable yields (conditions B, entry 2). Regioisomeric,
HMPA, -78 °C to 50 °C) failed, with the substrates either
not reacting or decomposing under more energetic reaction
conditions. In order to enhance the reactivity of the allylic
part of the molecule, the reaction was performed in the
presence of a catalytic amount of Pd(PPh3)4; in this case a
smooth reaction occurred; however, the product was not the
cyclohexane derivative 1, but the corresponding diene 2. Not
surprisingly, the ester enolate behaved more as a base than
as a nucleophile, promoting the elimination of HBr from the
π-allyl palladium species.11
Thus, softer nucleophiles were required, and we turned
our attention toward enamines, whose use in intermolecular
reactions with π-allyl palladium species has literature
precedents.12 However, instead of preparing the correspond-
(6) House, H., O. Modern Synthetic Reactions, 2nd ed.; The Benjamin/
Cummins Publishing Company: Menlo Park, 1972; p 494.
(7) Kim, D.; Lim, J. I.; Shin, K. J.; Kim, H. S. Tetrahedron Lett. 1993,
34, 6557.
(8) Watanabe, K.; Suzuki, J.; Aoki, K.; Sakakura, A.; Suenaga, K.;
Kigoshi, H. J. Org. Chem. 2004, 69, 7802.
(9) (a) Jo, H.; Li, J.; Kim, H.; Kim, S.; Kim, D. Tetrahedron Lett. 2003,
44, 7043. (b) Kim, D.; Choi, W. J.; Hong, J. Y.; Park, I. Y.; Kim, Y. B.
Tetrahedron Lett. 1996, 37, 1433.
(10) Unpublished results. For the isolation and structure elucidation of
abyssomicin, see: Bister, B.; Bishoff, D.; Strobele, M.; Riedlinger, J.;
Reicke, A.; Wolter, F.; Bull, A. T.; Zahner, H.; Fiedler, H. P.; Sussmuth,
R. D. Angew. Chem., Int. Ed. 2004, 43, 2574.
(12) (a) Hiroi, K.; Abe, J.; Suya, K.; Sato, S.; Koyama, T. J. Org. Chem.
1994, 59, 203. (b) Weix, D. J.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129,
7720.
(13) (a) Berkessel, A.; Groger, H. Asymmetric Organocatalysis: From
Biomimetic Concepts to Applications in Asymmetric Synthesis; Wiley:
Weinheim, 2005. For review articles on organocatalysis, see: (b) Dalko,
P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138. (c) Dalko, P. I.;
Moisan, L. Angew. Chem., Int. Ed. 2001, 40, 3726. (d) The 8th issue of
Acc. Chem. Res. 2004, 37, several reviews on organocatalysis.
(14) Ibrahem, I.; Cordova, A. Angew. Chem., Int. Ed. 2006, 45, 1952.
(11) A review article on eliminations of π-allyl palladium derivatives:
I. Shimizu, in ref 2a), p 1981.
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