Umpolung of the reactivity of allylsilanes. Palladium(II) catalyzed cyclization of allylsilyl alcohols: A new route to substituted 2- vinyltetrahydrofurans

Article abstract of DOI:10.1016/S0040-4039(99)02245-5

Functionalized allylsilanes 1-4 undergo palladium(II) catalyzed ring closure to afford 4- and/or 5-substituted 2-vinyltetrahydrofurans (5-8) under mild conditions. The catalytic reactions proceed through (η³- allyl)palladium intermediates forme

Full text of DOI:10.1016/S0040-4039(99)02245-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 1119–1122
Umpolung of the reactivity of allylsilanes. Palladium(II)
catalyzed cyclization of allylsilyl alcohols: a new route to
substituted 2-vinyltetrahydrofurans
István Macsári and Kálmán J. Szabó ∗
Stockholm University, Department of Organic Chemistry, S-106 91 Stockholm, Sweden
Received 8 November 1999; accepted 29 November 1999
Abstract
Functionalized allylsilanes 1–4 undergo palladium(II) catalyzed ring closure to afford 4- and/or 5-substituted
2-vinyltetrahydrofurans (5–8) under mild conditions. The catalytic reactions proceed through (η3-allyl)palladium
intermediates formed by palladadesilylation of the allylsilane substrates. © 2000 Elsevier Science Ltd. All rights
reserved.
Functionalized allylsilanes have proven to be a very useful class of organometallic synthons due to
their potential for highly selective transformations by electrophilic reagents.1a–c The driving force of the
electrophilic attack on allylsilanes is the formation of a β-silicon stabilized carbocation intermediate.1d
Nucleophilic attack on allylsilanes, however, does not benefit from this type of stabilization. Accordingly,
reaction of nucleophiles with allylsilanes requires special reaction conditions, such as an initial metal-
or metalloidal attack on the allylsilane substrate1e–g or oxidative cleavage of the carbon silicon bond.1h–i
For example, palladium(II) catalyzed oxidation of allylsilanes with UV light and molecular oxygen has
been used to prepare α,β-unsaturated carbonyl compounds.1j We have now found that palladium(II)
catalysis can also be employed for allylic substitution of the silyl functionality by nucleophiles. Thus,
in the presence of catalytic amounts of palladium salts, the hydroxy functionality of 6-trimethylsilyl
hexanol derivatives 1–4 easily undergo intramolecular nucleophilic attack on the allylic moiety affording
2-vinyltetrahydrofurans (5–8) in good yields (eq (1), Table 1).
(1)
The allylsilanes (1–4) could easily be obtained by reduction or Grignard reaction of functionalized
allylsilanes 9–11 (eq (2)) prepared by a recently reported efficient palladium(0) catalyzed process.2a The
∗
Corresponding author. E-mail: kalman@organ.su.se (K. J. Szabó)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(99)02245-5
tetl 16173

1120
Table 1
Palladium(II) catalyzed cyclization of allylsilanes 1–4a

1121
choice of solvent is of great importance for the successful accomplishment of the cyclization reaction.
We found that the cyclization is very fast and proceeds with good yield in a number of alcoholic solvents
i
t
(ROH, R=Me, Et, Pr and Bu). However, in other solvents, such as acetonitrile, THF, DMSO, CH2Cl2
and DMF, a slow reaction with a very low conversion occurred.
Since the palladium(II) catalyst is reduced to palladium(0) in the nucleophilic attack, a reoxidant has
to be applied to regenerate the palladium(II) catalyst source. For cyclization of allylsilanes, copper(II)
chloride proved to be the most efficient reoxidant for palladium (entries 1 and 3–8). We have also
tried other reoxidants, such as benzoquinone (BQ) and its derivatives, which are commonly used
in palladium(II) catalyzed allylic oxidation of alkenes and 1,4-oxidation of conjugated dienes.2b,c
Employment of BQ as the oxidant requires acidic reaction conditions2b since a protonation step is
involved in the reduction of BQ to hydroquinone. However, using acidic conditions and BQ as the
reoxidant leads to a very slow reaction with a low yield. The catalyst was usually deactivated before
the starting material was fully converted. The best results (entry 2) with BQ as a reoxidant were achieved
by employing 27 mol% phosphoric acid in a CH2Cl2/MeOH solvent mixture (10:1).
(2)
i
Using 5 mol% Li2[PdCl4] catalyst and CuCl2 as the reoxidant in PrOH 1–4 smoothly undergo
at rt or at a slightly elevated temperature (40°C).3 The reaction is fast with primary (1a–b) and
simple secondary alcohols (2a), and, even sterically hindered tertiary alcohols (2b, 4) are cyclized in
2–4 h at rt. The relatively short reaction time is important for cyclization of 2b and 4 since these
compounds can easily undergo dehydration even under mild reaction conditions. A longer reaction time
is required in the presence of methyl substituents at the three position of the substrate (3a–b). The regio-
and chemoselectivity of the reaction is excellent. The ring closure reaction provides exclusively five
membered rings with the formation of seven membered rings not being observed. The employed solvent
(iPrOH) is also a secondary alcohol, and therefore it is a potential nucleophile. However, products arising
from an external nucleophilic attack by the solvent have not been observed, suggesting that the internal
nucleophilic attack is much faster than the external one. The stereoselectivity of the ring closure is usually
rather poor, as seen by the fact that the two diastereomers of 5, 6a and 7 are formed in approximately the
same ratio.
Mechanism. It is well documented that allylsilanes react with Pd(II) salts affording (η3-allyl)palladium
complexes.4 We could also isolate the intermediary allylpalladium complex of the cyclization reaction (eq
(3)). We have found that the palladadesilylation process is facilitated by alcoholic solvents and chloride
salts, while addition of bases hindered the reaction. (η3-Allyl)palladium complex 12 is an air-stable
species, which does not undergo spontaneous cyclization. Therefore, complex 12 has to be activated to
allow a nucleophilic attack by the hydroxy group. This activation can be achieved by addition of 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ) or CuCl2 to the iPrOH solution of 12. It is interesting to note
that cyclization does not occur in the presence of BQ. This is probably due to the fact that BQ is less able
to activate nucleophilic attack on (η3-allyl)palladium complexes than DDQ, especially in the presence of
chloride ligands.5 Therefore it is important to perform the BQ mediated catalytic reaction under chloride
free conditions (entry 2). We have also found that an increase in the acidity slows down the rate of the

1122
nucleophilic attack. This can easily be explained by the fact that the ring closure involves deprotonation
of the OH group, which is hindered in the presence of acids.
(3)
The above results show that the basicity of the reaction medium has opposite effects on the palladade-
silylation and on the nucleophilic attack of the OH group. Accordingly, neutral conditions are expected
to give the best results, which can be ensured when CuCl2 is used as the reoxidant and activator of the
nucleophilic attack. Using alcoholic solvents is beneficial for both processes of eq (3). The alcoholic
solvents facilitate the elimination of the silyl group under the palladadesilylation through the formation
of stable alkyl-siloxanes, and hindering the silyl migration to the OH group of the substrate. Furthermore,
in the nucleophilic attack the solvent molecules may also act as weak bases providing assistance in the
deprotonation of the hydroxy group.
In summary, we have shown that under mild conditions allyl–silyl alcohols undergo a nucleophilic
substitution reaction in the presence of catalytic amounts of palladium salts and CuCl2. As far as we
know, this is the first example of palladium catalyzed allylic substitution of the silyl functionality by
nucleophiles. In addition, employment of a silyl leaving group offers an interesting alternative to acetate
and carbonate functionalities, which are commonly used in palladium catalyzed allylic substitution
reactions.
Acknowledgements
This work was supported by the Swedish Natural Science Research Council (NFR).
References
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solvent in vacuo and purification of the residual oil by chromatography in pentane/ether afforded the corresponding product.
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