Scheme 1. New Synthetic Strategy towards Acylsilanes
Scheme 2. Synthesis of R-Hydroxyallylsilanes
isomerization of allylic alcohols14 and the corresponding
tandem isomerizationꢀaldolization process,15 we envisaged
a new strategy for the preparation of acylsilanes (Scheme 1).
Starting from type 1 R-hydroxyallylsilanes, the isomer-
ization process should lead to the corresponding acylsi-
lanes 2 while, on reaction with aldehydes, the tandem
process should afford aldol-type derivatives 3. Both series
of acylsilanes appear as attractive intermediates for further
synthetic applications. This strategy requires first an easy
access to type 1 R-hydroxyallylsilanes with sufficient flex-
ibility to introduce the different substituents, especially
around silicon. Then appropriate catalysts and reaction
conditions, compatible with the sensitive acylsilane moi-
ety, must be designed for the transition-metal-mediated
reactions. Further, we considered it interesting to study the
effect of the different silyl groups on the diastereoselec-
tivity of the tandem isomerizationꢀaldolization process.
Three different strategies have been used to prepare the
desired R-hydroxyallylsilanes, and the results are reported
in Scheme 2. In one avenue, allylic alcohols are silylated
and then submitted toa retro-Brook rearrangement togive
the desired products.16 This versatile method allows the
introduction of different alkyl substituents around the
silicon (RSi), from trimethyl to triisopropyl and dimethyl
tert-butyl, as demonstrated by the preparation, in good
yield, of 1a to 1h. A second method (route B) involves the
addition of a silyl anion to an enal. Moreover, this direct
method requires at least one aryl substituent on silicon to
prepare the lithium anion.17 It is therefore complementary
to the previous one and has been employed for the pre-
paration, in moderate yield, of 1i. Further, in the case of 1i,
route A gives only a very poor yield (11%). The third route
uses a cross metathesis reaction18 between the preceding
R-hydroxyallylsilane 1i and an alkene. It is useful in the
case of derivatives with substituents R not compatible with
a Isolated yield; b all products were characterized by 1H NMR, 13C
NMR and Mass Spectral data.
the previous, strongly basic, reaction conditions and has
been demonstrated with ketone 1j.
With this series of intermediates in hand, it was possible
to study the transition-metal-mediated reactions. The iso-
merization of allylic alcohols to saturated carbonyls is a
well-known process,19 but to the best of our knowledge, it
has never been employed for the preparation ofacylsilanes.
Various types of catalysts could be used for this isomeriza-
tion, but in this particular case, they must be compatible
with the sensitive acylsilane moiety.20 We have selected
nickel hydride since it proved to be very mild and effi-
cient in our recent work for the tandem isomerizationꢀ
aldolization or isomerizationꢀMannich reactions.15 After
optimization of the reaction conditions, with 10 mol % of
this catalyst at 30 to 60 °C, the isomerization proved to
be efficient affording the desired acylsilanes 2aꢀ2j in good
to excellent yields (Table 1). For the most difficult cases,
an increase in catalyst quantity to 20 mol % (2f, 2g) or
40 mol % (2h) and higher temperatures were required to
obtain the products in fair-to-good yields and short reac-
tion times. All these silanes have spectral and analytical
data in agreement with the indicated structures.
ꢀ
(14) (a) Cherkaoui, H.; Soufiaoui, M.; Gree, R. Tetrahedron 2001, 57,
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2379. (b) Uma, R.; Davies, M. K.; Crevisy, C.; Gree, R. Eur. J. Org.
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(20) For instance due to the known sensitivity of acylsilanes to light,
Fe(CO)5 (under photochemical activation) cannot be used in that case
although it is an efficient catalyst in general.
(21) (a) Reactions of acyl silane enolates: Schinzer, D. Synthesis 1989,
179. (b) Tandem aldolꢀTishchenko reactions: Honda, M.; Iwamoto, R.;
Nogami, Y.; Segi, M. Chem. Lett. 2005, 34, 466. (c) Mukaiyamaꢀaldol
reactions: Honda, M.; Oguchi, W.; Segi, M.; Nakajima, T. Tetrahedron
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M.; Oshima, K.; Utimoto, K. Tetrahedron Lett. 1995, 36, 5353.
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