Newly designed acylsilanes as versatile tools in organic synthesis

Article abstract of DOI:10.1016/S0022-328X(98)00694-9

Structural variations in acylsilane molecules allow a number of new selective synthetic processes to be performed which lead to sulfur-containing heterocycles, highly functionalized and unsaturated polycarbonyl derivatives, polyenes, and β- and γ-aminoalcohols. The synthesis of these compounds, most of them not easily accessible through conventional routes, takes advantage of the site-selective reactions occurring at the C-Si bonds, of the increased stability of acylsilanes with respect to that of the corresponding aldehydes and of the high diastereofacial selectivity introduced by the SiR₃ group. Herein we report the different synthetic strategies leading to the synthesis of several functionalized acylsilanes and their synthetic applications. The use of new selective polymetallic reagents for the nucleophilic silylation will be presented as well.

Full text of DOI:10.1016/S0022-328X(98)00694-9

Journal of Organometallic Chemistry 567 (1998) 181–189
Newly designed acylsilanes as versatile tools in organic synthesis1
Bianca F. Bonini, Mauro Comes-Franchini, Mariafrancesca Fochi, Germana Mazzanti,
Alfredo Ricci *
Dipartimento di Chimica Organica ‘A. Mangini’, Facolta` di Chimica Industriale, Via Risorgimento No. 4, 40126 Bologna, Italy
Received 3 November 1997
Abstract
Structural variations in acylsilane molecules allow a number of new selective synthetic processes to be performed which lead to
sulfur-containing heterocycles, highly functionalized and unsaturated polycarbonyl derivatives, polyenes, and i- and k-aminoalco-
hols. The synthesis of these compounds, most of them not easily accessible through conventional routes, takes advantage of the
site-selective reactions occurring at the C–Si bonds, of the increased stability of acylsilanes with respect to that of the
corresponding aldehydes and of the high diastereofacial selectivity introduced by the SiR3 group. Herein we report the different
synthetic strategies leading to the synthesis of several functionalized acylsilanes and their synthetic applications. The use of new
selective polymetallic reagents for the nucleophilic silylation will be presented as well. © 1998 Elsevier Science S.A. All rights
reserved.
Keywords: Acysilanes; Polymetallic reagents; Chemioselectivity; Stereoselectivity
1. Introduction
organometallic (mono or polymetallic) reagent in which
the Si is bound to a metal (M), more electropositive
than silicon provides the source for the nucleophilic
silicon R3Si−.
In addition to these two procedures, many other
useful methods [4] have been proposed which, however,
lack generality. This article is aimed at demonstrating
how, through the design and the synthesis of new
acylsilanes, unprecedented synthetic protocols can be
envisioned which lead to a variety of highly functional-
ized and not otherwise easily accessible building blocks.
In spite of the long tradition of acylsilane chemistry
[1], these compounds are still intriguing molecules.
Thus far, several questions related to acylsilane ground
and excited state features are still unanswered and their
reaction behavior reveals striking differences with re-
spect to those observed for ordinary carbonyl
compounds.
The two main synthetic routes to acylsilanes, out-
lined in Scheme 1, are based on electrophilic silylation,
performed according to Corey and Seebach ([2]a) and
by Brook ([2]b) through the quenching of 1,3-lithium-
dithianyl derivatives with ‘R3Si+ equivalents’ such as
silyl halides and on the nucleophilic silylation of car-
boxylic acid derivatives. In the latter approach [3], an
2. Results and discussion
Three different approaches directed to the exploita-
tion of the synthetic usefulness of acylsilanes are shown
in Scheme 2, based on (i) the replacement of the O of
the carbonyl group with an S atom, (ii) the introduction
of unsaturated chains and (iii) the introduction of chiral
frameworks belonging to the class of natural products.
* Corresponding author. Tel.: +39 51 6443635; fax: +39 51
6443654; e-mail: ricci@ ms.fci.unibo.it
1 Dedicated to the memory of Professor Antonino Fava (deceased
December 19, 1997), Professore Emerito of the University of
Bologna.
0022-328X/98/$19.00 © 1998 Elsevier Science S.A. All rights reserved.
PII S0022-328X(98)00694-9

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B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
Scheme 1.
the presence of bases, intramolecular cyclization leading
to formation of 2-silylthiacycloalk-2-enes of different
sizes (Scheme 6).
The Z-h-silyl vinyl sulfides are interesting species as
they combine both vinylsilane and vinyl sulfide func-
tional groups with their opposing polarization on the
olefinic bond. They can be used as starting materials for
useful synthetic transformations according to their syn-
thetic equivalence to vinyl-anion and cation synthons.
Vinylsulfides and substituted vinyl silanes can be syn-
thesized in high yields [8] and with good stereochemical
control by F− induced protodesilylation and Ni-pro-
moted desulfurative alkylation with Grignard reagents,
respectively. On the other hand, open chain and cyclic
h-silyl vinyl sulfides, obtained from thioacylsilanes, re-
act with acid chlorides in the presence of a Lewis acid
to give open chain and thioannulated enones, respec-
tively [10], with byclic or tricyclic structures depending
upon the nature of the acyl chloride (Scheme 7).
In all cases, acylation is controlled by sulfur and
occurs at the i-position probably following the mecha-
nism outlined in Scheme 8. The cyclic compounds are
generated via a Nazarov-type cyclization.
Scheme 2.
The new compounds exhibit a much wider reaction
potential than that of their simpler counterparts and
through them a number of new highly functionalized
compounds can be synthesized.
2.1. Synthesis and synthetic applications of
enethiolizable thioacylsilanes
The replacement of the CꢀO with the CꢀS functional-
ity in acylsilanes has been reported to occur (Scheme 3)
in good yields by treatment [5] of the acylsilanes with
H2S/HCl or, under milder conditions, taking advantage
of the use of Me3Si–S–SiMe3 as the thionating agent
under CoCl2/6H2O catalysis [6].
Thiocarbonyl compounds do not enethiolize or give
mixtures of thione and enethiol [7]. On the contrary
aliphatic thioacylsilanes containing an hydrogen atom h
to the carbon–sulfur double bond, undergo quantita-
tive and stereoselective Z-enethiolization [8] (Scheme
4).
Quenching of the thiol moiety with suitable alkylat-
ing agents, gives rise to a variety of h-silyl vinyl
sulfides. In a similar way, ꢀ-haloacylsilanes synthe-
sized, as illustrated in Scheme 5, and transformed via
thioacylsilanes into Z-d-silylenethiols [9], undergo, in
Scheme 4.
Scheme 3.

B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
183
Scheme 5.
2.2. Synthetic applications of h,i-ethylenic and
-acetylenic silyl ketones
available by the synthesis devised by Reich in 1982 [11],
are very versatile building blocks. However, since the
beginning they have been involved only in a limited
number of synthetic applications mainly as acetylenic
The h,i-ethylenic and -acetylenic silyl ketones, made
Scheme 6.
Scheme 7.

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B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
Scheme 8.
Scheme 9.
Scheme 10.
dienophiles or in the application of the Brook rear-
rangement to the synthesis of not otherwise accessible
silyl enol ethers [12].
Their synthetic potential can be greatly expanded
taking into account the ability of these unsaturated
acylsilanes to act as Michael acceptors even more effec-
tively [13] than the organic counterparts and the benefi-
cial effect exerted by the R3Si group on the chemio- and
regioselectivity of the addition reactions.
Thus, propenoyltrimethylsilane reacts [14] with sily-
lated nucleophiles to yield the i-functionalized silyl
enol ethers of acylsilanes (Scheme 9). The reactions,
which proceed in the absence of solvent and without
Scheme 12.
any catalyst, lead to 95% configurationally pure E-silyl
enol ethers which have important applications in the
stereoselective synthesis of alicyclic molecules bearing
multiple asymmetric centers.
By acidic hydrolysis of these new silylated enol
ethers, saturated acylsilanes variously functionalized at
the i-position and readily convertible into the corre-
Scheme 11.

B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
185
Scheme 13.
sponding aldehydes by desilylation can be obtained in
good yields. Furthermore, these species undergo the
typical reactions of silyl enol ethers with electrophiles
leading to acylsilanes with different functional groups
at the h- and i-positions, thus exploiting the synthetic
equivalence of this class of compounds to the polysyn-
thon I (Scheme 10).
Ethynyl triphenylsilyl ketone, a synthetic equivalent
of propargylaldehyde, reacts readily with nucleophiles
to afford i-functionalized propenoylsilanes [15]. When
reacted with silylated nucleophiles, a spontaneous and
clean reaction occurs, similar to that of the ethylenic
series, yielding the corresponding Michael adducts in a
regiospecific fashion and in almost quantitative yields
(Scheme 11).
react under Wittig conditions to afford a new and
stereodefined class of silylated polyenes in which the
newly formed double bond has, because of the presence
of the R3Si moiety, Z stereochemistry. Successive desi-
lylation leads to the polyene with the E configuration
which is the contrary to classic Z stereoselectivity of the
Wittig reaction (Scheme 12). The use of unsaturated
acylsilanes for the stereoselective synthesis of conju-
gated polyenes, a class of compounds of high interest
since it includes natural products such as arachidonic
acid metabolites and insect pheromones, has great ad-
vantages with respect to the previously reported car-
bocupration of acetylenic esters, aldehydes and ketones
which suffers from extended isomerization.
With tributylstannylcuprate as the Michael donor,
the silylated acetylenic ketone affords the correspond-
ing bismetallated compounds in good yields [17]. The
presence of the stannyl moiety at position 3 of the
enonic framework, inverts the polarity at the C-3 car-
bon with respect to that observed in carbocupration.
It is worth noting that in the same reactions per-
formed on propargyl aldehyde itself, only the 1,2-ad-
ducts were formed in quantitative yields. When using
unsaturated carbocuprates dienoylsilanes are obtained
[16]. These synthetic equivalents of dienals can further
Scheme 14.

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B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
Scheme 15.
Scheme 16.
Coupling with electrophiles at the C–Sn bond of the
Michael adduct therefore occurs under mild conditions
(Scheme 13) according to the typical behavior of
vinyltin derivatives.
a real synthetic equivalent of polysynthons II and III in
which the polarity at position 3 can be tuned according
to synthetic needs, through the use of the suitable
Michael donors.
The intermediate cuprate can be further reacted in
situ with electrophiles to afford an easy entry into the
class of polyfunctionalized compounds such as ex-
omethylene 1,3-diketones, useful building blocks in nat-
ural product synthesis (Scheme 14).
The acetylenic silyl ketone can thus be considered as
Scheme 17.
.

B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
187
Table 1
curs (Scheme 17) with much higher diastereoselectivity
in the case of chiral acylsilanes with respect to the
corresponding aldehydes, due to the high diastereofa-
cial selectivity exerted by the R3Si moiety.
With these two major advantages in mind, the syn-
thesis of aminoacylsilanes was performed by means of
the nucleophilic silylation of the activated forms of the
protected aminoacids.
The most common sources of nucleophilic silicon
already reported in the literature, based on R3SiLi or
polymetallic reagents available through the transmetal-
lation procedure, are shown in Table 1.
Polymetallyc reagents Me2RSi–M as sources of ‘nucleophilic silicon’
Complex
Reference
[21]
Me2RSiLi or Me2RSiCu(CN)Li or
(Me2RSi)2Cu(CN)Li2
Me3Si–SiMe3/[(p3-C3H5)PdCl]2/P(OEt)3
LiAl(SiMe3)4 or LiMeAl(SiMe3)3
Al(SiMe3)3/CuCN: an ate complex?
[22]
[23]
[24]
2.3. Synthesis and synthetic applications of chiral acyl-
silanes deri6ed from naturally occurring compounds
The high degree of functionalization of the starting
materials required, however, a careful choice of the
nucleophilic silylation reagent and prompted us to
avoid reagents which are highly basic and unselective or
based on hard-to-handle starting materials. The excel-
lent transmetallation ability of zinc due to its low-lying
empty orbitals, as well as its use in a large number of
recent synthetic applications involving highly function-
alized compounds [25], suggested the design of a new
low-basicity and highly stable and selective polymetallic
reagent for the delivery of nucleophilic silicon [26]. The
new reagent was prepared (Scheme 18) according to the
procedure previously used by Yamamoto [27] for the
‘higher order’ (HO) zinc carbocuprate reagents.
As summarized in Chart 1, very clean cross-coupling
reactions took place with a variety of carboxylic acid
chlorides containing reactive functionalities leading to
the corresponding acylsilanes in high yields. It is impor-
tant to note that starting from N-protected aminoacids,
such as N-tosylproline and N-phtaloylphenylalanine,
the new h-aminoacylsilanes were obtained without any
loss of optical purity.
Among the limited number of chiral acylsilanes re-
ported in the literature, only recently [18] have natural
products like sugars been used as starting materials for
the preparation of these compounds (Scheme 15).
A good illustration of the usefulness of acylsilanes in
sugar chemistry is provided by the synthesis of C-difl-
uoro disaccharides with a difluoromethylene group in
place of the anomeric oxygen shown in Scheme 16.
To date, however, acylsilanes derived from homochi-
ral natural aminoacids are completely unknown. The
potential interest in these species stems from their syn-
thetic equivalence to amino aldehydes which are useful
precursors of homochiral aminoalcohols, structural
units found in a number of important bioactive
compounds.
The replacement of a hydrogen with a Me2PhSi
group conveys a generally [19] remarkable stability to
elusive molecules such as h- and i-amino aldehydes.
On the other hand, as previously demonstrated [20],
nucleophilic addition to the carbonyl functionality oc-
Scheme 18.
.
Scheme 19.

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B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
Although the precise structure of this new, less reac-
chemistry of homochiral aminoacylsilanes derived
from a wider range of natural aminoacids is likely to
be influential in achieving asymmetric synthesis.
tive but more stable polymetallic Si–Cu–Zn reagent
remains ambiguous, this compound appears superior
to the standard HO silylcyanocuprates. Its application
is preferable to the Me3Si–SiMe3/Pd procedure which
leads through complex reaction mixtures, to the ex-
pected products in much lower yields.
3. Conclusions
For the synthesis of i-aminoacylsilanes, synthetic
equivalents of highly unstable i-aminoaldehydes, N-
Pht-L-phenylalanine was homologated (Scheme 19) via
the Arndt–Eistert reaction, which is known to give
enantiopure i-aminoacids from their h-analogues, and
by using the Si–Cu–Zn reagent in the silylation step.
The first application of both h- and i-aminoacylsi-
lanes [28] was directed toward the synthesis of 1,2-
and 1,3-amino hydroxyl systems and was accom-
plished through a TiCl4-mediated addition of al-
lyltrimethylsilane (Scheme 20). Protodesilylation with
TBAF of the resulting hydroxysilanes led to the for-
mation of 6-Ph-5(S)-phthalimido-1-hexen-4-ol (60%)
and of (4R,6R)-7-Ph-6-phthalimido-1-epten-4-ol (80%)
as single diastereoisomers, thus suggesting d.e. values
\98%.
The aim of this article is to demonstrate that, even
though acylsilanes are not new compounds, their syn-
thetic potential can be further exploited toward the
synthesis of a variety of new highly functionalized
compounds, conditionally to the introduction of suit-
able structural modifications. The new synthetic strate-
gies, if on one side are based on the well known
reaction features resulting from the introduction of a
R3Si moiety into an organic molecule, on the other
hand take advantage of the use, among others, of new
highly selective Cu-based polymetallic reagents. This
combination between Group-14 and transition metal
chemistry, appears very promising for developing new
methodologies useful for regio-, chemio- and stereose-
lective organic synthesis. There remains a need to con-
tinue to develop a range of new acysilanes and to
optimize the procedures for their synthesis through the
‘invention’ of more reliable and selective nucleophilic
silylation reagents.
The effectiveness of the new homochiral aminoacyl-
silanes in the highly stereoselective synthesis of i- and
k-aminoalcohols reveals the high potential of these
compounds as powerful building blocks. As such, the
.

B.F. Bonini et al. / Journal of Organometallic Chemistry 567 (1998) 181–189
189
Scheme 20.
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Acknowledgements
Financial support by the Ministero dell’ Universita` e
della Ricerca Scientifica e Tecnologica (MURST, ex-
60%) and by the University of Bologna (Funds for
Selected Research Topics) is gratefully acknowledged.
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