Rapid and efficient entry to vinyl silanes from aldehydes employing a novel metalation-Peterson sequence

Article abstract of DOI:10.1039/b716897g

Bis(trimethylsilyl)chloromethane undergoes a rapid and selective metalation with s-BuLi, yielding the nucleophilic bis(trimethylsilyl)methyl anion and providing a straightforward general entry to vinyl silanes from aromatic, aliphatic and vinyl aldehydes. The Royal Society of Chemistry.

Full text of DOI:10.1039/b716897g

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Rapid and efficient entry to vinyl silanes from aldehydes employing a
novel metalation–Peterson sequencew
James McNulty* and Priyabrata Das
Received (in Maryland, USA) 5th November 2007, Accepted 18th January 2008
First published as an Advance Article on the web 7th February 2008
DOI: 10.1039/b716897g
Bis(trimethylsilyl)chloromethane undergoes a rapid and selective
metalation with s-BuLi, yielding the nucleophilic bis(trimethyl-
silyl)methyl anion and providing a straightforward general entry
to vinyl silanes from aromatic, aliphatic and vinyl aldehydes.
The two possible outcomes of the reaction of 1a with an
alkyl lithium reagent are outlined in Scheme 1. The reaction of
1a with n-BuLi and t-BuLi was problematic, however we
quickly determined that the desired lithium reagent 1b was
formed via lithium–halogen exchange upon treatment of 1a
with s-BuLi in THF at ꢀ78 1C (Scheme 1). Steric hindrance
around both the chloromethylene proton and the bulky base is
the likely rationale that directs the lithium–chlorine exchange
(path a) over the potential deprotonation path (path b). While
both the magnesium and lithium derivatives corresponding to
1b have been prepared through direct metalation,5k,5l to the
best of our knowledge, this is the first report of lithium–
halogen exchange on such a bis-(trialkylsilyl)chloroalkyl
group in the literature.
Vinyl silanes have proven to be of value in a variety of useful
synthetic transformations in view of their mild reactivity, and
the controlled regio- and stereoselectivity observed in their
reactions.1,2 However, applications of vinyl silanes in total
synthesis appear to be less common, possibly due to the lack of
a rapid general synthetic entry to this functional group.
Various methodologies are available for vinyl silane synthesis,
including alkyne hydrosilylation,1–3 aryl/alkenyl halide–silicon
exchange,4 as well as from carbonyl compounds.5 Peterson has
described an interesting route using a Wittig reaction of an a-
silylated ylide with an aldehyde.6 An obvious alternative for
this purpose is [bis(trimethylsilyl)methyl]lithium (1b, Scheme
1), employing a Peterson reaction with a carbonyl compound
to produce a vinyl silane. Unfortunately, precursor bis-
silamethylenes demonstrate problematic lithium–hydrogen
exchange,7 unless an additional stabilizing neighbouring het-
eroatom or electron-withdrawing group is present,8a compli-
cating this potentially valuable process.8 Product yields using
this deprotonation–Peterson route to vinyl silanes are low to
moderate (25–70%).5b Given the availability of a wide range
of simple aromatic and aliphatic aldehydes, we have been
interested in developing a direct synthesis of vinyl silanes from
aldehydes. Alternative routes to vinyl silanes from aldehydes
employ reagents that are not generally available or involve
several steps.9
The synthetic utility of this novel lithium–halogen exchange
as a route to vinyl silanes was investigated with a range of
aromatic aldehydes, the results of which are summarized in
Table 1. The isolated yields and (E)-stereoselectivities were
invariably good in all of the cases investigated. No significant
electronic effect was observed, with both electron donating
and electron withdrawing derivatives (Table 1, entries 1 to 9)
reacting equally well. Ortho-steric effects did not appear to be
detrimental (Table 1, entry 4) on the part of the aldehyde.
Most interestingly, cinnamaldehyde yielded the silyldiene
(Table 1, entry 3) in 81% isolated yield. The yield obtained
here is considerably higher than the reported 32–37% ob-
tained using literature methods for the preparation of inter-
mediate 1b.5b This literature route was considered but
abandoned in a previous report by Fleming et al. as a reliable
route to silylated butadienes.5e In addition, the reaction of
anion 1b, generated by lithium–proton exchange, has been
reported to give only low yields of vinyl silanes upon reaction
with enolizable aliphatic aldehydes (for example, 25% with
1-butanal and 45% with formaldehyde).5b,5e The reaction of
1b, generated via the new lithium–halogen exchange path, was
therefore investigated with undecanal. This led to the forma-
tion of the corresponding vinyl silane, surprisingly isolated in
77% yield and with 4 : 1 (E) : (Z) stereoselectivity (Table 1,
Herein, we report the novel finding that commercially
10
availablez bis(trimethylsilyl)chloromethane (1a) selectively
undergoes an efficient lithium–halogen exchange with s-BuLi,
resulting in rapid generation of the desired [bis(trimethylsilyl)-
methyl]lithium intermediate (1b). The resulting bis-trimethyl-
silyl carbanion readily enters into Peterson olefination
reactions with aldehydes, including enolizable aliphatic alde-
hydes, allowing a direct synthesis of vinyl silanes in high yield
and with good (E)-stereoselectivity.
Department of Chemistry, McMaster University, 1280 Main Street
West, Hamilton, Ontario, Canada L8S 4M1. E-mail:
jmcnult@mcmaster.ca; Fax: +1 905-522-2509; Tel: +1 905-525-
9140 ext. 27393
w Electronic supplementary information (ESI) available: Experimental
section. See DOI: 10.1039/b716897g
z This reagent is available from the Aldrich Chemical Company
Scheme 1 Halogen–lithium exchange (path a) vs. deprotonation (path b).
ꢁc
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Table 1 Reaction of (TMS)2CHLi with aldehydes
Entry
1
2
3
(E) : (Z) Yield (%)
49 : 1 90
2
3
4
5
49 : 1 95
49 : 1 81
49 : 1 90
49 : 1 80
Fig. 1 Favoured syn-periplanar elimination from conformer B.
In conclusion, we have shown that bis(trimethylsilyl)chlor-
omethane readily undergoes lithium–halogen exchange with
s-BuLi, and that the resulting anion adds readily to aromatic,
vinyl as well as enolizable aldehydes in a Peterson fashion to
yield vinyl silanes in good yield and (E)-stereoselectivity.
Further extension and application of the method is currently
under investigation.
6
7
8
49 : 1 85
49 : 1 87
49 : 1 93
Notes and references
9
49 : 1 65
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10
4 : 1
77
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entry 10). This result proves that there is no intrinsic barrier to
the use of this bis-(trimethylsilyl)-stabilized carbanion with
aliphatic aldehydes (such as enolization, aldolization, etc.).
The explanation for this unexpected higher efficiency may lie
with the method of generation of 1b via rapid lithium–chlorine
exchange. In contrast, the literature protocol for the synthesis
of lithium reagent 1b involves proton–lithium exchange on the
central methylene of bis(trimethylsilyl)methane using t-BuLi/
HMPA in THF over 7.5 h.5b Since it is well documented that
tetraalkylsilanes are very difficult to deprotonate,8 the pre-
vious lengthy anion generation procedure and/or presence of
unreacted t-BuLi may have adversely affected the yield of vinyl
silanes from sensitive aldehydes.
5 (a) D. Seebach, R. Burstinghaus, B. T. Grobel and M. Kolb, Justus
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Liebigs Ann. Chem., 1977, 830; (b) B. T. Grobel and D. Seebach,
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The trans-olefin selectivity in the product vinyl silanes can
be readily explained as follows. b-Hydroxysilanes can undergo
elimination to form olefins through either a concerted syn-
periplanar reaction pathway, typically under basic reaction
conditions, or through a stepwise anti-periplanar pathway,
typically occurring under acidic conditions.10 Conformational
analysis of the present relevant b-oxidosilane intermediate is
shown (conformers A and B) in Fig. 1. This intermediate
possesses two diastereotopic TMS groups capable of partici-
pating in the expected syn-elimination. Conformer A indicates
the presence of a steric non-bonding interaction that is absent
in conformer B, thus favouring elimination from conformer B
via an expected early transition state and leading to the (E)-
vinyl silanes as the kinetic reaction product under these
conditions.
6 D. J. Peterson, J. Org. Chem., 1968, 33, 780.
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10 F. P. Hudrlik, E. L. O. Agwaramgbo and M. A. Hudrlik, J. Org.
Chem., 1989, 54, 5613.
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