DOI: 10.1002/chem.201500475
Communication
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Organic Synthesis |Hot Paper|
Stereoselective Peterson Olefinations from Bench-Stable Reagents
and N-Phenyl Imines
¨
Manas Das, Atul Manvar, Maıwenn Jacolot, Marco Blangetti, Roderick C. Jones, and
Donal F. O’Shea*[a]
alkene stereoselectively.[3] For stabilized a-silyl carbanions (e.g.
Abstract: The synthesis of bench-stable a,a-bis(trimethyl-
R=Ar) these intermediates are not isolated and stereocontrol
silyl)toluenes and tris(trimethylsilyl)methane is described
has yet to be achieved making it a less attractive approach for
and their use in stereoselective Peterson olefinations has
such reactions.[4] A further disincentive to its use is that the
been achieved with a wide substrate scope. Product ste-
silyl anion 2 must be first generated often with strong bases
under nontrivial conditions prior to the addition of the alde-
reoselectivity was poor with carbonyl electrophiles (E/Z
~1:1 to 4:1) though this was significantly improved by
employing the corresponding substituted N-benzylidenea-
hyde.
Yet, if solutions to these two issues were in hand, an inher-
niline (up to 99:1) as an alternative electrophile. The olefi-
ent advantage of the Peterson olefination is its superior atom
nation byproduct was identified as N,N-bis(trimethylsilyl)a-
economy over the Wittig reaction as it produces low molecular
niline and could be easily separated from product by
silicon byproduct in the carbon–carbon double-bond-forming
aqueous acid extraction. Evidence for an autocatalytic
step rather than crystalline triphenylphosphine oxide.[5] An al-
cycle has been obtained.
ternative approach to the generation of the a-silyl carbanions
that does not require strong bases is to use geminal bis(tri-
methyl silanes) 4 as starting substrates and a fluoride source to
In the synthetic olefination toolbox the Peterson olefination, in
spite of its great value, remains one of the lesser utilized meth-
ods for the conversion of carbonyls to alkenes.[1] The transfor-
mation is considered as a silicon analogue of the Wittig reac-
tion with the reaction of a-silyl carbanions 2 (typically generat-
ed by deprotonation of 1 using strong lithium or magnesium
bases) with carbonyls providing the alkene product 3 and tri-
methylsilyl oxide byproduct (Scheme 1, route a).[2] Intermediate
promote generation of the a-silyl carbanion precursor 5
(Scheme 1, route b). Bis(silanes) 4 are bench stable (analogous
to the Wittig phosphonium salt), yet they have received very
limited use due to the lack of a general route for their synthe-
sis.[4e–g,6] The use of bis(silanes) as Peterson olefination reagents
offers an additional advantage in that they eliminate the need
to pre-form the carbanion species as it is generated in situ in
the presence of the aldehyde.
In this report we illustrate a new general two-step approach
for the synthesis of a,a-bis(trimethylsilyl)toluenes 7a–h from
their corresponding toluenes using identical synthetic condi-
tions for both steps. We have developed methods for their use
in olefination reactions and shown, for the first time, how ste-
reocontrol can be achieved by the use of aniline-derived N-aryl
imine electrophiles. In addition this method is extended to the
complementary tris(trimethylsilane) 9, which opens a new
route to vinyl trimethylsilanes; these compounds are in them-
selves important substrates for cross-coupling transformations
in alkene synthesis.[7]
Scheme 1. Peterson olefination.
Synthesis of (arylmethylene)bis(trimethylsilanes) 7a–h was
achieved by the regioselective benzylic metalation of the
parent toluene by using BuLi, KOtBu, and TMP(H) in THF (LiNK
conditions)[8] and TMSCl quench to form the substituted ben-
zylsilanes 6a–h with a repeat of these conditions providing
the desired olefination reagents (Scheme 2, top panel). Intro-
duction of a sensitive bromine functional group, which would
not be tolerant of the chemistry required for the geminal bis(-
silane) synthesis, was achieved from 7a to give p-bromo deriv-
ative 7i in a high 83% yield (Scheme 2, left bottom panel).
Tris(trimethylsilyl)methane 9 was generated by deprotonation
b-hydroxysilanes can be isolated when the silyl carbanion used
is not stabilized (e.g. R=alkyl), which upon treatment with
either base or acid can deliver the corresponding (E)- or (Z)-
[a] M. Das, Dr. A. Manvar, Dr. M. Jacolot, Dr. M. Blangetti, Dr. R. C. Jones,
Prof. Dr. D. F. O’Shea
Department of Pharmaceutical and Medicinal Chemistry
Royal College of Surgeons in Ireland
123 St. Stephen’s Green, Dublin 2 (Ireland)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500475.
Chem. Eur. J. 2015, 21, 1 – 5
1
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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