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G. Landelle et al. / Tetrahedron Letters 53 (2012) 2414–2416
when the aromatic ring is substituted at the para-position by an
electron donating group such as methoxy or methyl (entries 4
and 5 vs 1–3). Interestingly, the use of aliphatic aldehydes or ethyl
glyoxylate, for which the isolation of the imine remains tricky,
furnished good isolated yields albeit with modest 30% de (entries
8–11). In addition, it should be noted that the reaction involving
acetaldehyde requires a change in the order of introduction of
the reagents to ensure a decent isolated yield (entry 9). The amine
part is somewhat less tolerant to substitution as only aniline deriv-
atives provided the addition products (entries 12–19 vs 20) with
isolated yields ranging from 50% to 89% and diastereomeric ratio
up to 63:37. All attempts to use other amines such as N-
Acknowledgments
This work was supported by CNRS, University of Rouen and
INSA of Rouen, the région Haute-Normandie and the FEDER ‘FLU-
ORG’ (convention No. 33236). G.L. and A.C. thank, respectively,
the région Haute-Normandie and the CRUNCh for a Grant.
Supplementary data
Supplementary data (general informations, general procedure
for the synthesis of 5-substituted c-butenolides 4a–w and copies
of NMR spectra for products 4a–w) associated with this article
benzylamine,
a-methylbenzylamine, or n-propylamine failed
giving rise only to formation of the corresponding imines 5a. All
the anilines tested furnished preferentially the trans isomer
whatever the electronic nature of the substituents of the aromatic
ring. Finally, several substituted benzaldehydes and anilines were
tested providing good yields and diastereomeric ratio up to
69:31. It is noteworthy that the use of other silyl nucleophiles
(TMSCH2CO2Et, TMSCF3 or TMSOC(OMe) = CMe2) did not provide
the addition product.
References and notes
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In order to gain insights into the mechanism and more specifi-
cally into the role of the water in this one-pot reaction, additional
control experiments were conducted. We thus controlled that
TMSOH which is actually the only by-product of the reaction did
not act as a promoter of the vinylogous Mannich reaction by
mixing 5a, 3a, and 1 equiv of TMSOH. Moreover, no formation of
c-crotonolactone was observed when 3a was allowed to react with
1 equiv of TMSOH, while only 21% of -crotonolactone was de-
c
tected by 1H NMR after 20 min by adding 1 equiv of water to 3a.
All these experiments along with the mechanisms of activation
of silyl pro-nucleophiles by Lewis bases postulated in the litera-
ture7,10 led us to propose two possible intermediates where, water
acts as a dual activator of both imine 5a and trimethylsilyloxyfuran
3a as depicted in Figure 2. According to this hypothesis, water
would activate both imine 5a either via protonation (Fig. 2b) or
hydrogen bond (Fig. 2a) and trimethylsilyloxyfuran 3a through
the presence of oxygen lone pairs of the water acting as Lewis base.
In summary, we have reported a clean and easy to implement
one-pot vinylogous Mannich-type reaction of trimethylsilyloxyfu-
ran under solvent-free conditions. This methodology allows the ra-
pid access to a series of 5-substituted c-butenolides 4 with good
yields. The crucial role of the water generated during the imine for-
mation was underlined and a dual activation model was proposed
to account for high reactivity.