SHORT COMMUNICATION
DOI: 10.1002/ejoc.200701191
Reaction of Thiolesters with Nitrogen Ylides
Svatava Voltrova[a] and Jiri Srogl*[a]
Keywords: Thiolesters / Ylides / Ammonium salts / Sulfur heterocycles
The pairing of unstabilized nitrogen ylides generated in situ
with functionalized thiolesters under ambient conditions re-
sulted in a new intramolecular carbon–carbon bond forming
reaction. The scope of the reaction was illustrated with a
series of substituted thiolester substrates. This reaction repre-
Whereas nitrogen ylides have been used in synthesis pre-
viously, very few examples exist in which unstabilized nitro-
gen ylides have been utilized in synthetically meaningful
transformations.
sents a new method for the synthesis of 2-substituted tetra- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
hydrothienyl compounds through a unique 1,2-thiolate shift.
Germany, 2008)
containing functionalities. Although they found some syn-
thetic use, particularly in the form costabilized by other
substituents,[6] unstabilized nitrogen ylides have received
only marginal attention. The relative synthetic obscurity of
the such species is connected to problems with the forma-
tion of the ylides and their subsequent stability.[6]
As with their phosphorus counterparts, successful nitro-
gen ylide reaction patterns depend on abstraction of the α-
proton in the precursors Ϫ the ylide formation. In order to
gain some insight into this process, we evaluated different
nitrogen-containing functional groups influencing the pro-
ton abstraction and the ylide stability. The comparison of
ammonium derivatives 1a–d treated by alkali carbonates in
various solvents in the hydrogen/deuterium exchange ex-
periment pointed to the pyridinium (1a derivative) and, to
a lesser extent, to the 4-aminocarbonylpyridinium group (1c
derivative) as the best ylide stabilizing, synthetically feasible
functional groups (Table 1).
Introduction
Having an indispensable role in biological chemistry, the
electrophilic thiolester functionality has been one of the
most important chemical building blocks.[1] In the past cou-
ple of decades, their usefulness finally overreached the
boundaries of biochemistry and their role became firmly
embedded in the synthetic arsenal of organic chemists. The
chief advantages of thiolesters, such as their stability and
accessibility, have been used in the synthesis of highly func-
tionalized ketones[2] and aldehydes,[3] and they have also
played important parts in the synthetic chemistry of pro-
teins.[4] Various thiolester substrates can be easily prepared
from commercially available starting materials through very
mild methods.[5]
Results and Discussion
In our ongoing effort to investigate the reactivity of the
electrophilic thiolester functionality and its use in carbon–
carbon bond forming processes, we have been looking for
matching nucleophilic partners that could be prepared and
used under ambient reaction conditions. The candidates
that could fulfill those considerations are ylides. Although
processes involving heteroatom-stabilized ylides have been
extensively studied and their role in organic synthesis well
recognized, the chemistry of nitrogen ylides and their syn-
thetic application certainly deserves closer attention.[6] Be-
cause phosphorus ylides and their intramolecular reaction
with thiolesters have been already reported,[7] we turned our
attention to the reactivity of ylides stabilized by nitrogen-
Table 1. Isotope exchange experiment.[a]
X
Room temp., 10 min 90 °C, 1 h
H/D exchange [%]
H/D exchange [%]
1a pyridine
Ͻ2
Ͻ2
Ͼ99
decomp.
55
Ͻ2
Ͼ99
1b nicotinamide
1c isonicotinamide Ͻ2
1d Et3N
Ͻ2
Ͼ99
1e[b] Ph3P
[a] Institute of Organic Chemistry and Biochemistry, Academy of
Sciences of the Czech Republic,
[a] To the (CD3)2SO solution of bromide 1a–e (approx. 15 mg
bromide in 0.5 mL of the solvent) was added one drop of D2O.
Deuterium exchange was observed by NMR spectroscopy. [b] The
triphenylphosphonium compound was used as a benchmark for its
known reactivity.
Flemingovo nam. 2, 16610 Prague 6, Czech Republic
Fax: +420-220183578
E-mail: jsrogl@uochb.cas.cz
Supporting information for this article is available on the
Eur. J. Org. Chem. 2008, 1677–1679
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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