DOI: 10.1002/chem.201402368
Communication
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Carbon Dioxide Fixation
Direct Assembly of 2-Oxazolidinones by Chemical Fixation of
Carbon Dioxide
Teemu Niemi,[a] Jesus E. Perea-Buceta,[a] Israel Fernꢀndez,[b] Sami Alakurtti,[c] Erika Rantala,[c]
and Timo Repo*[a]
prevalence, which are resistant to other potent antibiotics such
Abstract: The reaction of b- and g-haloamines with
carbon dioxide to give pharmaceutically relevant 2-oxazo-
as the methicillins or vancomycins.[6a–d] Additionally, the analo-
gous 6-ring scaffold, 1,3-dioxazin-2-one, is found in novel anti-
lidinones and 1,3-dioxazin-2-ones, was found to proceed
retroviral and antibacterial drugs.[7a–b] Most industrial processes
efficiently in the presence of a base and in the absence of
contemplate the construction of the 2-oxazolidinone heterocy-
catalyst. After optimization of reaction conditions, the
clic core as the key step through phosgenation of b-aminoal-
system was successfully expanded to a variety of halo-
cohols or the use of expensive building blocks and/or sacrificial
amines, even at multigram scale. The reaction was further
reagents.[8a–e] Greener alternatives are mainly limited to
studied in silico by DFT calculations.
a recent report on the assembly of 2-oxazolidinones through
the catalytic condensation of readily available glycerol deriva-
tives with urea. However, this approach is hitherto hampered
The chemical activation and fixation of carbon dioxide has
been pivotal at the forefront of research development towards
sustainable chemical transformations.[1a–c] The structural diversi-
ty, value, and applications of those molecules accessible utiliz-
ing carbon dioxide are instrumental to stimulate research pro-
grams. These factors also predetermine the economic and en-
vironmental impact in addition to the viability of a given pro-
cess at the industrial and pharmaceutical level.[2] Furthermore,
the value-driven nature of this research is underpinned by the
abundance, low cost, optimum atom economy, and environ-
mental features underlying the use of carbon dioxide as a
C-1 feedstock.[3]
by modest selectivities and yields as well as a narrow substrate
scope.[9] This affects the costs associated with the industrial
production of 2-oxazolidinones significantly enough to restrict
their public administration, and trigger research on methods
that are simultaneously sustainable and effective, such as
those based on the chemical fixation of CO2.[5,10]
In the last decade, research on the construction of 2-oxazoli-
dinones by chemical fixation of CO2 has experienced consider-
able progress. However, a close examination reveals that care-
ful selection of substrates still continues to determine the suc-
cess of this task. In this sense, b-aminoalcohols represent the
most intuitive and highly desirable substrates given their avail-
ability and cost. However, previous studies required either high
temperatures and supercritical conditions,[11] toxic organome-
tallic catalysts,[12,13] electrochemical procedures based on pre-
cious metals,[14] or, more recently, stoichiometric additives to
capture the water generated in situ.[15a–c] In contrast, the use of
activated aziridine derivatives as substrates have widely met
with better results by employing either catalytic,[16a–e] or sol-
vent and catalyst-free conditions.[17a–b] Unfortunately, the rela-
tively high cost of these building blocks coupled with the pre-
functionalization generally required on the aziridine nitrogen
atom and other positions of the ring have a deleterious effect
on their industrial implementation.
In this connection, 2-oxazolidinones constitute a prominent
family of molecules amenable to be constructed by chemically
fixating CO2.[4] Widely applied in asymmetric synthesis as chiral
auxiliaries,[5a–b] these compounds have recently shown unparal-
leled biological profiles. In particular, N-aryl-2-oxazolidinones
(Scheme 1) are regarded as the last resort treatment against
a broad variety of gram-positive bacterial pathogens of rising
[a] T. Niemi, Dr. J. E. Perea-Buceta, Prof. T. Repo
Laboratory of Inorganic Chemistry
Department of Chemistry
University of Helsinki
P.O. Box 55, 00014 Helsinki (Finland)
Fax: (+358)9-191-50198
In the course of our ongoing research on the activation of
small molecules,[18a–c] we became aware of the non-existence
of a simple direct method involving CO2-based construction of
2-oxazolidinones and 1,3-dioxazin-2-ones with the structural
features showcased on any member of the 2-oxazolidinone
family of antibiotics, namely no substitution on ring position 3
(Scheme 1) and a hydroxymethyl or methyl group on position
4. Furthermore, we envisaged that such a method would be
compatible with subsequently performing a well-known and
efficient catalytic N-arylation protocol with a broad scope of
aryl halides.[19]
[b] Dr. I. Fernꢀndez
Departamento de Quꢁmica Orgꢀnica I
Facultad de Ciencias Quꢁmicas
Universidad Complutense de Madrid
28040 Madrid (Spain)
[c] Dr. S. Alakurtti, E. Rantala
VTT Technical Research Centre of Finland
P. O. Box 1000, FI-02044 (Finland)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201402368. It includes spectroscopic data,
methods used, and computational details.
Chem. Eur. J. 2014, 20, 1 – 6
1
ꢁ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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