DOI: 10.1002/chem.201505050
Communication
&
Synthetic Methods
Synthesis of Oxazolidin-2-ones by Oxidative Coupling of
Isonitriles, Phenyl Vinyl Selenone, and Water
[
a]
Thomas Buyck, Delphine Pasche, Qian Wang, and Jieping Zhu*
zation of allylic carbamate and carbonylation of b-aminoalco-
hols are the most popular ones.
Abstract: Reaction of alkyl isocyanides, phenyl vinyl sele-
none, and water in the presence of a catalytic amount of
Cs CO afforded oxazolidin-2-ones in good yields. This un-
Numerous isonitrile-based organic transformations have
been developed in the past decades, most of them being trig-
gered by an a-addition of the divalent carbon to both nucleo-
2
3
precedented heteroannulation process created four chem-
ical bonds in a single operation with the isocyano group
acting formally as a polarized double bond and phenyl
vinyl selenone as a latent 1,3-dipole. The phenylselenonyl
group played a triple role as an electron-withdrawing
group to activate the 1,4-addition, a leaving group, and
a latent oxidant in this transformation.
[
6]
philes and electrophiles. As a consequence, the isocyano
group acts generally as a one-carbon synthon in cycloaddition
[
7,8]
processes (Scheme 1a).
In connection with our ongoing re-
Oxazolidinones are of great importance as chiral auxiliaries in
[
1]
organic chemistry and as pharmacophores in medicinal
[
2]
chemistry. This 5-membered heterocycle, as illustrated by the
marketed antibiotic linezolid (1; Figure 1), is a key structural
Scheme 1. Synthesis of oxazolidinones.
search program aimed at exploiting unconventional reactivity
[
9]
of the isocyano group, we uncovered serendipitously a base-
catalyzed heteroannulation reaction between isonitriles 4 and
[
10]
phenyl vinyl selenone (5) leading to N-alkylated oxazolidi-
nones 6 (Scheme 1b). One CÀN, two CÀO, and one C=O bonds
were created in this unprecedented transformation with the
isocyano group acting formally as a polarized double bond (A)
Figure 1. Bioactive molecules containing oxazolidin-2-one.
[
11]
unit of a new class of antibacterial agents active against vanco-
and phenyl vinyl selenone as a latent 1,3-dipole (B). The phe-
nylselenonyl group served as an electron-withdrawing group
to activate the 1,4-addition, a leaving group, and a latent oxi-
[2]
mycin-resistant enterococci (VRE). In addition, converting a pri-
mary amine to N-substituted oxazolidin-2-one is a common
practice in drug development endeavors in order to improve
the activity profile of drug candidates; indeed, this structural
motif is found in many bioactive compounds, such as neuro-
[
12]
dant in this transformation.
The reaction between benzyl isonitrile (4a) and phenyl vinyl
selenone (5) was initially investigated. In the presence of a cata-
lytic amount of cesium hydroxide monohydrate, the reaction
between 4a and 5 in tert-butanol at room temperature afford-
ed unexpectedly oxazolidinone 6a in about 20% yield (Table 1,
entry 1). Realizing the synthetic potential of this transforma-
tion, the reaction conditions were systematically surveyed. This
allowed us to conclude the following optimum conditions:
Cs CO3 (0.1 equiv), CH Cl2 (ca. 0.5m), H O (1.0 equiv), 408C.
[
3]
[4]
leptic agent 2 and tyrosine kinase inhibitor 3 (Figure 1).
[5]
Among many known synthetic methods, the 5-exo-trig cycli-
[
a] Dr. T. Buyck, D. Pasche, Dr. Q. Wang, Prof. Dr. J. Zhu
Laboratory of Synthesis and Natural Products
Øcole Polytechnique FØdØrale de Lausanne
EPFL-SB-ISIC-LSPN, BCH 5304, 1015 Lausanne (Switzerland)
E-mail: Jieping.zhu@epfl.ch
2
2
2
Under these conditions, the reaction of 4a (1.1 equiv) with 5
1.0 equiv) and water furnished oxazolidinone 6a in 73% iso-
lated yield (entry 6). The yield is excellent considering that four
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(
Chem. Eur. J. 2016, 22, 2278 – 2281
2278
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