KI-catalyzed ring expansion reaction of trans-NH-ketoaziridines to new trans-oxazolidines

Article abstract of DOI:10.1016/j.tetlet.2015.12.025

In this work, the synthesis of a new class of trans-oxazolidines by the regio- and stereocontrolled reaction of NH-ketoaziridines with phenylisocyanate is reported. A plausible mechanism has been proposed.

Full text of DOI:10.1016/j.tetlet.2015.12.025

Tetrahedron Letters 57 (2016) 223–225
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
KI-catalyzed ring expansion reaction of trans-NH-ketoaziridines
to new trans-oxazolidines
b
Heshmat A. Samimi a, , Bohari M. Yamin
⇑
a Faculty of Science, Department of Chemistry, Shahrekord University, PO Box 115, Shahrekord, Iran
b School of Chemical Sciences and Food Technology, University Kebangsaan Malaysia, UKM, 43500 Bangi, Selangor, Malaysia
a r t i c l e i n f o
a b s t r a c t
Article history:
In this work, the synthesis of a new class of trans-oxazolidines by the regio- and stereocontrolled reaction
of NH-ketoaziridines with phenylisocyanate is reported. A plausible mechanism has been proposed.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 17 January 2015
Revised 23 September 2015
Accepted 4 December 2015
Available online 7 December 2015
Keywords:
Aziridines
Regio-controlled
Oxazolidine
Ring expansion
Aziridines are well known to be useful reagents for the synthesis
of many types of nitrogen-containing compounds1 and the coupling
with an isocyanate is an effectiveway to access heterocyclicring sys-
tems.2,3 1-Aroylaziridines are known to be readily isomerized into
oxazolines.4 The ring expansion of N-alkylaziridines with 1 equiv
of isocyanate leading to iminooxazolidinones has been reported4a–d
as well as
a few examples of the transformations of N-
alkylaziridines to 2-iminooxazolidines or iminoazoselenolidines.4
A literature survey revealed that no examples regarding the synthe-
sis of 2-iminiooxazolindines from the reaction of NH-aziridines with
2 equiv of phenylisocyanates have been reported.
In our previous work, we reported the ring expansion reaction
of trans-ketoaziridines to trans-oxazolidin-2-ones,5 as well as the
preparation of oxazoles and 2-aminothiazoles (Scheme 1).6 These
successful results,5–7 motivated us to further explore the ring
expansion of keto-aziridines to yield other types of
azaheterocycles.
Consequently, we investigated the regio- and stereoselective
synthesis of oxazolidines from the reaction of trans-ketoaziridines
and isocyanates. In preliminary studies, trans-2-aroyl-3-aryl
aziridines (1a,b) were reacted with phenylisocyanate in acetoni-
trile at room temperature to give trans-1-phenylcarbamoyl-2-
aroyl-3-aryl aziridines (2a,b) in excellent yield (Table 1).
We next examined the reaction of trans-2-benzoyl-1-pheny-
laziridine (1a) with phenylisocyanate in acetonitrile at 60 °C.
Scheme 1. Ring expansion of ketoaziridines to other heterocyclic compounds.
Table 1
Synthesis of trans-1-phenylcarbamoyl-2-aroyl-3-arylaziridines (2) from trans-2-
aroyl-3-arylaziridines (1)
Entry
Ar1
Ar2
Time (h)
Yield (%)a
a
b
Ph
Ph
Ph
7
7
87
76
3-NO2C6H4
⇑
Corresponding author. Tel./fax: +98 381 4424419.
E-mail address: samimi-h@sci.sku.ac.ir (H.A. Samimi).
a
Isolated yield.
http://dx.doi.org/10.1016/j.tetlet.2015.12.025
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

224
H. A. Samimi, B. M. Yamin / Tetrahedron Letters 57 (2016) 223–225
Surprisingly this gave trans-4-benzoyl-5-phenyl-2-(phenylimino)
oxazolididine-3-(N-phenylcarboxamide) (3a) in moderate yield
(38%). The addition of a 2 equiv of isocyanate resulted in an
increase in yield (55%), while interestingly, when the reaction
was examined in the presence of KI, compound (3a) was formed
in excellent yield (87%) (Scheme 2).
Since the spectral data (e.g., 1H and 13C NMR) were not conclu-
sive to assign the stereochemistry of the product, single crystal X-
ray crystallographic analysis was conducted on 3b to verify the
product structure which confirmed the trans-diastereoselectivity
of the reaction (Fig. 1).
Scheme 2. Ring expansion of 2-benzoyl-3-phenyl aziridines to the corresponding
oxazolidine.
These observations encouraged us to further develop this
methodology by reacting a wider range of ketoaziridines with
phenylisocyanate (Table 2).
According to the proposed mechanism presented in Scheme 3,
there are three possible routes for oxazolidine formation. In route
I, which produces the product in the absence of KI, the aryl moiety
at position C-3 makes the cation a suitable position for intramolec-
ular nucleophilic reaction of oxygen to give oxazolidine 3. Conse-
quently, the formation of only one stereo-isomer (3) with
retention of configuration occurs at both carbon atoms of the azir-
idine ring. Whereas in pathway II, it assumes that the aryl moiety
on C-3, and the presence of the carbamoyl on the nitrogen of the
ring, forms a partial positive charge on the C-3 carbon which is
in a suitable position for nucleophilic attack by the iodide ion for
ring cleavage of the aziridine, followed by attack of oxygen to the
iodide bearing carbon to give the oxazolidine. The reaction path-
way in route II takes place via a double inversion, subsequently
leading to a net retention of configuration in the two ring carbons
of oxazolidine (3).
The proposed mechanism is supported by the fact that the reac-
tion of trans-1-phenylcarbamoyl-2-aroyl-3-aryl aziridines (2) with
phenylisocyanate in the presence of KI or absence of KI leads to the
synthesis of trans-oxazolidine (3).
On the other hand, heating 2a without the isocyanate at 60 °C in
acetonitrile in the presence or absence of KI gave unknown prod-
ucts and neither A or B was obtained (Scheme 3, Route III).
Although this work indicates that the presence of the carbamoyl
group on the aziridine nitrogen makes C-3 a favorable position for
nucleophilic attack by iodide, previous work,5a,b has shown
(Scheme 4) the presence of an aroyl group on the nitrogen ring
(7) makes C-2 the most favorable position for attack by iodide to
give oxazoline 8. This observation shows a substituent-reactivity
relationship for the attack of the iodide on either C-2 or C-3 of
the aziridine ring (Scheme 3). On the other hand in the presence
of iodide and NiCl2 the reaction of aziridines with (Boc)2O affords
b-carbamoyl carbonyl compounds (6).7c
Figure 1. Single crystal X-ray crystal structure of 3b.
Table 2
Synthesis of trans-oxazolidines (3) from trans-2-aroyl-3-arylaziridines (1) with phenylisocyanate
Entry
Ar1
Ar2
Time (h)
Product
Yield (%)a
a
b
c
d
e
f
Ph
C6H5
4-MeOC6H4
2,4-Cl2C6H3
4-ClC6H4
4-BrC6H4
Ph
4-ClC6H4
Ph
Ph
Ph
Ph
1
1.5
1
1.5
1
1
3a
3b
3c
3d
3e
3f
83
87b
79
81
79
81
a
Isolated yield.
b
The structure of 3b was confirmed by single crystal X-ray crystallography (see SI).

H. A. Samimi, B. M. Yamin / Tetrahedron Letters 57 (2016) 223–225
225
Scheme 3. Plausible mechanism for the regio- and stereocontrolled synthesis of oxazolidines from aziridines and isocyanates in the presence (Route II) and the absence of KI
(Route I), heating 2 in the presence and absence of KI (Route III).
Supplementary data
Supplementary data (synthesis and spectral data (1H and 13C
NMR, IR and HRMS spectra) associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.
2015.12.025.
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Acknowledgments
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We are thankful to the Research Council of Shahrekord Univer-
sity for supporting this work. We thank Professor B.M.Y. of the
School of Chemical Sciences and Food Technology, University
Kebangsaan for single-crystal X-ray diffraction.