Efficient ring opening reactions of N-tosyl aziridines with amines and water in presence of catalytic amount of cerium(IV) ammonium nitrate

Article abstract of DOI:10.1246/cl.2003.82

While methyl- and benzylamines opened N-tosyl aziridines 1 very efficiently in acetonitrile with complete regio- and stereoselectivity to give the corresponding diamines 2 and 3, respectively, in excellent yields, similar openings with water could only be achieved in the presence of a catalytic amount of cerium(IV) ammonium nitrate under very mild conditions furnishing the amino alcohols 4.

Full text of DOI:10.1246/cl.2003.82

82
Chemistry Letters Vol.32, No.1 (2003)
Efficient Ring Opening Reactions of N-Tosyl Aziridines with Amines and Water in Presence of
Catalytic Amount of Cerium(IV) Ammonium Nitrate
Tushar K. Chakraborty,ꢀ Animesh Ghosh, and T. Venugopal Raju
Indian Institute of Chemical Technology, Hyderabad 500007, India
(Received September 17, 2002; CL-020792)
While methyl- and benzylamines opened N-tosyl aziridines 1
Table 1. Opening of N-tosyl aziridines (1) with amines RNH2 in
CH3CN
very efficiently in acetonitrile with complete regio- and stereo-
selectivity to give the corresponding diamines 2 and 3, respec-
tively, in excellent yields, similar openings with water could only
be achieved in the presence of a catalytic amount of cerium(IV)
ammonium nitrate under very mild conditions furnishing the
amino alcohols 4.
Entry Starting
Aziridines
Product
Diamines
Reaction
conditionsa
[Time (h); Yield (%)]
NHR
NTs
1.
OBn
OBn
NHTs
2a: R = Me
3a: R = Bn
1a
A [10; 82]
B [4; 98]
The importance of aziridinyl compounds as precursors of
amines, diamines, amino alcohols and various other nitrogen
containing products are attracting increasing attentions as organic
chemists develop new methodologies for regio- and stereoselec-
tive opening of aziridine rings using various nucleophiles.1{18 In
this paper we describe efficient openings of N-tosyl aziridines 1
with methyl- and benzylamines in CH3CN leading to the
formation of diamines 2 and 3. However, similar ring opening
reactions with water required catalytic amounts of cerium(IV)
ammonium nitrate (CAN)19{21 that provided amino alcohols 4 in
good yields under very mild conditions.
NHR
NTs
NHTs
2.
1b
2b: R = Me
3b: R = Bn
A [12; 81]
B [12; no reaction]
NHR
NTs
CO2Et
3.
CO2Et
NHTs
1c
2c: R = Me
3c: R = Bn
A [12; 84]
B [3; 73]
NHR
NTs
CO2Et
CO2Et
NHTs
R2
R3
4.
H
R1
NHTs
RNH2, CH3CN
Cl
Cl
Ts
N
NHR
R2
R3
1d
2d: R = Me
3d: R = Bn
A [8; 90]
B [5; 92]
H
2: R = Me; 3: R = PhCH2
NHTs
R1
CAN (cat.)
H2O:CH3CN (1:10)
NHR
H
R1
R2
R3
NTs
1
CO2Et
CO2Et
OH
5.
NHTs
4
O2N
O2N
1e
2e: R = Me
3e: R = Bn
A [10; 78]
B [4; 92]
The starting aziridines 1a–f were prepared from the corre-
sponding epoxides in four steps: (a) ring opening of the epoxides
with NaN3 in MeOH : H2O (8 : 1) in presence of NH4Cl;22 (b)
reduction of the resulting azides to amines using Ph3P in dry THF;
(c) protection of the amines as tosylates using TsCl, Et3N in
CH2Cl2 and (d) treatment of N-tosyl amino alcohols with diethyl
azodicarboxylate and Ph3P in dry THF. The remaining aziridines
1g and 1h were made by reacting the respective olefins with
chloramine-T and I2 (cat.) in CH3CN. The aziridines, thus
prepared, were treated with MeNH2ꢁHCl or benzylamine, with
equimolar amounts of Et3N for the former, at 0 ꢂC in dry CH3CN
under N2 atmosphere. Reactions were continued at room
temperature until the starting materials completely disappeared.
Aqueous work-up was followed by chromatographic purification
to furnish the diamines in excellent yields. Reactions with benzyl-
amine were faster compared to those with methylamine. The
results are summarized in Table 1.
NHR
NTs
CO2Et
CO2Et
Me
NHTs
6.
7.
Me
1f
2f: R = Me
3f: R = Bn
A [12; no reaction]
B [8;b 70]
NHR
NTs
NHTs
1g
2g: R = Me
3g: R = Bn
A [12, no reaction]
B [7; 87]
NHR
8.
NTs
NHTs
1h
2h: R = Me
3h: R = Bn
A [12, no reaction]
B [3;c 92]
a
.
A: MeNH2 HCl (10 eq), Et3N (10 eq), CH3CN, 0 °C to rt; B: PhCH2NH2
(10 eq), CH3CN, 0 °C to rt. b reaction went to completion only under
refluxing condition. c reaction was carried out at 55 °C.
Only one regioisomer was obtained in aryl-substituted
aziridines when the reactions were carried out at room tempera-
ture and the ring openings occurred exclusively at the benzylic
positions. The N-tosyl aziridine of styrene (1b, entry 2, Table 1)
did not undergo any reaction when treated with BnNH2 at room
temperature even after long reaction hours. When the temperature
was raised to 45 ꢂC, two regioisomers were obtained in 4 : 1 ratio,
the major one being formed by opening of the ring at the benzylic
position. The selectivity was completely lost at refluxing
temperature.
The trisubstituted aziridine 1f did not undergo any reaction
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.1 (2003)
83
with methylamine. However, with benzylamine, the opening
could be achieved only under refluxing condition to give the
expected diamine 3f. No double ring opening was observed in any
of these reactions.5 The aziridines with aliphatic substituents 1g
and 1h did not undergo any reaction with MeNH2.
(9 Hz, for example, for the oxazolidinone from 4c) confirmed the
cis orientations of the ring protons24 and that, in turn, supported
the assigned stereochemistries of the products.
In conclusion, the methods described here for efficient ring
openings of N-tosyl aziridines with amines and particularly, the
CAN-catalyzed openings with water under very mild conditions
will find useful applications in the synthesis of various diamines
and amino alcohols. Further work is under progress.
1
The structural assignments were made on the basis of H
NMR studies and decoupling experiments. The diamine 2a, for
example, showed connectivity among the CH2OBn,
CH(CH2OBn) and NHTs protons determined by irradiating the
CH(CH2OBn) signal that caused decoupling of the protons
attached to it. This was further supported by two-dimensional
double quantum filtered correlation spectroscopy (DQF COSY)
experiment.23 The structures of other diamines were similarly
assigned.
Authors wish to thank Drs. A. C. Kunwar and M. Vairamani
for NMR and mass spectroscopic assistance, respectively; CSIR,
New Delhi for research fellowship (A.G.).
References
1
For some recent reviews on aziridines see: a) R. S. Atkinson,
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Next, six of these aziridines 1a–d, 1g, and 1h were taken in
water–CH3CN (1 : 10), cooled to 0 ꢂC and treated with catalytic
amounts of CAN (0.1–0.2 eq). This led to facile opening of the
aziridine rings with hydroxyl group to furnish the amino alcohols
4a–d, 4g, and 4h in good yields. The results are summarized in
Table 2. Here, once again, only one regioisomer was obtained in
aryl-substituted aziridines. The structural assignments were made
in the same way as they were done for the diamines. Both H
NMR decouplings and DQF COSY experiments were utilized to
prove the observed regioselectivities.
2
3
4
5
6
7
8
9
1
Table 2. Opening of N-tosyl aziridines (1) with water using
catalytic amount of CANa
Entry
1.
Starting
Aziridines
Product
Amino alcohols
OH
Time (h);
Yield (%)
NTs
OBn
OBn
NHTs
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4a
2.5; 82
2; 85
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1b
4b
OH
NTs
CO2Et
CO2Et
NHTs
1c
4c
8; 75
OH
NTs
CO2Et
CO2Et
4.
5.
6.
NHTs
Cl
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1d
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7;b 88
OH
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OH
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a CAN (0.1 eq), H2O:CH3CN (1:10), 0 °C to rt (50 °C in entry 4). b 0.2 eq
CAN was used.
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