Catalyst-free highly regio- and stereoselective ring opening of epoxides and aziridines with sodium azide using poly(ethylene glycol) as an efficient reaction medium

Article abstract of DOI:10.1055/s-2007-965921

Ring opening of epoxides and aziridines has readily been carried out at room temperature using poly(ethylene glycol) (PEG-400) as the efficient reaction medium to form the corresponding 2-azido alcohols and 2-azido amines, respectively, in excellent yield

Full text of DOI:10.1055/s-2007-965921

666
SHORT PAPER
Catalyst-Free Highly Regio- and Stereoselective Ring Opening of Epoxides
and Aziridines with Sodium Azide Using Poly(ethylene glycol) as an Efficient
Reaction Medium1
R
ing-Opening of
i
E
poxid
s
es
a
nd A
z
w
iridines anath Das,* Vtukuri Saidi Reddy, Fouzia Tehseen, Maddeboina Krishnaiah
Organic Chemistry Division – I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)7160512; E-mail: biswanathdas@yahoo.com
Received 10 November 2006; revised 5 December 2006
NaN3
O
PEG
OH
N3
Abstract: Ring opening of epoxides and aziridines has readily been
carried out at room temperature using poly(ethylene glycol) (PEG-
400) as the efficient reaction medium to form the corresponding 2-
azido alcohols and 2-azido amines, respectively, in excellent yields
(95–99%) within 30–45 minutes and with high regio- and streose-
lectivity.
N3
OH
or
95–99%
r.t., 30–45 min
R
R
R
NHTs
N3
NaN3
PEG
NHTs
N3
NHTs
or
r.t., 30–45 min
Key words: epoxide, aziridine, PEG-400, 2-azido alcohol, 2-azido
amine
R
R
R
95–99%
Scheme 1
2-Azido alcohols are valuable precursors for 2-amino al-
cohols which are present in various natural products and
different bioactive compounds.2 They are also useful for
the synthesis of amino sugars and carbocyclic nucleo-
sides.3 2-Azido amines are important as intermediates for
the preparation of vicinal diamines which are medicinally
valuable4 and also have different applications in organic
syntheses.5 The useful synthetic route to 2-azido alcohols
and 2-azido amines involves ring opening of epoxides and
aziridines, respectively, with azide anion. The classical
protocol for the preparation of azidohydrins using NaN3
and NH4Cl requires a longer reaction time (12–48 h) and
forms side products.2a,b The modified methods for azido-
lysis of epoxides6 and aziridines6f,7 use a combination of
NaN3 or TMSN3 and a Lewis acid or a transition-metal
complex. Although these methods are valuable for the
preparation of 2-azido alcohols and 2-azido amines, many
are associated with drawbacks, such as longer reaction
times, high temperature, unsatisfactory yields and poor re-
gioselectivity. Thus, an improved protocol for the prepa-
ration of these compounds is essential.
was complete within a short period of time. Both epoxides
and azidridines afforded the products with equal ease.
The ring opening of epoxides and aziridines took place
with high regio- and stereoselectivity. 2-Alkylepoxides
and 2-alkyl-N-tosylaziridines yielded the products formed
by opening at the terminal position while 2-phenylep-
oxide (styrene oxide) and 2-phenyl-N-tosylaziridine af-
forded the products formed by cleavage at the benzylic
position. The structures of 2-azido alcohols and 2-azido-
N-tosyl amines were established from their spectral (IR,
1H NMR and MS) and analytical data.
The ring opening of bicyclic epoxides and aziridines with
NaN3 afforded the products with trans-configuration indi-
cating the conversion to be anti-stereoselective. In the 1H
NMR spectra, the ring protons of 2j appeared at d = 3.35
(1 H, ddd, J = 9.8, 9.2, 4.2 Hz) (CHOH) and 3.12 (1 H,
ddd, J = 9.5, 9.2, 4.2 Hz) (CHN3), while those of 2p at d =
3.73 (1 H, m) (CHNHTs) and 3.34 (1 H, ddd, J = 9.5, 9.2,
4.1 Hz) (CHN3).
Poly(ethylene glycol) (PEG-400)9 has been used in the
present conversion as an efficient reaction medium. This
is a biologically acceptable polymer and is inexpensive
and eco-friendly. However, its applications as a reaction
medium in organic syntheses have not yet been fully ex-
plored. In absence of PEG it was found that azidolysis of
epoxides and aziridines did not take place. The role of
PEG is possibly to activate these compounds through hy-
drogen bonding. The PEG was recovered from the reac-
tion mixture and was reused without loss of activity.
In continuation of our work8 on the development of useful
synthetic methodologies we have recently observed that
azidolysis of epoxides and aziridines can efficiently be
carried out with NaN3 in poly(ethylene glycol) (PEG-400)
(Scheme 1).
Several epoxides and N-tosylaziridines underwent ring
cleavage readily with NaN3 in PEG at room temperature
to form the corresponding azido alcohols and N-tosylazi-
do amines respectively (Table 1). No additional catalyst
was required. The products were formed in excellent
yields and no side products were detected. The conversion
SYNTHESIS 2007, No. 5, pp 0666–0668
x
x
.
x
x
.2
0
0
7
Advanced online publication: 08.02.2007
DOI: 10.1055/s-2007-965921; Art ID: Z23506SS
© Georg Thieme Verlag Stuttgart · New York

SHORT PAPER
Ring Opening of Epxides and Aziridines
667
Table 1 Ring Opening of Epoxides and Aziridines with NaN3 in PEG
Entry
Epoxide/Aziridine 1
Product 2
Time (min)
35
Isolated yield (%)a Ref.
O
N3
OH
OH
a
98
96
95
6f
6f
6g
O
O
O
N3
b
c
40
45
OH
O
O
O
O
O
N3
Cl
Cl
Cl
Cl
OH
O
N3
d
40
95
6f
Cl
Cl
OH
O
O
O
N3
e
f
40
45
96
95
6f
6f
OH
O
O
O
N3
OH
O
g
30
45
97
95
6f
6f
N3
OH
O
h
N3
OH
i
35
30
40
99
98
95
6f
6f
6f
O
N3
OH
j
O
N3
OH
k
O
N3
N3
NTs
NHTs
l
40
45
99
98
6f
6f
N3
NTs
NHTs
m
NHTs
NTs
n
o
45
40
96
95
6f
N3
NHTs
NTs
7e
N3
Synthesis 2007, No. 5, 666–668 © Thieme Stuttgart · New York

668
B. Das et al.
SHORT PAPER
Table 1 Ring Opening of Epoxides and Aziridines with NaN3 in PEG (continued)
Entry
Epoxide/Aziridine 1
Product 2
Time (min)
45
Isolated yield (%)a Ref.
NHTs
p
96
99
7e
6f
NTS
N3
NHTS
q
40
NTS
N3
a The structures of the products were established from their spectral (IR, 1H NMR and MS) and analytical data.
(3) (a) Horton, D.; Wander, J. D. The Carbohydrates, Vol. 1B;
Pigman, W.; Horton, D., Eds.; Academic Press: New York,
1980, 643. (b) Schubert, J.; Schwesinger, R.; Prinzbach, H.
Angew. Chem., Int. Ed. Engl. 1984, 23, 167.
(4) Reetz, M. T.; Jaeger, R.; Drewlies, R.; Hubel, M. Angew.
Chem., Int. Ed. Engl. 1991, 30, 103.
In conclusion, we have developed a simple and efficient
method for azidolysis of epoxides and aziridines with
NaN3 using PEG at room temperature. The mildness and
eco-friendly nature of the conversion, shorter reaction
times, impressive yields and excellent regio- and stereose-
lectivity are the considerable advantages to make the
present method superior to the existing methods for the
preparation of 2-azido alcohols and 2-azido amines.
(5) Lucet, D.; Le Gall, T.; Mioskowski, C. Angew. Chem. Int.
Ed. 1998, 37, 2850.
(6) (a) Chong, J. M.; Sharpless, K. B. J. Org. Chem. 1985, 50,
1560. (b) Nugent, W. A. J. Am. Chem. Soc. 1992, 114, 2768.
(c) Blandy, C.; Choukroun, R.; Gervais, D. Tetrahedron
Lett. 1993, 24, 4189. (d) Fringuelli, F.; Piermatti, O.; Pizzo,
F.; Vaccaro, L. J. Org. Chem. 1999, 64, 6094.
2-Azido Alcohols or Amines; General Procedure
To a stirred suspension of an epoxide (or N-tosyl aziridine) (1
mmol) in PEG-400 (2 g), was added NaN3 (78 mg, 1.2 mmol) and
the mixture was stirred at r.t. The reaction was monitored by TLC.
After completion, the mixture was poured onto H2O (10 mL) and
was extracted with EtOAc (2 × 10 mL). The solvent was removed
and the crude product was subjected to column chromatography
(silica gel, hexane–EtOAc) to obtain pure azidohydrin (or N-tosyl-
azido amine) (Table 1). The PEG was recovered from the aqueous
layer and was reused without loss of activity.
(e) Fringuelli, F.; Pizzo, F.; Vaccaro, L. J. Org. Chem. 2001,
66, 4719. (f) Sabitha, G.; Babu, R. S.; Rajkumar, M.; Yadav,
J. S. Org. Lett. 2002, 4, 343. (g) Yadav, J. S.; Reddy, B. V.
S.; Jyothirmai, B.; Murty, M. S. R. Tetrahedron Lett. 2005,
46, 6559.
(7) (a) Leung, W. H.; Yu, M. T.; Wu, M. C.; Yeung, L. L.
Tetrahedron Lett. 1996, 37, 891. (b) Ferrarsi, D.; Drury, W.
J. III; Cox, C.; Lectka, T. J. Org. Chem. 1998, 63, 4568.
(c) Li, Z.; Fernandez, M.; Jacobsen, E. N. Org. Lett. 1999, 1,
1611. (d) Wu, J.; Hou, X. L.; Dai, L. X. J. Org. Chem. 2000,
65, 1344. (e) Bisai, A.; Pandey, G.; Pandey, M. K.; Singh, V.
K. Tetrahedron Lett. 2003, 44, 5839.
Acknowledgment
(8) (a) Das, B.; Ramu, R.; Ravikanth, B.; Reddy, K. R.
Tetrahedron Lett. 2006, 47, 779. (b) Das, B.; Thirupathi, P.;
Reddy, V. S.; Rao, Y. K. J. Mol. Catal. A: Chem. 2006, 247,
233. (c) Das, B.; Krishnaiah, M.; Venkateswarlu, K.
Tetrahedron Lett. 2006, 47, 4457. (d) Das, B.; Ravikanth,
B.; Thirupati, P.; Rao, B. V. Tetrahedron Lett. 2006, 47,
5041.
(9) (a) Dickerson, T. J.; Reed, N. N.; Janda, K. D. Chem. Rev.
2002, 102, 3325. (b) Chandrasekhar, S.; Narsihmulu, Ch.;
Shameem Sultana, S.; Ramakrishna Reddy, N. Chem.
Commun. 2003, 1716.
The authors thank UGC and CSIR New Delhi for financial assis-
tance.
References
(1) Part 103 in the series ‘Studies on Novel Synthetic
Methodologies’; IICT Communication no. 061206.
(2) (a) The Chemistry of the Azido Group; Patai, S., Ed.; Wiley:
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Synthesis 2007, No. 5, 666–668 © Thieme Stuttgart · New York