NaIO4/LiBr-mediated aziridination of olefins using chloramine-T

Article abstract of DOI:10.1016/j.tetlet.2010.10.005

A new milder protocol for aziridination of a variety of olefins has been described. The process employs catalytic amount of sodium metaperiodate (NaIO₄) as an oxidant and LiBr and chloramine-T as the bromine and nitrogen sources, respectively. Interestingly, the formation of aziridine products in all the cases studied takes place presumably through a process of 1,2-aminobromination of alkenes.

Full text of DOI:10.1016/j.tetlet.2010.10.005

Tetrahedron Letters 51 (2010) 6460–6462
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NaIO4/LiBr-mediated aziridination of olefins using chloramine-T
Pratibha U. Karabal, Pandurang V. Chouthaiwale, Tanveer M. Shaikh, Gurunath Suryavanshi,
⇑
Arumugam Sudalai
Chemical Engineering and Process Development Division, National Chemical Laboratory, Pashan Road, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A new milder protocol for aziridination of a variety of olefins has been described. The process employs
catalytic amount of sodium metaperiodate (NaIO4) as an oxidant and LiBr and chloramine-T as the bro-
mine and nitrogen sources, respectively. Interestingly, the formation of aziridine products in all the cases
studied takes place presumably through a process of 1,2-aminobromination of alkenes.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 13 August 2010
Revised 28 September 2010
Accepted 1 October 2010
Available online 8 October 2010
Keywords:
Aziridination
Chloramine-T
Lithium bromide
Olefin
Sodium metaperiodate
Aziridines with a strained ring are of paramount importance in
organic synthesis since they are valuable precursors of amino sug-
chloramine-T (all 1 equiv) in CH3CN at 25 °C, the corresponding
N-tosylaziridine (2a) was obtained in 20% yield; however, the yield
could be significantly improved to 65% when 2 equiv of chlora-
mine-T was used. Interestingly, lowering the molar ratio of NaIO4
(30 mol %) resulted in a dramatic improvement in the yield of 2a
(81%) along with the formation of 3 as a minor product. However,
further lowering of the concentration of either H2SO4 or LiBr had a
deleterious effect on the yield (entries 4 and 7). In general, higher
chloramine-T concentration (2 equiv) gave better yields. After sev-
eral experimentation, it was finally found that a combination of
NaIO4 (30 mol %); olefin/LiBr/chloramine-T (1:1:2 equiv), and conc.
H2SO4 (30 mol %), in CH3CN, 25 °C, 12 h turned out to be the best
reaction condition in achieving a good conversion of alkenes with
excellent product selectivity. The reaction mixture became homo-
geneous as it proceeded. In the absence of either NaIO4 or LiBr, no
reaction occurred; also the reaction failed when other amine
sources such as p-TsNH2 and p-TsNCl2 were used. A brief compar-
ison of solvents demonstrated that CH3CN was the most suitable
ars, alkaloids, and substituted a
-amino acids1 or present in natural
products such as mitomycins2 and azinomycins3 that exhibit po-
tent biological activity. A variety of catalytic4 as well as non-cata-
lytic5 routes have been established for the direct aziridination of
alkenes. Recent studies mention the use of several halogenated
compounds6 in the aziridination of olefins with chloramine-T as
the nitrogen source. However, these methods suffer from certain
drawbacks: (i) the use of heavy transition metals as catalysts, (ii)
low yields possibly due to competing C–H abstraction and inser-
tion processes, (iii) the expense and inconvenience of PhI@NTs as
a nitrene source, and (iv) formation of significant amounts of allylic
amination products in the case of cyclohexene. During the course
of our study on NaIO4-mediated oxidative transformations of al-
kenes, we demonstrated the regiospecific halohydroxylation7 and
iodoazidation8 of olefins in the presence of water or NaN3, respec-
tively. This prompted us to explore the possibility of employing
chloramine-T9 as the nitrogen nucleophile in the 1,2-aminobro-
mination of alkenes mediated by NaIO4–LiBr combination. In this
communication, we describe a novel milder method that involves
a reaction of NaIO4/LiBr/H+/chloramine-T combination with ole-
fins; thus affording aziridines 2 in good yields (Scheme 1).
Ts
NHTs
N
i
+
R
R
R
Using styrene as a test substrate, the reaction conditions
were optimized to determine the optimal condition for aziridin-
ation, Table 1. When styrene was treated with NaIO4, LiBr, and
Br
1
2a : R = phenyl; 81%
3 : 7%
2k : R = cyclohexyl; 58%
4 : 30%
⇑
Corresponding author. Tel.: +91 20 25902174; fax: +91 20 25902676.
E-mail address: a.sudalai@ncl.res.in (A. Sudalai).
Scheme 1. Reagents and conditions: (i) NaIO4 (30 mol %); olefin/LiBr/chloramine-
T = 1:1:2 (equiv), conc. H2SO4 (30 mol %), CH3CN, 25 °C, 12 h.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.005

P. U. Karabal et al. / Tetrahedron Letters 51 (2010) 6460–6462
6461
Table 1
NaIO4-mediated aziridination of styrene with chloramine-T and LiBra
Entry
NaIO4 (equiv)
LiBr (equiv)
Chloramine-Tb (equiv)
Conc. H2SO4 (mol %)
Yield 2ac (%)
1
2
3
4
5
6
7
1
1
1
1
1
1
1
1
0.3
1.1
2
1.1
1.1
2
30
30
30
10
30
30
30
20
65
40
0.3
0.3
0.3
0.5
1
25
81d
62
2
2
35
Reaction conditions: aexperiments were conducted with styrene (1 equiv as substrate) in dry CH3CN as solvent; temp = 25 °C; time = 12 h; banhydrous chloramine-T was
used;9 cisolated yield after column chromatographic purification; d7% of 1-phenyl-1-(p-toluenesulfonamido)-2-bromoethane 3 was isolated.
Table 2
Scope of the aziridination reaction mediated by NaIO4–LiBr–chloramine-T combinationa
Entry
Substrate (1)
Productb (2)
Yieldc (%)
Mp (°C)
Ts
N
R
1
R
2a
2b
81 (R = H)
79 (R = Cl)
92–94
Gum
Ts
N
R
2
R
2c
2d
2e
2f
77 (R = Cl)
75 (R = F)
72 (R = Br)
40 (R = CH3)
115–116
136–138
127–129
130–131
N
2g
Ts
3
4
80
Gum
Ts
N
Cl
2h
65
101–103
Cl
Ph
Ts
Ph
N
2i
5
6
64
60
140–142
Gum
Ph
Ph
Ts
4
N
2j
4
Ts
N
58d
94–95
2k
7
8
N
Ts
n
n
2l
2m
60 (n = 1)
48 (n = 3)
55–57
122–123
Ts
N
2n
9
52
60
164–166
75–78
Br
Br
N
2o
10
Ts
Reaction conditions: aalkenes (3 mmol), LiBr (3 mmol), chloramine-T (6 mmol), NaIO4 (30 mol %), H2SO4 (30 mol %), 25 °C, 12 h; bproducts were characterized by mp, IR, 1
and 13C NMR and elemental analysis; cisolated yield after chromatographic purification; d30% of aminobrominated product (4) was formed.
H
solvent for aziridination as other solvents like CH2Cl2, CHCl3, THF,
and Et2O were found to be ineffective.
Encouraged by these results, substrate scope of NaIO4-mediated
aziridination was next examined using the conditions optimized
for the aziridination of styrene. As can be seen from Table 2, a wide
array of aromatic, cyclic, and acyclic olefins afforded the corre-
sponding aziridines, 2a–o in good isolated yields.10 With styrene
derivatives, the reaction proceeded well giving aziridines 2a–i in

6462
P. U. Karabal et al. / Tetrahedron Letters 51 (2010) 6460–6462
+
Acknowledgments
TsNClNa
-NaBr
styrene
H
TsNBrCl
NaIO4
+
LiBr
Br2
P.K. and P.V.C. thank the Department of Science andTechnology,
New Delhi (No. SR/S1/OC-72/2006) for financial support. The
authors also thank Dr. B.D. Kulkarni, Head, Chemical Engineering
and Process Development Division for his encouragement and
support.
Ts
Cl
+
N
Cl
Br
N
Cl
Br
H2O
N
Ts
+
+
Ts
-NaBr
References and notes
B
A
1. (a) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247; (b) McCoull, W.; Davis, F. A.
Synthesis 2000, 1347; (c) Moessner, C.; Bolm, C., In Transition Metals For Organic
Chemistry: Building Blocks and Fine Chemicals; 2nd ed.; Beller, M, Bolm, C., Eds.;
Wiley/VCH: Weinheim, 2004; Vol. II, p 389; (d) Yudin, A. K. Aziridines and
Epoxides in Organic Synthesis; Wiley-VCH: Weinheim, 2006. P 1; (e) Branco, P. S.
In Recent Research Developments in Heterocyclic Chemistry; Melo, T. M. V. D. P. e.,
Ed.; Research Signpost: India, 2007; p 1.
2. (a) Padwa, A.; Woolhouse, A. D. In Comprehensive Heterocyclic Chemistry;
Hassner, A., Ed.; Pergamon: Oxford, 1984; p 47; (b) Kasai, M.; Kono, M. Synlett
1992, 778.
Ts
+
N
TsNH2
Scheme 2. Plausible mechanistic pathway for NaIO4-mediated aziridination.
3. Hodgkinson, T. J.; Shipman, M. Tetrahedron 2001, 57, 4467.
4. (a) Mohan, J. M.; Uphade, B. S.; Choudhary, V. R.; Ravindranathan, T.; Sudalai, A.
Chem. Commun. 1997, 1429; (b) Muller, P.; Fruit, C. Chem. Rev. 2003, 103, 2905;
(c) Vyas, R.; Gao, G.-Y.; Harden, J. D.; Zhang, X. P. Org. Lett. 2004, 6, 1907; (d)
Sun, W.; Herdtweck, E.; Kühn, F. E. New J. Chem. 2005, 29, 1577; (e) Gao, G. Y.;
Jones, J. E.; Vyas, R.; Harden, J. D.; Zhang, X. P. J. Org. Chem. 2006, 71, 6655; (f)
Lebel, H.; Lectard, S.; Parmentier, M. Org. Lett. 2007, 9, 4797; (g) Mayer, A. C.;
Salit, A. F.; Bolm, C. Chem. Commun. 2008, 5975; (h) Branco, P. S.; Raje, V. P.;
Dourado, J.; Gordo, J. Org. Biomol. Chem. 2010, 8, 2968.
moderate to good yields (entries 1–4). The better results however
were achieved with allylbenzene (80%) and unsubstituted styrene
(81%). Monosubstituted terminal olefins, one of the most challeng-
ing substrates, such as 1-octene produced a reasonably good yield
(60%) of the corresponding N-tosyl aziridine. Allyl bromide also re-
acted very well (60%) under the reaction conditions without allylic
amination. Notably, cyclic alkenes were also transformed to the
corresponding aziridines 2l–m in moderate yields (entry 8). In con-
5. Deyrup, J. A.. In The Chemistry of Heterocyclic Compounds; Hassner, A., Ed.; Sage:
New York, 1983; Vol. 42,.
6. (a) Jeong, J. U.; Tao, B.; Sagasser, I.; Henniges, H.; Sharpless, K. B. J. Am. Chem.
Soc. 1998, 120, 6844; (b) Ando, T.; Kano, D.; Minakata, S.; Ryu, I.; Komatsu, M.
Tetrahedron 1998, 54, 13485; (c) Ali, S. I.; Nikalje, M. D.; Sudalai, A. Org. Lett.
1999, 1, 705; (d) Thakur, V.; Sudalai, A. Tetrahedron Lett. 2003, 44, 989; (e) Wu,
H.; Xu, L. W.; Xia, C. G.; Ge, J.; Yang, L. Synth. Commun. 2005, 35, 1413.
7. Dewkar, G. K.; Narina, S. V.; Sudalai, A. Org. Lett. 2003, 5, 4501.
8. Chouthaiwale, P. V.; Karabal, P. U.; Suryavanshi, G.; Sudalai, A. Synthesis, in
press, doi:10.1055/s-0030-1258250.
trast, electron-deficient olefins such as a,b-unsaturated esters and
ketones exhibited only low reactivity and yielded their aziridine
derivatives in only 10–20% yield. No byproduct other than p-tosa-
mide was detected by TLC or NMR in all the substrates examined.
Although the exact nature of the species involved in the reaction is
not known, our earlier studies7 had shown that 1 equiv of NaIO4
9. Sharpless, K. B.; Hori, T.; Truesdale, L. K.; Dietrich, C. O. J. Am. Chem. Soc. 1976,
98, 269.
10. General experimental procedure for aziridination of olefins:
was sufficient to oxidize 8 equiv of Brꢀ ions, ðIO4ꢀ þ 8Hþ þ 8eꢀ
!
4H2O þ IꢀÞ. Hence, only 30 mol % of NaIO4 was required to bring
about 100% conversions. From the above facts and the evidence
provided by the cyclic voltammetry study, it is believed that Br2,
generated by the NaIO4-mediated oxidation of LiBr in acidic condi-
tion, reacts with chloramine-T to give the reactive species TsNBrCl,
which then subsequently adds onto styrene to form bromonium
ion A. The stereospecific opening of A with TsNClꢀ at the benzylic
position occurs to give b-bromo-N-chloro-N-toluenesulfonamide
(B). Finally, cyclization of B with another molecule of chlora-
mine-T results in the formation of aziridine, along with the gener-
ation of 1 mole of TsNCl2; the hydrolysis of which leads to isolation
of TsNH2 as the by product (Scheme 2).
To a stirred solution of olefin (3 mmol) in dry CH3CN (25 mL), anhydrous
chloramine-T (1.365 g, 6 mmol), LiBr (0.257 g, 3 mmol), NaIO4 (0.192 g
30 mol %), and concd H2SO4 (0.088 g, 30 mol %) were added at 25 °C. The
resulting reaction mixture was stirred at 25 °C (monitored by TLC). After
completion, the reaction mixture was diluted with EtOAc (15 mL) and washed
with water followed by aq saturated Na2S2O3 (2 ꢁ 15 mL) solution. The organic
layer was dried over anhyd Na2SO4, concentrated under pressure to afford
crude product, which was purified by column chromatography on silica gel
using pet. ether and EtOAc (10:1) as eluent to afford pure aziridines 2a–o.
N-(p-Toluenesulfonyl)-2-benzylaziridine (2g): Yield: 80%; gum; IR (CHCl3, cmꢀ1):
675, 770, 840, 915, 1090, 1130, 1250, 1355, 1370, 1400, 1480, 2880, 2910,
2980, 3280; 1H NMR (200 MHz, CDCl3) d 2.14 (d, J = 4.5 Hz, 1H), 2.43 (s, 3H),
2.65–2.78 (m, 3H), 2.82–2.93 (m, 1H), 7.01–7.07 (m, 2H), 7.12–7.26 (m, 5H),
7.68 (d, J = 8.4 Hz, 2H); 13C NMR (50 MHz, CDCl3): 21.4, 32.5, 37.2, 40.9, 126.2,
127.7, 28.2, 128.5, 129.3, 134.4, 136.8, 143.9; Anal. Calcd for C16H17NO2S
requires C, 66.87%; H, 5.96%; N, 4.87%. Found: C, 66.80%; H, 6.01%; N, 4.90%.
N-(p-Toluenesulfonyl)-2-bromomethylaziridine (2o): Yield: 60%; mp: 75–78 °C;
IR (CHCl3, cmꢀ1): 1093, 1119, 1292, 1328, 1403, 1597, 2926, 2981, 3029, 3132,
3150, 3175, 3200, 3277; 1H NMR (200 MHz, CDCl3) d 2.45 (s, 3H), 3.50–3.65 (m,
1H), 3.75–3.80 (m 1H), 4.10–4.30 (m, 1H), 5.01–5.25 (m, 1H), 7.35 (d, J = 8.2 Hz,
2H), 7.85 (d, J = 8.2 Hz, 2H); 13C NMR (50 MHz, CDCl3): d 21.3, 32.8, 47.2, 49.92,
126.9 129.7, 136.6, 143.7; Anal. Calcd for C10H12BrNO2S requires C, 41.39%; H,
4.17%; N, 4.83%. Found: C, 41.35%; H, 4.19%; N, 4.80%.
In conclusion, a mild one-pot procedure for the preparation of
N-tosyl-2-substituted aziridines is reported. The method employs
catalytic amount of NaIO4 as an oxidant and LiBr and chlora-
mine-T as the bromine and nitrogen sources, respectively. Further
experiments to define the nature of the species involved in the
process and the stereochemical aspects of the reaction are in
progress.