A mild and efficient synthesis of α-tosylamino ketones from aryl aziridines in the presence of β-cyclodextrin and NBS in water

Article abstract of DOI:10.1016/j.tetlet.2004.12.125

NBS has been utilized for the first time for the oxidative cleavage of aryl aziridines involving β-cyclodextrin-aziridine complexes in water to give the corresponding α-amino ketones in high yields.

Full text of DOI:10.1016/j.tetlet.2004.12.125

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1299–1301
A mild and efficient synthesis of a-tosylamino ketones from aryl
q
aziridines in the presence of b-cyclodextrin and NBS in water
M. Somi Reddy, M. Narender and K. Rama Rao*
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 13 October 2004; revised 17 December 2004; accepted 22 December 2004
Available online 13 January 2005
Abstract—NBS has been utilized for the first time for the oxidative cleavage of aryl aziridines involving b-cyclodextrin–aziridine
complexes in water to give the corresponding a-amino ketones in high yields.
Ó 2005 Elsevier Ltd. All rights reserved.
a-Amino aryl ketones are an important class of organic
synthetic intermediates which have found use in organic
and medicinal chemistry. a-Amino arylketones also
Ts
N
O
NBS/H
O
2
NHTs
1
50 ºC,12 h
R
R
provide starting materials for the synthesis of biologi-
cally active b-aminoalcohols. Only a few direct methods
are available for the preparation of these amino ke-
β-CD
1
2
2
–4
tones.
These methods have various limitations such
R= H, p-Me, p-Cl, m-Cl, p-Br, p-OMe, p-COMe
as the use of transition metal catalysts, organic solvents,
controlled temperatures, long reaction times, and haz-
ardous reagents. Thus, there is still a need to develop
cleaner synthetic methodologies for the generation of
a-amino ketones.
Scheme 1.
ity. They promote reactions by supramolecular catalysis
involving reversible formation of host–guest complexes
using non-covalent bonding, as seen in enzymes. Com-
plexation depends on the size, shape, and hydrophobi-
city of the guest molecule. These attractive features of
cyclodextrins in the biomimetic modeling of chemical
reactions prompted us to investigate a variety of oxida-
tions using the substrate–b-cyclodextrin complexes with
NBS in water. The complexes were prepared with b-
cyclodextrin since it is easily accessible and least expen-
sive among the cyclodextrins.
One of the goals of present day organic synthesis is to
developenvironmentally benign and clean synthetic pro-
cedures with high atom economy. For example, the
development of chemical reactions in water shows
advantages over the use of organic solvents since water
is safe, economical, and environmentally benign. In con-
tinuation of our work on biomimetic modeling of chem-
5
ical reactions involving cyclodextrins in water, we
report here for the first time the direct synthesis of a-
tosylamino ketones from easily accessible and inexpen-
sive aryl aziridines using NBS as a mild oxidizing agent
in water as solvent (Scheme 1).
6
The N-tosylaziridines were synthesized as reported. The
b-cyclodextrin inclusion complexes of the aziridines
were prepared in water as described by us earlier. The
5
reactions were carried out by the in situ formation of
the b-cyclodextrin complex of the aziridine 1 in water
Cyclodextrins are cyclic oligosaccharides possessing
hydrophobic cavities, which bind substrates selectively
and catalyze chemical reactions with high regioselectiv-
7
followed by the addition of NBS and stirring at 50 °C
to give the corresponding a-tosylamino ketones 2 in very
high yields (Table 1). All the compounds were character-
1
ized by H NMR, mass and IR spectroscopy, and by ele-
Keywords: Aziridines; a-Amino ketones; b-Cyclodextrin; Water.
q
IICT Communication No. 041201.
mental analysis or otherwise compared with data for
8
*
Corresponding author. Tel.: +91 40 27193164; fax: +91 40
7160757; e-mail: drkrrao@yahoo.com
known compounds. b-Cyclodextrin can be easily recov-
ered and reused a number of times. These reactions did
2
0
040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.12.125

1300
M. S. Reddy et al. / Tetrahedron Letters 46 (2005) 1299–1301
not take place in the absence of b-CD. Succinimide, ob-
tained as a by-product, can be recycled to NBS as de-
scribed earlier. These cyclodextrin mediated water
based reactions proceed under mild conditions and
avoid flammable and anhydrous organic solvents.
Thus, we have demonstrated that a-tosylamino ketones
2 can be generated directly from easily accessible azir-
idines in the presence of b-cyclodextrin and NBS in
water. To our knowledge, this is the first report on the
synthesis of a-tosylamino ketones directly from azir-
idines and NBS in a single step.
9
The evidence for the inclusion complex of the aziridines
1
3
with b-cyclodextrin was derived through 1 C NMR
Physical data of novel compounds:
0
examination during our earlier studies.
observed that the methyl and tertiary carbons of the
It was
3-Chloro-1-(2-(4-methylphenylsulfonamino)acetyl)benz-
ene (Table 1, entry 4): solid, mp: 116 °C, IR (neat): 3448,
p-toluenesulfonyl groupas well as the methylene carbon
(
À1
1
b-position) of the aziridine ring are deshielded indica-
2923, 1701 cm . H NMR (CDCl , 300 MHz): d 2.42
3
ting their inclusion in the hydrophobic cavity of the
cyclodextrin. Thus, only the a-position of the aziridine
ring is exposed to attack leading to high regioselectivity.
We suggest that water can attack only at the exposed a-
position of the aziridine in the supramolecular complex
and is facilitated through hydrogen bonding with b-CD
to form a b-hydroxyamine, which is oxidized by NBS to
yield a-amino ketones.
(s, 3H), 4.44 (d, J = 4.5 Hz, 2H), 5.50 (br s, 1H, NHTs)
7.20–7.40 (m, 4H), 7.60 (d, 1H, J = 7.5 Hz), 7.70–7.90
+
(m, 3H). LSIMS: m/z: 324 (M + 1). Anal. Calcd for
C H O SNCl C: 55.64, H: 4.34, S: 9.90, N:4.33%;
1
5
14
3
Found : C: 55.90, H: 4.25, S: 9.80, N: 4.38%.
4-Bromo-1-(2-(4-methylphenylsulfonamino)acetyl)benz-
ene (Table 1, entry 5): solid, mp: 116 °C, IR (neat): 3447,
Table 1. Reaction of NBS with b-CD complexes of aziridines
a
b
Entry
Substrate
Product
Yield (%)
Ts
O
N
NHTs
1
85
2
a
Ts
N
O
NHTs
2
3
90
88
Me
Cl
Me
Cl
2
b
Ts
N
O
NHTs
2
c
Ts
N
O
NHTs
4
88
Cl
Cl
2
d
Ts
N
O
NHTs
5
6
80
90
Br
Br
2
e
Ts
O
N
NHTs
MeO
MeO
2
f
Ts
N
O
NHTs
7
86
O
O
2g
a
1
All the products were characterized by H NMR, mass and IR spectroscopy, and elemental analysis.
Yields of isolated products after column chromatography.
b

M. S. Reddy et al. / Tetrahedron Letters 46 (2005) 1299–1301
1301
À1 1
2
3
924, 1694 cm
H), 4.40 (d, J = 3.7 Hz, 2H), 5.50 (br s, 1H), 7.20–7.30
H NMR (CDCl , 300 MHz): d 2.41 (s,
3. Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Am. Chem.
Soc. 1994, 116, 2742–2753.
3
4
. Bois, J. Du.; Hong, J.; Carreira, E. M.; Day, M. W.
J. Am. Chem. Soc. 1996, 118, 915–916.
(m, 3H), 7.62 (d, J = 8.3, 2H), 7.70–7.80 (m, 3H).
LSIMS: m/z: 367 (M ). Anal. Calcd for C H O SNBr:
+
1
5
14
3
5
. (a) Reddy, M. A.; Surendra, K.; Bhanumathi, N.; Rao, K.
R. Tetrahedron 2002, 58, 6003–6008; (b) Reddy, M. A.;
Bhanumathi, N.; Rao, K. R. Chem. Commun. 2001, 1974–
C, 48.93; H, 3.83; S, 8.71; N,3.80. Found: C, 49.02; H,
3
.62; S, 8.51; N, 3.92.
1
975; (c) Reddy, L. R.; Bhanumathi, N.; Rao, K. R.
4
-Acetyl-1-(2-(4-methylphenylsulfonamino)acetyl)benz-
Chem. Commun. 2000, 2321–2322; (d) Reddy, L. R.;
Reddy, M. A.; Bhanumathi, N.; Rao, K. R. Synlett 2000,
339–340; (e) Reddy, M. A.; Reddy, L. R.; Bhanumathi,
N.; Rao, K. R. New J. Chem. 2001, 25, 359–360; (f)
Reddy, M. A.; Reddy, L. R.; Bhanumathi, N.; Rao, K. R.
Chem. Lett. 2001, 246–247.
ene (Table 1, entry 7): white solid, mp: 115 °C, IR (neat):
À1
1
3
448, 2925 cm . H NMR (CDCl , 300 MHz): d 2.31
3
(
s, 3H), 2.42 (s, 3H), 4.40 (d, J = 4.2 Hz, 2H), 5.51 (br
s, 1H), 7.10–7.40 (m, 4H), 7.70–7.80 (m, 2H), 7.90 (d,
+
J = 8.6 Hz, 2H). LSIMS: m/z: 332 (M + 1); Anal. Calcd
6
7
. (a) Moreau, S.-P.; Morisseau, C.; Zylber, J.; Archolas, A.;
Baratti, J.; Fursloss, R. J. Org. Chem. 1996, 61, 7402–
for C H O SN: C: 61.60, H: 5.17, S: 9.67, N: 4.23;
1
Found: C: 61.40, H: 5.24, S: 9.78, N: 4.12.
7
17
4
7
407; (b) Ando, T.; Kano, D.; Minakata, S.; Ryu, I.;
Komatsu, M. Tetrahedron 1998, 54, 13485–13494; (c)
Chanda, B. M.; Vyas, R.; Bedekar, A. V. J. Org. Chem.
2001, 66, 30–34.
Acknowledgements
. General procedure: b-Cyclodextrin (1 mmol) was dis-
solved in water (15 ml) at 60 °C, and the aziridine
M.S.R. and M.N. thank CSIR, New Delhi, India, for
the award of Research Fellowships.
(
1 mmol) dissolved in acetone (2 ml) was added slowly
with stirring. After 15 min, NBS (1.0 mmol) was added
and the mixture stirred for 12 h at 50 °C. The organic
material was extracted with ethyl acetate. The organic
phase was separated, filtered, and washed with brine then
dried over sodium sulfate and the solvent removed under
vacuum. The crude product was purified by column
chromatography with ethyl acetate:hexane (20:80) as
eluent. The aqueous layer was cooled to 5 °C to recover
precipitated CD by filtration. The filtrate which contained
succinimide was evaporated and the residue purified and
converted to NBS.
References and notes
1
. (a) Raduchel, B. Synthesis 1980, 292–295; (b) Tamura, Y.;
Yakura, T.; Haruta, J.-I.; Kita, Y. Tetrahedron Lett. 1985,
6, 3837–3840; (c) Tamura, Y.; Annoura, H.; Yamamoto,
H.; Kondo, H.; Kita, Y.; Fujioka, H. Tetrahedron Lett.
987, 28, 5709–5712; (d) Murahashi, S.-I.; Naota, T.;
Hanaoka, H. Chem. Lett. 1993, 1767–1770; (e) Phukan, P.;
Sudalan, A. Tetrahedron: Asymmetry 1998, 9, 1001–1005;
(f) Adam, W.; Roschmann, K. J.; Saha-Moller, C. R. Eur.
J. Org. Chem. 2000, 557–561.
. (a) Lociuro, S.; Pellacani, L.; Tardella, P. A. Tetrahedron
Lett. 1983, 24, 593–596; (b) Surendra, K.; Srilakshmi
Krishnaveni, N.; Reddy, M. A.; Nageswar, Y. V. D.; Rao,
K. R. J. Org. Chem. 2003, 68, 9119–9121; (c) Cipollone,
A.; Loreto, M. A.; Pellacani, L.; Tardella, P. A. J. Org.
Chem. 1987, 52, 2584–2586.
2
1
8. Lim, B -W.; Ahn, K -H. Synth. Commun. 1996, 26, 3407–
3412.
9. Fujiki, S.; Hamura, S.; Eguchi, H.; Nishida, A. Bull.
Chem. Soc. Jpn. 1993, 66, 2426–2428.
2
1
3
10. (a) The C NMR studies of aziridine–b-CD complexes in
our laboratory indicated the following significant down-
3 2
field shifts: –CH (+0.188); –CH (+0.138); –CH (+0.009)
(b) Banu, H. S.; Pitchumani, K.; Srinivasan, C. Tetrahe-
dron 1999, 55, 9601–9610.