A facile C-arylation of N-tosyl aziridines via Ag(I) catalysis

Article abstract of DOI:10.1016/j.tetlet.2007.07.200

N-Tosyl aziridines react with a variety of arenes and heteroarenes in the presence of 1-2% of silver hexafluorophosphate at room temperature to afford the corresponding β-aryl amine derivatives in excellent yields and with high regioselectivity.

Full text of DOI:10.1016/j.tetlet.2007.07.200

Tetrahedron Letters 48 (2007) 7144–7146
A facile C-arylation of N-tosyl aziridines via Ag(I) catalysis
Milan Bera and Sujit Roy*
Organometallics and Catalysis Laboratory, Chemistry Department, Indian Institute of Technology, Kharagpur 721 302, India
Received 30 June 2007; revised 20 July 2007; accepted 30 July 2007
Available online 2 August 2007
Abstract—N-Tosyl aziridines react with a variety of arenes and heteroarenes in the presence of 1–2% of silver hexafluorophosphate
at room temperature to afford the corresponding b-aryl amine derivatives in excellent yields and with high regioselectivity.
ꢀ 2007 Elsevier Ltd. All rights reserved.
R2
R1
NHTs
R2
R1
Aziridines are versatile building blocks, widely used for
the synthesis of many nitrogen-containing natural prod-
ucts and biologically interesting molecules.1 A diverse
range of organic architecture can be generated by the
regioselective ring opening reaction of aziridines with
various nucleophiles.2 The latter include organo-Li/
Mg/Cu reagents,3 silyl nucleophiles,4 Wittig reagents,5
amines,6 metal halides,7 hydroxyl compounds,8 boronic
acids,9 carbonyl compounds,10a nitriles10b and alkenes.11
In contrast to the above, there are only a few reports on
the regioselective ring opening of aziridines by an arene
nucleophile, which usually employs Lewis acid media-
tion. The Lewis acids used include stoichiometric AlCl3
(1 equiv),12 BF3ÆEt2O (3 equiv)13 and catalytic In(OTf)3
(5–10 mol %).14
Ar-H/Het-H
N
Ts
AgPF , DCE, 30-35 ºC
6
Ar/Het
0.5-3 h; 75-85 %
1a-1d
2-17
1a: R1= C6H5, R2= H; 1b: R1= 4-ClC6H4, R2= H;
1c: R1= 4-MeC6H4, R2= H; 1d: R1= R2= C6H5
Scheme 1. C-Arylation of N-tosyl aziridines.
50% yield of N-tosyl-2-phenyl-2-(4-methoxyphenyl)-eth-
ylamine 2. The reaction rate remained unaltered even at
higher temperature. The product yield also failed to
improve when the reaction was conducted with 2 equiv
of anisole and dichloromethane as solvent. However,
in dichloroethane (DCE) as solvent, the yield of 2
increased to 65% after 3 h. Gratifyingly, by employing
2 mol % of the catalyst, the reaction proceeded to com-
pletion within 1 h and amine 2 was isolated in 80% yield.
Screening of other solvents demonstrated the superiority
of DCE (Table 1). Notably the catalytic activity of
AgPF6 was completely inhibited in water, ethanol and
tetrahydrofuran as solvents. Amongst the other silver
Our recent interest in late transition metal catalyzed aro-
matic alkylation reactions15 prompted us to investigate
the reactivity of N-tosyl aziridines with arenes. This
endeavour led to the novel finding that under ambient
conditions, only 1–2% of AgPF6 promoted a highly
regioselective ring opening of N-tosyl aziridines with a
variety of arenes and heteroarenes leading to the corres-
ponding b-aryl amine derivatives in excellent yields
(Scheme 1). We believe that such reactivity might origi-
nate from the well-known binding ability of Ag(I)
towards arenes and aziridines.16,17
Table 1. C-Arylation of N-tosyl aziridine 1a: solvent screeninga
Entry
Solvent
Yield of 2 (%)
1
2
3
4
5
6
7
DCE
80
65
60
15
Nil
Nil
Nil
Reaction of N-tosyl-2-phenyl aziridine 1a with anisole as
the arene as well as the solvent, and AgPF6 (1 mol %) as
catalyst at room temperature did not proceed to comple-
tion even after 3 h (vide TLC), and work-up afforded a
DCM
MeNO2
MeCN
EtOH
H2O
THF
a Reagents and conditions: aziridine 1a (1 mmol), anisole (2 mmol),
AgPF6 (2 mol %), time (1 h).
*
Corresponding author. Tel.: +91 3222 283338; fax: +91 3222
282252; e-mail: sroy@chem.iitkgp.ernet.in
0040-4039/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.07.200

M. Bera, S. Roy / Tetrahedron Letters 48 (2007) 7144–7146
7145
Table 2. C-Arylation of N-tosyl aziridine 1a: catalyst screeninga
salts screened for their catalytic activity (Table 2), only
AgBF4 was promising.
Entry
Silver salt
Yield of 2 (%)
1
2
3
4
5
6
AgPF6
AgBF4
AgOAc
AgNO3
Ag2SO4
Ag3PO4
80
75
Trace
Nil
Nil
Nil
The generality of the reaction was successfully tested un-
der the optimized conditions with N-tosyl aziridines 1a–
1d and various arenes and heteroarenes as nucleophiles,
giving rise to the corresponding b-substituted ethylam-
ines 2–17 (Tables 3 and 4).18 The products were fully
characterized by 1H, 13C, IR, HRMS and by X-ray crys-
tallography (in the case of 6). The important observa-
tions are highlighted below.
a Reagents and conditions: aziridine 1a (1 mmol), anisole (2 mmol),
catalyst (2 mol %), DCE (3 ml), time (1 h).
Table 3. AgPF6 catalyzed regioselective ring opening of N-tosyl
aziridines with arenes as nucleophilesa
Table 4. AgPF6 catalyzed regioselective ring opening of N-tosyl
aziridines with heteroarenes as nucleophilesa
Entry Aziridine
Product
Time Yield
(h)
(%)
Entry Aziridine
Product
Time Yield
NHTs
Ts
(h)
(%)
N
1
1
80
Ts
NHTs
S
N
1a
OMe
2
1
2
0.5
80
1a
10
NHTs
NHTs
NHTs
O
2
3
1a
1a
3
75
78
1a
1a
0.5
0.5
80
85
Me
3
11
NHTs
S
1.5
3
4
5
6
Me
Me
Me
4
Me
12
NHTs
NHTs
O
OMe
4
5
1a
1a
1
82
85
1a
0.5
85
85
85
MeO
13
5
Ts
N
NHTs
TsHN
OMe
O
1
0.5
1b
Cl
Cl
14
MeO
OMe
Cl
6
NHTs
S
NHTs
Ts
N
1b
1
6
7
8
1.5
80
82
85
15
Cl
Cl
OMe
1b
Cl
7
Ts
N
NHTs
O
TsHN
OMe
7
0.5
85
1c
1b
1
Me
16
Me
OMe
MeO
8
Ts
NHTs
Ts
NHTs
S
N
N
8
3
75
1
Ph
1d
1c
Me
OMe
17
Me
9
a Reagents and conditions: aziridine (1 mmol), heteroarene (2 mmol),
AgPF6 (2 mol %), DCE (3 ml).
a Reagents and conditions: aziridine (1 mmol), arene (2 mmol), AgPF6
(2 mol %), DCE (3 ml).

7146
M. Bera, S. Roy / Tetrahedron Letters 48 (2007) 7144–7146
7. (a) Righi, G.; Franchini, T.; Bonini, C. Tetrahedron Lett.
1998, 39, 2385; (b) Ghorai, M. K.; Das, K.; Kumar, A.;
Ghosh, K. Tetrahedron Lett. 2005, 46, 4103.
8. (a) Prasad, B. A. B.; Sekar, G.; Singh, V. K. Tetrahedron
Lett. 2000, 41, 4677; (b) Li, P.; Forbeck, E. M.; Evans, C.
D.; Joullie, M. M. Org. Lett. 2006, 22, 5105.
9. Aydin, J. K. J.; Wallner, O. A.; Saltanova, I. V.; Szabo, J.
K. Chem. Eur. J. 2005, 11, 5260.
10. (a) Ghorai, M. K.; Ghosh, K. Tetrahedron Lett. 2007, 48,
3191; (b) Ghorai, M. K.; Ghosh, K.; Das, K. Tetrahedron
Lett. 2006, 47, 5399.
11. (a) Ungureanu, I.; Koltz, P.; Mann, A. Angew. Chem., Int.
Ed. 2000, 41, 4615; (b) Loh, T. P.; Hu, Q.-Y.; Ma, L. T. J.
Am. Chem. Soc. 2001, 123, 2450.
12. (a) Stamm, H.; Sommer, A.; Woderer, A.; Wiesert, W.;
Mall, T.; Assithianakis, P. J. Org. Chem. 1985, 50, 4946;
(b) Stamm, H.; Onistschenko, A.; Buchholz, B.; Mall, T.
J. Org. Chem. 1989, 54, 193.
13. Bergmeier, S. C.; Katz, S. J.; Huang, J.; McPherson, H.;
Donoghue, P. J.; Reed, D. D. Tetrahedron Lett. 2004, 45,
5011.
14. Yadav, J. S.; Reddy, B. V. S.; Rao, R. S.; Veerendhar, G.;
Nagaiah, K. Tetrahedron Lett. 2001, 42, 8067.
1. The ring opening of N-tosyl aziridines proved to be
highly regioselective with exclusive attack of the
arene/heteroarene at the benzylic position.
2. The trends in the reactivity of arenes show that for
ring-activated arenes, reactions were complete within
shorter reaction times, and the product yields were
very good. In contrast, benzene and ring-deactivated
arenes reacted more slowly giving rise to the desired
product in poor yields along with unreacted aziridine.
3. The reactions proceeded with greater facility in the
case of furan, and thiophene derivatives as indicated
by shorter reaction times, and consistently good
yields (Table 4). In all cases, the substitution took
place exclusively at the 2-position of the heteroarene.
4. It was further observed that the nature of the substi-
tuent on the aromatic ring of the N-tosyl aziridine
had some effect on the conversion, and the reactivity
followed the trend 1c > 1a > 1b > 1d. In contrast
reaction of an aziridine bearing an alkyl substituent,
for example, N-tosyl-2-hexyl aziridine failed.
15. (a) Choudhury, J.; Podder, S.; Roy, S. J. Am. Chem. Soc.
2005, 127, 6162; (b) Podder, S.; Choudhury, J.; Roy, S. J.
Org. Chem. 2007, 72, 3129; (c) Podder, S.; Choudhury, J.;
Roy, U. K.; Roy, S. J. Org. Chem. 2007, 72, 3100.
16. For arene–Ag(I) complexation: (a) Sharp, D. W. A.;
Sharpe, A. G. J. Chem. Soc., Chem. Commun. 1956,
1855; (b) Hill, A. E. J. Am. Chem. Soc. 1921, 43, 254; (c)
Hall, A. E.; Amma, L. E. J. Chem. Soc., Chem. Commun.
1968, 622; (d) Griffith, H. A. E.; Amma, L. E. J. Am.
Chem. Soc. 1974, 96, 5407; (e) Munakata, M.; Wu, P. L.;
Ning, L. G. Coord. Chem. Rev. 2000, 198, 171; (f)
Linderman, V. S.; Rathore, R.; Kochi, K. J. Inorg. Chem.
2000, 39, 5707.
In summary, we have presented an efficient method for
the preparation of b-aryl ethylamine derivatives from
N-tosyl aziridines and arenes/heteroarenes using cata-
lytic AgPF6. The very mild conditions, clean TLC pro-
files, high regioselectivity and operational simplicity
are expected to make this reaction attractive to chemists.
Efforts are underway to broaden the scope of the aryla-
tion to an asymmetric version.
Acknowledgements
17. For aziridine–Ag(I) complexation: (a) Faure, R.; Gebicki,
K. J. Crystallogr. Spec. Res. 1993, 23, 795, CAN 120:
123473; (b) Teil, B. Z. Naturforsch 1971, 26, 476.
18. General procedure: The procedure given below was fol-
S.R. thanks the DST for financial support. M.B. thanks
the CSIR for a fellowship.
lowed in all cases. All products showed satisfactory 1H, 13
C
Supplementary data
NMR, DEPT, IR and HRMS data, which are given in
Supplementary data. Synthesis of N-[2-(4-Methoxyphe-
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.2007.
07.200.
nyl)-2-phenyl-ethyl]-4-methyl-benzenesulfonamide (2):
A
mixture N-tosyl aziridine 1a (1 mmol, 273 mg), anisole
(2 mmol, 100ll) and AgPF6 (0.02 mmol, 5 mg) in 3 ml of
dry dichloroethane were stirred at room temperature.
Following completion (vide TLC), the reaction mixture
was diluted with water (5 ml) and extracted with dichlo-
roethane (4 · 5 ml). The combined organic layers were
dried over anhydrous sodium sulfate, concentrated in
vacuo and the resulting product was purified by column
chromatography on silica gel (100–200 mesh, ethyl ace-
tate–petroleum ether, 1:10) to afford pure b-aryl ethyla-
mine derivative 2 (305 mg, 80% with respect to 1a). 1H
NMR (400 MHz, CDCl3): d 2.46 (s, 3H), 3.46–3.57 (m,
2H), 3.78 (s, 3H), 4.02 (t, 1H, J = 8 Hz), 4.29 (t, 1H,
J = 6 Hz), 6.82 (d, 2H, J = 8.8 Hz), 7.01 (d, 2H,
J = 8.4 Hz), 7.09 (d, 2H, J = 6.8 Hz), 7.20–7.33 (m, 5H),
7.74 (d, 2H, J = 8.4 Hz); 13C NMR (100 MHz, CDCl3):
21.61, 47.40, 49.70, 55.30, 114.27, 127.09, 127.19, 127.84,
128.88, 128.96, 129.79, 132.63, 136.72, 141.04, 143.58,
158.62; HRMS (ESI) calcd for C22H23NO3S
[M+Na]+ = 404.1296, found 404.1293. IR (KBr): 3283,
References and notes
1. (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599;
(b) McCoull, W.; Davis, F. A. Synthesis 2000, 1347.
2. Hu, X. E. Tetrahedron 2004, 60, 2701, and references cited
therein.
3. (a) Kozikowski, A.; Ishida, H.; Isobe, K. J. Org. Chem.
1979, 44, 2788; (b) Osborn, H. M. I.; Sweeney, J. D.;
Howson, B. Synlett 1993, 676.
4. Wu, J.; Hou, X.-L.; Dai, L.-X. J. Org. Chem. 2000, 65,
1344.
5. Ibuka, T.; Nakai, K.; Habashita, H.; Fujii, N.; Garrido,
F.; Mann, A.; Chounan, Y.; Yamamoto, Y. Tetrahedron
Lett. 1993, 34, 7421.
6. (a) Meguro, M.; Asao, N.; Yamamoto, Y. Tetrahedron
Lett. 1994, 35, 7395; (b) Sekar, G.; Singh, V. K. J. Org.
Chem. 1999, 64, 2537.
2932, 1512, 1324, 1153, 1092, 820 cmÀ1
.