S. Peruncheralathan et al. / Tetrahedron Letters 48 (2007) 6743–6746
6745
Hu, X. E. Tetrahedron 2004, 60, 2701; (d) McCoull, W.;
Davis, F. A. Synthesis 2000, 1347.
amino sulfide 9a in 88% yield as a single trans-diastereo-
mer in the presence of 1 mol % InCl3 in CH2Cl2 at rt for
30 min (entry 7).
2. Reviews: (a) Schneider, C. Synthesis 2006, 3919; (b)
Pastor, I. M.; Yus, M. Curr. Org. Chem. 2005, 9, 1; (c)
Jacobsen, E. N.; Wu, M. H. In Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H.,
Eds.; Springer: Berlin, 1999; Vol. 2, p 649.
3. (a) Wu, J.; Sun, X.; Li, Y. Eur. J. Org. Chem. 2005, 4271;
(b) Bisai, A.; Bhanu Prasad, B. A.; Singh, V. K.
Tetrahedron Lett. 2005, 46, 7935; (c) Watson, I. D. G.;
Yudin, A. K. J. Org. Chem. 2003, 68, 5160; (d) Swamy, N.
R.; Venkateswarlu, Y. Synth. Commun. 2003, 33, 547; (e)
Yadav, J. S.; Reddy, B. V. S.; Rao, K. V.; Raj, K. S.;
Prasad, A. R. Synthesis 2002, 1061; (f) Cossy, J.; Bellosta,
V.; Alauze, V.; Desmurs, J. R. Synthesis 2002, 2211; (g)
Hou, X.-L.; Fan, R.-H.; Dai, L.-X. J. Org. Chem. 2002,
67, 5295; (h) Sekar, G.; Singh, V. K. J. Org. Chem. 1999,
64, 2537; (i) Meguro, M.; Asao, N.; Yamamoto, Y.
Tetrahedron Lett. 1994, 35, 7395.
Subsequently, employing 1 mol % of InCl3 as catalyst
N-phenylaziridine 4a was ring-opened with several
aromatic as well as aliphatic thiols furnishing 1,2-amino
sulfides 9a–d in excellent yields irrespective of the thiol
component (Table 2, entries 1–4).13 In the case of thio-
phenol, however, a significant background reaction was
observed delivering 9b in 30% yield in the absence of the
catalyst presumably due to the enhanced acidity of the
aromatic thiol serving as its own Brønsted acid catalyst.
Even the sterically hindered t-butyl thiol (5e) gave rise to
excellent yield with increased catalyst loading of
10 mol % and extended reaction times of 12 h (entry
5). In all cases examined we observed the trans ring-
opened products exclusively.
4. (a) Fukuta, Y.; Mita, T.; Fukuda, N.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2006, 128, 6312; (b)
Chandrasekhar, M.; Sekar, G.; Singh, V. K. Tetrahedron
Lett. 2000, 41, 10079; (c) Li, Z.; Fernandez, M.; Jacobsen,
E. N. Org. Lett. 1999, 1, 1611.
In order to investigate the scope of the reaction other
aziridines 4b–g were subsequently examined in indium-
catalyzed ring-opening reactions. Thus, the reaction of
N-phenylcyclohex-4-eneimine 4b with benzyl and 3-
methylbutyl thiol afforded the corresponding 1,2-amino
sulfides 10a and 10d, respectively, in excellent yields
(Table 2, entries 6 and 7). Similarly, cyclopentyl and
cycloheptyl aziridines 4c and 4d, respectively, were
smoothly ring-opened with benzyl and 3-methylbutyl
thiol and delivered the corresponding 1,2-amino sulfides
in good to very good yields within 2 h (entries 8–11).
Acyclic meso-aziridines such as 4e and 4f reacted like-
wise and gave rise to the products in 80–92% yields with
only 1 mol % of InCl3 (entries 12–15). Finally, a mono-
substituted aziridine, N-phenyl-2-hexylaziridine (4g),
was also investigated and furnished the regioisomers
15a and 16a in good yield and 4:1-isomeric ratio (entry
16). Some uncatalyzed background reaction, however,
was observed here under the reaction conditions, which
delivered the products in <10% yield.
5. (a) Bhanu Prasad, B. A.; Sanghi, R.; Singh, V. K. Tetra-
hedron 2002, 58, 7355; (b) Hou, X.-L.; Fan, R.-H.; Dai, L.-
X. J. Org. Chem. 2002, 67, 5295; (c) Bhanu Prasad, B. A.;
Sekar, G.; Singh, V. K. Tetrahedron Lett. 2000, 41, 4677.
6. (a) Yadav, J. S.; Reddy, B. V. S.; Baishya, G.; Venkatram
Reddy, P.; Narsaiah, A. V. Catal. Commun. 2006, 7, 807;
(b) Wu, J.; Sun, X.; Li, Y. Eur. J. Org. Chem. 2005, 4271;
(c) Yadav, J. S.; Subba Reddy, B. V.; Baishya, G.; Reddy,
P. V.; Harshavardhan, S. J. Synthesis 2004, 1854; (d) Hou,
X.-L.; Fan, R.-H.; Dai, L.-X. J. Org. Chem. 2002, 67,
5295; (e) Wu, J.; Hou, X.-L.; Dai, L.-X. J. Chem. Soc.,
Perkin Trans. 1 2001, 1314; (f) Hayashi, M.; Ono, K.;
Hoshimi, H.; Oguni, N. J. Chem. Soc., Chem. Commun.
1994, 2699; for the first catalytic, enantioselective process
see: (g) Luo, Z.-B.; Hou, X.-L.; Dai, L.-X. Tetrahedron:
Asymmetry 2007, 18, 443.
7. (a) Mita, T.; Fujimori, I.; Wada, R.; Wen, J.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2005, 127, 11252; (b)
Muller, P.; Nury, P. Org. Lett. 1999, 1, 439; (c) Matsu-
¨
bara, S.; Kodama, T.; Utimoto, K. Tetrahedron Lett.
1990, 31, 6379.
In conclusion, we have shown that indium(III) chloride
is a highly efficient catalyst for the ring-opening of N-
phenyl aziridines with aliphatic thiols giving rise to
1,2-amino sulfides in typically excellent yields, complete
diastereocontrol and with very low catalyst loading.
Work is being continued to develop this process into a
catalytic, enantioselective reaction through searching
for the optimal chiral indium ligand.
8. (a) Schneider, C.; Sreekanth, A. R.; Mai, E. Angew. Chem.
2004, 116, 5809; Schneider, C.; Sreekanth, A. R.; Mai, E.
Angew. Chem., Int. Ed. 2004, 43, 5691; (c) Tscho¨p, A.;
Marx, A.; Sreekanth, A. R.; Schneider, C. Eur. J. Org.
Chem. 2007, 2318.
9. (a) Mai, E.; Schneider, C. Chem. Eur. J. 2007, 13, 2729; (b)
Mai, E.; Schneider, C. Synlett, in press.
10. Nandakumar, M. V.; Tscho¨p, A.; Krautscheid, H.;
Schneider, C. Chem. Commun. 2007, 2756.
11. For recent reviews about indium-catalyzed reactions see:
(a) Loh, T.-P.; Chua, G.-L. Chem. Commun. 2006, 2739;
(b) Podlech, J.; Maier, T. C. Synthesis 2003, 633; (c) Ranu,
B. C. Eur. J. Org. Chem. 2002, 2347; (d) Babu, G.;
Perumal, P. T. Aldrichim. Acta 2000, 33, 16.
12. For previous use of In(OTf)3 as catalyst for aziridine ring-
opening with carboxylic acids see: Yadav, J. S.; Subba
Reddy, B. V.; Sadashiv, K.; Harikishan, K. Tetrahedron
Lett. 2002, 43, 2099.
Acknowledgments
The Humboldt foundation is gratefully acknowledged
for a postdoctoral fellowship awarded to S. Perunche-
ralathan. We thank BASF and Wacker for the generous
donation of chemicals.
13. General procedure for ring-opening of meso-aziridines: To a
solution of InCl3 (2 mg, 0.01 mmol) in CH2Cl2 (5 mL)
were added N-phenyl aziridine (1.00 mmol) and thiol
(1.50 mmol) and the mixture was stirred at room temper-
ature until the starting material was completely consumed
(monitored by TLC). The solvent was removed in vacuo
References and notes
1. Reviews: (a) Aziridines and Epoxides in Organic Synthesis;
Yudin, A. K., Ed.; Wiley-VCH: Weinheim (Germany),
2006; (b) Pineschi, M. Eur. J. Org. Chem. 2006, 4979; (c)