Aminolysis of aziridines catalyzed by samarium iodides

Article abstract of DOI:10.1007/s10562-011-0763-3

Samarium diiodide is an efficient catalyst for the aminolysis of either activated or non activated aziridines with aromatic amines. A variety of N-diprotected β-diamines has been prepared including new products. The comparison of the N-protecting groups o

Full text of DOI:10.1007/s10562-011-0763-3

Catal Lett (2012) 142:308–312
DOI 10.1007/s10562-011-0763-3
Aminolysis of Aziridines Catalyzed by Samarium Iodides
•
Aurelia Dinut Myriam Martin Jacqueline Collin
•
•
´
Sophie Bezzenine-Lafollee
´
Received: 26 September 2011 / Accepted: 28 December 2011 / Published online: 14 January 2012
Ó Springer Science+Business Media, LLC 2012
Abstract Samarium diiodide is an efficient catalyst for
the aminolysis of either activated or non activated aziri-
dines with aromatic amines. A variety of N-diprotected
b-diamines has been prepared including new products. The
comparison of the N-protecting groups of aziridines in
reactions catalyzed by samarium diiodide or by samarium
iodobinaphtholate indicates that N-Boc protection leads to
the best results.
nucleophiles have been recently reviewed by Hu [8]. Regio-
and enantioselective aminolyses of aziridines have been
developed with achiral and chiral Lewis acid catalysts.
Aminolysis of N-tosyl aziridines were reported using rare
earth triflates, indium bromide, rare earth or indium chlorides
and TaCl5 on silicagel [9–12]. LiClO4 has also been
employed as a catalyst for the ring opening of N-tosylaziri-
dines by aromatic amines [13] but in stoichiometric amount
for the opening of N-benzyl and N-alkyl aziridines with ali-
phatic amines [14]. Aminolyses of aziridines N-substituted
by aromatic or benzyl groups with aromatic amines were
performed in the presence of catalytic amounts of Sn(OTf)2
and Cu(OTf)2 [15]. Tris(pentafluorophenyl)borane catalyzes
the opening of N-benzyl and N-alkyl aziridines with benzyl
amine as the sole nucleophile [16]. A few catalysts such as
BiCl3 [17] and LiNTf2 [18] proved to be active for the ring
opening of both activated and non activated aziridines. The
comparison of scandium triflate-catalyzed reactions of vari-
ous N-substituted cyclic aziridines with aniline showed a
higher reaction rate for N-phenyl than for N-tosyl or N-ben-
zoyl aziridines. Aminolyses of N-phenyl aziridines with
various aromatic amines could be realized in mild conditions
(as low as 1 mol% scandium triflate) [19]. Other procedures
have been described for the transformation of aziridines in
1,2-diamines such as the use of b-cyclodextrin [20] and
phosphines as catalysts [21, 22] or by performing reactions in
the presence of silica gel [23] or montmorillonite K-10 under
microwave irradiation [24, 25].
Keywords Samarium diiodide Á Aminolysis Á Aziridine Á
Ring opening reaction Á Catalysis
1 Introduction
The ring opening of aziridines by amines gives a straight-
forward and atom economic access towards 1,2-diamines
which are important key scaffolds for biologically active
molecules [1–5] and widely used in enantioselective catalysis
as chiral ligands or organocatalysts [6, 7]. The reactivity of
aziridines towards ring opening reactions is lower than that of
epoxides and depends on the presence or not of an electron
withdrawing group on the nitrogen atom. Ring opening
reactions of aziridines including reactions with nitrogen
Electronic supplementary material The online version of this
article (doi:10.1007/s10562-011-0763-3) contains supplementary
material, which is available to authorized users.
Although very efficient catalysts have been developed
for the asymmetric ring opening of aziridines by trimeth-
ylsilyl azide [26], the first enantioselective catalysts for the
aminolyses of aziridines have been reported in the last
years. Niobium coordinated to a substituted binol ligand
afforded asymmetric inductions depending on the nitrogen
substituent of the aziridine, (up to 84% ee with an aziridine
´
A. Dinut Á M. Martin Á J. Collin Á S. Bezzenine-Lafollee (&)
´
Equipe de Catalyse Moleculaire, ICMMO, UMR 8182,
Universite Paris-Sud, 91405 Orsay, France
´
e-mail: sophie.bezzenine@u-psud.fr
J. Collin
CNRS, 91405 Orsay, France
123

Aminolysis of Aziridines
309
substituted by an o-anisyl group) [27, 28]. A tridentate
binol ligand associated to titanium [29] for the aminolysis
of N–o-anisyl aziridines and to zirconium [30] for
N-benzhydryl aziridines afforded high enantioselection. A
titanium/binol catalyst was highly enantioselective for the
opening of N-phenyl and N-p-anisyl aziridines by aromatic
amines [31]. Thus the nitrogen protecting group of aziri-
dine has a dramatic effect on the activity and enantiose-
lectivity of Lewis acid catalysts.
Aminolyses of epoxides have been performed in THF or in
chlorinated solvents, CH2Cl2 or C2H4Cl2 and the opening
reactions of cyclic epoxides containing nitrogen atoms
were realized at 60 °C. Since aziridines are expected to
require harsher conditions than epoxides for ring opening
reactions we tested first the catalytic reactions in DCE
(Scheme 1). We were pleased to find that using 10 mol%
samarium diiodide in DCE, the conversion of 1a was
nearly achieved after one night and b-diamine 3aa was
isolated in good yield (Table 1, entry 1). We further tried to
optimize reactions conditions. Using a higher amine/aziri-
dine ratio did not allow to decrease the reaction time or the
reaction temperature (entry 2). When a lower catalytic ratio
(5%) was used total conversion could be obtained but in an
increased reaction time (38 h) (entries 3–5). Similarly
when reaction was performed in THF with 10 mol %
samarium diiodide the b-diamine 3aa could be isolated in
high yield but a longer reaction time than in DCE was
required (compare entries 1 and 7). Using 5 mol% samar-
ium diiodide in THF at 60 °C led after one night to a
smaller conversion than in DCE (compare entries 3 and 8).
Thus, the ring opening of N-tosyl aziridine 1a by p-anisi-
dine catalyzed by samarium diiodide can be realized at
60 °C either in DCE or in THF albeit the reaction is slower
in the latter solvent. In these reactions samarium diiodide
acts as a precatalyst which generates a trivalent Lewis acid
catalyst as previously observed for the formation of various
carbon–nitrogen bonds with this catalytic system [32–34].
A mechanism similar to that proposed by Jacobsen for the
ring opening of epoxides by TMSN3 can be proposed for
these aminolyses of aziridines [38]. As a result, the dif-
ference of reactivity of samarium diiodide in DCE and
THF could be explained since Lewis acidity of lanthanides
decreases in coordinating solvent.
We have previously investigated the use of samarium
diiodide and samarium iodobinaphtholate as catalyst and
enantioselective catalyst for the formation of carbon–
nitrogen bonds [32]. Samarium diiodide revealed effi-
cient for the ring opening of epoxides by amines [33,
34], while high enantiomeric excesses were recorded for
the aminolysis of cyclic epoxides containing or not
another heteroatom by aromatic amines [35–37]. We
now present our results on the use of samarium diiodide
as a catalyst for the transformation of aziridines in
vicinal diamines.
2 Results
As a first step towards the preparation of enantioenriched
b-diamines by asymmetric lanthanide iodides we envis-
aged the study of the ring opening of meso aziridines
with aromatic amines catalyzed by samarium diiodide. For
test reactions we chose aziridines leading to cyclohexyl
diamines and focused on aminolyses involving o and
p-anisidine for a facile deprotection of the nitrogen of
reaction products. The activity of samarium diiodide was
first investigated on the reaction involving N-tosyl cyclo-
hexyl aziridine 1a and p-anisidine as aromatic amine.
H
N Ts
10 mol % SmI2
C2H4Cl2 or THF, 60°C
N Ts
1a
+
p-MeO-C6H4NH2
p-OMeC6H4
N
H
2a
3aa
Scheme 1 Ring opening of aziridine 1a by p-anisidine 2a catalyzed by SmI2
Table 1 Ring opening of
aziridine 1a by p-anisidine 2a
catalyzed by SmI2
Entry
Solvent
Mol% SmI2
t (h)
Conversion (yield)a
1
2
3
4
5
6
7
8
DCE
DCEb
DCE
DCE
DCE
THF
THF
THF
10
10
5
17
18
16
22
38
15
40
16
95 (73)
100 (71)
76
5
93
a
5
100
Conversion % (isolated yield
%), reaction performed with
10
10
5
83
ratio 2a/1a: 1.2
b
Reaction performed with 10%
SmI2 and ratio 2a/1a: 2
98 (70)
40
123

310
A. Dinut et al.
H
5). The reactivity of cyclohexyl aziridine 1b substituted by
benzyl for the ring opening by p- and o-anisidine was next
investigated. The total conversion in b-diamine was
observed in both cases but after a longer time for o-anisidine
which afforded product 3bb in good yield (entries 6–8).
N-Phenyl substituted aziridine 1c was transformed by o- and
p-anisidine after 17 h in b-diamines 3ca and 3cb which were
isolated in good yields (entries 9 and 10). For N-Boc aziri-
dine 1d the reaction was slower with o-anisidine than with p-
anisidine as observed for N-benzyl aziridine 1b (entries
11-13). Performing the aminolysis of N-tosyl aziridine 1a by
p-anisidine under microwaves irradiation either at 60 °C or at
80 °C allowed to decrease strongly the reaction time and to
isolate diamine 3aa in high yield (entries 2 and 3).
N R1
10 mol % SmI2
THF, 60°C
N R1
+
R2 NH2
N R2
H
1
2
3
R1 = Ts, Bn, Ph, Boc
R2 = p-MeO-C6H4, o-MeO-C6H4, CH2Ph
Scheme 2 Ring opening of aziridines 1 by amines 2 catalyzed by
SmI2
The influence of the nature of the nitrogen substituent of
aziridine and of the amine on the ring opening reactions
catalyzed by samarium diiodide was next examined
(Scheme 2; Table 2). Although reactions are more rapid in
DCE we chose to use THF as solvent for an easier proce-
dure. Since samarium diiodide is prepared in THF it avoids
the evaporation of the solvent and the manipulation of
SmI2(THF)2 which is far more sensitive to oxygen and
moisture than the commercially available THF solutions of
samarium diiodide. The ring opening of N-tosyl aziridine 1a
by o-anisidine 2b could be realized in similar conditions
than the reaction involving p-anisidine 2a (Table 2, entries 1
and 4). Benzyl amine 2c was further employed for the
aminolysis of 1a and afforded b-diamine 3ac in a smaller
reaction time than reactions with o- and p-anisidine (entry
While the ring opening of aziridines 1a with p-anisidine
[9–12] and 1c with o-and p-anisidine [19] have been tested
with other catalytic systems, aminolysis of N-benzyl azi-
ridine 1b and N-Boc aziridine 1d were not previously
described. The results gathered in Table 2 show that
samarium diiodide is an efficient catalytic system for
aziridines protected by tosyl and t-butoxycarbonyl group
but also by phenyl or benzyl groups. However, considering
the stability of the products and the reaction rates phenyl
and t-butoxycarbonyl seem the best protecting groups for
the transformation of aziridines into b-diamines.
Table 2 Ring opening of aziridines 1 by amines 2 catalyzed by SmI2
Entry
Aziridine
Amine R2NH2
Product
t (h)
Conversion (%)
Yield %a
1
2
3
4
5
6
7
8
2a p-MeO–C6H4–NH2
2a p-MeO–C6H4–NH2
2a p-MeO–C6H4–NH2
2b o-MeO–C6H4–NH2
2c C6H5–NH2
3aa
3aa
3aa
3ab
3ac
3ba
3bb
3bb
40
2b
2c
98
65
70
40
81d
N
Ts
Bn
90
e
1a
40
17
17
17
26
90
100
100
85
68
e
2a p-MeO–C6H4–NH2
2b o-MeO–C6H4–NH2
2b o-MeO–C6H4–NH2
N
N
100
74
1b
1c
9
2a p-MeO–C6H4–NH2
2b o-MeO–C6H4–NH2
3ca
3cb
17
17
100
100
70
65
10
Ph
11
12
13
2a p-MeO–C6H4–NH2
2b o-MeO–C6H4–NH2
2b o-MeO–C6H4–NH2
3da
3db
3db
16
17
26
100
90
74
59
N
Boc
100
1d
a
Isolated yield, reactions performed with 10% SmI2 and ratio 3/2: 1.2
b
c
d
e
Reaction performed with 10% SmI2 and ratio 3/2: 1.2 under microwaves at 60 °C, 60 watt
Reaction performed with 10% SmI2 and ratio 3/2: 1.2 under microwaves at 80 °C, 60 watt
Reaction realized in the same conditions without catalyst did not yield to diamine 3aa
The product decomposed on silica and could not be purified
123

Aminolysis of Aziridines
311
H
Comparing samarium diiodide and samarium io-
dobinaphtholate catalyzed ring opening of aziridines with
different protecting groups showed that t-butoxycarbonyl
gives the best results with both catalysts and is the pro-
tection that should be considered for the aminolysis of
aziridines. Studies on the desymmetrization of aziridines
by other asymmetric catalytic systems are ongoing.
N R1
4
10 mol %
N R1
+
R2
NH2
R2
N
C2H4Cl2
H
1
2
3
R1 = Ts, Bn, Ph, Boc
R2 = p-MeO-C6H4,o-MeO-C6H4
O
O
. (THF)
Sm I
2
Acknowledgments We thank the Centre National de la Recherche
4
`
Scientifique and the Ministere de l’Education Nationale de l’Ens-
eignement Superieur et de la Recherche for financial support.
´
Scheme 3 Aminolysis of aziridines with aromatic amines catalyzed
by samarium iodobinaphtolate
Table 3 Aminolysis of aziridines with aromatic amines catalyzed by
samarium iodobinaphtolate
References
Entry Aziridine Amine
T (°C) t (h) Conv. ee
(%)
1. Lucet D, Le Gall T, Mioskowski C (1998) Angew Chem Int Ed
37:2580–2627
(%)a
2. Gonzalez-Sabin J, Gotor V, Rebolledo F (2004) Chem Eur J
10:5788–5794
3. Yudin HK (2006) Aziridines and epoxides in organic synthesis.
Wiley-VCH, Weinheim
4. Assem N, Natarajan A, Yudin AKJ (2010) Am Chem Soc 132:
10986–10987
5. Krishnananda S, Gautam P (2011) Chem Asian J 6:189–197
6. Anaya de Parrodi C, Juaristi E (2006) Synlett 17:2699–2715
7. Yan Y-Q, Zhao G (2008) Chem Eur J 14:10888–10891
8. Hu XE (2004) Tetrahedron 60:2701–2743
9. Meguro M, Asao N, Yamamoto Y (1994) Tetrahedron Lett 35:
7395–7398
10. Meguro M, Yamamoto Y (1996) Heterocycles 43:2473–2482
11. Yadav JS, Reddy BVS, Rao KV, Raj KS, Prasad AR (2002)
Synthesis 8: 1061–1064
12. Chandsekhar S, Jaya Prakash S, Shyamsunder T, Ramachandar T
(2004) Synth Commun 34:3865–3873
13. Yadav JS, Reddy BVS, Jyothirmai B, Murty MSR (2002) Synlett
1: 53–56
1
2
3
4
5
6
7
a
1a
1b
1b
1c
1c
1d
1d
2a p-MeO–
C6H4–NH2
40
60
60
60
60
40
60
44
46
46
21
21
41
48
100
7
5
2b o-MeO–
C6H4–NH2
41
62
2a p-MeO–
C6H4–NH2
5
2b o-MeO–
C6H4–NH2
100
100
17
0
2b p-MeO–
C6H4–NH2
0
2b o-MeO–
C6H4–NH2
12
27
2b p-MeO–
C6H4–NH2
100
Enantiomeric excess measured by HPLC
14. Anaya de Parrodi C, Vazquez V, Quintero L, Juaristi E (2001)
Synth Commun 31:3295–3302
Since samarium iodobinaphtholate afforded interesting
15. Sekar G, Singh VKJ (1999) Org Chem 64:2537–2539
16. Watson IDG, Yudin AKJ (2003) Org Chem 68:5160–5167
17. Swamy NR, Venkateswarlu Y (2003) Synth Commun 33:
547–554
18. Cossy J, Bellosta V, Alauze V, Desmurs JR (2002) Synthesis 15:
2211–2214
19. Peruncheralathan S, Henez M, Schneider C (2007) Synlett
14:2289–2291
20. Reddy MA, Reddy LR, Bahnumathi N, Rao KR (2011) Chem
Lett 38:246–247
results for the enantioselective aminolysis of epoxides [35–
37] we have now tested this complex for the aminolysis of
aziridines (Scheme 3). We found it catalyzes the ring
opening of aziridines 1 with o- and p-anisidine affording
the corresponding 1,2 diamines with total conversion but
low enantioselectivities (Table 3). Encouraging results are
obtained with N-Boc aziridine 1d (entries 6, 7). The
enantioselective desymmetrization of various aziridines
with aromatic amines catalyzed by lanthanide iodobinaphth-
oxides is currently under study.
21. Hou X-L, Fan R-H, Dai L-XJ (2002) Org Chem 67:5295–5300
22. Fan R-H, Hou X-LJ (2003) Org Chem 68:726–730
23. Anand RV, Pandey G, Singh VK (2002) Tetrahedron Lett 43:
3975–3976
24. Nadir UK, Singh A (2005) Tetrahedron Lett 46:2083–2086
25. Crestey F, Witt M, Frydenvang K, Staerk D, Jaroszewski JW,
Franzyk HJ (2008) Org Chem 73:3566–3569
26. Schneider C (2009) Angew Chem Int Ed 48:2082–2084
27. Arai K, Lucarini S, Salter MM, Ohta K, Yamashita Y, Kobayashi
SJ (2007) Am Chem Soc 129:8103–8111
28. Arai K, Salter MM, Yamashita Y, Kobayashi S (2007) Angew
Chem Int Ed 46:955–957
29. Yu R, Yamashita Y, Kobayashi S (2009) Adv Synth Catal 351:
147–152
3 Conclusion
Samarium diiodide catalyzes the ring opening of aziridines
by aromatic amines in mild conditions to form b-diamines
in good yields. The reactions can be performed in THF and
within short times under microwaves conditions. We have
synthesized several new di-protected 1,2 diamines.
123

312
A. Dinut et al.
´
35. Carree F, Gil R, Collin J (2005) Org Lett 7:1023–1026
´
30. Seki K, Yu R, Yamasaki Y, Yamashita Y, Kobayashi S (2009)
Chem Commun 5722–5724
36. Martin M, Bezzenine-Lafollee S, Gil R, Collin J (2007) Tetra-
31. Peruncheralathan S, Teller H, Schneider C (2009) Angew Chem
Int Ed 48:4849–4852
hedron Asymmetry 18:2598–2605
37. Martin M, Bezzenine S, Collin J (2010) Tetrahedron Asymmetry
21:1721–1722
38. Hansen KB, Leighton JL, Jacobsen EN (1996) J Am Chem Soc
118:10924–10925
´
32. Collin J, Bezzenine-Lafollee S. Gil R, Jaber N, Martin, M, Re-
boule I (2009) Synlett 13: 2051–2067
33. Van de Weghe P, Collin J (1995) Tetrahedron Lett 36:1649
´
34. Carree F, Gil R, Collin J (2004) Tetrahedron Lett 45:7749–7752
123