Scandium triflate catalyzed aminolysis of meso-aziridines

Article abstract of DOI:10.1055/s-2007-984920

The aminolysis of meso-N-phenyl aziridines is efficiently catalyzed with just 1 mol% of Sc(OTf)₃ and furnishes valuable 1,2-diamines in good to excellent yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984920

LETTER
2289
Scandium Triflate Catalyzed Aminolysis of meso-Aziridines
A
S
minolysis of
a
m
eso-Azir
r
Institut für Organische Chemie, Universität Leipzig, Johannisallee 29, 04103 Leipzig, Germany
Fax +49(341)9736599; E-mail: schneider@chemie.uni-leipzig.de
Received 30 May 2007
Interestingly, the ring opening of N-phenyl aziridine (4a)
with aniline was complete within 15 minutes, affording
Abstract: The aminolysis of meso-N-phenyl aziridines is efficient-
ly catalyzed with just 1 mol% of Sc(OTf) and furnishes valuable
3
1
,2-diamine 9a in 92% yield (entry 4). Clearly, the phenyl
1
,2-diamines in good to excellent yields.
group was the suitable nitrogen substituent for the
scandium-catalyzed aminolysis of meso-aziridines.
Key words: amine, aziridine, catalysis, 1,2-diamine, scandium
Table 1 Screening of the Nitrogen Substituents
Nucleophilic ring-opening reactions of small-ring hetero-
cycles enjoy a prominent position in synthetic organic
chemistry and furnish valuable 1,2-difunctionalized fine
chemicals in just one step. While epoxide-opening reac-
H
Sc(OTf)3
N
N
(10 mol%)
R
N
R + PhNH2
Ph
CH2Cl2, r.t.
Ph
O
N
H
1
tions have been widely studied, the corresponding ring
5a
1
a–4a
7
a
opening of aziridines lags behind primarily due to their at-
6
a, 8a–9a
2
tenuated reactivity and less convenient accessibility. Yet,
3
Entry
Aziridine
Time
Product (yield)
6a, R = Ts, 31%
7a, 33%
important structural motifs such as 1,2-diamines, 1,2-
4
5
amino alcohols, and 1,2-amino sulfides have been
synthesized upon treatment with the suitable nucleophiles
according to this strategy. The recent elegant work of
1
2
3
4
1a, R = Ts
2a, R = COPh
3a, R = Bn
4a, R = Ph
48 h
24 h
6
Shibasaki and co-workers on catalytic, enantioselective
48 h
8a, R = Bn, 81%
9a, R = Ph, 92%
ring opening of meso-aziridines with trimethylsilyl
cyanide and azide and the application of this methodology
towards a practical synthesis of the antiviral agent
15 min
®
oseltamivir (Tamiflu ) clearly underline the importance
To further optimize this process a range of Lewis acids
was screened next. Thus, rare-earth metals such as
of such processes.
3
j
We have developed novel scandium and indium bipyri- Y(OTf) and Yb(OTf)3 were equally effective in the
3
dine catalyzed processes for the enantioselective ring aminolysis of aziridine 4a (Table 2, entries 1 and 2). Indi-
opening of meso-epoxides with alcohols, amines, and um(III) chloride (10 mol%) required extended reaction
7
thiols. Given the capacity of Sc(OTf)3 to activate times of up to 24 hours to reach completion (entry 4).
epoxides towards nucleophilic ring opening we wondered Scandium triflate turned out to be the only Lewis acid
whether it would also catalyze the ring opening of giving rise to full conversion at a 1 mol% level. Thus,
8
aziridines with amines. Herein we report that Sc(OTf) is reaction of N-phenyl aziridine (4a) with 1.5 equivalents
3
indeed a highly active catalyst for the aminolysis of meso- aniline afforded 1,2-diamine 9a in 90% yield in the
N-phenyl-aziridines at a 1 mol% level furnishing 1,2-di- presence of 1 mol% Sc(OTf) in dichloromethane at room
3
amines in typically excellent yields.
temperature for 1 hour (entry 6).
The ring opening of aziridines is strongly dependent on Subsequently, several aromatic amines were reacted with
the nature of the nitrogen substituent. Therefore, we first N-phenyl aziridine (4a) and 1 mol% Sc(OTf) under the
3
examined the reaction of cyclohexeneimines with differ- optimized reaction conditions and the corresponding 1,2-
ent substituents on the nitrogen atom and aniline in the diamines 9a–g were obtained in excellent yields irrespec-
presence of Sc(OTf) in dichloromethane (Table 1). Thus, tive of the substitution of the aromatic ring (Table 3, en-
3
N-tosyl aziridine (1a) was reacted with aniline affording tries 1–7). Only strongly deactivated or sterically hindered
1
,2-diamine 6a in low yield (Table 1, entry 1). N-Benzoyl anilines gave rise to reduced yields even with increased
aziridine (2a) did not yield the desired product, but instead catalyst loadings of up to 10 mol% and extended reaction
9
the oxazoline 7a was isolated (entry 2). On the other times of up to 12 hours (entries 8 and 9).
hand, N-benzyl aziridine (3a) furnished 1,2-diamine 8a in
In order to investigate the scope of the reaction other
8
1% yield after 48 hours at room temperature (entry 3).
aziridines 4b–e were subsequently examined in scandi-
um-catalyzed ring-opening reactions.10 Thus, the PMP-
substituted cyclohexyl aziridine (4b) was ring-opened
with both aniline and p-anisidine in excellent yields
(Table 3, entries 10 and 11). The reaction of cyclohexenyl
SYNLETT 2007, No. 14, pp 2289–2291
0
3
.0
9
.2
0
0
7
Advanced online publication: 24.07.2007
DOI: 10.1055/s-2007-984920; Art ID: G15707ST
©
Georg Thieme Verlag Stuttgart · New York

2
290
S. Peruncheralathan et al.
LETTER
Table 2 Optimization of the Ring-Opening Reaction
Table 3 Sc(OTf) -Catalyzed Aminolysis of N-Aryl Aziridines 4
3
H
N
Sc(OTf)3
1 mol%)
R
R
R
R
NHAr
Ar
(
Lewis acids
Ph
Ph
N
Ar +
H
N
N
Ph + PhNH2
R1
2 2
CH Cl , r.t.
1
NR Ar
CH2Cl2, r.t.
1
h
N
H
4
5
9–13
4a
5a
2 equiv)
(1.5 equiv)
(
9
a
Entry
Aziridine Amine products
Yield (%)a
Entry
Lewis acid
Time
Yield (%)a
NHPh
Ar
1
2
3
4
5
Y(OTf) (10 mol%)
15 min 93
15 min 96
15 min 79
N
Ph
H N
3
R1
1
NR Ar
Yb(OTf) (10 mol%)
3
1
1
2
3
4
5
6
7
8
9
4a
4a
4a
4a
4a
4a
4a
4a
4a
5a, 9a, Ar = Ph, R = H
5b, 9b, Ar = 4-MeOC H , R = H
90
Ce(OTf) (10 mol%)
3
1
96
6
4
InCl (10 mol%)
24 h
30 min 90
1 h
90b
82
3
1
5c, 9c, Ar = 2-MeOC H , R = H
85
6
4
Sc(OTf) (5 mol%)
3
1
5d, 9d, Ar = 4-ClC H , R = H
95
6
4
6
Sc(OTf) (1 mol%)
3
1
80b
88
5e, 9e, Ar = 4-FC H , R = H
6
4
a
Isolated yields.
.5 Equiv of aniline was used.
b
1
1
5f, 9f, Ar = 1-Naph, R = H
1
5g, 9g, Ar = Ph, R = Me
87
aziridine (4c) with aniline and p-anisidine afforded the
corresponding 1,2-diamines 11a and 11b in very good
yields (entries 12 and 13). Also, N-phenyl cycloheptyl
aziridine (4d) smoothly reacted with aniline and p-anisi-
dine giving rise to 1,2-diamines 12a and 12b in good to
excellent yields using 5 mol% of the catalyst (entries 14
and 15). Finally, N-phenyl-2,3-dimethylaziridine (4e)
upon reaction with aniline and p-anisidine furnished 1,2- 10
diamines 13a and 13b, respectively, in good to very good
yields with only 1 mol% of Sc(OTf) . Attempted scandi-
1
70c,d
65c,d
5h, 9h, Ar = 4-NO C H , R = H
2
6
4
1
5i, 9i, Ar = R = Ph
NHPMP
Ar
N
PMP
H N
R1
1
NR Ar
1
4b
4b
5a, 10a, Ar = Ph, R = H
89
1
1
1
5b, 10b, Ar = 4-MeOC H , R = H 93
6
4
3
um triflate catalyzed ring opening of aziridines with ali-
phatic amines such as benzyl amine failed, presumably
due to their more enhanced Lewis basicity leading to
tighter binding of Sc(OTf)3.
NHPh
Ar
N
Ph
H N
R1
1
NR Ar
1
12
4c
4c
5a, 11a, Ar = Ph, R = H
85
In conclusion, we have devised an efficient catalyst for the
aminolysis of meso-aziridines with aromatic amines fur-
nishing valuable 1,2-diamines in good to excellent yields.
Typically only 1 mol% of the catalyst was required for the
reaction to proceed to completion within short reaction
1
1
3
5b, 11b, Ar = 4-MeOC H , R = H 89
6
4
NHPh
Ar
N
Ph
H N
R1
1
NR Ar
1
78d,e
time. This compares favorably with previous methodolo- 14
4d
4d
Me
5a, 12a, Ar = Ph, R = H
3
gies, which require 5–20 mol% of catalyst. Work is being
5b, 12b, Ar = 4-MeOC H , R = H 90d,e
1
1
5
6
4
continued to develop this process into a catalytic, enantio-
selective reaction through searching for the optimal chiral
metal ligand.
Me
NHPh
Ar
N
Ph
H N
R1
1
Me
Me
NR Ar
1
1
1
6
7
4e
5a, 13a, Ar = Ph, R = H
60
Acknowledgment
1
4e
5b, 13b, Ar = 4-MeOC H , R = H 89
The Humboldt foundation is gratefully acknowledged for a post-
doctoral fellowship awarded to S. Peruncheralathan. We thank
BASF and Wacker for the generous donation of chemicals and
Christian Weise for performing preliminary experiments.
6
4
a
b
c
d
e
Isolated yields of chromatographed product.
The amount of 2 mol% of Sc(OTf) was used.
3
The amount of 10 mol% of Sc(OTf) was used.
3
Reaction time: 12 h.
The amount of 5 mol% of Sc(OTf) was used.
3
Synlett 2007, No. 14, 2289–2291 © Thieme Stuttgart · New York

LETTER
Aminolysis of meso-Aziridines
2291
References and Notes
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(
(
(
1) Reviews: (a) Schneider, C. Synthesis 2006, 3919.
(
(
b) Pastor, I. M.; Yus, M. Curr. Org. Chem. 2005, 9, 1.
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Catalysis, Vol. 2; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.,
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2) Reviews: (a) Aziridines and Epoxides in Organic Synthesis;
Yudin, A. K., Ed.; Wiley-VCH: Weinheim, 2006.
(
f) Hayashi, M.; Ono, K.; Hoshimi, H.; Oguni, N. J. Chem.
(
b) Pineschi, M. Eur. J. Org. Chem. 2006, 4979. (c) Hu, X.
Soc., Chem. Commun. 1994, 2699. (g) For the first catalytic,
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L.-X. Tetrahedron: Asymmetry 2007, 18, 443.
E. Tetrahedron 2004, 60, 2701. (d) McCoull, W.; Davis, F.
A. Synthesis 2000, 1347.
3) For select catalytic processes, see: (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.
(
6) (a) Mita, T.; Fujimori, I.; Wada, R.; Wen, J.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2005, 127, 11252.
(
b) Fukuta, Y.; Mita, T.; Fukuda, N.; Kanai, M.; Shibasaki,
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M. J. Am. Chem. Soc. 2006, 128, 6312. (c) For previous
catalytic, enantioselective azide addition to meso-aziridines,
see: Li, Z.; Fernandez, M.; Jacobsen, E. N. Org. Lett. 1999,
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,
1, 1611.
(7) (a) Schneider, C.; Sreekanth, A. R.; Mai, E. Angew. Chem.
Int. Ed. 2004, 43, 5691; Angew. Chem. 2004, 116, 5809.
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(
(
b) Mai, E.; Schneider, C. Chem. Eur. J. 2007, 13, 2729.
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(
2007, 2756. (e) Mai, E.; Schneider, C. Synlett 2007, 2136.
(
(
8) Scandium triflate has been shown to catalyze the addition of
acid anhydrides to aziridines, see: Yadav, J. S.; Reddy, B. V.
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(
6
b) Hou, X.-L.; Fan, R.-H.; Dai, L.-X. J. Org. Chem. 2002,
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(
10) General Procedure for Ring Opening of meso-Aziridines
To a solution of Sc(OTf) (5 mg, 0.01 mmol) in CH Cl
3
2
2
(
5 mL), were added N-phenyl aziridine (1.00 mmol) and
amine (1.50 mmol), and the mixture was stirred at r.t. for 1 h
monitored by TLC). The solvent was removed in vacuo and
(
the crude product was purified through flash chromatog-
raphy using pentane–EtOAc (15:1) as eluent. For analytical
and spectroscopic details of the products see ref. 3.
Synlett 2007, No. 14, 2289–2291 © Thieme Stuttgart · New York

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