Highly asymmetric cobalt-catalyzed aziridination of alkenes with trichloroethoxysulfonyl azide (TcesN3)

Article abstract of DOI:10.1039/b905727g

A Co(ii)-based catalytic system has been developed for asymmetric aziridination of alkenes with trichloroethoxysulfonyl azide (TcesN₃) under mild conditions, forming the corresponding N-Tces-aziridines in high yields and excellent enantioselect

Full text of DOI:10.1039/b905727g

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Highly asymmetric cobalt-catalyzed aziridination of alkenes
with trichloroethoxysulfonyl azide (TcesN3)wz
Velusamy Subbarayan, Joshua V. Ruppel, Shifa Zhu, Jason A. Perman and X. Peter Zhang*
Received (in College Park, MD, USA) 23rd March 2009, Accepted 26th May 2009
First published as an Advance Article on the web 11th June 2009
DOI: 10.1039/b905727g
A
Co(II)-based catalytic system has been developed for
trichloroethoxysulfonyl azide (TcesN3) as a new nitrene source
and Co(II) complexes of D2-symmetrical chiral porphyrins
([Co(Por*)]) (Fig. 1) as catalysts (Scheme 1).10 The [Co(Por*)]–
TcesN3-based system is operationally simple and capable of
aziridinating both aromatic and aliphatic olefins under mild
conditions, forming the corresponding N-Tces-aziridines in
high yields and excellent enantioselectivities. Furthermore,
the catalytic system could be conveniently recycled and reused
multiple times through a simple precipitation/filtration protocol
without significant loss of reactivity and selectivity. In addi-
tion, a noteworthy additive effect of Pd(OAc)2 on the yield of
the Co-catalyzed aziridination is also described.
asymmetric aziridination of alkenes with trichloroethoxysulfonyl
azide (TcesN3) under mild conditions, forming the corresponding
N-Tces-aziridines in high yields and excellent enantioselectivities.
Aziridines, the smallest nitrogen heterocyclic compounds,
exhibit numerous important applications, including serving
as essential motifs of biologically interesting compounds
and as valuable synthons for preparation of various amine
derivatives.1 Among several approaches, metal-catalyzed
asymmetric aziridination of alkenes with proper nitrene
sources represents one of the most general and direct methods
for stereoselective construction of the three-membered ring
structure.2 As the common nitrene source, iminoiodane
derivatives such as PhIQNTs and its variants have been
successfully employed for asymmetric aziridination of certain
types of alkenes in catalytic systems that are primarily based
on chiral Cu complexes.3 While some of the most promising
Cu-catalyzed systems can efficiently aziridinate internal alkenes
having additional functionalities (such as cinnamate esters)
with high enantioselectivity, they are significantly less effective
for simple terminal olefins (such as styrenes), suggesting the
requirement of secondary binding interactions.3 Despite the
perceived ineffectiveness of azides for metal-catalyzed nitrene
transfer reactions, recent results from several groups4–8 suggest
the potential of azides as a class of general nitrene sources with
several attractive features.9 Through the discovery of new
chiral catalysts, asymmetric aziridination with azides may be
further developed into a broad and useful catalytic process.
We recently disclosed the unique catalytic properties of
Co(II) complexes of porphyrins for olefin aziridination and
C–H amination with different azides, including diaryl-
phosphoryl and arylsulfonyl azides.8 To improve catalytic
efficacy and to control enantioselectivity, efforts have been
made to identify more effective azides and to employ suitable
chiral porphyrin ligands for the development of Co-catalyzed
asymmetric aziridination with azides. Herein, we report a
highly asymmetric aziridination process that consists of
Among the various azides that were evaluated, TcesN3, a
new azide that was readily synthesized from CCl3CH2OH in
high yield and on a multigram scale, turned out to be one of
the most promising nitrene sources for [Co(Por*)]-catalyzed
asymmetric aziridination due to its high reactivity and con-
venient usage.11,12 As summarized in Table 1 and Table S1
(ESIz) for the aziridination of styrene, although the Co(II)
complexes of P1 and P2 derived from chiral cyclopropane-
carboxamide could effectively catalyze the reaction at room
temperature, the enantioselectivities were low (entries 1 and 2).
Employment of P3 and P4, which contain chiral methoxy-
propionamide, improved both yield and enantioselectivity
(entries 3 and 4). While no further improvement was observed
with P5, high enantioselectivity was achieved by using
[Co(P6)] where the Co(II) center is surrounded by methoxy
and chiral tetrahydrofurancarboxamide units, albeit in lower
Department of Chemistry, University of South Florida, Tampa,
FL 33620-5250, USA. E-mail: pzhang@cas.usf.edu;
Fax: þ1 813 974 7249; Tel: þ1 813 974 1733
w This article is part of a ChemComm ‘Catalysis in Organic Synthesis’
web-theme issue showcasing high quality research in organic
chemistry. Please see our website (http://www.rsc.org/chemcomm/
organicwebtheme2009) to access the other papers in this issue.
z Electronic supplementary information (ESI) available: Experimental
procedures and analytical data for all compounds; crystallography
data for 2-(4-chlorophenyl)-1-aziridine-sulfonic acid 20,20,20-trichloro-
ethyl ester. CCDC 724786. For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/b905727g
Fig. 1 Structures of D2-symmetric chiral cobalt(II) porphyrins.
Scheme 1 Asymmetric Co(II)-catalyzed aziridination with TcesN3.
ꢀc
This journal is The Royal Society of Chemistry 2009
4266 | Chem. Commun., 2009, 4266–4268

Table 1 Enantioselective aziridination of styrene with trichloroethoxy-
sulfonyl azide by chiral cobalt(II) porphyrinsa
Table 2 [Co(P6)]-catalyzed enantioselective aziridination of different
alkenes with trichloroethoxysulfonyl azide (TcesN3)a
Yieldb Eec
Entry Olefin
Aziridine
Temp/1C (%)
(%) [a]d
1
2
0
0
91
89
94
90
(ꢁ)
(ꢁ)
Entry [Co(Por*)]b mol (%) Temp/1C Yieldc (%) Eed (%)
1
2
3
4
5
6
7
8
[Co(P1)]
[Co(P2)]
[Co(P3)]
[Co(P4)]
[Co(P5)]
[Co(P6)]
[Co(P6)]
[Co(P6)]
[Co(P6)]
[Co(P6)]
[Co(P6)]
[Co(P6)]
2.0
2.0
2.0
2.0
2.0
2.0
5.0
5.0
5.0
5.0
5.0
5.0
RT
RT
RT
RT
RT
RT
RT
RT
0
80
84
90
95
85
58
79
90
69
91
15
59
25
4
ꢁ39
ꢁ51
52
86
88
88
94
3f
4f
5
RT
RT
0
85
86
89
93
82
84
85
91
(ꢁ)
(ꢁ)
(ꢁ)
9
10e
11
12e
0
94
96
96
ꢁ10
ꢁ10
a
Performed under N2; styrene : TcesN3 ¼ 5.0 : 1.0; [styrene] ¼
6
0
(ꢁ)
b
c
0.25 M. See Fig. 1 and Fig. S1 (ESIz) for structures. Isolated
(R)e
d
e
yields. Measured by chiral HPLC. Added 5 mol% Pd(OAc)2.
7
8
0
0
92
90
91
90
(ꢁ)
(ꢁ)
yield (entries 5 and 6). The yield of [Co(P6)]-catalyzed reaction
could be greatly increased by raising catalyst loading without
affecting the high ee value (entries 7 and 8). When conducted
at lower temperatures, the enantioselectivity was further
improved to 94–96% ee, but at a sacrifice of yields (entries 9
and 11). Interestingly, addition of a catalytic amount of
Pd(OAc)2 resulted in a dramatic increase in yields with no
effect on the high enantioselectivity (entries 10 and 12),
presumably due to the activation of styrene by the p-electrophilic
Lewis acid, Pd(OAc)2.13
9
0
0
0
91
92
88
88
99
81
(ꢁ)
(ꢁ)
(ꢁ)
10
11
With the optimization of catalytic conditions, the substrate
scope of the [Co(P6)]–TcesN3-based system was examined
(Table 2). Like styrene (entry 1), its various derivatives were
also excellent substrates, including those substituted with alkyl
(entries 2–5) and halogen (entries 6–10) groups at different ring
positions. The corresponding aziridines were produced in high
yields and excellent enantioselectivities.4 In the case of 2-bromo-
styrene, the desired product was isolated in 92% yield and
99% ee (entry 10). Styrene derivatives containing strongly
electron-withdrawing groups were suitable substrates as well
albeit in lower ee (entries 11 and 12). Furthermore, the
aziridination of 2-vinylnaphthalene and a-methylstyrenes
was successfully performed (entries 13–15). When an enol
derivative was used as the substrate, the corresponding
a-amino ketone was obtained in high yield as a result of ring-
opening of the aziridine product (entry 16). In addition to
aromatic olefins, aliphatic olefins could be aziridinated in high
enantioselectivities, but low yields (entries 17–19).14 Finally, the
catalytic system could also be applied for the aziridination of
aliphatic dienes and cyclic olefins (entries 20 and 21).
12
0
82
85
48
43
80
90
80
80
(ꢁ)
(ꢁ)
(ꢁ)
(ꢁ)
13
0
14f
15f
RT
RT
16f
40
87
—
—
17g
18g
19f
40
40
0
42
30
26
91
90
94
(þ)
(þ)
(þ)
20h
RT
40
53
85
87
—
(ꢁ)
21f
—
The absolute configuration of the aziridination product of
4-chlorostyrene, 2-(4-chlorophenyl)-1-aziridine-sulfonic acid
20,20,20-trichloroethyl ester (Table 2, entry 6), was established
to be (R) by X-ray crystallographic analysis (Fig. 2). In view of
the same sign of optical rotations, all the other aziridine
derivatives from aromatic olefins and conjugate dienes
(Table 2, entries 1–15 and 20) are expected to have the same
a
Performed in C6H5Cl using 5 mol% [Co(P6)] for 48 h under N2 with 4 A
MS in the presence of 5 mol% Pd(OAc)2; alkene : TcesN3 ¼ 5 : 1; [alkene]
b
c
d
¼ 0.25 M. Isolated yields. Measured by chiral HPLC. Sign of optical
e
rotation. Determined by X-ray crystal structural analysis. 24 h without
f
g
Pd(OAc)2. Using [Co(P5)] in CH2Cl2 for 48 h. In MeCO2Et.
h
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 4266–4268 | 4267

Notes and references
1 (a) X. E. Hu, Tetrahedron, 2004, 60, 2701; (b) J. B. Sweeney, Chem.
Soc. Rev., 2002, 31, 247; (c) B. Zwanenburg and P. ten Holte, Top.
Curr. Chem., 2001, 216, 93; (d) W. McCoull and F. A. Davis,
Synthesis, 2000, 1347.
2 (a) P. Muller and C. Fruit, Chem. Rev., 2003, 103, 2905;
(b) E. N. Jacobsen, in Comprehensive Asymmetric Catalysis, ed.
E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Springer, Berlin, 1999,
vol. 2, 607; (c) J. A. Halfen, Curr. Org. Chem., 2005, 9, 657.
3 For select examples of asymmetric aziridination of alkenes, see:
(a) Z. Li, K. R. Conser and E. N. Jacobsen, J. Am. Chem. Soc.,
1993, 115, 5326; (b) D. A. Evans, M. M. Faul, M. T. Bilodeau,
B. A. Anderson and D. M. Barnes, J. Am. Chem. Soc., 1993, 115,
5328; (c) C. J. Sanders, K. M. Gillespie, D. Bell and P. Scott,
J. Am. Chem. Soc., 2000, 122, 7132; (d) X. Wang and K. Ding,
Chem.–Eur. J., 2006, 12, 4568; (e) H. Nishikori and T. Katsuki,
Tetrahedron Lett., 1996, 37, 9245; (f) P. Muller, C. Baud and
Y. Jacquier, Tetrahedron, 1996, 52, 1543; (g) J.-L. Liang, X.-Q. Yu
and C.-M. Che, Chem. Commun., 2002, 124; (h) M. Anada,
M. Tanaka, T. Washio, M. Yamawaki, T. Abe and
S. Hashimoto, Org. Lett., 2007, 9, 4559; (i) C. Fruit and
P. Muller, Tetrahedron: Asymmetry, 2004, 15, 1019.
Fig.
2
X-ray crystal structure of 2-(4-chlorophenyl)-1-aziridine-
sulfonic acid 20,20,20-trichloroethyl ester (Table 2, entry 6).
Table 3 Reusability of [Co(P6)] for asymmetric aziridinationa
Entry
Cycle
Temp/1C
Yieldb (%)
eec (%)
4 (a) S. Fantauzzi, E. Gallo, A. Penoni, F. Ragaini, P. Macchi,
N. Casati and S. Cenini, Organometallics, 2005, 24, 4710;
(b) C. Piangiolino, E. Gallo, A. Caselli, S. Fantauzzi, F. Ragaini
and S. Cenini, Eur. J. Org. Chem., 2007, 743; (c) S. Fantauzzi,
E. Gallo, A. Caselli, C. Piangiolino, F. Ragaini and S. Cenini, Eur.
J. Org. Chem., 2007, 6053; (d) A. Caselli, E. Gallo, S. Fantauzzi,
S. Morlacchi, F. Ragaini and S. Cenini, Eur. J. Org. Chem., 2008,
3009.
1
2
3
First
Second
Third
RT
RT
RT
95
89
81
96
94
94
a
Performed in C6H5Cl using 5 mol% [Co(P6)] for 48 h under N2 with
4 A MS in the presence of 5 mol% Pd(OAc)2: alkene–TcesN3 ¼ 5 : 1;
b
c
[alkene] ¼ 0.25 M. Isolated yields. Measured by chiral HPLC.
5 (a) K. Omura, M. Murakami, T. Uchida, R. Irie and T. Katsuki,
Chem. Lett., 2003, 354; (b) K. Omura, T. Uchida, R. Irie and
T. Katsuki, Chem. Commun., 2004, 2060; (c) H. Kawabata,
K. Omura and T. Katsuki, Tetrahedron Lett., 2006, 47, 1571;
(d) H. Kawabata, K. Omura, T. Uchida and T. Katsuki,
Chem.–Asian J., 2007, 2, 248.
6 (a) B. J. Stokes, H. Dong, B. E. Leslie, A. L. Pumphrey and
T. G. Driver, J. Am. Chem. Soc., 2007, 129, 7500; (b) M. Shen,
B. E. Leslie and T. G. Driver, Angew. Chem., Int. Ed., 2008, 47,
5056.
7 (a) Y. M. Badiei, A. Dinescu, X. Dai, R. M. Palomino,
F. W. Heinemann, T. R. Cundari and T. H. Warren, Angew.
Chem., Int. Ed., 2008, 47, 9961; (b) H. Han, S. B. Park, S. K. Kim
and S. Chang, J. Org. Chem., 2008, 73, 2862.
8 (a) G.-Y. Gao, J. E. Jones, R. Vyas, J. D. Harden and X. P. Zhang,
J. Org. Chem., 2006, 71, 6655; (b) J. V. Ruppel, R. M. Kamble and
X. P. Zhang, Org. Lett., 2007, 9, 4889; (c) J. V. Ruppel, J. E. Jones,
C. A. Huff, R. M. Kamble, Y. Chen and X. P. Zhang, Org. Lett.,
2008, 10, 1995; (d) J. E. Jones, J. V. Ruppel, G.-Y. Gao,
T. M. Moore and X. P. Zhang, J. Org. Chem., 2008, 73,
7260.
9 (a) T. Katsuki, Chem. Lett., 2005, 1304; (b) S. Cenini, E. Gallo,
A. Caselli, F. Ragaini, S. Fantauzzi and C. Piangiolino, Coord.
Chem. Rev., 2006, 250, 1234.
10 (a) Y. Chen, K. B. Fields and X. P. Zhang, J. Am. Chem. Soc.,
2004, 126, 14718; (b) S. Zhu, J. V. Ruppel, H. Lu, L. Wojtas and
X. P. Zhang, J. Am. Chem. Soc., 2008, 130, 5042; (c) M. P. Doyle,
Angew. Chem., Int. Ed., 2009, 48, 850.
11 For the use of trichloroethylsulfamate ester in the presence of an
oxidant for metal-catalyzed aziridination, see: (a) K. Guthikonda
and J. Du Bois, J. Am. Chem. Soc., 2002, 124, 13672;
(b) G. F. Keaney and J. L. Wood, Tetrahedron Lett., 2005, 46,
4031; (c) Z. Li, X. Ding and C. He, J. Org. Chem., 2006, 71, 5876;
(d) Q. Xu and D. H. Appella, Org. Lett., 2008, 10, 1497.
12 Control experiments showed TcesN3 was stable up to at least
100 1C. But it should be noted that certain azides may be
potentially explosive and should be handled with care.
(R) absolute configuration by analogy. It was interesting to
note that the aziridine products from the reactions of aliphatic
olefins exhibited the opposite sign of optical rotations
(Table 2, entries 17–19).
To enhance the practicality of the [Co(P6)]–TcesN3-based
catalytic system, a simple precipitation/filtration protocol was
established to allow for the recycling/reusing of the catalyst.
After each catalytic cycle, [Co(P6)] could be completely
precipitated without change (see ESIz) by adding hexanes
where it absorbed uniformly to the molecular sieves (MS)
preexisting in the system. The MS-absorbed [Co(P6)] was then
filtered, dried under vacuum with heating, and reused. As
demonstrated with the reaction of 2-bromostyrene, the cata-
lytic system could be recycled/reused three times without
significant loss of either yield or enantioselectivity (Table 3).
In summary, we have developed a highly efficient aziridina-
tion system based on [Co(P6)] and TcesN3. This represents the
first highly effective and enantioselective catalytic system for
asymmetric aziridination of a broad range of simple olefins,
without the need of additional functionalities in the substrates
for secondary binding interactions. In addition to the common
attributes associated with the use of azides as the nitrene
sources,9 a simple protocol has been established for the
[Co(P6)]–TcesN3-based system to allow for the recycling/reusing
of the catalyst, further enhancing its potential for practical
synthetic applications. This Co-catalyzed asymmetric aziridina-
tion with TcesN3 complements the previous Cu/ArIQNTs-based
systems,3 which are suitable for internal olefins having additional
functionalities.
13 Y. Yamamoto, J. Org. Chem., 2007, 72, 7817.
We are grateful to USF (Startup Funds), ACS-PRF
(AC Grant), NSF (CAREER Award) and NSF (CHE-0443611,
Mass Facility) for financial support of this work.
14 For examples of efficient aziridination of aliphatic olefins, see:
(a) ref. 11; (b) A. J. Catino, J. M. Nichols, R. E. Forslund and
M. P. Doyle, Org. Lett., 2005, 7, 2787.
ꢀc
This journal is The Royal Society of Chemistry 2009
4268 | Chem. Commun., 2009, 4266–4268