Asymmetric olefin aziridination using a newly designed Ru(CO)(salen) complex as the catalyst

Article abstract of DOI:10.1039/c2cc32997b

Highly enantioselective and good to high-yielding aziridination of conjugated and non-conjugated terminal olefins and cyclic olefins was achieved using a newly designed Ru(CO)(salen) complex as the catalyst in the presence of SESN₃ under mild conditions.

Full text of DOI:10.1039/c2cc32997b

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COMMUNICATION
Asymmetric olefin aziridination using a newly designed Ru(CO)(salen)
complex as the catalystw
Chungsik Kim,ab Tatsuya Uchidaab and Tsutomu Katsuki*b
Received 26th April 2012, Accepted 24th May 2012
DOI: 10.1039/c2cc32997b
Highly enantioselective and good to high-yielding aziridination of
conjugated and non-conjugated terminal olefins and cyclic olefins
was achieved using a newly designed Ru(CO)(salen) complex as the
catalyst in the presence of SESN3 under mild conditions.
Aziridines, three-membered ring heterocycles with one amino
group, have been recognized as versatile intermediates for
organic synthesis.1 Since Kwart and Khan’s first report on
metal-catalyzed nitrene-transfer reactions in 1967,2 much effort
Scheme 1 Asymmetric aziridination using a Ru(CO)(salen) complex
as a catalyst.
has been directed toward developing enantioselective aziridination
of alkenes with a nitrene source. Highly enantioselective reactions
the complex.11 Eventually, complex 2 having the 3,5-dichloro-
have been developed by using a chiral copper or manganese
4-trimethylsilylphenyl group at C200 was synthesized to catalyze
aziridination of conjugated terminal olefins using SESN3 at low
catalyst loading in a high enantioselectivity (92–>99% ee)
(Scheme 1); however, the reactions of non-conjugated 1-alkenes
such as 1-octene were slow even under reflux conditions and
showed moderate enantioselectivity.10d The turnover number
(TON) in the aziridination of styrene was 260 (Table 1, entry 1).
Recently, Zhang et al. reported that a Co(II)–porphyrin complex
catalyzed highly enantioselective aziridination of conjugated and
non-conjugated terminal olefins with trichloroethoxysulfonyl azide
(TcesN3) in the presence of a co-catalyst, Pd(OAc)2.12
complex as a catalyst in the last two decades.3 These aziridination
reactions, however, use N-arylsulfonyliminophenyliodinanes
(PhIQNTs) or their equivalents as a nitrene source, and the
reactions are thus not very atom-efficient. Although Kwart
and Khan used atom-efficient azide compounds as nitrene
sources,2 azide compounds had not been employed as nitrene
sources in the subsequent studies mainly because of two
reasons:4 (i) harsh conditions (heating or UV irradiation) are
needed for azide decomposition5,6 and (ii) N-deprotection is
difficult. Recently, azides having readily removable N-protecting
groups such as o- or p-nitrobenzenesulfonyl (o- or p-Ns)7 and
2-(trimethylsilyl)ethanesulfonyl (SES)8 groups have been developed.
However, there is still the need for identifying a catalyst that
expands the substrate scope and reduces the catalyst loading
and the additive amount of the substrate, effectively improving
the asymmetric catalytic aziridination. In order to address
these requirements, increasing the activity of a putative nitrenoid
In addition, Bach and Korber reported that iron(II) chloride
¨
decomposes azides and transfers nitrenes to sulfides under mild
conditions, though not with enantioselectivity.9
In previous reports, we also found that chiral Ru(CO)(salen)
complexes efficiently decompose azides at room temperature and
catalyze asymmetric imidation of sulfides and aziridination.10
For example, complex 1 catalyzes alkyl aryl sulfide imidation
with high enantioselectivity (93–99% ee).10a However, when
the substrate was olefin, aziridination occurred competitively
with intramolecular C–H amination at the C200-phenyl ring of
Table 1 Comparison of the aziridination reaction conditionsa
Entry Catalyst mol (%) Temp (1C) Time (h) Yieldb (%) eec (%)
1d
2
2
3
3
4
0.1
0.5
0.1
1
0
12
20
20
20
26
99
57
93
91
90
90
86
a Department of Chemistry, Faculty of Science, Graduate School,
Kyushu University, Hakozaki, Higashi-ku Fukuoka 812-8581, Japan
b International Institute for Carbon-Neutral Energy Research
(WPI-I2CNER) Kyushu University, Hakozaki, Higashi-ku,
Fukuoka 812-8581, Japan. E-mail: katsuscc@chem.kyushu-univ.jp;
Fax: +81 92 642 2607
w Electronic supplementary information (ESI) available: Procedure
for synthesis and experimental data for the products. CCDC 870579
and 870052. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c2cc32997b
RT
RT
RT
3e
4
a
Unless otherwise noted, reactions were carried out with styrene
b
(0.12 mmol) and azide (0.1 mmol) in 0.25 mL of CH2Cl2. Isolated
c
yield after silica gel column chromatography. Determined by chiral
d
e
HPLC. Taken from ref. 10d (styrene/SESN3 = 1/1). Run on a
0.3 mmol scale.
c
7188 Chem. Commun., 2012, 48, 7188–7190
This journal is The Royal Society of Chemistry 2012

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intermediate and enhancing catalyst durability are essential. Herein,
we report the highly enantioselective aziridination of conjugated
and non-conjugated olefins using a novel Ru(CO)(salen) complex
as a catalyst in the presence of SESN3 as a nitrene source.
olefin/azide = 3/1 at room temperature in a good yield (74% yield)
and excellent enantioselectivity (99% ee, entry 1). The reaction of
vinylcyclohexane also showed excellent enatioselectivity (99% ee)
under the same conditions (entry 2). To examine the regioselectivity
for the aziridination of alkadienes, reactions of 7-methyl-1,6-
octadiene and 1,4-hexadiene were carried out. Both reactions
solely produced the terminal aziridine products over the
internal aziridines in good yields (54% and 58%) and high
enantioselectivity (89% ee at 0 1C and 91% ee) (entries 3 and 4).
However, terminal allylic C–H amination was observed in the
reaction of 1,4-hexadiene.
It has been reported that a sulfonyl oxygen atom of
N-sulfonyl nitrenoid interacts with the electrophilic nitrenoid
N-atom or with the metal center and undergoes aziridination.13
Based on these reports, we inferred that the reactivity of the
nitrenoid intermediate would be enhanced if the sulfonyl oxygen
atom on the metal-nitrenoid were to interact with a ligand
having a vacant orbital in close proximity to the oxygen
atom.14 Moreover, if a C–F* antibonding orbital can interact
with the p-orbital of the aryl group at the C200 position,15 the
tolerance of the complex to an electrophile should also be
enhanced. As such, we expected that a Ru(CO)(salen) complex
bearing a C–F bond located at the appropriate position would
show good catalytic activity for aziridination. Thus, we synthesized
complexes 3 and 4 as having a 3,5-di(trifluoromethyl)phenyl group
at the C200 position. Complex 3 was stable under the conditions for
the aziridination of styrene (Table 1) and its turnover number
amounted to 570 without diminishing enantioselectivity (entry 3).
Complex 4 also showed good tolerability, though enantioselectivity
was slightly inferior to that of complex 3 (entry 4).
The reaction of 3-phenyl-1-propene was slower than that of
other 1-alkenes, but the reaction proceeded at 40 1C under
solvent-free conditions with high enantioselectivity (90% ee)
and yield (91%) (entry 5). Moreover, 6-bromo-1-hexene was
quite reactive and the reaction proceeded at 0 1C with high
enantioselectivity (91% ee) (entry 6). The reaction of 6-benzyloxy-1-
hexene also proceeded with a good yield and high enantioselectivity
at 0 1C (65% and 87% ee) (entry 7).
We also examined the aziridination of aromatic olefins
(Table 3). Styrene derivatives, possessing an alkyl (entries 1–3)
or a halogen (entries 4 and 5) group at different position,
efficiently underwent aziridination in excellent yields and high
enantioselectivity with low catalyst loading (0.5–1 mol%) under
mild conditions. In particular, o-methylstyrene produced the highly
enantioenriched aziridine (97% ee). Additionally, aziridination
of 2-vinylnaphthalene proceeded in excellent yield and high
enantioselectivity (entry 6). Moreover, the reactions of cis-
disubstituted olefins, cis-b-methylstyrene and indene proceeded
with excellent enantioselectivities ( Z 97% ee) and moderate
Based on these results, we examined the aziridination of
non-conjugated terminal olefins using 3 as the catalyst
(Table 2). To our delight, the aziridination of 1-hexene proceeded
smoothly using 3 mol% of the catalyst 3 with a molar ratio of
Table
3 Asymmetric aziridination of aromatic olefins using
Ru(CO)(salen) 3 as the complexa
mol
(%)
Temp
(1C)
Time
(h)
Yieldb
(%)
eec
(%)
Entry
1
Substrate
Table 2 Asymmetric aziridination of 1-alkenes using Ru(CO)(salen)
3 as the complexa
0.5
25
25
25
25
25
25
6
6
6
6
6
6
95
98
95
95
96
99
97
90
89
90
90
91
mol
(%)
Temp
(1C)
Time
(h)
Yieldb
(%)
eec
(%)
Entrty Substrate
1
2
3
4
5
6
7
0.5
0.5
1
3
3
25
25
24
24
74
45
99
99
2
3d
3
0
24
54
89
4e
5f
3
3
25
40
24
24
58
91
91
90
1
0.5
6
7
3
3
0
0
24
24
95
65
91
87
1
1
25
25
12
12
72
66
99
97
a
8
Unless otherwise noted, reactions were carried out on a 0.3 mol
b
scale in 0.4 mL of CH2Cl2. Isolated yield. Determined by chiral
c
a
d
HPLC analysis. A trace amount of the C–H amination product was
Unless otherwise noted, reactions were carried out on a 0.3 mol scale
b
with styrene/azide (1.2/1.0) in 0.4 mL of CH2Cl2. Isolated yield.
e
observed by TLC. 6-(SESamino)hexa-1,4-diene was obtained in 35%
c
f
yield. Neat reaction.
Determined by chiral HPLC analysis.
c
This journal is The Royal Society of Chemistry 2012
Chem. Commun., 2012, 48, 7188–7190 7189

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C. Fruit, Chem. Rev., 2003, 103, 2905; (d) C. Mossner and
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2 H. Kwart and A. Khan, J. Am. Chem. Soc., 1967, 89, 1951.
3 For selected examples of catalytic asymmetric aziridination and
related works reported in the last two decades: (a) D. A. Evans,
K. A. Woepel, M. H. Hinman and M. M. Faul, J. Am. Chem. Soc.,
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A. N. Vedernikov, J. Org. Chem., 2005, 70, 4833.
Fig. 1 X-ray crystal structures of 2-(naphthalene-2-yl)-1-[2-(tri-
methylsilylethane)sulfonyl]aziridine (a) and 2-(4-methylphenyl)-1-[2-
(trimethylsilylethane)sulfonyl]aziridine (b).
4 T. Katsuki, Chem. Lett., 2005, 1304.
yields (entries 7 and 8). The reaction of trans-b-methylstyrene
gave only the allylic amination product in ca. 40%.16
5 (a) S. Cenini, S. Tollari, A. Penoni and C. Cereda, J. Mol. Catal. A:
Chem., 1999, 37, 135; (b) S. Cenini, E. Gallo, A. Penoni, F. Ragaini
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and T. Kan, Tetrahedron Lett., 1997, 38, 5831.
The absolute configuration of the synthesized aziridines was
unknown, except for that of N-SES-2-phenylaziridine which was
determined by comparison of its optical rotation value with the
reported one.17 In this study, we obtained single crystals of
2-(naphthalen-2-yl)-1-[2-(trimethylsilylethane)sulfonyl]aziridine and
2-(4-methylphenyl)-1-[2-(trimethylsilylethane)sulfonyl]aziridine and
determined their configuration to be S by X-ray crystallographic
analysis (Fig. 1).17 Absolute configuration of 2-methyl-3-phenyl-
1-{[2-(trimethylsilyl)ethane]sulfonyl}aziridine was determined
to be 2R,3S by comparison of chemical rotation, after the
SES-group deprotection.17
8 S. M. Weinreb, D. M. Demko and T. A. Lessen, Tetrahedron Lett.,
1986, 27, 2099.
9 T. Bach and C. Korber, Eur. J. Org. Chem., 1999, 1033.
¨
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2001, 42, 7071; (b) K. Omura, M. Murakami, T. Uchida, R. Irie
and T. Katsuki, Chem. Lett., 2003, 32, 354; (c) K. Omura,
T. Uchida, R. Irie and T. Katsuki, Chem. Commun., 2004, 2060;
(d) H. Kawabata, K. Omura, T. Uchida and T. Katsuki, Chem.–
Asian J., 2007, 2, 248.
11 T. Uchida, Y. Tamura, M. Ohba and T. Katsuki, Tetrahedron
Lett., 2003, 44, 7965.
12 (a) J. E. Jones, J. V. Ruppel, G.-Y. Gao, T. M. Moore and
X. P. Zhang, J. Org. Chem., 2008, 73, 7260; (b) V. Subbarayan,
J. V. Ruppel, S. Zhu, J. A. Perman and X. P. Zhang, Chem.
Commun., 2009, 4266.
In conclusion, we were able to develop a durable and
catalytically active new Ru(CO)(salen) complex bearing 3,5-
ditrifluoromethylphenyl group 3, which efficiently facilitated
the highly enantioselective aziridination of conjugated and non-
conjugated olefins using low catalyst loading (0.5–1 mol%) for
conjugated olefins and 3 mol% for non-conjugated olefins.
Financial support from Nissan Chemical Industries, Ltd.
and World Premier International Research Center Initiative
(WPI), the Global COE Program, ‘Science for Future Molecular
Systems’ and Grants-in-Aid for Scientific Research No.
23245009 from MEXT, Japan, is gratefully acknowledged.
13 (a) K. M. Gillespie, E. J. Crust, R. C. Deeth and P. Scott, Chem.
Commun., 2001, 785; (b) P. Brandt, M. J. Sodergren,
¨
P. G. Andersson and P.-O. Norrby, J. Am. Chem. Soc., 2000,
122, 8013.
14 For examples of nO–s*XY interactions, see: (a) C. A. Kingsbury,
J. Phys. Org. Chem., 2010, 23, 513; (b) H. Komatsu, M. Iwaoka
and S. Tomoda, Chem. Commun., 1999, 205.
15 L. Goodman, H. Gu and V. Pophristic, J. Phys. Chem. A, 2005,
109, 1223.
Notes and references
1 Reviews on asymmetric aziridination: (a) H. Muchalski and
J. N. Johnston, Science of Synthesis, ed. J. G. de Vries, Georg
Thieme Velag KG, 2011, vol. 1, pp. 155–184; (b) D. Tanner,
Angew. Chem., Int. Ed. Engl., 1994, 33, 599; (c) P. Muller and
16 Yield was determined by 1H NMR analysis of the crude reaction
mixture. No aziridination product was detected.
17 For details, see the ESIw.
c
7190 Chem. Commun., 2012, 48, 7188–7190
This journal is The Royal Society of Chemistry 2012