Iron(III) porphyrin catalyzed aziridination of alkenes with bromamine-T as nitrene source

Article abstract of DOI:10.1021/ol049691k

Equation presented. Iron(III) porphyrin complexes Fe(Por)Cl are effective catalysts for aziridination of alkenes using bromamine-T as the nitrene source. The catalytic system can operate under mild conditions with alkenes as limiting reagents. The aziridi

Full text of DOI:10.1021/ol049691k

ORGANIC
LETTERS
2
004
Vol. 6, No. 12
907-1910
Iron(III) Porphyrin Catalyzed
1
Aziridination of Alkenes with
Bromamine-T as Nitrene Source
Renu Vyas, Guang-Yao Gao, Jeremiah D. Harden, and X. Peter Zhang*
Department of Chemistry, UniVersity of Tennessee, KnoxVille, Tennessee 37996-1600
pzhang@utk.edu
Received February 21, 2004 (Revised Manuscript Received May 6, 2004)
ABSTRACT
Iron(III) porphyrin complexes Fe(Por)Cl are effective catalysts for aziridination of alkenes using bromamine-T as the nitrene source. The catalytic
system can operate under mild conditions with alkenes as limiting reagents. The aziridination reaction is general and suitable for a wide
variety of alkenes, including aromatic, aliphatic, cyclic, and acyclic olefins, as well as r,â-unsaturated esters. For 1,2-disubstituted olefins, the
reactions proceeded with moderate to low stereospecificity.
Aziridination of alkenes mediated by a transition metal
complex is one of the most attractive methods for the
efficient and selective construction of synthetically and
interest in developing metal-catalyzed aziridination of alkenes
5
with alternative nitrene sources such as chloramine-T,
6
7
bromamine-T, and azides.
1
biologically important aziridines. The reagent [N-(p-tolu-
Metalloporphyrins have played a pivotal role in the
development of several important catalytic atom/group
enesulfonyl)imino]phenyliodinane (PhIdNTs) and related
iminoiodane derivatives, aza-analogues of iodosylbenzene,
have been extensively used as primary nitrene sources for
(4) For the use of in situ formed iminoiodane, see: (a) Yu, X.-Q.; Huang,
2
catalytic aziridination. Although great progress has been
J.-S.; Zhou, X.-G.; Che, C.-M. Org. Lett. 2000, 2, 2233. (b) Dauban, P.;
Saniere, L.; Tarrade, A.; Dodd, R. H. J. Am. Chem. Soc. 2001, 123, 7707.
made with PhIdNTs in a number of metal-catalyzed systems
(
c) Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc. 2002, 124, 13672.
(5) (a) Minakata, S.; Kano, D.; Fukuoka, R.; Oderaotoshi, Y.; Komatsu,
1,3
including asymmetric aziridination, the reagent suffers from
several drawbacks including its commercial unavailability,
high cost, and insolubility along with generation of the heavy
PhI byproduct.4 Consequently, there has been growing
M. Heterocycles 2003, 60, 289. (b) Jain, S. L.; Sain, B. J. Mol. Catal. A:
Chem. 2003, 195, 283. (c) Gullick, J.; Taylor, S.; McMorn, P.; Bethell, D.;
Page, P. B. C.; Hancock, F. E.; King, F.; Hutchings, G. J. Mol. Catal A:
Chem. 2002, 180, 85. (d) Jeong, J. U.; Tao, B.; Sagasser, I.; Henninges,
H.; Sharpless, K. B. J. Am. Chem. Soc. 1998, 120, 6844. (e) Albone, D. P.;
Aujla, P. S.; Taylor, P. C.; Challenger, S.; Derrick, A. M. J. Org. Chem.
1998, 63, 9569. (f) Ando, T.; Minakata, S.; Ryu, I.; Komatsu, M.
Tetrahedron Lett. 1998, 39, 309. (g) Aujla, P. S.; Baird, C. P.; Taylor, P.
C.; Mauger, H.; Vallee, Tetrahedron Lett. 1997, 38, 7453. (h) Minakata,
S.; Kano, D.; Oderaotoshi, Y.; Komatsu, M. Angew. Chem., Int. Ed. 2004,
43, 79.
(6) (a) Chanda, B. M.; Vyas, R.; Bedekar, A. V. J. Org. Chem. 2001,
66, 30. (b) Antunes, A. M. M.; Marto, S. J. M.; Branco, P. S.; Prabhakar,
S.; Lobo, A. M. Chem. Commun. 2001, 405. (c) Vyas, R.; Chanda, B. M.;
Belhekar, A. A.; Patel, D. R.; Ram, R. N.; Bedekar, A. V. J. Mol. Catal.
A: Chem. 2000, 160, 237. (d) Vyas, R.; Chanda, B. M.; Bedekar, A. V.
Tetrahedron Lett. 1998, 39, 4715.
(1) (a) Muller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905. (b) Sweeney,
J. B. Chem. Soc. ReV. 2002, 31, 247. (c) Jacobsen, E. N. In ComprehensiVe
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer-Verlag: Berlin, 1999; Vol. 2., pp 607-618. (d) Osborn, H. M.;
Sweeney, J. Tetrahedron: Asymmetry 1997, 8, 1693. (e) Tanner, D. Angew.
Chem., Int. Ed. Engl. 1994, 33, 599.
(2) (a) Dauban, P.; Dodd, R. H. Synlett 2003, 1571. (b) Koser, G. F.
Top. Curr. Chem. 2003, 224, 137. (c) Yamada, Y.; Yamamoto, T.; Okawara,
M. Chem. Lett. 1975, 361.
(3) For selected examples, see: (a) Li, Z.; Conser, K. R.; Jacobsen, E.
N. J. Am. Chem. Soc. 1993, 115, 5326. (b) Evans, D. A.; Faul, M. M.;
Bilodeau, M. T. J. Am. Chem. Soc. 1994, 116, 2742. (c) Vedernikov, A.;
Caulton, K. G. Org. Lett. 2003, 5, 2591. (c) Cui, Y.; He, C. J. Am. Chem.
Soc. 2003, 125, 16202.
(7) (a) Omura, K.; Murakami, M.; Uchida, T.; Irie, R.; Katsuki, T. Chem.
Lett. 2003, 354. (b) Li, Z.; Quan, R. W.; Jacobsen, E. N. J. Am. Chem.
Soc. 1995, 117, 5889.
1
0.1021/ol049691k CCC: $27.50 © 2004 American Chemical Society
Published on Web 05/18/2004

Table 1. Aziridination of Styrene by Metalloporphyrinsa
entry
nitrene source
metalloporphyrinb
yield (%)c
1
2
3
4
5
6
7
8
9
PhIdNTs
Fe(TPP)Cl
Fe(TPP)Cl
Fe(TPP)Cl
Mn(TPP)Cl
Co(TPP)
Ru(TPP)(CO)
Fe(OEP)Cl
Fe(TMeOPP)Cl
Fe(TDClPP)Cl
Fe(TPFPP)Cl
31d
5
60
12
27
47
0
25
38
80
chloramine-T
bromamine-T
bromamine-T
bromamine-T
bromamine-T
bromamine-T
bromamine-T
bromamine-T
bromamine-T
Figure 1. Structures of iron(III) porphyrin complexes.
transfer reactions, including aziridination of alkenes. In fact,
metalloporphyrins are the first transition metal complexes
that were demonstrated to catalyze aziridination of alkenes.
1
0
8
a
Reactions were carried out for 12 h at room temperature in CH3CN
Following this breakthrough, porphyrin complexes of several
metal ions such as Fe, Mn, and Ru have been disclosed for
aziridination catalytic activity with PhIdNTs. As a part of
under N2 in the presence of 5 Å molecular sieves with a styrene to nitrene
source mole ratio of 5:1. b Catalyst loading: 5 mol %; see Figure 1 for
c
structures of metalloporphyrins. Yields represent isolated yields of >95%
9
1
d
purity as determined by H NMR. From ref 3b.
our program of metalloporphyrin-based atom/group transfer
1
0
catalysis, we became interested in developing practical
catalytic aziridination processes with alternative nitrene
sources. We reveal herein that iron(III) porphyrin complexes
Fe(Por)Cl (Figure 1) are efficient and general catalysts for
aziridination of a wide variety of alkenes using bromamine-T
as a nitrene source (Scheme 1).11 The reactions can be
performed under mild conditions with alkenes as limiting
reagents and proceed with moderate to low stereospecificity
for 1,2-disubstituted alkenes.
5 mol % catalyst with a styrene to nitrene source mole ratio
of 5:1. The results are summarized in Table 1. Although
chloramine-T was ineffective for the aziridination by Fe-
(TPP)Cl (Table 1, entry 2), bromamine-T was found to be a
superior nitrene source in comparison with PhIdNTs,
affording the desired aziridine in 60% isolated yield (Table
1, entries 1 and 3). Other metal complexes of TPP such as
Mn(TPP)Cl, Ru(TPP)(CO), and Co(TPP) could also aziri-
dinate styrene, but with less efficiency (Table 1, entries 4-6).
Although porphyrin complexes of Fe, Mn, and Ru have been
8
,9
known to catalyze aziridination, to the best of our
knowledge, cobalt porphyrins have never been demonstrated
for aziridination activity previously. The catalytic activity
of Fe(Por)Cl with bromamine-T has a dramatic ligand
dependence. Whereas both Fe(MeOPP)Cl and Fe(TDClPP)-
Cl were less effective than Fe(TPP)Cl (Table 1, entries 8
and 9), no activity was observed with Fe(OEP)Cl (Table 1,
entry 7). However, the electron-deficient Fe(TPFPP)Cl
improved the isolated yield of the desired aziridine to 80%
Scheme 1. Aziridination of Alkenes Catalyzed by Iron(III)
Porphyrin Fe(TPP)Cl
We first surveyed the catalytic aziridination of styrene by
various metalloporphyrins (Figure 1) with different nitrene
sources. The reactions were carried out at room temperature
in acetonitrile in the presence of 5 Å molecular sieves using
(Table 1, entry 10).
The substrate scope of the aziridination reactions by Fe-
TPP)Cl with bromamine-T was then explored using a variety
(
of alkenes under the same conditions (Table 2, yield A,
bromamine-T as the limiting reagent). The catalytic system
is suitable for a variety of styrene derivatives with para-
substituted alkyl and halogen groups, affording the corre-
sponding aziridines in yields similar to or better than that of
styrene reaction (Table 2, entries 1-7). Sterically hindered
derivatives such as 2,4,6-trimethylstyrene could also be
aziridinated, albeit in a lower yield (Table 2, entry 8). Both
R- and â-substituted styrenes including ethyl trans-cinnamate
could be successfully converted to the desired aziridines in
moderate to good yields (Table 2, entries 9-16). The
stereospecificity ranged from moderate to low for the 1,2-
disubstituted olefins (Table 2, entries 12-16). Like ethyl
trans-cinnamate, the R,â-unsaturated ester tert-butyl acrylate
(
8) (a) Groves, J. T.; Takahashi, T. J. Am. Chem. Soc. 1983, 105, 2073.
b) Mansuy, D.; Mahy, J.-P.; Dureault, A.; Bedi, G.; Battioni, P. J. Chem.
Soc., Chem. Commun. 1984, 1161.
9) (a) Mahy, J.-P.; Bedi, G.; Battioni, P.; Mansuy, D. J. Chem. Soc.,
(
(
Perkin Trans. 2 1988, 1517. (b) Lai, T.-S.; Kwong, H.-L.; Che, C.-M.;
Peng, S.-M. Chem. Commun. 1997, 2373. (c) Simonato, J.-P.; Pecaut, J.;
Scheidt, W. R.; Marchon, J.-C. Chem. Commun. 1997, 989. (d) Au, S.-M.;
Huang, J.-S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am. Chem. Soc. 1999,
1
21, 9120. (e) Liang, J.-L.; Huang, J.-S.; Yu, X.-Q.; Zhu, N.; Che, C.-M.
Chem. Eur. J. 2002, 8, 1563.
10) (a) Chen, Y.; Huang, L.; Ranade, M. A.; Zhang, X. P. J. Org. Chem.
(
2
6
(
6
003, 68, 3714. (b) Chen, Y.; Huang, L.; Zhang, X. P. J. Org. Chem. 2003,
8, 5925. (c) Chen, Y.; Huang, L.; Zhang, X. P. Org. Lett. 2003, 5, 2493.
d) Huang, L.; Chen, Y.; Gao, G.-Y.; Zhang, X. P. J. Org. Chem. 2003,
8, 8179. (e) Lee, M.-Y.; Chen, Y.; Zhang, X. P. Organometallics 2003,
2, 4905.
2
(11) For a iron(IV) corrole/chloramine-T aziridination system, see:
Simkhovich, L.; Gross, Z. Tetrahedron Lett. 2001, 42, 8089.
1908
Org. Lett., Vol. 6, No. 12, 2004

Table 2. Aziridination of Alkenes with Bromamine-T
Catalyzed by Fe(TPP)Cla
Table 3. Aziridination of Styrene with Bromamine-T
Catalyzed by Fe(TPP)Cl under Various Conditionsa
[
Fe]
temp
(°C)
time
(h)
yield
(%)c
entry
S:BTb
(mol %)
solvent
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
5:1
5:1
5:1
5:1
5:1
5:1
5:1
5:1
5:1
5:1
5:1
10:1
100:1
1:1.5
1:2
1:2
1:2
1:5
5
5
5
5
5
5
5
5
5
2
10
5
5
5
5
5
10
5
toluene
THF
23
23
23
23
23
23
40
80
100
23
23
23
23
23
23
80
23
23
12
12
12
12
6
0
0
5
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
60
64
42
65
80
39
10
70
55
45
62
77
67
82
52
2
12
12
12
12
12
12
12
12
12
12
12
12
1
1
1
1
1
1
1
1
1
a
Reactions were carried out under N2 in the presence of 5 Å molecular
b
sieves with a concentration of 0.1 mmol styrene/2 mL solvent. S:BT )
the mole ratio of styrene substrate to bromamine-T. Yields represent
isolated yields of >95% purity as determined by H NMR.
c
1
chain alkenes are also suitable substrates (Table 2, entries
1
8-21). However, exo-methylene carbocycles such as me-
thylenecyclohexane could only be converted to the corre-
sponding spirocyclic aziridine in a trace of amount under
the conditions (Table 2, entry 22).
To further improve the Fe(TPP)Cl/bromamine-T aziridi-
nation system, detailed optimization of various reaction
parameters was carried out using styrene as the model
substrate (Table 3). CH
choice, as other solvents such as toluene, THF, and CH
gave none or only a trace amount of the desired aziridine
Table 3, entries 1-4). The reaction time could be shortened
3
CN appeared to be the solvent of
2
Cl
2
(
to 6 h without affecting the yield, but a lower yield was
obtained when the reaction was stopped at 2 h (Table 3,
entries 5 and 6). Increase in reaction temperature gave better
results. For example, the isolated yields were 64% and 80%
at 40 and 80 °C, respectively (Table 3, entries 7 and 8).
However, further increase of the reaction temperature to 100
°C resulted in dramatic decrease of the desired aziridine due
to formation of several unidentified side products (Table 3,
entry 9). Decreased yield was observed when a lower catalyst
loading was applied (Table 3, entry 10). The aziridine was
isolated in 70% yield for a room temperature reaction using
a higher catalyst loading (Table 3, entry 11). Whereas
increase of styrene to bromamine-T mole ratio worsened the
reaction (Table 3, entries 12 and 13), improved results were
observed when the reactions were carried out with styrene
as the limiting reagent. For example, the isolated yields
a
Carried out at room temperature in CH3CN for 12 h under N2 in the
presence of 5 Å molecular sieves using 5 mol %. Fe(TPP)Cl. Concentration:
.1 mmol alkene/2 mL CH3CN. Isolated yields with Bromamine-T as
b
0
c
limiting reagent (alkene/Bromamine-T ) 5:1). Isolated yields with alkene
as limiting reagent (alkene/Bromamine-T ) 1:2). cis:trans ratios. e Per-
d
f
g
formed at 60 °C. Fe(TPFPP)Cl was used. Contaminated with a small
amount of side product.
could also be aziridinated in a moderate yield (Table 2, entry
7). Cyclic alkenes with different ring sizes and straight-
1
Org. Lett., Vol. 6, No. 12, 2004
1909

The catalytic aziridinations by iron(III) porphyrins with
bromamine-T are assumed to proceed via a mechanism
similar to that proposed for other metalloporphyrin systems
Scheme 2. Possible Mechanism for Aziridination of Alkenes
Catalyzed by Iron(III) Porphyrin with Bromamine-T
8
,9
with PhIdNTs. As shown in Scheme 2, reaction of iron-
III) porphyrin with bromamine-T generates the iron-nitrene
(
intermediate A with concomitant formation of NaBr. Nitrene
transfer from intermediate A to alkene substrate produces
the aziridine product and regenerates iron(III) porphyrin to
turn over the catalytic cycle. However, the low to moderate
stereoselectivity observed for 1,2-disubstituted olefins could
imply the involvement of a radical intermediate.
In summary, we have revealed for the first time that
bromamine-T is an effective nitrene source for aziridination
of alkenes by porphyrin complexes of transition metal ions
including Mn, Fe, Ru, and Co. We demonstrated that the
new Fe(TPP)Cl/bromamine-T catalytic aziridination system
can be operated under mild and practical conditions with
alkenes as limiting reagents. The catalytic reaction is general
and suitable for a wide range of alkene substrates, forming
desired aziridines in good yields, although the stereospeci-
ficity is only moderate to low for 1,2-disubstituted olefins.
Further improvements are expected with iron(III) complexes
that are supported by different porphyrin ligands, as we have
already demonstrated with Fe(TPFPP)Cl for yield improve-
ment (Table 1, entry 10). The development of an asymmetric
version of the catalytic system is in progress.
reached 62% and 77% when styrene to bromamine-T mole
ratios were 1:1.5 and 1:2, respectively (Table 3, entries 14
and 15), but further increase of bromamine-T equivalence
gave a poor result due to the generation of side products
(Table 3, entry 18). Side products were also observed when
the reaction was done at elevated temperature with styrene
to bromamine-T mole ratios of 1:2 (Table 3, entry 16). The
best isolated yield (82%) of the desired N-(p-tolylsulfonyl)-
2-phenylaziridine was achieved when a higher catalyst
loading was employed at room temperature with the 1:2 ratio
(Table 3, entry 17).
On the basis of the above optimization and the consider-
ation of practicality, the aziridination of representative
examples of alkenes with bromamine-T was carried out again
at room temperature with alkenes as the limiting reagents
using 5 mol % Fe(TPP)Cl. As summarized in yield B of
Table 2, yields were improved in all of the cases examined.
For example, large increases in yields were obtained for
styrene derivatives (Table 2, entries 1, 2, and 6). For
â-substituted styrenes, good yields were achieved in most
cases, but stereospecificities remained almost the same (Table
Acknowledgment. We are grateful for financial support
of this work from the UT Department of Chemistry and Oak
Ridge Associated Universities (ORAU) for a Ralph E. Powe
Junior Faculty Enhancement Award. We wish to acknowl-
edge Dr. Al Tuinman of UT Mass Spectroscopy Center for
assistance with high-resolution mass spectroscopy.
2
, entries 11-15). Similar improvement in yield was also
Supporting Information Available: General experimen-
tal procedures and analytical data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
observed for cyclic and straight-chain alkenes (Table 2,
entries 20 and 21). Under this new condition, the previous
negative reaction of methylenecyclohexane was successfully
performed to afford the desired spirocyclic aziridine in 50%
yield (Table 2, entry 22).
OL049691K
1910
Org. Lett., Vol. 6, No. 12, 2004