Cobalt-catalyzed asymmetric olefin aziridination with diphenylphosphoryl azide

Article abstract of DOI:10.1021/jo801151x

(Chemical Equation Presented) The cobalt(II) complexes of D ₂-symmetric chiral porphyrins, such as 3,5-Di^tBu- ChenPhyrin P5, can catalyze asymmetric olefin aziridination with diphenylphosphoryl azide (DPPA) as a nitrene source. Accep

Full text of DOI:10.1021/jo801151x

Cobalt-Catalyzed Asymmetric Olefin Aziridination with
Diphenylphosphoryl Azide
Jess E. Jones, Joshua V. Ruppel, Guang-Yao Gao, Thomas M. Moore, and X. Peter Zhang*
Department of Chemistry, UniVersity of South Florida, Tampa, Florida 33620-5250, and
Department of Chemistry, UniVersity of Tennessee, KnoxVille, Tennessee 37996-1600
pzhang@cas.usf.edu
ReceiVed May 27, 2008
The cobalt(II) complexes of D2-symmetric chiral porphyrins, such as 3,5-DitBu-ChenPhyrin P5, can
catalyze asymmetric olefin aziridination with diphenylphosphoryl azide (DPPA) as a nitrene source.
Acceptable asymmetric inductions were observed for the [Co(P5)]-based catalytic system, forming the
desired N-phosphorus-substituted aziridines in moderate to high yields and good enantioselectivities.
Introduction
sources such as chloramine-T,5 bromamine-T,6 and tosyloxy-
carbamates.7 Along the same line, azides, a broad class of
compounds that are widely available or can be easily synthe-
sized,8 have also been pursued recently by several groups,
The fundamental and practical significance of aziridine
derivatives in chemistry and biology have stimulated intensive
research activities focused on their syntheses.1 Among several
synthetic schemes, metal-catalyzed aziridination of alkenes with
nitrene sources is a method that has received the most attention
because of its direct nature and the abundance of alkenes.2
Despite their general mechanistic similarity, aziridination is a
much less developed process than the analogous epoxidation
and cyclopropanation reactions partly due to the lack of effec-
tive nitrene sources. In the past three decades, several types of
nitrogen-containing reagents have been examined as potential
nitrene sources for metal-catalyzed aziridination.1,2 Currently,
the most widely used nitrene sources are PhIdNTs and related
iminoiodane derivatives,3 including their in situ variants that
have been recently implemented with notable success.4 Driven
by the desire to overcome some of the limitations associated
with the use of these hypervalent iodine reagents, growing
efforts have been devoted to developing alternative nitrene
(3) For select examples of metal-catalyzed aziridination with PhIdNTs, see:
(a) Mansuy, D.; Mahy, J.-P.; Dureault, A.; Bedi, G.; Battioni, P. J. Chem. Soc.,
Chem. Commun. 1984, 1161. (b) Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am.
Chem. Soc. 1993, 115, 5326. (c) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.
J. Am. Chem. Soc. 1994, 116, 2742. (d) Cui, Y.; He, C. J. Am. Chem. Soc.
2003, 125, 16202. (e) Klotz, K. L.; Slominski, L. M.; Hull, A. V.; Gottsacker,
V. M.; Mas-Balleste, R., Jr.; Halfen, J. A. Chem. Commun. 2007, 2063. (f) Zdilla,
M. J.; Abu-Omar, M. M. J. Am. Chem. Soc. 2006, 128, 16971.
(4) For select examples of metal-catalyzed aziridination with in situ formed
iminoiodans, see: (a) Yu, X.-Q.; Huang, 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. (c) Guthikonda, K.; Du Bois, J. J. Am. Chem. Soc.
2002, 124, 13672. (d) Esteoule, A.; Duran, F.; Retailleau, P.; Dodd, R. H.;
Dauban, P. Synthesis 2007, 1151. (e) Guthikonda, K.; Wehn, P. M.; Caliando,
B. J.; Du Bois, J. Tetrahedron 2006, 62, 11331. (f) Li, Z.; Ding, X.; He, C. J.
Org. Chem. 2006, 71, 5876. (g) Xu, Q.; Appella, D. H. Org. Lett. 2008, 10,
1497.
(5) (a) Simkhovich, L.; Gross, Z. Tetrahedron Lett. 2001, 42, 8089. (b)
Albone, D. P.; Aujla, P. S.; Taylor, P. C.; Challenger, S.; Derrick, A. M. J. Org.
Chem. 1998, 63, 9569. (c) Albone, D. P.; Challenger, S.; Derrick, A. M.; Fillery,
S. M.; Irwin, J. L.; Parsons, C. M.; Takada, H.; Taylor, P. C.; Wilson, D. J.
Org. Biomol. Chem. 2005, 3, 107. (d) Fructos, M. R.; Trofimenko, S.; Diaz-
Requejo, M. M.; Perez, P. J. J. Am. Chem. Soc. 2006, 128, 11784.
(6) (a) Chanda, B. M.; Vyas, R.; Bedekar, A. V. J. Org. Chem. 2001, 66,
30. (b) Vyas, R.; Gao, G.-Y.; Harden, J. D.; Zhang, X. P. Org. Lett. 2004, 6,
1907. (c) Gao, G.-Y.; Harden, J. D.; Zhang, X. P. Org. Lett. 2005, 7, 3191. (d)
Harden, J. D.; Ruppel, J. V.; Gao, G.-Y.; Zhang, X. P. Chem. Commun. 2007,
4644.
* To whom correspondence should be addressed at the University of South
Florida. Fax: 813-974-1733.
(1) (a) Hu, X. E. Tetrahedron 2004, 60, 2701. (b) Sweeney, J. B. Chem.
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2001, 216, 93. (d) McCoull, W.; Davis, F. A. Synthesis 2000, 1347. (e) Tanner,
D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599.
(2) (a) Muller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905. (b) Jacobsen, E. N.
In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto,
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10.1021/jo801151x CCC: $40.75 2008 American Chemical Society
Published on Web 08/19/2008

Cobalt-Catalyzed Asymmetric Olefin Aziridination
SCHEME 1. Cobalt-Catalyzed Olefin Aziridination with
DPPA
including Cenini,9 Katsuki,10 Driver,11 and us,12 as promising
nitrene sources for metal-catalyzed nitrene transfer reactions.13
An additional advantage of using azides as nitrene sources is
that environmentally benign dinitrogen is the only byproduct
of the process.
Most of the catalytic aziridination processes produce N-
sulfonylated aziridines.1,2 The deprotection of these N-sulfonyl
groups typically requires harsh conditions.14 However, com-
mercially available diphenylphosphoryl azide (DPPA)15 has
recently been shown by us as a new nitrene source to form
N-phosphorylated aziridines via olefin aziridination by a Co-
based catalytic system (Scheme 1).12a N-Phosphorylated and the
related N-phosphinylated aziridines are more advantageous
synthetic building blocks due to the easier deprotection of the
N-phosphoryl and N-phosphinyl groups.16-18 While the Co-
catalyzed aziridination with DPPA represented the first direct
preparation of N-phosphorus-substituted aziridines from alkenes,
the catalyst Co(TPP) that was initially employed suffers from
the low-yielding formation of desired products.12a To improve
its catalytic efficiency as well as to develop its asymmetric
variant, we have made considerable efforts to identify chiral
porphyrins to support the Co-based catalytic process with hopes
of enhancing its activity and selectivity. Herein, we describe
the results from our systematic studies regarding the use of D2-
FIGURE 1. Structures of chiral porphyrins and Co(II) complexes.
TABLE 1. Asymmetric Aziridination of Styrene with
Diphenylphosphoryl Azide Catalyzed by Cobalt(II) Complexes of
Different Chiral Porphyrinsa
(8) (a) Scriven, E. F. V.; Turnbull, K. Chem. ReV. 1988, 88, 297. (b) Brase,
S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem., Int. Ed. 2005, 44,
5188.
(9) (a) Fantauzzi, S.; Gallo, E.; Penoni, A.; Ragaini, F.; Macchi, P.; Casati,
N.; Cenini, S. Organometallics 2005, 24, 4710. (b) Piangiolino, C.; Gallo, E.;
Caselli, A.; Fantauzzi, S.; Ragaini, F.; Cenini, S. Eur. J. Org. Chem. 2007, 743.
(10) (a) Omura, K.; Murakami, M.; Uchida, T.; Irie, R.; Katsuki, T. Chem.
Lett. 2003, 354. (b) Omura, K.; Uchida, T.; Irie, R.; Katsuki, T. Chem. Commun.
2004, 2060. (c) Kawabata, H.; Omura, K.; Katsuki, T. Tetrahedron Lett. 2006,
47, 1571. (d) Kawabata, H.; Omura, K.; Uchida, T.; Katsuki, T. Chem. Asian J.
2007, 2, 248.
(11) (a) Stokes, B. J.; Dong, H.; Leslie, B. E.; Pumphrey, A. L.; Driver,
T. G. J. Am. Chem. Soc. 2007, 129, 7500. (b) Dong, H.; Shen, M.; Redford,
J. E.; Stokes, B. J.; Pumphrey, A. L.; Driver, T. G. Org. Lett. 2007, 9, 5191.
(12) (a) Gao, G.-Y.; Jones, J. E.; Vyas, R.; Harden, J. D.; Zhang, X. P. J.
Org. Chem. 2006, 71, 6655. (b) Ruppel, J. V.; Kamble, R. M.; Zhang, X. P.
Org. Lett. 2007, 9, 4889. (c) Ruppel, J. V.; Jones, J. E.; Huff, C. A.; Kamble,
R. M.; Chen, Y.; Zhang, X. P. Org. Lett. 2008, 10, 1995.
(13) (a) Katsuki, T. Chem. Lett. 2005, 1304. (b) Cenini, S.; Gallo, E.; Caselli,
A.; Ragaini, F.; Fantauzzi, S.; Piangiolino, C. Coord. Chem. ReV. 2006, 250,
1234.
(14) (a) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 2nd ed.; Wiley-Interscience: New York, 1991; p 379. (b) Alonso,
D. A.; Anderson, P. G. J. Org. Chem. 1998, 63, 9455.
(15) The low cost diphenylphosphoryl azide is a stable and distillable liquid
that has been widely used in various organic syntheses. For selected examples,
see: (a) Shioiri, T.; Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94,
6203. (b) Yamada, S.; Ikota, N.; Shioiri, T.; Tachibana, S. J. Am. Chem. Soc.
1975, 97, 7174. (c) Lal, B.; Pramanik, B. N.; Manhas, M. S.; Bose, A. K.
Tetrahedron Lett. 1977, 18, 1977. (d) Qian, L.; Sun, Z.; Deffo, T.; Mertes, K. B.
Tetrahedron Lett. 1990, 31, 6469.
a Reactions were carried out for 18 h in chlorobenzene under N2 in
the presence of 5 Å molecular sieves using 10 mol % of [Co(Por*)].
Concentration: 0.50 mmol of styrene/1 mL of chlorobenzene. Styrene/
azide ) 5:1. b See Figure 1. c Isolated yields. d Determined by chiral
f
HPLC. e Reference 12a. The optical rotation was measured: [R]20
)
D
-79.5 (c ) 0.088, CHCl3).
symmetric chiral porphyrins (Figure 1) for the Co-based
asymmetric olefin aziridination using DPPA. In addition to
improved yields under milder conditions, acceptable asymmetric
induction has been achieved. This represents the first Co(II)-
catalyzed asymmetric aziridination process.
Results and Discussion
(16) (a) Hu, X. E. Tetrahedron Lett. 2002, 43, 5315. (b) Hu, X. E.; Kim,
N. K.; Ledoussal, B.; Colson, A.-O. Tetrahedron Lett. 2002, 43, 4289. (c)
Osowska-Pacewicka, K.; Zwierzak, A. Synth. Commun. 1998, 28, 1127. (d)
Gajda, T.; Napieraj, A.; Osowska-Pacewicka, K.; Zwierzak, A. Tetrahedron 1997,
53, 4935. (e) Osowska-Pacewicka, K.; Zwierzak, A. Synthesis 1996, 333. (f)
Osowska-Pacewicka, K.; Zwierzak, A. Pol. J. Chem. 1994, 68, 1263.
(17) (a) Sweeney, J. B.; Cantrill, A. A. Tetrahedron 2003, 59, 3677. (b)
Cantrill, A. A.; Osborn, H. M. I.; Sweeney, J. B. Tetrahedron 1998, 54, 2181.
(c) Osborn, H. M. I.; Sweeney, J. B.; Howson, W. Tetrahedron Lett. 1994, 35,
2739. (d) Osborn, H. M. I.; Sweeney, J. B.; Howson, B. Synlett 1994, 145.
(18) For examples of biomedical applications of N-phosphorus-substituted
aziridines, see: (a) Perlman, M. E.; Bardos, T. J. J. Org. Chem. 1988, 53, 1761.
(b) Borkovec, A. B.; Woods, C. W.; Brown, R. T. J. Med. Chem. 1966, 9, 522.
For the aziridination of styrene with DPPA (Table 1),
Co(TPP) was previously shown to catalyze the aziridine
formation in the highest yield of 50% at 100 °C; lowering the
reaction temperature significantly reduced the yields (entries 12
and 13).12a A series of D2-symmetric chiral porphyrins (Figure
1), which were synthesized from bromoporphyrins via Pd-
mediated quadruple amidations,19 were employed to improve
(19) Chen, Y.; Fields, K. B.; Zhang, X. P. J. Am. Chem. Soc. 2004, 126,
14718.
J. Org. Chem. Vol. 73, No. 18, 2008 7261

Jones et al.
TABLE 2. Solvent Effect in [Co(P5)]-Catalyzed Asymmetric
Aziridination of Styrene with Diphenylphosphoryl Azidea
TABLE 4. [Co(P5)]-Catalyzed Asymmetric Aziridination of
Aromatic Olefins with Diphenylphosphoryl Azidea
a Reactions were carried out for 18 h under N2 in the presence of 5 Å
molecular sieves. Concentration: 0.50 mmol of styrene/1 mL of solvent.
Styrene/azide ) 5:1. b Catalyst loading of [Co(P5)]. c Isolated yields.
d Determined by chiral HPLC.
TABLE 3. Axial Ligand Effect in [Co(P5)]-Catalyzed Asymmetric
Aziridination of Styrene with Diphenylphosphoryl Azidea
a Reactions were carried out for 18 h in chlorobenzene at 40 °C
under N2 in the presence of 5 Å molecular sieves using 10 mol % of
[Co(P5)]. Concentration: 0.50 mmol of olefin/1 mL of chloro-
benzene. Olefin/azide ) 5:1. b Isolated yields. c Determined by chiral
HPLC. d Carried at 60 °C.
a Reactions were carried out for 18 h under N2 at 40 °C in the presence
of 5 Å molecular sieves using 10 mol % of [Co(P5)]. Concentration: 0.50
mmol of styrene/1 mL of solvent. Styrene/azide ) 5:1. b Axial ligand
yields (entries 6 and 7). Changing the 3,5-diMeO to 3,5-ditBu
substituents provided the catalyst [Co(P5)] that led to improve-
ments in both enantioselectivity and yield (entries 8 and 9). A
further increase in aziridine yield was achieved by employing
the less sterically imposing catalyst [Co(P6)] but with reduced
enantioselectivity (entries 10 and 11).
mol
% relative to azide; N-MeIm, N-methylimidazole; 3,5-DiMePy,
3,5-dimethylpyridine; DMAP, 4-(dimethylamino)pyridine. c Isolated yields.
d Determined by chiral HPLC.
the catalytic process and to control stereoselectivity. The Co(II)
complexes of ChenPhyrin P1 and its derivatives P2-P6 (Figure
1) were found to be much more effective catalysts than Co(TPP),
allowing for aziridination to occur at much lower temperatures
(Table 1). For example, the aziridination could be catalyzed by
[Co(P1)] at 80 °C to afford the desired product in 82% yield,
but with a low degree of asymmetric induction (entry 1). The
use of more sterically hindered [Co(P2)] and [Co(P3)] resulted
in lower yields without improving the stereocontrol (entries
2-5). Improved enantioselectivities were observed for the
reactions catalyzed by [Co(P4)] where the 3,5-positions of the
meso-phenyl groups contain MeO substituents, albeit in lower
A dramatic solvent effect was observed for the Co-catalyzed
asymmetric aziridination, as shown with the [Co(P5)]-catalyzed
styrene reaction (Table 2). In general, halogenated solvents
(entries 1-6) gave better results than the nonhalogenated ones
(entries 7 and 8). Potentially coordinating solvents, such as
tetrahydrofuran and acetonitrile, were detrimental to the catalytic
process (entries 9 and 10). Among various solvents employed,
chlorobenzene gave the best yields (entries 1 and 2). Dichlo-
romethane as solvent provided the highest enantioselectivity but
lower yields (entries 5 and 6).
7262 J. Org. Chem. Vol. 73, No. 18, 2008

Cobalt-Catalyzed Asymmetric Olefin Aziridination
literature methods.19 Proton, carbon, fluorine, and phosphorus
nuclear magnetic resonance spectra (1H NMR, 13C NMR, 19F NMR,
and 31P NMR) were recorded on a Varian Mercury 300 MHz
spectrometer or a Varian Inova 400 MHz spectrometer and
referenced with respect to residual solvent. Infrared spectra were
measured with a Nicolet Avatar 320 spectrometer with a Smart
Miracle accessory. HRMS data were measured on an Agilent 1100
LC/MS ESI/TOF mass spectrometer. Enantiomeric excess deter-
mination was measured on a Shimadzu LC-20AT HPLC with a
SPD-M20A diode array detector using a Pirkle Covalent WHELK-
O1 or a Chiralcel AD-H chiral column. Thin-layer chromatography
was carried out on E. Merck silica gel 60 F-254 TLC plates.
General Procedure for Aziridination of Alkenes. An oven-
dried Schlenk tube equipped with a stirring bar was degassed on a
vacuum line and purged with nitrogen. The tube was charged with
metalloporphyrin (10 mol %) and activated 5 Å molecular sieves (200
mg). The tube was capped with a Teflon screw cap and then evacuated
on a vacuum line for 30-45 min. The tube was backfilled with
nitrogen, the Teflon screw cap was replaced with a rubber septum,
and then 1 mL of solvent, diphenylphosphoryl azide (0.2 mmol), and
substrate (1.0 mmol) were added successively, followed by the
remaining solvent, giving 2 mL total. The tube was purged with
nitrogen for 1-2 min, and the septum was replaced with the Teflon
screw cap. The contents were stirred and heated at 40 or 60 °C
overnight. After completion of the reaction, the mixture was cooled
to room temperature and purified by flash chromatography (silica gel,
ethyl acetate/hexanes (v/v) ) 3:7) to afford the pure product.
A wide range of potentially coordinating reagents were
evaluated for a possible axial ligand effect for [Co(P5)]-
catalyzed aziridination of styrene (Table 3). In accord with its
inferiority as a solvent, the addition of a substoichiometric
amount of tetrahydrofuran lowered the product yield without
significantly influencing the enantioselectivity (entries 1 and 2).
A more negative axial ligand effect on yield was observed for
the nitrogen-based reagents, such as imidazole and pyridine
derivatives, presumably due to their stronger coordinating ability
(entries 3-11). Conversely, a considerably positive effect on
enantioselectivity was recognized, albeit with lower product
yields, through the addition of a substoichiometric amount of
DMAP in dichloromethane, which resulted in the near doubling
of the enantiomeric excess from 37% to 71% (entries 1 and
11). It is interesting to note a similar effect with tert-butyl
isocyanide (entry 12).20
In addition to styrene, the [Co(P5)]-based catalytic system
could be applied to a wide range of aromatic olefins (Table 4).
For example, styrene derivatives bearing electron-neutral sub-
stituents, such as methyl and tert-butyl groups, at different
positions could be equally aziridinated with DPPA in similar
yields and enantioselectivities (entries 1-5). The reactions of
styrenes substituted with halogen atoms afforded the N-
phosphorylated aziridines in good yields but with varied
enantioselectivities, depending on the nature of the halogen atom
and the position of substitution (entries 6-10). For example,
the aziridination of styrenes substituted with an o-, m-, or
p-bromo atom provided the corresponding products with 7%,
45%, and 28% ee, respectively (entries 6-8). The catalytic
system seemed equally suitable to styrene derivatives containing
strongly electron-withdrawing groups, as demonstrated with
4-trifluoromethylstyrene and 3-nitrostyrene, which are often
more challenging substrates (entries 11 and 12). However,
results indicted that the [Co(P5)]/DPPA catalytic system was
ineffective for multisubstituted aromatic olefins and aliphatic
olefins as well.
(2-Phenylaziridin-1-yl)phosphonic acid diphenyl ester. (Table
4, entry 1)12a was synthesized from the reaction of styrene with
DPPA at 40 °C and obtained as a yellow oil (61.5 mg, 88% yield).
1H NMR (400 MHz, CDCl3): δ 7.27-7.00 (m, 15H), 3.63 (ddd,
JP-H ) 16.5 Hz, JH-H ) 6.3, 3.6 Hz, 1H), 2.82 (ddd, JP-H ) 19.5
Hz, JH-H ) 6.3, 1.2 Hz, 1H), 2.24 (ddd, JP-H ) 15.6 Hz, JH-H
)
3.6, 1.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 150.7, 136.3,
129.6, 128.5, 128.1, 126.2, 125.2, 120.4, 38.9, 35.1. 31P NMR (121
MHz, CDCl3): δ 6.11 (s). FT-IR (film, cm-1): 1590, 1191, 941,
669. HRMS-EI ([M]+) for C20H18NO3P, calcd 351.1024, found
351.1022. Enantiomeric excess was determined via HPLC using a
Pirkle Covalent WHELK-O1 chiral column with a flow rate of 2
mL/min, 2-propanol/hexanes (v/v) ) 2:98 (tminor ) 50.4 min, tmajor
) 54.4 min).
(2-o-Tolylaziridin-1-yl)phosphonic acid diphenyl ester. (Table
4, entry 2) was synthesized from the reaction of o-methylstyrene
with DPPA at 60 °C and obtained as a yellow oil (51.1 mg, 70%
Conclusions
In summary, we have established the first Co-catalyzed
asymmetric olefin aziridination system that can employ the
commercially available DPPA as a convenient nitrene source.
The cobalt(II) complex of 3,5-DitBu-ChenPhyrin [Co(P5)] has
been demonstrated to be an effective catalyst for catalyzing the
aziridination of a range of aromatic olefins with DPPA under
mild conditions, affording the synthetically valuable N-phos-
phorylated aziridines in moderate to good yields with acceptable
degree of asymmetric induction. Continued efforts are underway
to develop a new generation of chiral porphyrins to improve
the Co-based catalytic aziridination system.
1
yield). H NMR (400 MHz, CDCl3): δ 7.32-7.08 (m, 14H), 3.79
(ddd, JP-H ) 16.6 Hz, JH-H ) 6.0, 3.6 Hz, 1H), 2.90 (ddd, JP-H
19.1 Hz, JH-H ) 6.2, 1.4 Hz, 1H), 2.36 (s, 3H), 2.20 (ddd, JP-H
)
)
15.3 Hz, JH-H ) 3.5, 1.4 Hz, 1H). 13C NMR (100 MHz, CDCl3):
δ 151.0, 136.7, 134.7, 130.0, 129.9, 128.0, 126.3, 125.7, 125.5,
120.6, 37.5, 34.3, 19.2. 31P NMR (161 MHz, CDCl3): δ 6.71 (s).
FT-IR (solid, cm-1): 1591, 1489, 1275, 1190, 941, 755. HRMS-
ESI ([M + H]+) for C21H20NO3P calcd 366.1254, found 366.1260.
Enantiomeric excess was determined via HPLC using a Chiralcel
AD-H chiral column and a flow rate of 1 mL/min, 2-propanol/
hexanes (v/v) ) 4:96 (tminor ) 64.5 min, tmajor ) 68.5 min).
(2-m-Tolylaziridin-1-yl)phosphonic acid diphenyl ester. (Table
4, entry 3)12a was synthesized from the reaction of m-methylstyrene
with DPPA at 60 °C and obtained as a yellow oil (57.3 mg, 78%
Experimental Section
1
yield). H NMR (400 MHz, CDCl3): δ 7.28-6.95 (m, 14H), 3.61
General Considerations. All catalytic reactions were carried
out under a nitrogen atmosphere in an oven-dried Schlenk tube.
Diphenylphosphoryl azide and all olefins were purchased com-
merically and used without further purification. Chlorobenzene and
dichloromethane were dried with calcium hydride in reflux. Toluene
and tetrahydrofuran was distilled under nitrogen from sodium
benzophenone ketyl. All other solvents were purchased as anhy-
drous forms. All chiral metalloporphyrins were synthesized using
(ddd, JP-H ) 16.5 Hz, JH-H ) 6.0, 3.3 Hz, 1H), 2.80 (dd, JP-H
)
19.2 Hz, JH-H ) 6.0 Hz, 1H), 2.22 (m, 4H). 13C NMR (100 MHz,
CDCl3): δ 150.7, 138.2, 136.2, 129.6, 128.8, 128.3, 126.8, 125.2,
123.4, 120.4, 38.9, 34.9, 21.3. 31P NMR (121 MHz, CDCl3): δ 6.19
(s). FT-IR (film, cm-1): 1711, 1585, 1482, 1190, 1010, 932, 762.
HRMS-EI ([M]+) for C21H20NO3P calcd 365.1181, found 365.1174.
Enantiomeric excess was determined via HPLC using a Pirkle
Covalent WHELK-O1 chiral column with a flow rate of 2 mL/
min, 2-propanol/hexanes (v/v) ) 2:98 (tminor ) 50.1 min, tmajor
57.3 min).
)
(20) No effect on yield and enantioselectivity was observed when sodium
methylthiolate was employed as potential axial ligand under the same conditions.
J. Org. Chem. Vol. 73, No. 18, 2008 7263

Jones et al.
(2-p-Tolylaziridin-1-yl)phosphonic acid diphenyl ester. (Table
4, entry 4) was synthesized from the reaction of p-methylstyrene
with DPPA at 40 °C and obtained as a yellow oil (42.2 mg, 58%
430.0202, found 430.0202. Enantiomeric excess was determined
via HPLC using a Pirkle Covalent WHELK-O1 chiral column with
a flow rate of 2 mL/min, 2-propanol/hexanes (v/v) ) 2:98 (tminor
48.5 min, tmajor ) 55.6 min).
)
1
yield). H NMR (400 MHz, CDCl3): δ 7.33-7.12 (m, 14H), 3.67
(ddd, JP-H ) 16.6 Hz, JH-H ) 6.1, 3.5 Hz, 1H), 2.88 (ddd, JP-H
19.4 Hz, JH-H ) 6.2, 1.0 Hz, 1H), 2.33 (s, 3H), 2.28 (ddd, JP-H
)
)
[2-(p-Chlorophenyl)aziridin-1-yl]phosphonic acid diphenyl
ester. (Table 4, entry 9)12a was synthesized from the reaction of
p-chlorostyrene with DPPA at 40 °C and obtained as a yellow oil
15.7 Hz, JH-H ) 3.5, 1.1 Hz 1H). 13C NMR (100 MHz, CDCl3): δ
151.0, 138.1, 133.5, 129.9, 129.4, 126.4, 125.4, 120.7, 39.1, 35.1,
21.4. 31P NMR (161 MHz, CDCl3): δ 6.20 (s). FT-IR (solid, cm-1):
1588, 1487, 1188, 948, 930, 770. HRMS-ESI ([M + H]+) for
C21H20NO3P, calc’d. 366.1254, found 366.1259. Enantiomeric
excess was determined via HPLC using a Pirkle Covalent WHELK-
O1 chiral column with a flow rate of 2 mL/min, 2-propanol/hexanes
(v/v) ) 2:98 (tminor ) 53.1 min, tmajor ) 58.4 min).
1
(49.4 mg, 64% yield). H NMR (400 MHz, CDCl3): δ 7.35-7.14
(m, 14H), 3.66 (ddd, JP-H ) 16.2 Hz, JH-H ) 6.0, 3.3 Hz, 1H),
2.89 (ddd, JP-H ) 19.2 Hz, JH-H ) 6.0, 1.2 Hz, 1H), 2.27 (ddd,
JP-H ) 15.3 Hz, JH-H ) 3.3, 1.2 Hz, 1H). 13C NMR (100 MHz,
CDCl3): δ 150.6, 134.9, 133.9, 129.7, 128.7, 127.5, 125.3, 120.3,
38.2, 35.0. 31P NMR (121 MHz, CDCl3): δ 5.79 (s). FT-IR (film,
cm-1): 1592, 1490, 1193, 943, 773, 689. HRMS-EI ([M]+) for
C20H17NO3PCl calcd 385.0635, found 385.0629. Enantiomeric
excess was determined via HPLC using a Pirkle Covalent WHELK-
O1 chiral column with a flow rate of 2 mL/min, 2-propanol/hexanes
(v/v) ) 1:99 (tminor ) 89.7 min, tmajor ) 97.1 min).
[2-(p-tert-Butylphenyl)aziridin-1-yl]phosphonic acid diphenyl
ester. (Table 4, entry 5)12a was synthesized from the reaction of
p-tert-butylstyrene with DPPA at 40 °C and obtained as a yellow
oil (63.0 mg, 77% yield). 1H NMR (400 MHz, CDCl3): δ 7.36-7.13
(m,14H), 3.70 (ddd, JP-H ) 16.5 Hz, JH-H ) 6.0, 3.6 Hz, 1H),
2.89 (ddd, JP-H ) 19.8 Hz, JH-H ) 6.6, 1.2 Hz, 1H), 2.33 (ddd,
JP-H ) 15.3 Hz, JH-H ) 3.6, 1.2 Hz, 1H), 1.32 (s, 9H). 13C NMR
(100 MHz, CDCl3): δ 151.2, 133.3, 130.9, 129.6, 126.0, 125.4,
125.2, 120.4, 38.9, 34.8, 34.6, 31.3. 31P NMR (121 MHz, CDCl3):
δ 6.24 (s). FT-IR (film, cm-1): 1592, 1490, 1193, 943, 773, 689.
HRMS-EI ([M]+) for C24H26NO3P calcd 407.1650, found 407.1658.
Enantiomeric excess was determined via HPLC using a Chiralcel
AD-H chiral column with a flow rate of 1 mL/min, 2-propanol/
hexanes (v/v) ) 4:96 (tmajor ) 36.3 min, tminor ) 46.9 min).
[2-(p-Bromophenyl)aziridin-1-yl]phosphonic acid diphenyl
ester. (Table 4, entry 6)12a was synthesized from the reaction of
p-bromostyrene with DPPA at 40 °C and obtained as a yellow oil
(56.1 mg, 65% yield). 1H NMR (400 MHz, CDCl3): δ 7.43 (d, J )
8.4 Hz, 2H), 7.35-7.09 (m, 10H), 7.01 (d, J ) 8.4 Hz, 2H), 3.64
[2-(p-Fluorophenyl)aziridin-1-yl]phosphonic acid diphenyl
ester. (Table 4, entry 10)12a was synthesized from the reaction of
p-fluorostyrene with DPPA at 60 °C and obtained as a yellow oil
1
(53.0 mg, 72% yield). H NMR (400 MHz, CDCl3): δ 7.35-7.13
(m, 12H), 7.00 (t, J ) 8.7 Hz, 2H), 3.68 (ddd, JP-H ) 16.5 Hz,
JH-H ) 6.0, 3.6 Hz, 1H), 2.89 (ddd, JP-H ) 19.5 Hz, JH-H ) 6.3,
0.7 Hz, 1H), 2.28 (ddd, JP-H ) 15.0 Hz, JH-H ) 3.3, 0.7 Hz, 1H).
13C NMR (100 MHz, CDCl3): δ 150.6, 140.5, 129.7, 126.5, 125.4,
120.3, 38.2, 35.1. Two peaks were not observed. 31P NMR (121
MHz, CDCl3): δ 5.96 (s). 19F NMR (376 MHz, CDCl3): δ -114.37
(s). FT-IR (film, cm-1): 1592, 1490, 1224, 1192, 932, 835, 689.
HRMS-EI ([M]+) for C20H17NO3FP calcd 369.0930, found 369.0946.
Enantiomeric excess was determined via HPLC using a Pirkle
Covalent WHELK-O1 chiral column with a flow rate of 2 mL/
min, 2-propanol: hexanes (V:V) ) 1:99 (tminor ) 87.8 min, tmajor
94.8 min).
)
(ddd, JP-H ) 16.2 Hz, JH-H ) 6.0, 3.3 Hz, 1H), 2.88 (ddd, JP-H
)
18.9 Hz, JH-H ) 6.0, 1.2 Hz, 1H), 2.26 (ddd, JP-H ) 15.3 Hz,
JH-H ) 3.3, 1.2 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 150.6,
135.4, 131.6, 129.7, 127.9, 125.3, 122.0, 120.4, 38.3, 35.0. 31P NMR
(121 MHz, CDCl3): δ 5.76 (s). FT-IR (film, cm-1): 1591, 1489,
1283, 1192, 1163, 1072, 1006, 945, 827, 774. HRMS-EI ([M]+)
for C20H17NO3PBr calcd 429.0129, found 429.0127. Enantiomeric
excess was determined via HPLC using a Pirkle Covalent WHELK-
O1 chiral column with a flow rate of 2 mL/min, 2-propanol/hexanes
(v/v) ) 1:99 (tminor ) 98.3 min, tmajor ) 105.9 min).
[2-(p-Trifluoromethylphenyl)aziridin-1-yl]phosphonic acid di-
phenyl ester. (Table 4, entry 11)12a was synthesized from the
reaction of p-trifluoromethylstyrene with DPPA at 40 °C and
obtained as a yellow oil (53.5 mg, 64% yield). 1H NMR (400 MHz,
CDCl3): δ 7.56 (d, J ) 7.80 Hz, 2H), 7.36-7.16 (m, 12H), 3.75
(ddd, JP-H ) 16.2 Hz, JH-H ) 6.0, 3.6 Hz, 1H), 2.93 (dd, JP-H
19.2 Hz, JH-H ) 6.3 Hz, 1H), 2.30 (dd, JP-H ) 15.3 Hz, JH-H
)
)
3.3 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 150.6, 140.5, 129.8,
126.5, 125.4, 120.3, 38.2, 35.1. (Three peaks were not observed).
31P NMR (121 MHz, CDCl3): δ 5.63 (s). 19F NMR (376 MHz,
CDCl3): δ -63.00 (s). FT-IR (film, cm-1): 1621, 1592, 1490, 1326,
1193, 1165, 1068, 1005, 947, 904, 774, 689. HRMS-EI ([M]+) for
C21H17NO3 F3P calcd 419.0898, found 419.0894. Enantiomeric
excess was determined via HPLC using a Pirkle Covalent WHELK-
O1 chiral column with a flow rate of 1 mL/min, 2-propanol/hexanes
(v/v) ) 1:99 (tminor ) 211.7 min, tmajor ) 224.8 min).
[2-(o-Bromophenyl)aziridin-1-yl]phosphonic acid diphenyl
ester. (Table 4, entry 7) was synthesized from the reaction of
o-bromostyrene with DPPA at 40 °C and obtained as a yellow oil
(58.7 mg, 68% yield). 1H NMR (400 MHz, CDCl3): δ 7.53 (d, J )
7.9 Hz, 1H), 7.36-7.13 (m, 13H), 4.00 (ddd, JP-H ) 16.3 Hz, JH-H
) 6.1, 3.5 Hz, 1H), 2.96 (ddd, JP-H ) 18.6 Hz, JH-H ) 6.2, 1.2
Hz, 1H), 2.21 (ddd, JP-H ) 15.2 Hz, JH-H ) 3.3, 1.2 Hz, 1H). 13
C
[2-(m-Nitrophenyl)aziridin-1-yl]phosphonic acid diphenyl es-
ter. (Table 4, entry 12)12a was synthesized from the reaction of
m-nitrostyrene with DPPA at 40 °C and obtained as a yellow oil
(45.6 mg, 58% yield). 1H NMR (400 MHz, CDCl3): δ 8.12 (dd, J
) 8.1, 0.9 Hz, 1H), 8.05 (s, 1H), 7.55 (d, J ) 7.7 Hz, 1H,), 7.47
(t, J ) 8.0 Hz, 1H), 7.35-7.12 (m, 10H), 3.76 (ddd, J P-H ) 16.2
NMR (100 MHz, CDCl3): δ 150.6, 135.8, 132.3, 129.7, 129.3,
127.5, 127.5, 125.3, 123.3, 120.3, 39.2, 34.6. 31P NMR (161 MHz,
CDCl3): δ 5.68 (s). FT-IR (solid, cm-1): 1590, 1488, 1289, 1189,
940, 752. HRMS-ESI ([M + H]+) for C20H17NO3PBr calcc
430.0202, found 430.0208. Enantiomeric excess was determined
via HPLC using a Chiralcel AD-H chiral column with a flow rate
of 1 mL/min, 2-propanol/hexanes (v/v) ) 4:96 (tminor ) 83.2 min,
tmajor ) 96.0 min).
Hz, J H-H ) 6.0, 3.3 Hz, 1H), 2.95 (dd, J P-H ) 18.6 Hz, J H-H
)
6.0 Hz, 1H), 2.33 (dd, J P-H ) 15.3 Hz, J H-H ) 3.3 Hz, 1H). 13
C
NMR (100 MHz, CDCl3): δ 148.4, 138.7, 132.3, 129.8, 129.8,
129.5, 125.5, 123.0, 121.1, 120.3, 37.9, 35.1. 31P NMR (121 MHz,
CDCl3): δ 5.27 (s). FT-IR (film, cm-1): 1591, 1531, 1488, 1350,
1190, 950. HRMS-EI ([M - H]+) for C20H17N2O5P calcd 395.0797,
found 395.0789. Enantiomeric excess was determined via HPLC
using a WHELK-O1 chiral column and a flow rate of 2 mL/min,
2-propanol/hexanes (v/v) ) 2:98 (tminor ) 103.5 min, tmajor ) 116.8
min).
[2-(m-Bromophenyl)aziridin-1-yl]phosphonic acid diphenyl
ester. (Table 4, entry 8) was synthesized from the reaction of
m-bromostyrene with DPPA at 40 °C and obtained as a yellow oil
1
(49.5 mg, 58% yield). H NMR (400 MHz, CDCl3): δ 7.40 (m,
1H), 7.34-7.12 (m, 13H), 3.64 (ddd, JP-H ) 16.4 Hz, JH-H ) 6.0,
3.4 Hz, 1H), 2.87 (ddd, JP-H ) 19.0 Hz, JH-H ) 6.1, 0.7 Hz, 1H),
2.26 (ddd, JP-H ) 15.5 Hz, JH-H ) 3.2, 0.8 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 150.6, 138.6, 131.2, 130.0, 129.7, 129.1,
125.3, 125.0, 122.6, 120.3, 38.1, 34.9. 31P NMR (161 MHz, CDCl3):
δ 5.73 (s). FT-IR (solid, cm-1): 1590, 1488, 1281, 1188, 935, 773,
751, 687. HRMS-ESI ([M + H]+) for C20H17NO3PBr calcd
Acknowledgment. We are grateful for financial support of
this work from the University of South Florida and the
7264 J. Org. Chem. Vol. 73, No. 18, 2008

Cobalt-Catalyzed Asymmetric Olefin Aziridination
1
University of Tennessee for Startup Funds, American Chemical
Society for a PRF-AC grant, National Science Foundation for
a CAREER Award, and National Science Foundation for a
RSEC grant. Funding for the USF Department of Chemistry
Mass Spectrometry Facility has been furnished in part by the
NSF (CRIF: MU-0443611).
Supporting Information Available: H NMR, 13C NMR,
31P NMR, and 19F NMR spectra and HPLC traces for all
products. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO801151X
J. Org. Chem. Vol. 73, No. 18, 2008 7265