Copper-nitrenoid formation and transfer in catalytic olefin aziridination utilizing chelating 2-pyridylsulfonyl moieties

Article abstract of DOI:10.1021/jo800134j

(Chemical Equation Presented) We have developed an efficient protocol for copper-catalyzed olefin aziridination using 5-methyl-2-pyridinesulfonamide or 2-pyridinesulfonyl azide as the nitrenoid source. The presence of a 2-pyridyl group significantly facil

Full text of DOI:10.1021/jo800134j

Copper-Nitrenoid Formation and Transfer in Catalytic Olefin
Aziridination Utilizing Chelating 2-Pyridylsulfonyl Moieties
Hoon Han, Seong Byeong Park, Sang Kyu Kim,* and Sukbok Chang*
Center for Molecular Design and Synthesis (CMDS), Department of Chemistry and School of Molecular
Science (BK21), Korea AdVanced Institute of Science and Technology (KAIST), Daejon 305-701, Korea
sangkyukim@kaist.ac.kr; sbchang@kaist.ac.kr
ReceiVed January 20, 2008
We have developed an efficient protocol for copper-catalyzed olefin aziridination using 5-methyl-2-
pyridinesulfonamide or 2-pyridinesulfonyl azide as the nitrenoid source. The presence of a 2-pyridyl
group significantly facilitates aziridination, suggesting that the reaction is driven by the favorable formation
of a pyridyl-coordinated nitrenoid intermediate. Using this chelation-assisted strategy, synthetically
acceptable yields of aziridines could be obtained with a range of aryl olefins even in the absence of
external ligands. Importantly, a large excess of olefin is not required. X-ray crystallography, ESI-MS,
Hammett plot analysis, kinetic studies, and computational undertakings strongly support that the observed
aziridination is driven by internal coordination.
I. Introduction
A range of catalytic aziridination reactions of olefins have
been developed using transition metal species including Cu,5
Ag,6 Au,7 Ru,8 Rh,9 Mn,10 Fe,11 Co,12 Pd,13 Ni,14 Re,15 or In16
in combination with suitable oxidants and coordinating ligands.
The aziridine group is found in a number of important
naturally occurring molecules, such as ficellomycin,1a porfiromy-
cin,1b mitomycin,1c miraziridine,1d azinomycine,1e FR-66979,1f
FR-900482,1g and maduropeptin.1h In addition to being synthetic
endpoints, aziridines are also highly important building blocks
in organic synthesis.2 This utility has stimulated the development
of a wide range of preparative procedures of aziridines via either
traditional syntheses3 or catalytic routes.4
(3) (a) Yudin, A. K. In Aziridines and Epoxides in Organic Synthesis;
Wiley-VCH: Weinheim, Germany, 2006. (b) Jacobsen. E. N. In Compre-
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Eds.; Springer-Verlag: Berlin, 1999; pp 607-618.
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Chem. Res. 2006, 39, 194-206. (f) Katsuki, T. Chem. Lett. 2005, 1304-
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10.1021/jo800134j CCC: $40.75 © 2008 American Chemical Society
Published on Web 03/08/2008
2862
J. Org. Chem. 2008, 73, 2862-2870

Copper-Nitrenoid Formation and Transfer
SCHEME 1. Strategy for the Chelation-Assisted
Aziridination
Catalyst options have been expanded in recent years, but known
nitrenoid sources remain limited. Thanks to the pioneering work
of Mansuy,17 N-(p-toluenesulfonyl)imino phenyliodinane (PhI
) NTs) has been most widely employed as an efficient nitrenoid
precursor in the olefin aziridination procedures.18 Although there
are several advantages of using PhI ) NTs, some drawbacks
limit its practical utility, for example, sensitivity to moisture or
air, generation of side products such as oxygenated molecules,
or difficulty in scaling up.19 As a result, for reasons of
convenience, practicality, and environmental concerns, N-
halogenated sulfonamide salts such as chloramine-T and bro-
mamine-T have emerged as alternative nitrogen sources in some
N-transfer reactions.20 However, these pathways are frequently
low yielding due to the competition between hydrogen abstrac-
tion and insertion reactions.
equivalent olefin amounts, and no external ligands.26 In addition,
the mechanism of aziridination has not been studied as much
as that for epoxidation27 or cyclopropanation.28
To overcome these drawbacks, various more convenient
nitrenoid sources have been investigated including sulfona-
mides,21 carbamates,22 and sulfamate derivatives23 in combina-
tion with iodonium salts24 and/or suitable additives.25 However,
reactions are sought that use more user-friendly oxidants,
There are mounting examples showing that the presence of
directing groups adjacent to reacting sites has significant
influence on the reaction outcomes, thus leading to a dramatic
change in efficiency and/or selectivity.29 Nitrogen-containing
organic functional groups readily coordinate to numerous
transition metal species,30 so that they are widely utilized as
effective chelating units.31 Among these, 2-pyridyl groups have
attracted much attention as an effective chelating group.32 We
also have successfully utilized 2-pyridyl moieties in the Ru-
catalyzed hydroesterification and hydroamidation of olefins and
alkynes.33 We previously reported initial results of chelation-
assisted Cu-catalyzed aziridination using 2-pyridinesulfonamides
as a nitrenoid source.34 Described herein are our detailed studies
on the aziridination using 2-pyridinesulfonyl azides and 2-py-
ridinesulfonamides (Scheme 1), focusing on reaction scope and
mechanism.
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J. Org. Chem, Vol. 73, No. 7, 2008 2863

Han et al.
SCHEME 2. Aziridination of Styrene with Various Nitrenoid Sources
II. Results and Discussion
mide gave a lower product yield (43%), implying that steric
bulkiness near the coordination site of the 2-pyridyl group has
a detrimental influence on the reaction efficiency. It should be
noted that copper(I) species could also carry out the reaction,
albeit with slightly lower activities compared to that of Cu(II)
catalysts. In fact, the product yield was 66% with Cu(OTf)•PhH
and 58% with [Cu(CH3CN)4][PF6] in the reaction of styrene
with 5-methyl-2-pyridinesulfonamide under otherwise the same
conditions.
A similar propensity was also observed in the Cu-catalyzed
aziridination with 1-naphthalene- and 8-quinolinesulfonamide
(eq 2). A significantly improved product yield was observed
when 8-quinolinesulfonamide was employed, whereas only
negligible aziridine was obtained using 1-naphthalenesulfona-
mide, clearly indicating the crucial effect of chelation.
II.A. Aziridination with 2-Pyridinesulfonamides. At the
outset of our studies, it was envisioned that the introduction of
a 2-pyridyl unit into nitrenoid precursors such as arenesulfona-
mides and aromatic amides could significantly influence the
course of metal-mediated aziridination through pyridyl-N metal
chelation (eq 1). It was anticipated that both nitrenoid generation
and subsequent alkene aziridination would be favorably driven
by coordination effects, resulting in efficient catalysis even in
the absence of added ligands.
We first investigated the chelation effects of a range of
nitrenoid sources in combination with mild oxidants such as
PhI(OAc)2 in the copper-catalyzed aziridination reactions
(Scheme 2). To examine the feasibility of such chelation, only
1.2 equiv of styrene was employed. Aziridination was sluggish
when benzenesulfonamide and its p-nitro derivatives were
employed in the absence of external ligands. This low reactivity
was not improved by increasing the amount of olefin employed
(up to 10 equiv). Reaction with benzamide did not afford the
desired aziridine under the same conditions.
In sharp contrast, efficiency of the transformation is signifi-
cantly enhanced when 2-pyridinesulfonamide and its derivatives
are employed. For example, the use of 2-pyridinesulfonamide
resulted in high yield of the corresponding aziridine (76% yield)
using 3 mol % of Cu(tfac)2 catalyst. Among a variety of
transition metal species previously known to catalyze aziridi-
nation, it was found that Cu(tfac)2 exhibited the highest catalytic
activity in acetonitrile in the presence of molecular sieves.35
Introduction of a methyl group at C-5 of the 2-pyridyl moiety
slightly improved the yield to 84%, as monitored by NMR
spectroscopy. However, the use of 6-methyl-2-pyridinesulfona-
The olefin aziridination procedure optimized above using
5-methyl-2-pyridinesulfonamide (1) was successfully applied
to a range of aromatic terminal olefins, resulting in moderate
to high product yields. However, internal olefins reacted less
efficiently compared to monosubstituted alkenes, and relatively
large excesses of olefin substrates were required to obtain
satisfactory yields. Whereas aziridination of trans-â-methyl
styrene gave only trans-aziridine product, that of cis-olefin took
place non-stereoselectively to provide a mixture of cis/trans
isomeric products, suggesting that the nitrene transfer process
in our system proceeds via a stepwise radical pathway.36 In
contrast to aryl olefins, the aziridination of aliphatic olefins was
(35) See the Supporting Information for details.
2864 J. Org. Chem., Vol. 73, No. 7, 2008

Copper-Nitrenoid Formation and Transfer
TABLE 1. Aziridination of Styrene with Various Sulfonyl Azides
much more sluggish, giving only moderate to low yields of the
corresponding products.37 The aziridination also was shown to
be possible on larger scale. For instance, reaction of styrene
(12 mmol) with 5-methyl-2-pyridine sulfonamide (1, 10 mmol)
afforded the corresponding aziridine (2.2 g, 81%) under the
optimized conditions.
II.B. Aziridination with 2-Pyridinesulfonyl Azides. Organic
azides have been extensively utilized in various synthetic areas
such as peptide synthesis, combinatorial chemistry, and cy-
cloaddition reactions.38,39 Despite their high utility in synthetic
chemistry, transition-metal-mediated aziridination reactions us-
ing sulfonyl azides have been far less studied,40 mainly due to
the lack of suitable protocols for the controlled thermal41 or
photolytic42 generation of reactive nitrenoids. Since molecular
nitrogen is released as a byproduct from aziridination reactions
using sulfonyl azides, this approach is very attractive from an
environmental perspective. In 1967, Khan and Kwart reported
that tosyl azide was decomposed upon the addition of Cu
catalysts in cyclohexene to afford aziridine and allylic insertion
species, strongly implying the intermediacy of a copper-
nitrenoid species.43 In 1995, Jacobsen and co-workers revealed
that chiral copper catalysts bearing bidentate ligands induce
asymmetric aziridination of olefins when sulfonyl azides are
used,36b again clearly implying the presence of a copper-
nitrenoid. More recently, Katsuki and co-workers utilized
various azides for the development of efficient nitrogen transfer
reactions such as aziridination, sulfimidation, and intramolecular
C-H amination reactions under mild conditions without pho-
tolysis.44 In particular, they developed an elegant protocol of
Ru-catalyzed asymmetric aziridination using sulfonyl azides.
We were intrigued by the possibility of developing a facile
aziridination procedure using chelating 2-pyridyl-containing
sulfonyl azides. Whereas the reaction of styrene with benze-
nesulfonyl azide using Cu(acac)2 (10 mol %) resulted in only a
negligible yield of aziridine (Table 1, entry 1), the use of
2-pyridinesulfonyl azide (2) enabled the formation of the
corresponding aziridine in a synthetically acceptable yield, even
entry
X
Y
R
yield (%)a
1
2
CH
N
N
CH
N
N
N
N
CH
N
SO2
SO2
SO2
SO2
SO2
SO2
SO2
SO2
CO
H
H
H
<5
69
43
7
70
72
9
29
<5
<5
3b
4
4-NO2
4-Me
5-Me
6-Me
5-CF3
H
5
6
7
8
9
10
CO
H
a 1H NMR yield using an internal standard (anisole). b In the presence
of 1,10-phenanthroline (0.4 equiv).
in the absence of external ligands (entry 2). Copper species
exhibited the most satisfactory activities among a wide range
of transition metal catalysts examined.35 In particular, Cu(acac)2
in acetonitrile at 50 °C gave the best results. It was interesting
to note that the addition of an external coordinating ligand
slightly decreased product yield (entry 3), suggesting competitive
copper coordination between the added external ligand and the
2-pyridyl moiety of the nitrenoid precursor. Binding of the
external ligand would interfere with nitrenoid precursor chela-
tion. When an electron-deficient benzenesulfonyl azide was
employed under the same conditions, small amounts of aziridine
formed (entry 4).
The presence of a 4- or 5-methyl substituent on the 2-py-
ridinesulfonyl group resulted in a slight increase of product
yields (entries 5-6). However, 6-methyl substitution afforded
the aziridine in poor yield (entry 7). In addition, when
5-trifluoromethyl-2-pyridinesulfonyl azide was employed, a
significant decrease in product yield was observed (entry 8).
Efficiency of aziridination became poor when acyl azides were
employed (entries 9 and 10).
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Aziridination of styrene with 8-quinolinesulfonyl azide
smoothly gave the desired aziridine in reasonable yield, whereas
it was very sluggish with 1-naphthalenesulfonyl azide under
otherwise identical conditions, again underscoring the role of
nitrogen atom chelation (eq 3).
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1962, 84, 3220-3221. (b) Mueller, P.; Baud, C.; Na¨geli, I. J. Phys. Org.
Chem. 1998, 11, 597-601. (c) Mueller, P.; Baud, C.; Jacquier, Y. Can. J.
Chem. 1998, 76, 738-750.
(43) Kwart, H.; Khan, A. A. J. Am. Chem. Soc. 1967, 89, 1951-1953.
(44) (a) Murakami, M.; Uchida, T.; Katsuki, T. Tetrahedron Lett. 2001,
42, 7071-7074. (b) Omura, K.; Murakami, M.; Uchida, T.; Irie, R.; Katsuki,
T. Chem. Lett. 2003, 354-355. (c) Omura, K.; Uchida, T.; Irie, R.; Katsuki,
T. Chem. Commun. 2004, 2060-2061. (d) Kawabata, H.; Omura, K.;
Katsuki, T. Tetrahedron Lett. 2006, 47, 1571-1574.
The scope of chelation-assisted olefin aziridination using
2-pyridinesulfonyl azide (2) was subsequently investigated using
more optimized conditions (Table 2). Reaction of aromatic
terminal olefins (3 equiv to azide 2) took place smoothly with
J. Org. Chem, Vol. 73, No. 7, 2008 2865

Han et al.
TABLE 2. Aziridination of Olefins with 2-Pyridinesulfonyl Azide
of 2-pyridinesulfonamide and 2-pyridinesulfonyl azide can be
made, the reaction with azides affords slightly lower aziridine
yields in general.
II.C. Mechanistic Studies of Chelation-Assisted Aziridi-
nation. The intrigue of transition-metal-mediated aziridination
of olefins lies in determining validity of the postulated metal-
nitrenoid intermediates, elucidating the oxidation state of the
metal centers, and understanding the comprehensive reaction
course of nitrene transfer. Even though involvement of the
metallonitrene intermediate is now well accepted, there is a
paucity of concrete experimental evidence, compared to that
for epoxidation and cyclopropanation reactions. Recently,
Prortasiewicz and co-workers reported a mechanistic detail of
aziridination by isolating an iodinane species in the copper-
catalyzed routes.45 Scott and co-workers have investigated the
oxidation state of active copper catalytic species in the aziri-
dination via Hammett plot analysis, UV spectroscopy, and
theoretical calculations.46 More recently, Che and co-workers
utilized a Ru-porphyrin system to elucidate mechanistic
pathways in the olefin aziridination by utilizing various
spectroscopic tools such as NMR, ESI-MS, UV, X-ray crystal-
lography, and cyclic voltammetry (CV).8 Warren and co-workers
also tried to verify the presence of transient Cu-nitrene
intermediates from discrete dicopper nitrenes.47 Despite these
significant contributions, more tangible evidence for the exist-
ence of the presumed metal-nitrenoid is highly desirable for
better understanding of the catalytic processes.
We envisaged that our present chelation-assisted system
would be suitable for the mechanistic studies of aziridination
since the copper-nitrenoid species was postulated to be
stabilized by the intramolecular coordination of the metal center
to the pyridyl nitrogen atom of 2-pyridylsulfonamide or its azide
analogue. At the outset of our studies using 1, we tried to capture
intermediate metal-nitrenoids by allowing 1 to react with a
stoichiometric oxidant PhI(OAc)2 in the presence of 0.5 equiv
of copper complex Cu(tfac)2 (eq 4).
a Isolated yields. b Ten equivalents of olefin was used. c A mixture of
trans/cis isomer (2:1).
10 mol % of Cu(acac)2 catalyst at 50 °C, providing the
corresponding monosubstituted aziridines in moderate to good
yield (entries 1-5). The plausible chelation effect was not
significantly altered by the electronic and/or steric environment
of the olefins. The reaction conditions demonstrated tolerance
of some functional groups such as halides or acetate. 2-Vinyl-
naphthalene was also a viable substrate, albeit with a moderate
efficiency (entry 8). The reaction of trans-â-methylstyrene (10
equiv) afforded the corresponding trans-aziridine in an accept-
able yield (entry 9). When cis-â-methylstyrene was subjected
to the reaction conditions, a mixture of two stereoisomeric
aziridne products was obtained with 2:1 ratio (trans/cis, entry
10). The reactivity of aliphatic olefins was low even when the
olefin was used in large excess (entry 11). Although no direct
comparison of reaction efficiency between two nitrenoid sources
A green solid (3) was isolated from the reaction mixture in
81% yield, and its structure was determined by the X-ray
crystallographic analysis (Figure 1). It reveals that the copper-
(II) complex 3 forms a pseudo-square-planar geometry with two
2-pyridinesulfonamido groups positioned trans to each other.
(45) Macikenas, D.; Skrzypczak-Jankun, E.; Prortasiewicz, J. D. J. Am.
Chem. Soc. 1999, 121, 7164-7165.
(46) Gillespie, K. M.; Crust, E. J.; Deeth, R. J.; Scott, P. Chem. Commun.
2001, 785-786.
(47) Badiei, Y. M.; Krishnaswamy, A.; Melzer, M. M.; Warren, T. H.
J. Am. Chem. Soc. 2006, 128, 15056-15057.
2866 J. Org. Chem., Vol. 73, No. 7, 2008

Copper-Nitrenoid Formation and Transfer
increasingly employed as an important tool for mechanistic
studies.50 After treating a solution of 1, PhI(OAc)2 (1.2 equiv),
and styrene (1.0 equiv) in CH3CN (0.01 M) with Cu(tfac)2 (0.5
equiv), aliquots were taken and subjected to ESI-MS analysis.
An intense ion at m/z ) 590 was observed after 10 min, which
was assigned to copper species 4, (tfac)Cu-PhINSO2(2-Py)-
(5-Me). In addition, a peak at m/z ) 464 was detected, which
was assigned as a bis(sulfonamido)copper complex bearing one
acetate ligand (3 + OAc). The observed isotopic distribution
of each peak is in good agreement with that of the calculated
ratio.35 After 60 min, the aziridine peak (m/z ) 275) appeared
with concomitant decrease in the intensity of the peak at m/z )
590 (Figure 2b).
Competition experiments with a series of p-substituted styrene
derivatives indicate that electron-withdrawing substituents slowed
the reaction with a F value of -0.60 (Figure 3).35 This result
suggests an asynchronous transition state model for the Cu-
mediated nitrene transfer reaction in accord with the previous
reports.51
Kinetic studies of styrene aziridination using 1 showed that
the reaction is first-order in olefin and second-order in copper
catalyst.35 This rate order dependence on the olefin concentration
is in good agreement with Jacobsen’s results,5e in which it was
argued that the rate-limiting step is the transfer of copper-
nitrenoid to double bonds. Thus, nitrenoid transfer of copper
intermediates to olefin may be also the rate-limiting process in
our case.
FIGURE 1. Structural diagram of compound 3.
Whereas the Cu-Npyridyl bond distance was determined to be
2.034 Å, the Cu-Nsulfonamido length of 1.928 Å is slightly
shorter.48 Infrared spectroscopy of 3 showed that the vibrational
peaks for SO2 of 2-pyridinesulfonyl group are shifted from 1329
and 1170 cm-1 to 1303 and 1142 cm-1, respectively, indicating
the existence of the copper-amido bond.49
A series of experiments were subsequently carried out, using
the isolated copper complex 3 as a mechanistic probe. When a
stoichiometric amount of 3 was allowed to react with excess
styrene in the presence of PhI(OAc)2, the aziridine was obtained
in 56% (eq 5), implying that 3 is readily transformed into the
active nitrenoid species under the reaction conditions.
On the basis of our experimental results above, we propose
a mechanism that requires the pyridyl chelation (Scheme 3). It
is envisioned that copper binds to the 2-pyridinesulfonamide
group, leading to facile ligand exchange to afford a copper
amido species (A). We postulate that conversion of A to an
active copper-nitrenoid species (C) is accelerated by chelation
assistance upon the release of iodobenzene and acetic acid
through B. It should be noted that the 2-pyridyl binding in C is
in contrast to Norrby’s postulate for the reaction with benze-
nesulfonyl precursors, in which nitrenoid copper center binds
to a sulfonyl oxygen atom (D).52 It is believed that the isolated
copper diamido species (3) can be converted into the active
copper-nitrenoid intermediate (C) by the action of additional
oxidant under the reaction conditions, supported by our observa-
tions described above.
Although it is not explicitly presented in Scheme 3, the final
nitrenoid transfer to copper-coordinated olefin is assumed to
take place via a stepwise sequence involving radical species,
evidenced by the generation of two stereoisomeric products in
the reaction of cis-â-methylstyrene.34 It is assumed that, since
the reaction is second-order in copper concentration, the
copper-nitrenoid is transferred onto the double bond that is
probably coordinated to a second copper species.
In addition, when a catalytic amount of 3 was employed under
the aziridination conditions, aziridine product could be obtained
in 86% yield (eq 6).
In order to rationalize the postulated chelation effects on the
aziridination pathway, geometry optimization of certain putative
intermediates and transition states was performed with both ab
initio at the Hartree-Fock (HF) level and DFT (B3LYP) levels
(50) (a) Hilderling, C.; Aldhart, C.; Chen, P. Angew. Chem., Int. Ed.
1998, 37, 2685-2689. (b) Chen, P. Angew. Chem., Int. Ed. 2003, 42, 2832-
2847.
(51) (a) Diaz-Requejo, M. M.; Perez, P. J.; Brookhart, M.; Templeton,
J. L. Organometallics 1997, 16, 4399-4402. (b) Ma, L.; Jiao, P.; Zhang,
Q.; Xu, J. Tetrahedron: Asymmetry 2005, 16, 3718-3734. (c) Ma, L.; Jiao,
P.; Zhang, Q.; Du, D.-M.; Xu, J. Tetrahedron: Asymmetry 2007, 18, 878-
884.
In order to further prove the putative chelation between the
copper and nitrogen atom of the 2-pyridyl moiety, we next
utilized an ESI-MS method since this analysis has been
(48) Nanthakumar, A.; Miura, J.; Diltz, S.; Lee, C.-K.; Aguirre, G.; Orega,
F.; Ziller, J. W.; Walsh, P. W. Inorg. Chem. 1999, 38, 3010-3013.
(49) Sumalan, S. L.; Casanova, J.; Alzuet, G.; Borhs, J.; Castifieiras,
A.; Supuran, C. T. J. Inorg. Biochem. 1996, 62, 31-39.
(52) Brandt, P.; So¨rdergren, M. J.; Andersson, P. G.; Norrby, P.-O. J.
Am. Chem. Soc. 2000, 122, 8013-8020.
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Han et al.
FIGURE 2. ESI-MS analysis of the aziridination (including 0.1% acetic acid in the positive mode): (a) 10 min and (b) 60 min.
FIGURE 3. Hammett plot fit against σ+ values.
using the 6-31G(d) basis set.53 The calculated structure for 3
agreed well with that of its X-ray structure (Figure 1), proving
that this method is suitable for the mechanistic studies in the
aziridination with 2-pyridinesulfonamide as a model reagent.
According to the B3LYP/6-31G(d) computation, the difference
of bond dissociation energy (BDE) between an olefin-bound
2868 J. Org. Chem., Vol. 73, No. 7, 2008

Copper-Nitrenoid Formation and Transfer
SCHEME 3. Proposed Pathway of the Chelation-Assisted Aziridination (L ) CH3CN or tfac)
copper-nitrenoid complex derived from benzenesulfonamide
(Ph-5) and that obtained from 2-pyridinesulfonamide (Py-8) was
determined to be 15.5 kcal/mol, revealing the stability produced
by chelation (Figure 4). In each case, styrene was employed as
olefin for the computation. It should be noted that the copper
center in Ph-5 is assumed to be coordinated with the nitrenoid
N and sulfonyl O based on Norrby’s postulate.52
Optimized geometries of transition states Ph-6 and Py-9 for
the nitrenoid transfer step resulting from olefin-bound copper-
nitrenoid complexes Ph-5 and Py-8, respectively, are also
depicted in Figure 4. It is interesting to note that, during the
transfer step, the bond length of Cu-N(nitrenoid) derived from
the benzenesulfonamide precursor is significantly elongated from
1.75 Å (Ph-5) to 3.34 Å (Ph-8), whereas this difference becomes
very small, changing from 1.81 Å (Py-8) to only 1.84 Å (Py-
9) in case of the 2-pyridyl-bound process. The difference in
bond dissociation energy between the two transition states of
Ph-6 and Py-9 (∆BDE ) 34.2 kcal/mol) turned out to be larger
than that between the prior states (Ph-5 and Py-8). Two aziridine
products (Ph-7 and Py-10), while being assumed to be bound
to copper species, were also geometrically optimized using the
computational study.
The overall energy profile along the reaction coordinates is
illustrated in Figure 5, showing that there are significant
chelation effects on the reaction progresses. The 2-pyridyl group-
chelated nitrenoid was calculated to be greatly stabilized by the
presence of the internal coordination. More importantly, the
transition states are found to be also dramatically influenced
by the postulated chelation effects, revealing that the 2-pyridyl-
sulfonyl moiety contributes to reduce the activation energy of
the aziridination reaction compared to the corresponding ben-
FIGURE 4. Optimized structures of Ph-5-7 and Py-8-10.
J. Org. Chem, Vol. 73, No. 7, 2008 2869

Han et al.
FIGURE 5. The energy profiles in the aziridination with PhSO2NH2 (left) and 2-PySO2NH2 (right).
diacetate (161 mg, 0.5 mmol), copper(II) trifluoroacetylacetonate
(9.2 mg, 0.025 mmol), olefin (0.6 mmol), and molecular sieves (4
Å, 500 mg) in anhydrous CH3CN (1 mL) was stirred for 12 h under
N2. After filtration through a pad of Celite, the filtrate was
concentrated in vacuo. The residue was purified by flash column
chromatography (EtOAc/hexane, 1:2) to give the desired aziridine.
zenesulfonyl group (∆Ea ) 18.8 kcal/mol). These theoretical
results agree well with our experimental studies including kinetic
data.
III. Conclusion
We have developed a new chelation-assisted Cu-catalyzed
aziridination protocol. New precursors of nitrenoid species
bearing a chelating group, such as 2-pyridinesulfonamide and
2-pyridylsulfonyl azide, are successfully utilized in combination
with a mild oxidant, PhI(OAc)2. A wide range of aryl terminal
alkenes could be readily employed under the optimized mild
conditions to provide satisfactory yields of aziridines in the
absence of external ligands. X-ray crystallography, ESI-MS,
competition experiments, kinetic and computational studies
support that the copper-catalyzed aziridination with 2-pyridyl-
sulfonamides and 2-pyridinesulfonyl azides is chelation-driven.
General Procedure for the Copper-Catalyzed Olefin Aziri-
dination with 2-Pyridinesulfonyl Azide. A mixture of 2-pyridine-
sulfonyl azide (100 mg, 0.54 mmol), Cu(acac)2 (14 mg, 10 mol
%), olefin (1.62 mmol, 3 equiv), and molecular sieves (4 Å, 500
mg) in anhydrous CH3CN (1 mL) was stirred for 12 h at 50 °C
under N2. After filtration through a pad of Celite, the filtrate was
concentrated in vacuo and the residue was purified by flash column
chromatography (EtOAc/hexane, 1:2) to give the desired aziridine.
N-(2-Pyridinesulfonyl)(2-chlorophenyl)aziridine (Table 2, en-
try 2): Colorless solid; mp 64-66 °C; 1H NMR (300 MHz, CDCl3)
δ 2.40 (1H, d, J ) 4.6 Hz), 3.23 (1H, d, J ) 7.2 Hz), 4.24 (1H, dd,
J ) 7.2, 4.6 Hz), 7.12-7.33 (4H, m), 7.56-7.58 (1H, m), 7.97
(1H, td, J ) 7.8, 1.5 Hz), 8.15 (1H, d, J ) 7.8 Hz), 8.74 (1H, d,
J ) 4.1 Hz); 13C NMR (100 MHz, CDCl3) δ 36.0, 39.2, 123.0,
126.9, 127.5, 127.6, 129.1, 132.8, 133.7, 138.1, 150.3, 155.6; IR
IV. Experimental Section
General Procedure for the Olefin Copper-Catalyzed Aziri-
dination with 5-Methyl-2-pyridinesulfonamide. A mixture of
5-methyl-2-pyridinesulfonamide (86.1 mg, 0.5 mmol), iodobenzene
(KBr pellet) 3061, 2923, 1596, 1578, 1480, 1452, 1428, 1379 cm-1
;
m/z (FAB) found [M + H]+ 295.0311/297.0276, C13H12ClN2O2S
requires m/z 295.0308/297.0281.
(53) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.;
Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich,
S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A.
D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A.
G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.;
Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03; Gaussian, Inc.: Pittsburgh, PA, 2003.
Acknowledgment. This work was supported by Korea
Research Foundation Grant (KRF-2004-041-C00212). We thank
Professor David G. Churchill for his helpful comments and
critical reading.
Supporting Information Available: Detailed experimental
procedures, characterization data of products, copies of 1H and 13
C
NMR spectra of the obtained aziridines, X-ray crystallographic data
of complex 3, and XYZ coordinates for the calculated intermediates
and transition states. This material is available free of charge via
the Internet at http://pubs.acs.org.
JO800134J
2870 J. Org. Chem., Vol. 73, No. 7, 2008