Sulfur ylide mediated three-component aziridination and epoxidation reactions using vinyl sulfonium salts

Article abstract of DOI:10.1055/s-2008-1078252

Coupling of diphenylvinyl sulfonium triflate with nucleophiles and either aldehydes or imines gives epoxides and aziridines, respectively, in a three-component reaction. cis-Aziridines could be formed in good diastereomeric ratio, and the selectivity was correlated to the reactivity of the imine. This represents the first study of cis/trans selectivity in the reactions of imines with non-stabilized sulfur ylides. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1078252

LETTER
2191
Sulfur Ylide Mediated Three-Component Aziridination and Epoxidation
Reactions Using Vinyl Sulfonium Salts
T
hree-Componen
h
t
A
ziridinati
r
on and
E
i
poxida
s
tion Reactions oforos G. Kokotos, Eoghan M. McGarrigle, Varinder K. Aggarwal*
School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK
Fax +44(117)9298611; E-mail: v.aggarwal@bristol.ac.uk
Received 18 July 2008
This paper is dedicated with deep respect to Prof. Sir Jack Baldwin on the occasion of his 70th birthday.
Although vinyl sulfonium salts such as 2 have been em-
ployed in two-component reactions (nucleophiles with
tethered electrophiles) generating 5-, 6-, and 7-membered
ring epoxides and aziridines and subsequently applied to
Abstract: Coupling of diphenylvinyl sulfonium triflate with nu-
cleophiles and either aldehydes or imines gives epoxides and aziri-
dines, respectively, in a three-component reaction. cis-Aziridines
could be formed in good diastereomeric ratio, and the selectivity
was correlated to the reactivity of the imine. This represents the first the synthesis of mitomycins3 and balanol,2b,c their use in
study of cis/trans selectivity in the reactions of imines with non-
stabilized sulfur ylides.
three-component coupling reactions has not been investi-
gated.4
Key words: sulfur ylides, epoxidations, aziridinations, multicom-
However, initial experiments with N-methyl tosylamide
ponent reactions, vinyl sulfonium salts
(1a), diphenylvinylsulfonium salt 2, and benzaldehyde in
the presence of NaH were not promising – a large number
of products were obtained, some of which were highly po-
lar. We believed that the ylide intermediate 3 was prefer-
Three-component coupling reactions have not only been
employed to enhance efficiency in organic synthesis but
entially reacting with the vinyl sulfonium salt instead of
have also played a central role in diversity-oriented syn-
the aldehyde. To minimize this side reaction we needed to
thesis.1 The key to success in the development of such re-
actions is controlled reactivity. Nucleophile A (e.g., a
cuprate) should react selectively with electrophile B (e.g.,
an enone) generating an intermediate nucleophile AB
which should then react selectively with electrophile C
(e.g., an aldehyde), all other permutations (e.g. A+C or
increase the concentration of the aldehyde and reduce the
concentration of the vinyl sulfonium salt. Indeed, carrying
out a slow addition of the vinyl sulfonium salt to a solu-
tion of the tosyl amide 1a, NaH and five equivalents of
benzaldehyde furnished the epoxide in good yield
(Table 1, entry 1). Brief optimization of the reaction con-
AB+C) should be slow or unproductive (Scheme 1). Our
ditions showed that KOt-Bu in CH2Cl2 was optimal (entry
interest in vinyl sulfonium salts2 led us to consider their
potential use in these types of processes. In particular, the
trapping of an intermediate ylide 3 with an aldehyde 4 or
2). The reaction could be extended to a range of alterna-
tive nucleophiles including malonate 1b (entry 3), an al-
cohol 1c (entry 4), a thiol 1d (entry 5), and an amine 1e
imine 5 would furnish an epoxide 6 or aziridine 7, which
(entry 6). In all cases, the epoxides 6 were obtained in
are very useful products for further elaboration
good yields but with poor diastereoselectivity. The low
(Scheme 2).
diastereoselectivities are typical of reactions of non-
stabilized ylides with aldehydes,5 but the moderate-to-
high yields are not (they usually give low yields). We be-
C
A
B
A
B
A
B
C
lieve the high yields are a consequence of rapid (in situ)
trapping of the ylide. The reaction, however, is limited to
nucleophiles with only one acidic proton. A different
pathway is followed in reactions of nucleophiles bearing
two acidic protons (Scheme 3). Thus, in the case of dieth-
yl malonate 8a, following ylide formation 1,3-proton
transfer occurred instead, followed by ring closure to give
Scheme 1 General scheme for three-component reaction
X
Ph
S+
–OTf
X
base
R
Ph
–
+
NuH
Ph
S+
4 X = O
Nu
R
5 X = NTs
Ph
Nu
1
2
3
6 X = O
7 X = NTs
SPh2
OTf
Scheme 2 Proposed three-component epoxidation and aziridination
reactions using vinyl sulfonium salt 2
2
Rn
X
RnHX
RnXH2
RnX
SPh2
SPh2
9
8
a: R = CO2Et, n = 2
b: R = Ts, n = 1
SYNLETT 2008, No. 14, pp 2191–2195
Advanced online publication: 05.08.2008
DOI: 10.1055/s-2008-1078252; Art ID: D27108ST
2
2
.0
8
.2
0
0
8
Scheme 3 Reaction of vinyl sulfonium salt 2 with nucleophiles 8
bearing two acidic protons
© Georg Thieme Verlag Stuttgart · New York

2192
C. G. Kokotos et al.
LETTER
a cyclopropane 9a. In the case of tosylamide 8b, an aziri- with moderate trans selectivity whilst stabilized ylides
dine 9b was formed by the same process.6
gave moderate cis selectivity.
In the event, application of our standard conditions with
N-methyl tosylamide and 2 but replacing benzaldehyde
for the corresponding N-Ts imine furnished aziridine 7a in
high yield as a 4:1 mixture of cis/trans-isomers (Table 3,
entry l). Further improvement in yield and diastereoselec-
tivity was observed when using NaH in THF (entry 2,
Table 3). The reaction could be extended to malonate de-
rivatives (entries 3, 4), an alcohol (entry 5), and a thiol
(entry 6) as before, but not amines (pyrrolidine was inef-
fective). Surprisingly, the major diastereomers derived
from the alcohol and thiol reactions were now the trans-
aziridines.
Table 1 Three-Component Epoxidation Reaction Using Vinyl Sul-
fonium Salt 2 and Benzaldehyde
base
–OTf
O
O
(1.2 equiv)
Ph
+
+
NuH
S+
0 °C to r.t.
18 h
Nu
Ph
4a
Ph
Ph
2
1
6
1 equiv
1.5 equiv
5 equiv
Conditions
NaH, THF
Entry NuH
Yield (%)a cis/transb
1
2
MeNHTs
MeNHTs
74
1.8:1
1.5:1
t-BuOK, CH2Cl2 87
Table 3 Three-Component Aziridination Using Vinyl Sulfonium
Salt 2 and N-Tosylbenzaldimine
O
O
3
t-BuOK, CH2Cl2 86
1.1:1
EtO
OEt
Ts
base
–OTf
Ts
Me
(1.2 equiv)
N
N
Ph
+
+
NuH
S+
4
5
6
PhCH2OH
PhSH
t-BuOK, CH2Cl2 77
t-BuOK, CH2Cl2 59
t-BuOK, CH2Cl2 57
1:1.4
1:1.3
1:1
0 °C to r.t.
18 h
Ph
Nu
Ph
Ph
1
2
5
7
1 equiv
1.5 equiv
5 equiv
Pyrrolidine
Entry NuH
Conditions
Yield (%)a cis/transb
a Isolated yield after purification.
b Determined from 1H NMR of the crude reaction mixture.
1
2
MeNHTs
MeNHTs
t-BuOK, CH2Cl2 91
4:1
5:1
NaH, THF
NaH, THF
95
89
The reaction (demonstrated for N-methyl tosylamide) was
easily extended to other aromatic and aliphatic aldehydes
(Table 2), giving moderate-to-good yields but low diaste-
reoselectivities.
O
O
O
3
4
3:1
3:1
EtO
OEt
Me
O
Table 2 Three-Component Epoxidation of Various Aldehydes
NaH, THF
91
t-BuOK
O
EtO
OEt
–OTf
(1.2 equiv)
O
NHAc
Ph
+
+
MeNHTs
S+
CH2Cl2
0 °C to r.t.
18 h
NMe
5
6
PhCH2OH
NaH, THF
NaH, THF
57
33
1:5
1:5
R
R
Ts
6a
Ph
2
PhSH
1a
4
1 equiv
1.5 equiv
5 equiv
a Isolated yield after purification.
b Determined from 1H NMR of the crude reaction mixture.
Entry
R
Yield (%)a
cis/transb
1.5:1
1
2
3
4
5
Ph
87
97
71
45
61
The aziridination reaction was extended to a range of imi-
nes (Table 4) with moderate-to-good yields being ob-
tained in all cases. The diastereoselectivity was also found
to be highly sensitive to the electronic nature of the imine:
electron-rich imines gave very high cis selectivity whilst
electron-poor imines gave low selectivity. In fact, the dia-
stereoselectivities correlated well with s+ (Hammer sub-
stituent constant) (Figure 1). This observation is
consistent with the development of positive charge in the
transition states (TS) and a larger dependence on the
imine’s electronic properties in one of the two TS. More
reactive imines show low selectivity while less reactive
imines give better selectivity in line with the Hammond
postulate. In the case of less reactive imines the later TS
should lead to closer contacts between the imine and ylide
4-O2NC6H4
4-MeOC6H4
Bu
1.1:1
1.3:1
1.6:1
Cy
1.0:1
a Isolated yield after purification.
b Determined from 1H NMR of the crude reaction mixture.
Related three-component coupling reactions with imines
as electrophiles were also considered. Of particular inter-
est were the diastereoselectivities of these processes as the
reactions of imines with non-stabilized sulfur ylides had
not been reported (except those of methylides).7,8 Semi-
stabilized ylides were known to react with N-Ts imines
Synlett 2008, No. 14, 2191–2195 © Thieme Stuttgart · New York

LETTER
Three-Component Aziridination and Epoxidation Reactions
2193
Table 4 Three-Component Aziridination of Various Imines
favourable
charge–charge
interaction
Ts
NaH
–OTf
Ts
(1.2 equiv)
N
N
Ts
H
Ts
H
Ph
Ts
N
+
+
NuH
Ts
N
+
N
R
N
S+
0 °C to r.t
THF, 18 h
Ph2S
R
R
Nu
Ph
R
Ph
H
H
Ph
SPh2
Ph
R
1
2
5
7
Ph
R
+
1 equiv
1.5 equiv
5 equiv
TS-1
TS-2
sterically
favoured
trans-aziridines
favoured by
Coulombic
interaction
cis-aziridines
Entry NuH
R
Yield (%)a cis/transb
1
2
3
4
5
MeNHTs
MeNHTs
4-O2NC6H4
4-ClC6H4
Ph
99
94
95
89
95
1.5:1
3:1
Scheme 4 Transition states proposed to lead to the betaine interme-
diates that give cis- and trans-aziridines
MeNHTs
MeNHTs
MeNHTs
O
5:1
group which dictates that the only substituent ‘allowed’ in
its vicinity is an H. Thus, two TS are believed to be re-
sponsible for product formation: TS1, in which the sulfo-
nium and N-Ts groups are gauche to each other leading to
the trans-aziridine and TS2, where the same two groups
are anti to each other leading to the cis-aziridine
(Scheme 4).
4-MeC6H4
4-MeOC6H4
6:1
15:1
O
6
4-O2NC6H4
83
2:1
EtO
OEt
NHAc
A possible explanation for the observed selectivity is that
because of the Bürgi–Dunitz angle of approach of the nu-
cleophile to the imine, one of the phenyl groups on the
ylide comes into close proximity to the aryl group of the
imine in TS2 but not in TS1.11 This p–p interaction (in-
duced dipole or p-HAr hydrogen bond) will be stabilizing
when the aryl group is electron rich since the Ph group at-
tached to sulfur is electron deficient and so TS2 will be fa-
vored, thus leading to the cis-aziridine. Subtle hydrogen-
bonding interactions between the b-alkoxy group of the
ylide component with the imine C–H may be responsible
for favoring TS1, thus leading to the trans-aziridine.
7
8
"
"
Ph
91
62
3:1
4-MeOC6H4
only cis
a Isolated yield after purification.
b Determined from 1H NMR of the crude reaction mixture.
In conclusion, it has been shown that vinyl sulfonium salt
2 participates in three-component coupling reactions with
a variety of nucleophiles and aldehydes/imines. Key to the
success of this transformation is to maintain a low concen-
tration of the vinyl sulfonium salt (by slow addition) and
a high concentration of the aldehyde/imine to ensure that
the ylide intermediate reacts with the electrophile required
and not with more vinyl sulfonium salt.
The scope of the reaction has been evaluated. Nucleo-
philes bearing one acidic proton give good results, where-
as those bearing two acidic protons lead to three-
membered rings without trapping the electrophile. Both
aromatic and aliphatic aldehydes work well but, as ex-
pected, give low diastereoselectivity. In contrast, aromatic
imines give high cis selectivity with electron-neutral/elec-
tron-rich aromatic imines. This work represents the first
study of cis/trans diastereoselectivity in aziridination re-
actions of non-stabilized ylides with imines.
Figure 1 Plot of log (cis/trans) vs. s+ for the three-component azi-
ridination using MeNHTs (2) and p-XC6H4C=NTs (see Table 4)
components and thus a more pronounced difference be-
tween the energies of the competing TS for the formation
of the betaine intermediates that lead to cis- and trans-
aziridines.
Semi-stabilized ylides have been shown to form betaine
intermediates nonreversibly on reaction with N-tosyl-
sulfonylimines9 and so the selectivities in reactions of
non-stabilized ylides should be determined by the relative
energies of the TS for betaine formation. The unexpected-
ly high cis selectivity can be rationalized using the model
derived by Robiette through DFT calculations.10 In this
model, approach of the ylide to the N-Ts imine is dominat-
ed by the steric interactions of the large sulfonamide
General Procedure for Three-Component Aziridinations
A solution of nucleophile (0.53 mmol) in THF (5 mL) was treated
with NaH (0.64 mmol) at 0 °C under N2 and stirred for 20 min while
warming to r.t. as H2 gas evolved. The reaction mixture was then
cooled to 0 °C and treated with imine (2.65 mmol) followed by a so-
lution of diphenyl(vinyl)sulfonium trifluoromethanesulfonate2a
(0.80 mmol) in THF (10 mL) dropwise over 20 min. After stirring
Synlett 2008, No. 14, 2191–2195 © Thieme Stuttgart · New York

2194
C. G. Kokotos et al.
LETTER
for 18 h at r.t., H2O (20 mL) was added and the mixture extracted
with CH2Cl2 (3 × 20 mL). The combined organic layers were
washed with brine (20 mL), dried (MgSO4), and concentrated under
reduced pressure. Purification by flash chromatography (SiO2,
EtOAc–PE) gave the product as a cis/trans mixture.12–16
in Asymmetric Synthesis; Yudin, A. K., Ed.; Wiley-VCH:
Weinheim, 2006, Chap. 1. Only cis-aziridine was obtained
in the reaction of(dimethylamino)-p-tolyloxosulfonium
ethylide with PhCH=NPh, see: (e) Johnson, C. R.; Janiga, E.
R. J. Am. Chem. Soc. 1973, 95, 7692.
(9) Aggarwal, V. K.; Charmant, J. P. H.; Ciampi, C.; Hornby, J.
M.; O’Brien, C. J.; Hynd, G.; Parsons, R. J. Chem. Soc.,
Perkin Trans. 1 2001, 3159.
Acknowledgment
(10) (a) Robiette, R. J. Org. Chem. 2006, 71, 2726.
(b) Janardanan, D.; Sunoj, R. B. Chem. Eur. J. 2007, 13,
4805.
(11) Seebach, D.; Golinsky, J. Helv. Chim. Acta 1981, 64, 1413.
(12) The products were characterized by NMR, IR, MS, and mp
(where appropriate). Satisfactory elemental analyses and/or
HRMS were obtained for all compounds. Full details and
spectra are available from the authors.
We thank Avecia/NPIL Pharma (Robin Fieldhouse/John Blacker),
Johnson Matthey (Mark Hooper), Syngenta (David Ritchie), and
the DTI for support of this work through an MMI grant. VKA
thanks the Royal Society for a Wolfson Research Merit Award and
EPSRC for a Senior Research Fellowship. We also thank Merck for
unrestricted research support.
(13) N,4-Dimethyl-N-{[1-(toluene-4-sulfonyl)-3-phenyl-2-
aziridinyl]methyl}benzenesulfonamide (Table 2, Entry
2)
References and Notes
(1) Reviews: (a) Syamala, M. Org. Prep. Proced. Int. 2005, 37,
103. (b) Noyori, R.; Suzuki, M. Chemtracts 1990, 3, 173.
(2) (a) Yar, M.; McGarrigle, E. M.; Aggarwal, V. K. Angew.
Chem. Int. Ed. 2008, 47, 3784; Angew. Chem. 2008, 120,
3844. (b) Unthank, M. G.; Tavassoli, B.; Aggarwal, V. K.
Org. Lett. 2008, 10, 1501. (c) Unthank, M. G.; Hussain, N.;
Aggarwal, V. K. Angew. Chem. Int. Ed. 2006, 45, 7066;
Angew. Chem. 2006, 118, 7224.
cis-Isomer as a colourless oil; Rf = 0.40 (EtOAc–PE, 3:7). IR
(film): 1598 (Ar), 1330 (SO2), 1160 (SO2) cm–1. 1H NMR
(400 MHz, CDCl3): d = 7.86 (2 H, d, J = 8.3 Hz, ArH), 7.50
(2 H, d, J = 8.3 Hz, ArH), 7.35 (2 H, d, J = 8.3 Hz, ArH),
7.27–7.16 (7 H, m, ArH), 3.93 (1 H, d, J = 7.0 Hz, NCHPh),
3.25–3.14 (2 H, m, NCHH and NCHCH2), 2.53 (1 H, dd, J =
14.3, 7.0 Hz, NCHH), 2.44 (6 H, s, 2 × CH3), 2.38 (3 H, s,
CH3). 13C NMR (100.5 MHz, CDCl3): d = 145.0 (C), 143.5
(C), 136.2 (C), 135.9 (C), 132.0 (C), 130.0 (CH), 129.9
(CH), 129.7 (CH), 128.6 (CH), 128.3 (CH), 127.4 (CH),
127.3 (CH), 47.6 (CH2), 44.4 (CH), 44.1 (CH), 35.4 (CH3),
21.7 (CH3), 21.5 (CH3). MS (CI): m/z (%) = 471 (14) [MH+],
(3) (a) Kim, K.; Jimenez, L. S. Tetrahedron: Asymmetry 2001,
12, 999. (b) Wang, Y.; Zhang, W.; Colandrea, V. J.;
Jimenez, L. S. Tetrahedron 1999, 55, 10659.
(4) There is one isolated report of an epoxidation reaction of a
butadienylsulfonium salt with a b-keto ester and aldehyde.
See: (a) Rowbottom, M. W.; Mathews, N.; Gallagher, T.
J. Chem. Soc., Perkin Trans. 1 1998, 3927. For a related
example using vinyl selenonium salts, see: (b) Watanabe,
Y.; Ueno, Y.; Toru, T. Bull. Chem. Soc. Jpn. 1993, 66, 2042.
(5) Corey, E. J.; Oppolzer, W. J. Am. Chem. Soc. 1964, 86,
1899.
(6) Nucleophiles with two acidic protons on the same atom have
been shown to react with vinyl sulfonium salts to give three-
membered rings: (a) Gosselck, J.; Béress, L.; Schenk, H.
Angew. Chem., Int. Ed. Engl. 1966, 5, 596; Angew. Chem.
1966, 78, 606. (b) Johnson, C. R.; Lockard, J. P.
+
198 (100) [Ts(Me)NCH2 ]; trans-isomer (obtained as a
mixture with cis-isomer) as a colorless oil; Rf = 0.40
(EtOAc–PE, 3:7). IR (film): nmax = 1599 (Ar), 1332 (SO2),
1161 (SO2) cm–1. 1H NMR (400 MHz, CDCl3): d = 7.77 (2
H, d, J = 8.3 Hz, ArH), 7.69 (2 H, d, J = 8.3 Hz, ArH), 7.31
(2 H, d, J = 8.3 Hz, ArH), 7.26–7.19 (7 H, m, ArH), 3.85 (1
H, d, J = 3.8 Hz, NCHPh), 3.55 (1 H, dd, J = 14.6, 8.6 Hz,
NCHH), 3.03 (1 H, ddd, J = 8.6, 8.6, 3.8 Hz, NCHCH2N),
2.43 (6 H, s, 2 × CH3), 2.42–2.38 (4 H, m, NCHH and CH3).
13C NMR (100.5 MHz, CDCl3): d = 144.9 (C), 143.6 (C),
136.2 (C), 134.0 (C), 132.0 (C), 129.9 (CH), 129.8 (CH),
128.6 (CH), 128.5 (CH), 127.4 (CH), 127.3 (CH), 126.9
(CH), 49.6 (CH), 49.0 (CH2), 48.8 (CH), 36.5 (CH3), 21.7
(CH3), 21.5 (CH3). MS (CI): m/z (%) = 471 (14) [MH+], 198
Tetrahedron Lett. 1971, 12, 4589. (c) Takaki, K.; Agawa, T.
J. Org. Chem. 1977, 42, 3303. (d) Matsuo, J.; Yamanaka,
H.; Kawana, A.; Mukaiyama, T. Chem. Lett. 2003, 32, 392.
In cases where the nucleophile can be resonance-stabilized
forming enolates, five-membered rings have also been
obtained: (e) Braun, H.; Huber, G. Tetrahedron Lett. 1976,
17, 2121. (f) Batty, J. W.; Howes, P. D.; Stirling, C. J. M. J.
Chem. Soc., Perkin Trans. 1 1973, 65; ref. 6b.
+
(100) [Ts(Me)NCH2 ].
(14) Diethyl 2-Methyl-2-({1-[(4-methylphenyl)sulfonyl]-3-
phenyl-2-aziridinyl}methyl)malonate (Table 3, Entry 3)
cis/trans-Isomers (3:1) as a colorless oil (89%); Rf = 0.30
(EtOAc–PE, 2:8). IR (film): 1761 (OCO), 1162 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d(cis) = 7.85 (2 H, d, J = 8.3
Hz, ArH), 7.32–7.17 (7 H, m, ArH), 4.19–4.02 (4 H, m, 2 ×
OCH2), 3.87 (1 H, d, J = 7.2 Hz, NCHPh), 2.99–2.91 (1 H,
m, NCHCH2), 2.43 (3 H, s, CH3), 1.87 (1 H, dd, J = 14.9, 5.8
Hz, CHH), 1.70 (1 H, dd, J = 14.9, 6.4 Hz, CHH), 1.31 (3 H,
s, CH3), 1.27–1.11 (6 H, m, 2 × CH3). 13C NMR (100.5 MHz,
CDCl3): d = 171.5 (C), 171.4 (C), 144.7 (C), 144.6 (C), 132.4
(C), 129.8 (CH), 129.6 (CH), 128.5 (CH), 128.2 (CH), 127.6
(CH), 61.8 (CH2), 61.6 (CH2), 52.4 (C), 45.1 (CH), 42.7
(CH), 31.1 (CH2), 21.6 (CH3), 19.5 (CH3), 13.9 (CH3), 13.8
(CH3). 1H NMR (400 MHz, CDCl3): d(trans) = 7.78 (2 H, d,
J = 8.3 Hz, ArH), 7.32–7.17 (7 H, m, ArH), 4.19–4.02 (4 H,
m, 2 × OCH2), 3.78 (1 H, d, J = 4.2 Hz, NCHPh), 2.99–2.91
(1 H, m, NCHCH2), 2.49–2.36 (5 H, m, CH2 and CH3), 1.31
(3 H, s, CH3), 1.27–1.11 (6 H, m, 2 × CH3). 13C NMR (100.5
MHz, CDCl3): d = 171.5 (C), 171.4 (C), 144.4 (C), 143.6
(C), 134.8 (C), 129.8 (CH), 128.8 (CH), 128.5 (CH), 127.4
(7) For leading references on aziridination reactions of
sulfonium methylides with imines, see: (a) Aggarwal, V.
K.; Coogan, M. P.; Stenson, R. A.; Jones, R. V. H.;
Fieldhouse, R.; Blacker, J. Eur. J. Org. Chem. 2002, 319.
(b) Aggarwal, V. K.; Stenson, R. A.; Jones, R. V. H.;
Fieldhouse, R.; Blacker, J. Tetrahedron Lett. 2001, 42, 1587.
(8) For leading references on aziridinations with other types of
sulfur ylides, see: (a) McGarrigle, E. M.; Myers, E. L.; Illa,
O.; Shaw, M. A.; Riches, S. L.; Aggarwal, V. K. Chem. Rev.
2007, 107, 5841. (b) Hou, X. L.; Wu, J.; Fan, R. H.; Ding, C.
H.; Luo, Z. B.; Dai, L. X. Synlett 2006, 181. (c) Tang, Y.;
Ye, S.; Sun, X.-L. Synlett 2005, 2720. (d) Aggarwal, V. K.;
Badine, D. M.; Moorthie, V. A. In Aziridines and Epoxides
Synlett 2008, No. 14, 2191–2195 © Thieme Stuttgart · New York

LETTER
Three-Component Aziridination and Epoxidation Reactions
2195
(CH), 126.7 (CH), 61.8 (CH2), 61.7 (CH2), 52.9 (C), 46.2
127.4 (CH), 48.9 (CH), 46.3 (CH), 35.6 (CH2), 21.7 (CH3).
MS (CI): m/z (%) = 396 (3) [MH+], 224 (100) [MH+ –
TsNH2], 155 (16) [Ts+].
(CH), 43.7 (CH), 31.9 (CH2), 21.6 (CH3), 20.7 (CH3), 13.9
(CH3), 13.8 (CH3). MS (CI): m/z (%) = 460 (28) [MH+] , 414
(17) [M+ – EtO], 286 (100) [M+ – C(CO2Et)2Me].
(16) Diethyl 2-(Acetylamino)-2-{[3-(4-methoxyphenyl)-1-(4-
toluene-sulfonyl)-2-aziridinyl]methyl}malonate(Table4,
Entry 8)
(15) 1-(4-Toluenesulfonyl)-2-phenyl-3-[(phenylsul-
fanyl)methyl]aziridine (Table 3, Entry 6)
cis:trans-Isomers (1:5) as a colorless oil (33%); Rf = 0.45
(EtOAc–PE, 3:7). IR (film): 1347 (SO2), 1164 (SO2) cm–1.
1H NMR (400 MHz, CDCl3): d(cis) = 7.58 (2 H, d, J = 8.3
Hz, ArH), 7.35–7.08 (12 H, m, ArH), 4.03 (1 H, d, J = 7.0
Hz, NCHPh), 3.29–3.19 (2 H, m, NCHCHH), 2.62 (1 H, dd,
J = 14.2, 7.0 Hz, CHH), 2.36 (3 H, s, CH3). 13C NMR (100.5
MHz, CDCl3): d = 143.5 (C), 137.0 (C), 135.2 (C), 134.6
(C), 129.8 (CH), 129.7 (CH), 129.1 (CH), 128.8 (CH), 128.1
(CH), 127.7 (CH), 127.1 (CH), 126.6 (CH), 46.2 (CH), 45.1
(CH), 35.4 (CH2), 21.6 (CH3). 1H NMR (400 MHz, CDCl3):
d(trans) = 7.81 (2 H, d, J = 8.3 Hz, ArH), 7.35–7.08 (12 H,
m, ArH), 4.70 (1 H, d, J = 4.2 Hz, NCHPh), 3.73 (1 H, ddd,
J = 7.0, 6.5, 4.2 Hz, NCHCH2), 3.12 (1 H, dd, J = 14.1, 6.5
Hz, CHH), 2.81 (1 H, dd, J = 14.1, 7.0 Hz, CHH), 2.42 (3 H,
s, CH3). 13C NMR (100.5 MHz, CDCl3): d = 144.7 (C), 137.2
(C), 135.0 (C), 134.4 (C), 129.9 (CH), 129.7 (CH), 129.6
(CH), 129.2 (CH), 129.0 (CH), 128.9 (CH), 128.2 (CH),
cis-Isomer as a colorless oil (62%); Rf = 0.40 (EtOAc–PE,
4:6). IR (film): 1762 (OCO), 1160 (SO2) cm–1. 1H NMR (400
MHz, CDCl3): d = 7.79 (2 H, d, J = 8.3 Hz, ArH), 7.29 (2 H,
d, J = 8.3 Hz, ArH), 7.21 (1 H, br s, NH), 6.95 (2 H, d, J =
8.7 Hz, ArH), 6.75 (2 H, d, J = 8.7 Hz, ArH), 4.41–4.09 (4
H, m, 2 × OCH2), 3.74 (1 H, d, J = 7.2 Hz, NCHAr), 3.73 (3
H, s, OCH3), 2.89 (1 H, ddd, J = 10.1, 7.2, 3.7 Hz, NCHCH2),
2.53 (1 H, dd, J = 15.1, 3.7 Hz, CHH), 2.41 (3 H, s, CH3),
2.10 (1 H, dd, J = 15.1, 10.1 Hz, CHH), 2.07 (3 H, s, CH3),
1.33–1.15 (6 H, m, 2 × CH3). 13C NMR (100.5 MHz,
CDCl3): d = 169.7 (C), 167.4 (C), 167.2 (C), 159.5 (C), 144.9
(C), 131.1 (C), 129.8 (CH), 128.5 (CH), 128.1 (CH), 123.8
(C), 114.0 (CH), 65.1 (C), 62.9 (CH2), 62.7 (CH2), 55.3
(CH3), 45.1 (CH), 41.1 (CH), 28.9 (CH2), 23.0 (CH3), 21.8
(CH3), 14.0 (CH3), 13.9 (CH3). MS (CI): m/z (%) = 533 (58)
[MH+], 320 (100) [MH+ – TsNHAc].
Synlett 2008, No. 14, 2191–2195 © Thieme Stuttgart · New York

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