Scope and limitations in sulfur ylide mediated catalytic asymmetric aziridination of imines: Use of phenyldiazomethane, diazoesters and diazoacetamides

Article abstract of DOI:10.1039/b102578n

Imine aziridination using diazo-compounds and catalytic quantities of metal salts and sulfides has been investigated. A range of imines derived from benzaldehyde bearing electron-withdrawing groups (N-Ts,N-SO₂CH₂CH₂SiMe

Full text of DOI:10.1039/b102578n

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Scope and limitations in sulfur ylide mediated catalytic
asymmetric aziridination of imines: use of phenyldiazomethane,
diazoesters and diazoacetamides†
1
Varinder K. Aggarwal,*‡a Marco Ferrara,a Christopher J. O’Brien,a Alison Thompson,a
Ray V. H. Jonesb and Robin Fieldhouseb
a Department of Chemistry, University of Sheffield, Sheffield, UK S3 7HF
b ZENECA Process Technology Department, Earls Road, Grangemouth, UK FK3 8XG
Received (in Cambridge, UK) 20th March 2001, Accepted 21st May 2001
First published as an Advance Article on the web 28th June 2001
Imine aziridination using diazo-compounds and catalytic quantities of metal salts and sulfides has been investigated.
A range of imines derived from benzaldehyde bearing electron-withdrawing groups (N-Ts, N-SO2CH2CH2SiMe3
(SES), N-P(O)Ph2, N-CO2Bn, N-CO2But, N-CO2(CH2)2SiMe3, N-CO2C(CH3)2CCl3) were prepared and tested
in the aziridination process using Me2S and phenyldiazomethane. High yields were obtained with all imines but
diastereoselectivity varied considerably (3 : 1–>10 : 1). A range of N-SES imines were tested with stoichiometric
amounts of sulfides and high yields were obtained with both aromatic and aliphatic imines. These imines were
subsequently tested with stoichiometric and sub-stoichiometric loadings of enantiomerically pure 1,3-oxathiane 3
with Rh2(OAc)4 and with Cu(acac)2. Good yields and high enantioselectivities (89–95%) were observed with
Rh2(OAc)4, although a small reduction in enantiomeric excess was observed with Cu(acac)2 (85–95%) especially
when sub-stoichiometric amounts of sulfide were employed. The same sulfide was also tested with a range of
electron-withdrawing groups on the imine nitrogen and in all cases good yields and high enantioselectivities were
maintained. Improved diastereoselectivity was observed with carbamate groups.
The aziridination process was extended to include diazoester and diazoacetamides with a range of N-Ts imines,
and again good yields were obtained although diastereoselectivity varied according to the diazo-compound
employed. Although the 1,3-oxathiane 3 could not be employed with these more stable diazo-compounds,
(R,R)-2,5-dimethylthiolane 5 was found to be a suitable chiral catalyst and gave moderate enantio- and
diastereoselectivities. Rationales for the origin of the diastereoselectivity and enantioselectivity are provided.
Introduction
In contrast to the well-developed methods for asymmetric
epoxidation1 there are few general methods for asymmetric
aziridination.2 There are a number of stoichiometric routes
to non-racemic aziridines. Atkinson described the addition
of enantiopure acetoxyaminoquinazolines2d to alkenes and
depending on the exact structure of the reagent and the reac-
tion conditions high diastereoselectivity was obtained with a
range of mono and trans disubstituted alkenes (Scheme 1).
Sweeney and co-workers reported the Darzens-type addition
of bromoacyl sultam 1 to imines and obtained the cis- or trans-
aziridines (depending on the substitution of the imine) with
Scheme 1 Atkinson’s aziridination.
a high level of diastereoselectivity relative to the auxilliary
(Scheme 2).3
The addition of simple amines to α-bromo acrylates provides
a complementary route to aziridines and using the Oppolzer
sultam4 or chiral imidazolidin-2-ones5 as a chiral auxiliary,
high levels of stereocontrol have been achieved. Davis and
co-workers6 have reported a Darzens-type reaction of ester
enolates with enantiopure sulfinimines and obtained aziridines
with high diastereoselectivity.
There are two direct routes to aziridines that lend themselves
to asymmetric catalysis: the addition of nitrenoids to alkenes
(route A) and the addition of carbenes/carbenoids to imines
(route B), as shown in Fig. 1.
Scheme 2 Darzens-type addition of a bromoacyl sultam. Reagents
and conditions: (i) RCH᎐NP(O)Ph2, LiHMDS, THF, Ϫ78 ЊC, 47–87%
᎐
yield.
Evans,7 Jacobsen8 and more recently Scott9 and their co-
workers reported processes for asymmetric aziridination of
† Electronic supplementary information (ESI) available: further
experimental details of imine synthesis and determination of enantio-
meric excesses. See http://www.rsc.org/suppdata/p1/b1/b102578n/
‡ Current address: School of Chemistry, Cantock’s Close, Bristol
University, Bristol, UK BS8 1TS. E-mail: V.Aggarwal@Bristol.ac.uk
alkenes using PhI᎐NTs as the nitrene precursor and a chiral
᎐
copper catalyst (Scheme 3).10,11 In the Evans’ case, high enantio-
selectivity was limited to cinnamate esters, and in the Jacobsen
DOI: 10.1039/b102578n
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This journal is © The Royal Society of Chemistry 2001
1635

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Fig. 1 Aziridination strategies.
Scheme 4 Metal carbenoid additions to imines; intermediacy of
azomethine ylides. Reagents: (i) EtO2CCH᎐CHCO2Et.
᎐
Scheme 3 Copper catalysed asymmetric aziridination of alkenes.
and Scott systems high enantioselectivity was achieved with
chromene derivatives. Related studies using chiral rhodium
catalysts have been less successful.12
Although PhI᎐NTs is usually employed, alternative reagents
᎐
have been developed which have more readily cleavable groups
on nitrogen than tosyl thereby enhancing the usefulness of this
asymmetric process.13
Compared to alkene aziridination, the asymmetric addition
of metal carbenoids to imines has met with less success.
Although many metals can catalyse the addition of diazo-
compounds to imines the enantioselectivity observed is often
poor.14,15 In a series of elegant experiments Jacobsen and co-
workers14 (Scheme 4) showed that there were two pathways
which led to the aziridine: one bearing the chiral metal species
which yielded non-racemic aziridine and the second a planar
azomethine ylide which gave racemic aziridine. This was proved
by trapping the azomethine ylide with a dipolarophile. Evi-
dently, the problem with the addition of metal carbenes to
imines is that the C–N bond is formed before the C–C bond
which leads to a planar azomethine ylide. If the C–C bond
could be formed ahead of the C–N bond, then there would be
no possibility of forming the achiral azomethine ylide.
Scheme 5 Wulff ’s asymmetric aziridination.
ylides to enantiopure sulfinimines has also been described but
only moderate diastereoselectivity was achieved.21
We previously reported a new catalytic process involving
sulfur ylides for the conversion of carbonyl compounds
into epoxides22 and described the highly effective use of simple
sulfide 3 for asymmetric epoxidation (Scheme 6).23
We therefore sought to exploit this new process for asym-
metric aziridination24 of imines and in this paper we describe
our results in the development of this process in full.
Such a situation has been achieved in a highly effective chiral
Lewis acid mediated aziridination of imines with ethyl diazo-
acetate using a biaryl boronate catalyst (Scheme 5). Excellent
yields and selectivities were obtained with a range of imines.16
Other chiral Lewis acids have been less successful in asymmetric
aziridination.17
Results
Another approach that allows C–C bond formation ahead of
C–N formation (thus avoiding formation of the planar azo-
methine ylide) is the reaction of a sulfur ylide with an imine.
Indeed sulfonium18 and sulfoxonium ylides19 have been
reported to react with imines to give aziridines although it was
found that sulfonium ylides were more efficient. Dai and co-
workers have reported the use of chiral sulfur ylides derived
from the camphor skeleton and whilst good diastereoselectivity
has been obtained in some cases,20 enantioselectivity was only
moderate. The addition of achiral sulfonium and sulfoxonium
We sought to develop an asymmetric aziridination process
analogous to the epoxidation process using catalytic amounts
of chiral sulfides (Scheme 7). In comparison to epoxidation of
carbonyl compounds, aziridination of imines is more complex
because an extra variable, namely the nature of the group on
the nitrogen has to be considered. As the ultimate step in our
proposed catalytic process is the reaction of a nucleophilic
sulfur ylide with an imine, it was deemed necessary to incor-
porate an electron-withdrawing group on nitrogen to promote
this process. In order to test which electron-withdrawing group
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Table 1 Effect of different nitrogen protecting groups on diastereo-
Table 2 Effect of sulfide structure on the diastereoselectivitya
selectivity with Me2Sa
Entry
Sulfide
R1
trans : cisb
Yield (%)
Entry
R1
trans : cisb
Yield (%)
1
2
3
4
5
6
7
8
Dimethyl sulfide
1,4-Oxathiane
Pentamethylene sulfide
Tetrahydrothiophene
Dimethyl sulfide
1,4-Oxathiane
Pentamethylene sulfide
Tetrahydrothiophene
SES
SES
SES
SES
Moc
Moc
Moc
Moc
3 : 1
4 : 1
3 : 1
92
89
95
84
73
70
95
nd
1
2
3
4
5
6
7
8
Ts
SES
P(O)Ph2
CO2Me
3 : 1
3 : 1
3 : 1
>10 : 1
>10 : 1
>10 : 1
>10 : 1
>10 : 1
82
92
86
73
56
71
85
74
3 : 1
>10 : 1
10 : 1
7 : 1
CO2Bn
CO2CH2CH2TMS
CO2But
4 : 1
CO2C(CH3)2CC13
a All reactions were performed in CH2Cl2 at RT with 1 mol%
Rh2(OAc)4, 1 eq. of sulfide, 1.5 eq. of phenyldiazomethane and 1 eq. of
benzaldimine. b Determined by 1H NMR of the crude reaction mixture.
a All reactions were performed in CH2Cl2 at RT with 1 mol%
Rh2(OAc)4, 1 eq. of dimethyl sulfide, 1.5 eq. of phenyldiazomethane
and 1 eq. of benzaldimine. b Determined by 1H NMR of the crude
reaction mixture.
Table 3 Exploring the range of N-SES imines in aziridinationa
Entry
R
trans : cisb
Yield (%)
1
2
3
4
5
6
7
Ph
p-ClC6H4
p-MeC6H4
3 : 1
3 : 1
3 : 1
3 : 1
2 : 1
1.2 : 1
—
92
88
96
(E)-PhCH᎐CH
67
᎐
But
81
C6H11
68c
<5
Bun
a All reactions were performed in CH2Cl2 at RT with 1 mol%
Rh2(OAc)4, 0.2 eq. of dimethyl sulfide, 1.5 eq. of phenyldiazomethane
and 1 eq. of N-SES imine. b Determined by 1H NMR of the crude
reaction mixture. c 20% of 4 was also obtained.
Scheme 6 Catalytic asymmetric process for epoxidation of aldehydes.
of dimethyl sulfide (20 mol%) and again good yields were
obtained with all of the non-enolisable imines tested, indicating
that we had a process of broad generality (Table 3). The enolis-
able imine derived from cyclohexanecarbaldehyde was also an
effective substrate (Table 3, entry 6), although lower yields of
the corresponding aziridines were obtained together with by-
product 4. Evidently, in this case, following tautomerisation of
the imine, insertion of the metal carbenoid into the NH bond
competes with sulfur ylide formation (Scheme 8). Valeraldimine
Scheme 7 Catalytic process for aziridination of imines.
would be the optimum, a range of imines bearing Ts,25 SES
(SO2CH2CH2SiMe3),25 P(O)Ph2,26 CO2Me,27 CO2Bn,28 CO2-
(CH2)2SiMe3, CO2But28 and TcBoc (CO2C(CH3)2CCl3)27 (see
electronic supplementary information for details) derived from
PhCHO were prepared. With a range of imines in hand we
tested how they performed in aziridination reactions using
reaction conditions that were broadly similar to those used in
the epoxidation reactions (Scheme 7, Table 1).
We were delighted to find that good to high yields were
obtained in all cases although the diastereoselectivity varied
considerably. Whilst large electron-withdrawing groups on
nitrogen only gave moderate trans selectivity (entries 1–3), the
alkoxycarbonyl groups gave high trans selectivity (entries 4–8)
(vide infra). These reactions were conducted with Me2S. We
were also interested to know how changes in the sulfide
structure affected the efficiency and the diastereoselectivity
of the process and so a range of simple sulfides were tested with
N-SES and N-Moc (methoxycarbonyl) imines derived from
PhCHO (Table 2). Whilst all the sulfides gave aziridines in
high yield, we were greatly surprised at how minor variations
in sulfide structure affected the diastereoselectivity in the
reactions of alkoxycarbonyl imines but not of the sulfonyl
imines (vide infra).
Scheme 8 Formation of by-product in aziridination.
only gave traces of the expected product possibly because of its
instability to the reaction conditions or due to tautomerisation
(Table 3, entry 7).
Our next goal was to explore asymmetric aziridination with
chiral sulfides and for this purpose we tested oxathiane 3 which
had worked so well in the related epoxidation process. The
effect of solvent on efficiency, enantioselectivity and diastereo-
selectivity was briefly investigated with the N-Ts imine derived
from benzaldehyde (Table 4). Substantial variation in yield and
enantioselectivity was observed whilst diastereoselectivity was
only marginally affected. Dichloromethane emerged as the
optimum solvent on all counts (entry 1).
Having established CH2Cl2 as the optimum solvent, we
screened a range of N-SES imines with both Rh2(OAc)4 and
Cu(acac)2 under stoichiometric and catalytic loadings of sulfide
(Table 5). From this study a number of general observations
were made.
The process was applied to a range of N-SES imines (these
are the easiest to prepare, the most stable and the SES
group can be easily removed) derived from aromatic, unsatur-
ated and aliphatic aldehydes with substoichiometric amounts
(i) High enantioselectivity was observed with all the imines
studied. The absolute configuration of all the aziridines is
assumed to be (R,R) and this has been proved in the case of the
aziridine derived from N-SES-benzaldimine.24
J. Chem. Soc., Perkin Trans. 1, 2001, 1635–1643
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(ii) Using stoichiometric amounts of sulfide 3, Rh2(OAc)4
and Cu(acac)2 gave similar yields and enantioselectivities,
except for the N-SES-cyclohexanecarbaldimine (vide infra).
(iii) Catalytic amounts of sulfide 3 often resulted in a reduc-
tion in yield compared to the use of stoichiometric amounts of
sulfide 3 with concomitant formation of stilbenes. Stilbenes
arise from the reaction of the metal carbenoid with phenyl-
diazomethane, a reaction which competes with the formation
of the intermediate sulfur ylide (Scheme 9). Reduced sulfide
reactions with sulfur ylides and so direct addition of the copper
carbenoid is minimised. In any case, using Rh2(OAc)4 the
same enantioselectivities are obtained with stoichiometric and
catalytic sulfide loading indicating the absence of direct
addition of the rhodium carbenoid to the imine.
The N-SES-cyclohexanecarbaldimine gave poor results using
catalytic amounts of sulfide with Rh2(OAc)4 or Cu(acac)2, and
the reason for these unexpected results is not known at present
and is currently under investigation.
A number of chiral sulfides have been prepared in our group
and so we screened some representative examples, based on
tetrahydrothiophene (entry 2,29 Table 6), thiane (entry 3,30 Table
6) and 1,3- and 1,4-oxathiane (entries 1 and 4,30 Table 6) to
investigate their effect on yield, diastereoselectivity and enantio-
selectivity by analogy to the series of achiral sulfides we had
used earlier (cf. Table 2). Although these sulfides gave good to
excellent levels of enantioselectivity, there was no advantage in
terms of diastereoselectivity and so 1,3-oxathiane 3 remains the
optimum sulfide in this process.
Another method we have discovered for influencing the
diastereoselectivity is through variation of the group on nitro-
gen. We therefore investigated the reactions of a range of
imines with the 1,3-oxathiane 3 (Table 7). Pleasingly, high
enantioselectivity was maintained with all of the imines studied
without significant variation between them. Furthermore, the
diastereoselectivity improved with alkoxycarbonyl groups com-
pared to sulfonyl groups just as we had observed with dimethyl
sulfide (cf. Table 1). Especially noteworthy is the high diastereo-
selectivity and enantioselectivity observed with Boc and TcBoc
groups as further manipulation of these groups is easy and well
documented (Table 7, entries 6 and 7).31
Scheme
9
Two competing modes of reaction for the rhodium
carbenoid.
loading allows a greater chance for the alternative competing
reaction to occur.
(iv) Although there was no variation in enantioselectivity on
changing from stoichiometric to catalytic loading of sulfide
with Rh2(OAc)4 there was a small reduction in enantioselectiv-
ity with Cu(acac)2. This implies that in the case of Cu(acac)2
there is a very small amount of direct addition of the copper
carbenoid to the imine, which competes with ylide formation.
With reduced sulfide loading there is a greater amount of direct
addition of the copper carbenoid to the imine leading to a
measurable reduction in enantiomeric excess. The direct addi-
tion of the copper carbenoid to the imine is well documented
although its efficiency is strongly dependent on the nature of
the group on the nitrogen: electron-rich imines give good
yields whilst electron-deficient imines give poor yields.15 Fortu-
nately, we require electron-deficient imines to obtain efficient
Origin of diastereoselectivity
Table 4 Effect of solvent on asymmetric aziridination of N-Ts-
benzaldimine using sulfide 3a
The reaction of the phenyl stabilised sulfur ylides with N-Ts
imines has been found to be under kinetic control (i.e. form-
ation of syn- and anti-betaines are irreversible).32 Thus, the
difference in energy between the transition states leading to the
syn- and anti-betaines is responsible for the diastereo- and
enantioselectivity. From calculations it has been suggested that
sulfur ylides react with aldehydes in an ‘‘end-on’’ approach.33
Assuming the same applies to reactions with N-Ts imines, this
would give rise to transition states A and B (Fig. 2), which
lead to trans- and cis-aziridines respectively. It is apparent that
transition state A leading to the trans-aziridines (which is the
major isomer observed) is less hindered than transition state B,
which has all four groups gauche to one another.
Entry
Solvent
trans : cisb
Yield (%)
Ee (%)c
1
2
3
4
5
CH2Cl2
Toluene
DME
1,4-Dioxane
CH3CN
3 : 1
3 : 1
3 : 1
3 : 1
2 : 1
82
41
78
48
41
92
61
60
82
56
a All reactions were performed at RT with 1 mol% Rh2(OAc)4, 0.2 eq. of
chiral sulfide 3, 1.5 eq. of phenyldiazomethane and 1 eq. of N-Ts benz-
aldimine. b Determined by 1H NMR of the crude reaction mixture. c Ee
of trans aziridine determined by HPLC using a Chiralcel OD column.
Table 5 Asymmetric aziridination of N-SES imines with sulfide 3a
Entry
R
Sulfide (eq.)
Metal salt
Yield (%) (trans : cis)b
Ee (%)c
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
1.0
0.2
1.0
0.2
1.0
0.2
1.0
0.2
1.0
0.2
1.0
0.2
1.0
0.2
1.0
0.2
1.0
Rh2(OAc)4
Rh2(OAc)4
Cu(acac)2
Cu(acac)2
Rh2(OAc)4
Rh2(OAc)4
Cu(acac)2
Cu(acac)2
Rh2(OAc)4
Rh2(OAc)4
Cu(acac)2
Cu(acac)2
Rh2(OAc)4
Rh2(OAc)4
Cu(acac)2
Cu(acac)2
Rh2(OAc)4
84 (5 : 1)
47 (3 : 1)
83 (3 : 1)
62 (3 : 1)
88 (3 : 1)
91 (3 : 1)
94 (3 : 1)
50 (3 : 1)
70 (3 : 1)
58 (3 : 1)
77 (3 : 1)
44 (3 : 1)
86 (5 : 1)
62 (5 : 1)
50 (5 : 1)
25 (5 : 1)
72 (1 : 1)
95
95
95
90
95
93
94
88
89
88
89
85
93
93
93
85
89
9
10
11
12
13
14
15
16
17
(E)-PhCH᎐CH
(E)-PhCH᎐CH
(E)-PhCH᎐CH
(E)-PhCH᎐CH
᎐
᎐
᎐
᎐
C6H11
a All reactions were performed in CH2Cl2 at RT with 1 mol% Rh2(OAc)4 or 5 mol% Cu(acac)2, 1.5 eq. of phenyldiazomethane and 1 eq. of imine.
1
b Determined by H NMR of the crude reaction mixture. c Ee of trans aziridine determined by HPLC using a Chiralcel OD column. The absolute
stereochemistry is R,R in all cases.
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Table 6 Effect of sulfide structure on asymmetric aziridinationa
Table 8 Reaction of ethyl diazoacetate with N-Ts benzaldimine using
tetrahydrothiophenea
Entry
Sulfide
trans : cisb
Yield (%)
Ee (%)c
95 (R,R)
95 (R,R)
Entry
R
trans : cisb
Yield (%)
1
2
3
4
p-MeOC6H4
Ph
p-ClC6H4
p-NO2C6H4
C6H11
2 : 3
1 : 3
1 : 5
1 : 12
1 : 11
2 : 1
62
83c
41
54
76
76
1
2
3 : 1
47
34
5
3 : 1
6d
Ph
a All reactions were performed in THF at 60 ЊC with 1 mol%
Rh2(OAc)4, 1 eq. of tetrahydrothiophene, 1.5 eq. of ethyldiazoacetate
and 1 eq. of N-Ts benzaldimine. b Determined by 1H NMR of the crude
reaction mixture. c 57% yield obtained with 0.2 eq. of tetrahydrothio-
phene. d Using N,N-diethyldiazoacetamide.
3
3 : 1
36
79 (S,S)
4
3 : 1
24
77 (R,R)
a All reactions were performed in CH2Cl2 at RT with 1 mol%
Rh2(OAc)4, 0.2 eq. of sulfide, 1.5 eq. of phenyldiazomethane and 1 eq.
of N-Ts benzaldimine. b Determined by 1H NMR of the crude reaction
mixture. c Ee of trans aziridine determined by HPLC using a Chiralcel
OD column.
Table 7 Effect of imine activating groups on aziridination with chiral
sulfide 3a
Entry
R1
trans : cisb
Yield (%)
Ee (%)c
Fig. 3 Model for enantioselectivity.
ation process23 using the same sulfide catalyst (Fig. 3). In this
model, ylide conformer A is favoured over conformer B due to
1,3-diaxial interactions and this conformer reacts with high face
selectivity as a result of both steric (attack opposite the methyl
group) and electronic (a combination of an anomeric effect and
Cieplak effect) control.23 It is believed that the minor enantio-
mer originates from the reaction of the minor conformation
of the ylide B, which again reacts with the same high facial
selectivity.
1
2
3
4
5
6
7
Ts
SES
CO2Me
CO2Bn
3 : 1
3 : 1
6 : 1
6 : 1
9 : 1
9 : 1
>10 : 1
71
84
75
58
55
60
58
92
95
92
90
91
92
92
CO2CH2CH2TMS
CO2But
d
CO2C(CH3)2CC13
a All reactions were performed in CH2Cl2 at RT with 1 mol%
Rh2(OAc)4, 1 eq. of sulfide 3, 1.5 eq. of phenyldiazomethane and 1 eq.
of benzaldimine. b Determined by 1H NMR of the crude reaction
mixture. c Ee of trans aziridine determined by HPLC using a Chiralcel
OD column.d The same results were obtained using 0.2 eq. of 3.
Alternative diazo-compounds
The reactions of alternative diazo-compounds with N-Ts
imines were also investigated and it was found that both diazo-
esters and diazoacetamides34 could be used although higher
temperatures were required to effect decomposition of these
more stable diazo-compounds (Tables 8 and 9). Interestingly
the reactions of diazoesters gave predominantly the cis-
aziridines rather than the trans isomer observed with phenyl-
diazomethane and a range of imines. To understand this reverse
diastereoselectivity with diazoesters several factors need to be
considered. We have recently found that ester-stabilised ylides
react reversibly with imines35 and so the diastereoselectivity
(and enantioselectivity) of the process is controlled in the ring
closure step rather than the betaine-forming step. Thus cis-
aziridines must be thermodynamically more stable than the
corresponding trans isomers. Indeed, this has been verified
experimentally as palladium catalysed isomerisation of
unsaturated aziridines36 and base catalysed isomerisation of
aziridinyl ketones37 give cis-aziridines predominantly. The
thermodynamic preference for the cis-aziridine can be under-
stood in terms of steric hindrance. The largest group on the
three membered ring is the Ts group and this will prefer to be
anti to the other substituents to minimise 1,2 steric interactions.
Thus, the remaining two groups are cis to each other.
Fig. 2 End-on addition of sulfur ylide to imine.
Using this model one can understand the variation in
diastereoselectivity with groups on nitrogen. Large bulky
groups on nitrogen will increase the congestion in the transition
state A leading to reduced trans selectivity. However, small
groups on nitrogen (e.g. alkoxycarbonyl) will be accommodated
in this transition state more easily leading to increased amounts
of the trans isomer. These factors may account for the increased
trans selectivity observed with alkoxycarbonyl groups com-
pared to sulfonyl/phosphinyl groups but does not account for
the variation in diastereoselectivity amongst the different
alkoxycarbonyl groups. This aspect is difficult to explain. The
variation in diastereoselectivity with sulfide structure is also not
easy to explain.
Interestingly, sulfur ylides stabilised by ester groups are too
stable and do not react with aldehydes38 but evidently are suf-
ficiently reactive to react with activated imines. This difference
in reactivity between the two electrophiles can be ascribed to
the difference in position of the equilibria for betaine form-
ation. As epoxides are not obtained there must be at least a
Origin of enantioselectivity
We propose a similar model to account for the enantioselectiv-
ity of aziridination to that we proposed in the related epoxid-
J. Chem. Soc., Perkin Trans. 1, 2001, 1635–1643
1639

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Table 9 Reaction of different diazo-compounds with N-Ts benzald-
imine using chiral sulfide 5
general route to a range of aziridines bearing a variety of
groups on nitrogen. As many of these groups are readily cleaved
(SES, POPh2, CO2Bn, CO2But, CO2(CH2)2SiMe3, CO2C(CH3)2-
CCl3) this process offers certain advantages over alkene azirid-
ination where the Ts group is usually the group attached to
nitrogen. Considerable variation in diastereoselectivity was
observed in relation to the activating group on nitrogen, with
alkoxycarbonyl groups providing higher diastereoselectivity
than the much larger sulfonyl or phosphinyl groups. This
improved diastereoselectivity has been rationalised by consider-
ing the steric interactions present in the transition state.
The chiral 1,3-oxathiane 3 was tested in the aziridination
process and good yields and high enantioselectivities were
achieved with a range of N-SES imines. Rh2(OAc)4 provided
slightly higher enantioselectivities than Cu(acac)2 especially
when substoichiometric loadings of sulfide were employed.
This was believed to be due to a small amount of direct
addition of the copper carbenoid to the imine, a reaction that
can begin to compete with ylide formation at low sulfide con-
centrations. The same sulfide was also employed with imines
bearing a variety of activating groups. Good yields and high
enantioselectivities were maintained and as with simple sulfides,
improved diastereoselectivities were observed with alkoxy-
carbonyl groups.
Entry
Ra
X
trans : cisb
Yield (%)
Ee (%)c
1
2
3
4
5
6
p-MeOC6H4
Ph
p-ClC6H4
p-NO2C6H4
C6H11
OEt
OEt
OEt
OEt
OEt
NEt2
2 : 3
1 : 3
1 : 5
1 : 12
1 : 11
1 : 1
53
80d
72
83
76
98
45
58
54
56
44
30
Ph
a All reactions were performed with 1 mol% Rh2(OAc)4, 1 eq. of chiral
sulfide 5, 1.5 eq. of diazo compound in THF at 60 ЊC. b Diastereomeric
ratios were determined by 1H NMR of the crude reaction mixture. c Ee
of cis aziridine determined by HPLC using a Chiralcel OD column.
d 0.2 eq. of chiral sulfide 5.
Extension of the methodology to include the use of diazo-
esters and diazoacetamides with tetrahydrothiophene was also
successful. N,N-Diethyldiazoacetamide gave predominantly
trans-aziridines whilst ethyl diazoacetate gave cis-aziridines
preferentially. The cis selectivity is due to the reversible addition
of the ester-stabilised ylide to the imine, which leads to the
thermodynamically more stable cis-aziridine. Although the 1,3-
oxathiane 3 was not a suitable sulfide with these more stable
diazo-compounds, trans-(R,R)-2,5-dimethylthiolane provided
the corresponding compounds in good yield and with moderate
enantioselectivity.
The process described herein provides a potentially useful
method for the asymmetric aziridination of imines using
phenyldiazomethane, although new chiral sulfides are required
to extend this asymmetric process to include diazoesters and
diazoacetamides. Nevertheless we have demonstrated that it is
possible to use such diazo-compounds in this catalytic process,
thus providing access to more functionalised aziridines.
Scheme 10 Stabilised ylide reacting with aldehyde/imine.
factor of 102 difference in the position of the equilibrium
relative to imines (Scheme 10). The weaker π-bond strength of
imines relative to aldehydes (average bond strengths: 296 vs. 372
kJ molϪ1 respectively39) together with the lower pKa of NH2Ts
relative to HOPri (16.1 and 30.25 respectively in DMSO40) will
both contribute to a greater equilibrium concentration of
betaine in the case of the reaction with imines relative to alde-
hydes. Clearly the position of the equilibrium will also be
affected by reaction conditions. Indeed, Dai and co-workers
have reported that no reaction occurred between the same ester-
stabilised sulfonium ylide and imine in the presence of metal
salts.41
Unfortunately, oxathiane 3 was not compatible with the
use of these more stable diazo compounds. However, 2,5-
dimethyltetrahydrothiophene 529 was a suitable catalyst and
moderate enantioselectivity was obtained with a range of
imines (Table 9).
Experimental
Flash chromatography was performed on silica gel (Merck
Kiesegel 60 F254 230–400 mesh) and TLC on aluminium backed
silica plates (60 F254). Melting points were determined on a
Köfler hot stage. Infrared spectra were recorded on a Perkin-
Elmer 157G Grating FT-IR spectrometer. Only selected
absorbances (νmax) are reported. 1H NMR spectra were
recorded at either 250 or 400 MHz, on Bruker AC-250 or
Bruker AM-400 instruments, respectively. Chemical shifts (δH)
are quoted in parts per million (ppm), referenced to the
appropriate residual solvent peak, and J values are given in Hz.
13C NMR spectra were recorded at either 63 or 101 MHz on
Bruker AC-250 or Bruker AM-400 instruments, respectively.
Chemical shifts (δC) are quoted in parts per million (ppm),
referenced to the appropriate solvent peak. Low resolution
mass spectra (m/z) were recorded on either VG Platform or VG
Prospec spectrometers, with only molecular ions (Mϩ), and
major peaks being reported with intensities quoted as percent-
ages of the base peak. High-resolution mass spectra were
recorded on a VG Prospec spectrometer. Microanalyses were
performed using a Perkin Elmer 2400 CHN elemental analyzer.
Diazoacetamides were also successfully used in the aziridin-
ation process but only low selectivity with chiral sulfide 5 was
observed (Table 9, entry 6). Alternative chiral sulfides are
clearly required for the asymmetric aziridination process with
these more stable diazo-compounds.
Conclusion
We have found that imines bearing electron-withdrawing
groups on nitrogen are excellent substrates for aziridination
using phenyldiazomethane and catalytic quantities of Rh2-
(OAc)4 and sulfides (e.g. Me2S). This provides a versatile and
General procedure for the preparation of aziridines using
phenyldiazomethane
To a stirred solution of sulfide (1.0 or 0.2 eq., 0.5 or 0.1 mmol),
1640
J. Chem. Soc., Perkin Trans. 1, 2001, 1635–1643

View Article Online
rhodium acetate (0.01 eq., 5 µmol) or copper acetoacetate (0.05
eq., 25 µmol) and imine (1.0 eq., 0.5 mmol) in solvent (0.5 mL),
was added a solution of phenyldiazomethane (1.5 eq., 0.75
mmol) in solvent (0.5 mL) at room temperature via syringe
pump over 3 hours. After a further hour, the solvent was
removed in vacuo and the residue absorbed onto silica gel.
Chromatography, eluting with petroleum ether–EtOAc gave the
corresponding aziridine.
65.41; H, 7.05; N, 3.63%); νmax(KBr)/cmϪ1 1141 (SO2N), 969
(Si(CH3)3); m/z (EI) 385 (Mϩ, 25%), 220 (100, Mϩ Ϫ SES)
(Found: Mϩ, 385.1524. C21H27NO2SSi requires 385.1532). trans:
Rf 0.48 (90 : 10 petroleum ether–EtOAc); δH(250 MHz; CDCl3)
0.00 (9H, s, Si(CH3)3), 1.00–1.35 (2H, m, CH2Si), 3.00–
3.30 (2H, m, SO CH ), 3.50 (1H, dd, J 10, 4, PhHC᎐CH-
᎐
2
2
HCCHPh), 4.05 (1H, d, J 4, PhHC᎐CH-HCCHPh), 6.55
᎐
(1H, dd, J 14, 10, PhHC᎐CH-HCCHPh), 6.90 (1H, d, J 14,
᎐
PhHC᎐CHCCHPh), 7.20–7.50 (10H, m, Ar); δ (63 MHz;
᎐
C
N-Tosyl-2,3-diphenylaziridine.7 White solid as a mixture of
cis and trans. trans: Rf 0.30 (90 : 10 petroleum ether–EtOAc);
δH(250 MHz; CDCl3) 2.38 (3H, s, ArCH3), 4.24 (2H, s,
2 × CHPh), 7.00–7.10 (10H, m, Ar), 7.34 (2H, m, Ar), 7.98
(2H, m, Ar). cis: Rf 0.32 (90 : 10 petroleum ether–EtOAc);
δH(250 MHz; CDCl3) 2.42 (3H, s, ArCH3), 4.21 (2H, s,
2 × CH), 7.22 (2H, m, Ar), 7.30–7.44 (10H, m, Ar), 7.60 (2H,
m, Ar).
CDCl3) Ϫ2.1, 9.9, 48.9, 50.9, 54.5, 122.2, 126.3, 126.8, 128.3,
128.5, 128.6, 128.8, 137.7. cis Rf 0.49 (90 : 10 petroleum ether–
EtOAc); δH(250 MHz; CDCl3) 0.10 (9H, s, Si(CH3)3), 1.00–1.35
(2H, m, CH2Si), 3.10–3.25 (2H, m, SO2CH2), 3.50 (1H,
m, PhHC᎐CH-HCCHPh), 4.05 (1H, d, J 7, PhHC᎐CH-
᎐
᎐
HCCHPh), 6.55 (1H, dd, J 12, 10, PhHC᎐CH-HCCHPh), 6.90
᎐
(1H, d, J 12, PhHC᎐CHCCHPh), 7.20–7.50 (10H, m, Ar).
᎐
N-(ꢀ-Trimethylsilylethylsulfonyl-2-tert-butyl-3-phenylazirid-
ine. trans as a white solid: Rf 0.45 (90 : 10 petroleum ether–
EtOAc); mp 110 ЊC; νmax(KBr)/cmϪ1 1313 (SO2N), 1252
(Si(CH3)3), 1144 (SO2N), 952 (Si(CH3)3); δH(250 MHz; CDCl3)
0.00 (H, s, Si(CH3)3), 1.04 (9H, s, C(CH3)3), 1.04–1.15 (2H, m,
CH2Si), 2.75–2.88 (2H, m, SO2CH2), 3.46 (1H, d, J 4, CHCH),
3.75 (1H, d, J 4, CHCH), 7.30–7.36 (3H, m, Ar), 7.45–7.52
(2H, m, Ar); δC(62.9 MHz; CDCl3) (one quaternary carbon
signal not visible) Ϫ2.1, 9.6, 26.5, 48.3, 50.5, 53.3, 128.2, 129.0,
130.1; m/z (CI) 340 (MHϩ, 44%), 324 (51, Mϩ Ϫ CH3), 174
(100, Mϩ Ϫ SES), 73 (Si(CH3)3, 98) (Found: MHϩ, 340.1759.
C17H30NO2SiS requires m/z, 340.1767). cis: Rf 0.59 (90 : 10
petroleum ether–ethyl acetate); δH(250 MHz; CDCl3) 0.00 (9H,
s, Si(CH3)3), 0.72 (9H, s, C(CH3)3), 1.20–1.27 (2H, m, CH2Si),
2.72 (1H, d, J 6, CHCH), 3.08–3.15 (2H, m, SO2CH2), 3.78
(1H, d, J 6, CHCH), 7.20–7.38 (5H, m, Ar); δC(63 MHz;
CDCl3) Ϫ2.0, 9.9, 27.7, 32.1, 46.0, 48.8, 53.4, 127.6, 128.0,
128.3, 128.7.
N-(ꢀ-Trimethylsilylethylsulfonyl)-2,3-diphenylaziridine. White
solid as a mixture of cis and trans (Found: C, 63.63; H, 6.87; N,
3.91. C19H25NO2SSi requires C, 63.61; H, 6.96; 3.90%);
νmax(KBr)/cmϪ1 1246 (Si(CH3)3), 1142 (SO2N); m/z (EI) 359
(Mϩ, 20%), 344 (96, Mϩ Ϫ CH3), 196 (100, Mϩ Ϫ SES), 73
(Si(CH3)3, 100). trans: Rf 0.35 (90 : 10 petroleum ether–EtOAc);
δH(250 MHz; CDCl3) 0.01 (9H, s, Si(CH3)3), 0.93–1.20 (2H, m,
CH2Si), 2.95–3.10 (2H, m, SO2CH2), 4.26 (2H, s, 2 × CH),
7.35–7.60 (10H, m, Ar); δC(63 MHz; CDCl3) Ϫ2.1, 9.8, 50.6,
51.6, 128.1, 128.6, 128.9, 133.4. cis: Rf 0.37 (90 : 10 petroleum
ether–EtOAc); δH(250 MHz; CDCl3) 0.13 (9H, s, Si(CH3)3),
1.16–1.25 (2H, m, CH2Si(CH3)3), 3.15–3.25 (2H, m, SO2CH2),
4.27 (2H, s, 2 × CH), 7.32–7.59 (10H, m, Ar).
N-(ꢀ-Trimethylsilylethylsulfonyl)-2-(p-chlorophenyl)-3-
phenylaziridine. White solid as a mixture of cis and trans
(Found: C, 57.73; H, 6.16; N, 3.32. C19H24ClNO2SSi requires C,
57.94; H, 6.10; 3.56%); νmax(KBr)/cmϪ1 1250 (Si(CH3)3), 1143
(SO2N); m/z (FAB) 394 (Mϩ, 21%), 228 (100, Mϩ – SES)
(Found: Mϩ, 394.1071. C19H25ClO2SSi requires 394.1064).
trans: Rf 0.40 (90 : 10 petroleum ether–EtOAc); δH(250 MHz;
CDCl3) 0.01 (9H, s, Si(CH3)3), 1.15–1.19 (2H, m, CH2Si), 2.96–
3.08 (2H, m, SO2CH2), 4.15 (1H, d, J 5, CHCH), 4.22 (1H, d,
J 5, CHCH), 7.10–7.28 (2H, m, Ar), 7.35–7.54 (7H, m, Ar);
δC(63 MHz; CDCl3) Ϫ2.1, 9.7, 50.1, 50.3, 51.5, 127.9, 128.8,
129.0, 129.7, 133.2. cis: Rf 0.42 (90 : 10 petroleum ether–
EtOAc); δH(250 MHz; CDCl3) 0.14 (9H, s, Si(CH3)3), 0.76–1.30
(2H, m, CH2Si), 3.24–3.35 (2H, m, SO2CH2), 4.15–4.28 (2H, m,
2 × CH), 7.35–7.62 (9H, m, Ar).
N-(ꢀ-Trimethylsilylethylsulfonyl)-2-cyclohexyl-3-phenyl-
aziridine. trans as a white solid: Rf 0.37 (15 : 1 petroleum
ether–EtOAc); mp 110–112 ЊC (Found: C, 62.39; H, 8.78; N,
3.74. C19H31NO2SSi requires C, 62.42; H, 8.55; N, 3.83%);
νmax(CDCl3)/cmϪ1 1320 (SO2N), 1253 (Si(CH3)3), 1142 (SO2N);
δH(250 MHz; CDCl3) 0.00 (9H, s, Si(CH3)3), 0.90–2.10 (12H,
m), 2.38–2.50 (1H, m, CH2CHCH2), 2.72 (1H, dd, J 8, 4,
PhCHCH), 3.05–3.14 (2H, m, SO2CH2), 3.70 (1H, d, J 4,
PhCHCH), 7.28–7.45 (5H, m, Ar); δC(101 MHz; CDCl3)
Ϫ2.2, 10.0, 25.3, 25.6, 26.0, 31.5, 32.1, 37.8, 47.8, 51.1, 58.3,
126.4, 128.2, 128.6, 135.7; m/z (CI) 366 (MHϩ, 80%), 350
(75, Mϩ Ϫ CH3), 200 (100) (Found: MHϩ, 366.1927.
C19H32NO2SSi requires 366.1923). cis as a colourless oil: Rf 0.31
(15 : 1 petroleum ether–EtOAc); νmax(CDCl3)/cmϪ1 2931, 1322
(SO2N), 1253 (Si(CH3)3), 1142 (SO2N); δH(250 MHz; CDCl3)
0.00 (9H, s, Si(CH3)3), 0.85–1.60 (9H, m), 1.65–1.74 (1H, m),
1.75–1.92 (1H, m), 2.05–2.12 (1H, m), 2.18–2.28 (1H, m), 2.73
(1H, dd, J 8, 6, PhCHCH), 3.06–3.14 (2H, m, SO2CH2), 3.84
(1H, d, J 6, PhCHCH), 7.25–7.31 (5H, m, Ar); δC(101 MHz;
CDCl3), Ϫ2.1, 9.8, 25.1, 25.2, 26.0, 29.0, 31.2, 34.5, 45.9, 48.7,
50.2, 127.3, 128.3, 133.1; m/z (CI) 366 (MHϩ, 80%), 350 (100,
Mϩ Ϫ CH3) (Found: MHϩ, 366.1926. C19H32NO2SSi requires
366.1923).
N-(ꢀ-Trimethylsilylethylsulfonyl)-2-(p-methylphenyl)-3-
phenylaziridine. White solid as a mixture of cis and trans
(Found: C, 64.17; H, 7.05; N, 3.66. C20H27NO2SSi requires C,
64.34; H, 7.24; 3.75%); νmax(KBr)/cmϪ1 1170 (SO2N), 918
(Si(CH3)3). trans: m/z (FAB) 374 (Mϩ, 21%), 208 (100,
Mϩ Ϫ SES) (Found: Mϩ, 374.1617. C20H27NO2SSi requires
374.1610); δH(250 MHz; CDCl3) 0.00 (9H, s, Si(CH3)3), 0.90–
1.15 (2H, m, CH2Si), 2.42 (3H, s, ArCH3), 2.96–3.18 (2H, m,
SO2CH2), 4.18 (1H, d, J 5, CHCH), 4.28 (1H, d, J 5, CHCH),
7.25 (2H, m, Ar), 7.31–7.58 (7H, m, Ar); δC(63 MHz; CDCl3)
Ϫ2.1, 9.7, 21.3, 49.9, 51.1, 51.4, 127.9, 128.3, 128.6, 128.7,
129.3. cis: m/z (FAB) 208 ((M Ϫ SES)ϩ, 100) (Found: Mϩ,
374.1617. C20H27NO2SSi requires 374.1610); δH(250 MHz;
CDCl3) 0.14 (9H, s, Si(CH3)3), 1.14–1.23 (2H, m, CH2Si), 2.22
(3H, s, ArCH3), 3.13–3.22 (2H, m, SO2CH2), 4.20 (1H, d, J 7,
CHCH), 4.30 (1H, d, J 7, CHCH), 6.90–7.18 (9H, m, Ar);
δC(63 MHz; CDCl3) Ϫ2.0, 9.8, 21.1, 46.9, 47.1, 49.1, 127.7,
127.8, 128.1, 128.8, 129.0, 132.2, 137.6.
N-Benzyl-N-cyclohexylidenemethyl-2-trimethylsilylethane-
sulfonamide (4). White solid: Rf 0.31 (15 : 1 petroleum ether–
EtOAc); mp 110–112 ЊC; νmax(CDCl3)/cmϪ1 1333 (SO2N), 1252
(Si(CH3)3), 1143 (SO2N) (Found: C, 62.19; H, 8.68; N, 3.35.
C19H31NO2SSi requires C, 62.42; H, 8.55; N, 3.83%); δH(250
MHz; CDCl3) 0.00 (9H, s, Si(CH3)3), 1.01 (2H, m, SiCH2),
1.06–1.43 (6H, m, CH2CH2CH2CH2CH2), 1.94–2.04 (4H, m,
CH2CCH2), 2.87 (2H, m, SO2CH2), 4.38 (2H, s, CH2N), 5.40
(1H, br s, CHN), 7.23–7.31 (5H, m, Ar); δC(63 MHz; CDCl3)
Ϫ1.9, 9.9, 26.2, 26.6, 27.9, 28.7, 33.2, 46.9, 54.9, 117.2, 127.7,
N-(ꢀ-Trimethylsilylethylsulfonyl)-2-phenyl-3-[(E)-2-phenyleth-
1-enyl]aziridine. White solid as a mixture of cis and trans
(Found: C, 65.26; H, 7.07; N, 3.85. C21H27NO2SSi requires C,
J. Chem. Soc., Perkin Trans. 1, 2001, 1635–1643
1641

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128.3, 129.2, 136.5, 148.4 (Ar); m/z (EI) 365 (Mϩ, 29%), 200
(59), 91 (C7H7ϩ, 82), 73 (Si(CH3)3, 100) (Found: Mϩ, 365.1843.
C19H31NO2SSi requires 365.1845).
s, CH3), 3.76 (2H, s, 2 × PhCH), 7.20–7.30 (10H, m, Ar);
δC(63 MHz, CDCl3) 20.7, 21.2, 48.2, 89.4, 105.6, 128.4, 128.6,
128.8, 135.2, 158.0. cis: Rf 0.29 (93 : 7 petroleum ether–EtOAc);
δH(250 MHz, CDCl3) 1.65 (6H, s, 2 × CH3), 3.95 (2H, s,
2 × PhCH), 7.10–7.25 (10H, m, Ar).
N-Diphenylphosphinoyl-2,3-diphenylaziridine. White solid as
a mixture of cis and trans. νmax(KBr)/cmϪ1 1204 (P᎐O); m/z
᎐
(FAB) 396 (MHϩ, 100%) (Found: MHϩ 396.1514. C26H23NOP
requires 396.1517). trans: Rf 0.24 (95 : 5 petroleum ether–
EtOAc); δH(250 MHz; CDCl3) 4.10 (2H, d, J 15, 2 × PhCH),
7.23–7.54 (16H, m, Ar), 7.55–7.66 (2H, m, Ar), 7.81–7.95 (2H,
m, Ar); δC(63 MHz; CDCl3) 47.1, 47.2, 127.8, 128.0, 128.1,
128.2, 128.4, 128.6, 131.3, 131.5, 131.6, 131.8, 132.1; δP(250
MHz; CDCl3) 28.1. cis: Rf 0.26 (95 : 5 petroleum ether–EtOAc);
δH(250 MHz; CDCl3) 4.23 (2H, d, J 16, 2 × CHPh), 7.23–7.54
(20H, m, Ar); δP(250 MHz; CDCl3) 34.0.
General procedure for the preparation of aziridines using
alternative diazo compounds
To a stirred solution of sulfide (1.0 or 0.2 eq., 0.5 or 0.1 mmol),
rhodium acetate (0.01 eq., 5 µmol) and imine (1.0 eq., 0.5
mmol) in THF (0.5 mL), was added a solution of diazo com-
pound (1.5 eq., 0.75 mmol) in THF (0.5 mL) via syringe pump
over 3 hours at 60 ЊC. After a further hour, the solvent was
removed in vacuo and the residue absorbed onto silica gel.
Chromatography eluting with petroleum ether–EtOAc gave the
corresponding aziridine.
N-(Methoxycarbonyl)-2,3-diphenylaziridine. Viscous colour-
less oil as a mixture of cis and trans. νmax(CDCl3)/cmϪ1 1700
(C᎐O); m/z (EI) 253 (Mϩ, 10%), 194 ((M Ϫ CO Meϩ), 100)
N-Tosyl-2-ethoxycarbonyl-3-(4-methoxyphenyl)aziridine.
Viscous colourless oil as a mixture of cis and trans. Rf 0.30
(90 : 10 petroleum ether–EtOAc); νmax(CDCl3)/cmϪ1 1741
᎐
2
(Found: Mϩ, 253.1105. C16H15NO2 requires 253.1103). trans: Rf
0.29 (90 : 10 petroleum ether–EtOAc); δH(250 MHz; CDCl3)
3.50 (3H, s, OCH3), 3.70 (2H, s, 2 × PhCH), 7.20–7.45 (10H,
m, Ar); δC(63 MHz; CDCl3) 48.4, 53.3, 126.4, 128.2, 128.6,
135.4, 160.9. cis: Rf 0.28 (90 : 10 petroleum ether–EtOAc);
δH(250 MHz; CDCl3) 3.75 (3H, s, OCH3), 3.92 (2H, s, CH),
7.00–7.20 (10H, m, Ar).
(C᎐O); m/z (EI) 376 (MHϩ, 40%), 222 (100) (Found: MHϩ,
᎐
376.1204. C19H22NO5S requires 376.1218). trans: δH(250 MHz;
CDCl3) 1.25 (3H, t, J 7, CH3CH2O), 2.30 (3H, s, CH3Ar), 3.75–
4.90 (7H, m, CH-CH, CH2CH3, CH3O), 6.80 (2H, m, Ar), 7.15
(2H, m, Ar), 7.60 (2H, m, Ar), 7.90 (2H, m, Ar). cis: δH(250
MHz; CDCl3) 0.95 (3H, t, J 7, CH3CH2O), 2.32 (3H, s,
CH3Ar), 3.55 (1H, d, J 7, CH-CH), 3.65 (3H, s, CH3O), 3.75–
3.95 (2H, m, CH2CH3), 3.98 (1H, d, J 7, CH-CH), 6.75 (2H, m,
Ar), 7.10 (2H, m, Ar), 7.25 (2H, m, Ar), 7.85 (2H, m, Ar); δC(63
MHz; CDCl3) (quaternary carbons not observed) 13.8, 21.7,
43.5, 45.0, 55.2, 61.5, 113.6, 128.1, 128.7, 129.8.
N-(Benzyloxycarbonyl)-2,3-diphenylaziridine. White solid as
a mixture of cis and trans (Found: C, 80.24; H, 5.77; N, 4.25.
C22H19NO2 requires C, 80.23; H, 5.96; N, 4.25%); νmax(CDCl3)/
cmϪ1 1719 (C᎐O); m/z (EI) 329 (Mϩ, 10%), 194 (100,
᎐
Mϩ Ϫ CO2Bn) (Found: Mϩ, 329.1414. C22H19NO2 requires
329.1416). trans: Rf 0.31 (90 : 10 petroleum ether–EtOAc);
δH(250 MHz; CDCl3) 3.75 (2H, s, 2 × PhCH), 4.95–5.15 (2H,
AB system, CH2), 6.90 (2H, m, Ar), 7.10–7.40 (13H, m, Ar);
δC(63 MHz; CDCl3) 48.4, 68.2, 126.6, 126.6, 128.2, 128.3, 128.4,
128.6, 129.2, 135.4, 162.0. cis: Rf 0.30 (90 : 10 petroleum ether–
EtOAc); δH(250 MHz, CDCl3) 3.90 (2H, s, 2 × PhCH), 5.20
(2H, s, CH2), 7.00–7.40 (15H, m, Ar).
N-Tosyl-2-ethoxycarbonyl-3-phenylaziridine. Viscous oil as a
mixture of cis and trans. Rf 0.30 (90 : 10 petroleum ether–
EtOAc); νmax(CDCl3)/cmϪ1 1743 (C᎐O); m/z (EI) 345 (MHϩ,
᎐
11%), 190 (100, Mϩ Ϫ Ts), 117 (87) (Found: Mϩ, 345.1025.
C18H19NO4S requires 345.1025). trans: δH(250 MHz; CDCl3)
1.35 (3H, t, J 7, CH3CH2O), 2.35 (3H, s, CH3Ar), 3.45 (1H, d,
J 4, CHCH), 4.15–4.35 (2H, m, CH2CH3), 4.40 (1H, d, J 4,
CHCH), 7.10–7.20 (7H, m, Ar), 7.90 (2H, m, Ar). cis: δH(250
MHz; CDCl3) 0.85 (3H, t, J 7, CH3CH2O), 2.40 (3H, s, CH3-
Ar), 3.60 (1H, d, J 7, CHCH), 3.75–4.00 (2H, m, CH2CH3),
4.05 (1H, d, J 7, CHCH), 7.10–7.20 (5H, m, Ar), 7.25 (2H, m,
Ar), 7.90 (2H, m, Ar); δC(63 MHz; CDCl3) (one quaternary
carbon and carbonyl not observed) 14.0, 21.6, 47.1, 47.7, 62.5,
127.4, 127.5, 128.6, 128.9, 129.6, 132.7, 137.2.
N-(ꢀ-Trimethylsilylethoxycarbonyl)-2,3-diphenylaziridine.
Viscous colourless oil as
a mixture of cis and trans.
νmax(CDCl3)/cmϪ1 1714 (C᎐O); m/z (EI) 340 (MHϩ, 10%), 194
᎐
(Mϩ Ϫ CO2CH2CH2SiMe3, 100) (Found: Mϩ, 339.1670.
C20H25NO2Si requires 339.1655). trans: Rf 0.32 (90 : 10 petrol-
eum ether–EtOAc); δH(250 MHz, CDCl3) 0.00 (9H, s,
Si(CH3)3), 0.65–0.95 (2H, m, CH2Si), 3.75 (2H, s, 2 × PhCH),
4.00–4.25 (2H, m, CH2O), 7.25–7.50 (10H, m, Ar); δC(63 MHz,
CDCl3) Ϫ1.6, 17.3, 48.2, 64.9, 126.7, 128.2, 128.6, 129.3, 161.0.
cis: Rf 0.30 (90 : 10 petroleum ether–EtOAc); δH(250 MHz;
CDCl3) 0.10 (9H, s, Si(CH3)3), 1.20–1.45 (2H, m, CH2Si), 4.25
(2H, s, 2 × PhCH), 4.30–4.45 (2H, m, CH2O), 7.15–7.25 (10H,
m, Ar).
N-Tosyl-2-ethoxycarbonyl-3-(4-chlorophenyl)aziridine.
Viscous colourless oil as a mixture of cis and trans. Rf 0.30
(90 : 10 petroleum ether–EtOAc); νmax(CDCl3)/cmϪ1 1744
(C᎐O); m/z (EI) 380 (MHϩ, 15%), 226 (100) (Found: MHϩ,
᎐
380.0724. C18H19NO4SCl requires 380.0723). trans: δH(250
MHz; CDCl3) 1.25 (3H, t, J 7, CH3CH2O), 2.35 (3H, s,
CH3Ar), 3.45 (1H, d, J 4, CH-CH), 4.00–4.30 (2H, m,
CH2CH3) 4.35 (1H, d, J 4, CH-CH), 7.15–7.25 (6H, m, Ar),
7.70 (2H, m, Ar). cis: δH(250 MHz; CDCl3) 0.95 (3H, t, J 7,
CH3CH2O), 2.35 (3H, s, CH3Ar), 3.55 (1H, d, J 7, CH-CH),
3.75–3.95 (2H, m, CH2CH3), 4.00 (1H, d, J 7, CH-CH), 7.15
(4H, m, Ar), 7.25 (2H, m, Ar), 7.85 (2H, m, Ar); δC(63 MHz;
CDCl3) (quaternary Ar carbons not observed) 13.8, 21.7, 43.4,
44.5, 61.7, 128.1, 128.4, 128.9, 129.9.
N-(tert-Butoxycarbonyl)-2,3-diphenylaziridine.
Colourless
viscous oil as a mixture of cis and trans. νmax(CDCl3)/cmϪ1 1716
(C᎐O); m/z (CIϩ) 296 (MHϩ, 10%), 219 (100) (Found: Mϩ,
᎐
295.1561. C19H21NO2 requires 295.1572). trans: Rf 0.33 (90 : 10
petroleum ether–EtOAc); δH(250 MHz; CDCl3) 1.20 (9H, s,
OC(CH3)3), 3.75 (2H, s, 2 × PhCH), 7.20–7.30 (10H, m, Ar);
δC(63 MHz; CDCl3) 27.6, 47.6, 81.4, 127.0, 127.8, 128.5, 135.5,
156.4. cis: Rf 0.32 (90 : 10 petroleum ether–EtOAc); δH(250
MHz; CDCl3) 1.45 (9H, s, OC(CH3)3), 3.80 (2H, s, 2 × PhCH),
7.00 (15H, m, Ar).
N-Tosyl-2-ethoxycarbonyl-3-(4-nitrophenyl)aziridine. Viscous
pale yellow oil as a mixture of cis and trans. Rf 0.30 (90 : 10
petroleum ether–EtOAc) (Found: C, 53.36; H, 4.80; N,
7.01. C18H18N2O6S requires C, 53.38; H, 4.63; N, 7.18%);
N-(2-Trichloromethylisopropoxycarbonyl)-2,3-diphenyl-
aziridine. Pale yellow viscous oil as a mixture of cis and trans.
νmax(CDCl3)/cmϪ1 1712 (C᎐O); m/z (EI) 397 (Mϩ, 35%), 194
νmax(CDCl3)/cmϪ1 1741 (C᎐O); m/z (EI) 390 (Mϩ, 5%), 235
᎐
᎐
(100, Mϩ Ϫ TcBoc) (Found: Mϩ, 397.0403. C19H18NO2Cl3
requires 397.0391). trans: Rf 0.31 (93 : 7 petroleum ether–
EtOAc); δH(250 MHz, CDCl3) 1.50 (3H, s, CH3), 1.80 (3H,
((M Ϫ Ts)ϩ, 100) (Found: Mϩ, 390.0900. C18H18N2O6S requires
390.0886). trans: δH(250 MHz; CDCl3) 1.25 (3H, t, J 7,
CH3CH2O), 2.35 (3H, s, CH3Ar), 3.45 (1H, d, J 4, CH-CH),
1642
J. Chem. Soc., Perkin Trans. 1, 2001, 1635–1643

View Article Online
6 (a) F. A. Davis and W. McCoull, Tetrahedron. Lett., 1999, 40, 249;
(b) F. A. Davis, H. L. Ping Zhou, T. Fang, G. V. Reddy and Y. Zhang,
J. Org. Chem., 1999, 64, 7559.
7 (a) D. A. Evans, M. M. Faul, M. T. Bilodeau, B. A. Anderson and
D. M. Barnes, J. Am. Chem. Soc., 1993, 115, 5328; (b) D. A. Evans,
M. M. Faul and M. T. Bilodeau, J. Am. Chem. Soc., 1994, 116, 2742.
8 (a) Z. Li, K. R. Conser and E. N. Jacobsen, J. Am. Chem. Soc., 1993,
115, 5326; (b) Z. Li, R. W. Quan and E. N. Jacobsen, J. Am. Chem.
Soc., 1995, 117, 5889; (c) R. W. Quan, Z. Li and E. N. Jacobsen,
J. Am. Chem. Soc., 1996, 118, 8156.
4.20–4.30 (2H, m, CH2CH3), 4.45 (1H, d, J 4, CH-CH), 7.25–
7.50 (6H, m, Ar), 7.75 (2H, m, Ar). cis: δH(250 MHz; CDCl3)
0.95 (3H, t, J 7, CH3CH2O), 2.40 (3H, s, CH3Ar), 3.65 (1H, d,
J 7, CH-CH), 3.75–3.95 (2H, m, CH2CH3), 4.00 (1H, d, J 7,
CH-CH), 7.25 (2H, m, Ar), 7.45 (2H, m, Ar), 7.75 (2H, m, Ar),
8.05 (2H, m, Ar); δC(63 MHz; CDCl3) (quaternary Ar carbons
not observed) 13.8, 21.7, 43.4, 44.5, 61.9, 123.4, 128.1, 128.7,
129.9, 163.8.
9 C. J. Sander, K. M. Gillespie, D. Bell and P. Scott, J. Am. Chem. Soc.,
2000, 122, 7132.
10 For asymmetric manganese catalysed aziridination, see: (a) H.
Nishikori and T. Katsuki, Tetrahedron Lett., 1996, 37, 9245;
(b) S. Minakata, A. Takeya, M. Nishimura, I. Ryu and M. Komatsu,
Angew. Chem., Int. Ed., 1998, 3392.
11 For an interesting new process for alkene aziridination using Br2 and
chloramine-T, see: J. U. Jeong, B. Tao, I. Sagasser, H. Hennigs
and K. B. Sharpless, J. Am. Chem. Soc., 1998, 120, 6844.
12 P. Muller, B. Corine and Y. Jacquier, Can. J. Chem., 1998, 76, 738.
13 (a) M. J. Sodergren, D. A. Alonso, A. V. Bedekar and P. G.
Andersson, Tetrahedron. Lett., 1997, 38, 6897; (b) M. J. Sodergren,
D. A. Alonso and P. G. Andersson, Tetrahedron: Asymmetry, 1997,
8, 3563; (c) P. Dauban and R. H. Dodd, J. Org. Chem., 1999, 64,
5304.
N-Tosyl-2-ethoxycarbonyl-3-cyclohexylaziridine.
Viscous
colourless oil as a mixture of cis and trans. Rf 0.29 (93 : 7 pet-
roleum ether–EtOAc); νmax(CDCl3)/cmϪ1 1746 (C᎐O); m/z (CI)
᎐
369 (MNH4ϩ, 20%), 352 (MHϩ, 100) (Found: MHϩ, 352.1577.
C18H26NO4S requires 352.1582). trans: δH(250 MHz; CDCl3)
0.95–1.75 (14H, m, CH3CH2O, Cy), 2.45 (3H, s, CH3Ar), 3.00
(1H, dd, J 9, 4, CH2CHCH2), 3.20 (1H, d, J 4, CH-CH), 3.75–
3.95 (3H, m, CH2CH3, CH-CH), 7.23 (2H, m, Ar), 7.80 (2H,
m, Ar). cis: δH(250 MHz; CDCl3) 1.25 (3H, t, J 7, CH3CH2O),
0.95–1.75 (11H, m, Cy), 2.45 (3H, s, CH3Ar), 2.75 (1H, dd, J 9,
7, CH2CHCH2), 3.40 (1H, d, J 7, CH-CH), 3.75–3.95 (2H, q,
J 7, CH2CH3), 7.25 (2H, m, Ar), 7.90 (2H, m, Ar); δC(63 MHz;
CDCl3) (quaternary Ar carbons not observed) 14.1, 21.7, 25.9,
29.5, 31.0, 35.0, 41.0, 49.5, 62.0, 128.3, 129.7, 167.0.
14 K. B. Hansen, N. S. Finney and E. N. Jacobsen, Angew. Chem., Int.
Ed. Engl., 1995, 34, 676.
15 K. G. Rasmussen and K. A. Jorgensen, J. Chem. Soc, Chem.
Commun., 1995, 1401.
16 (a) J. C. Antilla and W. D. Wulff, J. Am. Chem. Soc., 1999, 121, 5099;
(b) J. C. Antilla and W. D. Wulff, Angew. Chem., Int. Ed., 2000, 39,
4518.
N,N-Diethyl-1-tosyl-3-phenylaziridine-2-carboxamide. A vis-
cous colourless oil as a mixture of cis and trans. trans:
νmax(CDCl3)/cmϪ1 1655 (C᎐O); δ (250 MHz; CDCl ) 1.20 (3H,
᎐
H
3
t, J 7, CH2CH3), 1.26 (3H, t, J 7, CH2CH3), 2.40 (3H, s,
CH3Ar), 3.23 (1H, m, NCHH), 3.39 (1H, m, NCHH), 3.50 (H,
d, J 4, CH-CH), 3.67 (1H, m, NCHH), 3.83 (1H, m, NCHH),
4.49 (H, d, J 4, CH-CH), 7.00–7.25 (7H, m, Ar), 7.95 (2H, m,
Ar); δC(63 MHz; CDCl3) 12.4, 21.6, 14.3, 40.6, 42.1, 47.1, 48.4,
127.1, 127.7, 128.5, 128.5, 129.5, 133.5, 136.6, 162.6 (one
quaternary Ar carbon not observed); m/z (EI) 372 (Mϩ, 10%),
91 (C7H7ϩ, 100) (Found: MHϩ, 372.1506. C20H24N2O3S requires
372.1508). cis: νmax(CDCl3)/cmϪ1 1655; δH(250 MHz; CDCl3)
0.65 (3H, t, J 7, CH2CH3), 0.95 (3H, t, J 7, CH2CH3), 2.35 (3H,
s, CH3Ar), 2.85 (1H, m, NCHH), 3.00 (1H, m, NCHH), 3.27–
3.40 (2H, m, NCH2), 3.68 (H, d, J 8, CH-CH), 4.05 (H, d, J 8,
CH-CH), 7.00–7.25 (5H, m, Ar), 7.25 (2H, m, Ar), 7.90 (2H, m,
Ar); δC(63 MHz; CDCl3) 12.2, 14.1, 21.8, 39.8, 41.1, 45.1, 46.0,
127.2, 127.9, 128.2, 128.5, 129.8, 131.8, 134.5, 144.8 (carbonyl
carbon not observed); m/z (EI) 372 (Mϩ, 10%), 207 (100)
(Found: MHϩ, 372.1502. C20H24N2O3S requires 372.1508).
17 (a) K. G. Rasmussen and K. A. Jorgensen, J. Chem. Soc., Perkin
Trans. 1, 1997, 1287; (b) K. Juhl, R. G. Hazell and K. A. Jorgensen,
J. Chem. Soc., Perkin Trans. 1, 1999, 2293.
18 (a) V. Franzen and H.-E. Driesen, Chem. Ber., 1963, 96, 1881; (b)
R. S. Tewari, A. K. Awasthi and A. Awasthi, Synthesis, 1983, 330.
19 E. J. Corey and M. Chaykovsky, J. Am. Chem. Soc., 1965, 87, 1353.
20 (a) A.-H. Li, Y.-G. Zhou, L.-X. Dai, X.-L. Hou, L.-J. Xia and
L. Lin, J. Org. Chem., 1998, 63, 4338; (b) L.-X. Dai, X.-L. Hou
and Y.-G. Zhou, Pure Appl. Chem., 1999, 71, 369.
21 J. L. Garcia-Ruano, I. Fernandez, M. Prado Catalina and A. A.
Cruz, Tetrahedron: Asymmetry, 1996, 7, 3407.
22 (a) V. K. Aggarwal, H. Abdel-Rahman, R. V. H. Jones, H. Y. Lee
and B. D. Reid, J. Am. Chem. Soc., 1994, 116, 5973; (b) V. K.
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Standen, Chem. Eur. J., 1996, 2, 1024.
23 (a) V. K. Aggarwal, J. G. Ford, A. Thompson, R. V. H. Jones and
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Aggarwal, G. J. Ford, S. Fonquerna, H. Adams, R. V. H. Jones and
R. Fieldhouse, J. Am. Chem. Soc., 1998, 120, 8328.
24 For a preliminary account, see: V. K. Aggarwal, A. Thompson,
R. V. H. Jones and M. C. H. Standen, J. Org. Chem., 1996, 61, 8368.
25 W. R. McKay and G. R. Proctor, J. Chem. Soc., Perkin Trans. 1,
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26 W. B. Jennings and C. J. Lovely, Tetrahedron, 1991, 47, 5561.
27 E.-U. Wurthwein and S. Meier, Synthesis, 1984, 689.
28 J. Vidal, S. Damestoy, L. Guy, J.-C. Hannachi, A. Aubry and
A. Collet, Chem. Eur. J., 1997, 3, 1691.
Acknowledgements
We thank A.H. Jones of the Department of Chemistry,
University of Sheffield for performing microanalyses.
29 K. Julienne and P. Metzner, J. Org. Chem., 1998, 63, 4532.
30 The synthesis of these sulfides will be described in a full paper on
epoxidation with a range of chiral sulfides.
31 T. W. Greene and P. G. M. Wuts, Protective Groups in Organic
Synthesis, 3rd edn., John Wiley & Sons, New York, 1999.
32 Full details of these results will be described in due course.
33 M. K. Lindvall and A. M. P. Koskinen, J. Org. Chem., 1999, 64,
4596.
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