Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 2: Inversion of diastereoselectivity

Article abstract of DOI:10.1016/j.tet.2006.01.069

The aza-Darzens ('ADZ') reactions of N-diphenylphosphinyl ('N-Dpp') imines with chiral enolates derived from N-bromoacetyl 2S-2,10-camphorsultam proceed in generally good yield to give N-diphenylphosphinyl aziridinoyl sultams. However, the stereoselectivi

Full text of DOI:10.1016/j.tet.2006.01.069

Tetrahedron 62 (2006) 3694–3703
Asymmetric aziridine synthesis by aza-Darzens reaction of
N-diphenylphosphinylimines with chiral enolates.
Part 2: Inversion of diastereoselectivity
b
a
J. B. Sweeney,a,b, Alex A. Cantrill, Michael G. B. Drew,
*
Andrew B. McLarena and Smita Thobhania
aSchool of Chemistry, University of Reading, Reading RG1 5JN, UK
bSchool of Chemistry, University of Bristol, Bristol BS8 1TS, UK
Received 28 November 2004; revised 31 December 2005; accepted 19 January 2006
Available online 28 February 2006
Abstract—The aza-Darzens (‘ADZ’) reactions of N-diphenylphosphinyl (‘N-Dpp’) imines with chiral enolates derived from N-bromoacetyl
2S-2,10-camphorsultam proceed in generally good yield to give N-diphenylphosphinyl aziridinoyl sultams. However, the stereoselectivity of
the reaction is dependent upon the structure of the imine substituent: when the chiral enolate was reacted with arylimines substituted in the
ortho-position, mixtures of cis- and trans-20R,30R-aziridines were obtained, often with a complete selectivity in favour of the trans-isomer.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
from acrolein, cis-aziridine† 1a was obtained as the only
product of the reaction, in moderate yield. However, when
the analogous reaction was carried out using the imine
from 3,3-dimethylacrolein, we obtained two products
(Scheme 1). The first was 1b, an aziridine with 2JHZ
2.9 Hz, indicative of a trans-stereochemistry. The second
product was a non-crystalline, non-aziridine product,
tentatively identified as pyrroline (2, obtained in 20% yield).
We have recently described our studies of the aza-Darzens
reaction (‘ADZ’) of N-diphenylphosphinyl (‘N-Dpp’)
imines with enolates derived from N-bromoacetylcamphor-
sultam, which proceed with good efficiency and high levels
of stereoselectivity.1 In the reactions of N-Dpp aryl imines
with these enolates, in common with other such reactions,
there often is an inherent propensity for the formation of cis-
aziridines as the major products. This is a consequence of
the stepwise nature of the mechanism involved (vide infra).
In this manuscript, we describe how the presence of
sterically-demanding imine substitutents can invert the
diastereoselectivity of the ADZ reaction, allowing for the
obtention of trans-aziridines from this process.
The lattercompound would be obtained via 1,4-additionof the
chiralenolatefollowedby5-exo-tetcyclizationoftheresulting
amide anion. Despite many attempts, we have been unable to
confirm either the gross structure or stereochemistry of the
fragile by-product 2. Given that we had previously observed
only cis-configured aziridines (often the products of asym-
metric aziridination reactions)2 in these aza-Darzens
reactions, we were intrigued by the observation and we
postulated that the inverted stereoselectivity might be due to
the extra steric demand present in the more substituted imine
due to the gem-dimethyl substitution pattern. We set out to
examine the scope of the trans-selective reaction.
2. Results and discussion
2.1. ADZ reaction of unsaturated imines
The first sign that the ADZ reaction might be tunable
according to substituent pattern in the imine was observed
in the reactions of a,b-unsaturated imines. Thus, in the
reaction of the camphor enolate with Dpp–imine derived
2.2. ADZ reaction of ortho-substituted aryl imines
In the first instance, we chose a range of ortho-substituted aryl
imines as suitable substrates to provide pertinent information
about the breadth of the process. N-Dpp-2-chlorobenzaldi-
minereactedunderthestandardconditionstogivea mixtureof
Keywords: Aziridine; Sultam; Aza-Darzens.
*
Corresponding author. Tel.: C118 931 6585; fax: C118 378 6331;
e-mail: j.b.sweeney@rdg.ac.uk
† Decoupling experiments indicated Jw6 Hz.
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.069

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
Dpp Dpp
3695
O
Dpp
H
H
N
N
H
H
i, ii
N
R
C
or
Br
+
N
R
C
R
C
R
R
S
O
O
O
O
O
R
R
2
(R =(2S)-Camphorsultam)
C
Conditions: i. LiHMDS, THF, -78ºC;
ii R C=CH=NP(O)Ph
1a, R = H, 47% yield, cis: trans =100:0
1b, R = Me, 40% yield, cis: trans =0:100
2
2
Scheme 1.
Dpp
Dpp
H
O
H
O
N
N
H
H
LiHMDS, THF, -78”C
Cl
RC
RC
Br
+
N
Cl
Cl
NDpp
S
O
O
O
cis-3
trans-3
20:80, 68% yield
[R =(2S)-Camphorsultam]
c
Scheme 2.
Figure 1. Selected 13C NMR data for cis-3 and trans-3.
cis- and trans-aziridines 3 (cis:trans Z20:80, JZ6.1, 2.8 Hz,
respectively) in a combined yield of 68% (Scheme 2).
chemical shift value of only one of the non-aromatic
resonances recorded for each compound. Since we had
previously demonstrated in an unambiguous manner‡ that
this resonance belonged to the benzylic aziridine carbon
(i.e., position 30), we felt confident in stating that the
stereochemistry of trans-3 was (20S, 30R), as shown in
Figure 1. To our delight, when we subsequently obtained
single crystals of trans-3, which were suitable for X-ray
analysis, our initial stereochemical assignment was vindi-
cated (Fig. 2).
Although the obtention of a mixture of diastereoisomers, and
the coupling constants shown by these products, gave a clear
indicationthat the diastereoselectivity of the reactionhad been
inverted to favour the trans-isomer, cis-3 and trans-3 did not
initially produce crystals suitable for analysis by X-ray
crystallography. We were, therefore, forced to seek an
alternative means to confirm the actual stereochemistry of
the compounds. Although we felt it was reasonable to assume
thatthediastereofaceselectivityofthereaction(videinfra)was
unaltered (meaning that the absolute stereochemistry at C0-2
would be S), we were, of course, motivated to provide more
compelling evidence for the stereochemistry engendered by
the reaction. As a first means of assessing the compounds, we
examined the 13C NMR spectra of cis-3 and trans-3 (Fig. 1).
When the reaction was repeated with a range of ortho-
substituted aryl imines, a pattern began to emerge (Table 1).
In all but one of the ADZ reactions of ortho-substituted
benzaldimines examined, trans-aziridines were observed in
the product mixture and in several cases (entries 5–7, 10) the
reaction provided only the trans-isomer; only in the reaction of
Thus, we observed that in the NMR spectra of cis-3 and
trans-3 there was significant (R5%) divergence in the
‡ Using homo- and heteronuclear correlated spectroscopy.

3696
J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
Thesedataarecompletelyatoddswithamechanismcontrolled
by steric demand and may suggest that there are several
mechanism at play, as discussed below.
2.3. Mechanism of ADZ Reaction§
General principles
Though there are many possible arrangements of reagents, the
preferred rationalization for asymmetric aldol reactions
Figure 2.
Table 1. Effect of imine substitution upon diastereoselectivity of ADZ reactions
Dpp
Dpp
H
O
H
O
N
N
H
H
LiHMDS, THF, -78”C
S
S
R
S
R N
2
R N
2
Br
N
+
Ar
Ar
R
NDpp
S
O
O
O
Entry
Ar
Ph
Yield (%)
cis:trans
3J cis/trans (Hz)
1
2
3
4
5
6
7
8
9
10
71
72
84
68
67
73
65
87
93
69
100:0
100:0
50:50
20:80
0:100
0:100
0:100
50:50
63:37
0:100
6.2
5.8
6.2/2.8
6.1/2.8
2.6
2.8
3.1
6.0/2.8
6.1/2.8
2.7
2-NO2–C6H4
2-F–C6H4
2-Cl–C6H4
2-Br–C6H4
2-I–C6H4
2-OMe–C6H4
2-Me–C6H4
2-Et–C6H4
2-CF3–C6H4
the-iminederivedfrom2-nitrobenzaldehydewascis-aziridine
exclusively isolated. The latter observation might lead one to
the conclusion that the polarity of the 2-substituent is
unimportant in influencing the diastereoselectivity of the
reaction and that the formation of cis-aziridine is due to the
relatively small steric demands of the planar NO2 substituent.
This conclusion is endorsed by the results obtained from the
ADZ reactions of the imines derived from ortho-halo
benzaldehydes (Table 1, entries 3–6), which seem to indicate
a clear connection between size and selectivity: 2-fluoroben-
zaldimine gives a 50:50 mixture of cis- and trans-aziridines,
2-chlorobenzaldiminea20:80ratio(asdescribedabove),while
the 2-bromo- and 2-iodobenzaldimines furnish only trans-
aziridines. Inallthereactionsofthehalogenatedsubstrates,the
overall yields were similar to, or better than (in the case of the
2-fluoro and 2-iodo compounds) the reaction of the parent
imine. The presence of a more powerfully p-donating
electronegative substituent, a 2-methoxy group, had a similar
effect upon the diastereoselectivity of the reaction, with only
trans-aziridineobtained.However,whentheADZreactionwas
carried out using 2-methylbenzaldimine, in which the
substituenthasagreaterstericdemandthananyofthehalogens,
a 50:50 mixture of cis- and trans-aziridines was obtained, in
excellentyield.GiventherelativeA-values(forinstance,ABrZ
2.01–2.80 kJ molK1, whereas AMeZ7.28 kJ molK1), this
result does not tally with a reaction proceeding purely under
the control of steric effects (vide infra). Furthermore, the
2-trifluoromethylphenyliminegaveonlytrans-aziridine(entry
9), whereas the ethyl substituted analogue reacted to give the
cis-isomerasthedominantproduct(cis:transZ1.7:1,entry10).
mediated by lithium enolates of camphorsultam derivatives
invokes a twisted boat-like transition state, in which there is a
chelation between one of the S]O bonds and the apical
lithium atomof the enolate.3 Thus, in the (Z)-enolate produced
by deprotonation of N-bromoacetyl-(2S)-camphorsultam, the
si-face is powerfully shielded by the methyl group, which
is syn- to the sultam unit, and these enolates inherently favour
re-face interactions with incoming electrophiles.
Althoughlikely tosharethe generalfeaturesofaldol reactions,
the ADZ reaction is complicated by several additional factors:
firstly, the reaction is considerably slower than the aldol
reaction. Secondly, there is an additional (and polar)
substituent in the shape of the diphenylphosphinyl group.
Finally, there is the question of imine stereochemistry: the
barrier to imine inversion is variable, but such isomerizations
are relatively facile under a range of conditions.4 As in sultam
aldol reactions, the enolate’s re-face is, in all cases, more
accessible: as the imine approaches the enolate, its substituent
is placed anti- to the sultam sub-unit, leading to the transition
state shown in Scheme 3 (note that in any of the chelated
transition states there is an unavoidable interaction of the
imine substituent and the a-bromo group-vide infra). In
addition, it is likely that the Dpp group will coordinate to the
lithium atom of the enolate, through the polar P]O bond,
§ In our original description (McLaren, A. B.; Sweeney, J. B. Org. Lett.,
1999, 1, 1339) of the trans-selective ADZ reaction, the diagrammatic
representaion of the transition states involved were reproduced
incorrectly; we thank Professor D. Tanner for drawing our attention to
this fact.

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
3697
Scheme 3.
thoughthisinteractionmaybeweak(afullcoordinationwould
form a four-membered ring).
likely that a twisted boat TS is in operation. In this
arrangement, one of the gem-dimethyl groups of the terpene
bridge still provides a powerful shielding influence, the
pseudoequatorial S]O–Li interaction is in place and the R
substituent is anti-to the camphor ring. This is a re–re
interaction, leading to the 20S,30S-configured aziridine
products observed.
This preferred, re–re, interaction would lead to a 20S,30S-
aziridine when using (2S)-sultam, via the corresponding 20R,
30S-bromoamide 4: this hypothetical prediction is fulfilled in
practice. However, although it is clear that the reaction
proceeds via a re–re interaction, it is not a trivial matter to
deduce the precise nature of the TS: we must consider three
options.
Inversion of diastereoselectivity
As described above, ADZ reaction of ortho-substituted
imines can give 20S,30R-aziridines from 2S-bromoacyl
camphorsultam and we must modify our mechanistic
Chair, boat or open TS?
ˆ
As adumbrated above, the face selectivity of the ADZ
reaction can be easily ascertained from the stereochemistry
of the products (assuming Z-configuration in the enolate and
E-configuration in the imine). It is less clear whether this
stereochemical course of action arises from a closed or open
transition state: it is even less obvious whether the closed TS
would prefer a chair or boat arrangement.
rationale accordingly. Such products arise from a re-
enolate–si-imine interaction, which cannot be easily
accommodated within a closed transition state: the chelated
nature of the enolate precludes a simple change in the
direction of approach of the reagents. We suggest that an
open transition state is in operation, as shown in Scheme 5;
this open TS is favoured, we believe, due to the repulsive
interaction between the imine g-substituent (an ortho-
substituent in the case of aryl imines and an allylic
substituent in the case of an a,b-unsaturated imine) and
the enolate bromine in a cyclic TS. Thus, there is an
equilibrium between conformers in which the R substituent
is either syn- or anti-to the enolate a-bromo substituent.
Closed TS, chair or boat conformation
It is difficult to construct a convincing re–re Zimmerman–
Traxler-like transition state (Scheme 4) for this ADZ reaction:
there clearly is a unfavourable interaction between the imine
CH and the methylene group adjacent to the C–N bond of the
camphor sub-unit. As shown in the figure, this repulsive
interaction is not greatly ameliorated by a change in
conformation from chair/boat. The tetracyclic TS is
configured in this manner when coordination to the lithium
atom of the enolate occurs through the pseudoaxial rather than
the pseudoequatorial S]O bond.
In both conformers, there are repulsive interactions, which
can destabilize the arrangement though the major
contributor is certainly the Br–R interaction (indicated by
bold arrows on the Scheme). A switch to an open TS, though
not without steric interactions, is certainly less compressed
than the closed TS, and so a0re-enolate-si-imine interaction
is favoured, leading to 20S,3 R-configured aziridines.
If the pseudoequatorial S]O bond is used in coordination, an
alternative Zimmerman–Traxler TS is still accessible, but
evenmoreseverestericinteractionsare evident. Thus,itseems
As alluded to above, the variation in selectivity is not
controlled by purely steric demands: recall that the
Scheme 4.

3698
J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
Scheme 5.
Table 2. Hydrolytic removal of auxiliary from cis- and trans-aziridines
Dpp
O
Dpp
N
N
O
N
H
H
S
1. LiOH, THF/H O, room temp.
2
S
R
S
2. 2N HCl
R
HO C
2
O
Entry
R
Yield (%)
1
2
3
4
5
trans-Me2C]CH
trans-2-Cl–C6H4
trans-2-F3C–C6H4
cis-2-Me–C6H4
cis-2-Et–C6H4
50
45
57
81
65
reaction with RZMe is less selective than with RZ
OMe, despite the effective smaller size of the methoxy
substituent (O vs CH2). This suggests that there is a
polar phenomenon also in play, perhaps due to the lone-
pair/lone-pair repulsion, which would be present with
oxygen or halogeno substituents, but not with alkyl ones.
Such a phenomenon would also rationalize the obser-
vation that an ortho-CF3 group causes a complete
inversion in stereoselectivity, whereas the ortho-CH3
group engenders a non-selective reaction (giving a 50:50
mixture of cis- and trans-isomers). It does not, however,
explain why an ortho-ethyl group gives a mixture of
aziridines dominated by the cis-form (cis:transZ63:37).
3. Conclusion
We have developed a practical ADZ reaction, which allows
the preparation of chiral aziridine derivatives in good yield.
Depending on the substitution pattern of the imine, the
inherent cis-selectivity of the process can be inverted to give
exclusively trans-configured products. We are currently
attempting to expand further the scope of this process, and
studying the underlying factors responsible for the
stereoselectivity observed.
4. Experimental
Cleavage of the auxiliary
4.1. General techniques
We have also demonstrated that a representative cross-
section of these trans-aziridines can be hydrolyzed to
give the corresponding aziridine carboxylates, in a
manner analogous to that described for the cis-
compounds (Table 2). However, the yields of hydrolysis
are lower than observed in the hydrolysis of analogous
cis-aziridines, perhaps reflecting a more hindered trajec-
tory for the incoming nucleophile.
All organic solvents were distilled prior to use and all
reagents were purified by standard procedures.5 ‘Petrol’
refers to the fraction of petroleum ether with the boiling
range 40–60 8C and ‘ether’ refers to diethyl ether. Ether and
THF were distilled from sodium benzophenone ketyl;
toluene from sodium; dichloromethane, triethylamine,
acetonitrile from calcium hydride, methanol from magne-
sium methoxide and diisopropylethylamine from potassium

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
3699
hydroxide. Imines were prepared according to literature
methods.6 Other chemicals were purchased from Aldrich
Chemical Co. or prepared by literature methods.
(336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL, 1.0 M,
1.1 mmol) and P,P-diphenyl-N-(2-methylpropenyl-
methylene)phosphinic amide (283 mg, 1.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford 1b, as a colourless
solid (214 mg, 40%); Rf 0.55 (EtOAc); [a]2D0 C74.1 (c 1,
CHCl3); IR nmax (CCl4) 3058, 2966, 1698, 1440, 1338,
1168, 1268, 1127, 735, 705 cmK1; dH (400 MHz, CDCl3)
0.85 (3H, s), 0.93 (3H, s), 1.13–1.26, 1.76–1.81 and 1.95–
2.01 (7H, m), 1.28 (3H, s), 1.53 (3H, s), 3.29 and 3.38 (2H,
2!d, JZ13.9 Hz), 3.45–3.51 (1H, m), 3.73–3.91 (2H, m),
5.32 (1H, d, JZ9.2 Hz), 7.29–7.41 (6H, m), 7.76–7.81 and
7.92–7.97 (4H, m); dC (100 MHz, CDCl3) 17.5, 25.5, 19.7,
20.6, 26.2, 32.6, 38.2, 40.0, 44.4, 44.5, 47.7, 49.0, 52.6,
64.8, 118.6, 127.9, 128.0, 128.2, 128.4, 128.5, 128.5, 131.2,
131.4, 131.5, 131.6, 131.8, 131.9, 132.1, 132.2, 132.7,
133.0, 134.1, 142.0, 166.7; MS (CI) m/z 538 ([M]C, 11%),
417 (9), 296 (62), 219 (29), 201 (100), 77 (18); HRMS
found: [M]C538.2099 C29H36N2O4PS requires 538.2055.
Melting points were recorded on a Kofler hot-stage
apparatus and are uncorrected. Spectra were recorded on
Perkin Elmer 881 or Paragon 1000 spectrophotometers.
Optical rotations were measured using a Perkin Elmer 241
MC polarimeter and are quoted in 10K1 deg cm2 gK1. Mass
spectra were recorded on VG9090 or Fisons Autospec mass
1
spectrometers. H and 13C NMR spectra were recorded on
Jeol GX-270, Jeol GX-400, Lambda 300, Bruker DPX-250
or Bruker AX-400 spectrometers. Unless otherwise stated,
deuterochloroform was used as solvent and tetramethyl-
silane was the internal standard. Chemical shifts in 1H NMR
spectra are expressed as ppm downfield from tetramethyl-
silane, and in 13C NMR, relative to the internal solvent
standard. Coupling constants (J) are quoted in Hz.
Reactions involving chemicals or intermediates sensitive to
air or moisture were conducted under a nitrogen or argon
atmosphere in oven- or flame-dried apparatus. Flash
chromatography was performed using Merck Kieselgel 60
or Fluka Kieselgel 60 silica gel. Analytical thin-layer
chromatography was performed using either precoated
Merck Kieselgel 60 F254 glass-backed plates, or precoated
Merck Kieselgel 60 F254 aluminium backed plates and were
visualised under UV at 254 nm and by staining with iodine
and/or an acidic ammonium molybdate dip.
4.2.2. 2S-N-[10-Diphenylphosphinyl-40,40-dimethyl-20,30-
dihydro-1H-pyrrole-50-carbonyl]bornane-10, 2-sultam
(2). Following the general procedure described above
N-bromoacetyl-2S-bornane-10,
2-sultam
(336 mg,
1.0 mmol), LiHMDS in THF (1.1 mL, 1.0 M, 1.1 mmol)
and P,P-diphenyl-N-(2-methylpropenylmethylene)phosphi-
nic amide (283 mg, 1.0 mmol) were reacted to produce
the crude aziridine. The resulting colourless solid was
purified by flash chromatography eluting with petrol–
EtOAc (1/9) to afford 2 as a colourless solid (109 mg,
20%); Rf 0.36 (EtOAc); [a]2D0 C66.4 (c 1, CHCl3); IR
nmax (CCl4) 3056, 2968, 1687, 1440, 1342, 1168, 1267,
1125, 741, 705 cmK1; dH (400 MHz, CDCl3) 0.85 (3H, s),
0.94 (3H, s), 1.23 (3H, s), 1.51 (3H, s), 1.01–1.36 and
1.80–2.11 (7H, 2!m), 3.39 and 3.41 (2H, 2!d, JZ
13.2 Hz), 3.85 (1H, m), 4.17 (1H, m), 4.80 (1H, m), 4.99
(1H, m), 7.36–7.41 (6H, m), 7.82–7.90 (4H, m); dC
(100 MHz, CDCl3) 18.1, 25.5, 19.7, 20.6, 26.3, 32.8, 38.0,
44.6, 47.7, 48.5, 52.8, 53.3, 56.5, 65.5, 122.3, 128.1,
128.2, 128.3, 128.3, 128.4, 128.6, 131.2, 131.4, 131.5,
131.7, 131.8, 131.9, 132.0, 132.1, 132.2, 132.3, 132.4,
132.4, 133.6, 137.9, 167.2; MS (CI) m/z 539 ([M]C,
13%), 475 (6), 419 (16), 324 (20), 284 (100), 218 (68),
152 (34); HRMS found: [M]C539.2127, C29H35N2O4PS
requires 539.2133.
X-ray data obtained from trans-3 has been deposited at
CCDC (reference number CCDC 291092).
13C NMR spectra of N-Dpp compounds are complicated by
rotameric isomers, which often leads to the appearance of
‘excess’ resonances in the aromatic region of the spectra;
the situation is further complicated by the difficulty in
obtaining precise coupling constants. Rather than refer to
the entire region of the spectra as being a ‘multiplet’, the
data quoted describes the actual appearance of the spectra.
4.2. General procedure for aza-Darzens reaction:
synthesis of cis- and trans-2,3 substituted aziridines
(2R)-(K)-(N-Bromoacetyl)bornane-10,2-sultam, (1.0 equiv),
was dissolved in THF (25 mL) and cooled to K78 8C.
LiHMDS in THF (1.1 equiv) was then added dropwise, and
the resulting pale yellow solution stirred for 30 min.
Phosphinylimine (typically 1.0 equiv) was then added at
K78 8C as a solution in THF (10 mL). The reaction mixture
was then stirred for over 2 h at K78 8C, after which time the
reaction was judged to have reached completion by TLC and
the mixture was quenched with saturated ammonium
chloride solution (20 mL). The aqueous layer was extracted
with EtOAc (20 mL, 2!10 mL), the organic layers were
then combined, washed with brine, dried (MgSO4), filtered,
and the solvent removed in vacuo, to afford the crude
aziridine.
4.2.3.
cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-
(2-fluorophenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 3). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL,
1.0 M, 1.1 mmol) and P,P-diphenyl-N-(2-fluorophenyl-
methylene)phosphinic amide (323 mg, 1.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (243 mg, 42%); Rf 0.50 (petrol/EtOAc 1:3);
[a]2D0 C16.6 (c 1, CHCl3); IR nmax (CCl4) 3057, 2964, 1703,
1441, 1340, 1176, 1271, 1129, 758, 733, 704 cmK1; dH
(400 MHz, CDCl3) 0.89, (3H, s), 0.93 (3H, s), 1.19–1.28
and 1.80–1.99 (7H, 2!m), 3.27 and 3.38 (2H, 2!d,
JZ13.6 Hz), 3.64 (1H, m), 4.18 and 4.48 (2H, 2!dd,
4.2.1. cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-(2-
methylpropenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (cis-1b). Following the general procedure
described above N-bromoacetyl-2S-bornane-10, 2-sultam

3700
J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
JPZ15.8 Hz, JZ6.2 Hz), 6.94–7.59 (10H, m), 7.92–8.15
(4H, m); dC (100 MHz, CDCl3) 19.7, 20.6, 26.3, 32.5, 38.0,
38.5, 41.4, 44.6, 47.7, 49.0, 52.4, 64.5, 114.7, 123.4, 128.4,
128.6, 128.7, 129.1, 129.6, 129.7, 130.8, 130.9, 131.5,
131.6, 131.7, 131.8, 132.0, 132.2, 160.8, 163.4; MS (CI) m/z
579 ([MH]C, 96%), 515 (42), 419 (40), 379 (27), 297 (28),
218 (100), 135 (30); HRMS found: [MH]C579.1874,
C31H33FN2O4PS requires 579.1883.
2-sultam (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL,
1.0 M, 1.1 mmol) and P,P-diphenyl-N-(2-chlorophenyl-
methylene)phosphinic amide (340 mg, 1.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (325 mg, 55%); Rf 0.56 (EtOAc); [a]D20
C59.4 (c 1, CHCl3); IR nmax (CCl4) 3056, 2985, 1705,
1440, 1338, 1168, 1266, 1126, 738, 706, 623 cmK1; dH
(400 MHz, CDCl3) 0.75 (3H, s), 0.80 (3H, s), 1.01–1.29 and
1.65–1.89 (7H, 2!m), 3.23 and 3.28 (2H, 2!d, JZ
13.6 Hz), 3.72 (1H, m), 4.16 and 4.30 (2H, 2!dd, JPZ
13.3 Hz, JZ2.8 Hz), 7.03–7.10 and 7.19–7.34 (10H, 2!m),
7.63–7.67 and 7.79–7.83 (4H, 2!m); dC (100 MHz, CDCl3)
19.7, 20.6, 26.3, 32.5, 37.8, 41.3, 44.0, 44.4, 47.6, 48.8,
52.7, 65.1, 126.5, 128.0, 128.1, 128.1, 128.3, 128.4, 128.9,
129.4, 131.2, 131.6, 131.7, 132.5, 133.0, 134.3, 135.5,
164.9; MS (CI) m/z 594 ([M]C, 19%), 559 (49), 219 (68),
201 (100), 77 (27); HRMS found: [M]C594.1559,
C31H34N2O4PS requires 594.1509.
4.2.4. trans-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-
(2-fluorophenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 3). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL,
1.0 M, 1.1 mmol) and P,P-diphenyl-N-(2-fluorophenyl-
methylene)phosphinic amide (323 mg, 1.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (243 mg, 42%); Rf 0.45 (petrol/EtOAc 1:3);
[a]2D0 C83.5 (c 1, CHCl3); IR nmax (CCl4) 3057, 2964, 1687,
1440, 1339, 1169, 1287, 1139, 742, 700 cmK1; dH
(400 MHz, CDCl3) 0.83 (3H, s), 0.87 (3H, s), 1.16–1.36
and 1.70–1.97 (7H, 2!m), 3.03 and 3.36 (2H, 2!d, JZ
13.9 Hz), 3.78 (1H, m), 4.20 and 4.33 (2H, 2!dd, JPZ
13.4 Hz, JZ2.8 Hz), 6.71–7.90 (14H, m); dC (100 MHz,
CDCl3) 20.1, 21.0, 26.7, 33.0, 38.2, 40.8, 41.2, 44.8, 48.0,
49.2, 53.1, 65.5, 115.1, 124.2, 128.3, 128.4, 128.5, 128.6,
128.7, 128.8, 129.1, 130.4, 130.4, 131.7, 131.8, 131.9,
132.0, 132.4, 132.5, 163.9, 165.6; MS (CI) m/z 579 ([MH]C,
100%), 515 (71), 419 (67), 379 (41), 297 (35), 201 (78);
HRMS found: [MH]C579.1902, C31H33FN2O4PS requires
579.1883.
4.2.7. trans-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-
(2-bromophenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 5). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL,
1.0 M, 1.1 mmol) and P,P-diphenyl-N-(2-bromophenyl-
methylene)phosphinic amide (386 mg, 1.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (428 mg, 67%); Rf 0.53 (EtOAc); [a]D20
C13.5 (c 1, CHCl3); IR nmax (CCl4) 3056, 2966, 1705,
1441, 1336, 1188, 1267, 1128, 740, 705 cmK1; dH
(400 MHz, CDCl3) 0.88 (3H, s), 0.89 (3H, s), 1.21–1.38
and 1.80–2.02 (7H, 2!m), 3.37 and 3.42 (2H, 2!d, JZ
13.9 Hz), 3.86 (1H, m), 4.24 and 4.43 (2H, 2!dd, JPZ
13.2 Hz, JZ2.6 Hz), 7.10–7.14, 7.24–7.28 and 7.35–7.45
(10H, m), 7.78–7.83 and 7.92–7.97 (4H, m); dC
(100 MHz, CDCl3) 9.8, 20.6, 26.4, 32.7, 37.9, 41.9,
46.1, 44.5, 47.7, 48.8, 52.8, 65.7, 125.4, 127.2, 127.6,
128.1, 128.2, 128.4, 128.4, 128.6, 128.7, 129.5, 129.7,
129.9, 131.3, 131.5, 131.6, 131.7, 131.8, 131.9, 132.4,
132.5, 133.0, 133.3, 133.3, 133.7, 134.4, 134.5, 164.8; MS
(CI) m/z 639 ([MH]C, 32%), 573 (30), 419 (50), 357 (11),
219 (100), 135 (23); HRMS found: [MH]C639.1089,
C31H33BrN2O4PS requires 639.1082.
4.2.5.
cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-
(2-chlorophenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 4). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL,
1.0 M, 1.1 mmol) and P,P-diphenyl-N-(2-chlorophenyl-
methylene)phosphinic amide (340 mg, 1.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (81 mg, 13%); Rf 0.63 (EtOAc); [a]D20
C28.7 (c 1, CHCl3); IR nmax (CCl4) 3057, 2964, 1703,
1440, 1341, 1128, 1266, 1169, 745, 705, 644 cmK1; dH
(400 MHz, CDCl3) 0.78–0.83 (6H, m), 1.12–1.20 and 1.72–
1.97 (7H, 2!m), 3.22 and 3.30 (2H, 2!d, JZ13.9 Hz),
3.57–3.60 (1H, m), 4.11–4.50 (2H, 2!dd, JPZ15.9 Hz, JZ
6.1 Hz), 7.10–7.57 and 7.85–8.03 (14H, 2!m); dC
(100 MHz, CDCl3) 19.7, 20.6, 26.3, 32.5, 38.1, 40.7, 42.3,
44.6, 47.7, 49.0, 52.5, 64.6, 126.0, 128.4, 128.6, 128.7,
129.1, 129.2, 129.6, 130.6, 130.8, 131.6, 131.7, 131.7,
131.8, 131.8, 131.9, 132.1, 132.3, 134.6, 163.7; MS (CI) m/z
595 ([MH]C, 66%), 531 (60), 419 (100), 313 (43), 201 (91),
77 (32); HRMS found: [MH]C595.1594, C31H34N2O4PS
requires 595.1588.
4.2.8. trans-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-(2-
iodophenyl)-2-aziridinyl)carbonyl]bornane-10, 2-sultam
(Table 1, entry 6). Following the general procedure
described above N-bromoacetyl-2S-bornane-10, 2-sultam
(202 mg, 0.6 mmol), LiHMDS in THF (0.66 mL, 1.0 M,
0.66 mmol) and P,P-diphenyl-N-(2-iodophenylmethylene)-
phosphinic amide (259 mg, 0.6 mmol) were reacted to
produce the crude aziridine. The resulting colourless solid
was purified by flash chromatography eluting with petrol–
EtOAc (1/9) to afford the product, as a colourless solid
(300 mg, 73%); Rf 0.51 (EtOAc); [a]2D0 C73.5 (c 1, CHCl3);
dH (400 MHz, CDCl3) 0.77 (3H, s), 0.79 (3H, s), 1.07–1.35,
1.70–1.97 (7H, 2!m), 3.03 and 3.37 (2H, m), 3.78 (1H, m),
4.10 and 4.26 (2H, 2!dd, JPZ13.1 Hz, JZ2.8 Hz), 6.86
(1H, m), 7.19–7.35 (8H, m), 7.58–7.87 (5H, m); dC
4.2.6. trans-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-
(2-chlorophenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 4). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
3701
(60 MHz, CDCl3) 20.2, 21.2, 26.9, 33.1, 38.3, 43.1, 50.8,
44.9, 48.1, 49.3, 53.3, 65.7, 100.6, 128.5, 128.5, 128.6,
128.7, 128.8, 128.9, 130.4, 131.3, 132.0, 132.2, 132.3,
132.4, 133.0, 133.3, 135.1, 136.9, 136.9, 139.5, 165.0; MS
(CI) m/z 687 ([MH]C, 10%), 234 (33), 216 (100), 152 (29);
HRMS found: [MH]C687.0969, C31H33IN2O4PS requires
687.0943.
2-sultam (270 mg, 0.8 mmol), LiHMDS in THF (0.9 mL,
1.0 M, 0.9 mmol) and P,P-diphenyl-N-(2-methylphenyl-
methylene)phosphinic amide (255 mg, 0.8 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (200 mg, 43%); Rf 0.49 (EtOAc); [a]D20
C53.0 (c 1, CHCl3); IR nmax (CCl4) 3057, 2965, 1698,
1440, 1337, 1168, 1267, 1125, 740, 707 cmK1; dH
(400 MHz, CDCl3) 0.56 (3H, s) 0.59 (3H, s), 0.91–1.07
and 1.48–1.79 (7H, 2!m), 3.06 and 3.11 (2H, 2!d, JZ
14.3 Hz), 3.54 (1H, m), 3.87 and 3.97 (2H, 2!dd, JPZ
11.9 Hz, JZ2.8 Hz), 6.70–7.17 (10H, m), 7.50–7.66 (4H,
m); dC (100 MHz, CDCl3) 18.7, 19.7, 20.7, 26.3, 32.5, 37.7,
42.2, 44.0, 44.4, 47.6, 48.7, 52.8, 65.2, 125.7, 126.3, 127.9,
128.0, 128.1, 128.2, 128.2, 128.4, 129.7, 131.5, 131.6,
131.6, 131.7, 131.9, 132.1, 132.2, 136.4, 137.9, 165.3; MS
(CI) m/z 575 ([MH]C, 28%), 511 (25), 419 (37), 219 (100),
131 (16), 77 (19); HRMS found: [MH]C575.2109,
C32H36N2O4PS requires 575.2134.
4.2.9. trans-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-
(2-methoxyphenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 7). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (202 mg, 0.6 mmol), LiHMDS in THF (0.7 mL,
1.0 M, 0.7 mmol) and P,P-diphenyl-N-(2-methoxyphenyl-
methylene)phosphinic amide (200 mg, 0.6 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (227 mg, 65%); Rf 0.37 (EtOAc); [a]D20
C86.4 (c 1, CHCl3); IR nmax (CCl4) 3057, 2965, 1686,
1441, 1343, 1172, 1267, 1124, 735, 702 cmK1; dH
(400 MHz, CDCl3) 0.82 (3H, s), 0.83 (3H, s), 1.16–1.29
and 1.72–1.96 (7H, 2!m), 3.23 (3H, s), 3.29 and 3.36 (2H,
2!d, JZ13.7 Hz), 3.77–3.78 (1H, m), 4.24–4.31 (2H, m),
6.52 (1H, m), 6.81–6.85 (1H, m), 7.12–7.36 (8H, m), 7.69–
7.74 and 7.83–7.88 (4H, m); dC (100 MHz, CDCl3) 19.7,
20.7, 26.3, 32.6, 38.0, 39.6, 43.4, 44.5, 47.7, 48.8, 52.8,
54.4, 65.1, 109.5, 120.1, 121.8, 121.8, 127.8, 127.9, 128.0,
128.2, 128.3, 129.6, 131.1, 131.3, 131.4, 131.6, 131.6,
131.7, 131.7, 132.0, 133.3, 133.6, 134.9, 158.9, 166.1; MS
(CI) m/z 591 ([MH]C, 9%), 391 (100), 350 (24), 201 (66),
148 (75), 77 (39); HRMS found: [MH]C591.2072,
C32H36N2O5PS requires 591.2083.
4.2.12. cis-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-
(2-ethylphenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 9). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (672 mg, 2.0 mmol), LiHMDS in THF (2.1 mL,
1.0 M, 2.1 mmol) and P,P-diphenyl-N-(2-ethylphenyl-
methylene)phosphinic amide (667 mg, 2.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (700 mg, 59%); Rf 0.51 (petrol/EtOAc 1:3);
[a]2D0 C40.0 (c 1, CHCl3); dH (250 MHz, CDCl3) 0.79 (6H,
m), 1.07 (3H, t, JZ7.6 Hz), 1.04–1.20 and 1.68–1.86 (7H,
2!m), 2.53–2.68 and 2.74–2.89 (2H, 2!dt, JZ15.1,
7.6 Hz), 3.17 and 3.29 (2H, 2!d, JZ13.8 Hz), 3.52 (1H,
m), 4.15 and 4.31 (2H, 2!dd, JPZ15.9 Hz, JZ6.1 Hz),
7.05–7.09 (3H, m), 7.29–7.40 (H, m), 7.88–8.00 (4H, m); dC
(60 MHz, CDCl3) 15.0, 20.2, 21.0, 25.3, 26.7, 32.9, 38.4,
41.2, 43.2, 44.9, 48.1, 49.2, 53.0, 65.2, 125.4, 127.9, 128.3,
128.5, 128.8, 128.4, 129.0, 129.1, 130.3, 130.4, 132.0,
132.1, 132.2, 132.2, 132.6, 132.6, 132.7, 144.0, 164.4; MS
(CI) m/z 589 ([MH]C, 100%), 419 (10), 389 (17), 216 (27),
134 (14), 66 (11); HRMS found: [MH]C589.2295,
C33H38N2O4PS requires 589.2290.
4.2.10.
cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-
(2-methylphenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 8). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (270 mg, 0.8 mmol), LiHMDS in THF (0.9 mL,
1.0 M, 0.9 mmol) and P,P-diphenyl-N-(2-methylphenyl-
methylene)phosphinic amide (255 mg, 0.8 mmol) were
reactedtoproducethecrudeaziridine.Theresultingcolourless
solid was purified by flash chromatography eluting with
petrol–EtOAc (1/9) to afford the product, as a colourless solid
(200 mg, 43%); Rf 0.63 (EtOAc); [a]2D0 C34.8 (c 1, CHCl3);
IR nmax (CCl4) 3059, 2964, 1704, 1440, 1337, 1167, 1268,
1128, 770, 737, 705 cmK1; dH (400 MHz, CDCl3) 0.98 (6H,
2s), 1.30–1.38, 1.87–1.90 and 1.98–2.09 (7H, m), 2.53 (3H, s),
3.37 and 3.49 (2H, 2!d, JZ13.7 Hz), 3.70–3.73 (1H, m),
4.35 and 4.49 (2H, 2!dd, JPZ11.7 Hz, JZ6.0 Hz), 7.16–
7.28 (3H, m), 7.49–7.63 and 7.73–7.75 (7H, 2!m), 8.10–8.21
(4H, m); dC (100 MHz, CDCl3) 19.6, 20.2, 21.0, 26.7, 32.9,
38.4, 40.9, 43.6, 44.9, 48.2, 49.3, 53.1, 65.2, 125.4, 128.2,
128.3, 128.8, 128.9, 129.1, 129.1, 130.1, 130.7, 130.9, 131.0,
131.2, 132.1, 132.2, 132.7, 133.2, 138.3, 164.3; MS (CI) m/z
575([MH]C, 100%), 510(12), 375(24), 201 (59), 131(25), 77
(16); HRMS found: [MH]C575.2101, C32H36N2O4PS
requires 575.2134.
4.2.13. trans-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-
(2-ethylphenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 9). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (672 mg, 2.0 mmol), LiHMDS in THF (2.1 mL,
1.0 M, 2.1 mmol) and P,P-diphenyl-N-(2-ethylphenyl-
methylene)phosphinic amide (667 mg, 2.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (400 mg, 34%); Rf 0.29 (EtOAc); [a]D20
C63.5 (c 1, CHCl3); dH (250 MHz, CDCl3) 0.77 (3H, s),
0.80 (3H, s), 0.95 (3H, t, JZ7.5 Hz), 1.15–1.27 and 1.71–
1.90 (7H, 2!m), 3.27 and 3.33 (2H, 2!d, JZ13.8 Hz),
3.77 (1H, m), 4.05 and 4.26 (2H, 2!dd, JPZ13.3 Hz, JZ
2.8 Hz), 6.99–7.37 (10H, m), 7.78–7.80 (4H, m); dC
(60 MHz, CDCl3) 15.1, 20.2, 21.2, 25.6, 26.9, 33.1, 38.2,
4.2.11. trans-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-
(2-methylphenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam (Table 1, entry 8). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,

3702
J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
43.3, 43.7, 44.9, 48.2, 49.2, 53.3, 65.7, 126.3, 126.5, 128.3,
128.4, 128.5, 128.6, 128.7, 128.8, 129.0, 131.7, 132.0,
132.1, 132.2, 132.3, 132.6, 133.2, 133.8, 135.3, 144.2,
165.6; MS (CI) m/z 589 ([MH]C, 100%), 387 (17), 334
(10), 201 (39), 135 (11); HRMS found: [MH]C589.2275,
C33H38N2O4PS requires 589.2290.
129.8, 130.1, 130.2, 130.3, 130.4, 132.2, 132.4, 132.6,
132.8, 133.5, 133.6, 133.8, 134.0, 134.3, 134.6, 142.7,
175.1; MS (CI) m/z 342 ([MH]C, 15%), 314 (8), 297 (24),
219 (100), 130 (7), 84 (64), 66 (24); HRMS found:
[MH]C342.1273, C19H21NO3P requires 342.1259.
4.3.2. trans-2-Carboxy-N-diphenylphosphinyl-3-(2-
chlorophenyl)aziridine (Table 2, entry 2). Following the
general procedure described above cis-2S,20S,30S-N-[(1-
diphenylphosphinyl-3-(2-chlorophenyl)-2-aziridinyl)carbon-
yl]bornane-10, 2-sultam (119 mg, 0.2 mmol) afforded the
product as a colourless oil (34 mg, 45%). [a]2D0 C13.6 (c
1, CHCl3); IR nmax (CCl4) 1733, 1439, 1130, 755, 729,
697 cmK1; dH (250 MHz, CDCl3) 3.52 and 4.29 (2H, 2!dd,
JPZ13.6 Hz, JZ3.0 Hz), 7.12–7.80 (14H, m); MS (CI) m/z
354 ([MHKCO2]C, 35%), 318 (6), 219 (100), 154 (5),
130 (8), 77 (9); HRMS found: [MHKCO2]C354.0805,
C20H18ClNOP requires 354.0815.
4.2.14. trans-2S,20S,30R-N-[(1-Diphenylphosphinyl-3-(2-
trifluoromethylphenyl)-2-aziridinyl)carbonyl]bornane-
10, 2-sultam (Table 1, entry 10). Following the general
procedure described above N-bromoacetyl-2S-bornane-10,
2-sultam (672 mg, 2.0 mmol), LiHMDS in THF (2.1 mL,
1.0 M, 2.1 mmol) and P,P-diphenyl-N-(2-trifluoromethyl-
phenylmethylene)phosphinic amide (747 mg, 2.0 mmol)
were reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
eluting with petrol–EtOAc (1/9) to afford the product, as a
colourless solid (860 mg, 69%); Rf 0.50 (EtOAc); [a]D20
C52.6 (c 1, CHCl3); dH (250 MHz, CDCl3) 0.74 (3H, s),
0.80 (3H, s), 1.09–1.33 and 1.72–1.97 (7H, 2!m), 3.31
(2H, m), 3.79 (1H, m), 4.02 and 4.48 (2H, 2!dd, JPZ
13.0 Hz, JZ2.7 Hz), 7.29–7.46 (10H, m), 7.79–7.87 (4H,
m); dC (60 MHz, CDCl3) 20.2, 21.2, 26.9, 33.1, 38.1, 41.8,
44.8, 44.9, 48.2, 49.2, 53.3, 65.8, 126.1, 126.2, 127.9, 128.6,
128.7, 128.8, 128.9, 129.9, 130.4, 131.3, 132.0, 132.1,
132.2, 132.3, 132.3, 132.8, 133.3, 134.9, 164.3; MS (CI) m/z
629 ([MH]C, 35%), 565 (25), 419 (78), 347 (20), 219 (100),
185 (32), 77 (10); HRMS found: [MH]C629.1843, C32H33-
N2O4PSF3 requires 629.1851.
4.3.3. trans-2-Carboxy-N-diphenylphosphinyl-3-(2-tri-
fluoromethylphenyl)aziridine (Table 2, entry 3).
Following the general procedure described above cis-
2S,20S,30S-N-[(1-diphenylphosphinyl-3-(2-trifluoromethyl-
phenyl)-2-aziridinyl)carbonyl]bornane-10,
2-sultam
(126 mg, 0.2 mmol) afforded the product as a colourless
oil (49 mg, 57%). [a]2D0 C15.4 (c 1, CHCl3); IR nmax (CCl4)
1723, 1440, 1129, 1036, 757, 730, 695 cmK1; dH (250 MHz,
CDCl3) 3.43 and 4.48 (2H, 2!dd, JPZ12.7 Hz, JZ2.7 Hz),
7.45–8.00 (14H, m); dC (60 MHz, CDCl3) 42.5, 47.3, 123.9,
127.3, 127.3, 128.8, 130.1, 130.2, 130.2, 130.3, 130.4,
130.5, 132.8, 133.0, 133.1, 133.1, 133.2, 133.8, 133.9,
134.0, 169.9; MS (CI) m/z 432 ([MH]C, 35%), 388 (21),
235 (100), 201 (11); HRMS found: [MH]C432.0984,
C22H18NO3PF3 requires 432.0976.
4.3. General procedure for hydrolytic cleavage
of camphorsultam auxiliary
2,3-Disubstituted N-diphenylphosphinyl aziridines bearing
the camphor sultam moiety (typically 0.2 mmol), were
dissolved in a THF–water (4/1) mixture (5 mL). Lithium
hydroxide monohydrate (0.4 mmol) was then added and the
resulting suspension stirred vigorously overnight. The
excess solvent was removed under reduced pressure and
the aqueous layer basified to pH 10 with saturated NaHCO3
solution, and extracted with CHCl3 (3!30 mL). The
combined organic layers were washed with saturated
NaHCO3 solution (10 mL), dried (MgSO4), filtered and
the solvent removed under reduced pressure to afford the
2S-bornane-10, 2-sultam. The aqueous layer was then
combined with the base washings and acidified to pH 2
with saturated citric acid solution, and extracted with CHCl3
(3!50 mL). The organic layers were combined, dried
(MgSO4), filtered and the solvent removed under reduced
pressure to afford the N-diphenylphosphinyl-2-substituted-
3-carboxyaziridines.
4.3.4. cis-2-Carboxy-N-diphenylphosphinyl-3-(2-methyl-
phenyl)aziridine (Table 2, entry 4).0Following the general
procedure described above cis-2S,2 S,30S-N-[(1-diphenyl-
phosphinyl-3-(2-methylphenyl)-2-aziridinyl)carbonyl]-
bornane-10, 2-sultam (115 mg, 0.2 mmol) afforded the
product as a colourless oil (61 mg, 81%). [a]2D0 C2.6 (c 1,
MeOH); IR nmax (CCl4) 1729, 1439, 1128, 1041, 755,
694 cmK1; dH (250 MHz, CDCl3) 2.16 (3H, s), 3.47 and
3.94 (2H, 2!dd, JPZ15.7 Hz, JZ6.6 Hz), 6.88–7.95 (14H,
m); dC (60 MHz, CDCl3) 19.3, 41.8, 42.1, 126.8, 128.9,
129.5, 130.3, 130.4, 130.5, 130.6, 131.1, 132.6, 132.8,
133.0, 133.1, 133.3, 133.5, 134.4, 134.4, 134.5, 138.4,
169.6; MS (CI) m/z 378 ([MH]C, 35%), 334 (100), 235 (9),
201 (19), 134 (17); HRMS found: [MH]C378.1248,
C22H21NO3P requires 378.1259.
4.3.5. cis-2-Carboxy-N-diphenylphosphinyl-3-(2-ethyl-
phenyl)aziridine (Table 2, entry 5).0Following the general
procedure described above cis-2S,2 S,30S-N-[(1-diphenyl-
phosphinyl-3-(2-ethylphenyl)-2-aziridinyl)carbonyl]-
bornane-10, 2-sultam (118 mg, 0.2 mmol) afforded the
product as a colourless oil (51 mg, 65%). [a]2D0 K5.7 (c 1,
4.3.1. trans-2-Carboxy-N-diphenylphosphinyl-3-(2-
methylpropenyl)aziridine (Table 2, entry 1). Following
the general procedure described above cis-2S,20S,30S-N-[(1-
diphenylphosphinyl-3-(2-methylpropenyl)-2-aziridinyl)-
carbonyl]bornane-10, 2-sultam (108 mg, 0.2 mmol)
afforded the product as a colourless oil (33 mg, 50%).
[a]2D0 C17.8 (c 1, CHCl3); IR nmax (CCl4) 1718, 1440, 1127,
1028, 757, 728, 697 cmK1; dH (250 MHz, CDCl3) 1.26 (6H,
2s), 4.26 (1H, dd, JPZ13.4 Hz, JZ5.8 Hz), 5.83 (1H, ddd,
JZ13.4, 13.4, 5.8 Hz), 5.93 (1H, d, JZ13.4 Hz), 7.46–7.95
(10H, m); dC (60 MHz, CDCl3) 30.0, 30.2, 57.0, 71.4, 125.1,
CHCl3); IR nmax (CCl4) 1718, 1439, 1130, 756, 697 cmK1
;
dH (400 MHz, CDCl3) 1.03 (3H, t, JZ7.5 Hz), 2.57 (2H, q,
JZ7.5 Hz), 3.47 and 4.02 (2H, 2!dd, JPZ15.7 Hz, JZ
6.6 Hz), 6.66–7.97 (14H, m); dC (60 MHz, CDCl3) 15.7,
26.7, 41.8, 42.3, 126.8, 129.2, 129.4, 129.8, 130.3, 130.4,
130.5, 130.6, 132.6, 132.8, 132.9, 133.1, 133.3, 133.4,

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3694–3703
3703
Sweeney, J. Tetrahedron: Asymmetry 1997, 8, 1693. Padwa, A.;
Murphree, S. S. In Gribble, G. W., Gilchrist, T. L., Eds.;
Progress in Heterocyclic Chemistry; Oxford: Pergamon
Elsevier Science, 2000; Vol. 12, Chapter 4.1, p 57. Sweeney,
J. B. Chem. Soc. Rev. 2002, 31, 247. Huang, D.; Yan, M.; Shen,
Q. Clin. J. Org. Chem. 2004, 24, 1200. For recent reports of
aziridination reactions, see: Padwa, A.; Flick, A. C.; Leverett,
C. A.; Stengel, T. J. Org. Chem. 2004, 69, 6377. Omura, K.;
Uchida, T.; Irie, R.; Katsuki, T. Chem. Commun. 2004, 2060.
Xu, J. X.; Ma, L. G.; Jiao, P. Chem. Commun. 2004, 1616.
Weller, R. L.; Rajski, S. R. Tetrahedron Lett. 2004, 45, 5807.
Kim, S. K.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2004, 43,
3952. Avenier, F.; Latour, J. M. Chem. Commun. 2004, 1544.
Morton, D.; Pearson, D.; Field, R. A.; Stockman, R. A. Org.
Lett. 2004, 6, 2377. Vyas, R.; Gao, G. Y.; Harden, J. D.; Zhang,
X. P. Org. Lett. 2004, 6, 1907. Kumar, G. D. K.; Baskaran, S.
Chem. Commun. 2004, 1026. Watson, I. D. G.; Styler, S. A.;
Yudin, A. K. J. Am. Chem. Soc. 2004, 126, 5086. Siu, T.; Yudin,
A. K. J. Am. Chem. Soc. 2002, 124, 530.
134.4, 134.5, 134.6, 144.6, 169.5; MS (CI) m/z 348 ([MHK
CO2]C, 100%), 219 (47), 201 (31), 146 (9), 77 (7); HRMS
found: [MHKCO2]C348.1526, C22H22NOP requires
348.1517.
Acknowledgements
We acknowledge the financial support of the EPSRC
(A.McL. and A.A.C.) and Parke Davis Neuroscience
Research Centre (A.A.C.). J.B.S. thanks Zeneca for an
award from the Strategic Research Fund. We also acknowl-
edge the contributions of Mr. Kenneth Matheson.
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