Asymmetric aziridine synthesis by aza-Darzens reaction of N-diphenylphosphinylimines with chiral enolates. Part 1: Formation of cis-aziridines

Article abstract of DOI:10.1016/j.tet.2006.01.068

The aza-Darzens ('ADZ') reactions of N-diphenylphosphinyl ('N-Dpp') imines with chiral enolates derived from oxazolidinones and camphorsultam have been studied. Whilst oxazolidinone enolates reacted poorly in terms of aziridination, the use of the chiral

Full text of DOI:10.1016/j.tet.2006.01.068

Tetrahedron 62 (2006) 3681–3693
Asymmetric aziridine synthesis by aza-Darzens reaction
of N-diphenylphosphinylimines with chiral enolates.
Part 1: Formation of cis-aziridines
a
b
b
J. B. Sweeney,a,b, Alex A. Cantrill, Andrew B. McLaren and Smita Thobhani
*
aSchool of Chemistry, University of Bristol, Bristol BS8 1TS, UK
bSchool of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK
Received 27 November 2004; revised 31 December 2005; accepted 19 January 2006
Available online 24 February 2006
Abstract—The aza-Darzens (‘ADZ’) reactions of N-diphenylphosphinyl (‘N-Dpp’) imines with chiral enolates derived from oxazolidinones
and camphorsultam have been studied. Whilst oxazolidinone enolates reacted poorly in terms of aziridination, the use of the chiral enolate
derived from both antipodes of N-bromoacetyl 2,10-camphorsultam, 2R-(5) and 2S-(5), with N-diphenylphosphinyl aryl and tert-butylimines
proceeded in generally good yield to give, respectively, (20R,30R)- or (20S,30S)-cis-N-diphenylphosphinyl aziridinoyl sultams of high de.
q 2006 Elsevier Ltd. All rights reserved.
1. Introduction
3. Results and discussion
Though aziridines are regarded as valuable synthetic
intermediates, there remain few generally applicable methods
for the one-step preparation of these compounds in high
enantiomeric purity from readily available precursors.1,2
Furthermore, the methodology previously described is often
compromised by the fact that the substituents present on
nitrogen (often sulfonyl groups) frequently are not compatible
with further immediate synthetic manipulation.
3.1. Feasibility study: reaction of achiral ester enolates
with N-Dpp imines
ADZ reactions of N-Dpp imines had not been reported
before we embarked upon our work, which meant that our
first task was to assess the feasibility of the proposed
reaction using achiral reagents. Thus, when N-diphenyl-
phosphinybenzaldimine6 was added to the lithium enolate
of methyl bromoacetate at K78 8C, a diastereoselective
reaction was observed, affording methyl N-diphenylpho-
sphinyl-2-phenyl aziridine carboxylate 1a in 60% yield; the
product was obtained as 90:10 mixture of cis- and trans-
diastereoisomers (JcisZ6.5 Hz, JtransZ2.8 Hz, Scheme 1).
The isomers were separable by flash chromatography; the
predominance of the cis-isomer is consistent with results
obtained in many other aziridine syntheses.1
2. Background
We have previously investigated the preparation and ring-
opening reactions of N-diphenylphosphinyl aziridines,3 and
were keen to devise an asymmetric synthesis of these
aziridines; we were especially interested in facilitating the
preparation of chiral 2-carboxyaziridines, because of the
potential use of such compounds as precursors to related
non-proteinogenic 2-amino acids. We report here in detail
the results of our preliminary studies4 into the aza-Darzens
(ADZ) reaction5 of N-Dpp imines with chiral, camphor-
sultam-derived a-bromoenolates, which show that the
routine preparation of chiral N-Dpp-2-carboxyaziridines
with high levels of diastereomeric and enantiomeric purity
is indeed feasible.
When a bulkier ester was used in the same procedure, the
diastereoselectivity of the reaction was similar (the cis-
isomer, cis-1b, again dominated the product mixture), but
lower (cis:transZ60:40, Scheme 1). In this case, a precise
measurement of the diastereoselectivity was hampered by
the fact that these diastereoisomers could not easily be
separated, either by flash chromatography, or by
crystallisation.
Keywords: Aza-Darzens; Aziridination; Imine; Camphorsultam.
*
When NaHMDS was used as base in the preparation of the
tbutyl aziridine carboxylate, only cis-1b was produced, but
Corresponding author. Tel.: C44 118 931 6585; fax: C44 118 378 6331;
e-mail: j.b.sweeney@rdg.ac.uk
0040–4020/$ - see front matter q 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.01.068

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J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
Dpp
Dpp
1. LiHMDS, THF, –78 °C
2. PhCH=NP(O)Ph2, THF, –78 °C
O
H
H
O
N
N
+
H
H
Br
RO
RO
RO
Ph
Ph
2 equiv
O
1a, R = Me, 59% yield, cis:trans = 93:7
1b, R = tBu, 60% yield, cis:trans = 60:40
Scheme 1.
the efficiency of the transformation was greatly reduced
(Scheme 2). Under these conditions, the major product of
the reaction was the starting imine, even when prolonged
reaction time and/or increased temperatures were employed.
a reaction pathway known for processes conducted above
0 8C.8 The use of NaHMDS, thereby furnishing the
corresponding sodium enolate, was more encouraging:
when the reaction was started at K78 8C and allowed to
warm to ambient temperatures, an unequal mixture of two
diastereomeric cis-aziridines (4a and 4b) was obtained, in
mediocre yield (Scheme 3). Again the major reaction
pathway furnished oxazolidinone 3, in 60% yield. These
aziridines are non-crystalline, and the analysis of their
stereochemistry was carried out using NMR spectroscopy
and computer modelling, which led us tentatively to assign
the absolute configurations of the new asymmetric centres in
the major product 4a as (20R,30R) (Scheme 3).
Armed with a set of conditions for our new ADZ reaction,
we turned to an asymmetric version of these reactions.
3.2. Aziridination via reaction of 4S-N-bromoacetyl-4-
isopropyloxazolidinone enolates with N-Dpp-imines
As a first goal, we sought a reagent-controlled process and
chose to examine the use of an Evans’ auxiliary. Thus, (4S)-
N-bromoacetyl-4-isopropyloxazolidinone (2)7 was deproto-
nated at K78 8C in THF by LiHMDS and to the resultant
lithium enolate was added a solution of N-Dpp benzaldi-
mine. Under these (and a range of other) reaction
conditions, no product of Darzens-like reaction were
observed: instead, the only product isolated from these
reactions was the parent oxazolidinone 3, its presence
presumably resulting from elimination to generate ketene,
In an effort to improve the yield of aziridination at the
expense of the elimination pathway, we experimented with
many variations of the precise conditions of these reactions,
but found little success in these endeavours; noteworthy
observations include the obtention of a mixture of 4a and
trans-aziridines 4c and 4d when using diethyl ether as
solvent for the reaction (Scheme 4).
Dpp
1. NaHMDS, THF, –78 °C
2. PhCH=NP(O)Ph2, THF, –78 °C
O
H
N
H
12% yield
Br
tBuO
tBuO
Ph
2
equiv
O
cis-1b
Scheme 2.
Scheme 3.
Scheme 4.
O
O
O
Dpp
O
Dpp
N
Br
H
O
N
i, ii
N
N
+
+
O
O
NR2
NR2
Ph
Ph
H
4a
H
H
H
2
4b
~2% yield
3
32% yield
60% yield
Conditions: i. NaHMDS, THF, –78 °C; ii. PhCH=NP(O)Ph2
.
O
Dpp
N
O
O
Dpp
N
Dpp
N
Br
O
O
O
H
i, ii
N
N
+
+
+
O
O
NR2
NR2
NR2
Ph
Ph
Ph
H
H
H
4c
H
H
4d
H
2
4a
16% yield
3
60% yield
13% yield
Conditions: i. NaHMDS, Et2O, –78 °C; ii PhCH=NP(O)Ph2
.

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
3683
In this case, the trans-aziridines were obtained as an
inseparable mixture of (20R,30R) and (20S,30S) isomers.
Thus, it seemed that the use of chiral oxazolidinones in ADZ
reactions was problematic: we turned our attention to
another chiral controller.
(20R,30R). This observation implies that the reaction proceed
via a syn-selective aza-aldol reaction, involving nucleophi-
lic attack of the si-face of the enolate upon the si-face of the
imine, followed by ring-closure. The obtention of aziridine
rather than the intermediate aminobromide is noteworthy,
because previously-reported asymmetric Darzens and aza-
Darzens reactions using boron-containing asymmetric
reagents or catalysts did not proceed directly to the
heterocyclic product (epoxide, or aziridine, respectively),
relying instead on a subsequent, separate, ring-closing step
(Scheme 6).
3.3. Aziridination via reaction of 2R-N-bromoacetyl-
camphorsultam enolates with N-Dpp-imines
2R-N-Bromoacetylcamphorsultam (5) was prepared in 71%
yield in routine fashion (Scheme 5); to our surprise, this
compound had not been reported in the literature
previously.9
Encouraged by this result, we immediately turned our
attention to an examination of the scope of the reaction. The
results of the first part of our study are collated in Table 1.
Thus, a range of aromatic imines was found to undergo
ADZ reaction in acceptable yield and with virtually
complete diastereo- and enantiocontrol. In all these
examples (and despite significant variation in reaction
conditions), a small amount of deacetylated sultam (!10%)
was always isolated in addition to the desired aziridines;
presumably this by-product arises by elimination from the
initially formed bromoenolate, or by a self-condensation. As
expected, the use of the enantiomeric auxiliary (Table 1,
entries 10–16) yielded aziridine products of opposite
stereochemistry, with similar selectivity. In most of the
reactions the yield of aziridine was good, the only exception
being the reaction of the N-Dpp imine derived from
pivaldehyde (vide infra), and spectroscopic analysis of
crude products again did not indicate the presence of other
diastereoisomers. In the reaction of N-Dpp pivaldehyde
imine (Table 1, entry 9) the mediocre yield (40%) of
aziridine 7i was due, in part, to the fact that the precursor
1,2-aminobromide 8 (13%) was also isolated (Scheme 7). It
would seem that the additional barrier to rotation caused
by the presence of a substituent of considerable steric
demand retards the necessary bond rotation, which must
occur prior to the second step, cyclization to give the
aziridine product.
i
Br
75% yield
NH
N
S
S
O
O
O
O
O
5
Conditions: i. nBuLi, BrCH2C(O)Br, THF, –78 °C.
Scheme 5.
Deprotonation of 5 in THF at K78 8C using LiHMDS gave
a-bromo lithioenolate 6, to which was immediately added a
THF solution of N-diphenylphosphinylbenzaldimine
(Scheme 6). The reaction was allowed to proceed for 3 h
at K78 8C, after which aqueous work-up gave aziridinyl
sultam 7a. Spectroscopic examination (1H and 13C NMR) of
this crude product indicated that only one, cis-configured
(JZ6.2 Hz), diastereoisomer had been formed: no evidence
of the alternate diastereoisomer could be found. Chromato-
graphic purification subsequently furnished pure (20R,30R)-
7a in 71% yield, accompanied by a small amount of
deacetylated sultam (8%); no trace of any trans-configured
aziridine, nor could any of the alternative cis-diastereo-
isomer be isolated from the reaction.
Single crystal X-ray analysis of 7a confirmed the
stereochemical analysis, and revealed the absolute con-
figurations of the newly-created asymmetric centres to be
As mentioned above, the identification of cis-aziridines as
the only products of the reaction was based on analysis of 1H
Scheme 6.

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J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
Table 1. Asymmetric aza-Darzens reaction of N-bromoacetyl camphorsultams
Dpp
1. NaHMDS, THF, –78 °C
2. RCH=NP(O)Ph2, THF, –78 °C
H
O
N
H
Br
N
R
R
N
R
S
S
O
O
O
O
O
5
7a–p
Entry
R
Yield 7 (%)
cis:trans
dr
1
2
3
4
5
6
7
8
Ph
7a 71
7b 75
7c 78
7d 70
7e 60
7f 72
7g 67
7h 68
7i 40b
7j 71
7k 57
7l 60
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
O95:!5a
O95:!5a
O95:!5a
O95:!5a
O95:!5a
O95:!5a
O95:!5a
O95:!5a
O95:!5a
O95:! 5d
O95:! 5d
O95:! 5d
O95:! 5d
O95:! 5d
O95:! 5d
O95:! 5d
4-O2N–C6H4
4-MeO–C6H4
2-O2N–C6H4
4-Br–C6H4
2-Naphthyl
2-Fluorenyl
2-Furyl
9
tBu
10
11
12
13
14
15
16
Phc
4-F–C6H4
c
c
2,6-Cl2–C6H4
c
3-Br–C6H4
4-MeO–C6H4
2-Pyridylc
7m 60
7n 60
7o 67
7p 47
c
CH2]CHc
a (20R,30R):(20S,30S).
b (20S,30R)-syn-(2-Bromo-3-(diphenylphosphinyl)amino)sultam (8) also isolated in 13% yield.
c (2S)-Sultam used as auxiliary.
d (20S,30S):(20R,30R).
Dpp
Br
H
N
NHD
pp
R
i, ii
H
Br
+
S
R
R
N
N
N
S
S
S
O
O
O
O
O
O
O
O
O
7i
40% yield
8
13% yield
R2N
NLiDpp
R2N
H
Conditions:
Li SLOW
O
O
i. NaHMDS, THF, –78 °C;
N
ii tBuCH=NP(O)Ph2, THF, –78 °C.
H
Dpp
Br
Br
Scheme 7.
coupling constants (aziridines exhibit 3JcisZ4.5–7 Hz while
3JtransZ1.5–3 Hz). In certain cases, however, the relatively
restricted rotation induced by the bulky N-substituent led to
broad and overlapping resonances, which initially precluded
assignment of cis- or trans-stereochemistry. Thus, the
identification of the product of the reaction of para-
nitrophenylbenzaldimine 7b with the camphorsultam
enolate (Table 1, entry 5) was complicated by the fact that
the 1H resonances of the aziridine protons were not resolved
in deuteriochloroform. The signals were, however, resolved
in deuteriobenzene, allowing identification of the 3J
coupling constant as 6.4 Hz, again indicative of a cis-
configured product (Fig. 1).
3.4. Hydrolytic cleavage of auxiliary from
(aziridinyl)acyl sultams
As the utility of the Dpp group as an aziridine activator had
alreadybeendemonstratedwithinourgroup,wenextsoughtto
cleave the chiral auxiliary (to give the corresponding
N-diphenylphosphinyl aziridine carboxylic acids) thereby
allowing preparation of simple esters, for use in subsequent
synthetic endeavours. Since the acylsultam linkage is labile
under basic conditions, whereas the Dpp group is normally
removed under acidic conditions, we were confident that this
selective hydrolysis would be routine. Reaction of aziridinyl
sultams with 1 equiv of lithium hydroxide monohydrate,
proceeded smoothly, yielding the corresponding N-Dpp
aziridine carboxylates 9 in generally good yield (Table 2,
Scheme 8). These heterocycles are ideal precursors to a range
of aziridine esters or other derivatives, valuable compounds
both for synthesis and biological studies.
A similar situation was encountered in the analysis of the
para-bromo analogue 7e (Table 1, entry 2) (Fig. 2): the
3
C6D6 spectrum revealed a J value similar in magnitude to
the para-nitro compound.

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
3685
Dpp
H
O
N
H
N
S
O
O
7b
NO2
4.40
4.35
4.30
PPM
4.25
4.20
5.0
4.9
4.8
4.7
4.6
4.5
4.4
4.3
PPM
1H NMR in CDCl3
1H NMR in C6D6
Figure 1.
Dpp
H
O
N
H
N
S
O
O
7e
Br
5.0
4.9
4.8
4.7
PPM
4.6
4.5
4.4
4.3
4.30
4.25
4.20
4.15
4.10
PPM
1H NMR in CDCl3
1H NMR in C6D6
Figure 2.
Table 2. Removal of auxiliary from (aziridinyl)acylcamphorsultams
process; the subsequent paper in this series will describe our
observations of factors controlling the diastereoselectivity
of the aziridine-forming reactions, and comments concer-
ning the mechanism of the reaction.
Entry
R
Sultam Aziridine
configuration configuration
Yield 9 (%)
(20R,30R)
1
2
3
4
5
6
7
8
9
Ph
R
R
R
R
9a 64
9b 60
9c 67
9d 61
9e 67
9f 47
9g 80
9h 45
9i 100
(20R,30R)
4-O2N–C6H4
2-O2N–C6H4
4-Br–C6H4
2-Naphthyl
tBu
3-Br–C6H4
2,6-Cl2–C6H3
2-Pyridyl
(20R,30R)
(20R,30R)
5. Experimental
(20R,30R)
R
(20R,30R)
(20S,30S)
(20S,30S)
(20S,30S)
R
S
S
S
5.1. General techniques
All organic solvents were distilled prior to use and all
reagents were purified by standard procedures.10 ‘Petrol’
refers to the fraction of petroleum ether with the boiling
range 40 to 60 8C and ‘ether’ refers to diethyl ether.
Ether and THF were distilled from sodium benzo-
phenone ketyl; toluene from sodium; dichloromethane,
triethylamine, acetonitrile from calcium hydride, methanol
from magnesium methoxide and diisopropylethylamine
from potassium hydroxide. Chemicals were purchased from
Aldrich Chemical Co. or prepared by literature methods.
Dpp
N
Dpp
1. LiOH, THF/H2O, room tempe. rature
N
2. 2 M HCl
HO2C
Sultam
R
O
R
9
Scheme 8.
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
4. Conclusion
We have demonstrated the use of the previously unreported
N-bromoacylcamphorsultams as efficient precursors to a
range of cis-N-Dpp-aziridine-2-carboxylates by a two-step

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J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
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 Hertz.
5.1.3. (G)-tButyl cis- and trans-N-diphenylphosphinyl-3-
phenylaziridine-2-carboxylate (1b). To a solution of tert-
butyl 2-bromoacetate (0.08 mL, 0.52 mmol) in THF
(10 mL) at K78 8C, was added LiHMDS in THF
(0.52 mL, 1.0 M, 0.52 mmol), dropwise. After 30 min, a
THF (10 mL) solution of N-(phenylmethylene)diphenyl-
phosphinamide (80 mg, 0.26 mmol), was slowly added at
K78 8C. The reaction was then stirred for 2.5 h, before
being quenched with water, and diluted with EtOAc at
K78 8C. The solution was then partitioned between H2O
(10 mL), and EtOAc (2!10 mL), the combined organic
layers were then washed with brine (15 mL), dried
(MgSO4), filtered, and the solvent removed in vacuo to
leave a yellow oil. This was purified by flash chromato-
graphy (EtOAc/petrol 1:1) to give a mixture of cis-1b and
trans-1b (cis:transZ60:40) as a colourless oil (65 mg,
60%). Rf 0.6 (EtOAc); IR nmax (CHCl3) 2985, 1737, 1438,
1369, 1180, 1127, 729, 697 cmK1; dH (270 MHz, CDCl3)
1.15 and 1.35 (9H, 2!s), 3.56 (0.4H, dd, JPZ13.3 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.
J(trans)Z2.8 Hz), 3.58 (0.6H, dd, JPZ15.2 Hz, J(cis)
Z
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.
6.6 Hz), 4.08 (0.4H, dd, JPZ11.5 Hz, J(trans)Z2.8 Hz),
4.10 (0.6H, dd, JPZ15.4 Hz, J(cis)Z6.6 Hz), 7.22–8.21
(15H, m), dC (67.5 MHz, CDCl3) 27.7, 27.8, 41.2, 41.4,
43.4, 43.5, 44.7, 44.8, 127.6, 127.9, 128.4, 132.4, 135.1,
165.2, 166.8; m/z (CI) 420 (MHC, 5%), 364 (MKtBu, 27),
320 (MKCOt2Bu, 100), 201 (17), 120 (48), 79 (72); HRMS
found: [MH]C420.1722, C25H27NO3P requires 420.1729.
5.1.4. (G)-tButyl cis-N-diphenylphosphinyl-3-phenyl-
aziridine-2-carboxylate (cis-1b). By following the pro-
cedure above, tert-butyl 2-bromoacetate (0.2 mL, 1.3 mmol),
NaHMDS in THF (1.3 mL, 1.0 M, 1.3 mmol), N-(phenyl-
methylene)diphenylphosphinamide (200 mg, 0.66 mmol),
were reacted together in THF (15 mL) at K78 8C for 3 h, to
give a yellow oil. Purification by flash chromatography
(EtOAc/petrol 1:1) gave cis-1b as a colourless oil (33 mg,
12%). Rf 0.6 (EtOAc); IR nmax (CHCl3) 2976, 1743, 1439,
1368, 1180, 1127, 729, 697 cmK1; dH (270 MHz, CDCl3)
1.15 (9H, s), 3.58 (1H, dd, JPZ15.4 Hz, JZ6.6 Hz), 4.10
(1H, dd, JPZ15.6 Hz, JZ6.6 Hz), 7.23–7.56 (11H, m),
7.91–8.21 (4H, m); dC (67.5 MHz, CDCl3) 27.8, 41.4, 43.5,
44.8, 127.6, 127.9, 128.4, 132.4, 135.1, 166.8; m/z (CI) 420
(MHC, 18%), 364 (MKtBuCHC, 51), 320 (MKCOt2BuC
HC, 100), 218 (15), 120 (14); HRMS found:
[MH]C420.1720, C25H27NO3P requires 420.1729.
5.1.1. (G)-Methyl cis N-diphenylphosphinyl-3-phenyl-
aziridine-2-carboxylate (cis-1a). To a solution of methyl
2-bromoacetate (0.18 mL, 1.83 mmol) in THF (10 mL) at
K78 8C, was added LiHMDS in THF (1.83 mL, 1.0 M,
1.83 mmol), dropwise. After 30 min, a THF (10 mL)
solution of N-(phenylmethylene)diphenylphosphinamide
(280 mg, 0.92 mmol), cooled to K78 8C, was slowly
added. The reaction was then stirred for 2.5 h, before
being quenched with water, and diluted with EtOAc at
K78 8C. The solution was partitioned between H2O
(10 mL), and EtOAc (2!10 mL), the organic layers
separated, washed with brine (15 mL), dried (MgSO4),
filtered, and the solvent removed in vacuo to leave a yellow
oil. Purification by flash chromatography (EtOAc/petrol
1:1) gave cis-1a as an oil (190 mg, 55%). Rf 0.7 (EtOAc); IR
nmax (CHCl3) 2982, 1751, 1437, 1175, 1126, 729 cmK1; dH
(270 MHz, CDCl3) 3.48 (3H, s), 3.71 (1H, dd, JPZ14.9 Hz,
JZ6.5 Hz), 4.16 (1H, dd, JPZ15.8 Hz, JZ6.5 Hz), 7.30–
7.55 (11H, m), and 7.92–8.18 (4H, m); dC (67.5 MHz,
CDCl3) 40.7, 41.7, 52.2, 127.5, 128.4, 130.5, 132.4, 137.0,
166.6; m/z (CI) 378 (MHC, 100%), 346 (40), 320 (18), 201
(19), 79 (18); HRMS found: [MH]C378.1260, C22H21NO3
requires 378.1259.
5.1.5. (4S,20R,30R)-(D)-3-[(10-Diphenylphosphinyl-30-
phenyl-20-aziridinyl)carbonyl]-4-(1-methylethyl)oxazoli-
din-2-one (4a).11 (4S)-(C)-3-Bromoacetyl-4-(1-methy-
lethyl)-2-oxazolidinone (150 mg, 0.6 mmol), was
dissolved in THF (15 mL), and cooled to K78 8C.
NaHMDS in THF (0.66 mL, 1.0 M, 0.66 mmol) was then
added dropwise, and the resulting pale yellow solution
stirred for 30 min. N-(Diphenylmethylene)diphenylpho-
sphinamide (900 mg, 0.3 mmol), was then added at
K78 8C as a solution in THF (5 mL). The reaction mixture
was then stirred for 3 h and allowed to reach ambient
temperature, at which point the reaction was quenched with
saturated ammonium chloride solution (20 mL) and 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 a yellow oil. Purification by
flash chromatography (gradient 20–80% EtOAc in petrol),
5.1.2. (G)-Methyl trans N-diphenylphosphinyl-3-phenyl-
aziridine-2-carboxylate (trans-1a). Trans-1a was also
isolated from the reaction, as a viscous oil (15 mg, 4%).
Rf 0.4 (EtOAc); IR nmax (film) 2924, 1747, 1439, 1211,
1124, 728, 696 cmK1; dH (270 MHz, CDCl3) 3.57 (1H, dd,
JPZ13.6 Hz, JZ2.8 Hz), 3.60 (3H, s), 4.03 (1H, dd, JPZ
14.2 Hz, JZ2.9 Hz), 7.30–7.46 (11H, m), and 7.65–8.06
(4H, m); m/z (CI) 378 (MHC, 100%), 346 (26), 320 (17),
201 (17), 201 (17), 176 (13); HRMS found:
[MH]C378.1274, C22H21NOP requires 378.1259.

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
3687
provided a clear oil, which was crystallised from EtOAc/
Hexane to afford 4a as colourless needles (40 mg, 32%). Rf
0.5 (EtOAc); mp 183–184 8C; [a]2D0 C110.9 (c 1.5,
CH2Cl2); IR nmax (film) 2964, 1785, 1708, 1439, 1209,
1126, 729, 698 cmK1; dH (400 MHz, CD2Cl2) 0.00 (3H, d,
JZ7.0 Hz), 0.61 (3H, d, JZ7.0 Hz), 1.71–1.74 (1H, m),
3.94–3.98 and 4.05–4.12 (3H, 2!m), 4.33 and 4.38 (2H,
2!dd, JPZ15.2 Hz, JZ6.6 Hz), 7.12–8.19 (15H, m); dC
(67.5 MHz, CDCl3) 13.1, 17.6, 27.9, 42.1, 42.5, 58.1, 63.7,
127.3, 128.5, 131.4, 132.2, 135.2, 153.2, 164.7; m/z (CI) 475
([MH]C, 100%), 346 (56), 320 (43), 275 (28), 201 (23), 130
(63); HRMS found: [MH]C475.1775, C27H28N2O4P
requires 475.1787; Found: C, 68.3; H, 5.8; N, 6.1;
C27H27N2O4P requires C, 68.4; H, 5.8; N, 5.9%.
(20 mL) added. The organic layer was partitioned and the
aqueous layer washed with EtOAc (2!10 mL). The
combined organic layers were then dried (MgSO4), filtered,
and the solvent removed in vacuo. The resulting pale yellow
oil was then purified by flash chromatography, (gradient
0–10% EtOAc in hexane), affording (R)-5 as a clear oil,
which was crystallised from CHCl3/hexane to provide
colourless needles (220 mg, 71%). Rf 0.4 (EtOAc/heptane
3:7); mp 113–114 8C; [a]2D0 K118.5 (c 1, CH2Cl2); IR nmax
(CHCl3) 2959, 1705, 1330, 1170 cmK1; dH (400 MHz,
CDCl3) 0.98 and 1.16 (6H, 2!s), 1.37–1.43, and 1.90–2.16
(7H, 2!m), 3.44–3.55 (2H, 2!d, JZ14.0 Hz), 3.91 (1H,
dd, JZ7.6, 5.1 Hz), 4.20 and 4.34 (2H, 2!d, JZ13.0 Hz);
dC (100 MHz, CDCl3), 19.9, 20.7, 26.4, 27.5, 32.8, 37.9,
44.5, 47.9, 49.1, 52.7, 65.5, 164.5; m/z (CI) 336 ([MH]C,
86%), 258 (16), 192 (42), 135 (100); HRMS found:
[MH]C336.0259, C12H19BrNO3S requires 336.0269;
Found: C, 43.0; H, 5.5; N, 4.1; C12H18BrNO3S requires C,
42.9; H, 5.4; N, 4.2%.
5.1.6. (4S,20S,30S)-(D)-3-[(10-Diphenylphosphinyl-30-
phenyl-20-aziridinyl)carbonyl]-4-(1-methylethyl)oxazoli-
din-2-one (4b). From the reaction described above a small
quantity of a different cis diastereoisomer, 4b, was also
isolated (2–3 mg, w2%), as a colourless oil. This product
could not be satisfactorily separated from (4S)-4-(1-
methylethyl) oxazolidinone generated by enolate decompo-
sition and only partial physical data were collected: Rf 0.6
(EtOAc); dH (400 MHz, CDCl3) 0.74 and 0.78 (6H, 2!d,
JZ7.1 Hz), 2.13–2.20 (1H, m), 3.86–3.91 and 4.09–4.12
(3H, 2!m), 4.27 and 4.45 (2H, 2!dd, JPZ15.4 Hz, JZ
6.6 Hz), 7.28–8.26 (15H, m); m/z (CI) 475 ([MH]C, 65%),
390 (10), 346 (40), 320 (41), 275 (25), 201 (23), 130 (100);
HRMS found: [MH]C475.1796, C27H28N2O4P requires
475.1787.
5.1.9. (2S)-(D)-(N-Bromoacetyl)bornane-10,2-sultam
(S-5). Bornane-10,2-sultam (1.00 g, 4.7 mmol) was dissolved
in anhydrous THF (30 mL) under a nitrogen atmosphere and
cooled to K78 8C. n-BuLi in hexanes (2.1 mL, 2.5 M,
5.1 mmol) was added dropwise to the solution and left to stir
for approximately 1 h. After this time bromoacetyl bromide
(0.4 mL, 4.7 mmol) dissolved in anhydrous THF (20 mL)
was added dropwise to the reaction mixture. The reaction
mixture was allowed to stir for 3 h at K78 8C and the course
of the reaction was followed by TLC. Once all starting
materials had been consumed, water (20 mL) was added to
quench the reaction followed by the addition of ether
(20 mL). The combined organic layers were dried (MgSO4),
filtered and the solvent removed in vacuo. Flash chromato-
graphy of the resultant colourless solid (petrol/ether, 6:4),
affording the desired product as a colourless needles (1.23 g,
77%). Rf 0.34 (petrol/ether, 1:1); mp 113 8C; [a]2D0 C118.5
5.1.7. trans-(4S)-3-[(10-Diphenylphosphinyl-30-phenyl-20-
aziridinyl)carbonyl]-4-(1-methylethyl)oxazolidin-2-one
(4c and 4d). Following the procedure above, (4S)-(C)-3-
bromoacetyl-4-(1-methylethyl)-2-oxazolidinone (200 mg,
0.8 mmol), NaHMDS in THF (0.9 mL, 1.0 M,
0.88 mmol), and N-(phenylmethylene)diphenylphosphina-
mide (120 mg, 0.4 mmol) were reacted together in ether
(25 mL). Purification by flash chromatography (gradient
20–100% EtOAc in petrol), provided 4a a yellow oil
(20 mg, 16%), and a mixture of trans-aziridine diastereoi-
somers, 4c and 4d as a clear oil (25 mg, 13%). Rf 0.2
(EtOAc); [a]D20 C59.8 (c 0.5, CH2Cl2); IR nmax (film) 2965,
1782, 1704, 1438, 1204, 1124, 727, 696 cmK1; dH
(400 MHz, CDCl3) 0.64 and 0.79 (6H, 2!d, JZ7.2 Hz),
2.14–2.26 (1H, m), 4.11–4.29 (3H, m), 4.39–4.44 (1H, m),
4.81 (1H, dd, JPZ12.6 Hz, JZ2.8 Hz), 7.01–7.46 (11H, m),
7.72–7.95 (4H, m); dC (100 MHz, CDCl3) 14.6, 17.9, 28.1,
43.2, 45.3, 58.6, 63.9, 127.6, 132.2, 135.9, 153.8, 166.4; m/z
(CI) 475 ([MH]C, 100%), 346 (39), 320 (13), 275 (10), 201
(10), 130 (26); HRMS found: [MH]C475.1776,
C27H28N2O4P requires 475.1787.
(c 1, CHCl3); IR nmax (CCl4) 2959, 1705, 1330, 1170 cmK1
;
dH (400 MHz, CDCl3) 0.91 (3H, s), 1.09 (3H, s), 1.25–1.40
and 1.72–2.11 (7H, 2!m), 3.38–3.48 (2H, 2!d, JZ
13.7 Hz), 3.90 (1H, dd, JZ7.5, 5.0 Hz), 4.14 and 4.27 (2H,
2!d, JZ13.2 Hz); dC (100 MHz, CDCl3) 19.8, 20.7, 26.4,
28.0, 32.7, 37.9, 44.5, 47.8, 49.0, 52.7, 65.4, 164.5; m/z (CI)
36 ([MH]C, 86%), 258 (16), 192 (42), 135 (100); HRMS
found: [MH]C336.0259, C12H19BrNO3S requires 336.0269.
5.2. General procedure for asymmetric aza-Darzens
reaction using R-5
(2R)-(K)-(N-Bromoacetyl)bornane-10,2-sultam (R-5),
(1.1 equiv), was dissolved in THF (25 mL) and cooled to
K78 8C. LiHMDS in THF (1.2 equiv) was then added
dropwise, and the resulting pale yellow solution stirred for
30 min. Phosphinylimine, (typically 0.7 mmol) 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.
5.1.8. (2R)-(L)-(N-Bromoacetyl)bornane-10,2-sultam
(R-5). (2R)-Bornane-10,2-sultam (200 mg, 9.3 mmol), was
dissolved in THF (25 mL), under a nitrogen atmosphere and
cooled to K78 8C. n-BuLi in hexanes (2.5 M, 0.41 mL,
1.0 mmol), was then added dropwise and the solution stirred
for 20 min. Bromoacetyl bromide (0.1 mL, 1.0 mmol), was
then dissolved in THF (10 mL), and this was then added
dropwise to the anion. The reaction was stirred at K78 8C
and was determined to be complete by TLC after 2 h. Water
(10 mL) was added to quench the reaction, and EtOAc

3688
J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
5.2.1. (2R,20R,30R)-(L)-N-[(10-Diphenylphosphinyl-30-
phenyl-20-aziridinyl)carbonyl]bornane-10,2-sultam
(7a). By following the procedure above, (2R)-(K)-(N-
bromoacetyl)bornane-10,2-sultam (490 mg, 1.4 mmol),
LiHMDS in THF (1.6 mL, 1.0 M, 1.6 mmol), and N-
in THF (40 mL) at K78 8C to produce a yellow oil.
Purification by flash chromatography (gradient 20–80%
EtOAc in petrol, containing 0.05% v/v acetic acid),
provided a colourless oil. Crystallisation from CHCl3/
hexane afforded 7c (460 mg, 74%). Rf 0.5 (EtOAc); mp
138–140 8C; [a]2D0 K14.0 (c 1, CH2Cl2); IR nmax (film)
2964, 3840, 1698, 1439, 1330, 1188, 1275, 1126, 730, 703,
652 cmK1; dH (400 MHz, CDCl3) 0.89 (3H, s), 0.94 (3H, s),
1.21–1.30 and 1.79–1.98 (7H, 2!m), 3.28 and 3.39 (2H,
2!d, JZ14.0 Hz), 3.61 (1H, m), 3.75 (3H, s), 4.11–4.26
(2H, 2!dd, JPZ15.9, 6 Hz, JZ0.2 Hz), 6.80 (2H, app. d,
JZ8.5 Hz), 7.34–7.54 (8H, m), and 8.10–8.15 (4H, m); dC
(75 MHz, CDCl3) 19.8, 20.7, 26.3, 32.5, 38.1, 41.7, 43.8,
44.6, 47.7, 49.0, 52.6, 55.1, 64.7, 113.2, 124.7, 124.8, 128.6,
131.5, 131.7, 131.8, 159.4, 163.9; m/z (CI) 591 ([MH]C,
100%), 526 (15), 419 (47), 373 (32), 219 (36), 135 (14);
HRMS found: [MH]C591.2064, C32H36N2O5PS requires
591.2082.
(phenylmethylene)diphenylphosphinamide
(400 mg,
1.3 mmol), were reacted together in THF (35 mL) at
K78 8C to produce a yellow oil. Purification by flash
chromatography (gradient 20–70% EtOAc in petrol contain-
ing 0.05% v/v acetic acid) provided a colourless oil.
Crystallisation from CHCl3/hexane afforded 7a as a colour-
less solid (520 mg, 71%). Rf 0.5 (EtOAc); mp 197–198 8C;
[a]2D0 K11.3 (c 1, CH2Cl2); IR nmax (CHCl3) 2961, 1705,
1439, 1336, 1270, 1213, 1137, 837, 654 cmK1; dH
(400 MHz, CDCl3) 0.89 (3H, s), 0.95 (3H, s), 1.20–1.32
and 1.79–1.96 (7H, 2!m), 3.27 and 3.38 (2H, 2!d, JZ
13.6 Hz), 3.57–3.61 (1H, m), 4.18 and 4.27 (2H, 2!dd,
JPZ14.4 Hz, JZ6.1 Hz), 7.19–7.55 (11H, m), and 7.93–
8.15 (4H, m), dC (75 MHz, CDCl3) 19.8, 19.9, 26.3, 32.5,
38.1, 41.6, 44.0, 44.6, 47.7, 49.0, 52.6, 64.7, 127.7, 128.4,
128.7, 130.9, 131.9, 132.7, 163.7; m/z (CI) 561 ([MH]C,
72%), 483 (11), 361 (42), 346 (44), 320 (70), 216 (100), 135
(67); HRMS found: [MH]C561.1987, C31H34N2O4PS
requires 561.1977; Found: C, 66.6; H, 6.0; N, 5.0;
C31H33N2O4PS requires C, 66.4; H, 5.9; N, 5.0%.
5.2.4. (2R,20R,30R)-(L)-N-[(10-Diphenylphosphinyl-30-
(2-nitrophenyl)-20-aziridinyl)carbonyl]bornane-10,2-
sultam (7d). By following the procedure above, (2R)-(K)-
(N-bromoacetyl)bornane-10,2-sultam (320 mg, 0.94 mmol),
LiHMDS in THF (1.0 mL, 1.0 M, 1.0 mmol), and N-(2-
nitrophenylmethylene)diphenylphosphinamide (300 mg,
0.9 mmol), were reacted together in THF (35 mL) at
K78 8C to produce a yellow solid. Purification by flash
chromatography (gradient 20–70% EtOAc in petrol,
containing 0.05% v/v acetic acid) provided a colourless
oil. Crystallisation from EtOAc/hexane afforded 7d
(380 mg, 72%). Rf 0.55 (EtOAc); [a]2D0 K112.4 (c 1,
CH2Cl2); mp 190–192 8C; IR nmax (film) 2960, 1700, 1438,
1342, 1212, 1136, 730, 696 cmK1; dH (300 MHz, CDCl3)
0.88 (3H, s), 0.89 (3H, s), 1.17–1.32 and 1.79–1.96 (7H, 2!
m), 3.28 and 3.36 (2H, 2!d, JZ13.8 Hz), 3.51–3.55 (1H,
m), 4.25 (1H, br dd, JPZ14.9 Hz, JZ5.8 Hz), 5.05 (1H, dd,
JPZ15.2 Hz, JZ6.2 Hz), 7.38–7.58 (10H, m), and 7.80–
8.12 (4H, m); dC (75 MHz, CDCl3) 19.8, 20.6, 26.3, 32.5,
38.1, 40.8, 42.2, 44.6, 47.8, 49.0, 52.4, 64.5, 124.9, 128.8,
128.9, 128.7, 128.7, 131.0, 131.2, 131.2, 131.6, 131.8,
132.4, 132.9, 148.7, 164.1; m/z (CI) 606 ([MH]C, 2.5%),
419 (15), 321 (20), 272 (32), 219 (25), 201 (12), 135 (100);
HRMS found: [MH]C606.1832, C31H33N3O6PS requires
606.1828; Found: C, 61.4; H, 5.35; N, 6.9; C31H32N3O6PS
requires C, 61.5; H, 5.3, H, 7.0%.
5.2.2. (2R,20R,30R)-(L)-N-[(10-Diphenylphosphinyl-30-
(4-nitrophenyl)-20-aziridinyl)carbonyl]bornane-10,2-
sultam (7b). By following the procedure above, (2R)-(K)-
(N-bromoacetyl)bornane-10,2-sultam (250 mg, 0.74 mmol),
LiHMDS in THF (0.8 mL, 1.0 M, 0.8 mmol), and N-(4-
nitrophenylmethylene)diphenylphosphinamide (240 mg,
0.7 mmol), were reacted together in THF (35 mL) at
K78 8C to produce a yellow oil. Purification by flash
chromatography (gradient 20–70% EtOAc in petrol,
containing 0.05% v/v acetic acid) provided a colourless
oil. Crystallisation from CHCl3/hexane afforded 7b as a
colourless solid (320 mg, 77%). Rf 0.55 (EtOAc); [a]D20
K28.6 (c 1, CH2Cl2); mp 213 8C (EtOAc/hexane); IR nmax
(film) 2960, 1703, 1439, 1347, 1215, 1127, 730, 695 cmK1
;
dH (400 MHz, CDCl3) 0.90 (3H, s), 0.98 (3H, s), 1.21–1.31
and 1.81–2.05 (7H, 2!m), 3.28 and 3.42 (2H, 2!d, JZ
13.7 Hz), 3.54–3.57 (1H, m), 4.29–4.33 (2H, m), 7.38–7.64
(10H, m) and 7.90–8.15 (4H, m); dH (300 MHz, C6H6) 0.26
(3H, s), 0.65 (3H, s), 0.53–0.89, 1.07–1.16 and 1.65–1.85
(7H, m), 2.42 and 2.46 (2H, 2!d, JZ13.9 Hz), 3.14–3.18
(1H, m), 4.44 (1H, dd, JPZ15.4 Hz, JZ6.4 Hz), 4.85 (1H,
dd, JPZ14.8 Hz, JZ6.4 Hz) 6.93–7.86 and 8.09–8.43 (14H,
m); dC (75 MHz, CDCl3) 19.8, 20.7, 26.3, 32.5, 38.0, 42.0,
42.8, 44.5, 47.8, 49.1, 52.7, 64.8, 123.0, 128.7, 131.9, 131.9,
131.9, 140.2, 140.2, 147.7, 163.3; m/z (CI) 606 ([MH]C,
100%), 541 (10), 419 (44), 406 (47), 219 (25), 201 (12), 135
(22); HRMS found: [MH]C606.1824, C31H33N3O6PS
requires 606.1828; Found: C, 61.8; H, 5.6; N, 6.9;
C31H32N3O6PS requires C, 61.5; H, 5.3, H, 7.0%.
5.2.5. (2R,20R,30R)-(L)-N-[(30-(4-Bromophenyl)-10-
diphenylphosphinyl-20-aziridinyl)carbonyl]bornane-
10,2-sultam (7e). By following the procedure above, (2R)-
(K)-(N-bromoacetyl)bornane-10,2-sultam
(270 mg,
0.8 mmol), LiHMDS in THF (0.9 mL, 1.0 M, 0.9 mmol),
and N-(4-bromophenylmethylene)diphenylphosphinamide
(280 mg, 0.73 mmol), were reacted together in THF
(25 mL) at K78 8C to produce a yellow oil. Purification
by flash chromatography (gradient 20–80% EtOAc in
petrol, containing 0.05% v/v acetic acid) provided a
colourless oil. Crystallisation from CHCl3/hexane afforded
7e as a colourless crystalline solid (300 mg, 65%); mp 135–
136 8C (CHCl3/hexane). Rf 0.55 (EtOAc); [a]2D3 K16.0 (c 1,
CH2Cl2); IR nmax (film) 2940, 1708, 1442, 1347 and 1170,
1272, 1137, 750, 720, 684 cmK1; dH (400 MHz, CDCl3)
0.90, (3H, s), 0.97 (3H, s), 1.22–1.33 and 1.80–1.97 (7H,
2!m), 3.28 and 3.41 (2H, 2!d, JZ3.7 Hz), 3.58–3.62
5.2.3. (2R,20R,30R)-(L)-N-[(10-Diphenylphosphinyl-30-
(4-methoxyphenyl)-20-aziridinyl)carbonyl]bornane-
10,2-sultam (7c). By following the procedure above, (2R)-
(K)-(N-bromoacetyl)bornane-10,2-sultam
(390 mg,
1.2 mmol), LiHMDS in THF (1.25 mL, 1.0 M,
1.25 mmol), and N-(4-methoxyphenylmethylene)diphenyl-
phosphinamide (350 mg, 1.0 mmol), were reacted together

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
3689
(1H, m), 4.17–4.22 (2H, 2!m), 7.31–7.56 (10H, m) and
7.89–8.13 (4H, m); dC (300 MHz, C6D6) 0.28 (3H, s), 0.68
(3H, s), 0.21–0.56, 0.83–0.93, 1.11–1.29 and 1.65–1.88 (7H,
m), 2.45 and 2.59 (2H, 2!d, JZ13.9 Hz), 3.10–3.14 (1H,
m), 4.43 (1H, dd, JPZ15.8 Hz, JZ6.2 Hz), 4.81 (1H, br dd,
JPZ14.1 Hz, JZ6.2 Hz), 6.92–7.16 (6H, m), 7.26 (4H, d,
JZ8.6 Hz), and 7.47 (4H, d, JZ8.6 Hz), 8.09–8.44 (4H, m);
dC (75 MHz, CDCl3) 19.8, 20.7, 26.3, 32.5, 38.1, 41.4, 43.3,
44.6, 47.8, 49.0, 52.7, 64.8, 122.2, 128.5, 131.9, 163.5; m/z
(CI) 641 and 639 ([MH]C, Br isotopic pattern, 24%), 576
(19), 574 (19), 561 (5), 424 (20), 358 (15), 219 (70), 201
(100), 135 (55); HRMS found: [MH]C639.1068, C31H33-
BrN2O4PS requires 639.1082.
By following the procedure above, (2R)-(K)-(N-bromoa-
cetyl)bornane-10,2-sultam (500 mg, 1.49 mmol), LiHMDS
in THF (1.6 mL, 1.0 M, 1.6 mmol), and N-(2-furylmethyl-
ene)diphenylphosphinamide (400 mg, 1.4 mmol), were
reacted together in THF (35 mL) at K78 8C to produce a
pale yellow oil. Purification by flash chromatography
(gradient 20–70% EtOAc in petrol, containing 0.05% v/v
acetic acid), provided a pale yellow oil. Crystallisation from
EtOAc/hexane afforded 7h, as a colourless crystalline solid
(530 mg, 71%). Rf 0.5 (EtOAc); [a]2D0 K18.9 (c 3, CH2Cl2);
IR nmax (film) 2961, 1701, 1438, 1336, 1217, 1137, 728,
695 cmK1; dH (300 MHz, CDCl3) 0.91 (3H, s), 0.98 (3H, s),
1.16–1.36 and 1.83–1.89 (7H, 2!m), 3.31 and 3.41 (2H,
2!d, JZ13.5 Hz), 3.73–3.76 (1H, m), 4.09–4.22 (2H, 2!
dd, JPZ16.1 Hz, JZ5.9 Hz), 6.29 (1H, dd, JZ3.4, 1.9 Hz),
6.36 (1H, d, JZ3.2 Hz), 7.33–7.58 (7H, m), and 7.84–8.12
(4H, m); dC (75 MHz, CDCl3) 19.8, 20.6, 26.4, 32.6, 37.6,
38.1, 41.0, 44.6, 47.8, 49.2, 52.5, 64.7, 109.1, 110.5, 128.6,
131.7, 142.8, 148.5, 165.0; m/z (CI) 551 ([MH]C, 35%), 487
(15), 447 (10), 419 (70), 351 (100), 219 (80), 201 (12), 135
(30); HRMS found: [MH]C551.1779, C29H32N2O5PS
requires 551.1770.
5.2.6. (2R,20R,30R)-(L)-N-[(10-Diphenylphosphinyl-30-
(2-naphthyl)-20-aziridinyl)carbonyl]bornane-10,2-sul-
tam (7f). By following the procedure above, (2R)-(K)-(N-
bromoacetyl)bornane-10,2-sultam (370 mg, 1.1 mmol),
LiHMDS in THF (1.2 mL, 1.0 M, 1.2 mmol), and N-(2-
naphthylmethylene)diphenylphosphinamide (350 mg,
1.0 mmol), were reacted together in THF (40 mL) at
K78 8C to produce a yellow oil. Purification by flash
chromatography (gradient 20–70% EtOAc in petrol,
containing 0.05% v/v acetic acid), afforded 7f as a clear
oil (440 mg, 73%). Rf 0.55 (EtOAc); [a]2D0 K16.6 (c 1,
CH2Cl2); IR nmax (film) 2962, 1702, 1438, 1336, 1214,
1126, 646, 618 cmK1; dH (300 MHz, CDCl3) 0.85 (3H, s),
0.94 (3H, s), 1.15, 1.72–1.93 (7H, 2!m), 3.21 and 3.36 (2H,
2!d, JZ13.9 Hz), 3.49–3.51 (1H, m), 4.11 and 4.42 (2H,
2!dd, JPZ15.9 Hz, JZ6.2 Hz), 7.31–8.20 (17H, m); dC
(75 MHz, CDCl3) 19.7, 20.7, 26.2, 32.4, 38.0, 41.8, 44.1,
44.5, 47.6, 48.9, 52.6, 64.6, 125.8, 125.9, 127.2, 127.6,
127.7, 128.4, 131.9, 133.1, 163.6; m/z (CI) 611 ([MH]C,
100%), 546 (22), 419 (82), 411 (70), 393 (37), 219 (64), 201
(30), 135 (28); HRMS found: [MH]C611.2126,
C35H36N2O4PS requires 611.2133.
5.2.9. (2R,20R,30R)-(D)-N-[(30-(tert-Butyl)-10-diphenyl-
phosphinyl-20-aziridinyl)carbonyl]bornane-10,2-sultam
(7i). By following the procedure above, (2R)-(K)-(N-
bromoacetyl)bornane-10,2-sultam (260 mg, 0.77 mmol),
LiHMDS in THF (0.8 mL, 1.0 M, 0.8 mmol), and N-(tert-
butylmethylene)diphenylphosphinamide
(200 mg,
0.7 mmol), were reacted together in THF (40 mL) at
K78 8C to produce a yellow oil. Purification by flash
chromatography (gradient 20–70% EtOAc in petrol,
containing 0.05% v/v acetic acid) provided a colourless
oil. Crystallisation from ethyl acetate/hexane afforded (7i)
as a colourless crystalline solid (150 mg, 40%). Rf 0.55
(EtOAc); mp 204 8C (EtOAc/hexane); [a]2D0 C11.9 (c 1,
CH2Cl2); IR nmax (film) 2960, 1703, 1439, 1339, 1203,
1127, 1064, 729, 704 cmK1; dH (400 MHz, CDCl3) 0.82
(9H, s), 0.83 and 0.91 (6H, 2!s), 1.26–1.44 and 1.80–2.08
(7H, 2!m), 3.03 (1H, dd, JPZ17.8 Hz, JZ6.3 Hz), 3.36
and 3.42 (2H, 2!d, JZ13.7 Hz) 3.61 (1H, br dd, JPZ
17.3 Hz, JZ5.9 Hz), 3.85 (1H, m), 7.40–7.53 (6H, m), and
7.94–8.10 (4H, m); dC (75 MHz, CDCl3) 19.8, 20.4, 27.9,
26.4, 32.6, 38.0, 32.4, 39.6, 44.4, 47.8, 49.0, 52.5, 53.5,
65.1, 128.4, 131.8, 131.7, 132.0, 165.5; m/z (CI) 541
([MH]C, 100), 471 (42), 419 (20), 298 (56), 201 (23), 135
(9); HRMS found: [MH]C541.2294, C29H38N2O4PS
requires 541.2290; Found: C, 64.6; H, 6.9; N, 5.2;
C29H37N2O4PS requires C, 64.4; H, 6.9, H, 5.2%.
5.2.7. (2R,20R,30R)-(L)-N-[(10-Diphenylphosphinyl-30-
(2-fluorenyl)-20-aziridinyl)carbonyl]bornane-10,2-sul-
tam (7g). By following the procedure above, (2R)-(K)-(N-
bromoacetyl)bornane-10,2-sultam (330 mg, 1.0 mmol),
LiHMDS in THF (1.1 mL, 1.0 M, 1.1 mmol), and N-
(fluorenemethylene)diphenylphosphinamide (350 mg,
0.9 mmol), were reacted together in THF (40 mL) at
K78 8C to produce a yellow oil. Purification by flash
chromatography (gradient 20–70% EtOAc in petrol,
containing 0.05% v/v acetic acid), afforded 7g as a pale
yellow oil (390 mg, 68%). Rf 0.5 (EtOAc); [a]2D0 K20.0 (c 1,
CH2Cl2); IR nmax (film) 2962, 1702, 1439, 1337, 1217,
1127, 730, 646, 619 cmK1; dH (400 MHz, CDCl3) 0.87 (3H,
s), 0.95 (3H, s), 1.19–1.21 and 1.76–1.97 (7H, 2!m), 3.25
and 3.38 (2H, 2!d, JZ13.9 Hz), 3.58 (1H, m), 3.85 (2H, d,
JZ3.7 Hz), 4.22 and 4.38 (2H, 2!dd, JPZ15.9 Hz, JZ
6.2 Hz), 7.26–7.72 and 7.97–8.20 (17H, 2!m); dC
(75 MHz, CDCl3) 19.7, 20.6, 26.2, 32.4, 38.0, 36.8, 41.9,
44.3, 44.5, 47.6, 48.9, 52.5, 64.6, 119.0, 119.8, 124.9, 126.6,
127.0, 128.6, 131.9, 141.3, 141.6, 142.6, 143.4, 163.6; m/z
(CI) 649 ([MH]C, 21%), 585 (7), 449 (43), 419 (100), 219
(60), 135 (22); HRMS found: [MH]C649.2282,
C38H38N2O4PS requires 649.2290.
5.2.10. (2R)-N-[20-Bromo-40-dimethyl-30-(diphenyl-
phosphinamido)-10-oxopentyl]bornane-10,2-sultam (8).
The above reaction also gave compound 8 as a clear oil
(60 mg, 13%). Rf 0.65 (EtOAc); IR nmax (film) 3368, 2960,
1706, 1438, 1332, 1216, 1122, 724, 698 cmK1; dH
(400 MHz, CDCl3) 0.93 (9H, s), 0.95 (3H, s), 1.24 (3H,
s), 1.26–1.41 and 1.80–1.91 (6H, 2!m), 2.37–2.42 (1H, m),
3.37–3.43 and 3.53–3.63 (2H, 27!m), 3.45–3.53 (2H, 2!
d, JZ13.7 Hz), 3.90 (1H, dd, JZ7.8, 4.6 Hz), 5.52 (1H, s),
7.38–7.52 (6H, m), and 7.82–7.94 (4H, m), dC (100 MHz,
CDCl3) 20.0, 20.8, 27.8, 26.5, 33.1, 37.0, 37.9, 44.6, 47.8,
48.5, 53.1, 53.3, 58.8, 66.4, 128.2, 132.2, 166.2; m/z (CI)
623 and 621 ([MH]C, Br isotope pattern, 26%), 543 (14),
5.2.8. (2R,20R,30S)-(L)-N-[(10-Diphenylphosphinyl-30-(2-
furyl)-20-aziridinyl)carbonyl]bornane-10,2-sultam (7h).

3690
J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
485 (27), 326 (17), 270 (100), 216 (20), 57 (54); HRMS
found: [MH]C621.1539, C29H39BrN2O4PS requires
621.1552.
128.6, 129.9, 129.9, 130.9, 131.4, 131.4, 131.6, 131.7,
131.9, 132.2, 161.2, 163.6; m/z (CI) 579 ([MH]C, 14%), 515
(12), 419 (32), 379 (7), 297 (19), 219 (100), 77 (17); HRMS
found: [MH]C579.1870, C31H33FN2O4PS requires
579.1883.
5.3. General procedure for asymmetric aza-Darzens
reactions using S-5
5.3.3. cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-(2,6-
dichlorophenyl)-2-aziridinyl)carbonyl]bornane-10,2-
sultam (7l). Following the general procedure described
above, S-5 (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL,
1.0 M, 1.1 mmol) and P,P-diphenyl-N-(2,6-dichlorophenyl-
methylene)phosphinic amide (337 mg, 0.9 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
(petrol/EtOAc 1:1), affording 7l, as a colourless solid
(493 mg, 87%). Rf 0.18 (petrol/EtOAc 1:1); mp 192 8C;
[a]2D0 C6.2 (c 1, CHCl3); IR nmax (CCl4) 3057, 2964, 1704,
1441, 1333, 1168, 1274, 1125, 737, 708, 698 cmK1; dH
(250 MHz, CDCl3) 0.70–0.83 (6H, m), 1.18 and 1.74–1.93
(7H, m), 3.33 (1H, m), 3.45 and 3.50 (2H, 2!d, JZ
14.0 Hz), 4.18 and 4.21 (2H, 2!dd, JPZ15.6 Hz, JZ
5.3 Hz), 7.00–7.10 (3H, m), 7.34–7.44 (6H, m), 7.90–7.96
(3H, m); dC (60 MHz, CDCl3) 19.7, 21.1, 26.2, 32.8, 38.2,
38.9, 42.6, 44.7, 47.7, 48.9, 52.7, 65.2, 128.1, 128.2, 128.3,
128.7, 129.1, 131.6, 131.7, 132.1, 132.2, 132.5, 132.6,
135.6, 165.2; m/z (CI) 629 ([MH]C, 18%), 565 (12), 419
(12), 219 (100), 151 (26), 78 (39); HRMS found:
[MH]C629.1197, C31H32Cl2N2O4PS requires 629.1197.
Compound S-5 (336 mg, 1.0 mmol) was dissolved in
anhydrous THF (20 mL) and cooled to K78 8C under an
inert atmosphere. LiHMDS in THF (1.1 mL, 1.0 M,
1.1 mmol) was added dropwise and the resulting yellow
solution stirred for approximately 30 min. Phosphinylimine
(0.9 mmol) was added as a THF solution (15 mL) to the
reaction mixture. The reaction mixture was then left stirring
at K78 8C for approximately 3–4 h and followed by TLC.
After this time the reaction was quenched via addition of a
saturated ammonium chloride solution (20 mL). The
aqueous layer was then extracted with ether (3!20 mL)
and the organic layers combined, washed with brine, dried
(MgSO4), filtered and the solvent removed in vacuo to
afford the crude aziridine.
5.3.1.
cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-
(phenyl)-2-aziridinyl)carbonyl]bornane-10,2-sultam
(7j). Following the general procedure described above, S-5
(336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL, 1.0 M,
1.1 mmol) and P,P-diphenyl-N-(phenylmethylene)phos-
phinic amide (275 mg, 0.9 mmol) were reacted to produce
the crude aziridine. The resulting colourless solid was
purified by flash chromatography (petrol/EtOAc 1:9),
affording 7j as a colourless solid (358 mg, 71%). Rf 0.53
(EtOAc); mp 198 8C; [a]2D0 C11.3 (c 1, CH2Cl2); IR nmax
(CCl4) 2961, 1705, 1439, 1336, 1270, 1213, 1137, 837,
654 cmK1; dH (400 MHz, CDCl3) 0.88 (3H, s), 0.94 (3H, s),
1.21–1.26 and 1.78–1.96 (7H, 2!m), 3.27, 3.39 (2H, 2!d,
JZ13.9 Hz), 3.58 (1H, m), 4.25 and 4.29 (2H, 2!dd, JPZ
15.8 Hz, JZ6.2 Hz), 7.23–7.52 (11H, m), 7.93–7.98 and
8.11–8.15 (4H, m); dC (100 MHz, CDCl3) 19.6, 20.5, 26.2,
32.3, 37.9, 41.5, 43.8, 44.4, 47.6, 48.8, 52.5, 64.6, 127.6,
127.9, 128.2, 128.3, 128.4, 128.6, 128.7, 130.9, 131.0,
131.4, 131.5, 131.6, 131.7, 132.0, 132.1, 132.2, 132.3,
132.5, 132.6, 163.5; m/z (CI) 561 ([MH]C, 60%), 483 (11),
361 (42), 346 (44), 320 (70), 216 (100), 135 (67); HRMS
found: [MH]C561.1987, C31H34N2O4PS requires 561.1977.
5.3.4. cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-(3-bro-
mophenyl)-2-aziridinyl)carbonyl]bornane-10,2-sultam
(7m). Following the general procedure described above, S-5
(300 mg, 0.89 mmol), LiHMDS in THF (1.0 mL, 1.0 M,
1.0 mmol) and P,P-diphenyl-N-(3-bromophenylmethylene)-
phosphinic amide (346 mg, 0.89 mmol) were reacted to
produce the crude aziridine. The resulting colourless solid
was purified by flash chromatography (petrol/EtOAc 1:9),
affording 7m, as a colourless solid (343 mg, 60%). Rf 0.75
(EtOAc); [a]D20 C16.5 (c 1, CHCl3); IR nmax (CCl4) 3057,
2964, 1705, 1441, 1339, 1188, 1267, 1128, 740, 705 cmK1
;
dH (250 MHz, CDCl3) 0.90 (3H, s), 0.97 (3H, s), 1.20–1.34
and 1.67–1.98 (7H, 2!m), 3.30 and 3.41 (2H, 2!d, JZ
13.9 Hz), 3.61–3.64 (1H, m), 4.18 and 4.22 (2H, 2m), 7.11–
7.15 and 7.30–7.60 (10H, m), 7.92–7.97 and 8.09–8.14 (4H,
m); dC (60 MHz, CDCl3) 19.7, 20.6, 26.3, 32.4, 38.0, 41.6,
43.0, 44.5, 47.7, 49.0, 52.6, 64.6, 121.7, 126.6, 127.0, 128.0,
128.1, 128.4, 128.6, 128.7, 129.2, 129.8, 130.7, 130.8,
130.9, 131.1, 131.4, 131.4, 131.5, 131.7, 131.8, 131.9,
132.0, 132.1, 132.2, 135.1, 135.1, 141.0, 163.4; m/z (CI) 639
([MH]C, 23%), 573 (28), 419 (57), 359 (10), 219 (100), 135
(24); HRMS found: [MH]C639.1187, C31H33BrN2O4PS
requires 639.1182.
5.3.2. cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-(4-
fluorophenyl)-2-aziridinyl)carbonyl]bornane-10,2-sul-
tam (7k). Following the general procedure described above,
S-5 (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL, 1.0 M,
1.1 mmol) and P,P-diphenyl-N-(4-fluorophenylmethylene)-
phosphinic amide (323 mg, 1.0 mmol) were reacted to
produce the crude aziridine. The resulting colourless solid
was purified by flash chromatography (petrol/EtOAc 1:9),
affording 7k, as a colourless solid (328 mg, 57%). Rf 0.51
(EtOAc); mp 197 8C; [a]2D0 C8.5 (c 1, CHCl3); IR nmax
(CCl4) 3056, 2968, 1705, 1441, 1338, 1188, 1267, 1127,
740, 705 cmK1; dH (400 MHz, CDCl3) 0.89 (3H, s), 0.96
(3H, s), 1.20–1.29, 1.79–1.81 and 1.95–1.97 (7H, m), 3.28
and 3.40 (2H, 2!d, JZ13.6 Hz), 3.57–3.60 (1H, m), 4.19–
4.26 (2H, 2!dd, JPZ16.1 Hz, JZ6.2 Hz), 6.92–6.97 and
7.35–7.54 (10H, m), 7.91–7.96 and 8.09–8.14 (4H, m); dC
(100 MHz, CDCl3) 19.7, 20.6, 26.3, 32.4, 37.9, 41.6, 43.2,
44.4, 47.6, 48.9, 52.5, 64.6, 114.5, 114.8, 128.3, 128.5,
5.3.5. cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-(4-
methoxyphenyl)-2-aziridinyl)carbonyl]bornane-10,2-
sultam (7n). Following the general procedure described
above, S-5 (336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL,
1.0 M, 1.1 mmol) and P,P-diphenyl-N-(4-methoxyphenyl-
methylene)phosphinic amide (337 mg, 1.0 mmol) were
reacted to produce the crude aziridine. The resulting
colourless solid was purified by flash chromatography
(petrol/EtOAc 1:9), affording 7n, as a colourless solid
(355 mg, 60%). Rf 0.45 (EtOAc); mp 139 8C; [a]2D0 C11.4

J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
3691
(c 1, CHCl3); IR nmax (CCl4) 2964, 1698, 1439, 1330, 1188,
5.4. General procedure for the removal of the sultam
auxiliary
1275, 1126, 730, 703, 652 cmK1; dH (400 MHz, CDCl3)
0.89 (3H, s), 0.95 (3H, s), 1.22–1.30, 1.79–1.81 and 1.96–
1.97 (7H, m), 3.28 and 3.39 (2H, 2!d, JZ13.7 Hz), 3.61
(1H, m), 3.76 (3H, s), 4.11 and 4.25 (2H, 2!dd, JPZ
16.1 Hz, JZ5.9 Hz), 6.79–6.81 and 7.36–7.52 (10H, m),
7.91–7.96 and 8.10–8.15 (4H, m); dC (100 MHz, CDCl3)
19.7, 20.6, 26.3, 32.5, 38.1, 41.6, 43.7, 44.5, 47.7, 48.9,
52.6, 55.1, 64.6, 113.2, 124.7, 124.7, 128.4, 128.5, 128.7,
129.4, 131.1, 131.2, 131.5, 131.6, 131.8, 131.9, 132.1,
132.1, 132.4, 132.5, 159.3, 163.9; m/z (CI) 591 ([M]C,
18%), 419 (37), 219 (92), 148 (100), 77 (49); HRMS found:
[M]C591.2089, C32H36N2O5PS requires 591.2083.
(20R,30R)-N-Sultamoyl-N-diphenylphosphinylaziridines
(typically 0.2 mmol) were dissolved in a mixture of THF
and water (4:1), 5 mL. Lithium hydroxide monohydrate
(0.4 mmol) was then added. The resulting suspension was
then stirred vigorously overnight, after which the THF was
removed in vacuo, the aqueous layer basified to pH 10 with
saturated NaHCO3, and extracted with CHCl3 (30 mL and
2!20 mL). The combined organic layers were washed with
saturated NaHCO3 solution (10 mL) dried (MgSO4), filtered
and the solvent removed in vacuo. The aqueous layer was
then combined with the base washings and acidified to pH 2
with 2 M HCl. Further CHCl3 was added (3!45 mL), the
layers separated, the organic layers combined, dried
(MgSO4), filtered and the solvent removed in vacuo, to
5.3.6. cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-(2-
pyridinyl)-2-aziridinyl)carbonyl]bornane-10,2-sultam
(7o). Following the general procedure described above, S-5
(336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL, 1.0 M,
1.1 mmol) and P,P-diphenyl-N-(2-pyridinylmethylene)pho-
sphinic amide (306 mg, 1.0 mmol) were reacted to produce
the crude aziridine. The resulting colourless solid was
purified by flash chromatography (petrol/EtOAc 1:9),
affording 7o, as a colourless solid (376 mg, 67%). Rf 0.37
(EtOAc); mp 195 8C; [a]2D0 C11.8 (c 1, CHCl3); IR nmax
(CCl4) 3059, 2965, 1703, 1440, 1342, 1171, 1268, 1129,
776, 738, 705 cmK1; dH (250 MHz, CDCl3) 0.89 (6H, 2s),
1.21–1.29 and 1.82–2.04 (7H, m), 3.25 and 3.34 (2H, 2!d,
JZ13.9 Hz), 3.72 (1H, m), 4.11 and 4.34 (2H, 2!dd, JPZ
15.8 Hz, JZ6.6 Hz), 7.14–7.17 (1H, m), 7.37–7.64 (8H, m),
7.91–7.96 and 8.13–8.18 (4H, m), 8.50–8.51 (1H, m); dC
(60 MHz, CDCl3) 19.8, 20.5, 26.3, 32.7, 38.2, 41.5, 44.3,
44.8, 47.7, 49.2, 52.2, 64.4, 122.2, 123.1, 128.4, 128.6,
128.6, 128.8, 130.8, 131.4, 131.5, 131.8, 131.9, 132.1,
132.2, 132.3, 136.2, 150.3; m/z (CI) 562 ([MH]C, 100%),
498 (75), 419 (97), 362 (34), 319 (50), 280 (73), 219 (93),
119 (31); HRMS found: [MH]C562.1942, C30H33N3O4PS
requires 562.1930.
afford
carboxyaziridines.
the
N-diphenylphosphinyl-2-substituted-3-
5.4.1. (20R,30R)-N-Diphenylphosphinyl-2-carboxy-3-
phenylaziridine (9a). By following the general procedure
described above (2R,20R,30R)-(K)-N-[(10-diphenylphos-
phinyl-30-phenyl-20-aziridinyl)carbonyl]bornane-10,2-
sultam (90 mg, 0.15 mmol) afforded 9a as a colourless oil
(33 mg, 64%). [a]D20 K6.0 (c 1, MeOH); IR nmax (film)
1717, 1438, 1128, 1025, 727, 691 cmK1; dH (300 MHz,
d6-DMSO) 3.40 (1H, dd, JPZ15.4 Hz, JZ6.6 Hz), 3.97
(1H, dd, JPZ15.9 Hz, JZ6.7 Hz), 7.04–8.00 (15H, m); dC
(75 MHz, d6-DMSO) 40.5, 40.7, 127.5, 128.6, 131.9, 133.5,
166.9; m/z (CI) 364 ([MH]C, 0.5%), 320 (83), 242 (9), 218
(20), 201 (12), 89 (47), 61 (100); HRMS found:
[MH]C364.1113, C21H19NO3P requires 364.1102.
5.4.2. (20R,30R)-N-Diphenylphosphinyl-2-carboxy-3-(4-
nitrophenyl)aziridine (9b). By following the general
procedure described (2R,20R,30R)-(K)-N-[(10-diphenyl-
phosphinyl-30-(4-nitrophenyl)-20-aziridinyl)carbonyl]-
bornane-10,2-sultam (100 mg, 0.17 mmol) afforded 9b as a
colourless oil (40 mg, 60%). [a]2D0 K4.4 (c 2, DMSO); IR
nmax (film) 1719, 1517, 1347, 1437, 1128, 1025, 727,
691 cmK1; dH (300 MHz, d6-DMSO) 3.59 (1H, dd, JPZ
15.2 Hz, JZ6.8 Hz), 4.49 (1H, dd, JPZ15.0 Hz, JZ
6.8 Hz), 7.47–8.31 (14H, m); dC (75 MHz, d6-DMSO)
39.5, 124.6, 128.5, 131.9, 135.9, 148.1, 167.2; m/z (CI) 409
([MH]C, 1%), 365 (1.5), 335 (2), 219 (100), 201 (8) 141
(23); HRMS found: [MKCO2] 365.1050, C20H18N2O3P
requires 365.1056.
5.3.7.
cis-2S,20S,30S-N-[(1-Diphenylphosphinyl-3-
(ethenyl)-2-aziridinyl)carbonyl]bornane-10,2-sultam
(7p). Following the general procedure described above, S-5
(336 mg, 1.0 mmol), LiHMDS in THF (1.1 mL, 1.0 M,
1.1 mmol) and P,P-diphenyl-N-(ethenylmethylene)phos-
phinic amide (255 mg, 1.0 mmol) were reacted to produce
the crude aziridine. The resulting colourless solid was
purified by flash chromatography (petrol/EtOAc 1:9),
affording 7p, as a colourless solid (239 mg, 47%). Rf 0.49
(EtOAc); [a]D20 C10.2 (c 1, CHCl3); IR nmax (CCl4) 3056,
5.4.3. (20R,30R)-N-Diphenylphosphinyl-2-carboxy-3-(2-
nitrophenyl)aziridine (9c). By following the general
procedure described (2R,20R,30R)-(K)-N-[(10-diphenylpho-
sphinyl-30-(2-nitrophenyl)-20-aziridinyl)carbonyl]bornane-
10,2-sultam (100 mg, 0.17 mmol) afforded 9c as a colour-
less oil (45 mg, 67%). [a]2D0 C2.3 (c 4, DMSO); IR nmax
2966, 1704, 1440, 1338, 1168, 1267, 1129, 735, 703 cmK1
;
dH (400 MHz, CDCl3) 0.85 (3H, s), 0.93 (3H, s), 1.08–1.36,
1.77–1.81 and 1.97–2.02 (7H, m), 3.30 and 3.38 (2H, 2!d,
JZ13.7 Hz), 3.52–3.60 (1H, m), 3.77–3.95 (2H, m), 5.19
(1H, d, J(cis)Z10.5 Hz), 5.36 (1H, d, J(trans)Z17.4 Hz), 5.65
(1H, ddd, JZ17.4, 10.5, 7.3 Hz), 7.33–7.43 (6H, m), 7.81–
7.86 and 7.92–8.00 (4H, m); dC (100 MHz, CDCl3) 19.8,
20.3, 26.3, 32.7, 38.2, 39.7, 42.9, 44.6, 47.7, 49.2, 52.7,
64.8, 121.4, 128.3, 128.4, 128.6, 128.7, 130.7, 130.8, 131.2,
131.4, 131.5, 131.6, 131.7, 131.7, 131.8, 132.0, 132.3,
132.4, 132.4, 164.7; m/z (CI) 511 ([MH]C, 30%), 419 (18),
268 (100), 201 (76), 77 (22); HRMS found:
[MH]C511.1820, C27H32N2O4PS requires 511.1820.
(film) 1718, 1516, 1343, 1436, 1123, 1024, 727, 691 cmK1
;
dH (300 MHz, d6-DMSO) 3.61 (1H, dd, JPZ15.2 Hz, JZ
6.6 Hz), 4.26 (1H, dd, JPZ15.4 Hz, JZ6.8 Hz), 7.40–8.20
(14H, m); dC (75 MHz, d6-DMSO) 39.5, 123.2, 128.5,
131.4, 134.1, 135.8, 147.4, 167.3; m/z (CI) 409 ([MH]C,
7%), 365 (10), 347 (45), 219 (100), 201 (70), 120 (60);
HRMS found: [MH]C409.0956, C21H18N2O5P requires
409.0953.

3692
J. B. Sweeney et al. / Tetrahedron 62 (2006) 3681–3693
5.4.4. (20R,30R)-N-Diphenylphosphinyl-3-(4-bromo-
phenyl)-2-carboxyaziridine0(9d). By following the general
procedure described (2R,2 R,300R)-(K)-N-[(30-(4-bromo-
phenyl)-10-diphenylphosphinyl-2 -aziridinyl)carbonyl]bor-
nane-10,2-sultam (55 mg, 0.09 mmol) afforded 9d as a
colourless oil (26 mg, 61%). [a]2D0 K6.6 (c 1.5, DMSO); IR
nmax (film) 1735, 1437, 1131, 1011, 730, 692 cmK1; dH
(300 MHz, d6-DMSO) 3.49 (1H, dd, JPZ15.3 Hz, JZ
6.6 Hz), 4.08 (1H, dd, JPZ15.8 Hz, JZ6.8 Hz), 7.44–8.07
(14H, m); dC (75 MHz, d6-DMSO) 39.5, 122.2, 128.4,
131.7, 167.4; m/z (CI) 442 and 444 ([MH]C, bromine
isotope pattern, 3.3%) 398 (31), 400 (31), 320 (26), 219
(100), 201 (35), 141 (12); HRMS found: [MH]C442.0201,
C21H18BrNO3P requires 442.0208.
2-sultam (126 mg, 0.2 mmol) afforded 9h as a colourless oil
(37 mg,45%).[a]D20 K10.8(c1,CHCl3);IRnmax (CCl4)1718,
1439,1131,1028,751,714,695 cmK1;dH(250 MHz,CDCl3)
3.39and4.08(2H,2!dd,JPZ16.0 Hz,JZ6.0 Hz),7.11–7.92
(13H,m);dC(60 MHz,CDCl3)40.9,42.6,129.9,130.0,130.1,
130.5, 130.7, 131.2, 132.6, 132.8, 133.2, 133.3, 133.7, 133.8,
134.4,134.4,134.6,134.7,137.2,170.7;m/z(CI)432([MH]C,
100%), 388(40), 354 (10), 236 (91), 201 (21), 66(36);HRMS
found:[MH]C432.0303,C21H17Cl2NO3Prequires432.0323.
5.4.9. (20S,30S)-2-Carboxy-N-diphenylphosphinyl-3-(2-
pyridinyl)aziridine (9i). Foll0owing the general procedure
described above cis-2S,20S,3 S-N-[(1-diphenylphosphinyl-
3-(2-pyridinyl)-2-aziridinyl)carbonyl]bornane-10,2-sultam
(105 mg, 0.187 mmol) afforded 9j as a yellow oil (68 mg,
99%). [a]2D0 K25.8 (c 1, CHCl3); IR nmax (CCl4) 1718, 1439,
1130, 757, 695 cmK1; dH (250 MHz, CDCl3) 3.58 and 4.06
(2H, 2!dd, JPZ15.6 Hz, JZ6.6 Hz), 7.22–8.35 (14H, m);
dC (60 MHz, CDCl3) 42.1, 43.4, 124.5, 125.4, 129.8, 130.0,
130.3, 130.5, 130.6, 130.7, 132.6, 132.8, 132.9, 133.0,
133.1, 133.2, 133.4, 134.5, 134.6, 134.7, 139.3, 149.9,
154.5, 169.1; m/z (CI) 321 ([MHKCO2]C, 13%), 236 (63),
218 (100), 150 (17), 121 (23); HRMS found: [MHK
CO2]C321.1171, C19H17N2OP requires 321.1157.
5.4.5. (20R,30R)-N-Diphenylphosphinyl-2-carboxy-3-(2-
naphthyl)aziridine (9e). By following the general pro-
cedure described (2R,20R,30R)-(K)-N-[(10-diphenyl-
phosphinyl-30-(2-naphthyl)-20-aziridinyl)carbonyl]bornane-
10,2-sultam (100 mg, 0.16 mmol) afforded 9e as a yellow
oil (35 mg, 51%). [a]2D0 K10.0 (c 2, DMSO); IR nmax (film)
1719, 1437, 1129, 1034, 727, 692 cmK1; dH (300 MHz,
d6-DMSO) 3.57 (1H, dd, JPZ15.4 Hz, JZ6.6 Hz), 4.21
(1H, dd, JPZ15.7 Hz, JZ6.6 Hz), 7.44–8.11 (17H, m); dC
(75 MHz, d6-DMSO) 39.5, 125.1, 126.1, 126.2, 127.4,
127.6, 128.4, 131.9, 167.3; m/z (CI) 414 ([MH]C, 0.5%),
370 (17), 247 (16), 219 (100), 201 (8), 141 (14); HRMS
found: [MKCO2] 370.1350, C24H21NOP requires
370.1361.
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.
5.4.6. (20R,30R)-N-Diphenylphosphinyl-3-(tert-butyl)-2-
carboxyaziridine (9f). By following the general pr0ocedure
described (2R,20R,30R)-(C)-N-[(30-(tert-Butyl)-1 -diphe-
nylphosphinyl-20-aziridinyl)carbonyl]bornane-10,2-sultam
(50 mg, 0.1 mmol) afforded 9f as a colourless oil (15 mg,
47%). [a]2D0 C3.7 (c 1.5, DMSO); IR nmax (film) 2960, 1718,
1438, 1129, 1027, 730, 675 cmK1; dH (300 MHz,
d6-DMSO) 0.72 (9H, s), 2.56 (1H, dd, JPZ16.8 Hz, JZ
6.8 Hz), 3.06 (1H, dd, JPZ16.6 Hz, JZ6.8 Hz), 7.40–8.10
(10H, m); dC (75 MHz, d6-DMSO) 26.7, 39.5, 128.5, 128.6,
131.8, 167.4; m/z (CI) 344 ([MH]C, 62%), 298 (22), 274
(23), 219 (100), 201 (54), 141 (12); HRMS found:
[MH]C344.1414, C19H23N2O3P requires 344.1416.
References and notes
1. For reviews, see: Kemp, J. E. G. In Trost, B. M., Fleming, I.,
Eds.; Comprehensive Organic Synthesis; Oxford: Pergamon,
1991; Vol. 7, p 467. Tanner, D. Angew. Chem., Int. Ed. Engl.
1994, 33, 599. Pearson, W. H.; Lian, B. N.; Bergmeier, S. C. In
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Comprehensive Heterocyclic Chemistry II; Oxford: Perga-
mon, 1996; Vol. 1A, p 1. (d) Rai, K. M. L.; Hassner, A. In
Katritzky, A. R., Rees, C. W., Scriven, E. F., Padwa, A., Eds.;
Comprehensive Heterocyclic Chemistry II; Oxford: Perga-
mon, 1996; Vol. 1A, p 61. Osborn, H. M. I.; Sweeney, J.
Tetrahedron: Asymmetry 1997, 8, 1693. Padwa, A.; Murphree,
S. S. In Gribble, G. W., Gilchrist, T. L., Eds.; Progress in
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Rev. 2002, 31, 247.
5.4.7. (20S,30S)-2-Carboxy-N-diphenylphosphinyl-3-(3-
bromophenyl)aziridine (9g). Following the general pro-
cedure described above, cis-2S,20S,30S-N-[(1-diphenyl-
phosphinyl-3-(2-bromophenyl)-2-aziridinyl)carbonyl]-
bornane-10,2-sultam (128 mg, 0.2 mmol) afforded 9g as a
colourless oil (70 mg, 80%). [a]2D0 K12.8 (c 1, CDCl3); IR
nmax (CCl4) 1718, 1439, 1131, 1028, 751, 695 cmK1; dH
(250 MHz, CDCl3) 3.51 and 3.98 (2H, 2!dd, JPZ15.6 Hz,
JZ6.6 Hz), 7.06–8.05 (14H, m); dC (60 MHz, CDCl3) 42.3,
42.6, 123.5, 128.1, 129.8, 130.1, 130.3, 130.4, 130.5, 130.6,
131.4, 132.0, 132.6, 132.8, 132.8, 133.0, 133.2, 133.4,
134.6, 134.6, 137.4, 169.2; m/z (CI) 444 ([MH]C, 10%), 398
(7), 236 (67), 219 (100); HRMS found: [MH]C444.0214,
C21H18BrNO3P requires 444.0188.
2. For reviews of aziridine syntheses, see: Kemp, J. E. G. In
Trost, B. M., Fleming, I., Eds.; Comprehensive Organic
Synthesis; Oxford: Pergamon, 1991; Vol. 7, p 467. Tanner, D.
Angew. Chem., Int. Ed. Engl. 1994, 33, 599. Pearson, W. H.;
Lian, B. N.; Bergmeier, S. C. In Katritzky, A. R., Rees, C. W.,
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Chemistry II; Oxford: Pergamon, 1996; Vol. 1A, p 1. Rai,
K. M. L.; Hassner, A. In Katritzky, A. R., Rees, C. W., Scriven,
E. F., Padwa, A., Eds.; Comprehensive Heterocyclic Chem-
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5.4.8. (20S,30S)-2-Carboxy-N-diphenylphosphinyl-3-(2,6-
dichlorophenyl)aziridine(9h).Followingthegeneralprocedure
described above cis-2S,20S,30S-N-[(1-diphenylphosphinyl-3-
(2,6-dichlorophenyl)-2-aziridinyl)carbonyl]bornane-10,

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