Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

Article abstract of DOI:10.3762/bjoc.9.98

Predominantly (E)-N-diphenylphosphinyl vinyl aziridines are prepared by a reaction of N-diphenylphosphinyl imines with α-bromoallyllithium in the presence of freshly fused ZnCl₂. These aziridines undergo a ring-opening reaction with a variety of carbon and heteronucleophiles, in good yield, and generally with good regioselectivity.

Full text of DOI:10.3762/bjoc.9.98

Preparation and ring-opening reactions of
N-diphenylphosphinyl vinyl aziridines
Ashley N. Jarvis1, Andrew B. McLaren1, Helen M. I. Osborn1
and Joseph Sweeney*1,2
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2013, 9, 852–859.
1Department of Chemistry, University of Reading, Reading RG6 6AD,
U. K. and 2Department of Chemical and Biological Sciences,
University of Huddersfield, Huddersfield HD1 3DH, U. K.
doi:10.3762/bjoc.9.98
Received: 21 January 2013
Accepted: 07 April 2013
Published: 02 May 2013
Email:
Joseph Sweeney* - j.b.sweeney@hud.ac.uk
Associate Editor: J. A. Murphy
* Corresponding author
© 2013 Jarvis et al; licensee Beilstein-Institut.
License and terms: see end of document.
Keywords:
aziridines; catalytic; heterocycles; palladium; ring opening
Abstract
Predominantly (E)-N-diphenylphosphinyl vinyl aziridines are prepared by a reaction of N-diphenylphosphinyl imines with
α-bromoallyllithium in the presence of freshly fused ZnCl2. These aziridines undergo a ring-opening reaction with a variety of
carbon and heteronucleophiles, in good yield, and generally with good regioselectivity.
Introduction
Vinyl aziridines are useful molecules that have attracted the reports of the ring opening of vinyl aziridines, synthetic
attention of synthetic chemists for many years. These strained chemists still appear reluctant to employ these potentially valu-
bifunctional heterocycles possess considerable synthetic flexi- able synthetic intermediates in target-directed research
bility and undergo a range of efficient transformations [1-9]. programmes.
Whilst there has been a recent resurgence in the development of
reactions using vinyl aziridines, there have been few contempo- Our group has shown that the diphenylphosphinyl (‘Dpp’)
rary reports of new methods for their synthesis [10-29]. group is a practical alternative to N-sulfonylation in aziridine
However, a key limitation to the synthetic application of chemistry, due to the ability of the group to activate the ring and
aziridines in general is the nature of the N-substituent: most the relative ease of its removal at the conclusion of a synthetic
synthetic routes to aziridines deliver N-sulfonylated products, manipulation. We report here in full [30] the results of our
and the cleavage of the sulfonamide bond is often challenging. studies on the synthesis of N-Dpp vinyl azidirines, and selected
Perhaps for this reason, and despite the plethora of modern ring-opening reactions of these heterocycles.
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Beilstein J. Org. Chem. 2013, 9, 852–859.
Results and Discussion
Optimization studies
Synthesis of N-Dpp vinyl aziridines
Initial studies
We next sought to improve the yields of the vinyl aziridination
and thus modified our experimental rubric by carrying out the
We anticipated that the reaction of α-lithio allyl bromide [31- fusion of ZnCl2 under vacuum, rather than at atmospheric pres-
38] with an N-Dpp imine would furnish vinyl aziridines by an sure. Using this minor modification, the reaction of
aza-Darzens-like reaction. This hypothesis was validated by a N-diphenylphosphinylbenzaldimine furnished vinyl aziridine 1
reaction of this anion with N-Dpp benzaldimine at −78 °C in the in a substantially improved yield (71% versus 58%). Moreover,
presence of solid ZnCl2, which delivered predominantly (E)- reactions of the other imines described above were also more
aziridine 1 (3J = 2.6 Hz; d.r. = 10:1) [39] in 58% yield (after efficient. Using the improved method, N-Dpp imines derived
purification by column chromatography) at the first attempt from 2-chloro-, 2-bromo- and 2,6-dichlorobenzaldehyde also
(Scheme 1).
reacted efficiently, yielding vinyl aziridines 7–9 in good yields
(Table 1) and always in favour of the E-isomers (d.r. = 10:1).
To our knowledge, this was the first reported direct synthesis of
a vinyl aziridine bearing a phosphorus group on nitrogen [40]. Mechanism
Encouraged by this promising result, we next examined the Some discussion of the mechanism of the reaction is apposite,
scope of the reaction by using the same anion and N-Dpp especially in the light of the single stereochemical anomaly, i.e.,
imines derived from 4-bromo- and 4-fluorobenzaldehyde, the propensity for (Z)-vinyl aziridine shown in the reaction of
furfural and 2,2-dimethylpropionaldehyde. Disappointingly, the N-diphenyphosphinyl-(2,2-dimethyl)ethylimine. To rationalize
yields of aziridines 2–5 obtained from these reactions were poor this divergence, we propose that a closed transition state is in
(21–32%), though the diastereoselectivity of the transformation operation in the reactions of aryl imines, and an open TS in the
remained good (Table 1). All of the N-Dpp imines derived from reaction of the pivaldehyde-derived imine.
aromatic aldehydes favoured the formation of (E)-vinyl
aziridines, with diastereomeric ratios very similar to that of the Thus, in the reaction of aryl imines we presume that
initial reaction. In particular, the imine derived from furfural lithium–zinc exchange gives an equilibrating allylzinc mixture
yielded only (E)-vinyl aziridine 4. In the case of the vinyl in which the less-hindered isomer reacts more rapidly, through a
aziridination of 2,2-dimethylpropionaldehyde, an inversion in chair-like cyclic transition state 10 in which the aryl and bromo
stereoselectivity was observed, with Z–5 being the dominant substituents are placed in pseudo-equatorial positions, with the
partner of the mixture (d.r. = 5:1). (2-Carboxyvinyl)aziridines Dpp-imine. This conformation delivers anti-bromoamide 11,
are particularly useful reagents due, amongst other properties, to which cyclizes spontaneously to (E)-aziridine 12 (Scheme 2).
their facile conversion into a range of peptidomimetic candi-
dates [41-44]. In an attempt to use our method to deliver these In the reaction of N-Dpp pivaldimine, we propose that the
trifunctional aziridines, we reacted the lithium anion derived increased steric demands of the tert-butyl group require an open
from methyl (E)-3-bromocrotonate with N-diphenylphosphinyl- transition state, leading to syn-bromo amide anion 13, which
benzaldimine. Despite extension optimization studies, the (E)- closes to give (Z)-aziridine 5 (Scheme 3).
N-diphenylphosphinyl-3-[2′-methoxycarbonyl)ethenyl]-2-
phenylaziridine (6) could only be delivered in mediocre yield Ring opening of N-Dpp vinyl aziridines
(though with excellent diastereoselectivity). Reaction of the Having established and optimized the method for the prepar-
same bromocrotonate with N-diphenylphosphinyl-4-bromo- ation of N-Dpp vinyl aziridines, we next turned to an examina-
benzaldimine did not proceed at all when LDA was employed tion of their reactions with a range of nucleophiles, first consid-
as base. A mixture containing stereochemically inhomogeneous ering reactions with organometallic reagents. Thus N-Dpp vinyl
N-diphenylphosphinyl-3-[(E)-2′-methoxycarbonyl)ethenyl]-2- aziridines 1, 2 and 4 reacted with lithio dialkylcuprates with
(4-bromophenyl)aziridine was obtained when other bases were complete regioselectivity, in favour of an SN2′ pathway, to give
used in place of LDA.
1,3-disubstituted N-Dpp allylamines, generally with good yield
Scheme 1: Aza-Darzens synthesis of an N-Dpp vinyl aziridine.
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Beilstein J. Org. Chem. 2013, 9, 852–859.
Table 1: Aza-Darzens synthesis of N-Dpp vinyl aziridines.
Ar
R
H
Product
Methoda
Yield/%
Z:E
A
B
58
71
1:10
1:10
1
A
B
30
62
1:10
1:10
H
2
A
B
32
64
1:10
1:10
H
H
3
4
A
B
25
45
0:100
0:100
A
B
21
50
5:1
5:1
H
5
6
A
B
8
25
0:100
0:100
CO2Me
H
H
7
8
B
B
67
55
1:10
1:10
H
9
B
68
1:10
aMethod A: 1 equiv bromide and LDA, 1.5 equiv ZnCl2 (fused under Argon); Method B: 1.5 equiv bromide and LDA, 2 equiv ZnCl2 fused under
vacuum.
Scheme 2: Closed transition state delivers E-aziridines.
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Beilstein J. Org. Chem. 2013, 9, 852–859.
with a range of nucleophiles [41]. The π-allyl complexes
derived from aziridines 1 and 2, formed in situ by using substoi-
chiometric Pd(PPh3)4, underwent successful reaction with
sodiomalonate and sodium bisphenylsulfonylmethide, again
with complete regiocontrol via an SN2′-like reaction to give
ring-opened products in acceptable yield (Table 2, entries 7, 8,
11, 12).
When aziridines 1 and 2 were reacted with methyl magnesium
iodide in Et2O solution, the previously good regiocontrol we
had observed in the ring opening was not maintained: unlike the
reaction of allyl magnesium chloride (Table 2, entry 5) a mix-
ture of products arising from nucleophilic attack at both C-2 and
C-4 was isolated, with a preference for a SN2′-like reaction
again observed (Scheme 4).
Scheme 3: Open transition state leading to (Z)-5.
(Table 2). In all cases, (E)-isomers were obtained. At the time,
these data represented the first examples of a 100% regioselec- The reactions of N-Dpp vinyl aziridines with heteronucle-
tive ring opening of simple vinyl aziridines by using lower- ophiles (tributylstannyl, phenylselanyl and phenylsulfanyl
order organocuprates. Previously, only 2-(2-carboxyethenyl)- anions) proceeded with variable regioselectivity (Table 3).
aziridines had been shown to undergo ring-opening reactions Thus, bis(tributylstannyl)copper(I) lithium reacted with
Table 2: SN2′-Ring-opening of N-Dpp vinyl aziridines by organometallic reagents.
Entry
Ar
Nucleophile
R
Product
Yield
1
2
Ph
Ph
Me2CuLi
Et2CuLi
Me
14
15
71%
40%
3
4
Ph
Ph
n-Bu2CuLi
s-Bu2CuLi
16
17
74%
47%
5
6
7
Ph
Ph
Ph
CH2=CH2CH2MgCl
18
19
20
74%
70%
68%
t-Bu2CuLi
t-Bu
CH2CO2Et2,
Pd(PPh3)4, NaH
CH(CO2Et)2
CH2(SO2Ph)2,
Pd(PPh3)4, NaH
8
Ph
CH(SO2Ph)2
21
22
23
24
62%
47%
44%
60%
9
4-Br-C6H4
4-Br-C6H4
4-Br-C6H4
Et2CuLi
10
11
n-Bu2CuLi
CH2CO2Et2,
Pd(PPh3)4, NaH
CH(CO2Et)2
CH(SO2Ph)2
CH2(SO2Ph)2,
Pd(PPh3)4, NaH
12
13
14
4-Br-C6H4
t-Bu
25
26
27
57%
61%
66%
Et2CuLi
t-Bu
n-Bu2CuLi
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Beilstein J. Org. Chem. 2013, 9, 852–859.
Scheme 4: Ring opening by Grignard reagent.
Table 3: Ring opening of N-Dpp vinyl aziridines by heteronucleophiles.
Entry
Ar
Heteronucleophile
R
Yield/%
Product
C-1:C-2:C-4a
1
2
3
4
5
Ph
(n-Bu3Sn)2CuLi
(n-Bu3Sn)2CuLi
(n-Bu3Sn)2CuLi
PhSLi
Bu3Sn
Bu3Sn
Bu3Sn
PhS
65
66
68
75
73
31
32
33
34
35
C-4 only
C-4 only
C-4 only
19:38:43
34:51:15
4-Br-C6H4
t-Bu
Ph
Ph
[PhSeBH3]Na
PhSe
aEstimated from 1H NMR.
aziridines 1, 2 and 4 with complete regiocontrol, as would have reaction with stannylcuprate. Complex mixtures of products
been predicted for a copper-based organometallic species, to were obtained from these reactions.
give N-Dpp-4-aminoallylstannanes in good yield (Table 3,
Conclusion
entries 1–3). To our knowledge, such allylstannanes had not
We have achieved the first syntheses and ring-opening reac-
tions of N-Dpp vinyl aziridines. The ring-opening reactions are
selective only when the nucleophilic co-reagent has a natural
propensity for SN2′-like reaction. A clearer understanding of the
features of these reactions is a subject of close scrutiny in our
laboratories at this time.
previously been prepared. Gratified by the good selectivity
shown in the ring openings effected by the stannylcuprate, we
next examined the reactions of PhSLi and [PhSeBH3]Na,
predicting that the soft nature of these nucleophiles might also
predispose them to react in a manner analogous to that of the
stannyl anion. However, our premise was not justified, because
these reactions were the most complex we had yet observed,
with an inseparable mixture of all three possible ring-opened
products being isolated. Two of these compounds arose from
SN2-like reaction at C-1 and C-2 while the other is produced via
an SN2′-like reaction at C-4.
Experimental
General methods
All organic solvents were distilled prior to use and all reagents
were purified by standard procedures. Light petroleum refers to
the fraction boiling in the range 40 to 60 °C. Diethyl ether, THF
Clearly, the "softness" of the nucleophile does have an effect on and DME were distilled from sodium benzophenone ketyl;
the regiochemistry of the ring-opening process (witness the toluene from sodium; dichloromethane, triethylamine, diiso-
difference in isomer distribution of entries 4 and 5), but there propylamine and acetonitrile from calcium hydride; and pyri-
does not yet seem to be any predictability about the reactions. dine and diisopropylethylamine from potassium hydroxide.
Particularly curious was the poor result obtained when our vinyl
aziridines 1, 2 and 4 were reacted with PhSCu, a reagent which Melting points were recorded on a Kofler hot-stage apparatus
might have been expected to mimic the high selectivity of the and are uncorrected. IR spectra were recorded on a Perkin
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Beilstein J. Org. Chem. 2013, 9, 852–859.
Elmer 881 spectrophotometer. Mass spectra were recorded on a fifteen minutes. The solution was further stirred at −78 °C for
VG9090 mass spectrometer or on a Fisons Autospec machine. 1 h and then at room temperature overnight. The resulting
1H and 13C NMR spectra were recorded on a Jeol GX-270 spec- suspension was diluted with H2O (10 mL) and extracted with
trometer or a Jeol L-300 spectrometer. Unless otherwise stated, ethyl acetate (3 × 20 mL). The organic layers were combined,
deuterochloroform was used as the solvent and tetramethylsi- washed with brine (20 mL), dried (MgSO4) and filtered, and the
lane was used as the internal standard. Chemical shifts in solvent was removed in vacuo to give a yellow oil, which was
1H NMR spectra are expressed as parts per million downfield purified by flash column chromatography on silica gel (typi-
from tetramethylsilane, and in 13C NMR, relative to the internal cally, diethyl ether/light petroleum, 3:2, as an eluent).
solvent standard. Coupling constants are quoted in hertz.
General procedures for the ring-opening
reactions of N-diphenylphosphinyl vinyl
aziridines
Reactions involving chemicals or intermediates sensitive to air
and/or moisture were performed under a nitrogen atmosphere in
flame- or oven-dried apparatus. Flash column chromatography
was performed using Merck Kieselgel 60 or Fluka Kieselgel 60
silica. Analytical thin-layer chromatography (TLC) was
performed on precoated Merck Kieselgel 60 F254 aluminium
backed plates and was visualised under UV conditions at
254 nm and by staining with an acidic ammonium molybdate
spray.
Ring-opening reaction with lower-order cuprates: To dry
CuI (5 equiv) in a flame-dried flask, under N2, was added
diethyl ether (10 mL), and the suspension was degassed. For the
preparation of Me2CuLi the suspension was then cooled to
0 °C, and MeLi (0.25 mL, 1.4 M in diethyl ether, 0.35 mmol,
1.7 equiv) was added dropwise (the solution becomes yellow
after addition of the first equivalent of MeLi and colourless
after the addition of the second equivalent). For the preparation
of Et2CuLi, n-Bu2CuLi, s-Bu2CuLi and t-Bu2CuLi the suspen-
sion was cooled to −20 °C and the alkyl lithium (3.5 equiv) was
added dropwise affording a dark brown or black suspension. In
all cases the solution was stirred for 20 min prior to further
cooling to −78 °C. A degassed solution of the vinyl aziridine
(1 equiv), in ether (4 mL)/THF (1 mL), was added dropwise,
and the solution was stirred at −78 °C for 1 h and then at room
temperature for 6 h, and then quenched by the addition of a
saturated, aqueous solution of ammonium chloride (15 mL).
The mixture was partitioned between ammonium chloride and
ethyl acetate, the aqueous layer extracted with ethyl acetate (3 ×
15 mL), the organic layers combined and washed with brine
(15 mL), dried (MgSO4) and filtered, and the solvent removed
in vacuo to give a yellow oil. The oil was purified by flash
column chromatography on silica gel with ethyl acetate/light
petroleum (1:1) as an eluent.
General procedures for the synthesis of
N-diphenylphosphinyl vinyl aziridines
Method A: To freshly distilled diisopropylamine (typically
0.14–0.42 mL, 1–3 mmol, 1.5 equiv) in THF (5 mL) at 0 °C,
under argon, was added n-butyllithium (2.5 M in hexanes,
1.5 equiv) dropwise. The resulting pale yellow solution was
then stirred at 0 °C for 30 min. To a suspension of ZnCl2
(1.5 equiv, fused under argon in the reaction vessel) and allyl
bromide (1 equiv) in THF (5 mL), under argon, at −78 °C was
then added the freshly prepared LDA dropwise. The suspension
was stirred at −78 °C for 30 min after which time the
N-diphenylphosphinylimine (1 equiv) in THF (5 mL) was added
dropwise. The solution was further stirred at −78 °C for 1 h and
then at room temperature overnight. The solution was diluted
with H2O (10 mL) and extracted with ethyl acetate (3 × 20 mL).
The organic layers were combined, washed with brine (20 mL),
dried (MgSO4) and filtered, and the solvent was removed in
vacuo to leave a yellow oil, which was purified by flash column Palladium-catalyzed ring-opening with malonate: To diethyl
chromatography on silica gel (typically, ethyl acetate/light malonate (typically 0.3–0.6 mmol, 1.1 equiv) in THF (1.5 mL),
petroleum, 1:1, as an eluent).
at room temperature, under argon, was added sodium hydride
(1.1 equiv), and the colourless solution was left to stir for
Method B: To freshly distilled diisopropylamine (typically 30 min. Pd(PPh3)4 (3 mol %) was added to the reaction mixture
0.14–0.42 mmol, 1–3 mmol, 2 equiv) in THF (5 mL) at 0 °C, and the dark orange suspension was further stirred for twenty
under argon, was added n-butyllithium (2.5 M in hexanes, five minutes. A solution of vinyl aziridine (1 equiv) in THF
2 equiv) dropwise. The resulting pale yellow solution was then (2.5 mL) was added dropwise, and the orange suspension was
stirred at 0 °C for 30 min. To a solution of ZnCl2 (2 equiv, stirred at room temperature for four hours. The reaction mix-
freshly fused under vacuum), and allyl bromide (1.5 equiv) in ture was quenched by the addition of a saturated aqueous solu-
THF (5 mL), under argon, at −78 °C was then added the freshly tion of ammonium chloride (15 mL). The solution was parti-
prepared LDA dropwise. The resulting solution was stirred at tioned between ammonium chloride and ethyl acetate, the
−78 °C for 30 min, after which time the N-diphenylphos- aqueous layer extracted with ethyl acetate (3 × 15 mL), the
phinylimine (1 equiv) in THF (3 mL) was added dropwise over organic layers combined and washed with brine (15 mL), dried
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Beilstein J. Org. Chem. 2013, 9, 852–859.
(MgSO4) and filtered, and the solvent removed in vacuo to give n-Bu3SnLi [13] solution was cooled to −20 °C and CuBr·Me2S
a yellow oil. The oil was purified by flash column chromatog- (0.5 equiv) added in one portion. The brown reaction mixture
raphy on silica gel (ethyl acetate/light petroleum (1:4); gradient was left to stir for 30 min and subsequently cooled to −78 °C. A
elution to ethyl acetate).
solution of the vinyl aziridine (1 equiv) in THF (5 mL) was
added dropwise. The solution was stirred at −78 °C for 1 h and
P a l l a d i u m - c a t a l y z e d r i n g o p e n i n g w i t h left to warm to room temperature overnight, after which time it
bis(phenylsulfonyl)methane: To bis(phenylsulfonyl)methane was quenched by the addition of a saturated aqueous solution of
(typically 0.3–0.7 mmol, 1.1 equiv) in THF (2 mL), at room ammonium chloride (15 mL). The solution was partitioned
temperature, under argon, was added sodium hydride between ammonium chloride and light petroleum, the aqueous
(1.1 equiv), and the suspension was left to stir for 30 min. layer extracted with light petroleum (3 × 15 mL), the organic
Pd(PPh3)4 (3 mol %) was added to the reaction mixture, and the layers combined and washed with brine (15 mL), dried
dark orange suspension was further stirred for twenty five (MgSO4) and filtered, and the solvent removed in vacuo to give
minutes. A solution of vinyl aziridine (1 equiv) in THF (3 mL) a yellow solid. This was purified by flash column chromatog-
was added dropwise, and the orange suspension was stirred at raphy on silica gel with ethyl acetate/light petroleum (1:1) as an
room temperature for six hours. The reaction mixture was eluent.
quenched by the addition of a saturated, aqueous solution of
ammonium chloride (15 mL). The solution was partitioned Ring-opening reaction with thiophenolate: To a solution of
between ammonium chloride and ethyl acetate, the aqueous thiophenol (0.08 mL, 0.78 mmol) in THF (15 mL), under argon,
layer extracted with ethyl acetate (3 × 15 mL), the organic at −42 °C was added n-BuLi (0.34 mL, 2.5 M in hexanes,
layers combined and washed with brine (15 mL), dried 0.86 mmol) dropwise. The solution was stirred at −42 °C for
(MgSO4), filtered and the solvent removed in vacuo to give a 30 min, after which time a solution of aziridine 1 (0.09 g,
yellow oil. The oil was purified by flash column chromatog- 0.26 mmol) in THF (5 mL) was added. The solution was
raphy on silica gel (ethyl acetate/light petroleum (1:4); gradient allowed to warm to room temperature, and stirring was
elution to ethyl acetate).
continued overnight. The solution was then partitioned between
water (10 mL) and ethyl acetate (15 mL), the aqueous layer
Ring-opening reaction with methyl magnesium Grignard: extracted with ethyl acetate (2 × 10 mL), the organic layers
To magnesium (5 equiv) in diethyl ether (5 mL), under washed with brine (15 mL), dried (Na2SO4) and filtered, and
nitrogen, at 0 °C, was added MeI (5.4 equiv) in diethyl ether the solvent removed in vacuo to give a yellow oil, which was
(1 mL) and the resulting mixture was stirred for 30 min, purified by flash column chromatography on silica gel (ethyl
creating a grey suspension. A solution of the vinyl aziridine acetate/light petroleum (1:4)) to give 34a (0.038 g, 32%), as a
(1 equiv) in THF (10 mL) was cooled to −78 °C and the ethe- colourless oil and 34b and 34c (0.047 g, 43%, 34b/34c ≈ 2:1,
real suspension added dropwise. Immediately, magnesium colourless oil) as an inseparable mixture.
iodide precipitated as a colourless solid, and the suspension was
left to stir at −78 °C for 1 h and then at room temperature for
Supporting Information
6–8 hours. The reaction mixture was quenched by the addition
of a saturated aqueous solution of ammonium chloride (15 mL).
Supporting Information features detailed experimental data
The solution was partitioned between ammonium chloride and
for all compounds.
ethyl acetate, the aqueous layer extracted with ethyl acetate (3 ×
Supporting Information File 1
Experimental procedures and data.
15 mL), the organic layers combined and washed with brine
(15 mL), dried (MgSO4) and filtered, and the solvent removed
in vacuo to give a yellow oil. The oil was purified by flash
column chromatography on silica gel with ethyl acetate/light
petroleum (1:1) as an eluent.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-9-98-S1.pdf]
Ring-opening reaction with stannyl cuprate: To freshly Acknowledgements
distilled diisopropylamine typically (0.4–0.8 mmol, 1 equiv) in We acknowledge the financial support of the EPSRC (PhD
THF (5 mL) at 0 °C, under nitrogen, was added n-butyllithium support for ANJ, AMcL and HMIO), the University of Reading,
(2.5 M in hexanes, 1 equiv) dropwise. The resulting pale yellow Parke Davis Neuroscience Research Centre (Cambridge, UK),
solution was then stirred at 0 °C for fifteen minutes, tri-n- the Nuffield Foundation, AstraZeneca (for an award from the
butyltin hydride (1 equiv) was added dropwise, and the reac- Strategic Research Fund to JBS), and the Royal Society
tion mixture left to stir for a further 15 min. The resulting (Industry Fellowship to JBS).
858

Beilstein J. Org. Chem. 2013, 9, 852–859.
30.Cantrill, A. A.; Jarvis, A. N.; Osborn, H. M. I.; Ouadi, A.; Sweeney, J. B.
Synlett 1996, 847. doi:10.1055/s-1996-5605
References
1. Sweeney, J. B. Product Subclass 5: Aziridines. In Amines and
Ammonium Salts; Enders, D.; Schaumann, E., Eds.; Science of
Synthesis, Vol. 40a; Georg Thieme Verlag: Stuttgart, 2008;
pp 643–772.
31.Deyrup, J. A.; Greenwald, R. B. Tetrahedron Lett. 1965, 6, 321.
doi:10.1016/S0040-4039(01)83880-6
32.Deyrup, J. A. J. Org. Chem. 1969, 34, 2724. doi:10.1021/jo01261a052
33.Wartski, L. J. Chem. Soc., Chem. Commun. 1977, 602.
doi:10.1039/C39770000602
(See for a review.)
2. Hirner, J. J.; Roth, K. E.; Shi, Y.; Blum, S. A. Organometallics 2012, 31,
6843. doi:10.1021/om300671j
34.Mauzé, B. J. Organomet. Chem. 1980, 202, 233.
doi:10.1016/S0022-328X(00)92670-6
3. Di Bussolo, V.; Frau, I.; Pineschi, M.; Crotti, P. Synthesis 2012, 44,
2863. doi:10.1055/s-0031-1291137
35.Mauzé, B. Tetrahedron Lett. 1984, 25, 843.
doi:10.1016/S0040-4039(01)80042-3
4. Mack, D. J.; Njardarson, J. T. Chem. Sci. 2012, 3, 3321.
doi:10.1039/c2sc21007j
36.Reutrakul, V.; Prapansiri, V.; Panyaotipun, C. Tetrahedron Lett. 1984,
25, 1949. doi:10.1016/S0040-4039(01)90084-X
5. Brichacek, M.; Navarro Villalobos, M.; Plichta, A.; Njardarson, J. T.
Org. Lett. 2011, 13, 1110. doi:10.1021/ol200263g
6. Craig, D.; Lu, P.; Mathie, T.; Tholen, N. T. H. Tetrahedron 2010, 66,
6376. doi:10.1016/j.tet.2010.04.096
37.Coutrot, P.; El Gadi, A. J. Organomet. Chem. 1985, 280, C11.
doi:10.1016/0022-328X(85)87075-3
38.Mallaiah, K.; Satyanarayana, J.; Ila, H.; Junjappa, H. Tetrahedron Lett.
1993, 34, 3145. doi:10.1016/S0040-4039(00)93402-6
39.As described previously [30], nOe experiments supported the
stereochemical deduction: irradiation of the ArCH signal led to an
enhancement of 33% at H2C=CHCH for the minor isomer (identified
accordingly as Z), compared to an enhancement of only 8% for the
major isomer (deduced to be the E-product).
7. Brichacek, M.; Lee, D.-E.; Njardarson, J. T. Org. Lett. 2008, 10, 5023.
doi:10.1021/ol802123e
8. Zuo, G.; Zhang, K.; Louie, J. Tetrahedron Lett. 2008, 49, 6797.
doi:10.1016/j.tetlet.2008.09.056
9. Trost, B. M.; Dong, G. Org. Lett. 2007, 9, 2357. doi:10.1021/ol070742y
10.Scheiner, P. J. Org. Chem. 1967, 32, 2628. doi:10.1021/jo01283a063
11.Scheiner, P. Tetrahedron 1968, 24, 349.
40.Arini, L. G.; Sinclair, A.; Szeto, P.; Stockman, R. A. Tetrahedron Lett.
2004, 45, 1589. doi:10.1016/j.tetlet.2004.01.002
doi:10.1016/0040-4020(68)89033-7
(See for subsequently reported synthetic routes to Dpp-vinyl
aziridines.)
12.Scheiner, P. Tetrahedron 1968, 24, 2757.
doi:10.1016/S0040-4020(01)82547-3
41.Wipf, P.; Fritch, P. C. J. Org. Chem. 1994, 59, 4875.
doi:10.1021/jo00096a033
13.Schultz, A. G.; Dittami, J. P.; Myong, S. O.; Sha, K.-C.
J. Am. Chem. Soc. 1983, 105, 3273. doi:10.1021/ja00348a051
14.Mishra, A.; Rice, S. N.; Lwowski, W. J. Org. Chem. 1968, 33, 481.
doi:10.1021/jo01266a001
42.Ohno, H.; Mimura, H.; Otaka, A.; Tamamura, H.; Fujii, N.; Ibuka, T.;
Shimizu, I.; Satake, A.; Yamamoto, Y. Tetrahedron 1997, 53, 12933.
doi:10.1016/S0040-4020(97)00817-X
15.Atkinson, R. S.; Rees, C. W. Chem. Commun. 1967, 1232.
doi:10.1039/c1967001232a
43.Fujii, N.; Nakai, K.; Tamamura, K. H.; Otaka, A.; Mimura, N.; Miwa, Y.;
Taga, T.; Yamamoto, Y.; Ibuka, T. J. Chem. Soc., Perkin Trans. 1
1995, 1359. doi:10.1039/P19950001359
16.Atkinson, R. S.; Rees, C. W. J. Chem. Soc. C 1969, 778.
doi:10.1039/J39690000778
44.Ibuka, T.; Akaji, M.; Mimura, N.; Habashita, H.; Nakai, K.;
Tamamura, H.; Fujii, N.; Yamamoto, Y. Tetrahedron Lett. 1996, 37,
2849. doi:10.1016/0040-4039(96)00403-0
17.Anderson, D. J.; Gilchrist, T. L.; Horwell, D. C.; Rees, C. W.
J. Chem. Soc. C 1970, 576. doi:10.1039/J39700000576
18.Hoes, L.; Drieding, A. S. Chimia 1972, 26, 629.
19.Knight, J. G.; Muldowney, M. P. Synlett 1995, 949.
doi:10.1055/s-1995-5128
20.Åhman, J.; Somfai, P. Tetrahedron Lett. 1995, 36, 303.
doi:10.1016/0040-4039(94)02236-5
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21.Åhman, J.; Somfai, P. Tetrahedron 1995, 51, 9747.
doi:10.1016/0040-4020(95)00558-P
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22.Ferrerro, L.; Rouillard, M.; Decouzon, M.; Azzaro, M. Tetrahedron Lett.
1974, 15, 131. doi:10.1016/S0040-4039(01)82155-9
23.Chabouni, R.; Laurent, A. Synthesis 1975, 464.
doi:10.1055/s-1975-23809
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24.Borel, D.; Gelas-Mialhe, Y.; Vessière, R. Can. J. Chem. 1976, 54,
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25.Li, A.-H.; Dai, L.-X.; Hou, X.-L.; Chen, M.-B. J. Org. Chem. 1996, 61,
4641. doi:10.1021/jo952245d
26.Wang, D.-K.; Dai, L.-X.; Hou, X.-L. Chem. Commun. 1997, 1231.
doi:10.1039/a702955a
(http://www.beilstein-journals.org/bjoc)
27.Li, A.-H.; Dai, L.-X.; Hou, X.-L. J. Chem. Soc., Perkin Trans. 1 1996,
867. doi:10.1039/P19960000867
The definitive version of this article is the electronic one
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28.Li, A.-H.; Dai, L.-X.; Hou, X.-L. J. Chem. Soc., Perkin Trans. 1 1996,
2725. doi:10.1039/P19960002725
doi:10.3762/bjoc.9.98
29.Morton, D.; Pearson, D.; Field, R. A.; Stockman, R. A. Org. Lett. 2004,
6, 2377. doi:10.1021/ol049252l
859