β-Elimination of an aziridine to an allylic amine: A mechanistic study

Article abstract of DOI:10.1002/poc.1838

The base-induced rearrangement of aziridines has been examined using a combination of calculations and experiment. The calculations show that the substituent on nitrogen is a critical feature that greatly affects the favorability of both α-deprotonation,

Full text of DOI:10.1002/poc.1838

Research Article
Received: 30 September 2010,
Revised: 14 December 2010,
Accepted: 14 December 2010,
Published online in Wiley Online Library: 18 February 2011
(wileyonlinelibrary.com) DOI 10.1002/poc.1838
b-Elimination of an aziridine to an allylic
amine: a mechanistic study
a
a
a
*
Kathleen M. Morgan , Garry Brown, Jr. , Monique A. Pichon
and Geannette Y. Greena
The base-induced rearrangement of aziridines has been examined using a combination of calculations and exper-
iment. The calculations show that the substituent on nitrogen is a critical feature that greatly affects the favorability of
both a-deprotonation, and b-elimination to form an allylic amine. Experiments were carried out to determine whether
E2-like rearrangement to the allylic amine with lithium diisopropyl amide (LDA) is possible. N-tosyl aziridines were
found to deprotonate on the tosyl group, preventing further reaction. A variety of N-benzenesulfonyl aziridines
having both a- and b-protons decomposed when treated with LDA in either tetrahydrofuran or hexamethylpho-
sphoramide. However, when a-protons were not present, allylic amine was formed, presumably via b-elimination.
Copyright ß 2011 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this paper.
Keywords: aziridine; allylic amine; a-elimination; b-elimination
mechanisms for epoxide rearrangement has been studied by
Collum et al.[13]
INTRODUCTION
The chemistry of aziridines is rich and varied.[1] In recent years,
the reactions of aziridine a-anions have been the subject of many
fruitful studies.[2] In this report, the potentially competitive
base-promoted E2-like rearrangement of aziridines to form allylic
amines is investigated.
The base-induced E2-like rearrangement of epoxides to allylic
alcohols is a well-known reaction that can occur with high regio-
and stereoselectivity.[3] The analogous rearrangement of azir-
idines to allylic amines is virtually unknown. Allylic amines are
important intermediates in the synthesis of many nitrogenous
natural products. Historically, there have been a limited number
of ways to make them,[4,5] but in recent years, new methods
have been developed.[6–8] Given the utility and selectivity of
epoxide rearrangements, it would be useful to study whether the
aziridine analog is feasible.
The rearrangement of epoxides in base is mechanistically
complicated.[3] Even with a bulky, non-nucleophilic base such
as lithium diisopropyl amide (LDA), there are two competing
reactions: a-deprotonation that initially forms the epoxide
a-anion, and b-elimination to form the allylic alcohol by an
E2-like reaction. The a-deprotonation is favored when epoxides
have added strain, such as cyclopentene oxide,[9] or when using
strong bases such as butyl lithium.[3] The a-anion behaves as
a carbenoid,[10] and typically undergoes CH bond insertion
reactions. Interestingly, allylic alcohols can also form through
this competing pathway, as well as ketones and other products,
though often with loss of selectivity. The solvent is also known
to influence the mechanism; cyclopentene oxide undergoes
a-elimination in ether or benzene, but b-elimination in
hexamethylphosphoramide (HMPA).[11] The stereochemistry of
b-elimination of 4-tert-butylcyclohexene oxide is syn in ether[12]
but anti in HMPA.[9] The importance of the solvent-dependent
aggregation state of the base on the a- versus b-elimination
Because the preparation of allylic alcohols from epoxides
continues to be a useful reaction, we were interested in
determining whether the b-elimination of aziridines to allylic
amines could also be carried out. Reports of aziridine
rearrangement are few, and do not appear to occur via the
stereoselective E2-like pathway. In 1993, da Zhang and
Scheffold[14] reported the isomerization of the N-acyl aziridines
derived from cyclohexene and cyclopentene to optically
active allylic amines using cob(I)alamin in methanol; this
transformation is thought to begin with nucleophilic addition
to form an organocobalamin intermediate. While this transform-
ation appears to be promising, this methodology has not
been utilized since. Other reports of allylic amine synthesis from
aziridines involve the use of chiral alkyl lithium base to remove
a bridgehead proton, generating the a-anion. In their studies
on the desymmetrization of achiral aziridines, Mu¨ller and
Nury[15] generated some allylic amines as well as other interesting
rearrangement products from simple N-tosyl aziridines
(Scheme 1). Note that the a-anion is shown as a resonance
structure of the carbene; this has been demonstrated compu-
tationally for the a-anion of cyclopentene oxide,[10] and is likely
the case with the aziridine anions as well.
Additional examples, with an eye to the mechanistic and
synthetic potential of the a-elimination mechanism, have been
reported by O’Brien et al.[16,17]
*
Correspondence to: K. M. Morgan, Department of Chemistry, Xavier University
of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
E-mail: kmmorgan@xula.edu
a
K. M. Morgan, G. BrownJr., M. A. Pichon, G. Y. Green
Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New
Orleans, Louisiana 70125, USA
J. Phys. Org. Chem. 2011, 24 1144–1150
Copyright ß 2011 John Wiley & Sons, Ltd.

b-ELIMINATION OF AZIRIDINES TO ALLYLIC AMINES
Scheme 1.
An extensive study of aziridine rearrangements was published
by Mordini et al.[18] Cyclic and acyclic aziridines were treated with
superbasic mixtures of butyl lithium/potassium tert-butoxide
(LICKOR) or lithium diisopropylamide/potassium tert-butoxide
(LIDACOR). A series of nitrogen substituents was investigated,
with the tosyl substituent being most productive; acyl sub-
stituents could not withstand the reaction conditions. Allylic
amines were generally obtained in low to moderate yield,
generally below 50%. Given the use of such strong base and the
presence of a-elimination products, notably the bicyclooctane
shown in Scheme 1, a-elimination is likely occurring under these
conditions.
sulfonamide derivative having N–SO2H. The expectation was
that the parent aziridine would be less reactive than the epoxide,
due to the high energy of the unstabilized nitrogen anion
produced, but the sulfonamide, having a stabilized anionic
intermediate, would be at least competitive with the epoxide.
Two aziridine structures were considered in each case, with the
nitrogen group cis versus trans to the methyl. In addition, three
conformations around the N–SO2H bond were explored. The
**
calculations were carried out at both the MP2/6-31þG //MP2/
*
*
6-31þG and B3LYP/6-31þG levels of theory. As in the Gronert
study, zero point energies were included to give enthalpies at
zero degrees. In general, the two computational methods give
similar results, and in the ensuing analysis only the MP2 results
are discussed.
RESULTS AND DISCUSSION
In both cases, the aziridine conformers having the nitrogen
substituent trans to the ring methyl were more stable than the
cis conformers. For methyl aziridine, this preference is
In order to evaluate the feasibility of the b-elimination
rearrangement, a series of ab initio and density functional theory
calculations were performed. Briefly, the calculations suggest
that E2-like rearrangement of aziridines is a favorable reaction,
though competing a-deprotonation may be problematic. Not
surprisingly, the nitrogen substituent plays a significant role.
Experimental studies described herein reveal that allylic amine is
obtained when a-protons are not present on the aziridine,
consistent with rearrangement via b-elimination.
0.8 kcal molꢀ1 at the MP2/6-31þG //MP2-6-31þG level of
theory. For the sulfonamide derivative, the lowest energy trans
conformation has the SO2H proton oriented away from the ring
methyl, with H–S–N–C(CH3) ¼ 1698. The next lowest structure is
þ0.3 kcal molꢀ1 and has H–S–N–C(CH3) ¼ ꢀ1028, while the
final conformer is þ2.6 kcal molꢀ1 and has H–S–N–C(CH3)¼ 368.
Only two conformers of the cis structure were obtained,
**
*
having H–S–N–C(CH3) ¼ ꢀ1788 and þ2.6 kcal molꢀ1
;
and
H–S–N–C(CH3) ¼ 478 and þ6.0 kcal molꢀ1
.
Inversion of the trans to cis methyl aziridine conformers
Computational analysis
was explored. For the parent methyl aziridine, the barrier is
**
*
The computational study was modeled after Gronert’s report
on the gas-phase rearrangement of methyloxirane with
hydroxide.[19] While hydroxide is not known to promote the E2
rearrangement of epoxides in solution, the results thus obtained
are consistent with all known experimental data, and hence
provide a reasonable model of the various reaction pathways.
Overall, the goal of this computational study is to predict the
inherent reactivity of aziridines compared to epoxides, to
determine whether aziridine b-elimination might be possible.
The effects of solvent are evaluated using a Self-Consistent
Reaction Field, specifically Tomasi’s Polarized Continuum
Model,[20] using benzene as a nonpolar solvent and DMSO as
a polar aprotic solvent. The role of the lithium counterion in
this type of reaction is complicated, and beyond the scope of this
study.
17.9 kcal molꢀ1 at the MP2/6-31þG //MP2-6-31þG level of
theory. A previous computational study[21] that used a cc-pVQZ
MP2 method found the barrier to be similar, 19.1 kcal molꢀ1. The
trans to cis inversion barrier calculated for the sulfonamide
derivative is significantly lower, 13.7 kcal molꢀ1
*
.
Figure 1 shows the MP2/6-31þG optimized structures for
methyl aziridine having the NH trans to the methyl (Fig. 1a), as
well as the ion–molecule complex formed with hydroxide
(Fig. 1b); the transition states to anti and syn elimination with
hydroxide (Fig. 1c and d); and the lowest energy of three possible
a-anions (Fig. 1e). Selected structural parameters are shown in
Table 1, and in general are not surprising. Formation of the
ion–molecule complex causes only minor structural changes,
and positions the base near the reactive methyl protons.
The geometries for the anti and syn E2 transition states for the
reactions of hydroxide with the aziridine show expected patterns,
such as C–N bond lengthening, C2–C4 bond shortening as the
alkene forms, and opening of the N–C3–C2 bond angle as the ring
opens. Similar geometries are found for the other aziridine series,
and are included in the supplemental information. In general,
Gronert’s study considered three epoxide reactions: syn
b-elimination, anti b-elimination, and a-deprotonation. In
the gas phase, the epoxide and base also form a stabilized
ion–molecule complex. In this study, these pathways were
calculated for the parent 2-methylaziridine (NH), and the
J. Phys. Org. Chem. 2011, 24 1144–1150
Copyright ß 2011 John Wiley & Sons, Ltd.
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K. M. MORGAN ET AL.
ꢀ
*
Figure 1. MP2/6-31þG optimized geometries for trans methyl aziridine series of compounds. (a) trans methyl aziridine. (b) Complex with HO . (c)
Transition state for anti b-elimination with HOꢀ. (d) Transition state for syn b elimination with HOꢀ. (e) Lowest energy a-anion.
the structural deformations are more pronounced for the
sulfonamide transition states, consistent with the greater
reactivity expected for the sulfonamides. For example, at the
transition state to anti b-elimination for the trans sulfonamide,
complex having the NH cis to the ring methyl is due to an
additional interaction between the N–H proton and the
hydroxide oxygen that is not available in any of the other
complexes. Not surprisingly, for all substrates anti b-elimination is
more favorable than syn elimination in the gas phase. Note
that negative activation enthalpies result because at the
transition states, the charge initially localized on hydroxide is
now delocalized in the transition state complex. As anticipated,
methyl aziridine is calculated to be less reactive than the epoxide.
The calculated activation enthalpy for anti elimination in the
sulfonamide is significantly lower than the epoxide, suggesting
that this reaction pathway could be viable and rapid. The
various sulfonamide conformations all give similar transition state
energies. Similar trends were found for syn eliminations, with the
sulfonamide again having the lowest calculated barrier, com-
pared to the aziridine plus hydroxide.
˚
the C2–N bond lengthens to 1.63 A, the C2–C4 bond shortens to
˚
1.46 A, and the N–C3–C2 angle opens to 66.18. Note that the
transition states for syn elimination of the cis aziridines were not
found, despite numerous attempts.
The energies of a variety of pathways were calculated, and are
reported in Table 2. The aziridine used for reference in both the
trans and cis methyl aziridine calculations is the lower energy
trans conformation, and for the sulfonamides, the lowest energy
conformer of the trans structure is used. The enthalpies of
ion–molecule complex formation, and activation enthalpies for
E2 transition state formation, are calculated with respect to
starting epoxide or aziridine plus hydroxide. A range of values
is tabulated for the sulfonamides because multiple conformers
around the N–S bond were considered for the transition states.
In all cases, stabilized ion–molecule complexes with hydroxide
form as expected in the gas phase. The added stabilization of the
Reaction enthalpies are also reported in Table 2 for the gas
phase reaction of the epoxide or aziridine plus hydroxide,
forming the a-anion plus water. There are three ring protons,
and hence three possible a-anions that could form from each
*
Table 1. Selected structural parameters for trans methyl aziridine series of compounds, MP2/6-31þG
Aziridine
Complex with HOꢀ
anti b-elim TS
syn b elim TS
a-Anion
˚
rC2–N (A)
1.48
1.48
1.48
1.50
1.10
1.49
1.50
1.48
1.51
1.10
2.25
59.98
1.54
1.49
1.48
1.48
1.60
1.13
62.78
ꢀ161.38
1.51
1.49
1.49
1.49
1.56
1.15
60.98
ꢀ32.78
1.53
1.49
1.50
1.52
˚
rC3–N (A)
rC2–C3 (A)
˚
rC2–C4 (A)
˚
rC4–Hmethyl (A)
˚
˚
rO–Hmethyl (A)
uNC3C2
59.78
61.88
tNC2C4H
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Copyright ß 2011 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2011, 24 1144–1150

b-ELIMINATION OF AZIRIDINES TO ALLYLIC AMINES
Table 2. Enthalpies of aziridine and epoxide reactions with hydroxide (kcal molꢀ1
)
DHrxn, ion–molecule
complex
DHz, anti
b-elimination
DHz, syn
b-elimination
DHrxn, a-anion
formationa
Methyl oxirane[19]
ꢀ15.9
ꢀ11.1
ꢀ23.0
ꢀ25.8
ꢀ17.8
ꢀ9.6
ꢀ1.9
ꢀ5.0
þ15.9 to þ17.3
þ19.0 to þ22.8
þ19.2 to þ25.5
ꢀ11.3 to ꢀ3.3
ꢀ8.5 to þ3.3
Methyl aziridine NH trans methyl
Methyl aziridine NH cis methyl
Methyl aziridine NSO2H trans methyl
Methyl aziridine NSO2H cis methyl
þ0.5
ꢀ5.7
n/a
ꢀ14.9 to ꢀ13.9
n/a
ꢀ18.8 to ꢀ18.2
ꢀ17.8
a Three isomeric a-anions can form; the range shows the variation in DHrxn to form them.
heterocycle, and the range is tabulated. The a-deprotonation of
methyl aziridine was calculated to be least favorable, and the
sulfonamide the most favorable. The a-anions have significant
carbenoid character. This has previously been observed
computationally for a-deprotonation of cyclopentene oxide,[10]
and similar results are found here. The carbenoid nature of the
anions is exhibited structurally in the lengthening of the bond
between the heteroatom and the carbanion/carbenoid carbon. In
the three anions generated from methyl oxirane, this bond has
from the a-anion; all starting structures either reverted to the
a-anion, or gave carbene CH bond insertion products.
Ionic reaction coordinates are highly sensitive to the effects
of solvent, so the reactions were also examined in solution using
the Polarized Continuum Model,[20] in both benzene and DMSO
*
solvent. The optimized MP2/6-31þG gas phase structures
were used for simplicity, and single point energies were
**
calculated at MP2/6-31þG with the PCM correction. Solvation
had a minimal impact, if any, on the relative stabilities of
conformers, if applicable, and on the relative stabilities of the
isomeric a-anions. The calculated reaction enthalpies in solution
are shown in Table 3. Not surprisingly, all the reactions have
barriers in solution. This is largely due to the highly favorable
solvation of hydroxide; benzene was calculated to stabilize
hydroxide by ꢀ47.6 kcal molꢀ1 and DMSO stabilizes hydroxide
even more, ꢀ85.9 kcal molꢀ1. For comparison, the solvation of
˚
lengthened to 1.55–1.58 A compared to the other C–O bond
˚
in the ring, 1.42–1.44 A. In the anions generated from the anti
conformation of methyl aziridine, the analogous bonds are
˚
1.53–1.57 A versus 1.47–1.49 A, and in the sulfonylated derivative
˚
˚
˚
these are 1.54–1.58 A versus 1.47–1.49 A. The carbenoid character
of the a-anions is also apparent in the atomic charges, as
calculated using Reed and Weinhold’s Natural Population
Analysis.[22,23] For example, in the anion generated from methyl
aziridine shown in Figure 1e, the charges are ꢀ0.83 on N, ꢀ0.38
on C2, ꢀ0.33 on C3, and ꢀ0.67 on C4. The CH proton charges
are all þ0.15 to þ0.19, and the amine proton is þ0.36. These
charges are more similar to the a-anion/carbenoid derived
from cyclopentene oxide rather than the corresponding neutral
a-hydroxycarbene, in which the oxygen does not complex to the
carbene. In this anion, the anionic/carbenoid carbon was ꢀ0.22,
while in the true carbene, the charge was ꢀ0.05. Further, as in the
case of the cyclopentene oxide a-anion, it was not possible to
find a discrete structure for the nitrogenous carbene separate
water is not nearly so significant, ꢀ4.0 and ꢀ9.2 kcal molꢀ1
,
respectively. The trends observed in the gas phase are generally
maintained in solution. Anti b-elimination is again the most
favorable reaction, and the sulfonylated aziridines are more
reactive than epoxides. One significant difference in solution is
that deprotonation at the a-position becomes competitive
with b-elimination in both solvents for the trans isomer of the
sulfonylated aziridine.
To summarize the computational results, substituents that
can stabilize the incipient nitrogen anion are predicted to favor all
three aziridine reactions studied, compared to epoxides. It is
Table 3. Reaction enthalpies calculated in benzene and DMSO (PCM) (kcal molꢀ1
)
DHz, anti
b-elimination
DHz, syn
b-elimination
DHrxn, a-anion
formationa
Benzene
DMSO
Benzene
DMSO
Benzene
DMSO
Methyl oxirane
Methyl aziridine
NH trans methyl
Methyl aziridine
NH cis methyl
þ6.9
þ19.0
þ26.9
þ11.4
þ17.2
þ23.5
þ29.2
þ27.0 to þ28.2 þ32.8 to þ33.2
þ31.2 to þ34.4 þ37.6 to þ39.7
þ15.0
þ11.9
þ25.1
n/a
n/a
þ31.0 to þ35.7 þ37.6 to þ40.2
Methyl aziridine
NSO2H trans methyl
Methyl aziridine
NSO2H cis methyl
þ1.5 to þ2.7 þ16.5 to þ17.5 þ5.6 to þ7.7 þ21.9 to þ23.2
þ1.7 þ17.4 n/a n/a
þ6.6 to þ13.9
þ9.5 to þ19.6
þ19.3 to þ23.9
þ22.5 to þ29.3
a Three isomeric a-anions can form; the range shows the variation in DHrxn to form them.
J. Phys. Org. Chem. 2011, 24 1144–1150
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K. M. MORGAN ET AL.
Scheme 2.
curious, then, why b-elimination of aziridines to allylic amines has
not yet been demonstrated. Certainly the role of a-deprotonation
must be considered as a factor.
Reactions of aziridines with base
Buoyed by these promising computational results, we have also
explored the rearrangements of ten aziridines with LDA. The first
aziridines prepared were N-tosyl compounds 1–3 (Scheme 2);
tosyl aziridines are common, and simple to make. These were
easily synthesized from cyclopentene, cyclohexene, and cyclooc-
tene with PhI ¼ NTs, according to literature precedent.[24]
Treatment of the N-tosyl aziridines 1–3 with 2.5 molar
equivalents of LDA in either THF or HMPA gave recovered
aziridine. During some of the runs, a mixture of aziridine and
cyclohexene oxide was used, and the epoxide rearranged
successfully, showing that active LDA was in fact present. This
finding is consistent with O’Brien’s observation that N-tosyl
aziridines are substantially less reactive than epoxides to lithium
amide bases.[25] Because the calculations predicted so convin-
cingly that the sulfonylated aziridines would react even more
favorably than epoxides, the apparent inertness of the aziridines
was surprising. However, a competing reaction of the N-tosyl
aziridines was found: methyl deprotonation of the tosyl group.
This was determined by subjecting 3 to LDA in THF, then
quenching with D2O. GC/MS analysis of the recovered aziridine
showed an increase in one mass unit compared to the reactant.
Further, the fragmentation was consistent with incorporation of
deuterium in the tosyl group, rather than deprotonation of the
aziridine bridgehead; for example, the SO2Ar fragment increased
in mass from 155 to 156. This methyl deprotonation apparently
prevents or retards subsequent reactions.
Scheme 3.
reported by Davis et al.[26] when certain N-sulfinyl aziridines were
treated with LDA at ꢀ78 8C. Davis also noted that other N-tosyl
aziridines can rearrange to vinylic amines; both processes are
thought to begin with a-deprotonation of the aziridine. Note that
the highly strained bicyclic azirine that would form from
aziridines 5 and 7–9 has only recently been detected spectro-
scopically, in situ, by Banert and Meier.[27] Another possible
decomposition pathway, reductive alkylation, was reported by
O’Brien for aziridines treated with sec-butyl lithium;[17] however,
the likelihood of the bulky diisopropylamide exhibiting this
reaction is low.
The formation of the azirine receives some computational
support, in addition to the observed GC/MS signal with m/z 96.
The structures of a few a-anions were not obtainable at the
*
B3LYP/6-31þG level of theory. In one case, dissociation to the
azirine and SO2H anion was observed instead. Still, that it was
found at all may give some insight into the possible
decomposition of the aziridines.
The final aziridine studied differs from all others in that it
possesses no a-protons on the aziridine ring. When treated with
LDA in THF, 10 yields allylic amine 11 (Scheme 4).
Aziridines 4–6 do not have the reactive methyl group.
Treatment with LDA in either THF or HMPA at room temperature
led to degradation of the reactant without formation of the
desired allylic amine. Note that the anticipated product appears
to be stable to the reaction conditions; some samples of aziridine
5 were contaminated with 1–2% of the allylic amine, which
persisted through the workup and into the GC analysis. Aziridines
7–8 with the activating electron-withdrawing groups also
degraded. In some runs, a product having a much shorter GC
retention time was observed, in low yield. The product could not
be isolated or identified definitively, despite numerous attempts.
However, a GC/MS was obtained for this product formed from 7,
and m/z of 96 was found, consistent with loss of the sulfonyl
group. The N-Boc-substituted aziridine 9 was also studied. Again,
only decomposition of the aziridine was observed.
The reaction mixtures were analyzed by GC, and 11 was the
only major product observed; a few baseline impurities were also
seen. In one run, rearrangement gave approximately 2/3
conversion of aziridine to allylic amine in 2 h. In an in situ
competition experiment, 10 was shown to react faster than
cyclohexene oxide. After 3 h, 1/3 of aziridine and 1/4 of epoxide
had rearranged, and overnight, the aziridine was fully rearranged
to allylic amine but 1/4 of the epoxide remained. While these
results are promising, the reaction is not without its vagaries. In
another run of 10, the initial yellow-orange reaction mixture
It is possible that removal of the a-proton leads to formation of
an unstable azirine (Scheme 3); this type of reaction has been
Scheme 4.
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b-ELIMINATION OF AZIRIDINES TO ALLYLIC AMINES
turned brown within a couple hours, and only decomposition and
an insoluble brown coating on the stir bar were observed.
Regardless, it is unambiguous that 10 rearranges to 11. Clearly,
the allylic amine cannot be formed via a-elimination in the case
of 10, suggesting that b-elimination of an aziridine has been
observed for the first time.
142.9, 132.6, 129.0, 126.9, 53.6, 20.5; MS (m/z, %) 240 (0.4, Mþ1),
224 (3.1), 141 (6.5), 98 (100), 77 (36.3); Anal calc. for C12H17NO2S: C
60.22, H 7.16, N 5.85, O 13.37, S 13.40; found: C 60.33, H 7.26, N
5.87, O 13.53, S 13.36.
Aziridine rearrangement[3]
Dry THF or HMPA (2.7 mL) was added by syringe to an oven-dried
flask under N2. The flask was cooled to 0 8C, then 0.189 mL
(1.34 mmol) diisopropyl amine that had been distilled from
NaOH, and 0.53 mL of 2.5 M BuLi in hexanes (1.33 mmol) were
added by syringe. The solution was stirred for 15 min, at which
time a solution of aziridine, or a mixture of aziridine and epoxide
(total of 0.54 mmol), in 0.45 mL THF or HMPA was added by
syringe. The reaction was warmed to room temperature after
30 min and stirred under N2 for several hours. The reaction was
quenched by adding 2 mL water. Solid NaCl was added to
separate the phases, and the organic layer was isolated. The
aqueous phase was extracted once more with ether, and the
combined organic fraction was dried over Na2SO4. Analysis was
performed by GC and GC/MS.
EXPERIMENTAL
Computational methods
Calculations were performed using Gaussian 03W.[28] Vibrational
frequency analysis was carried out to verify that structures were,
as appropriate, energy minima or transition states. GaussView
was used to animate the imaginary frequency to ensure that
the mode corresponded to the desired transition state. Using the
Gronert study[19] as a guide, geometries were optimized at the
*
MP2/6-31þG level of theory, and single point energies were
**
*
evaluated at MP2/6-31þG . In addition, B3LYP/6-31þG optim-
izations were carried out. However, several of the structures that
*
could be obtained using the MP2/6-31þG method could not be
found. Relative enthalpies were obtained using unscaled zero point
**
*
energies and energies calculated at MP2/6-31þG /MP2/6-31þG .
The effects of solvation were modeled using the Polarized
Continuum Model[20] as implemented in Gaussian 03W, by carrying
N-(2,3-dimethylbut-3-en-2-yl)benzenesulfonamide 11
1H NMR (CDCl3, 500 MHz) d 7.88 (d, 2H, J ¼ 7.5 Hz), 7.54 (t, 1H,
J ¼ 7.0 Hz), 7.49 (m, 2H), 4.95 (s, 1H), 4.83 (br s, 1H), 4.80 (s, 1H),
1.64 (s, 3H), 1.34 (s, 6H); 13C NMR (CDCl3, 75.4 MHz) d 148.5, 143.1,
132.4, 129.0, 127.4, 112.0, 59.7, 27.6, 19.0; MS (m/z, %) 224 (100),
198 (80.9), 141 (65.8), 98 (7.9), 77 (71.9).
**
*
out single point calculations at the MP2/6-31þG //MP2/6-31þG
level of theory, using both benzene and DMSO as the solvent.
General methods
GC analysis was performed on an instrument with a flame
ionization detector, equipped with a 30 m HP-1 capillary column.
GC/MS were obtained using a 30 m HP5MS capillary column,
interfaced to a mass selective detector. NMR spectra were
obtained using spectrometers operating at 499.9 MHz or at
300.0 MHz.
CONCLUSION
A computational analysis of three reactions of aziridines with
base suggest that while methyl aziridine should be less reactive
than methyl oxirane towards a-deprotonation, syn- and anti
b-elimination, the N-sulfonylated aziridine should react faster
than the epoxide in all three reactions. The rearrangement of
tetrasubstituted aziridine 10 to allylic amine 11 using LDA is
reported. Without competing a-deprotonation as a possible
reaction path, this reaction presumably occurs via an E2-like
mechanism.
Synthesis of aziridines
Most of the aziridines studied are known compounds and
were prepared using the copper triflate-catalyzed reaction of
PhI ¼ NSO2Ar with an alkene.[24] The nitrene precursors were
synthesized from iodosobenzene diacetate and sulfonamides,
and were recrystallized from methanol/water.[29] The aziridines
were purified by column chromatography using 4:1 hexanes/
ethyl acetate on silica. The N-Boc aziridine was prepared
according to the literature.[14,18] Two of the aziridines were not
previously described in the literature.
Acknowledgements
We would like to acknowledge the National Institutes of Health
MBRS SCORE Program (grant no. 1S06GM08008) for support of
this work. GB thanks the NIH-sponsored MBRS RISE program at
Xavier University of Louisiana (GM060926-07). We are grateful to
Gaussian, Inc., for providing software following Hurricane Katrina.
We thank Corinne Gibb (University of New Orleans) for assistance
with NMR spectra, and Leslee McElrath for assistance with syn-
thesis.
N-benzenesulfonyl-9-azabicyclo[6.1.0]nonane 6
1H NMR (CDCl3, 500 MHz) d 7.94 (d, 2H, J ¼ 8.0 Hz) 7.62 (t, 1H,
J ¼ 7.5 Hz), 7.54 (m, 2H), 2.82 (dd, 2H, J ¼ 17.3, 7 Hz), 2.02 (dd, 2H,
J ¼ 13.8, 3.3 Hz), 1.63–1.52 (m, 4H), 1.48–1.40 (m, 4H), 1.33–1.26
(m, 2H); 13C NMR (CDCl3, 75.4 MHz) d 139.2, 133.4, 129.2, 127.8,
44.3, 26.6, 26.4, 25.4; MS (m/z, %) 236 (0.9), 196 (6.6), 141 (4.9), 124
(100), 77 (2.7); Anal calc. for C14H19NO2S: C 63.36, H 7.22, N 5.28, O
12.06, S 12.08; found: C 63.45, H 7.22, N 5.11, O 11.91, S 11.94.
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J. Phys. Org. Chem. 2011, 24 1144–1150
Copyright ß 2011 John Wiley & Sons, Ltd.
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