Synthesis of oxazolidinones and 1,2-diamines from N-alkyl aziridines

Article abstract of DOI:10.1055/s-2004-831174

Reactions of N-alkyl-substituted aziridines with Lil followed by an electrophile are discussed. In the first series of reactions, the electrophile is carbon dioxide and the product is an oxazolidinone. In all cases, either no reaction occurred or a high y

Full text of DOI:10.1055/s-2004-831174

PAPER
2347
Synthesis of Oxazolidinones and 1,2-Diamines from N-Alkyl Aziridines
Synthesis of
O
xazolidi
a
nones and
1
t
,2-Dia
t
mine
s
h
N
-Alky
e
Aziridinesw T. Hancock,a Allan R. Pinhas*b
a
Millennium Pharmaceuticals, Inc., Cambridge, MA, 02139, USA
Fax +1(617)4441480; E-mail: matt.hancock@mpi.com
b
Department of Chemistry, University of Cincinnati, P. O. Box 210172, Cincinnati, OH 45221-0172, USA
Fax +1(513)5569239; E-mail: allan.pinhas@uc.edu
Received 22 January 2004; revised 25 May 2004
O
Abstract: Reactions of N-alkyl-substituted aziridines with LiI fol-
lowed by an electrophile are discussed. In the first series of reac-
tions, the electrophile is carbon dioxide and the product is an
oxazolidinone. In all cases, either no reaction occurred or a high
yield of product was obtained. HMPA had to be added to some re-
actions to dramatically improve the regiochemistry. Net retention of
stereochemistry was observed. In the second series of reactions, the
electrophile is an iminium salt and the product is a 1,2-diamine.
Here the reaction is highly regioselective in THF without the addi-
tion of HMPA. Unlike the oxazolidinone chemistry, the diamine
formation works equally well with or without the addition of LiI.
With respect to the regiochemistry, the results are the same with and
without added LiI. However, with respect to the stereochemistry, in
the presence of added LiI, the reaction with the iminium salt goes
with net retention of stereochemistry. In contrast, with no added LiI,
in some cases the reaction goes with net retention and in some cases
with net inversion of stereochemistry.
R1
N
O
R2
R3
1. LiI
2. CO2
R1
N
R4
1. LiI
R1 NH
N
R5
R4
2.
+
CH2
N
R2
R3
R5
R2
R3
R1
LiI
R2
N
R3
R2
Key Words: heterocycles, ring opening, aziridines, oxazolidin-
ones, diamines
R3
N
R1
Scheme 1
Because N-alkyl-substituted aziridines are readily avail-
able and highly reactive three-membered heterocyclic
ring systems,1 we have been interested in their conversion
Synthesis of Aziridines and Iminium Salts
to
other
organic
compounds,
especially
to
oxazolidinones2 and 1,2-diamines3 (Scheme 1). These
conversions involve reacting the aziridine with LiI fol-
lowed by an electrophile. It was found that when no elec-
trophile is added to the reaction mixture, after the aqueous
work-up, a six membered ring dimer of the aziridine (a
piperazine) is obtained. Unlike many reactions of aziri-
dines,4 for our reactions, neither an electron-withdrawing
group nor pre-formation of an aziridinium salt is required.
As shown in Scheme 2, almost all the aziridines were syn-
thesized from the corresponding epoxide and primary
amine. The epoxide was treated with the primary amine in
the presence of lithium perchlorate to afford the 1,2-ami-
noalcohol. Then, the aminoalcohol was cyclized using
triphenylphosphine and bromine.5 The exception to this
was cis-2,3-diphenylaziridine, which was prepared by the
treatment of tribenzylamine N-oxide with n-butyllithium.6
Also as shown in Scheme 2, the iminium salts were syn-
thesized from the corresponding secondary amine. The
secondary amine was treated with MeOH and paraformal-
dehyde to generate a gem-aminoether, which, without any
purification, was added to methyltrichlorosilane to yield
the iminium salt.7
In this paper, we summarize our previously reported re-
sults. In addition, we discuss the synthesis of the aziri-
dines, give yields and isomeric ratios for all reactions, and
give full experimental and spectroscopic details. Most im-
portantly, for the first time, we show that the diamine for-
mation reaction can be done with or without the addition
of LiI. Although the regiochemistry is the same with and
without added LiI, the stereochemistry is not.
Conversion of an Aziridine to an Oxazolidinone
Oxazolidinones are important as chiral auxiliaries and as
protecting groups in organic synthesis, as ligands for met-
al catalysts, and as biologically active pharmaceutical
agents.8–13 In spite of these facts, there are very few re-
ports in the literature of the conversion of a readily avail-
able N-alkyl aziridine, such as 1, and carbon dioxide
SYNTHESIS 2004, No. 14, pp 2347–2355
Advanced online publication: 17.08.2004
DOI: 10.1055/s-2004-831174; Art ID: M00704SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
4
(CO2) into an oxazolidinone, such as
2 or 3

2348
M. T. Hancock, A. R. Pinhas
PAPER
R1
N
O
NHR1
R3
HO
R2
LiClO4
PPh3/Br2
+
R1-NH2
R2
R2
R3
R3
R4
R5
R4
R4
R5
H3C-SiCl3
N+=CH2
+ H2CO + CH3OH
NH
N
CH2
O
CH3
R5
Scheme 2
(Scheme 3).14–17 The primary obstacles for this direct con-
version are the relative inertness of CO2, and the large
amount of polymer typically formed.18–24 In contrast, CO2
has been successfully utilized in the ring expansion of an
epoxide to a carbonate.25
Table 1 Products and Yields for the Reactions of 1 with LiI and CO2
Aziridine
Product(s) and Ratio
Overall Yield
83%
1a
61% 2a
39% 3a
As shown in Scheme 3 and Table 1, we have accom- 1b
plished the transformation of an N-alkyl aziridine to an
66% 2b
34% 3b
86%
oxazolidinone in good yield. The R1 and R2 groups on the
aziridine were varied in order to determine the regiochem-
1c
3c
99%
1d
1e
no reaction
no reaction
istry of this reaction. These reactions were run by heating
aziridine 1 with LiI and then bubbling CO2 into the solu-
tion for an extended period of time at room temperature to
give the product. When the reaction of 1a was run without
the addition of LiI, or in the presence of LiClO4 or I2 in
place of LiI, no product was obtained and the starting azir-
idine was recovered. Thus, the presence of I– ion is impor-
tant for the reaction to occur.
Hoping that a higher pressure/concentration of CO2 might
allow for a more facile reaction, and thus, only one regio-
isomer of the product, the reaction conditions were
changed from two separate steps at atmospheric pressure
to one step under a higher pressure. The aziridine, 0.25
equivalents, 1 equivalent, or 2 equivalents of LiI, and an
excess of powdered dry ice were mixed together in a
sealed thick-walled flask. For the reactions of compounds
1a and 1c–e, the results from this higher-pressure reac-
tion, regardless of the amount of LiI, are no different from
those reported in Table 1 for the reaction in which CO2
was bubbled into the reaction mixture.
O
O
R1
N
R1
R1
1) LiI
O
O
N
N
+
2) CO2
R2
R3
R3
R2
R2
R3
1
2
3
a R1 = CH2Ph
b R1 = pentyl
c R1 = CH2Ph
d R1 = Ph
R2 = CH3 R3 = H
In another effort to obtain only one product rather than a
mixture from the reaction of 1a, one equivalent of hexa-
methylphosphoramide (HMPA) was added as a co-sol-
vent. HMPA has been shown to be a potent lithium-
complexing agent. Many lithium-complexing agents have
been shown to activate organolithium reagents by increas-
ing the ion pair separation.26 It was hypothesized that by
increasing the ion pair separation of the LiI, the I– ion
would be more reactive and a reduction in the mixture of
isomers might occur.
R2 = CH3
R2 = Ph
R2 = Ph
R3 = H
R3 = H
R3 = H
e R1 = Ph
R2 = butyl R3 = H
f
R
1 = CH2Ph R2, R3 = -(CH2)4-
g R1 = CH2Ph R2 = CH3
h R1 = CH2Ph R2 = Ph
R3 = CH3
R3 = Ph
Scheme 3
When R1 and R2 are both alkyl groups and R3 is H, about
a 2:1 mixture of the two regioisomers was obtained. In
contrast, when R1 is an alkyl group and R2 is a phenyl,
there is formation of exclusively one product, the regio-
isomer in which the more substituted carbon-nitrogen is
carboxylated. Finally, when R1 is a phenyl group, regard-
less of R2, no reaction is observed and the starting aziri-
dine can be isolated in high yield.
As shown in Table 2, the reaction of aziridine 1a with LiI
and CO2 under the higher pressure/concentration condi-
tions with added HMPA generated oxazolidinone 2a and
only a very small amount of 3a. To further test our hy-
pothesis, the same reaction with compound 1b was run,
and oxazolidinone 2b and only a very small amount of 3b
was obtained. Unfortunately, adding HMPA to the reac-
tions of 1d and 1e still gave only the starting material and
no oxazolidinone.
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York

PAPER
Synthesis of Oxazolidinones and 1,2-Diamines from N-Alkyl Aziridines
2349
Table 2 Products and Yields for the Reactions of 1 with LiI,
HMPA, and CO2
the carbons were substituted by two alkyl groups, either
cis or trans, net retention of stereochemistry was ob-
served.27–29
Aziridine
Product(s) and Ratio
Overall Yield
91%
1a
97% 2a
3% 3a
Conversion of an Aziridine to a 1,2-Diamine
1,2-Diamines, also known as vicinal diamines, are biolog-
ically and medically important compounds. In addition,
they are prominent in organic synthesis as starting materi-
als, as chiral auxiliaries, and as chiral ligands to a variety
of metal complexes.30–34
1b
95% 2b
5% 3b
88%
1d
1e
no reaction
no reaction
Although there are known conversions of aziridines to
1,2-diamines, the number of reactions that start with an N-
alkyl aziridine is rather small.4,30,35–40 Most of these aziri-
dine to diamine reactions require an electron-withdrawing
group on the nitrogen, and usually a strong nucleophile,
such as azide, to open the ring. Alternatively, the aziridine
first can be converted to an aziridinium ion, which can
then be ring-opened with a large variety of nucleo-
philes.41–44 As shown in Scheme 4 and Table 4, we have
accomplished the conversion of an N-alkyl aziridine to a
1,2-diamine using neither an electron-withdrawing group
nor pre-formation of an aziridininum ion.
Using (CH3)2N+=CH2 as the iminium salt, the R1 and R2
groups of the aziridine were varied to determine the regio-
chemistry of this transformation. These reactions were run
by refluxing the aziridine and LiI, and then stirring with
the iminium salt at room temperature for an extended pe-
riod.
In order to determine the stereochemistry of this conver-
sion, 2,3-disubstituted aziridines 1f, 1g, and 1h were used
under the CO2 bubbling reaction conditions. In all cases,
either no reaction occurred or less than a 20% yield of
product was obtained.
Switching to the higher-pressure reaction conditions, us-
ing a single equivalent of LiI, improved the yields a great
deal, but unfortunately, mixtures of cis and trans isomers
of the products were formed. Hypothesizing that a stereo-
chemical mixture might be due to an intermediate under-
going multiple SN2 reactions with the I– ion to scramble
the stereochemistry, the reaction was attempted using
0.25 equivalents of LiI. As shown in Table 3, high yields
and very clean reaction products were obtained.
Table 3 Products and Yields for the Reactions of 1 with LiI and
CO2
Aziridine
1f
Product
2f
Yield
Table 4 Products and Yields for the Reactions of 1 with LiI and
Dimethylmethylene Iminium Chloride
90%
Aziridine
Product
4a
Yield
85%
71%
71%
16%
22%
cis-1g
cis-2g
trans-2g
86%
1a
1b
1c
1d
1e
trans-1g
cis-1h
trans-1h
84%
4b
no reaction
no reaction
5c
5d
When the carbons were substituted by two phenyl groups,
no reaction occurred and the starting aziridine was recov-
ered unchanged even in refluxing THF. However, when
5e
R1
R1
R1
N
1) LiI
N(CH3)2
N(CH3)2
R2
NH
R2
NH
+
+
2)
(H3C)2N CH2
R3
R3
R2
R3
1
4
5
a R1 = CH2Ph
b R1 = pentyl
c R1 = CH2Ph
d R1 = Ph
R2 = CH3 R3 = H
R2 = CH3
R2 = Ph
R2 = Ph
R3 = H
R3 = H
R3 = H
e R1 = Ph
R2 = butyl R3 = H
f
R
1 = CH2Ph R2, R3 = -(CH2)4-
g R1 = CH2Ph R2 = CH3
h R1 = CH2Ph R2 = Ph
R3 = CH3
R3 = Ph
Scheme 4
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York

2350
M. T. Hancock, A. R. Pinhas
PAPER
For compounds 1a and 1b, when the nitrogen and a car- For the reaction with CO2, it was found that the ste-
bon are both substituted by alkyl groups, it is the less sub- reospecificity improved as the amount of LiI added was
stituted carbon-nitrogen bond that is broken to give decreased. In contrast, for the reaction with the iminium
products 4a and 4b, respectively. Unlike the reactions of salt, the product is stereospecific even when one equiva-
alkyl substituted aziridines with LiI and CO2 using only lent of LiI was added.
THF as the solvent, for the iminium reactions, at most
As shown in Scheme 5 and Table 5, aziridine 1a was re-
acted with a variety of iminium salts (6) to determine the
variety of substituents that could be used.
only a trace of the other regioisomer can be detected by 1H
NMR spectroscopy or GC–MS. When carbon-2 is substi-
tuted by a phenyl group as in 1c, the more substituted car-
bon-nitrogen bond is broken to give 5c. This change in
Ph
regiochemistry also was observed in the oxazolidinone
chemistry.
R4
N
1) LiI
Ph
N
R5
NH
In contrast to the oxazolidinone chemistry, an N-phenyl
aziridine does react under the iminium reaction condi-
tions. With 1d (the diphenyl case), the more substituted
carbon-nitrogen bond is broken to give 5d. Unfortunately,
the isolated yield is very low and a large amount of intrac-
table material is obtained. For aziridine 1e, in which the
nitrogen is substituted by a phenyl and the carbon by an
alkyl, it is also the more substituted carbon-nitrogen bond
that is broken to give 5e. Only a trace of 4e was observed.
As with 1d, the yield is rather low. For the two N-phenyl
aziridines, the lack of reactivity with CO2 and the low
yield in the reaction with the iminium salt probably is due
to the reduced nucleophilicity/basicity of a phenyl-substi-
tuted nitrogen (an aniline derivative) versus an alkyl-sub-
stituted nitrogen (an alkyl amine derivative).
R4
2)
+
N
CH2
H3C
H3C
1a
7
R5
6
a R4 = CH3
b R4 = CH3
c R4 = CH2CH3
d R4 = CH2Ph
R5 = CH3
R5 = CH2CH3
R5 = CH2CH3
R5 = CH3
e R4 = CH(CH3)2 R5 = CH3
f
R4 = CH(CH3)2 R5 = CH(CH3)2
g R4, R5 = -(CH2)4
-
Scheme 5
Table 5 Products and Yields for the Reactions of 1a with LiI and
Various Dialkylmethylene Iminium Chlorides 6
Dialkylmethylene iminium chloride Product
Yield
85%
69%
63%
78%
65%
0%
To determine the stereochemistry of this transformation,
we studied 2,3-disubstituted aziridines 1f and 1g. Com-
pound 1h was not used because, as discussed above, it is
inert to our LiI reaction conditions. The reaction of aziri-
dine 1f gives 1,2-diaminocyclohexane 4f as the product. If
the two amino groups are trans, a large diaxial coupling
between the hydrogen at C-1 and the hydrogen at C-2
should be observed. In contrast, if the two amines are cis,
the J value will be small.44 A J value of 2.4 Hz was ob-
tained, which indicates that the two amino groups are cis.
Thus, this transformation goes with net retention of
stereochemistry.
6a
6b
6c
6d
6e
6f
7a (= 4a)
7b
7c
7d
7e
7f
6g
7g
80%
In all cases, the methylene is lost and the two alkyl groups
are retained in the product diamine (7). This result implies
that the iminium salts are stable to hydrogen scrambling
under the reaction conditions. All reactions proceed in
For 2,3-dimethylaziridine 1g, the reaction is stereospecif-
ic, i.e., the cis stereoisomer of the starting material gives
one stereoisomer of the product and the trans stereoiso-
mer of the starting material gives the other stereoisomer of
the product. (This was determined by the differences in good yield except for the diisopropyl case (6f), which
the chemical shifts of the two products. The product from does not react at all. We suspect this lack of reactivity is
cis-1g has its methyl groups at 1.09 ppm and 1.14 ppm and due to the large size of the two isopropyl groups.
the hydrogens at C-1 and C-2 at 2.3 ppm and 2.9 ppm. The
product from trans-1g has its methyl groups at 0.8 ppm
and 1.0 ppm and the hydrogens at C-1 and C-2 at 2.2 ppm
and 2.3 ppm.)
Because a gem-aminoether, as shown in Scheme 2, is the
immediate precursor to the iminium salt, it was of interest
to determine if an aminoether would undergo similar reac-
tions with an aziridine. Although the aminoethers have the
advantage of being less air-sensitive than the iminium
salts, in most cases, they were very difficult to isolate due
to their volatility. An exception is the aminoether corre-
sponding to iminium salt 6d, which has a benzyl substitu-
ent. It was found that the yield was much higher when
using the iminium salt (78% yield) than when using the
aminoether (53% yield).
The stereochemistry of the product diamine was deter-
mined by the chemical shifts and coupling constants of the
hydrogens at C-1 and C-2.45 We found that cis-1g gener-
ates erythro-4g and that trans-1g generates threo-4g.
Thus, as with the cyclohexane case, this reaction goes
with net retention of stereochemistry.
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York

PAPER
Synthesis of Oxazolidinones and 1,2-Diamines from N-Alkyl Aziridines
2351
Conversion of an Aziridine to a 1,2-Diamine Without
Using LiI
There are two major exceptions to the similarity of these
two reactions:
(1) For the reaction of cyclohexane derivative 1f, in the
presence of LiI, the product diamine 4f has cis stereo-
chemistry (Scheme 4). In contrast, for the reaction with-
out added LiI, a J value of 9.7 Hz was obtained, which
indicates that the two amino groups are trans. Thus, un-
like the reaction with LiI, this transformation goes with
net inversion of stereochemistry.
As discussed above, no reaction occurred when an aziri-
dine and CO2 are mixed in the absence of LiI. In contrast,
simply stirring an N-alkyl aziridine and an iminium salt at
room temperature generates a diamine. Comparing the
data in Tables 6 and 7 with the data in Tables 4 and 5
shows that the product is exactly the same and the yield is
nearly the same in the presence of and in the absence of
added LiI.
(2) With either cis- or trans-diphenylaziridine 1h, as men-
tioned above, there is no reaction with LiI. However, the
direct reaction of 1h with the dimethylmethylene iminium
chloride does generate diamine 4h. This reaction is ste-
Table 6 Products and Yields for the Reactions of 1 with Dimethyl-
methylene Iminium Chloride
1
reospecific, i.e., the H NMR spectrum of the product
Aziridine
Product
4a
Yield
98%
76%
79%
10%
46%
from cis-1h has the hydrogens at C-1 and C-2 at 3.2 ppm
1a
1b
1c
1d
1e
1
and 4.2 ppm and the H NMR spectrum of the product
from trans-1h has the hydrogens at C-1 and C-2 at 3.7
ppm and 4.0 ppm. As with dimethylazirdine 1g, based on
the chemical shifts and coupling constants,45 cis-1h gen-
erates erythro-4h and trans-1h generates threo-4h. Thus,
this reaction, which does not require LiI, goes with net re-
tention of stereochemistry.
4b
5c
5d
5e
The formation of an oxazolidinone or a 1,2-diamine from
a readily available N-alkyl substituted aziridine was stud-
ied. Our reaction involves starting with an N-alkyl aziri-
dine and LiI, and then adding an electrophile. When the
electrophile is CO2, an oxazolidinone is formed. When the
electrophile is an iminium salt, after an aqueous work-up,
a 1,2-diamine is formed. It was found that when the aziri-
dine is substituted by only alkyl groups, it is the less sub-
stituted carbon-nitrogen bond that is broken; whereas,
when the aziridine is substituted by a phenyl group at ei-
ther the nitrogen or the carbon, it is the more substituted
carbon-nitrogen bond that is broken. For a 2,3-disubstitut-
ed aziridine, the reaction with CO2 or with the iminium
salt goes with net retention of stereochemistry.
Table 7 Products and Yields for the Reactions of 1a with Various
Dialkylmethylene Iminium Chlorides 6
Dialkylmethylene
iminium chloride
Product
Yield
6a
6b
6c
6d
6e
6f
7a ( = 4a)
98%
74%
76%
94%
73%
0%
7b
7c
7d
7e
7f
It was also discovered that the iminium salt reaction
works without added LiI. Here the regiochemistry is the
same as in the presence of LiI. In addition, for a 2,3-dis-
6g
7g
70%
The similarity of the results with and without added LiI ubstituted aziridine with no added LiI, the reaction goes
naturally raised concern about the reactivity of compound with net retention. However, the cyclohexane-substituted
1 and LiI. In other words, were 1 and LiI actually reacting aziridine goes with net inversion of stereochemistry.
to give an intermediate, or was LiI not doing anything and
so its presence made no difference to the reaction? When
a dilute solution of compound 1 is concentrated, com-
Note Added to the Proof
pound 1 is stable and can be isolated. However, as dis- In a paper published after this paper was accepted (Miller,
cussed above (Scheme 1), when the reaction solution of 1 A. W.; Nguyen, S. T. Org. Lett. 2004, 6, 2301), it was
found that CO2 in the presence of a (salen)Cr(III) complex
can be used to convert an aziridine into an oxazolidine.
For a 2-phenylaziridine, they found results very similar to
with LiI is concentrated, a piperazine, which is a six-
membered ring dimer of compound 1, is formed. There-
fore, immediately after compound 1 was refluxed with
LiI, some of the reaction solution was removed and con- ours. For a 2-alkylaziridine, our major product is the 4-
centrated. For all the aziridines except 1h, which does not alkyloxazolidinone and their major product is the 5-alkyl-
react with LiI, the resulting product was not 1 but was ex- oxazolidinone, and thus, the two methods are complemen-
clusively the dimer of 1. Thus, it is believed that a reaction tary. No comparison of stereochemistry between the two
with LiI did occur prior to the addition of the iminium salt. methods can be made because the only 2,3-disubstituted
Therefore, these two different reactions (the reaction with compound used by Miller and Nguyen is the cyclohexane
and the reaction without added LiI) give similar results.
derivative.
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York

2352
M. T. Hancock, A. R. Pinhas
PAPER
All reactions were carried out using oven-dried glassware that was
cooled under an Ar atmosphere or in a desiccator. All reactions were
carried out under an Ar atmosphere unless otherwise noted. In all
cases, the product is an oil that could be easily purified (when nec-
essary) by using a short alumina column in a disposable pipette,
eluting with CH2Cl2 and EtOAc, to give the corresponding product.
All yields, except where it is indicated that an inseparable mixture
was obtained, are of isolated material.
Reaction of Aziridine 1d
The reaction of aziridine 1d (0.20 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and CO2 generated no oxazolidinone. Aziridine 1d (0.19 g,
0.95 mmol) was recovered.
Reaction of Aziridine 1e
The reaction of aziridine 1e (0.18 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and CO2 generated no oxazolidinone. Aziridine 1e (0.18 g,
1.0 mmol) was recovered.
THF was freshly distilled from potassium benzophenone ketyl.
Benzyl bromide was distilled prior to use. Et3N was distilled from
barium oxide. All other chemicals were purchased from Aldrich and
used without further purification, unless otherwise noted. Appropri-
ate precautions were taken because 2-methylaziridine, according to
Aldrich, is highly toxic and a cancer suspect agent.
High Pressure CO2 Method for the Conversion of an Aziridine
to an Oxazolidinone with or without Added HMPA; General
Procedure
A mixture of the aziridine, LiI, and HMPA (when needed) in THF
(15 mL) was added to a 25 mL heavy walled round bottom flask that
contained a threaded Teflon plug (Ace Glass). This reaction mixture
was then cooled to –78 °C, and powdered dry ice (CO2, 8.0 g 180
mmol) was added in two portions. The round bottom flask was then
capped with the threaded Teflon plug and allowed to warm to r.t.
The reaction mixture was stirred overnight at r.t., unless otherwise
noted. After that, the mixture was again cooled to –78 °C and the
pressure was released by slowly removing the Teflon plug. The
mixture was added to Et2O (50 mL) and washed with 10% sodium
bisulfite (25 mL). The ethereal solution was washed with water (3
× 30 mL). The ethereal solution was dried with anhyd K2CO3, fil-
tered, and evaporated to dryness yielding the corresponding oxazo-
lidinone.
All NMR spectra were recorded on a Bruker 250 MHz NMR spec-
trometer in CDCl3, unless otherwise noted, with chemical shifts ref-
erenced to TMS at 0.00 ppm. All GC–MS spectra were recorded on
a Hewlett Packard 6890, equipped with a SPB-1 capillary column.
The initial injection temperature was 70 °C; the temperature was
then raised to 315 °C at 10 °C/min and held at 315 °C for 5 min. IR
spectra were recorded on a Perkin Elmer Spectrum One FTIR spec-
trophotometer using a KBr cell with a path length of 0.05 mm. All
spectra were recorded in CHCl3 unless otherwise noted. HRMS
spectra were obtained on an Ion Spec FT-ICR using electrospray
ionization. Spectroscopic data for compounds 2a, 2f, 3a, 3c, 4, 5,
and 7 have been reported previously.5,19,23,27,28
CO2-Bubbling Method for the Conversion of an Aziridine to an
Oxazolidinone; General Procedure
Reaction of Aziridine 1a with Added HMPA
The reaction of aziridine 1a (0.059 g, 0.40 mmol), LiI (0.056 g, 0.40
mmol), and CO2 with added HMPA (0.072 g, 0.40 mmol) generated
2a (0.067 g, 0.35 mmol, 88% yield) and 3a (0.002 g, 0.01 mmol, 3%
yield).
A mixture of the aziridine and LiI in THF (30 mL) was allowed to
reflux for 15 min. CO2 was then bubbled through this reaction mix-
ture for 4 h at r.t. After this time, the mixture was added to Et2O (50
mL) and washed with 10% sodium bisulfite (25 mL). The ethereal
solution was washed with water (3 × 30 mL). The ethereal solution
was dried with anhyd K2CO3, filtered, and evaporated to dryness
yielding the corresponding oxazolidinone.
Reaction of Aziridine 1b with Added HMPA
Aziridine 1b (0.051 g, 0.40 mmol), LiI (0.056 g, 0.40 mmol), and
CO2 with added HMPA (0.072 g, 0.40 mmol) generated 2b (0.058
g, 0.34 mmol, 84% yield) and 3b (0.002 g, 0.01 mmol, 4% yield).
Reaction of Aziridine 1a
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and CO2 generated 2a (0.098 g, 0.51 mmol, 51% yield) and
3a (0.062 g, 0.32 mmol, 32% yield).
2b
IR: 1747 cm–1.
1H NMR: d = 0.91 (t, J = 6.7 Hz, 3 H), 1.27 (d, J = 5.9 Hz, 3 H),
1.30–1.39 (m, 4 H), 1.46–1.58 (m, 2 H), 2.93–3.17 (m, 1 H), 3.33–
3.47 (m, 1 H), 3.79–3.95 (m, 2 H), 4.39 (t, J = 7.3 Hz, 1 H).
13C NMR: d = 14.09, 18.30, 22.47, 27.19, 41.72, 50.96, 68.98,
158.21.
Reaction of Aziridine 1b
The reaction of aziridine 1b (0.13 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and CO2 generated 2b (0.097 g, 0.57 mmol, 57% yield) and
3b (0.049 g, 0.29 mmol, 29% yield). Compounds 2b and 3b were
obtained as an inseparable mixture, and thus, the reported data are
for a mixture of both 2b and 3b.
Reaction of Aziridine 1f
The reaction of aziridine 1f (0.075 g, 0.40 mmol), LiI (0.014 g, 0.10
mmol), and CO2 generated 2f (0.083 g, 0.36 mmol, 90% yield).
IR: 1747 cm–1.
1H NMR: d = 0.91 (t, J = 6.7 Hz, 3 H), 1.27 (d, J = 5.9 Hz, 2 H),
1.30–1.39 (m, 0.33 H), 1.43 (d, J = 6.1 Hz, 0.67 H), 1.46–1.58 (m,
1.67 H), 1.63 (br s, 0.67 H), 2.83 (d, J = 4.9 Hz, 0.33 H), 2.93–3.17
(m, 1.33 H), 3.20–3.30 (m, 0.67 H), 3.33–3.47 (m, 0.67 H), 3.63 (t,
J = 8.5 Hz, 0.33 H), 3.79–3.95 (m, 1.33 H), 4.39 (t, J = 7.3 Hz, 0.67
H), 4.58–4.68 (m, 0.33 H).
Reaction of Aziridine cis-1g
The reaction of aziridine cis-1g (0.064 g, 0.40 mmol), LiI (0.014 g,
0.10 mmol), and CO2 at 70 ºC generated cis-2g (0.070 g, 0.34 mmol,
86% yield).
IR: 1739 cm–1.
1H NMR: d = 1.10 (d, J = 6.2 Hz, 3 H), 1.33 (d, J = 5.6 Hz, 3 H),
3.65 (pent, J = 6.8 Hz, 1 H), 4.03 (d, J = 14.9 Hz, 1 H), 4.61 (pent,
J = 6.7 Hz, 1 H), 4.82 (d, J = 15.5 Hz, 1 H), 7.26–7.34 (m, 5 H).
13C NMR: d = 14.09, 18.30, 20.87, 22.47, 27.19, 28.89, 29.02,
41.72, 44.21, 50.96, 51.47, 68.98, 69.90, 158.21.
MS: m/z = 171 (5.4), 156 (19.0), 142 (34.8), 115 (28.8), 114 (82.6),
70 (100), 56 (9.8).
13C NMR: d = 12.61, 15.05, 45.85, 53.19, 73.78, 127.96–128.88,
136.40, 158.08.
+
HRMS: m/z calcd for C9H18NO2 : 172.1337; found: 172.1331.
MS: m/z = 205 (30.4), 150 (40.8), 106 (33.7), 92 (14.1), 91 (100),
79 (14.2), 65 (20.7), 56 (17.9).
Reaction of Aziridine 1c
The reaction of aziridine 1c (0.21 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and CO2 generated 3c (0.25 g, 0.99 mmol, 99% yield).
+
HRMS: m/z calcd for C12H16NO2 : 206.1181; found: 206.1171.
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York

PAPER
Synthesis of Oxazolidinones and 1,2-Diamines from N-Alkyl Aziridines
2353
Reaction of Aziridine trans-1g
mmol) generated 5d (0.04 g, 0.16 mmol, 16% yield), plus a trace
amount of an isomeric compound that is believed to be 4d.
The reaction of aziridine trans-1g (0.064 g, 0.40 mmol), LiI (0.014
g, 0.10 mmol), and CO2 at 70 ºC generated trans-2g (0.068 g, 0.33
mmol, 84% yield).
1H NMR: d = 1.18 (d, J = 6.2 Hz, 3 H), 1.33 (d, J = 6.1 Hz, 3 H),
3.18 (pent, J = 6.5 Hz, 1 H), 4.09 (d, J = 14.9 Hz, 1 H), 4.11 (pent,
J = 6.5 Hz, 1 H), 4.76 (d, J = 15.2 Hz, 1 H), 7.26–7.34 (m, 5 H).
Reaction of Aziridine 1e with Lithium Iodide and N,N-Dimeth-
ylmethylene Iminium Chloride
The reaction of aziridine 1e (0.18 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-dimethylmethylene iminium chloride (0.10 g, 1.0
mmol) generated 5e (0.05 g, 0.22 mmol, 22% yield), plus a trace
amount of an isomeric compound that is believed to be 4e.
13C NMR: d = 17.46, 19.32, 45.90, 57.46, 127.96–128.93, 136.19,
158.08.
13C NMR (CD3CN): d = 17.55, 19.32, 46.25, 58.65, 78.47, 128.47–
129.61, 138.05.
Reaction of Aziridine 1f with Lithium Iodide and N,N-Dimeth-
ylmethylene Iminium Chloride
The reaction of aziridine 1f (0.19 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-dimethylmethylene iminium chloride (0.10 g, 1.0
mmol) generated cis-4f (0.19 g, 0.83 mmol, 83% yield).
The determination of the stereochemistry of oxazolidinones cis-1g
1
and trans-1g was accomplished by comparing the H NMR spec-
trum for each compound. It has been shown in the literature29 that
for similar oxazolidinones, the methyl groups at C-4 and C-5 are at
higher field in the cis isomer than in the trans isomer. In addition,
the methine protons at C-4 and C-5 are at lower field in the cis iso-
mer than in the trans isomer.
Reaction of Aziridine 1g with Lithium Iodide and N,N-Dimeth-
ylmethylene Iminium Chloride
The reaction of aziridine trans-1g (0.16 g, 1.0 mmol), LiI (0.20 g,
1.5 mmol), and mmol) N,N-dimethylmethylene iminium chloride
(0.10 g, 1.0 mmol) generated one stereoisomer 4g (0.18 g, 0.90
mmol, 90% yield) and the reaction of aziridine cis-1g (0.16 g, 1.0
mmol), LiI (0.20 g, 1.5 mmol), and N,N-dimethylmethylene imini-
um chloride (0.10 g, 1.0 mmol) generated the other stereoisomer of
4g (0.19 g, 0.94 mmol, 94% yield).
Reaction of Aziridine cis-1h
The reaction of aziridine cis-1h (0.11 g, 0.40 mmol), LiI (0.054 g,
0.40 mmol), and CO2 at 70 ºC generated no oxazolidinone. Aziri-
dine cis-1h (0.10 g, 0.36 mmol) was recovered.
Reaction of Aziridine trans-1h
Reaction of Aziridine 1a with Lithium Iodide and N,N-Ethyl-
methylmethylene Iminium Chloride (6b)
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-ethylmethylmethylene iminium chloride (6b, 0.11
g, 1.0 mmol) generated 7b (0.14 g, 0.69 mmol, 69% yield).
The reaction of aziridine trans-1h (0.11 g, 0.40 mmol), LiI (0.054
g, 0.40 mmol), and CO2 at 70 ºC generated no oxazolidinone. Azir-
idine trans-1h (0.11 g, 0.40 mmol) was recovered.
Conversion of an Aziridine to a Diamine in the Presence of Lith-
ium Iodide; General Procedure
Reaction of Aziridine 1a with Lithium Iodide and N,N-Diethyl-
methylene Iminium Chloride (6c)
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-diethylmethylene iminium chloride (6c, 0.12 g, 1.0
mmol) generated 7c (0.14 g, 0.63 mmol, 63% yield).
A mixture of the aziridine and LiI in THF (30 mL) was allowed to
reflux for 15 min. This reaction was cooled to r.t. Then the iminium
salt was added and the solution was stirred at 25 °C. After 20 h, the
reaction mixture was added to Et2O (50 mL). Then the mixture was
treated with water (100 mL) and made acidic (pH = 2 or 3, as deter-
mined by pH paper) with HCl. The water was removed and made
basic (pH = 10 or 11, as determined by pH paper) with NaOH. Fi-
nally, the water was extracted with Et2O (3 × 50 mL). The Et2O so-
lutions were mixed together, dried with anhyd K2CO3, filtered, and
evaporated to dryness.
Reaction of Aziridine 1a with Lithium Iodide and N,N-Benzyl-
methylmethylene Iminium Chloride (6d)
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-benzylmethylmethylene iminium chloride (6d,
0.17 g, 1.0 mmol) generated 7d (0.21 g, 0.78 mmol, 78% yield).
Reaction of Aziridine 1a with Lithium Iodide and N,N-Dimeth-
ylmethylene Iminium Chloride
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-dimethylmethylene iminium chloride (0.10 g, 1.0
mmol) generated 4a (0.16 g, 0.85 mmol, 85% yield).
Reaction of Aziridine 1a with Lithium Iodide and N,N-Isopro-
pylmethylmethylene Iminium Chloride (6e)
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-isopropylmethylmethylene iminium chloride (6e,
0.12 g, 1.0 mmol) generated 6e (0.14 g, 0.65 mmol, 65% yield).
Reaction of Aziridine 1b with Lithium Iodide and N,N-Dimeth-
ylmethylene Iminium Chloride
The reaction of aziridine 1b (0.13 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-dimethylmethylene iminium chloride (0.10 g, 1.0
mmol) generated 4b (0.12 g, 0.71 mmol, 71% yield), plus a trace
amount of an isomeric compound that is believed to be 5b.
Reaction of Aziridine 1a with Lithium Iodide and N,N-Diiso-
propylmethylene Iminium Chloride (6f)
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-diisopropylmethylene iminium chloride (6f, 0.15
g, 1.0 mmol) gave 1a (0.13 g) and a dimer of 1a in a 1:6 ratio.
Reaction of Aziridine 1a with Lithium Iodide and N,N-Pip-
eridylmethylene Iminium Chloride (6g)
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-piperidylmethylene iminium chloride (6g, 0.13 g,
1.0 mmol) generated 7g (0.19 g, 0.80 mmol, 80% yield).
Reaction of Aziridine 1c with Lithium Iodide and N,N-Dimeth-
ylmethylene Iminium Chloride
The reaction of aziridine 1c (0.21 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-dimethylmethylene iminium chloride (0.10 g, 1.0
mmol) generated 5c (0.18 g, 0.71 mmol, 71% yield), plus a trace
amount of an isomeric compound that is believed to be 4c.
Reaction of Aziridine 1a with Lithium Iodide and Benzyl Meth-
oxymethyl Methylamine
The reaction of aziridine 1a (0.15 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and benzyl methoxymethyl methylamine (0.17 g, 1.0 mmol)
gave 7d (0.14 g, 0.53 mmol, 53% yield).
Reaction of Aziridine 1d with Lithium Iodide and N,N-Dimeth-
ylmethylene Iminium Chloride
The reaction of aziridine 1d (0.20 g, 1.0 mmol), LiI (0.20 g, 1.5
mmol), and N,N-dimethylmethylene iminium chloride (0.10 g, 1.0
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York

2354
M. T. Hancock, A. R. Pinhas
PAPER
+
Conversion of an Aziridine to a Diamine in the Absence of Add-
ed Lithium Iodide; General Procedure
HRMS: m/z calcd for C15H25N2 : 233.2018; found: 233.2055.
A mixture of the aziridine and the iminium salt in THF (30 mL) was
allowed to stir at 25 °C. After 20 h, the reaction mixture was added
to Et2O (50 mL). Then the mixture was treated with water (100 mL)
and made acidic (pH = 2 or 3, as determined by pH paper) with HCl.
The water was removed and made basic (pH = 10 or 11, as deter-
mined by pH paper) with NaOH. Finally, the water was extracted
with Et2O (3 × 50 mL). The Et2O solutions were mixed together,
dried with anhyd K2CO3, filtered, and evaporated to dryness.
Reaction of Aziridine trans-1g with N,N-Dimethylmethylene
Iminium Chloride
The reaction of aziridine trans-1g (0.16 g, 1.0 mmol) and N,N-di-
methylmethylene iminium chloride (0.10 g, 1.0 mmol) generated
0.18 g (0.90 mmol, 90% yield) of the same product as is obtained in
the presence of LiI.
Reaction of Aziridine cis-1g with N,N-Dimethylmethylene Imi-
nium Chloride
Reaction of Aziridine 1a with N,N-Dimethylmethylene Iminium
Chloride
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and N,N-dimethyl-
methylene iminium chloride (0.10 g, 1.0 mmol) generated 4a (0.19
g, 0.98 mmol, 98% yield), plus a trace amount of an isomeric com-
pound that is believed to be 5a.
The reaction of aziridine cis-1g (0.16 g, 1.0 mmol) and N,N-di-
methylmethylene iminium chloride (0.10 g, 1.0 mmol) generated
0.19 g (0.93 mmol, 93% yield) of the same product as is obtained in
the presence of LiI.
Reaction of Aziridine trans-1h with N,N-Dimethylmethylene
Iminium Chloride
Reaction of Aziridine 1b with N,N-Dimethylmethylene Iminium
Chloride
The reaction of aziridine 1b (0.13 g, 1.0 mmol) and N,N-dimethyl-
methylene iminium chloride (0.10 g, 1.0 mmol) generated 4b (0.13
g, 0.76 mmol, 76% yield), plus a trace amount of an isomeric com-
pound that is believed to be 5b.
The reaction of aziridine trans-1h (0.28 g, 1.0 mmol) and N,N-di-
methylmethylene iminium chloride (0.10 g, 1.0 mmol) generated
threo-4h (0.17 g, 0.50 mmol, 50% yield).
IR: 3064 (w), 3029 (m), 2956 (w), 2865 (w), 2824 (m), 2781 (m),
2250 (m), 1494 (w), 1454 (m), 1367 (w), 1250 (w), 1029 (w), 918
(s), 732 (s), 651 (s) cm–1.
1H NMR: d = 2.07 (s, 6 H), 3.46 (d, J = 13.5 Hz, 1 H), 3.69 (d, J =
10.8 Hz, 1 H), 3.76 (d, J = 13.5 Hz, 1 H), 4.04 (d, J = 10.7 Hz, 1 H),
6.92–7.35 (m, 15 H).
13C NMR: d = 40.66, 51.13, 61.34, 74.33, 126.91–130.07, 133.25,
140.84, 141.32.
Reaction of Aziridine 1c with N,N-Dimethylmethylene Iminium
Chloride
The reaction of aziridine 1c (0.21 g, 1.0 mmol) and N,N-dimethyl-
methylene iminium chloride (0.10 g, 1.0 mmol) generated 5c (0.20
g, 0.79 mmol, 79% yield), plus a trace amount of an isomeric com-
pound that is believed to be 4c.
MS: m/z = 331 (0.1), 196 (13.2), 135 (13.2), 134 (100), 118 (6.9),
+
91 (47.1), 77 (4.9), 65 (8.0); HRMS: m/z calcd for C23H27N2 :
Reaction of Aziridine 1d with N,N-Dimethylmethylene Iminium
Chloride
331.2174; found: 331.2140.
The reaction of aziridine 1d (0.20 g, 1.0 mmol) and N,N-dimethyl-
methylene iminium chloride (0.10 g, 1.0 mmol) generated 5d (0.02
g, 0.10 mmol, 10% yield), plus a trace amount of an isomeric com-
pound that is believed to be 4d.
Reaction of Aziridine cis-1h with N,N-Dimethylmethylene Imi-
nium Chloride
The reaction of aziridine cis-1h (0.28 g, 1.0 mmol) and N,N-di-
methylmethylene iminium chloride (0.10 g, 1.0 mmol) generated
erythro-4h (0.06 g, 0.18 mmol, 18% yield).
Reaction of Aziridine 1e with N,N-Dimethylmethylene Iminium
Chloride
The reaction of aziridine 1e (0.18 g, 1.0 mmol) and N,N-dimethyl-
methylene iminium chloride (0.10 g, 1.0 mmol) generated 5e (0.10
g, 0.46 mmol, 46% yield), plus a trace amount of an isomeric com-
pound that is believed to be 4e.
IR: 3064 (w), 3029 (m), 2956 (w), 2865 (w), 2824 (m), 2781 (m),
2250 (m), 1494 (w), 1454 (m), 1367 (w), 1250 (w), 1029 (w), 918
(s), 732 (s), 651 (s) cm–1.
1H NMR: d = 2.09 (s, 6 H), 3.21 (d, J = 6.0 Hz, 1 H), 3.38 (d, J =
13.4 Hz, 1 H), 3.69 (d, J = 13.4 Hz, 1 H), 4.20 (d, J = 6.0 Hz, 1 H),
6.96–7.32 (m, 15 H).
Reaction of Aziridine 1f with N,N-Dimethylmethylene Iminium
Chloride
The reaction of aziridine 1f (0.19 g, 1.0 mmol) and N,N-dimethyl-
methylene iminium chloride (0.10 g, 1.0 mmol) generated trans-4f
(0.19 g, 0.81 mmol, 81% yield).
13C NMR: d = 43.66, 51.38, 62.40, 77.24, 126.92–129.94, 137.09,
140.74, 141.55.
MS: m/z = 331 (0.1), 196 (13.2), 135 (13.2), 134 (100), 118 (6.9),
+
91 (47.1), 77 (4.9), 65 (8.0). HRMS: m/z calcd for C23H27N2 :
331.2174; found: 331.2152.
IR: 3065 (w), 3028 (w), 2936 (m), 2858 (m), 2822 (m), 2776 (m),
2247 (w), 2200 (w), 1495 (w), 1453 (w), 1378 (w), 1359 (w), 1339
(w), 1180 (w), 1130 (w), 1042 (w), 918 (s), 899 (s), 749 (s), 732 (s)
cm–1.
1H NMR: d = 1.15–1.34 (m, 3 H), 1.65–1.78 (m, 3 H), 2.11–2.26 (m,
8 H), 2.60 (td, J = 4.0, 9.8 Hz, 1 H), 3.71 (d, J = 13.1 Hz, 1 H), 3.84
(td, J = 4.1, 9.6 Hz, 1 H), 3.90 (d, J = 13.0 Hz, 1 H), 7.22–7.34 (m,
5 H).
Reaction of Aziridine 1a with N,N-Ethylmethylmethylene Imin-
ium Chloride 6b
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and N,N-ethylmeth-
ylmethylene iminium chloride (6b, 0.11 g, 1.0 mmol) generated 7b
(0.15 g, 0.74 mmol, 74% yield), plus a trace amount of an isomeric
compound that is believed to be the other regioisomer.
13C NMR: d = 20.71, 24.25, 26.02, 31.59, 36.19, 38.60, 50.84,
62.73, 65.96, 127.07–128.59, 140.45.
Reaction of Aziridine 1a with N,N-Diethylmethylene Iminium
Chloride 6c
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and N,N-diethyl-
methylene iminium chloride (6c, 0.12 g, 1.0 mmol) generated 7c
(0.17 g, 0.76 mmol, 76% yield).
MS: m/z = 231 (20.6), 187 (65.0), 141 (37.2), 124 (54.0), 106 (42.5),
96 (49.1), 91 (100), 84 (61.7), 58 (67.7).
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York

PAPER
Synthesis of Oxazolidinones and 1,2-Diamines from N-Alkyl Aziridines
2355
Reaction of Aziridine 1a with N,N-Benzylmethylmethylene Imi-
nium Chloride 6d
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and N,N-benzyl-
methylmethylene iminium chloride (6d, 0.17 g, 1.0 mmol) generat-
ed 7d (0.25 g, 0.94 mmol, 94% yield).
(14) Arakawa, H.; Aresta, M.; Armor, J. N.; Barteau, M. A.;
Beckman, E. J.; Bell, A. T.; Bercaw, J. E.; Creutz, C.;
Dinjus, E.; Dixon, D. A.; Domen, K.; DuBois, D. L.; Eckert,
J.; Fujita, E.; Gibson, D. H.; Goddard, W. A.; Goodman, D.
W.; Keller, J.; Kubas, G. J.; Kung, H. H.; Lyons, J. E.;
Manzer, L. E.; Marks, T. J.; Morokuma, K.; Nicholas, K. M.;
Periana, R.; Que, L.; Rostrup-Nielson, J.; Sachtler, W. M.
H.; Schmidt, L. D.; Sen, A.; Somorjai, G. A.; Stair, P. C.;
Stults, B. R.; Tumas, W. Chem. Rev. 2001, 101, 953.
(15) Tascedda, P.; Dunach, E. Chem. Commun. 2000, 449.
(16) Matsuda, H.; Ninagawa, A.; Hasegawa, H. Bull. Chem. Soc.
Jpn. 1985, 58, 2717.
Reaction of Aziridine 1a with N,N-Isopropylmethylmethylene
Iminium Chloride 6e
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and N,N-isopropyl-
methylmethylene iminium chloride (6e, 0.12 g, 1.0 mmol) generat-
ed 7e (0.16 g, 0.73 mmol, 73% yield).
Reaction of Aziridine 1a with N,N-Diisopropylmethylene Imin-
ium Chloride 6f
(17) Soga, K.; Hosoda, S.; Nakamura, H.; Ikeda, S. Chem.
Commun. 1976, 617.
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and N,N-diisopro-
pylmethylene iminium chloride (6f, 0.15 g, 1.0 mmol) gave 1a (0.13
g) and a dimer of 1a in a 5:1 ratio.
(18) Espino, C. G.; DuBois, J. Angew. Chem. Int. Ed. 2001, 40,
598.
(19) Callier-Dublanchet, A.; Quiclet Sire, B.; Zard, S. Z.
Tetrahedron Lett. 1995, 36, 8791.
Reaction of Aziridine 1a with N,N-Piperidylmethylene Iminium
Chloride 6g
(20) Pyun, D. K.; Lee, C. H.; Ha, H.-J.; Park, C. S.; Chang, J.-W.;
Lee, W. K. Org. Lett. 2001, 3, 4197.
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and N,N-piperidyl-
methylene iminium chloride (6g, 0.13 g, 1.0 mmol) generated 7g
(0.16 g, 0.70 mmol, 70% yield).
(21) Kumaragurubarab, N.; Juhl, K.; Zhuang, W.; Bogevig, A.;
Jorgensen, K. A. J. Am. Chem. Soc. 2002, 124, 6254.
(22) Chiarotto, I.; Feroci, M. Tetrahedron Lett. 2001, 42, 3451.
(23) Sepulveda-Arques, J.; Armero-Alarte, T.; Acero-Alarcon,
A.; Zaballos-Garcia, E.; Solesio, B. Y.; Carrera, J. E.
Tetrahedron 1996, 52, 2097.
Reaction of Aziridine 1a with Benzyl Methoxymethyl Methyl-
amine
The reaction of aziridine 1a (0.15 g, 1.0 mmol) and benzyl meth-
oxymethyl methylamine (0.17 g, 1.0 mmol) generated 7d (0.12 g,
0.45 mmol, 45% yield).
(24) Banks, M. R.; Cadogan, J. I. G.; Gosney, I.; Hodgson, P. K.
G.; Thomson, D. E. J. Chem. Soc. Perkin Trans. 1 1991, 961.
(25) (a) Kihara, N.; Hara, N.; Endo, T. J. Org. Chem. 1993, 58,
6198. (b) Paddock, R. L.; Nguyen, S. T. J. Am. Chem. Soc.
2001, 123, 11498. (c) Calo, V.; Nacci, A.; Monopoli, A.;
Fanizzi, A. Org. Lett. 2002, 4, 2561. (d) Huang, J.-W.; Shi,
M. J. Org. Chem. 2003, 68, 6705. (e) Li, F.; Xia, C.; Xu, L.;
Sun, W.; Chen, G. Chem. Commun. 2003, 2042.
(26) Reich, H.; Sanders, A.; Fiedler, A.; Bevan, M. J. Am. Chem.
Soc. 2002, 124, 13386.
Acknowledgment
MTH thanks the Department of Chemistry of the University of Cin-
cinnati for a Laws-Shubert Fellowship.
(27) Stojanovic, A.; Renaud, P. Helv. Chim. Acta 1998, 81, 353.
(28) Das, J. Synth. Commun. 1988, 18, 907.
(29) Wohl, R. A. J. Org. Chem. 1973, 38, 3858.
(30) Lucet, D.; LeGall, T.; Mioskowski, C. Angew. Chem. Int.
Ed. 1998, 37, 2581.
(31) Kulkarni, Y. S. Aldrichim. Acta 1999, 32, 18.
(32) Asami, M.; Sata, S.; Watanabe, H. Chem. Lett. 2000, 990.
(33) Knof, U.; von Zelewsky, A. Angew. Chem. Int. Ed. 1999, 38,
302.
(34) del Olmo, E.; Macho, A.; Alves, M.; Lopez, J. L.; el Banoua,
F.; Munoz, E.; San Feliciano, A. Bioorg. Med. Chem. Lett.
2002, 12, 2621.
References
(1) See for example, the following series: (a) Progress in
Heterocyclic Chemistry; Gribble, G. W.; Gilchrist, T. L.,
Eds.; Pergamon Press: Oxford, 2002. (b) Heterocyclic
Chemistry; Katritzky, A. R., Ed.; Academic Press: San
Diego, 2001. (c) Comprehensive Heterocyclic Chemistry;
Katritzky, A. R., Ed.; Pergamon Press: Oxford, 1984, 1996.
(2) Hancock, M. T.; Pinhas, A. R. Tetrahedron Lett. 2003, 44,
5457.
(3) Hancock, M. T.; Pinhas, A. R. Tetrahedron Lett. 2003, 44,
7125.
(4) Sweeney, J. B. Chem. Soc. Rev. 2002, 31, 247.
(5) Hancock, M. T.; Pinhas, A. R. Organometallics 2002, 21,
5155.
(6) Takayama, H.; Nomot, T. J. Chem. Soc., Chem. Commun.
1982, 408.
(35) Li, Z.; Fernandez, M.; Jacobsen, E. N. Org. Lett. 1999, 1,
1611.
(36) Sabitha, G.; Babu, R. S.; Rajkumar, M.; Yadav, J. S. Org.
Lett. 2002, 4, 343.
(37) (a) Anand, R. V.; Pandey, G.; Singh, V. K. Tetrahedron Lett.
2002, 43, 3975. (b) Sekar, G.; Singh, V. K. J. Org. Chem.
1999, 64, 2537.
(7) Rochin, C.; Babot, O.; Dunogues, J.; Duboudin, F. Synthesis
1986, 228.
(8) Barta, N. S.; Sidler, D. R.; Somerville, K. B.; Weissman, S.
A.; Larsen, R. D.; Reider, P. J. Org. Lett. 2000, 2, 2821.
(9) Katz, S. J.; Bergmeier, S. C. Tetrahedron Lett. 2002, 43,
557.
(10) Murakata, M.; Tsutsui, H.; Hoshino, O. Org. Lett. 2001, 3,
299.
(38) Fan, R.-H.; Hou, X.-L. J. Org. Chem. 2003, 68, 726.
(39) Kim, B. M.; So, S. M.; Choi, H. J. Org. Lett. 2002, 4, 949.
(40) Hu, X. E. Tetrahedron Lett. 2002, 43, 5315.
(41) O’Brien, P.; Towers, T. D. J. Org. Chem. 2002, 67, 304; and
references cited therein.
(42) Xiong, C.; Wang, W.; Cai, C.; Hruby, V. J. J. Org. Chem.
2002, 67, 1399.
(43) Chuang, T.-H.; Sharpless, K. B. Org. Lett. 2000, 2, 3555.
(44) (a) Caiazzo, A.; Dalili, S.; Yudin, A. K. Org. Lett. 2002, 4,
2597. (b) Watson, I. D. G.; Yudin, A. K. J. Org. Chem. 2003,
68, 5160.
(11) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Zappia, G. Org.
Lett. 2001, 3, 2539.
(12) Park, C. S.; Kim, M. S.; Sim, T. B.; Pyun, D. K.; Lee, C. H.;
Choi, D.; Lee, W. K. J. Org. Chem. 2003, 68, 43.
(13) (a) Sim, T. B.; Kang, S. H.; Lee, K. S.; Lee, W. K. J. Org.
Chem. 2003, 68, 104. (b) Barbachyn, M. R.; Ford, C. W.
Angew. Chem. Int. Ed. 2003, 42, 2010.
(45) Olofsson, B.; Somfai, P. Tetrahedron Lett. 2003, 44, 1279.
Synthesis 2004, No. 14, 2347–2355 © Thieme Stuttgart · New York