Chemistry Letters Vol.32, No.4 (2003)
393
(Table 2, entries 1-5). The reactions proceeded smoothly to produce
various N-substituted aziridines in high yields. In the case of
aziridination with 1-phenylethylamine, a mixture of diastereomeric
aziridines was obtained in 98% combined yield without any
significant diastereoselectivity (entry 4). The aziridination with
tert-butylamine proceeded very slowly, and it was carried out
without the solvent to afford N-tert-butylaziridine in 96% yield
(entry 5). N-nonsubstituted aziridine was synthesized in 82% yield
with gaseous ammonia (entry 6). Similar to the primary amines,
benzenesulfonamide also reacted with 4 by using sodium hydride as
a base to give the corresponding aziridine in 97% yield (entry 7).
One-pot synthesis of aziridines from the corresponding
styrenes and benzylamine without isolating the intermediate, 2-
arylethenyl(diphenyl)sulfonium salts, was examined(Table 3). The
results of entries 1 and 5 indicated that the one-pot procedure
(Method A) was more effective than the stepwise one (Method B)
and that it was useful especially when 2-arylethenyl(diphenyl)sul-
fonium salts were not stable enough for the isolation. In the case of
1,1-diphenylethylene, the aziridination proceeded very slowly
compared to the others, which was probably due to its steric effects
(entry 6). Aziridination of trans- and cis-ꢀ-methylstyrene with
benzylamine gave the two diastereomeric aziridines in almost the
same yields and diastereomeric ratios (1:1) (entries 7 and 8). The
result suggested that the stereochemistry of aziridines was not
influenced by the configurations of olefins.
A proposed reaction mechanism is shown in Scheme 2: a
primary amine reacts initially with the 2-arylethenyl(diphenyl)sul-
fonium salt to form the intermediate 6,8 in which internal proton
transfer takes place to give 7. A subsequent intramolecular
nucleophilic substitution of an amino group gives aziridinium
triflate 8 and diphenyl sulfide. It was considered that the excess
amount of a primary amine captured triflic acid from 8, and the
protonation of R3NH2 with 8 was suppressed.9
Typical experimental procedure for the one-pot synthesis of
aziridines is as follows (Table 3, entry 1, Method A): triflic
anhydride (0.082 mL, 0.50 mmol) was added to a solution of
diphenyl sulfoxide (101 mg, 0.50 mmol) in dichloromethane (2 mL)
under an argon atmosphere at ꢂ78 ꢁC, and then a solution of 2-
benzylstyrene (97 mg, 0.50 mmol) in dichloromethane (1.5 mL)
R3NH2
OTf
OTf
R3NH2
R1
H+ transfer
R1
Ar
SPh2
R2
SPh2
R2
Ar
6
R3 OTf
NH
R3HN
OTf
SPh2
R1
Ar
R1
Ar
R2
Ph2S
+
R2
7
8
Scheme 2.
was added dropwise at ꢂ78 ꢁC. After the reaction mixture was
stirred and warmed up to 0 ꢁC, a solution of benzylamine (268 mg,
2.50 mmol) in dichloromethane (1.5 mL) was added, and the
mixture was stirred at room temperature for additional 2 h. The
reaction was quenched with 0.1 M (1 M = mol dmꢂ3) aqueous
sodium hydroxide, and the mixture was extracted with dichlor-
omethane. The organic layer was dried over anhydrous sodium
sulfate. After filtration and evaporation, the crude product was
purified by preparative TLC to give 1-benzyl-2-(2-benzylphenyl)
aziridine (149 mg, 99%).
Thus, an effective and convenient method for the synthesis of
aziridines from styrene derivatives and primary amines was
established according to the following two-step reaction: prepara-
tion of 2-arylethenyl(diphenyl)sulfonium salts from styrenes and
subsequent treatment of thus formed salts with primary amines.10
This study was supported in part by the Grant of the 21st
Century COE Program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
References and Notes
1
J. A. Deyrup, in ‘‘Small Ring Heterocycles,’’ ed. by A. Hassner, John Wiley and
Sons, New York (1983), Part 1, p 1.
D. Tanner, Angew. Chem., Int. Ed. Engl., 33, 599 (1994).
2
3
a) O. C. Dermer and G. E. Ham, ‘‘Ethylenimine and Other Aziridines,’’
Academic Press, New York (1969), p 403. b) Y. Kishi, J. Nat. Prod., 42, 549
(1979).
a) N. H. Cromwell, G. V. Hudson, R. A. Wankel, and P. J. Vanderhorst, J. Am.
Chem. Soc., 75, 5384 (1963). b) D. L. Nagel, P. B. Woller, and N. H. Cromwell, J.
Org. Chem., 36, 3911 (1971). c) G. Cardillo, L. Gentilucci, C. Tomasini, and M.
P. V. Castejon-Bordas, Tetrahedron: Asymmetry, 7, 755 (1996).
4
`
5
6
G. Aumaitre, J. Chanet-Ray, J. Durand, and R. Vessiere, Synthesis, 1983, 816.
Table 3. One-pot synthesis of aziridines from styrenes and benzylamine
a) C. R. Johnson and J. P. Lockard, Tetrahedron Lett., 12, 4589 (1971). b) C. R.
Johnson, J. P. Lockard, and E. R. Kennedy, J. Org. Chem., 45, 264 (1980).
a) V. G. Nenajdenko, P. V. Vertelezkij, I. D. Gridnev, N. E. Shevchenko, and E. S.
Balenkova, Tetrahedron, 53, 8173 (1997). b) K. Hartke, D. Teuber, and H.-D.
Gerber, Tetrahedron, 44, 3261 (1988). c) For a review, see: A. J. Mancuso and D.
Swern, Synthesis, 1981, 165.
The use of 2-arylethenyl(dimethyl)sulfonium salts instead of 2-arylethenyl(di-
phenyl)sulfonium salts resulted in N-methylation of primary amines to afford 2-
arylethenyl methyl sulfides.
This consideration is based on the data that pKa’s of conjugate acids of aziridines
are usually in the range of 8-9.5, whereas they are ca. 10 for primary amines. See:
P. E. Fanta, in ‘‘Heterocyclic Compounds with Three- and Four-Membered
Rings,’’ ed. by A. Weissberger, John Wiley and Sons, New York (1964), Part 1, p
527.
Ph2SO
Tf2O
Bn
N
7
Ar
BnNH2
Ar
R1
R1
R2
CH2Cl2
-78−0°C
R2
8
9
Styrene Methoda Y. / %b Entry Styrene Methoda Y. / %b
Entry
Ph
A
B
89
78
A
B
99
73
Cl
5
6
1
Me
Ph
Ph
2c
3
A
71
C
66
10 Cyclopropanation was also carried out successfully according to the similar two-
step sequence involving preparation of 2-arylethenylsulfonium salts from
styrenes, followed by treatment with sodium salts of active methylene
compounds. For example, dimethyl[(E)-2-phenylethenyl]sulfonium triflate,
prepared from styrene, dimethyl sulfoxide, and Tf2O, was added to a solution
of the sodium salt of diethyl malonate (1.2 equiv.) or ethyl cyanoacetate (1.2
equiv.) in THF. The reaction mixture was stirred at rt for 2 h, and diethyl 2-
phenyl-1,1-cyclopropanedicarboxylate (77%) or ethyl 1-cyano-2-phenylcyclo-
propanecarboxylate (76%) was obtained respectively. Similarly, diphenyl[(E)-2-
phenylethenyl]sulfonium triflate also reacted with the sodium salt of diethyl
malonate to give diethyl 2-phenyl-1,1-cyclopropanedicarboxylate (76%, 2 steps
from styrene). Preparation of cyclopropanes via sulfonium salts had already been
39d
39d
Ph
7
8
A
A
A
A
94
95
Ph
Me
Me
4 O2N
Ph
aMethod A: one-pot procedure described in the text. Method B: benzylamine
(1.2 equiv.) and tert-butylamine (3 equiv.) were added to the isolated sulfonium
salt in DMSO at rt, and the reaction mixture was stirred at rt for 1 h. Method C: a
mixture of benzylamine (9 equiv.) and the isolated sulfonium salt was stirred at
rt for 1 day. bIsolated yields of aziridines from styrene unless otherwise noted.
cThe reaction time for the second step was 12 h. dCombined yield of the
chromatographically separable diastereomers (1:1).
´
reported, see: a) J. Gosselck, L. Beress, and H. Schenk, Angew. Chem., 78, 606
(1966). b) J. Gosselck, H. Ahlbrecht, F. Dost, H. Schenk, and G. Schmidt,
Tetrahedron Lett., 9, 995 (1968).