Regiospecific reductive cleavage of the C(2)-N bond of aziridines substituted with an electron acceptor mediated by Mg/MeOH

Full text of DOI:10.1021/jo9806963

10006
J . Org. Chem. 1998, 63, 10006-10010
R,â- and â,γ-unsaturated δ-amino esters. We have previ-
Regiosp ecific Red u ctive Clea va ge of th e
ously demonstrated the regiospecific C(2)-N ring opening
of an aziridine tethered to an R,â-unsaturated ester by
using magnesium in methanol which gives the corre-
sponding â,γ-unsaturated δ-amino ester as a single
regioisomer (eq 1).7 In other work done on the same kind
of substrates, regiospecific C(2)-N bond cleavage was
realized by adding a carbon nucleophile via the SN2′
reaction.8
C(2)-N Bon d of Azir id in es Su bstitu ted
w ith a n Electr on Accep tor Med ia ted by
Mg/MeOH
Chwang Siek Pak,*,† Tae Hoon Kim, and Sung J in Ha
Korea Research Institute of Chemical Technology, P.O. Box
107, Yusung, Taejeon 305-606, Korea
Received April 14, 1998
In tr od u ction
Molander et al. have recently reported9 the regiospe-
cific reductive cleavage of the C(2)-N bond of 2-acyl or
-(carboalkoxy) acylaziridines activated by N-Ts, Boc, and
Tr groups by using SmI2 in THF in the presence of a
proton source such as methanol or N,N-dimethylamino-
ethanol. That reaction method affords the corresponding
â-amino ester and ketone exclusively (eq 2).
In the preparation of R- and â-amino acid units, which
can be utilized as building blocks for the synthesis of
biologically important compounds, considerable efforts
have been made to open aziridine rings activated by an
adjacent carboxyl group.1 By comparison to the numerous
examples of nucleophilic addition reactions that result
in the selective cleavage of the C(3)-N bond leading to
an R-amino acid,2 the methods used for the regiospecific
cleavage of the C(2)-N bond that lead to â-amino acids
are quite limited.3 For that reason, the nonselective
manner has usually been employed.4 Until now, the only
known ways to open the ring of aziridine-2-carboxylate
in a regiospecific manner are the reductive cleavage
reactions that use catalytic hydrogenation by Pd/EtOH
for C(2)-N cleavage3 or catalytic transfer hydrogenation
that uses Pd/HCOOH/EtOH for C(3)-N cleavage.5 It has
been reported6 that the C(2)-N bond of an aziridine
tethered to an R,â-unsaturated ester can be opened
selectively by using catalytic transfer hydrogenation
conditions that afford various regioisomer mixtures of
Cleavage of the CR-heteroatom bond tethered to a
ketone or ester group by using SmI210 has been reported,
but the same type of reaction is not known for magne-
sium in methanol since isolated electron acceptors such
as ketones, esters, or nitriles are reported to be inert to
magnesium in methanol.11a Because we have been inter-
ested to expand the synthetic utility of magnesium in
methanol as a remarkably simple, convenient, and
economic electron-transfer reagent11 compared to SmI2,
it prompted us to study C(2)-N bond cleavage of aziri-
dines substituted with various electron acceptors.
† Tel: 82(42)8607010. Fax: 82(42)8610307. E-mail: cspak@
pado.krict.re.kr.
(1) ) (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599. (b)
Arai, H.; Kanda, Y.; Ashizawa, T.; Morimoto, M.; Gomi, K.; Kono, M.;
Kasai, M. J . Med. Chem. 1994, 37, 1805. (c) Coleman, R. S.; Carpenter,
A. J . J . Org. Chem. 1992, 57, 5813. (d) Armstrong, R. W.; Moran, E. J .
J . Am. Chem. Soc. 1992, 114, 371.
(2) (a) Ho, M.; Wang, W.; Douvlos, M.; Pham, T.; Klock, T. Tetra-
hedron Lett. 1991, 32, 1283. (b) Kruper, W. J . J un.; Emmons, A. H. J .
Org. Chem. 1991, 56, 3323. (c) Burgaud, B. G. M.; Horwell, D. C.;
Padova, A.; Pritchard, M. C. Tetrahedron 1996, 52, 13035. (d) Farthing,
C. N.; Baldwin, J . E.; Russell, A. T.; Schofield, C. J .; Spivey, A. C.
Tetrahedron Lett. 1996, 37, 5225. (e) Solomon, M. E.; Lynch, C. L.;
Rich, D. H. Tetrahedron Lett. 1995, 36, 4955. (f) Kapron, J . T.;
Santarsiero, B. D.; Vederas, J . C. J . Chem. Soc., Chem. Commun. 1993,
1074. (g) Tanner, D.; Birgersson, C.; Dhaliwal, H. K. Tetrahedron Lett.
1990, 31, 1903. (h) Shima, I.; Hashimoto, M. Chem. Pharm. Bull. 1990,
38, 564. (i) Church, N. J .; Young, D. W. Tetrahedron Lett. 1995, 3,
151. (j) Legters, J .; Thijs, L.; Zwanenburg, B. Recl. Trav. Chim. Pays-
Bas 1992, 111, 16. (k) Legters, J .; Willems, J . G. H.; Thijs, L.;
Zwanenburg, B. Recl. Trav. Chim. Pays-Bas 1992, 111, 59.
(3) ) (a) Ambrosi, H.-D.; Duczek, W.; Ramm, M.; J aehnisch, K.
Tetrahedron Lett. 1994, 35, 7613. (b) Lim, Y.; Lee, W. K. Tetrahedron
Lett. 1995, 36, 8431.
(4) (a) Righi, G.; D’Achille, R.; Bonini, C. Tetrahedron Lett. 1996,
37, 6893. (b) Baldwin, J . E.; Spivey, A. C.; Schofield, C. J .; Sweeney,
J . B. Tetrahedron 1993, 49, 6309. (c) Bucciarelli, M.; Forni, A.; Moretti,
I.; Prati, F.; Torre, G. Tetrahedron Asymmetry 1995, 6, 2073. (d) Davoli,
P.; Forni, A.; Moretti, I.; Prati, F. Tetrahedron Asymmetry 1995, 6,
2011. (e) Bouayad, Z.; Chanet-Ray, J .; Ducher, S.; Vessiere, R. J .
Heterocycl. Chem. 1991, 28, 1757. (f) Davis, F. A.; Zhou, P.; Reddy, G.
V. J . Org. Chem. 1994, 59, 3243. (g) Eastwood, F. W.; Perlmutter, P.;
Yang, Q. Tetrahedron Lett. 1994, 35, 2039.
Resu lts a n d Discu ssion
Aziridine substrates 1a -k ,n -p were prepared from
the corresponding R,â-unsaturated ketones, esters, and
(7) Lee, G. H.; Lee, E.; Pak, C. S. J . Org. Chem. 1993, 58, 1523.
(8) (a) Ibuka, T.; Akaji, M.; Mimura, N.; Habashita, H.; Nakai, K.;
Tamamura, H.; Fujii, N.; Yamamoto, Y. Tetrahedron Lett. 1996, 37,
2849. (b) Ibuka, T.; Nakai, K.; Habashita, H.; Hotta, Y.; Fujii, N.;
Mimura, N.; Miwa, Y.; Taga, T.; Yamamoto, Y. Angew. Chem. 1994,
106, 693. (c) Fujii, N.; Nakai, K.; Tamamura, H.; Otaka, A.; Mimura,
N.; Miwa, Y.; Taga, T.; Yamamoto, Y.; Ibuka, T. J . Chem. Soc., Perkin
Trans. 1 1995, 11, 1359. (d) Wipf, P.; Fritch, P. C. J . Org. Chem. 1994,
59, 4875. (f) Satake, A.; Shimizu, I.; Yamamoto, A. Synlett 1995, 64.
(9) Molander, G. A.; Stengel, P. J . J . Org. Chem. 1995, 60, 6660.
(10) (a) Molander, G. A.; Hahn, G. J . Org. Chem. 1986, 51, 2596.
(b) Otsubo, K.; Inanaga, J .; Yamaguchi, M. Tetrahedron Lett. 1987,
28, 4437. (c) Molander, G. A.; Mckie, J . A. J . Org. Chem. 1991, 56,
4112. (d) Batey, R. A.; Motherwell, W. B. Tetrahedron Lett. 1991, 32,
6649. (e) Kim, Y. H.; Lee, I. S. Heteroat. Chem. 1992, 3, 509. (f) Enholm,
E. J .; Schreier, J . A. J . Org. Chem. 1995, 60, 1110. (g) Molander, G.
A.; Hahn, G. J . Org. Chem. 1986, 51, 1135. (h) Castro, J .; Sorensen,
H.; Riera, A.; Morin, C.; Movano, A.; Pericas, M. A.; Greene, A. E. J .
Am. Chem. Soc. 1990, 112, 9388. (i) White, J , D.; Somers, T. C. J . Am.
Chem. Soc. 1987, 109, 4424. (j) Holton, R. A.; Williams, A. D. J . Org.
Chem. 1988, 53, 5981.
(5) (a) Davis, F. A.; Zhou, P.; Reddy, G. V. J . Org. Chem. 1994, 59,
3243. (b) Davis, F. A.; Liu, H.; Reddy, G. V. Tetrahedron Lett. 1996,
37, 5473. (c) Evans, F. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B.
A.; Barnes, D. M. J . Am. Chem. Soc. 1993, 115, 5328.
(6) Satake, A.; Shimizu, I.; Yamamoto, A. Synlett 1995, 1, 64.
10.1021/jo9806963 CCC: $15.00 © 1998 American Chemical Society
Published on Web 12/05/1998

Notes
entry
J . Org. Chem., Vol. 63, No. 26, 1998 10007
Ta ble 1. Red u ctive Clea va ge of Azir id in es Su bstitu ted w ith Electr on Accep tor s
aziridines
R3
products
R2 R3
1
R1
R2
EWG
A
2
R1
EWG
A
methoda yieldsb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
h
H
H
COMe
COMe
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ts
Ph
2a
2b
2c
2d
2e
2f
2g
2h
2i
H
H
Me
H
H
H
COMe
COMe
Ts
Ts
Ts
Ts
A
A
A
B
C
C
D
D
D
D
D
C
C
D
D
D
D
D
C
97
97
98c
75d
e
Me
Ph
Ph
Ph
Ph
H
Me
Et
Ph
H
Ph
H
H
H
Ph
h
Me
Ph
Ph
Me COMe
H
H
Me COPh
H
H
Me COMe
H
COMe
COPh
H
COMe
f
CO2Me
CO2Me
H
H
H
H
H
H
H
H
CO2Me
CO2Me
Ts
Ts
Ts
Ts
96
94
95c
35g
85
h
Me
Et
Ph
H
Me CO2Me
Me CO2Me
H
H
H
H
H
H
H
CO2Me
CO2t-Bu
CO2Et
CO2Et
CN
2j
2k
2l
CO2Me
CO2t-Bu Ts
HC(Me)Ph 2m
Ts
Ts
Ts
Bn
p-ClBn
h
2n
2o
2p
2q
2r
H
H
Ph
H
H
H
H
H
H
H
H
H
CN
Ts
Ts
Ts
Bn
p-ClBn
Boc
83
85
80
93
95
94
Me CN
H
h
H
H
Me CN
CN
CH2Br
CH2Br
H
H
H
H
CN
dCH2
dCH2
dCH2
H
H
H
1s
BNOCH2
PhSO2CH Boc
2s
BnOCH2
a
b
d
See Experimental Section. Isolated yield. c A mixture of 1:1 diastereoisomer is obtained. Benzalacetone is obtained as a minor
product. e R-N-Tosylamino chalcone is obtained in 65% yield. f Starting material is completely recovered. Rest of the product is
desulfonylated aziridine. Only ester exchange occurs.
g
h
Sch em e 1
Sch em e 2
nitriles by employing Evans’s aziridination procedure.12
Other substrates, N-phenyl- and N-phenethylaziridine
(1l,m ),13,14 bromomethylaziridines (1q,r ),15 and phenyl-
sulfonylmethylaziridine (1s),7 were obtained by applying
published procedures.
Reductive cleavage of C(2)-N bonds of substituted
aziridines by using magnesium in methanol is carried
out as depicted in Scheme 1.
Various substituted aziridines were subjected to Mg/
MeOH to provide the corresponding â-amino products.
The results are summarized in Table 1.
Treatment of 2-acylaziridines 1a -c with 3 equiv of
magnesium powder (-50 mesh) in methanol at -23 °C
provided the corresponding C(2)-N cleavage products,
â-N-tosylamino ketones 2a -c in excellent yields within
1
1 h (Table 1). According to H and 13CNMR analysis, a
1:1 diastereomeric mixture, which is difficult to separate,
was obtained in the case of 1c. The expected product 2d
was obtained from 1d in somewhat lower yield (75%)
along with benzalacetone as a minor product (20%) which
resulted from elimination of tosyl group by Mg(OMe)2 in
solution. To minimize elimination reaction acid workup
at 0 °C was necessary because cleavage product 2d was
completely changed into benzalacetone within 15 min
when the temperature of the reaction mixture was raised
at room temperature. Due to a solubility problem the
reaction of 3-benzoylaziridine 1e was run at room tem-
perature. Surprisingly it afforded the unexpected ring
opening product as shown in Scheme 2.
Deprotonation, instead of a cleavage, must have oc-
curred by the use of Mg(OMe)2 in solution. Thus the
incipient carbanion undergoes rearrangement to an R-N-
tosylamino chalcone (2e) in 65% yield without any trace
of the expected cleavage product. A blank test with
commercial Mg(OMe)2 solution in methanol at room
temperature afforded the same product. In an attempt
to prevent deprotonation, the R-proton was substituted
with the methyl group that gave 1f. In contrast to 1c,
the reaction did not take place for 1f as shown in Scheme
3.
(11) (a) For a review: Hutchins, R. O. Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.-in-chief; J ohn Wiley and Sons
Ltd: Chichester, U.K., 1995; Vol. 5, pp 3202-3204 and references
therein. (b) Lee, G. H.; Choi, E. B.; Lee, E.; Pak, C. S. Tetrahedron
Lett. 1994, 35, 2195. (c) Lee, G. H.; Choi, E. B.; Lee, E.; Pak, C. S.
Tetrahedron Lett. 1993, 34, 4541. (d) Youn, I. K.; Pak, C. S. Bull.
Korean Chem. Soc. 1987, 8, 434. (e) Youn, I. K.; Yon, G. H.; Pak, C. S.
Tetrahedron Lett. 1986, 27, 2409. (f) Zarecki, A.; Wicha, J . Synthesis
1996, 455. (g) Lee, G. H.; Choi, E. B.; Lee, E.; Pak, C. S. J . Org. Chem.
1994, 59, 1428. (h) Lee, G. H.; Lee, H. K.; Choi, E. B.; Pak. C. S. Bull.
Korean Chem. Soc. 1995, 16, 1141. (i) Chaban, S. P.; Ethiraj, K. S.
Tetrahedron Lett. 1995, 36, 2281. (j) Lee, G. H.; Lee, H. K.; Choi, E.
B.; Kim, B. T.; Pak, C. S. Tetrahedron Lett. 1995, 36, 5607.
(12) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J . Org. Chem.
1991, 56, 6744. (b) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J . Am.
Chem. Soc. 1994, 116, 2742. Aziridination of R,â-unsaturated ketones,
esters, and nitriles was performed using N-(p-tolylsulfonyl)imino
phenyliodinane (PhIdNTs) as the nitrene precursor and Cu(acac)2 as
catalyst to give the corresponding 2-substituted N-tosylaziridines in
moderate yields (35-50%). Only major isomers of which structures
were assigned tentatively as trans were separated and subjected to
reductive cleavage reaction. All the spectral data were in accord with
the structure assigned.
(13) Rasmussen, K. G.; J oergensen, K. A. J . Chem. Soc., Chem.
Commun. 1995, 1401.
(14) Substrate 1m was kindly provided from Professor Won Ku Lee
(see ref 3b).
(15) Kimpe, N. D.; J olie, R.; Smaele, D. D. J . Chem. Soc., Chem.
Commun. 1994, 1221.

10008 J . Org. Chem., Vol. 63, No. 26, 1998
Notes
Sch em e 3
Sch em e 4
Since aryl ketones have a higher electron affinity than
alkyl ketones,16 ketyls derived from aryl ketones 1e,f are
expected to be more stable than those from alkyl ketones
1c,d . However, ketyl reactions of phenyl ketones using
SmI2 were known to be sluggish and resulted in poor
yields compared to those of aliphatic ketones.17 Probably
due to these unfavorable characteristics, reactions of aryl
ketones are rare in the literature in contrast to numerous
examples of aliphatic ketones.18 According to the electron-
transfer mechanism studied for the enone system using
with a phenyl or a phenethyl group like 1l-m , the
expected reaction did not proceed. Only ester exchange
was observed. As previously noted,2k,5a activation of a
C-N bond by substitution with electron withdrawing
group such as N-Ts or N-Boc seems to be necessary for
ring opening reaction. The reductive cleavage of cy-
anoaziridine 1n -p took place smoothly to afford â-amino-
N-tosyl nitriles 2n -p in excellent yield. Although isolated
cyano groups are reported to be inert to magnesium in
methanol,11a R,â-unsaturated nitriles were reduced to the
saturated nitriles21 and underwent intramolecular hy-
drodimerization via radical anion mechanism.22 It reveals
that the cyano group can play a role as electron acceptor
if tethered to a proper functional group which can
stabilize the resulting radical anion. By analogy of ketyl
reaction mechanism,9 electron transfer from magnesium
metal to substrate will generate CdN radical anion from
which subsequent ring cleavage will occur via the ketimine
as shown in Scheme 4.
the polarographic method presented by House et al.,19
a
fast equilibrium exists between the starting material and
ketyl which has a suffcient half-life (ca. 10 min). Con-
sidering these precedents and in the absence of kinetic
data, we may speculate that ketyls from 1c,f are so stable
that there may only be an equilibrium of fast electron
transfer between ketyl and starting material so that no
further reaction proceeds while magnesium is being
consumed by methanol.
By comparison to the reaction conditions used for
2-acylaziridines, the 2-(carbomethoxy)aziridines, 1g-k ,
required slightly more magnesium (4 equiv). The added
magnesium provided the corresponding â-amino-N-tosyl
esters in excellent yields. This result is in contrast to the
use of SmI2 in THF/EtOH9 where C(3)-N bond cleavage
and C(2)-N bond cleavage gave a mixture of R- and
â-amino acids. J ust as it was for 1c, 1i gave a 1:1 mixture
of diastereoisomers. Although each diastereoisomer could
be separated and identified, the relative stereochemistry
of C(2) and C(3) was not determined. Under standard
reaction conditions, ester 1j provided a mixture of de-
sulfonylated aziridine and the expected cleavage product
2j in 60% and 35% yield, respectively. Attempts to
desulfonylate 1j by Mg(OMe)2 in methanol failed. In this
case the starting material was completely recovered.
Because desulfonylation of arenesulfonamides by an
electron-transfer reagent is known,16 direct electron
transfer may have caused desulfonylation instead of
methanolysis catalyzed by Mg(OMe)2. When modified
reaction conditions11c (10 equiv of Mg, EtOH/THF, cata-
lyst HgCl2, room temperature) were employed, desulfon-
ylation was avoided to provide ethyl ester of 2j in
excellent yield (95%). In the case of t-Bu ester 1k ester
exchange did not happen which contrasts with the case
of the ethyl ester.11d When the nitrogen was substituted
Reaction of 2-(bromomethyl)aziridines 1q,r was slow
at -23 °C so the temperature was elevated to room
temperature which produced the corresponding allyl-
amine 2q,r smoothly even though the C-N bond was not
activated. The identical cleavage product was obtained
in moderate yields (50-53%) by a sonochemical cleavage
of the 2-(bromomethyl)aziridines in the presence of a
zinc-copper couple.15 As suggested by Kimpe et al.,15
a
radical anion generated by single electron transfer from
magnesium to (bromomethyl)aziridines 1q,r will lose
bromide ion to give methyl radical which might undergo
either radical cleavage or anionic cleavage by accepting
another electron. We have previously reported the de-
sulfonylation of alkyl sulfones11h and the reductive elimi-
nation of â-acetates or benzoate-substituted alkylsulfones11c
which afford the corresponding olefins. In the case of
(19) Bowers, K. W.; Giese, R. W.; Grimshaw, J .; House, H. O.;
Kolodny, N. H.; Kronberger, K.; Roe, D. K. J . Am. Chem. Soc. 1970,
92, 2783.
(16) Moyano, A.; Pericas, M. A.; Riera, A.; Luche, J .-L. Tetrahedron
Lett. 1990, 31, 7619. This was provided by a reviewer.
(17) (a) Molander, G. A.; McKie, J . A. J . Org. Chem. 1995, 60, 872
(b) Molander, G. A.; Kenny, C. J . Org. Chem. 1988, 53, 2132 (c)
Fukuzawa, S.; Nakanishi, A.; Fujinami, T.; Sakai, S. J . Chem. Soc.,
Chem. Commun. 1986, 624.
(20) Vedejs, E.; Lin, S. J . Org. Chem. 1994, 59, 1602.
(21) (a) Corey, E. J .; Watt, D. S. J . Am. Chem. Soc. 1973, 95, 2303.
(b) Kandil, A. A.; Slessor, K. N. J . Org. Chem. 1985, 50, 5649. (c)
Heissler, D.; Riehl, J . J . Tetrahedron Lett. 1979, 20, 3957. (d) Aberhart,
D. J .; Hsu, C. T. J . Org. Chem. 1978, 43, 4374
(22) Osborn, M. E.; Pegues, J . F.; Paquette, L. A. J . Org. Chem. 1980,
45, 16711.
(18) Molander, G. A. Chem. Rev. 1992, 92, 29.

Notes
J . Org. Chem., Vol. 63, No. 26, 1998 10009
4.49 (m, 2 H), 2.95 (m, 2 H), 2.33 and 2.30 (two s, 6 H), 2.00 and
sulfone 1s the corresponding olefin 2s was obtained as a
sole product. Similar radical anion intermediate for
(bromomethyl)aziridine can be assumed for reductive
desulfonylation. Garst et al. have recently demonstrated23
that radical species formed on the surface of Mg in
Grignard reagent formation undergo mostly reduction on
the surface to Grignard reagent, but at the same time a
certain amount of it diffused into solvent is in an
equilibrium with one on the surface so as to form a
coupling product and hydrogen abstraction product. In
the same context, we might assume that radical species
formed on the surface of Mg in methanol undergo either
further reduction to carbanion or ring cleavage to form
aminyl radical. Although we could not detect any of C(2)-
C(3) cleavage product in our cases, it has been reported
that homolytic cleavage can occur both on the C(2)-N
and C(2)-C(3) bond from aziridinylmethyl radical15,24 or
oxyranylmethyl radical25 depending on the substituent
at C(3). Thus, the cleavage reaction pathway can be
explained either by a carbanionic or a radical species.
In summary, a remarkably simple, convenient, and
economic method for highly regiospecific C(2)-N bond
reduction of various 2-acyl-, (carboalkoxy)-, cyano-,
(halomethyl)-, and (phenylsulfonylmethyl)aziridines has
been established by employing magnesium in methanol
as the electron-transfer reagent.
1.80 (two s, 6 H), 1.15 and 1.07 (two d, J ) 7.1, 7.1 Hz, 6 H); 13
C
NMR (125.7 MHz) δ 212.3, 210.2, 143.1, 142.8, 138.9, 138.7,
137.7, 137.6, 129.2, 129.1, 128.3, 127.4, 127.3, 127.0, 126.9, 126.6,
60.3, 59.5, 52.5, 52.3, 29.6, 21.4, 15.1, 13.4. Anal. Calcd for
C
18H21NO3S: C, 65.23; H, 6.39; N, 4.23; S, 9.67. Found: C, 65.53;
H, 6.57;N, 4.09;S, 9.91.
4-(p-Tosyla m in o)-4-p h en yl-2-bu ta n on e (2d ). Meth od B:
yield 75%, white solid, mp 104.5-105.5 °C; Rf 0.21 (2/1 hexane/
1
EtOAc); H NMR (500 MHz) δ 7.52 (d, J ) 8.3 Hz, 2 H), 7.07-
7.13 (m, 5 H), 7.00-7.05 (m, 2 H), 5.71 (d, J ) 7.4 Hz, 1 H), 4.63
(m, 1 H), 2.97 (dd, J ) 17.2, 5.8 Hz, 1 H), 2.83 (dd, J ) 17.2, 6.2
Hz, 1 H), 2.31 (s, 3 H), 1.96 (s, 3 H); 13C NMR (125.7 MHz) δ
206.6, 143.2, 139.7, 137.2, 129.4, 128.5, 127.6, 127.1, 126.5, 54.0,
49.6, 30.7, 21.4. Anal. Calcd: C, 64.33; H, 6.03; N, 4.41; S, 10.10.
Found: C, 63.72; H, 6.23; N, 4.36; S, 9.85. HRMS (CI): calcd
for C17H20NO3S, m/ e 318.1164; found, m/ e 318.1167.
Ben za la ceton e: yield 20%, oil; 1H NMR (200 MHz) δ 7.39-
1
7.58 (m, 6 H), 6.73 (d, J ) 16.2 Hz, 1 H), 2.40 (s, 3 H). H NMR
data are identical with the literature values.26
2-(p-Tosylam in o)-1,3-diph en yl-2-pr open -1-on e (2e). Meth -
od C: yield 65%, oil; 1H NMR (500 MHz) δ 6.80-7.90 (m, 16 H),
2.36 (s, 3 H); 13C NMR (125.7 MHz) δ 193.6, 144.1, 139.1, 136.3,
136.2, 132.7, 132.3, 131.3, 130.8, 130.5, 129.5, 129.1, 128.6, 128.5,
128.3, 127.5, 21.5. Anal. Calcd for C22H19NO3S: C, 70.01 H, 5.07;
N, 3.71; S, 8.49. Found: C, 70.11; H, 5.12;N, 3.63;S, 8.37
HRMS: calcd for
377.1083.
C22H19NO3S, m/ e 377.1086; found, m/ e
Meth yl 3-(p-Tosyla m in o)bu ta n oa te (2h ). Meth od D: yield
94%, oil; 1H NMR (300 MHz) δ 7.74 (d, J ) 7.7 Hz, 2 H), 7.28 (d,
J ) 7.7 Hz, 2 H), 5.15 (br d, J ) 8.6 Hz, 1 H), 3.68 (m, 1 H), 3.60
(s, 3 H), 2.41 (d, J ) 5.3 Hz, 2 H), 2.40 (s, 3 H), 1.12 (d, J ) 6.7
Hz, 3 H); 13C NMR (75.4 MHz) δ 171.5, 143.3, 137.9, 129.6, 127.0,
51.6, 48.5, 40.5, 21.4, 21.0. Anal. Calcd for C12H17NO4S: C, 53.12;
H, 6.32; N, 5.16; S, 11.82. Found: C, 53.28; H, 6.41; N, 5.11; S,
11.78.
Meth yl 3-(p-Tosylam in o-2-m eth ylpen tan oate (2i). Meth od
D: yield 95%, oil. Isomer A: Rf 0.39 (2/1 hexane/EtOAc); 1H NMR
(300 MHz) δ 7.65-7.85 (m, 2 H), 7.20-7.39 (m, 2 H), 5.03 (br d,
J ) 9.6 Hz, H), 3.60 (s, 3 H), 3.25-3.42 (m, 1 H), 2.52 (m, 1 H),
2.42 (s, 3 H), 1.20-1.58 (m, 2 H), 1.06 (d, J ) 7.2 Hz, 3 H), 0.75
(t, J ) 7.6 Hz, 3 H); 13C NMR (75.4 MHz) δ 175.2, 143.1, 138.7,
129.5, 126.9, 57.7, 51.8, 41.8, 30.9, 27.0, 21.5, 14.4, 10.5. Anal.
Calcd for C14H21NO4S: C, 56.17; H, 7.07; N, 4.68; S, 10.71.
Found: C, 56.28; H, 7.11; N, 4.59; S, 10.78. Isomer B: 1H NMR
(300 MHz) δ 7.65-7.85 (m, 2 H), 7.20-7.39 (m, 2 H), 5.35 (br d,
J ) 9.1 Hz, 1 H), 3.64 (s, 3 H), 3.25-3.42 (m, 1 H), 2.70 (m, 1
H), 2.42 (s, 3 H), 1.20-1.58 (m, 2 H), 1.07 (d, J ) 7.2 Hz, 3 H),
0.78 (t, J ) 7.4 Hz, 3 H); 13C NMR (75.4 MHz) δ 174.3, 143.3,
138.3, 129.6, 127.0, 57.7, 51.8, 43.0, 29.7, 24.6, 21.5, 13.2, 10.4.
HRMS (CI): calcd for C14H22NO4S, m/ e 300.1270; found, m/ e
300.1289.
Exp er im en ta l Section
Methanol was dried over magnesium powder. Magnesium
powder, purchased from Aldrich (-50 mesh, 99+%), was used
without any special activation. The reaction was routinely
monitored by TLC using precoated silica gel plates (0.25 mm
60 F-254 E. Merck). Flash column chromatography was per-
formed with Merck Kiesegel 60 (230-400 mesh ASTM) silica.
1H and 13C NMR spectra were recorded in CDCl3 at a specified
magnetic field.
P r oced u r es for Rin g Clea va ge of Azir id in e. Meth od A.
To 3.0 equiv of vacuum-dried magnesium powder, which was
immersed in a dry ice/CCl4 bath (-23 °C) and kept under a
nitrogen atmosphere, a solution of the aziridine substrate in dry
methanol (0.2 M) was added by syringe. After stirring of the
mixture for 2 h, an equal volume of ethyl acetate was added to
the gray colored reaction mixture. The whole mixture was then
filtered through a silica gel pad and concentrated in vacuo. The
residue was then purified by flash column chromatography
(silica gel, 3/1 hexane/ethyl acetate) to give the desired product-
(s).
Meth od B. To 3.0 equiv of vacuum-dried magnesium powder,
which was immersed in a dry ice/CCl4 bath (-23 °C) and kept
under a nitrogen atmosphere, a solution of the aziridine sub-
strate (0.5 mmol) in dry methanol (3mL) was added by syringe.
After being stirred for 4 h, the whole mixture was poured into
ice cold 2 N HCl (1.6 mL). The mixture was extracted with
EtOAc (3 × 10 mL), and the organic layer was dried with MgSO4.
After evaporation of the solvent, the residue was flash column
chromatographed (silica gel, 3/1 hexane/ethyl acetate) to give
the desired product(s).
Meth yl 3-(p-Tosylam in o)-3-ph en ylpr opan oate (2j). Meth -
od D: yield 35%, white solid, mp 102-102.5 °C; Rf 0.18 (3/1
hexane/EtOAc); 1H NMR (500 MHz) δ 7.55-7.65 (m, 2 H), 7.05-
7.25 (m, 7 H), 5.80 (d, J ) 7.8 Hz, 1 H), 4.73 (m, 1 H), 3.54 (s, 3
H), 2.84 (dd, J ) 9.6, 6.4 Hz, 1 H), 2.75 (dd, J ) 9.6, 6.2 Hz, 1
H), 2.32 (s, 3 H); 13C NMR (125.7 MHz) δ 171.0, 143.2, 139.4,
137.3, 129.4, 128.5, 127.7, 127.1, 126.4, 54.3, 51.8, 41.1, 21.4.
HRMS (CI): calcd for C17H20NO4S (M + H+), m/ e 334.1113;
found, m/ e 334.1112.
Meth yl 3-P h en yla zir id in e-2-ca r boxyla te (Desu lfon yla t-
ed P r od u ct). Meth od D: yield 60%, oil; Rf 0.47 (3/1 hexane/
EtOAc); 1H NMR (500 MHz) δ 7.20-7.40 (m, 5 H), 3.79 (s, 3 H),
3.26 (dd, J ) 9.6, 2.3 Hz, 1 H), 2.58 (dd, J ) 8.0, 2.3 Hz, 1 H),
1.85-2.00 (m, 1 H); 13C NMR (125.7 MHz) δ 172.1, 137.7, 128.3,
Meth od C. Virtually the same procedure was used as method
A except reaction temperature (room temperature).
Meth od D. Virtually the same procedure as method A was
employed except amount of magnesium (4 equiv).
4-(p-Tosyla m in o)-4-p h en yl-3-m eth yl-2-bu ta n on e (2c), Di-
a ster eom er ic Mixtu r e. Meth od A: yield 98%, oil; Rf 0.37 (4/1
hexane/EtOAc); 1H NMR (300 MHz) δ 7.40-7.60 (m, 4 H), 6.90-
7.25 (m, 14 H), 6.18 and 5.66 (two br d, J ) 9.1, 8.6 Hz, 2 H),
127.7, 126.0, 52.6, 40.3, 39.2. HRMS (ESI): calcd for C10H12
-
NO2 (M + H+), m/ e 178.0868; found, m/ e 178.0866.
Eth yl 3-(p-Tosyla m in o)-3-p h en ylp r op a n oa te (Eth yl Es-
ter of 2j). A solution of 1j (25 mmol) in dry ethanol (1 mL) and
THF (7 mL) mixture was added to magnesium powder (100
mmol). To the stirred reaction mixture, a few crystals of mercuric
chloride were added. Stirring was continued under nitrogen
(23) Garst, J . F.; Ungvary, F.; Baxter, J . J . Am. Chem. Soc. 1997,
119, 253.
(24) Schwan, A. L.; Refvik, M. D. Tetrahedron Lett. 1993, 34, 4901.
(25) Dickinson, J . M.; Murphy, J . A.; Patterson, C. W.; Wooster, N.
F. J . Chem. Soc., Perkin Trans. 1 1990, 1179.
(26) Pouchert, C. J .; Behnke, J . The Aldrich Library of 13C and 1H
FT NMR Spectra, 1st ed. Aldrich: Milwaukee, WI, 1993; Vol. 2, p 779
C.

10010 J . Org. Chem., Vol. 63, No. 26, 1998
Notes
atmosphere for 1.5 h at room temperature. The reaction mixture
was poured into 0.2 N HCl (10 mL) and then extracted with ethyl
acetate (40 mL × 2). The combined organic layer was washed
with saturated aqueous NaHCO3 solution, dried over anhydrous
MgSO4, filtered, and concentrated in vacuo. The residue was
purified by silica gel flash column chromatography to give the
desired product in 95% yield: 1H NMR (300 MHz) δ 7.59 (d, J
) 8.4 Hz, 2 H), 7.05-7.25 (m, 7 H), 5.99 (d, J ) 7.9 Hz, 1 H),
4.74 (m, 1 H), 3.99 (q, J ) 7.1 Hz, 2 H), 2.81 (dd, J ) 15.7, 6.4
Hz, 1 H), 2.72 (dd, J ) 15.7, 6.5 Hz, 1 H), 2.35 (s, 3 H), 1.11 (t,
J ) 7.1 Hz, 3 H); 13C NMR (125.7 MHz) δ 170.5, 143.0, 139.3,
137.3, 129.3, 128.4, 127.5, 127.0, 126.7, 126.4, 107.7, 60.8, 54.4,
41.4, 21.4, 139. HRMS (CI): calcd for C18H21NO4S (M + H+),
m/ e 348.1266; found, m/ e 348.1269.
(s, 3 H); 13C NMR (75.4 MHz) δ 144.1, 137.1, 136.5, 129.8, 128.2,
128.0, 127.1, 126.2, 116.4, 54.1, 30.9, 26.2, 22.6, 14.2. Anal. Calcd
for C16H16N2O2S: 63.98; H, 5.37; N, 9.33; S, 10.67. Found: C,
64.01; H, 5.42; N, 9.30; S, 10.65. HRMS: calcd for C16H16N2O2S,
m/ e 300.0932; found, m/ e 300.0921.
N-Allyl-N-ben zyla m in e (2q). Meth od D: yield 93%, oil; 1H
NMR (300 MHz) δ 7.30-7.60 (m, 5 H), 5.85-6.05 (m, 1 H), 5.30-
5.50 (m, 2 H), 4.02 (s, 2 H), 3.49 (m, 2 H); 13C NMR (125.7 MHz)
δ 133.4, 133.3, 130.4, 128.5, 121.5, 49.6, 48.8. Anal. Calcd for
C10H13N: C, 81.59; H, 8.90; N, 9.51. Found: C, 81.62; H, 8.94;
N, 9.44.
N-Allyl-N-p-ch lor oben zyla m in e (2r ). Meth od D: yield
95%, oil; 1H NMR (300 MHz) δ 9.65 (br s, 1 H), 7.40-7.70 (m, 4
H), 5.85-6.10 (m, 1 H), 5.30-5.55 (m, 2 H), 4.10 (s, 2 H), 3.55
(m, 2 H); 13C NMR (125.7 MHz) δ 134.2, 132.2, 131.2, 129.1,
128.2, 122.1, 49.0. Anal. Calcd for C10H12ClN: C, 66.12; H, 6.66;
N, 7.71. Found: C, 66.18; H, 6.69; N, 7.69.
Ben zyl 3-(N-(ter t-bu toxyca r bon yl)a m in o)-1-bu ten -4-yl
Eth er (2s). Meth od C: yield 94%, oil; 1H NMR (300 MHz) δ
7.15-7.40 (m, 5 H), 5.70-5.95 (m, 1 H), 5.10-5.30 (m, 2 H), 4.85
(br s, 1 H), 4.51 (s, 2 H), 4.21-4.39 (m, 1H), 3.40-3.55 (m, 2 H),
1.42 (s, 9H); 13C NMR (125.7 MHz) δ 155.4, 137.9, 136.4, 128.4,
127.7, 127.5, 115.6, 109.3, 79.5, 73.2, 72.1, 28.3. Anal. Calcd for
C16H23NO3: C, 69.29; H, 8.36; N, 5.05. Found: C, 69.42; H, 8.58;
N, 5.11. HRMS (CI): calcd for C16H23NO3 (M + H+), m/ e
277.1677; found, m/ e 277.1659.
ter t-Bu tyl 3-(p-Tosyla m in o)p r op a n oa te (2k ). Meth od D:
1
yield 85%, oil; H NMR (300 MHz) δ 7.75 (d, J ) 8.2 Hz, 2 H),
7.30 (d, J ) 8.2 Hz, 2 H), 5.20 (br s, 1 H), 3.05-3.20 (m, 2 H),
2.43 (t, J ) 7.2 Hz, 2 H), 2.42 (s, 3 H), 1.40 (s, 9 H); 13C NMR
(75.4 MHz) δ 171.5, 143.4, 137.0, 129.7, 127.0, 81.6, 38.9, 34.9,
28.0, 21.5. Anal. Calcd for C14H21NO4S: C, 56.17; H, 7.07; N,
4.68; S, 10.71. Found: C, 56.16; H, 7.06; N, 4.61; S 10.81.
3-(p-Tosyla m in o)p r op ion itr ile (2n ). Meth od D: yield 83%,
oil; 1H NMR (500 MHz) δ 7.76 (d, J ) 8.0 Hz, 2 H), 7.33 (d, J )
8.0 Hz, 2 H), 5.65 (br s, 1 H), 3.22 (t, J ) 6.6 Hz, 2 H), 2.59 (t,
J ) 6.6 Hz, 2 H), 2.43 (s, 3 H); 13C NMR (125.7 MHz) δ 144.0,
136.2, 129.9, 126.9, 117.5, 39.8, 21.4, 19.2. Anal. Calcd for
C
10H12N2O2S: C, 53.55; H, 5.39; N, 12.49; S, 14.30. Found: C,
Ack n ow led gm en t. We greatly acknowledge for the
generous financial support from the Ministry of Science
and Technology and thank Dr. B. Vincent Crist (XPS
International, Inc.) for his assistance.
53.42; H, 5.31; N, 12.38; S 14.30. HRMS: calcd for C10H12N2O2S,
m/ e 224.0619; found, m/ e 224.0618.
3-(p-Tosyla m in o)-2-m eth ylp r op ion itr ile (2o). Meth od D:
1
yield 85%, oil; H NMR (300 MHz) δ 7.76 (d, J ) 8.0 Hz, 2 H),
7.34 (d, J ) 8.0 Hz, 2 H), 5.35 (t, J ) 6.8 Hz, 1 H), 3.12 (m, 2 H),
2.86 (m, 1 H), 2.44 (s, 3 H), 1.30 (d, J ) 7.1 Hz, 3 H); 13C NMR
(125.7 MHz) δ 207.8, 143.4, 137.0, 129.7, 129.0, 42.9, 38.0, 30.0,
21.5. Anal. Calcd for C11H14N2O2S: C, 55.44; H, 5.92; N, 11.76;
S, 13.45. Found: C, 55.53; H, 5.98; N, 11.74; S, 13.42. HRMS:
calcd for C11H14N2O2S, m/ e 238.0775; found, m/ e 238.0774.
3-(p-Tosyla m in o)-3-p h en ylp r op ion itr ile (2p ). Meth od D:
yield 80%, oil; 1H NMR (500 MHz) δ 7.65-7.75 (m, 2 H), 7.05-
7.40 (m, 7 H), 5.07 (br s, 1 H), 4.57 (m, 1 H), 2.95 (m, 2 H), 2.42
Su p p or tin g In for m a tion Ava ila ble: Text providing spec-
tral data for the substrates 1a -s and products 2a ,b,g (7
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
J O9806963