Aza-Payne rearrangement of α,α-disubstituted-aziridinemethanols

Article abstract of DOI:10.1016/j.tetasy.2006.04.035

The aza-Payne rearrangement of activated N-Ts-α,α-disubstituted-aziridinemethanols, induced by NaOH in the mixed solvent ^tBuOH/H₂O/THF (4:5:1) or NaH in a mixed solvent of THF/HMPA (10:1), as well as some N-Boc-α,α-disubstituted-azir

Full text of DOI:10.1016/j.tetasy.2006.04.035

Tetrahedron: Asymmetry 17 (2006) 1394–1401
Aza-Payne rearrangement of a,a-disubstituted-aziridinemethanols
Feng Xichun,* Qiu Guofu, Liang Shucai, Teng Hanbing, Wu Lamei and Hu Xianming*
State Key Laboratory of Virology, College of Pharmacy, Wuhan University, Wuhan 430072, China
Received 3 April 2006; accepted 14 April 2006
Abstract—The aza-Payne rearrangement of activated N-Ts-a,a-disubstituted-aziridinemethanols, induced by NaOH in the mixed solvent
tBuOH/H2O/THF (4:5:1) or NaH in a mixed solvent of THF/HMPA (10:1), as well as some N-Boc-a,a-disubstituted-aziridinemethanols
with the latter reagent/solvent combination, provides the corresponding epoxides in up to 99% yield.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
be 18.6 kcal/mol lower than that of oxa anion 55a
(Scheme 2).
Owing to the utility of aziridines as chiral building blocks1
and their biological activity,2 the aza-Payne rearrangement
of aziridinemethanols has been of much interest especially
as a synthetic route to bioactive compounds.3
N Ms
ΔE= -18.59 kcal/mol
Ms
N
O
H
O
H
The Payne rearrangement, as exemplified by the conversion
of 1 to 2 in Scheme 1, has been the object of much study4 as
has been the ‘aza-Payne’5 variant (conversion of 3 to 4 as
shown in Scheme 1). Clean intramolecular SN2 substitution
is observed.6 The aza-Payne reaction is reversible5a and the
epoxide can be favored over the aziridine if the nitrogen
anion is well stabilized. For example, from ab initio calcula-
tions, the energy minimum of aza anion 6 was predicted to
6
5
Scheme 2.
To induce the aza-Payne rearrangement of 3, where R is
either H or alkyl, BuLi can be used for anion formation
n
in THF, but reasonable yields are obtained only when a
Lewis acid (AlMe3) is added.7 As predicted from the calcu-
lated relative stabilities of 5 and 6, the reaction becomes
easier and requires less drastic reagents when proceeding
in the other direction (in general terms from 4 to 3 in
Scheme 2), providing the aziridine nitrogen is activated
with a strongly electron withdrawing group. For example,
tosylation of the nitrogen atom as illustrated for 7a, leads
to excellent yields (65–99%) of 7b on rearrangement
(Scheme 3). The use of mesyl as an activating group is also
effective: rearrangement of 8a under standard Payne condi-
tions (potassium hydride in THF–HMPA as solvent)
affords 8b in good (80%) yield.5a However, the protecting
groups Boc and trityl, 9a and 9b, on the nitrogen atom
are reported to be not effective in promoting rearrangement
under analogous conditions (Scheme 3).8
O
O
O
O
2
1
O
O
R
N
N
R
4
3
Scheme 1.
The role of the substituents in aza-Payne rearrangements
is quite important. N-Tosyl-oxiranemethyl amines a,a-
disubstituted adjacent to the nitrogen-bearing carbon are
*
Corresponding authors. Tel.: +86 27 6875 3532; fax: +86 27 6875
4629; e-mail addresses: springfengxc@yahoo.com.cn; xmhu@whu.edu.
cn
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.04.035

F. Xichun et al. / Tetrahedron: Asymmetry 17 (2006) 1394–1401
1395
2. Results and discussion
2.1. The aza-Payne rearrangement of N-tosyl a,a-disubsti-
tuted-aziridinemethanols
KH (4 equiv.)
0 oC, 30 min
THF-HMPA(12:1)
H
H
OH
H
O
H
H
Me
Me
N
92%
Ts NH
Ts
7a
The reaction of methyl N-tritylaziridine-2-carboxylates 13
and 14, readily obtained from L-serine and L-threonine,10
with a Grignard reagent in THF at room temperature, fol-
lowed by removal of the trityl group in situ with H2SO4 in
MeOH/H2O solvent,11 provided aziridinemethanols 15a–d
and 16a–d in 69–90% yield. Tosylation of aziridinemetha-
nols 15a–d and 16a–d led to 17a–d and 18a–c in 87–96%
yield. Tosylation of 16d failed to provide an isolable pro-
duct. The subsequent aza-Payne rearrangement reactions
of these tosylates to epoxy sulfonamides 19a–d and 20a–c
are shown in Scheme 5 and the results are summarized in
Table 1.
7b
NaH (1.5 equiv.)
0 oC, 2 h
THF-HMPA(10:1)
H
H
H
O
OH
H
Me
Me
N
80%
Ms NH
8b
Ms
8a
H
H
H
OH
OH
Me
Me
N
N
Trt
Boc
9b
9a
The rearranged products were obtained in high isolated
yields. HPLC analysis revealed single peaks in all cases
indicative of diastereomeric purity 18a–c. On the basis of
extensive literature precedents,5a all products are assumed
to be the result of SN2 substitution and are enantiomeri-
cally pure. There are significant differences in conversion
times for the various alcohols with the use of NaOH as
base and phenyl substituted 17a and 18a seem to be most
reactive. However, when using a stronger base, NaH, the
differences in conversion times are far less. It does appear
that n-butyl substituted compounds 17b and 18b do react
in general somewhat more slowly.
Scheme 3.
reported to rearrange (5% aqueous NaOH at 100 ꢁC) to
N-tosyl-aziridines (3 to 4 in Scheme 1). On the other
hand, aziridinemethanols having a primary (7a and 8a)
or secondary hydroxymethyl group (10a) all afford high
yields of epoxides as rearrangement products (4 to 3 in
Scheme 1) as illustrated with the examples shown in
Scheme 4. The potential reversibility of aza-Payne rear-
rangements has been pointed out.5a Aziridinemethanol
11a, possessing a tertiary hydroxyl group, also rearranged
slowly in THF in the presence of KH to give solely epoxy
sulfonamide 11b.5a We have also reported that 12a, which
bears a phenyl adjacent to the hydroxyl group, rearranges
smoothly to 12b.9
Disubstitution on the hydroxy-bearing carbon of the N-tos-
yl aziridines studied here clearly promotes rearrangement
to the corresponding epoxide (4 to 3 in Scheme 1). The
a,a-disubstitution will, of course, lead to an increase in
basicity of the alkoxide as anticipated from inductive
effects and ion pairing, as has previously been discussed.6
KH (4 equiv.)
THF, 0 oC, 2 h
H
O
H
H
N
N
Ts
Ts
2.2. The aza-Payne rearrangement of N-Boc a,a-disubsti-
tuted-aziridinemethanols
Bu
NHTs
Bu
88%
H
OH
10a
10b
To determine whether N-Boc protected aziridinemetha-
nols (Boc should stabilize the nitrogen anion by reso-
nance) would give analogous results, N-Boc aziridine-
methanols 21 and 22 were synthesized in high yield
(Scheme 6). N-Boc aziridinemethanol 21a rearranged to
epoxy sulfonamide 23a in 70% yield after stirring for
24 h with NaOH in mixed tBuOH/H2O/THF (4:5:1).
The yield increased to 96% on reaction with NaH in
THF/HMPA (10:1) for a period of 4 h. In a similar man-
ner, N-Boc aziridine 21d afforded a low yield (30%) of
aza-Payne rearrangement product 23d with the NaOH
reaction system and a higher yield (80%) with NaH reac-
tion system. The other N-Boc aziridines 21b, 21c, 22a,
22b, 22c provided no rearrangement products with either
NaOH or NaH and the starting materials were recovered
(Table 2).
H
KH (4 equiv.)
THF, rt, 18 h
H
O
OH
NHTs
99%
11a
11b
NaOH
tBuOH/H2O
rt 4 h
OH
H
H
O
TsHN
12b
H
N
98%
H
Ts
12a
Scheme 4.
Herein we examine the scope and potential of the aza-
Payne rearrangement more closely for the specific case of
enantiomerically pure a,a-disubstituted-aziridinemetha-
nols, that is, examples where the oxygen-bearing carbon
is a,a-disubstituted in anticipation that this fully substi-
tuted carbon would end up in the three-membered ring,
an epoxide in contrast to the literature.8
A methyl group on the C-3 position of aziridine 21a ap-
pears to favor the rearrangement of N-Boc aziridinemetha-
nols (compare entries 1 and 5 in Table 2). This is also in
line with our failure to prepare 18d and 22d (Scheme 7).

1396
F. Xichun et al. / Tetrahedron: Asymmetry 17 (2006) 1394–1401
H
H
H
H
H
H
R2
R2
R2
R2
CO2Me
i
iii
R1
N
R1
R1
N
H
N
ii
OH
OH
Trt
Ts
(2S) or (2S,3S)
(2S) or (2S,3S)
(2S) or (2S,3S)
17a-d R1=Me
18a-c R1=H
13 R1=Me
14 R1=H
15a-d R1=Me
16a-c R1=H
O
H
R2
R2
a
b
c
R2=Ph
R2=nBu
R2=Bn
R1
iv or v
NH
d
R2=p-C6H4OCH3
Ts
(2R) or (2R,3S)
19a-d R1=Me
20a-c R1=H
Scheme 5. Reagents and conditions: (i) R2Br, Mg, THF; (ii) MeOH/H2O/H2SO4 (60:8:3); (iii) TsCl (1 equiv), Py; (iv) 0.28 N NaOH in tBuOH/H2O/THF
(4:5:1) rt; (v) NaH in THF/HMPA (10:1) rt.
Table 1. Aza-Payne rearrangement of N-tosyl-aziridinemethanols 17 and
18 to epoxy sulfonamides 19 and 20
Table 2. Aza-Payne rearrangement of N-Boc-aziridinemethanol 21 to
epoxy sulfonamide 23
Entry
Starting
material
NaOHa
NaHb
Yieldd
Product
Entry
Starting
material
NaOHa
NaHb
Product
Time
Yieldc
(%)
Time
Time
Yield
(%)
Time
Yield
(%)
(h)
(%)
(h)
(h)
1
2
3
4
5
6
7
17a
17b
17c
17d
18a
18b
18c
1
8
2
24
1
8
96
86
90
97
95
83
89
5 min
1 h
30 min
2 h
10 min
1 h
1 h
99
90
96
96
98
95
96
19a
19b
19c
19d
20a
20b
20c
1
2
3
4
5
6
7
21a
21b
21c
21d
22a
22b
22c
24
24
24
24
24
24
24
70d
4
4
4
4
4
4
4
96c
23a
23d
e
e
—
—
e
e
—
—
30d
80c
e
e
—
—
e
e
—
—
e
e
10
—
—
a Solvent: BuOH/H2O/THF (4:5:1).
b Solvent: THF/HMPA (10:1).
c Isolated yield.
a Solvent: BuOH/H2O/THF (4:5:1).
b Solvent: THF/HMPA (10:1).
c Isolated yield.
t
t
d Determined by HPLC.
d Detected by HPLC.
e No reaction.
H
H
H
H
R2
R2
H
H
R2
R2
p-C6H4OCH3
p-C6H4OCH3
p-C6H4OCH3
p-C6H4OCH3
i
i
R1
R1
N
N
H
N
N
a
R2=Ph
R2=nBu
R2=Bn
OH
OH
OH
OH
Boc
b
c
H
(2S)
R1
(2S) or (2S,3S)
(2S) or (2S,3S)
(2S)
18d R1=Ts
22d R1=Boc
d
R2=p-C6H4OCH3
15a-d R1=Me
16a-c R1=H
21a-d R1=Me
22a-c R1=H
16d
H
H
O
H
Ph
Ph
Ph
Ph
H
H
O
H
R2
R2
R1
R2
R2
ii
Me
ii or iii
R1
N
Me
N
OH
NH
OH
Trt
Boc
NH
Trt
Boc
(2S) or (2S,3S)
(2R) or (2R,3S)
26 R1=Me
27 R1=H
(2S) or (2S,3S)
(2R) or (2R,3S)
24 R1=Me
25 R1=H
21a R2=Ph
21d R2=p-C6H4OCH3
23a R2=Ph
23d R2=p-C6H4OCH3
Scheme 7. Reagents and conditions: (i) (Boc)2O, NEt3, THF or TsCl
(1 equiv), Py; (ii) 0.28 M NaOH in BuOH/H2O/THF (4:5:1) or NaH in
t
Scheme 6. Reagents and conditions: (i) (Boc)2O, NEt3, THF; (ii) 0.28 M
NaOH in BuOH/H2O/THF (4:5:1); (iii) NaH in THF/HMPA (10:1).
THF/HMPA (10:1).
t
3. Conclusion
In conclusion, the effective aza-Payne rearrangement of
Not unexpectedly, aziridinemethanols 24 and 25 do not
N-Ts aziridinemethanols and N-Boc aziridinemethanols
undergo the rearrangement.

F. Xichun et al. / Tetrahedron: Asymmetry 17 (2006) 1394–1401
1397
provides a potential synthesis of functional amino alcohol.
The substituted groups (on C-3 position and hydroxy-bear-
ing carbon) of aziridinemethanols clearly effected the
rearrangement.
dinecarboxylate 13 (8.93 g, 25.0 mmol) and 1-bromobutane
(10.77 mL, 100 mmol, 4.0 equiv) to afford 15b (3.88 g,
78%). Purified by flash column chromatography (hexane–
20
ethyl acetate, 2:1). Colorless oil. ½aꢀD ¼ ꢁ10:5 (c 0.5,
1
CHCl3); H NMR (CDCl3): d 0.91–0.92 (m, CH3, 6H),
1.31–1.54 (m, (CH2,CH3), 15H), 1.98 (m, C(3)H, 1H),
2.10 (m, C(2)H, 1H); IR (mmax/cmꢁ1): 3303, 2957, 2862,
1467, 1416, 1379, 1259, 1144, 998, 846.
4. Experimental
4.1. General
4.2.3. (2S,3S)-3-Methylaziridin-2-yl(dibenzyl)methanol 15c.
Prepared as described in the general procedure from aziri-
dinecarboxylate 13 (8.93 g, 25.0 mmol) and benzyl bromide
(11.96 mL, 100 mmol, 4.0 equiv) to afford 15c (5.00 g,
1H NMR and 13C NMR spectra were obtained at a Varian
Mercy 300 MHz spectrometer. IR spectra were recorded
on a Perkin Elmer 983 spectrometer. MS spectra were
recorded on a Finnigan-LC Qadvantage spectrometer
(ESI), and the Optical rotations were measured at 20 ꢁC
using the D-line by means of a Perkin–Elmer 343 plus
polarimeter. Melting points were determined on a XT-4
apparatus (uncorrected). Elemental analyses were carried
out on a VarioEL III(German) instrument. Silica gel was
used for analytical and flash chromatography. Organic ex-
tracts were dried over MgSO4 and filtered before removal
of the solvent. All reactions employing dry solvents were
run under nitrogen. THF was dried (sodium/benzophe-
none) and distilled.
75%). Purified by flash column chromatography (hexane–
20
ethyl acetate, 3:1). White solid. Mp 50–51 ꢁC; ½aꢀD
¼
1
ꢁ23:2 (c 0.5, CHCl3); H NMR (CDCl3): d 1.24 (d, CH3,
3H, J = 5.1), 2.06–2.10 (m, (C(3)H, C(2)H), 2H), 2.93 (m,
CH2(Bn), 2H), 3.08 (m, CH2(Bn), 2H), 7.31–7.45 (m, Ar,
10H); IR (mmax/cmꢁ1): 3314, 3083, 3060, 3027, 2924,
1602, 1495, 1454, 1417, 1353, 1301, 1087, 1047, 844.
4.2.4. (2S,3S)-3-Methylaziridin-2-yl(bis(4-methoxyphenyl))-
methanol 15d. Prepared as described in the general proce-
dure from aziridinecarboxylate 13 (8.93 g, 25.0 mmol) and
1-bromo-4-methoxybenzene
(12.52 mL,
100 mmol,
4.2. General procedure for the synthesis of 15 and 16
4.0 equiv) to afford 15d (5.23 g, 70%). Purified by flash col-
umn chromatography (hexane–ethyl acetate, 3:1).
20
1
To a stirred suspension of magnesium turnings (2.40 g,
100 mmol, 4.0 equiv) in THF (100 mL) was gradually
added bromide (100 mmol, 4.0 equiv). After heating the
Grignard reagent for 2 h, aziridinecarboxylate 13 or 14
(25.0 mmol) in THF (20 mL) was added dropwise over a
period of 20 min. The reaction was monitored with TLC
(hexane–ethyl acetate, 3:1). After 3 h the reaction was
quenched with saturated aqueous NH4Cl (60 mL). The
crude reaction mixture was extracted with ethyl acetate
(3 · 100 mL) and the combined organic layers dried over
MgSO4 and concentrated. The crude product was dissolved
in a mixture of MeOH, water and concentrated H2SO4
(60:8:3) (150 mL) by sonication for 5 min. After stirring
for 24 h and subsequent addition of water (100 mL) under
ice conditions, the solution was basified with 30% NaOH to
pH = 10. After the mixture was extracted with ethyl acetate
(3 · 100 mL), the organic phase was washed with satd
NaHCO3 (3 · 50 mL), satd NaCl (3 · 50 mL) dried over
MgSO4, and concentrated in vacuo. The crude was purified
by flash column chromatography to yield 15 or 16.
White solid. Mp 138 ꢁC; ½aꢀD ¼ þ58:7 (c 0.5, CHCl3); H
NMR (CDCl3): d 1.08 (d, CH3, 3H, J = 6.0), 2.33 (m,
C(3)H, 1H), 2.83 (d, C(2)H, 1H, J = 6.3), 3.76 (s, OCH3,
3H), 3.80 (s, OCH3, 3H), 6.79–7.42 (m, Ar, 8H); IR
(mmax/cmꢁ1): 3324, 3000, 2956, 2930, 2837, 1607, 1582,
1509, 1461, 1420, 1295, 1245, 1172, 1109, 1033, 1003, 984.
4.2.5. (2S)-Aziridin-2-yl(diphenyl)methanol 16a. Prepared
as described in the general procedure from aziridinecarb-
oxylate 14 (8.59 g, 25.0 mmol) and bromobenzene
(10.5 mL, 100 mmol, 4.0 equiv) to afford 16a (5.06 g,
90%). Purified by flash column chromatography (hexane–
20
ethyl acetate, 5:1). White solid. Mp 155–157 ꢁC; ½aꢀD
¼
ꢁ22:6 (c 1.0, CHCl3); 1H NMR (CDCl3): d 1.73 (d,
C(3)H, 1H, J = 3.3), 1.82 (d, C(3)H, 1H, J = 3.6), 2.87
(m, C(2)H, 1H), 7.22–7.45 (m, Ar, 10H); IR (mmax/cmꢁ1):
3309, 3000, 1599, 1488, 1425, 1363, 1312, 1271, 1242,
1217, 1199, 1179, 1106, 1082.
4.2.6. (2S)-Aziridin-2-yl(dibutyl)methanol 16b. Prepared
as described in the general procedure from aziridinecarb-
oxylate 14 (8.59 g, 25.0 mmol) and 1-bromobutane
(10.77 mL, 100 mmol, 4.0 equiv) to afford 16b (3.19 g,
4.2.1. (2S,3S)-3-Methylaziridin-2-yl(diphenyl)methanol 15a.
Prepared as described in the general procedure from aziri-
dinecarboxylate 13 (8.93 g, 25.0 mmol) and bromobenzene
(10.5 mL, 100 mmol, 4.0 equiv) to afford 15a (4.84 g, 81%).
69%). Purified by flash column chromatography (hexane–
20
ethyl acetate, 2:1). Colorless oil. ½aꢀD ¼ ꢁ21:4 (c 10.0,
Purified by flash column chromatography (hexane–ethyl
THF); 1H NMR (CDCl3): d 0.84 (m, CH3, 6H), 1.26–
1.44 (m, CH2, 12H), 1.53 (m, C(3)H2, 2H), 1.92 (m,
C(2)H, 1H); IR (mmax/cmꢁ1): 3472, 3061, 3025, 1597,
1490, 1445, 1331, 1180, 1158, 1031, 1011, 932, 913, 891.
20
acetate, 5:1). White solid. Mp 91 ꢁC; ½aꢀD ¼ þ80:0 (c 1.0,
1
CHCl3); H NMR (CDCl3): d 1.08 (d, CH3, 3H, J = 5.7),
2.40 (m, C(3)H, 1H), 2.95 (d, C(2)H, 1H, J = 6.0), 7.17–
7.54 (m, Ar, 10H); IR (mmax/cmꢁ1): 3444, 3256, 3087,
3055, 3021, 2986, 2958, 2928, 1599, 1492, 1447, 1425,
1360, 1172, 1061.
4.2.7. (2S)-Aziridin-2-yl(dibenzyl)methanol 16c. Prepared
as described in the general procedure from aziridine-
carboxylate 14 (8.59 g, 25.0 mmol) and benzyl bro-
mide (11.96 mL, 100 mmol, 4.0 equiv) to afford 16c
(4.81 g, 76%). Purified by flash column chromatography
4.2.2. (2S,3S)-3-Methylaziridin-2-yl(dibutyl)methanol 15b.
Prepared as described in the general procedure from aziri-

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F. Xichun et al. / Tetrahedron: Asymmetry 17 (2006) 1394–1401
(hexane–ethyl acetate, 2:1). White solid. Mp 75–76 ꢁC;
(CH3), 23.2 (CH2), 23.5 (CH2), 25.3 (CH2), 25.9 (CH2),
35.6 (C-3), 40.8 (CH2), 41.3 (CH2), 50.4 (C-2), 72.3
(CHOH), 128.2 (2·, @CH), 126.1 (2·, @CH), 135.3 (1·,
@Cquat), 144.9 (1·, @Cquat): IR (mmax/cmꢁ1): 3503,
2939, 2867, 1597, 1083, 997; MS-ESI 352 m/z (Mꢁ1). Anal.
Calcd for C19H31NO3S: C, 64.55; H, 8.84 N, 3.96 S, 9.07.
Found: C, 64.52; H, 8.87; N, 3.95; S, 9.04.
20
1
½aꢀD ¼ ꢁ28:4 (c 1.0, CHCl3); H NMR (CDCl3): d 1.16
(s, C(3), 1H), 1.48 (s, C(3), 1H), 2.06 (s, C(2), 1H), 2.87
(d, CH2(Bn), 4H), 7.23–7.45 (s, Ar, 10H); IR (mmax
/
cmꢁ1): 3261, 3057, 3030, 3004, 2946, 2912, 1602, 1496,
1452, 1311, 1266, 1192, 1099, 1082, 1060, 1050.
4.2.8. (2S)-Aziridin-2-yl(bis(4-methoxyphenyl))methanol 16d.
Prepared as described in the general procedure from aziri-
dinecarboxylate 14 (8.59 g, 25.0 mmol) and 1-bromo-4-
methoxybenzene (12.52 mL, 100 mmol, 4.0 equiv) to afford
4.3.3. (2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)dibenzylmetha-
nol 17c. Prepared as described in the general procedure
from aziridinemethanol 15c (2.67 g, 10.0 mmol) to afford
20
16d (5.77 g, 81%). Purified by flash column chromato-
17c (3.84 g, 91%) as a solid. Mp 102–103 ꢁC; ½aꢀD ¼
20
1
graphy (hexane–ethyl acetate, 2:1). Colorless oil. ½aꢀD
¼
ꢁ58:5 (c 1.0, CHCl3); H NMR (CDCl3): d 0.50 (d, CH3,
3H, J = 5.7), 1.82 (s, OH, 1H), 2.42 (s, CH3, 3H), 2.61
(m, C(3)H, 1H), 2.78 (m, CH2(Bn), 2H), 2.91 (m, CH2(Bn),
2H), 2.96 (d, C(2)H, 1H, J = 7.2), 7.12–7.84 (m, Ar, 14H);
13C NMR (CDCl3): d 11.7 (CH3), 21.9 (CH3), 42.7 (CH2),
43.3 (CH2), 49.1 (C-3), 50.1 (C-2), 73.5 (CHOH), 126.8 (1·,
@CH), 127.0 (1·, @CH), 128.1 (2·, @CH), 128.2 (2·,
@CH), 128.5 (2·, @CH), 130.0 (2·, @CH), 131.1 (2·,
@CH), 131.2 (2·, @CH), 135.4 (·, @Cquat), 136.3 (1·,
@Cquat), 136.7 (1·, @Cquat), 144.9 (1·, @Cquat); IR
(mmax/cmꢁ1): 3485, 3063, 3030, 2934, 1596, 1496, 1454,
1401, 1304, 1290, 1242, 1157, 1111, 1091, 1048, 1017,
976; MS-ESI 420 m/z (Mꢁ1). Anal. Calcd for
C25H27NO3S: C, 71.23; H, 6.46; N, 3.32; S, 7.61. Found:
C, 71.18; H, 6.56; N, 3.41; S, 7.82.
þ67:0 (c 9.0, THF); 1H NMR (CDCl3): d 2.79 (m,
C(3)H2, 1H), 3.09 (m, C(3)H2, 1H), 3.77 (s, OCH3, 3H),
3.80 (s, OCH3, 3H), 4.78 (m, C(2)H, 1H), 6.86–7.61 (m,
Ar, 8H); IR (mmax/cmꢁ1): 3338, 2939, 2839, 1668, 1599,
1574, 1510, 1489, 1449, 1420, 1303, 1253, 1168, 1111,
1032, 832.
4.3. General procedure for the synthesis of 17 and 18
To a stirred solution of aziridinemethanol 15 or 16
(10.0 mmol) in pyridine (20 mL) was gradually added 4-
methylbenzene-1-sulfonyl chloride (1.91 g, 10.0 mmol) in
THF (5 mL) at 0 ꢁC, and then the mixture allowed to warm
to rt and the stirring continued for 24 h. The reaction was
quenched with 50 mL of 5% HCl at 0 ꢁC with stirring. The
mixture was extracted with ethyl acetate and the extract
washed successively with 5% HCl, satd CuSO4
(3 · 50 mL), satd NaHCO3 (3 · 50 mL), and brine
(3 · 50 mL), and dried over MgSO4. The usual workup
was followed by flash chromatography over silica gel with
petroleum ether–ethyl acetate (5:1) to yield 17 or 18.
4.3.4. (2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)bis(4-methoxy-
phenyl)methanol 17d. Prepared as described in the general
procedure from aziridinemethanol 15d (2.99 g, 10.0 mmol)
to afford 17d (3.99 g, 88%) as a solid. Mp 153–154 ꢁC;
20
1
½aꢀD ¼ þ32:3 (c 1.0, CHCl3); H NMR (CDCl3): d 1.30
(d, CH3, 3H, J = 6.3), 2.41 (s, CH3, 3H), 3.11 (m, C(3)H,
1H), 3.61 (d, C(2)H, 1H, J = 7.2), 3.77 (s, OCH3, 3H),
3.78 (s, OCH3, 3H), 6.65–7.60 (m, Ar, 12H); 13C NMR
(CDCl3): d 12.3 (CH3), 21.6 (CH3), 40.4 (C-3), 52.2 (C-2),
55.18 (CH3O), 55.22 (CH3O), 74.2 (CHOH), 113.4 (2·,
@CH), 113.6 (2·, @CH), 126.9 (2·, @CH), 127.2 (2·,
@CH), 127.8 (2·, @CH), 129.6 (2·, @CH), 134.6 (1·,
@Cquat), 135.9 (1·, @Cquat), 139.5 (·, @Cquat), 144.4
(1·, @Cquat), 158.5 (1·, @Cquat), 158.7 (1·, @Cquat);
IR (mmax/cmꢁ1): 3479, 3030, 2952, 2930, 2835, 1610, 1510,
1463, 1451, 1416, 1317, 1304, 1251, 1154, 968; MS-ESI
452 m/z (Mꢁ1). Anal. Calcd for C25H27NO5S: C, 66.20;
H, 6.00; N, 3.09; S, 7.07. Found: C, 66.31; H, 5.86; N,
2.98; S, 7.05.
4.3.1. (2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)diphenylmetha-
nol 17a. Prepared as described in the general procedure
from aziridinemethanol 15a (2.39 g, 10.0 mmol) to afford
17a (3.74 g, 95%) as a crystalline mass. Mp 175 ꢁC;
20
1
½aꢀD ¼ þ22:1 (c 1.0, CHCl3); H NMR (CDCl3): d 1.28
(d, CH3, 3H, J = 5.7), 2.40 (s, CH3, 3H), 3.15 (m, C(3)H,
1H), 3.69 (d, C(2)H, 1H, J = 6.9), 7.12–7.57 (m, Ar,
14H); 13C NMR (CDCl3): d 12.5 (CH3), 21.9 (CH3), 40.5
(C-3), 52.4 (C-2), 74.7 (CHOH), 125.8 (2·, @CH), 126.1
(2·, @CH), 127.1 (1·, @CH), 127.7 (1·, @CH), 128.0
(2·, @CH), 128.4 (2·, @CH), 128.5 (2·, @CH), 129.9
(2·, @CH), 134.6 (·, @Cquat), 143.7 (1·, @Cquat), 144.7
(1·, @Cquat), 147.2 (1·, @Cquat); IR (mmax/cmꢁ1): 3473,
3088, 3059, 3027, 1597, 1495, 1448, 1315, 1152, 1053;
MS-ESI 392 m/z (Mꢁ1). Anal. Calcd for C23H23NO3S:
C, 70.20; H, 5.89; N, 3.56; S, 8.15. Found: C, 70.25; H,
5.88; N, 3.55; S, 8.10.
4.3.5. (2S)-(1-Tosylaziridin-2-yl)diphenylmethanol 18a.
Prepared as described in the general procedure from aziri-
dinemethanol 16a (2.25 g, 10.0 mmol) to afford 18a (3.68 g,
20
97%) as a solid. Mp 163–164 ꢁC; ½aꢀD ¼ ꢁ35:3 (c 1.0,
1
CHCl3); H NMR (CDCl3): d 2.41 (s, CH3, 3H), 2.54 (d,
4.3.2. (2S,3S)-(3-Methyl-1-tosylaziridin-2-yl)dibutylmetha-
nol 17b. Prepared as described in the general procedure
C(3)H2, 1H, J = 4.5), 2.61 (s, OH, 1H), 2.71 (d, C(3)H2,
1H, J = 6.9), 3.74 (m, C(2)H, 1H), 7.17–7.66 (m, Ar,
14H); 13C NMR (CDCl3): d 21.9 (CH3), 30.0 (C-3), 47.0
(C-2), 74.8 (CHOH), 126.3 (2·, @CH), 126.5 (2·, @CH),
127.6 (1·, @CH), 127.9 (1·, @CH), 128.1 (2·, @CH),
128.5 (2·, @CH), 128.6 (2·, @CH), 129.9 (2·, @CH),
134.6 (·, @Cquat), 143.4 (1·, @Cquat), 144.8 (1·,
@Cquat), 145.1 (1·, @Cquat); IR (mmax/cmꢁ1): 3463,
3025, 1596, 1494, 1447, 1336, 1319, 1186, 1161, 1094,
from aziridinemethanol 15b (1.99 g, 10.0 mmol) to afford
20
17b (3.39 g, 96%) as a solid. Mp 95–96 ꢁC; ½aꢀD ¼ ꢁ5:2 (c
1.0, CHCl3); 1H NMR (CDCl3): d 0.83–0.91 (m, CH3,
6H), 1.15–1.63 (m, (CH2,CH3), 15H), 2.44 (s, CH3, 3H),
2.70 (d, C(3)H, 1H, J = 7.5), 2.88 (m, C(2)H, 1H), 7.33
(d, Ar, 2H, J = 7.5), 7.81 (d, Ar, 2H, J = 8.1); 13C NMR
(CDCl3): d 13.0 (CH3), 14.1 (CH3), 14.2 (CH3), 21.8

F. Xichun et al. / Tetrahedron: Asymmetry 17 (2006) 1394–1401
1399
1002, 983, 922, 901; MS-ESI 378 m/z (Mꢁ1). Anal. Calcd
for C22H21NO3S: C, 69.63; H, 5.58; N, 3.69; S, 8.45.
Found: C, 69.72; H, 5.54; N, 3.65; S, 8.36.
CH, 1H), 3.32 (d, C(3)H, 1H, J = 8.7), 4.81 (d, NH, 1H,
J = 5.1), 7.04–7.70 (m, Ar, 14H); 13C NMR (CDCl3): d
18.4 (CH3), 21.8 (CH3), 50.0 (C(NH)), 67.6 (C-3), 67.7
(C-2), 127.5 (4·, @CH), 127.7 (1·, @CH), 128.1 (1·,
@CH), 128.4 (2·, @CH), 128.5 (2·, @CH), 128.6 (2·,
@CH), 129.8 (2·, @CH), 136.4 (·, @Cquat), 137.2 (1·,
@Cquat), 139.7 (1·, @Cquat), 143.5 (1·, @Cquat); IR
(mmax/cmꢁ1): 3471, 3293, 3059, 3029, 1599, 1493, 1446,
1332, 1151, 1090; MS-ESI 392 m/z (Mꢁ1). Anal. Calcd
for C23H23NO3S: C, 70.20; H, 5.89; N, 3.56; S, 8.15.
Found: C, 70.10; H, 5.76; N, 3.60; S, 8.11.
4.3.6. (2S)-(1-Tosylaziridin-2-yl)dibutylmethanol 18b. Pre-
pared as described in the general procedure from aziridine-
methanol 16b (1.85 g, 10.0 mmol) to afford 18b (2.95 g,
20
87%) as a solid. Mp 100–101 ꢁC; ½aꢀD ¼ ꢁ24:1 (c 1.0,
1
CHCl3); H NMR (CDCl3): d 0.82 (m, CH3, 3H), 0.90
(m, CH3, 3H), 1.13–1.63 (m, CH2, 12H), 2.42 (m,
C(3)H2, 1H), 2.45 (s, CH3, 3H), 2.60 (d, C(3)H2, 1H,
J = 6.0), 2.82 (m, C(2)H, 1H), 7.35 (d, Ar, 2H, J = 8.1),
7.83 (d, Ar, 2H, J = 8.4); 13C NMR (CDCl3): d 14.3
(CH3), 14.4 (CH3), 22.0 (CH3), 23.4 (CH2), 23.6 (CH2),
25.6 (2·, CH2), 30.6 (C-3), 36.1 (CH2), 40.0 (CH2), 46.3
(C-2), 70.9 (CHOH), 128.4 (2·, @CH), 130.0 (2·, @CH),
134.9 (1·, @Cquat), 145.0 (1·, @Cquat); IR (mmax/cmꢁ1):
3486, 2949, 2866, 1597, 1465, 1360, 1332, 1304, 1288,
1242, 1157, 1136, 1085, 1035, 966; MS-ESI 338 m/z
(Mꢁ1). Anal. Calcd for C18H29NO3S: C, 63.68; H, 8.61;
N, 4.13; S, 9.44. Found: C, 63.52; H, 8.78; N, 4.18; S, 9.39.
4.4.2. (2R,3S)-N-(1-(3,3-Dibutyloxiran-2-yl)ethyl)-4-methyl-
benzenesulfonamide 19b. Prepared as described in the
general procedure from 17b (0.88 g, 2.5 mmol) for 8 h to
20
afford 19b (0.76 g, 86%) as a solid. Mp 50 ꢁC; ½aꢀD ¼ þ36:2
1
(c 0.5, CHCl3); H NMR (CDCl3): d 0.83–0.88 (m, CH3,
6H), 1.16–1.65 (m, (CH2,CH3) 15H), 2.41 (s, CH3, 3H),
2.54 (d, CH, 1H, J = 4.2), 3.05 (m, C(3)H, 1H), 7.29 (d,
Ar, 2H, J = 4.2), 7.77 (d, Ar, 2H, J = 3.9); 13C NMR
(CDCl3): d 14.1 (CH3), 14.2 (CH3), 19.6 (CH3), 21.7 (CH3),
22.9 (CH2), 23.0 (CH2), 27.2 (CH2), 27.3 (CH2), 29.9
(CH2), 30.5 (CH3), 35.0 (CH(NH)), 49.5 (C-3), 65.6 (C-2),
127.6 (2·, @CH), 129.7 (2·, @CH), 137.4 (1·, @Cquat),
143.5 (1·, @Cquat); IR (mmax/cmꢁ1): 3298, 3029, 2957,
2860, 1600, 1496, 1467, 1417, 1376, 1351, 1325, 1309, 1167,
1090, 1044, 982, 947; MS-ESI 352 m/z (Mꢁ1). Anal. Calcd
for C19H31NO3S: C, 64.55; H, 8.84; N, 3.96; S, 9.07. Found:
C, 64.56; H, 8.79; N, 3.98; S, 9.01.
4.3.7. (2S)-(1-Tosylaziridin-2-yl)dibenzylmethanol 18c.
Prepared as described in the general procedure from aziri-
dinemethanol 16c (2.53 g, 10.0 mmol) to afford 18c (3.71 g,
20
91%) as a solid. Mp 106–107 ꢁC; ½aꢀD ¼ ꢁ47:4 (c 1.0,
CHCl3); 1H NMR (CDCl3): d 2.42 (s, CH3, 3H), 2.81
(dd, CH2(Bn), 2H), 2.94 (dd, CH2(Bn), 2H), 2.90 (m,
C(3)H2, 1H), 3.45 (m, C(3)H2, 2H), 3.63 (m, C(2)H, 1H),
4.94 (s, NH, 1H), 7.11–7.81 (m, Ar, 14H); 13C NMR
(CDCl3): d 21.6 (CH3), 43.8 (CH2), 44.9 (CH2), 47.7 (C-
3), 59.2 (C-2), 75.2 (CHOH), 126.s (1·, @CH), 127.1 (1·,
@CH), 128.0 (2·, @CH), 128.3 (2·, @CH), 128.6 (2·,
@CH), 129.6 (2·, @CH), 130.6 (2·, @CH), 130.8 (2·,
@CH), 134.8 (·, @Cquat), 135.7 (1·, @Cquat), 136.1 (1·,
@Cquat), 144.8 (1·, @Cquat); IR (mmax/cmꢁ1): 3486,
3257, 3086, 3062, 3028, 2944, 2921, 1736, 1597, 1496,
1454, 1368, 1318, 1229, 1157, 1117, 1093, 968, 938; MS-
ESI 406 m/z (Mꢁ1). Anal. Calcd for C24H25NO3S: C,
70.73; H, 6.18; N, 3.44; S, 7.87. Found: C, 70.72; H, 6.38;
N, 3.43; S, 7.83.
4.4.3. (2R,3S)-N-(1-(3,3-Dibenzyloxiran-2-yl)ethyl)-4-methyl-
benzenesulfonamide 19c. Prepared as described in the
general procedure from 17c (1.05 g, 2.5 mmol) for 2 h to
afford 19c (0.95 g, 90%) as a solid. Mp 130–131 ꢁC;
20
1
½aꢀD ¼ ꢁ28:9 (c 1.0, CHCl3); H NMR (CDCl3): d 1.29
(d, CH3, 3H, J = 6.6), 2.37 (s, CH3, 3H), 2.43 (s, CH,
1H), 2.53 (dd, CH2(Bn), 2H), 2.79 (dd, CH2(Bn), 2H),
3.27 (m, C(3)H, 1H), 4.87 (s, NH, 1H), 7.02–7.81 (m, Ar,
14H); 13C NMR (CDCl3): d 19.6 (CH3), 21.7 (CH3), 36.1
(CH2), 40.9 (CH2), 49.7 (C(NH)), 64.7 (C-3), 65.6 (C-2),
127.0 (1·, @CH), 127.1 (1·, @CH), 127.6 (2·, @CH),
128.6 (2·, @CH), 128.7 (2·, @CH), 129.7 (2·, @CH),
129.8 (4·, @CH), 136.4 (·, @Cquat), 136.6 (1·, @Cquat),
137.4 (1·, @Cquat), 143.7 (1·, @Cquat); IR (mmax/cmꢁ1):
3301, 3063, 3028, 2925, 1604, 1495, 1456, 1438, 1318,
1302, 1155, 1093, 1062, 1002, 802; MS-ESI 420 m/z
(Mꢁ1). Anal. Calcd for C25H27NO3S: C, 71.23; H, 6.46;
N, 3.32; S, 7.61. Found: C, 71.25; H, 6.58; N, 3.28; S, 7.65.
4.4. General procedure for aza-Payne rearrangement with
NaOH in a mixture of BuOH–H2O–THF
t
To a stirred solution a 10 mL of 0.28 M NaOH in a mix-
t
ture of BuOH–H2O–THF (4:5:1) was added 17 or 18
(2.5 mmol) at room temperature, and then stirring was
continued for several hours. The reaction was quenched
with 20 mL of water at 0 ꢁC with stirring. The mixture
was extracted with diethyl ether and the extract washed
successively with saturated citric acid, brine, 5% NaHCO3,
and brine, and dried over MgSO4. The usual workup fol-
lowed by flash chromatography over silica gel with petro-
leum ether–ethyl acetate (5:1) to yield 19 or 20.
4.4.4. (2R,3S)-N-(1-(3,3-Bis(4-methoxyphenyl)oxiran-2-yl)-
as
ethyl)-4-methylbenzenesulfonamide
19d. Prepared
described in the general procedure from 17d (1.13 g,
2.5 mmol) for 24 h to afford 19d (1.10 g, 97%) as a solid.
20
Mp 65–66 ꢁC; ½aꢀD ¼ ꢁ26:2 (c 1.0, CHCl3); 1H NMR
(CDCl3): d 1.43 (d, CH3, 3H, J = 6.3), 2.44 (s, CH3, 3H),
3.77 (s, OCH3, 3H), 3.80 (s, OCH3, 3H), 3.89 (m, C(3)H,
1H), 4.80 (m, CH(NH), 1H), 6.70–7.42 (m, Ar, 12H); 13C
NMR (CDCl3): d 14.3 (CH3), 21.5 (CH3), 48.9 (C-3),
54.3 (C-2), 55.2 (CH3O), 55.5 (CH3O), 76.2 (CHOH),
113.2 (2·, @CH), 113.5 (2·, @CH), 126.3 (2·, @CH),
127.2 (2·, @CH), 127.8 (2·, @CH), 129.6 (2·, @CH),
143.1 (1·, @Cquat), 143.4 (1·, @Cquat), 146.0 (·,
4.4.1. (2R,3S)-N-(1-(3,3-Diphenyloxiran-2-yl)ethyl)-4-methyl-
benzenesulfonamide 19a. Prepared as described in the
general procedure from 17a (0.98 g, 2.5 mmol) for 1 h to
afford 19a (0.94 g, 96%) as a crystalline mass. Mp 179–
20
1
180 ꢁC; ½aꢀD ¼ þ130:7 (c 1.0, CHCl3); H NMR (CDCl3):
d 1.20 (d, CH3, 3H, J = 6.6), 2.46 (s, CH3, 3H), 2.67 (m,

1400
F. Xichun et al. / Tetrahedron: Asymmetry 17 (2006) 1394–1401
@Cquat), 158.4 (1·, @Cquat), 159.7 (1·, @Cquat), 162.9
(1·, @Cquat); IR (mmax/cmꢁ1): 3478, 3304, 3025, 2964,
2836, 1611, 1581, 1513, 1461, 1330, 1301, 1250, 1183,
1150, 1089, 1027; MS-ESI 452 m/z (Mꢁ1). Anal. Calcd
for C25H27NO5S: C, 66.20; H, 6.00; N, 3.09; S, 7.07.
Found: C, 66.25; H, 5.94; N, 3.01; S, 6.98.
4.5. General procedure for the synthesis of 21 and 22
To a stirred solution of aziridinemethanol 15 or 16
(10.0 mmol) and NEt3 (2.78 mL 20.0 mmol) in THF
(20 mL) was gradually added (Boc)2O (2.62 g, 12.0 mmol)
in THF (5 mL) at 0 ꢁC, and then the mixture was allowed
to warm to rt and the stirring was continued for 24 h. To
the mixture was added ethyl acetate and washed succes-
sively with saturated citric acid, brine, 5% NaHCO3, and
brine, and dried over MgSO4. The usual workup followed
by flash chromatography over silica gel with petroleum
ether–ethyl acetate (5:1) to yield 21 (or 22).
4.4.5. (2R)-N-((3,3-Diphenyloxiran-2-yl)methyl)-4-methyl-
benzenesulfonamide 20a. Prepared as described in the gen-
eral procedure from 18a (0.95 g, 2.5 mmol) for 1 h to afford
20
20a (0.90 g, 95%) as a solid. Mp 114–115 ꢁC; ½aꢀD ¼ þ84:3
1
(c 1.0, CHCl3); H NMR (CDCl3): d 2.39 (s, CH3, 3H),
2.82 (m, CH2, 1H), 3.02 (m, CH2, 1H), 3.58 (m, C(2)H,
1H), 7.12–7.64 (m, Ar, 14H); 13C NMR (CDCl3): d 21.8
(CH3), 44.6 (C(NH)), 47.0 (C-3), 73.7 (C-2), 125.4 (2·,
@CH), 125.6 (2·, @CH), 126.3 (1·, @CH), 1265 (1·,
@CH), 128.4 (2·, @CH), 128.5 (2·, @CH), 128.8 (2·,
@CH), 129.9 (2·, @CH), 136.3 (·, @Cquat), 137.5 (1·,
@Cquat), 139.9 (1·, @Cquat), 143.8 (1·, @Cquat); IR
(mmax/cmꢁ1): 3463, 3265, 3062, 1597, 1496, 1461, 1422,
1343, 1328, 1164, 1091, 1049; MS-ESI 378 m/z (Mꢁ1).
Anal. Calcd for C22H21NO3S: C, 69.63; H, 5.58; N, 3.69;
S, 8.45. Found: C, 69.68; H, 5.60; N, 3.71; S, 8.42.
4.5.1. (2S,3S)-tert-Butyl 2-(hydroxydiphenylmethyl)-3-meth-
ylaziridine-1-carboxylate 21a. Prepared as described in
the general procedure from 15a (2.39 g, 10.0 mmol) to
afford 21a (3.22 g, 95%) as a solid. Mp 141–142 ꢁC;
20
1
½aꢀD ¼ ꢁ1:5 (c 1.0, CHCl3); H NMR (CDCl3): d 1.21 (d,
CH3, 3H, J = 6.0), 1.40 (s, (CH3)3C, 9H), 2.65 (m,
C(3)H, 1H), 3.34 (d, C(2)H, 1H, J = 6.6), 3.36 (s, OH,
1H), 7.19–7.52 (m, Ar, 10H); 13C NMR (CDCl3): d 13.4
(CH3), 28.2 (3·, (CH3)3C)) 38.8 (C-3), 49.4 (C-2), 74.9
(CHOH), 82.0 (C), 126.4 (2·, @CH), 126.7 (2·, @CH),
127.3 (2·, @CH), 128.2 (4·, @CH), 144.2 (1·, @Cquat),
148.1 (1·, @Cquat), 162.5 (C@O); IR (mmax/cmꢁ1): 3486,
3026, 3003, 1720, 1494, 1449, 1391, 1296, 1247, 1152,
1006; MS-ESI 338 m/z (Mꢁ1). Anal. Calcd for
C21H25NO3: C, 74.31; H, 7.42; N, 4.13. Found: C, 74.30;
H, 7.38; N, 4.07.
4.4.6.
(2R)-N-((3,3-Dibutyloxiran-2-yl)methyl)-4-methyl-
benzenesulfonamide 20b. Prepared as described in the
general procedure from 18b (0.85 g, 2.5 mmol) for 8 h to
afford 20b (0.70 g, 83%) as a solid. Mp 57–58 ꢁC;
20
1
½aꢀD ¼ þ37:4 (c 0.5, CHCl3); H NMR (CDCl3): d 0.87–
0.89 (m, CH3, 6H), 1.26–1.59 (m, CH2, 12H), 2.43 (s,
CH3, 3H), 2.81 (d, CH2(NHTs), 1H, J = 2.1), 2.96 (m,
CH2(NHTs), 1H), 3.31 (m, C(3)H, 1H), 4.63 (d, NH,
1H), 7.33 (s, Ar, 2H), 7.77 (s, Ar, 2H); 13C NMR (CDCl3):
d 14.1 (CH3), 14.2 (CH3), 21.7 (CH3), 22.9 (CH2), 23.1
(CH2), 26.9 (CH2), 27.5 (C-3), 30.2 (CH2), 34.7 (CH2),
42.7 (CH(NH)), 60.9 (C-3), 64.6 (C-2), 127.3 (2·, @CH),
130.0 (2·, @CH), 137.0 (1·, @Cquat), 143.9 (1·, @Cquat);
IR (mmax/cmꢁ1): 3295, 3028, 2958, 2933, 2867, 1597, 1465,
1436, 1330, 1304, 1288, 1158, 1091, 1073, 1051, 884; MS-
ESI 338 m/z (Mꢁ1). Anal. Calcd for C18H29NO3S: C,
63.68; H, 8.61; N, 4.13; S, 9.44. Found: C, 63.62; H, 8.70;
N, 4.08; S, 9.43.
4.5.2. (2S,3S)-tert-Butyl 2-(hydroxybis(4-methoxyphenyl))-
3-methylaziridine-1-carboxylate 21d. Prepared as de-
scribed in the general procedure from 15d (2.99 g,
10.0 mmol) to afford 21d (3.76 g, 94%) as a solid. Mp
20
146–148 ꢁC; ½aꢀD ¼ ꢁ9:8 (c 0.5, CHCl3); 1H NMR
(CDCl3): d 1.22 (d, CH3, 3H, J = 5.4), 1.42 (s, (CH3)3C,
9H), 2.60 (m, C(3)H, 1H), 3.25 (d, C(2)H, 1H, J = 6.3),
3.76 (s, OCH3, 3H), 3.79 (s, OCH3, 3H), 6.78–7.41 (m,
Ar, 8H); IR (mmax/cmꢁ1): 3509, 3009, 2980, 2956, 2834,
1708, 1609, 1585, 1509, 1466, 1439, 1421, 1369, 1303,
1254, 1170, 1151, 1040, 1012; MS-ESI 398 m/z (Mꢁ1).
Anal. Calcd for C23H29NO5: C, 69.15; H, 7.32; N, 3.51.
Found: C, 69.23; H, 7.28; N, 3.69.
4.4.7. (2R)-N-((3,3-Dibenzyloxiran-2-yl)methyl)-4-methyl-
benzenesulfonamide 20c. Prepared as described in the gen-
eral procedure from 18c (1.02 g, 2.5 mmol) for 10 h to
afford 20c (0.91 g, 89%) as a solid. Mp 105–106 ꢁC;
4.6. General procedure for aza-Payne rearrangement with
NaH in a mixture of HMPA–THF
20
1
½aꢀD ¼ þ40:5 (c 1.0, CHCl3); H NMR (CDCl3): d 2.42
(s, CH3, 3H), 2.43 (s, CH, 1H), 2.68 (dd, CH2(Bn), 2H),
2.78 (dd, CH2(Bn), 2H), 2.95 (m, C(3)H2, 1H), 3.11 (m,
C(3)H2, 1H), 3.42 (m, C(2)H, 1H), 4.87 (s, NH, 1H),
7.04–7.75 (m, Ar, 14H); 13C NMR (CDCl3): d 21.8
(CH3), 36.7 (CH2), 40.7 (CH2), 42.9 (C(NH)), 60.0 (C-3),
64.5 (C-2), 127.0 (1·, @CH), 127.1 (1·, @CH), 127.3 (2·,
@CH), 128.6 (2·, @CH), 128.9 (2·, @CH), 129.5 (2·,
@CH), 130.0 (2·, @CH), 130.1 (2·, @CH), 136.1 (·,
@Cquat), 136.7 (1·, @Cquat), 136.9 (1·, @Cquat), 143.9
(1·, @Cquat); IR (mmax/cmꢁ1): 3290, 3085, 3061, 3028,
2924, 1601, 1496, 1453, 1437, 1332, 1320, 1306, 1149,
1094, 1065, 1041, 945; MS-ESI 406 m/z (Mꢁ1). Anal.
Calcd for C24H25NO3S: C, 70.73; H, 6.18; N, 3.44; S,
7.87. Found: C, 70.69; H, 6.25; N, 3.41; S, 7.73.
To a stirred suspension of NaH (24 mg, 1 mmol) in a mix-
ture of THF (2 mL) and HMPA (0.33 mL) at ꢁ30 ꢁC
under nitrogen was added 21 (0.25 mmol) in THF
(2 mL), and then the mixture allowed to warm to rt and
the stirring continued for 4 h. The reaction was quenched
with 2 mL of 5% citric acid at ꢁ30 ꢁC with stirring. The
mixture was extracted with diethyl ether and the extract
was washed successively with saturated citric acid (3 ·
50 mL), brine (3 · 50 mL), 5% NaHCO3 (3 · 50 mL), and
brine (3 · 50 mL), and dried over MgSO4. The usual work-
up followed by flash chromatography over silica gel with
petroleum ether–ethyl acetate (5:1) to yield 23 as a crystal-
line mass.

F. Xichun et al. / Tetrahedron: Asymmetry 17 (2006) 1394–1401
1401
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4.6.1. (2R,3S)-tert-Butyl 1-(3,3-diphenyloxiran)-2-yl)ethyl-
carbamate 23a. Prepared as described in the general proce-
dure from 21a (84.9 mg, 0.25 mmol) to afford 23a (81.5 mg,
20
96%) as a solid. Mp 103–104 ꢁC; ½aꢀD ¼ þ78:0 (c 1.0,
1
CHCl3); H NMR (CDCl3): d 1.18 (d, CH3, 3H, J = 6.0),
1.39 (s, (CH3)3C, 9H), 3.28 (m, C(3)H, 1H), 3.38
(d, C(2)H, 1H), 7.26–7.43 (m, Ar, 10H); 13C NMR (CDCl3):
d 18.4 (CH3), 28.6 (3·, (CH3)3C)) 46.5 (CH(NH)), 66.6
(C-3), 68.4 (C-2), 82.0 (C), 127.4 (1·, @CH), 127.7 (1·,
@CH), 128.1 (2·, @CH), 128.2 (2·, @CH), 128.5 (2·,
@CH), 128.6 (2·, @CH), 136.9 (1·, @Cquat), 140.6 (1·,
@Cquat), 155.2 (C@O); IR (mmax/cmꢁ1): 3434, 2976,
1716, 1497, 1448, 1394, 1370, 1291, 1230, 1163, 1050,
1027, 942; MS-ESI 338 m/z (Mꢁ1). Anal. Calcd for
C21H25NO3: C, 74.31; H, 7.42; N, 4.13. Found: C, 74.28;
H, 7.45; N, 4.05.
4.6.2. (2R,3S)-tert-Butyl 1-(3,3-bis(4-methoxyphenyl)oxi-
ran)-2-yl)ethylcarbamate 23d. Prepared as described in
the general procedure from 21d (100 mg, 0.25 mmol) to
4. (a) Behrens, C. H.; Ko, S. Y.; Sharpless, K. B.; Walker, F. J.
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1375.
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A.; Tamamura, H.; Fujii, N. J. Org. Chem. 1995, 60,
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154.
6. Bouyacoub, A.; Volatron, F. Eur. J. Org. Chem. 2002, 24,
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7. Najime, R.; Pilard, S.; Vaultier, M. Tetrahedron Lett. 1992,
33, 5351–5354.
20
afford 23d (80 mg, 80%) as a liquid. Mp 40 ꢁC; ½aꢀD ¼ þ20:0
1
(c 0.6, CHCl3); H NMR (CDCl3): d 1.12 (d, CH3, 3H,
J = 5.7), 1.38 (s, (CH3)3C, 9H), 2.61 (m, CH, 1H), 3.32
(d, C(2)H, 1H, J = 6.3), 3.71 (s, OCH3, 3H), 3.74 (s,
OCH3, 3H), 6.76–7.28 (m, Ar, 8H); IR (mmax/cmꢁ1): 3369,
2958, 2956, 2854, 1711, 1611, 1583, 1514, 1461, 1366,
1298, 1247, 1172, 1032, 833; MS-ESI 398 m/z (Mꢁ1). Anal.
Calcd for C23H29NO5: C, 69.15; H, 7.32; N, 3.51. Found:
C, 69.13; H, 7.26; N, 3.50.
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