A mild and regioselective ring-opening of aziridines with acid anhydride using TBD or PS-TBD as a catalyst

Article abstract of DOI:10.3390/molecules201018482

The ring-opening of N-tosylaziridines with various acid anhydrides catalyzed by 5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) afforded the corresponding β-amino esters in excellent yields under mild reaction conditions. Polymer-supported catalyst,

Full text of DOI:10.3390/molecules201018482

Molecules 2015, 20, 18482-18495; doi:10.3390/molecules201018482
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
A Mild and Regioselective Ring-Opening of Aziridines with Acid
Anhydride Using TBD or PS-TBD as a Catalyst
Satoru Matsukawa * and Yasutaka Mouri
Department of Science Education, Faculty of Education, Ibaraki University, Ibaraki 310-8512, Japan;
E-Mail: c32amg777@yahoo.co.jp
* Author to whom correspondence should be addressed; E-Mail: satoru.matsukawa.1@vc.ibaraki.ac.jp;
Tel.: +81-29-228-8234; Fax: +81-29-228-8329.
Academic Editor: Choon-Hong Tan
Received: 2 September 2015 / Accepted: 23 September 2015 / Published: 9 October 2015
Abstract: The ring-opening of N-tosylaziridines with various acid anhydrides catalyzed by
5 mol % of 1,5,7-triazabicyclo[4,4,0]dec-5-ene (TBD) afforded the corresponding β-amino
esters in excellent yields under mild reaction conditions. Polymer-supported catalyst,
PS-TBD also acts as a good catalyst for this reaction. PS-TBD was easily recovered and
reused with minimal loss of activity.
Keywords: organocatalyst; basecatalyst; polymercatalyst; guanidine; aziridine; amino alcohols
1. Introduction
Aziridines are very useful intermediates for the synthesis of numerous nitrogen-containing biologically
active compounds [1–3]. Therefore, nucleophilic ring-opening of aziridines by various approaches has
been widely examined and developed [4–10]. β-amino alcohols, which can be synthesized from the
nucleophilic ring-opening reactions of aziridines are useful intermediates in organic synthesis [4,7].
The ring-opening of aziridines with water is the most common method to prepare free β-amino alcohols.
Many examples are reported to this day [11–22]. On the other hand, selectively protected β-amino alcohols
are convenient intermediate to synthesize highly functionalized products. Therefore, the ring-opening
reaction of aziridines with acid or acid anhydrides as the nucleophiles have been recently studied.
To date, reactions using indium rtiflate [23], tributylphosphine [24], scandium triflate [25], ammonium-
12-molybdophosphate [26], N-heterocyclic carbine [27] and tetrabutyl ammonium bromide [28] as

Molecules 2015, 20
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catalysts have been reported. To develop of a more efficient reaction, we examined the use of TBD
(1,5,7-Triazabicyclo[4,4,0]dec-5-ene) as a catalyst.
TBD is known as a superbase due to the high pKa of its conjugate acid [29,30]. Many unique
reactions have been reported using TBD as an organocatalyst, such as the Henry reaction [31], Wittig
and Horner-Wadsworth-Emmons reaction [32], Michael reaction [33], ring-opening polymerization [34],
conjugate addition to activated alkenes [35], aminolysis of esters [36,37], intramolecular aldol
reaction [38], and synthesis of pyrazolines [39], etc. [40–43]. Mechanistic studies of these reactions
also have been discussed [44–47]. In some cases, it is considered that TBD acts as an acid-base
bifunctional catalyst. Recently, we have also reported the trifluoromethylataion of aldehydes [48], and
the ring-opening of aziridines with TMSCN [49] catalyzed by TBD as an organocatalyst. Herein, we
report that TBD acts as an effective organobase catalyst for the ring-opening reaction of aziridines with
acid anhydride.
2. Results and Discussion
Initially, the ring-opening reaction of N-tosylaziridine 1a with acetic anhydride was examined. The
reaction was carried out by adding the 1a and acetic anhydride in the presence of 5 mol % of TBD in
DMF at 50 °C. The reaction was monitored by TLC. Hydrolytic work up with saturated NH4Cl at room
temperature followed by flash column chromatography afforded the ring-opened products. The product
was obtained at 78% yield in 24 h along with 18% of the starting material. Although the reaction was
performed for 48 h, the starting material did not disappear. Then the reaction was examined at elevated
temperature (80 °C), and the reaction proceeded smoothly. The desired product was obtained at 94%
yield in 4 h (Table 1, entry 2). This reaction also proceeded smoothly when 2 mol % of TBD was used
(Table 1, entry 3). Among the screened solvents, DMF has proved to be the most effective for this reaction
(Table 1, entries 1 vs. 4–6). The product was obtained in lower yield when other bases, such as DBU,
TMG, TTMPP and DMAP (Figure 1) were used instead of TBD (Table 1, entries 1 vs. 7–10). An
approximately comparable yield was observed when MTBD was used as a catalyst (Table 1, entry 11).
N
N
N
N
N
N
N
H
N
CH
3
(TBD)
(MTBD)
(DBU)
OMe
NH
N
N
MeO
P
N
N
OMe
3
(TTMPP)
(DMAP)
(TMG)
Figure 1. Various bases.

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Table 1. Optimization of the reaction conditions.
NHTs
OCOCH
Catalyst
NTs
H
3
(5 mol%)
+ (CH CO) O
3
2
H
solvent
80 °C, 4 h
1a
2a
Entry
Catalyst
Solvent
DMF a,b
DMF
Yield (%)
1
2
TBD
78
94
90
45
10
71
55
33
34
61
80
3
DMF c
THF b,d
MeCN b,e
toluene b
DMF b
DMF b
DMF b
DMF
4
5
6
7
DBU
TMG
8
9
DMAP
TTMPP
MTBD
10
11
DMF b
a
b
c
d
e
at room temperature. in 24 h. 2 mol % of TBD was used. at 66 °C (reflux condition). at 82 °C
(reflux condition).
To clarify the scope of this reaction, several N-tosylaziridines and acid anhydrides were examined in the
presence of 5 mol % TBD. In all cases, reactions were very clean and the desired products were afforded
in good to excellent yields. Almost complete regioselectivity was observed when using alkyl-N-tosyl
aziridines as substrates, and reaction on the less-substituted aziridine carbon was observed (Table 2,
entries 7–10). For aryl-N-tosyl aziridines, in the case of a Lewis acid catalyzed reaction, selectivity
demonstrated an opposite trend with alkyl-N-tosyl aziridines due to an electronic effect. Thus, the attack
of the nucleophile at the benzylic position of aziridine occurred. However, in this Lewis base catalyzed
reaction, the selectivity demonstrated the same trend: the reaction occurred on the less-substituted
aziridine carbon (Table 2, entries 11–14). Reaction of propionic anhydride and benzoic anhydride also
proceeded smoothly to afford the corresponding β-amino acetals in high yield. When propionic anhydride
was used, regioselectivity was slightly higher than the reaction using acetic anhydride. In addition,
cycloalkyl-N-tosyl aziridines also worked well. Unfortunately, no reaction occurred when non-acitivated
aziridine such as N-benzylcyclohexylaziridine was employed.
Furthermore, we applied a polymer-supported TBD, PS-TBD [50–53] to this reaction.
Polymer-supported catalysts have attracted significant attention in recent decades due to their inherent
advantages in synthetic chemistry, e.g., simplification of reaction procedures including easy recovery
of the catalyst by filtration, application to automated systems, and recycling of the catalyst [54–59]. Some
unique reactions have been reported using TBD as an organocatalyst [31,60–65]. Thus, we examined
the ring-opening reaction of N-tosylaziridine 1a with acetic anhydride in the presence of 10 mol % of
PS-TBD. As shown in Table 3, the reaction proceeded smoothly and the desired product was obtained
at 85% yield in 10 h at 80 °C in DMF. A variety of N-tosylaziridines reacted well with acetic
anhydrides to give β-amino acetates. The reaction also occurred on the less substituted aziridine carbon
regardless of the type of aziridine. In addition, the recovery and reuse of PS-TBD for the reaction of

Molecules 2015, 20
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N-tosylaziridine 1a with acetic anhydrides also examined. After the reaction was completed, ethyl
acetate was added to the reaction mixture and the catalyst was recovered by filtration. The recovered
catalyst was washed, dried and then reused. The catalyst was reused, maintaining its catalytic activity
after 4 uses (Table 3, entries 1–4).
Table 2. TBD catalyzed ring-opening of various aziridines with acid anhydrides.
TBD
(5 mol%)
TsNH
H
H
RCOO
H
OCOR
H
NTs
NHTs
H
+
H
(RCO) O
R
R
2
1
1
R
1
DMF
R
2
R
R
2
2
80 °C, time
1a - f
3c - f
Yield (%) a
2a - f
Product
Entry
Aziridine
R
Time
NTs
H
OCOCH3
1
CH3
4 h
94
89
91
H
2a
NTs
NTs
H
OCOC2H5
2
3
C2H5 4 h
C6H5 8 h
H
2aʹ
1a
NTs
H
OCOPh
H
2aʹʹ
NTs
NTs
H
4 b
5
CH3 12 h
C2H5 18 h
OCOCH3
H
85
83
NTs
2b
H
1b
OCOC2H5
H
2bʹ
NTs
OCOCH32c
6
7
8
CH3
4 h
86
87
88
n-C4H9
n-C4H9
NTs
NTs
n-C4H9
OCOC2H52cʹ
C2H5 6 h
C6H5 12 h
NTs
1c
OCOPh
n-C4H9
H5C6
2cʹʹ
NTs
NTs
NTs
NTs
9
CH3
C2H5 8 h
CH3 1 h
C2H5 4 h
CH3 1 h
C2H5 4 h
4 h
92
98
OCOCH3
H5C6
2d
1d
1e
10
H5C6
OCOC2H5
2dʹ
NTs
NTs
11
OCOCH3
OCOC2H5
97 b
H5C6
H5C6
2e
H5C6
12
13
14
95 c
98 d
96 e
2eʹ
NTs
NTs
OCOCH
32f
p-CH3C6H4
p-CH3C6H4
NTs
1f
OCOC2H5
p-CH3C6H4
2fʹ
a
b
c
d
Isolated yield. Regioisomer ratio 2e:3e = 85:15. Regioisomer ratio 2eʹ:3eʹ = 94:6. Regioisomer ratio
2f:3f = 87:13. e Regioisomer ratio 2fʹ: 3fʹ = 90:10.

Molecules 2015, 20
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Table 3. PS-TBD catalyzed ring-opening of various aziridines with acetic anhydride.
N
N
N
PS-TBD
(10 mol%)
TsNH
H
H
OCOCH
H
NTs
3
+
(CH CO) O
R
H
R
3
2
1
1
DMF
R
2
R
2
80 °C, time
2a - f
1a - g
Entry
Aziridine
Product
Time Yield (%) a
NTs
1
2
3
10 h
10 h
10 h
85
NTs
H
88 b
80 c
OCOCH
3
H
82 d
2a
1a
4
10 h
NTs
NTs
H
OCOCH3
H
5
24 h
89
2b
1b
NTs
NTs
OCOCH3
n-C4H9
1c
6
7
8
16 h
4 h
78
92
86
n-C4H9
2c
NTs
NTs
NTs
H5C6
H5C6
OCOCH3
2d
NTs
1d
OCOCH3
H5C6
8 h
H5C6
1e
2e
NTs
NTs
OCOCH3
p-CH3C6H4
p-CH3C6H4
2f
9
8 h
80
1f
a Isolated yield. b 2nd run. c 3rd run. d 4th run.
A possible mechanism is illustrated in Scheme 1. First, TBD activated the anhydride to form
N+C(O)R, RC(O)O− intermediate A. Next, this intermediate immediately reacts with aziridines to give
the ring-opening product B. Finally, acylation occurs to give the N-acylated adduct with regeneration
of TBD.
In this transition state, a steric effect has greater priority over the electronic effect (Scheme 2).
Therefore, in this Lewis base catalyzed reaction, selectivity is not dependent on a substituent. The reaction
occurred on the less-substituted aziridine carbon even in the case of phenyl substituted aziridine 1e.

Molecules 2015, 20
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H
COR
TsN
TsN
+
H
OCOR
OCOR
R
1
R
1
(RCO) O
2
R
2
R
2
N
2
N
N
H
N
O
N
N
N +
R
H
N
H
N +
O
R
-
-
TsN
OCOR
OCOR
R
A
1
R
H
2
NTs
B
R
H
1
R
2
1
Scheme 1. Proposed mechanism.
L.A.
Ts
N
+
TsN
Ph
TBD-COCH
3
+
Ph
COCH
COCH
3
-
:
O
OCOCH
3
3
CH COO
TsN
Ph
3
NTs
OCOCH
3
Ph
3e
2e
Scheme 2. The origin of regioselectivity.
3. Experimental Section
3.1. General
All reactions were performed under an argon atmosphere using oven-dried glassware. Flash column
chromatography was performed using silica gel Wakogel C-200 (Wako Chemical, Osaka, Japan).
Preparative thin-layer chromatography was carried out on silica gel Wakogel B-5F (Wako Chemical).
Dehydrate DMF, THF, toluene and CH3CN were purchased from Wako Chemical. Other commercially
available reagent was used as received without further purification. The aziridines were prepared
according to literature procedure [66]. Yields refer to isolated compounds estimated to be >95% pure, as
1
determined by H-NMR spectroscopy. IR spectra were recorded on a JUSCO FT/IR-430 spectrometer
(JASCO Corporation, Tokyo, Japan). 1H- and 13C-NMR spectra were determined for solutions in CDCl3
with Me4Si as internal standard on a Bruker Avance III instrument (Bruker Corporation, Billerica, MA,
USA). HRMS data were measured on a JEOL JMS-700 mass spectrometer (JEOL Ltd., Tokyo, Japan).

Molecules 2015, 20
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3.2. Method
3.2.1. General Procedure for TBD-Catalyzed Ring-Opening of Aziridines with Acid Anhydride
To a solution of TBD (0.05 mmol) in DMF (1 mL) was added aziridine (1.0 mmol) and acid
anhydride (1.25 mmol) at room temperature. After the reaction was complete (as determinedby TLC),
the reaction mixture was washed with saturated NH4Cl and extracted with EtOAc (2 × 10 mL).
The combined organic layers were dried over Na2SO4, concentrated in vacuo and purified by column
chromatography on silica gel (EtOAc:hexane = 1:3) to give the corresponding product.
3.2.2. General Procedure for PS-TBD Catalyzed Ring-Opening of Aziridines with Acid Anhydride
To a solution of PS-TBD (0.10 mmol) in DMF (1 mL) was added aziridine (1.0 mmol) and acid
anhydride (1.25 mmol) at room temperature. After the reaction was complete (as determined by TLC),
EtOAc (5 mL) was added to the mixture and PS-TBD was separated by filtration. The filtrate was washed
with saturated NH4Cl, dried over Na2SO4. The organic layer was concentrated in vacuo and purified by
column chromatography on silica gel (EtOAc:hexane = 1:3) to give the corresponding product. The
recovered catalyst is reusable after washing (acetone and water) and drying in vacuo.
3.3. General Characterization of the Products
2-(4-Methylphenylsulfonamido)cyclohexyl acetate (2a) [23]. Colorless plate; m.p. 108–110 °C; yield:
1
294 mg (94%); IR (KBr): 3030, 2929, 2195, 1644, 1598, 1449, 823, 700 cm−1; H-NMR (500 Hz,
CDCl3) δ 1.16–1.32 (m, 4H), 1.57–1.61 (m, 1H), 1.62–1.66 (m, 1H), 1.74 (s, 3H), 1.85–1.89 (m, 1H),
1.96–2.00 (m, 1H), 2.38 (s, 3H), 3.12–3.18 (m, 1H), 4.53 (dt, J = 4.6, 10.4 Hz, 1H), 4.95 (d, J = 6.8 Hz,
13
1H), 7.25 (d, J = 8.0 Hz, 2H), 7.71 (d, J = 8.0 Hz, 2H); C-NMR (125 MHz, CDCl3) δ 20.9, 21.5,
23.6, 24.2, 31.1, 33.5, 56.9, 74.1, 126.9, 129.6, 138.7, 143.0, 171.4; HRMS (FAB): m/z: cald for
C15H22NO4S: 312.1270; found: 312.1280 [M + H]+.
2-(4-Methylphenylsulfonamido)cyclohexyl propionate (2aʹ) [23]. Colorless cube; m.p. 92–94 °C; yield:
1
289 mg (89%); IR (KBr): 3284, 2957, 1736, 1460, 1331, 1162, 1092, 815, 666 cm−1; H-NMR
(500 Hz, CDCl3) δ 1.02 (t, J = 7.5 Hz, 3H), 1.20–1.39 (m, 4H), 1.62–1.67 (m, 1H), 1.68–1.71 (m, 1H),
1.95–1.99 (m, 1H), 2.00–2.05 (m, 1H), 2.07 (q, J = 7.5 Hz, 2H), 2.42 (s, 3H), 3.19-3.24 (m, 1H), 4.59
(dq, J = 3.4, 10.4 Hz, 1H), 5.04 (d, J = 10.4 Hz, 1H), 7.29 (d, J = 8.6 Hz, 2H), 7.74 (d, J = 8.6 Hz, 2H);
13C-NMR (125 MHz, CDCl3) δ 8.8, 21.4, 23.6, 24.1, 27.4, 31.0, 33.3, 56.9, 73.8, 126.8, 129.5, 138.7,
142.9, 174.8; HRMS (FAB): m/z: cald for C16H24NO4S: 326.1426; found: 326.1410 [M + H]+.
2-(4-Methylphenylsulfonamido)-1-phenylcarbonyloxyclohexane (2aʹʹ) [24]. White solid; m.p. 128–130 °C;
yield: 340 mg (91%); IR (KBr): 3321, 2926, 1786, 1702, 1598, 1450, 1320, 1212, 1155, 1014, 715,
1
666 cm−1; H-NMR (500 Hz, CDCl3) δ 1.20–1.28 (m, 2H), 1.27–1.42 (m, 2H), 1.64–1.66 (m, 1H),
1.67–1.71 (m, 1H), 1.95–2.01 (m, 1H), 2.10–2.17 (m, 1H), 2.15 (s, 3H), 3.26–3.32 (m, 1H), 4.79 (dt,
J = 4.7, 10.7 Hz, 1H), 5.16 (d, J = 7.4 Hz, 1H), 6.88 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.50
(d, J = 6.4 Hz, 1H), 7.55 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 7.0 Hz, 2H); 13C-NMR (125 MHz, CDCl3) δ

Molecules 2015, 20
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21.2, 23.6, 24.1, 31.1, 33.8, 57.1, 74.5, 126.4, 128.0, 128.8, 129.3, 129.6, 130.4, 132.8, 138.0, 142.5,
166.6; HRMS (FAB): m/z: cald for C20H24NO4S: 374.1426; found: 374.1420 [M + H]+.
2-(4-Methylphenylsulfonamido)cyclopentyl acetate (2b) [23]. Colorless oil; yield: 253 mg (85%); IR
1
(neat): 3278, 2925, 1732, 1455, 1326, 1158, 1092, 815, 666 cm−1; H-NMR (500 Hz, CDCl3) δ
1.44–1.50 (m, 2H), 1.57–1.64 (m, 2H), 1.84 (s, 3H), 1.95–1.99 (m, 2H), 2.39 (s, 3H), 3.40–3.44 (m, 1H),
4.82 (dt, J = 5.5, 7.5 Hz, 1H), 5.33–5.39 (brs, 1H), 7.26 (d, J = 8.1 Hz, 2H), 7.72 (d, J = 8.1 Hz, 2H);
13C-NMR (125 MHz, CDCl3) δ 20.7, 20.8, 21.4, 29.3, 31.0, 59.7, 79.5, 127.1, 129.5, 137.3, 143.3,
171.0; HRMS (FAB): m/z: cald for C14H20NO4S: 298.1113; found: 298.1118 [M + H]+.
2-(4-Methylphenylsulfonamido)cyclopentyl propionate (2bʹ) [25]. Colorless oil; yield: 258 mg (83%);
1
IR (neat): 3276, 2941, 1741, 1462, 1356, 1165, 813, 666 cm−1; H-NMR (500 Hz, CDCl3) δ 0.94
(t, J = 7.6 Hz, 3H), 1.40–1.45 (m, 2H), 1.50–1.57 (m, 2H), 1.85–1.95 (m, 2H), 2.00–2.10 (m, 2H), 2.32
(s, 3H), 3.33–3.40 (m, 1H), 4.80 (dt, J = 5.4, 7.4 Hz, 1H), 5.70 (d, J = 7.4 Hz, 1H), 7.21 (d, J = 8.1 Hz,
13
2H), 7.68 (d, J = 8.1 Hz, 2H); C-NMR (125 MHz, CDCl3) δ 8.7, 20.6, 27.2, 29.2, 30.8, 59.4, 79.2,
126.9, 129.3, 137.3, 143.1, 174.2; HRMS (FAB): m/z: cald for C15H22NO4S: 312.1270; found:
312.1285 [M + H]+.
2-(4-Methylphenylsulfonamido)hexyl acetate (2c) [23]. Colorless oil; yield: 269 mg (86%); IR (neat):
1
3281, 2957, 2871, 1741, 1598, 1431, 1329, 1239, 1162, 1093, 815, 666 cm−1; H-NMR (500 Hz,
CDCl3) δ 0.76 (t, J = 7.2 Hz, 3H), 1.06–1.30 (m, 4H), 1.32–1.45 (m, 2H), 1.90 (s, 3H), 2.39 (s, 3H),
3.38–3.43 (m, 1H), 3.85 (dd, J = 4.3, 11.4 Hz, 1H), 3.94 (dd, J = 5.4, 11.4 Hz, 1H), 4.90 (d, J = 8.5 Hz,
13
1H), 7.26 (d, J = 7.9 Hz, 2H), 7.73 (d, J = 7.9 Hz, 2H); C-NMR (125 MHz, CDCl3) δ 13.7, 20.6,
21.4, 22.2, 27.4, 32.0, 52.8, 65.7, 127.0, 129.6, 138.1, 143.3, 170.8; HRMS (FAB): m/z: cald for
C15H24NO4S: 314.1426; found: 314.1409 [M + H]+.
2-(4-Methylphenylsulfonamido)hexyl propionate (2cʹ) [26]. Colorless oil; yield: 285 mg (87%); IR
1
(neat): 3283, 2957, 1740, 1462, 1330, 1162, 1092, 815, 667 cm−1; H-NMR (500 Hz, CDCl3) δ 0.76
(t, J = 7.1 Hz, 3H), 1.05 (t, J = 7.6 Hz, 3H), 1.15–1.25 (m, 4H), 1.35–1.48 (m, 2H), 2.18 (q, J = 7.6 Hz,
2H), 2.39 (s, 3H), 3.36-3.45 (m, 1H), 3.86 (dd, J = 4.3, 11.4 Hz, 1H), 3.96 (dd, J = 5.5, 11.4 Hz, 1H),
4.77–4.82 (m, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H); 13C-NMR (125 MHz, CDCl3) δ
8.9, 13.7, 21.4, 22.2, 27.1, 27.4, 32.0, 52.9, 65.6, 126.9, 129.6, 138.1, 143.3, 174.2; HRMS (FAB):
m/z: cald for C16H26NO4S: 328.1583; found: 328.1596 [M + H]+.
2-(4-Methylphenylsulfonamido)-1-phenylcarbonyloxyhexane (2cʹʹ) [23]. White solid; m.p. 65–69 °C;
yield: 330 mg (88%); IR (KBr): 3288, 2929, 1787, 1560, 1452, 1273, 1162, 815, 708, 615 cm−1;
1H-NMR (500 Hz, CDCl3) δ 0.78 (t, J = 7.2 Hz, 3H), 1.13–1.31 (m, 4H), 1.45–1.59 (m, 2H), 2.29 (s, 3H),
3.53–3.62 (m, 1H), 4.11 (dd, J = 4.2, 11.5 Hz, 1H), 4.22 (dd, J = 5.6, 11.5 Hz, 1H), 5.16 (d, J = 8.3 Hz,
1H), 7.11 (d, J = 8.0 Hz, 2H), 7.36 (t, J = 7.5 Hz, 2H), 7.52 (t, J = 7.5 Hz, 1H), 7.71 (d, J = 8.3 Hz,
2H), 7.89 (d, J = 7.1 Hz, 2H); 13C-NMR (125 MHz, CDCl3) δ 13.7, 21.4, 22.2, 27.5, 32.2, 53.0, 66.2,
126.8, 128.2, 129.6, 133.1, 138.0, 143.2, 166.2; HRMS (FAB): m/z: cald for C20H26NO4S: 376.1583;
found: 374.1564 [M + H]+.

Molecules 2015, 20
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2-(4-Methylphenylsulfonamido)-3-phenylpropyl acetate (2d) [23]. White solid; m.p. 67–69 °C; yield:
320 mg (92%); IR (KBr): 3280, 2953, 1742, 1455, 1329, 1160, 1092, 815, 667 cm−1; 1H-NMR (500 Hz,
CDCl3) δ 1.93 (s, 3H), 2.37 (s, 3H), 2.75 (d, J = 7.0 Hz, 2H), 3.62–3.69 (m, 1H), 3.90 (dd, J = 5.3, 15.0 Hz,
1H), 3.92 (dd, J = 5.4, 15.0 Hz, 1H), 5.18 (d, J = 8.1 Hz, 1H), 7.00 (d, J = 8.0 Hz, 2H), 7.14–7.22 (m,
5H), 7.62 (d, J = 8.2 Hz, 2H); 13C-NMR (125 MHz, CDCl3) δ 20.6, 21.3, 38.5, 53.8, 64.8, 126.7, 126.8,
128.6, 129.1, 129.5, 136.2, 137.5, 143.2, 170.7; HRMS (FAB): m/z: cald for C18H22NO4S: 348.1270;
found: 348.1254 [M + H]+.
2-(4-Methylphenylsulfonamido)-3-phenylpropyl propionate (2dʹ) [25]. Colorless oil; yield: 354 mg
(98%); IR (neat): 3281, 2942, 1740, 1456, 1330, 1160, 1092, 814, 666 cm−1; 1H-NMR (500 Hz, CDCl3)
δ 1.08 (t, J = 7.6 Hz, 3H), 2.20 (q, J = 7.6 Hz, 2H), 2.40 (s, 3H), 3.34-3.41 (m, 1H), 3.92 (dd, J = 4.7,
11.5 Hz, 1H), 3.97 (dd, J = 5.5, 11.5 Hz, 1H), 4.84 (d, J = 7.9 Hz, 1H), 7.02 (d, J = 7.3Hz, 2H), 7.16–7.23
(m, 5H), 7.63 (d, J = 8.3 Hz, 2H); 13C-NMR (125 MHz, CDCl3) δ 8.9, 21.4, 27.2, 38.5, 53.9, 64.7, 126.8,
126.9, 128.7, 129.2, 129.6, 136.2, 137.6, 143.3, 174.1; HRMS (FAB): m/z: cald for C19H24NO4S:
362.1426; found: 362.1445 [M + H]+.
2-(4-Methylphenylsulfonamido)-2-phenylethyl acetate (2e) [23]. Colorless oil; yield: 300 mg (90%); IR
1
(neat): 3280, 2923, 1742, 1434, 1328, 1160, 1092, 814, 666 cm−1; H-NMR (500 Hz, CDCl3) δ 1.91
(s, 3H), 2.35 (s, 3H), 4.14 (dd, J = 4.9, 11.6 Hz, 1H), 4.18 (dd, J = 7.9, 11.6 Hz, 1H), 4.60 (dt, J = 4.9,
7.3 Hz, 1H), 5.43 (d, J = 7.0 Hz, 1H), 7.08–7.12 (m, 4H), 7.16–7.18 (m, 2H), 7.26–7.30 (m, 1H), 7.57
13
(d, J = 8.4 Hz, 2H); C-NMR (125 MHz, CDCl3) δ 20.6, 21.3, 56.9, 66.5, 126.8, 127.1, 128.6, 129.4,
137.0, 137.5, 143.3, 170.8; HRMS (FAB): m/z: cald for C17H20NO4S: 334.1113; found: 334.1119 [M + H]+.
2-(4-Methylphenylsulfonamido)-2-phenylethyl propionate (2eʹ) [25]. Colorless oil; yield: 306 mg (88%);
IR (neat): 3280, 2924, 1741, 1516, 1438, 1160, 1090, 813, 666 cm−1; 1H-NMR (500 Hz, CDCl3) δ 1.02
(t, J = 7.6 Hz, 3H), 2.18 (q, J = 7.6 Hz, 2H), 2.35 (s, 3H), 4.17 (dd, J =5.0 Hz, 11.6 Hz, 1H), 4.20 (dd,
J = 7.4, 11.6 Hz, 1H), 4.62 (dt, J = 4.9, 7.3 Hz, 1H), 5.72 (d, 6.6 Hz, 1H), 7.12–7.15 (m, 4H), 7.17–7.19
(m, 2H), 7.27–7.30 (m, 1H), 7.59 (d, J = 8.3 Hz, 2H); 13C-NMR (125 MHz, CDCl3) δ 8.8, 21.3, 27.1,
56.9, 66.3, 126.8, 127.0, 128.5, 129.3, 137.1, 137.4, 143.1, 174.2; HRMS (FAB): m/z: cald for
C18H22NO4S: 348.1270; found: 348.1262 [M + H]+.
2-(4-Methylphenylsulfonamido)-2-(4-methylphenyl)ethyl acetate (2f) [23]. White solid; m.p. 88–90 °C;
1
yield: 316 mg (91%); IR (neat): 3278, 2925, 1742, 1495, 1330, 1161, 1044, 815, 668 cm−1; H-NMR
(500 Hz, CDCl3) δ 1.93 (s, 3H), 2.28 (s, 3H), 2.38 (s, 3H), 4.14 (dd, J = 4.8, 11.6 Hz, 1H), 4.19
(dd, J = 7.6, 11.6 Hz, 1H), 4.56 (dt, J = 4.9, 7.3 Hz, 1H), 5.66 (dd, J = 5.0, 7.3 Hz, 1H), 7.00–7.02
(m, 4H), 7.17 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 8.0 Hz, 2H); 13C-NMR (125 MHz, CDCl3) δ 20.6, 21.0,
21.4, 56.5, 66.4, 126.7, 127.0, 129.2, 129.3, 133.9, 137.4, 137.8, 143.2, 170.8; HRMS (FAB): m/z: cald
for C18H22NO4S: 348.1270; found: 348.1288 [M + H]+.
2-(4-Methylphenylsulfonamido)-2-(4-methylphenyl)ethyl acetate (2fʹ) [25]. White solid; m.p. 98–100 °C;
yield: 310 mg (83%); IR (neat): 3283, 2982, 1740, 1598, 1462, 1348, 1161, 1088, 814, 666 cm−1;
1H-NMR (500 Hz, CDCl3) δ 1.04 (t, J = 7.6 Hz, 3H), 2.20 (q, J = 7.6 Hz, 2H), 2.28 (s, 3H), 2.38
(s, 3H), 4.15 (dd, J =4.8, 11.6 Hz, 1H), 4.20 (dd, J = 7.6, 11.6 Hz, 1H), 4.57 (dt, J = 4.8, 7.2 Hz, 1H),

Molecules 2015, 20
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5.22 (d, J = 6.8 Hz, 1H), 7.00–7.02 (m, 4H), 7.17 (d, J = 8.0 Hz, 2H), 7.59 (d, J = 8.0 Hz, 2H);
13C-NMR (125 MHz, CDCl3) δ 8.8, 21.0, 21.4, 56.7, 66.3, 126.7, 127.0, 129.2, 129.4, 134.0, 137.4,
137.9, 143.2, 174.3; HRMS (FAB): m/z: cald for C19H24NO4S: 362.1426; found: 362.1415 [M + H]+.
Copies of 1H- and 13C-NMR Spectra of products 2a–2f, 2aʹ–2fʹ, 2aʹʹ, and 2cʹʹ could be found in the
supplementary materials.
4. Conclusions
In conclusion, we have demonstrated TBD catalyzed ring-opening reactions of N-tosylaziridine
with acid anhydrides. A broad range of N-tosylaziridine and acid anhydrides could be applied using
5 mol % TBD. Furthermore, polymer-supported catalyst, PS-TBD also act as a good catalyst for this
reaction. PS-TBD was easily recovered and reused with minimal loss of activity. These reactions
provide a simple and convenient method for the synthesis of highly functionalized β-amino alcohols.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/20/10/18482/s1.
Author Contributions
S.M. conceived the ideas, analyzed the data, and wrote the paper; Y.M. performed the experiments,
analyzed the data; All authors read and approved the final manuscript.
Conflicts of Interest
The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds 2a–2f, 2aʹ–2fʹ, 2aʹʹ, 2cʹʹ are available from the authors.
© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution license
(http://creativecommons.org/licenses/by/4.0/).