Efficient synthesis of α, β-diamino acid derivatives by in(III)-catalyzed regioselective addition of amines to aziridines

Article abstract of DOI:10.1080/00397911.2011.582977

An efficient catalytic method for the synthesis of α, β-diamino acid derivatives has been developed via regioselective ring opening of aziridines by amines in the presence of indium(III) salt under very mild reaction conditions. Supplemental materials are

Full text of DOI:10.1080/00397911.2011.582977

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Efficient Synthesis of α,β-Diamino
Acid Derivatives by In(III)-Catalyzed
Regioselective Addition of Amines to
Aziridines
Xiao-Yu Hu a b , Xiang-Yu Yang a b , Ming Cheng a b , Qiang Zhang a b
Wei Wei a b & Jian-Xin Ji a
,
a Chengdu Institute of Biology , Chinese Academy of Sciences ,
Chengdu , China
b Graduate University of the Chinese Academy of Sciences , Beijing ,
China
Accepted author version posted online: 11 Nov 2011.Published
online: 02 Aug 2012.
To cite this article: Xiao-Yu Hu , Xiang-Yu Yang , Ming Cheng , Qiang Zhang , Wei Wei & Jian-Xin Ji
(2012) Efficient Synthesis of α,β-Diamino Acid Derivatives by In(III)-Catalyzed Regioselective Addition
of Amines to Aziridines, Synthetic Communications: An International Journal for Rapid Communication
of Synthetic Organic Chemistry, 42:23, 3403-3412, DOI: 10.1080/00397911.2011.582977
To link to this article: http://dx.doi.org/10.1080/00397911.2011.582977
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Synthetic Communications1, 42: 3403–3412, 2012
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.582977
EFFICIENT SYNTHESIS OF a,b-DIAMINO ACID
DERIVATIVES BY In(III)-CATALYZED REGIOSELECTIVE
ADDITION OF AMINES TO AZIRIDINES
Xiao-Yu Hu,1,2 Xiang-Yu Yang,1,2 Ming Cheng,1,2
Qiang Zhang,1,2 Wei Wei,1,2 and Jian-Xin Ji1
1Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China
2Graduate University of the Chinese Academy of Sciences, Beijing, China
GRAPHICAL ABSTRACT
Abstract An efficient catalytic method for the synthesis of a, b-diamino acid derivatives has
been developed via regioselective ring opening of aziridines by amines in the presence of
indium(III) salt under very mild reaction conditions.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Amines; aziridines; catalytic synthesis; a,b-diamino acid; indium(III) salt
INTRUCTION
a,b-Diamino acid derivatives, a special class of non-proteinogenic amino acids,
have increasingly attracted attention for their great importance as key structural
motifs in the synthesis of various biologically active compounds and therapeutic
agents.[1] For example, a, b-diamino acid derivatives I, II, and III are used as crucial
intermediates in the synthesis of G protein-coupled receptor kinase (GRK) inhibitors,
which are applied in therapy of circulatory diseases such as heart failure, hypertension,
and arteriosclerosis.[2] Compound IV and its derivatives can be used to construct
vanadium pharmaceutical agents (Fig. 1).[3]
Because of the biological and chemical significance of a, b-diamino acid
derivatives, a variety of synthetic approaches have been developed,[4] such as nucleo-
philic addition of glycinates to imines and related compounds,[5] electrophilic
Received February 28, 2011.
Address correspondence to Jian-Xin Ji, Chengdu Institute of Biology, Chinese Academy of
Sciences, Chengdu 610041, China. E-mail: jijx@cib.ac.cn
3403

3404
X.-Y. HU ET AL.
Figure 1. Biologically active a,b-diamino acid derivatives.
amination of b-amino enolates,[6] and introduction of the nitrogen atoms to amino
acids, a, b-unsaturated alkenoates, or b-keto esters.[7] Nevertheless, most of these
methods usually need relatively severe or cumbersome reaction conditions. There-
fore, both for scientific interest and practical applications, it is highly desirable to
develop simple, mild, and efficient catalytic methods for the preparation of a, b-dia-
mino acid derivatives. Herein, we report an In(OTf)3-catalyzed efficient method for
the synthesis of a, b-diamino acid derivatives via regioselective ring opening of 2-car-
boxylate aziridines by amines under very mild conditions.
Catalytic methods for the ring opening of aziridines with amines usually
generated simple 1,2-diamines.[8] So far, only a few noncatalytic approaches have
been available for the synthesis of a, b-diamino acid derivatives, but such processes
were only compatible with aliphatic primary amines and usually required much
excess of amines.[9] To the best of our knowledge, the present method is the first
example of catalytic synthesis of a,b-diamino acid derivatives via regioselective
ring opening of N-tosylaziridine-2-carboxylate (1)[10] by aromatic and aliphatic
amines.
RESULTS AND DISCUSSION
Initial attempts to achieve the regioselective ring opening of N-tosylaziridine
-2-carboxylate 1 with p-methoxyaniline in the presence of silver(I) catalyst were
encouraging, providing the C-3 regioselective ring-opening product 2a in 65% yield
along with another component 3a (only 5%), which was a C-2 ring-opening product
(Table 1, entry 1), indicating that the steric effect of carbonyl group in substrate 1
determined the regioselectivity. This result was further confirmed by the x-ray crystal
diffraction of product 2g when p-nitroaniline was used as substrate; see Fig. 2. We
then switched our efforts to other transition-metal catalysts, such as Au(III), In(III),
Zn(II), and Cu(I)=(II) salts (Table 1). Among those catalysts examined, In(OTf)3
exhibited the best catalytic activity and regioselectivity (entry 5). AuBr3, AuCl3,
and Zn(OTf)2 could also give the desired product in moderate yields (entries 3, 4,
and 6). However, AgNO3, Cu(OTf)2, and CuOTf ꢀ 0.5C6H5CH3 showed much less
efficiency for this transformation (entries 2, 7, and 8).
Next, other factors (solvent and temperature) were examined using In(OTf)3 as
catalyst (Table 2). The screening of a range of solvents showed that dichloromethane
(DCM) was the optimal reaction medium in terms of yield and regioselectivity (entries
1–4). The preferred temperature for the reaction was 25 ꢁC (rt), with lower tempera-
tures resulting in poor yields, and higher temperatures leading to less regioselectivity
(entries 5–7).

CATALYTIC SYNTHESIS OF a,b-DIAMINO ACIDS
3405
a
Table 1. Effect of catalyst variations on the reaction of 1 and PMPNH2
Entry
Catalyst
AgOTf
AgNO3
Yield (%)b
Ratio (2a:3a)c
1
2
3
4
5
6
7
8
9
70
<10
62
13:1
only 2a
14:1
AuBr3
AuCl3
58
88
14:1
20:1
In(OTf)3
Zn(OTf)2
Cu(OTf)2
CuOTf ꢀ 0.5C6H5CH3
—
65
32
12:1
only 2a
only 2a
—
38
0
aReaction conditions: compound 1 (0.4 mmol) and PMPNH2 (0.6 mmol) in DCM (1 mL), time (24 h).
bIsolated yields based on substrate 1.
cThe ratio of 2a:3a refers to isolated yields.
To establish the general utility of this methodology, In(OTf)3-catalyzed regiose-
lective ring opening of 2-carboxylate aziridine 1 with various aromatic and aliphatic
amines were performed under the optimized conditions, and the results are summar-
ized in Table 3. The electronic effect on the aromatic ring of amines showed signifi-
cant influence on this process. Those containing electron-donating groups, such as
p-methoxyaniline, and p-methylaniline, gave the desired products in good yields
(entries 1 and 5). However, amines bearing electron-withdrawing groups generated
comparatively lower yields of the targets even with prolonged reaction times (entries
3, 6, and 7). Ortho-substituted amines also gave relatively lower yields, because of the
steric effect (entries 4 and 8). With respect to aliphatic amines such as benzylamine
Figure 2. X-ray crystal diffraction of product 2g.

3406
X.-Y. HU ET AL.
a
Table 2. Effect of reaction condition variations on the reaction of compound 1 and PMPNH2
Entry
Solvent
T (ꢁC)
Yield (%)b
Ratio (2a:3a)c
1
2
3
4
5
6
7
DCM
THF
25
25
25
25
0
88
68
32
<5
22
86
87
20:1
10:1
15:1
only 2a
19:1
7:1
toluene
hexane
DCM
DCM
DCM
40
60
8:1
aReaction conditions: In(OTf)3 (10 mol %), compound 1 (0.4 mmol), PMPNH2 (0.6 mmol), solvent
(1 mL), time (24 h).
bIsolated yields based on substrate 1.
cThe ratio of 2a:3a refers to isolated yields.
and morpholine, the reaction proceeded smoothly with good regioselectivity, and the
desired products were obtained in moderate to excellent yields (entries 9 and 10).
It is worth mentioning that when p-methoxyaniline and benzylamine were used
as substrates (Table 3, entries 1 and 9), the produced N-PMP- and N-Bn-protected
a,b-diamino acid derivatives (Scheme 1) provide convenience and flexibility for
further structure elaboration, which is attractive in synthetic chemistry.
CONCLUSIONS
In summary, we have developed a simple and effective catalytic method for the
synthesis of a, b-diamino acid derivatives via In(OTf)3-catalyzed regioselective ring
opening of 2-carboxylate aziridines with aromatic and aliphatic amines under very
mild reaction conditions. This methodology provides a novel strategy for the con-
struction of dual protected a, b-diamino acid derivatives, which can be used for
further structural elaboration. Taking into account the desirable features, such as
atom efficiency, operation simplicity, and high regioselectivity, this catalytic system
is expected to provide a convenient method to construct versatile building blocks
for applications in increasingly important protein engineering and peptide-based
pharmaceutical research. The asymmetric version and synthetic application of this
reaction are under investigation.
EXPERIMENTAL
All experiments were carried out under an inert atmosphere of nitrogen. All
reagents and solvents were purchased and used without prior purification unless
otherwise stated. Dichlormethane (DCM) was distilled from CaH2 and kept over
˚
4-A molecular sieves. NMR spectra were recorded in CDCl3 on a Bruker Avance

CATALYTIC SYNTHESIS OF a,b-DIAMINO ACIDS
3407
Table 3. In(OTf)3-catalyzed regioselective addition of amines to N-tosylaziridine-2-carboxylate 1a
Entry
1
Amine
Yield (%)b
Ratio (2:3)c
20:1 (2a:3a)
88
2
3
72
50
18:1 (2b:3b)
only 2c
4
48
only 2d
5
6
75
42
22:1 (2e:3e)
only 2f
7
30
only 2g
8
9
46
62
25:1 (2h:3h)
only 2i
10
92
16:1 (2j:3j)
aReaction conditions: compound 1 (0.4 mmol), amine (0.6 mmol), In(OTf)3 (10 mol %), DCM (1 mL).
bIsolated yields based on substrate 1.
cThe ratio of 2:3 refers to isolated yields.

3408
X.-Y. HU ET AL.
Scheme 1. N-PMP and N-Bn protected a,b-diamino acid derivatives.
1
600 spectrometer with tetramethylsilane (TMS) as internal standard (600 MHz H,
150 MHz 13C) at room temperature, and the chemical shifts (d) were expressed in
parts per million (ppm) and J values were given in hertz (Hz). The following
abbreviations are used to indicate the multiplicity: s (singlet), d (doublet), t (triplet),
m (multiplet), and br (broad). Mass analyses and high-resolution mass spectra
(HRMS) were obtained on a Finnigan-LCQDECA mass spectrometer and a Bruker
Daltonics Bio-TOF-Q mass spectrometer by the elecrospray ionization (ESI)
method, respectively. Column chromatography was performed on silica gel (200–
300 mesh).
General Procedure for Regioselective Ring Opening of Aziridine
The N-Ts-protected aziridine 1 (0.4 mmol) was added to a stirred mixture of
amine (0.6 mmol) and In(OTf)3 (0.04 mmol) in DCM (1 mL). The reaction mixture
was stirred at room temperature (25 ꢁC) for the indicated time until complete
consumption of starting material, and then the suspension was filtered through silica
gel and washed with EtOAc (10 mL) to give a brown solution. The solution was
concentrated in vacuum, and the affording residue was purified with flash chroma-
tography (petroleum ether = EtOAc, 6:1) to give the desired addition products as
light-yellow oils.
Spectral Data for All Compounds
Ethyl 1-tosylaziridine-2-carboxylate (1). Light-yellow oil; 1H NMR
(600 MHz, CDCl3): d ¼ 1.25 (t, J ¼ 7.2 Hz, 3H), 2.45 (s, 3H), 2.55 (d, J ¼ 4.1 Hz,
1H), 2.75 (d, J ¼ 7.1 Hz, 1H), 3.32 (dd, J1 ¼ 7.1 Hz, J2 ¼ 4.1 Hz, 1H), 4.14–4.19 (m,
2H), 7.35 (d, J ¼ 8.2 Hz, 2H), 7.85 (d, J ¼ 8.2 Hz, 2H); ESIMS (positive mode) m=z:
270 [M þ H]þ, 292 [M þ Na]þ.
Ethyl 2-(4-methoxyphenylamino)-3-(4-methylphenylsulfonamido)pro-
panoate (Table 3, Entries 1 and 2a). Light-yellow oil; 1H NMR (600 MHz,
CDCl3): d ¼ 1.12 (t, J ¼ 7.1 Hz, 3H), 2.40 (s, 3H), 3.38 (dd, J1 ¼ 13.3 Hz, J2 ¼ 5.8 Hz,
1H), 3.47 (dd, J1 ¼ 13.3 Hz, J2 ¼ 4.5 Hz, 1H), 3.74 (s, 3H), 3.98–4.01 (m, 2H),
4.04–4.06 (m, 1H), 5.47 (d, J ¼ 7.8 Hz, 1H), 6.55 (d, J ¼ 8.8 Hz, 2H), 6.75 (d,
J ¼ 8.8 Hz, 2H), 7.26 (d, J ¼ 8.2 Hz, 2H), 7.70 (d, J ¼ 8.2 Hz, 2H); 13C NMR
(150 MHz, CDCl3): d ¼ 13.9, 21.5, 47.7, 55.4, 55.7, 62.2, 114.9, 115.2, 127.3, 129.7,
136.4, 141.0, 143.9, 152.9, 170.3; ESIMS (positive mode) m=z: 393 [M þ H]þ, 415
[M þ Na]þ; HRESIMS (positive ion) m=z: 415.1284 [M þ Na]þ (calcd. for C19H24N2
Na1O5S1, 415.1298).

CATALYTIC SYNTHESIS OF a,b-DIAMINO ACIDS
3409
Ethyl 3-(4-methoxyphenylamino)-2-(4-methylphenylsulfonamido)pro-
panoate (Table 3, Entries 1 and 3a). Light-yellow oil; 1H NMR (600 MHz,
CDCl3): d ¼ 1.24 (t, J ¼ 7.2 Hz, 3H), 2.43 (s, 3H), 3.21–3.26 (m, 1H), 3.36–3.40 (m,
1H), 3.74 (s, 3H), 4.03 (t, J ¼ 5.3, 1H), 4.14–4.19 (m, 2H), 5.01 (t, J ¼ 6.2 Hz, 1H),
6.54 (d, J ¼ 8.8 Hz, 2H), 6.73 (d, J ¼ 8.8 Hz, 2H), 7.29 (d, J ¼ 8.1 Hz, 2H), 7.73 (d,
J ¼ 8.1 Hz, 2H); 13C NMR (150 MHz, CDCl3): d ¼ 14.1, 21.5, 44.6, 55.7, 57.8, 62.0,
114.9, 116.0, 127.1, 129.8, 136.7, 139.8, 143.7, 153.5, 171.7; ESIMS (positive mode)
m=z: 393 [M þ H]þ, 415 [M þ Na]þ; HRESIMS (positive ion) m=z: 415.1283
[M þ Na]þ (calcd. for C19H24N2Na1O5S1, 415.1298).
Ethyl
3-(4-methylphenylsulfonamido)-2-(phenylamino)propanoate
1
(Table 3, Entries 2 and 2b). Colorless oil; H NMR (600 MHz, CDCl3): d ¼ 1.12
(t, J ¼ 7.2 Hz, 3H), 2.39 (s, 3H), 3.43 (dd, J1 ¼ 13.4 Hz, J2 ¼ 6.0 Hz, 1H), 3.52 (dd,
J1 ¼ 13.4 Hz, J2 ¼ 4.6 Hz, 1H), 3.97–4.02 (m, 2H), 4.06–4.09 (m, 1H), 5.54 (d,
J ¼ 8.0 Hz, 1H), 6.57 (d, J ¼ 8.0 Hz, 2H), 6.72 (t, J ¼ 7.3 Hz, 1H), 7.14 (t, J ¼ 8.0 Hz,
Hz, 2H), 7.25 (d, J ¼ 8.0 Hz, 2H), 7.70 (d, J ¼ 8.0 Hz, 2H); 13C NMR (150 MHz,
CDCl3): d ¼ 13.9, 21.5, 46.6, 55.4, 62.2, 113.5, 118.4, 127.3, 129.3, 129.7, 136.4,
143.9, 147.0, 170.3; ESIMS (positive mode) m=z: 385 [M þ Na]þ, HRESIMS (posi-
tive ion) m=z: 385.1181 [M þ Na]þ (calcd. for C18H22N2Na1O4S1, 355.1192).
Ethyl
2-(4-methylphenylsulfonamido)-3-(phenylamino)propanoate
1
(Table 3, Entries 2 and 3b). Colorless oil; H NMR (600 MHz, CDCl3): d ¼ 1.25
(t, J ¼ 6.8 Hz, 3H), 2.42 (s, 3H), 3.29–3.33 (m, 1H), 3.36–3.40 (m, 1H), 4.14 (t,
J ¼ 5.3 Hz, 1H), 4.16–4.21 (m, 2H), 4.94 (t, J ¼ 6.2 Hz, 1H), 6.56 (d, J ¼ 8.2 Hz,
2H), 6.78 (t, J ¼ 7.5 Hz, 1H), 7.15 (t, J ¼ 7.5 Hz, 2H), 7.28 (d, J ¼ 8.0 Hz, 2H), 7.72
(d, J ¼ 8.0 Hz, 2H); 13C NMR (150 MHz, CDCl3): d ¼ 11.4, 21.5, 44.4, 56.4, 62.1,
113.9, 119.2, 127.1, 129.4, 129.8, 136.7, 143.7, 145.9, 171.4; ESIMS (positive mode)
m=z: 363 [M þ H]þ, 385 [M þ Na]þ; HRESIMS (positive ion) m=z: 385.1194
[M þ Na]þ (calcd. for C18H22N2Na1O4S1, 355.1192).
Ethyl
2-(3-bromophenylamino)-3-(4-methylphenylsulfonamido)pro-
1
panoate (Table 3, Entries 3 and 2c). Colorless oil; H NMR (600 MHz, CDCl3):
d ¼ 1.15 (t, J ¼ 7.3 Hz, 3H), 2.41 (s, 3H), 3.41 (dd, J1 ¼ 13.0 Hz, J2 ¼ 5.7 Hz, 1H), 3.50
(br d, J ¼ 13.0 Hz, 1H), 4.00–4.05 (m, 3H), 4.11 (br s, 1H), 5.53 (d, J ¼ 7.6 Hz, 1H),
6.49 (d, J ¼ 8.0 Hz, 1H), 6.68 (s, 1H), 6.84 (d, J ¼ 8.0 Hz, 1H), 6.99 (t, J ¼ 8.0 Hz,
1H), 7.27 (d, J ¼ 8.1 Hz, 2H), 7.71 (d, J ¼ 8.1 Hz, 2H); 13C NMR (150 MHz, CDCl3):
d ¼ 13.9, 21.5, 46.2, 55.3, 62.5, 112.2, 115.9, 121.1, 123.2, 127.3, 129.8, 130.5, 136.2,
144.0, 148.3, 170.0; ESIMS (positive mode) m=z: 463 [M þ Na]þ; HRESIMS (posi-
tive ion) m=z: 463.0274 [M þ Na]þ (calcd. for C18H21Br1N2Na1O4S1, 463.0298).
Ethyl
2-(o-toluidino)-3-(4-methylphenylsulfonamido)propanoate
1
(Table 3, Entries 4 and 2d). Colorless oil; H NMR (600 MHz, CDCl3): d ¼ 1.12
(t, J ¼ 7.1 Hz, 3H), 2.08 (s, 3H), 2.38 (s, 3H), 3.42–3.44 (m, 1H), 3.55–3.57 (m, 1H),
3.94 (br s, 1H), 3.99–4.03 (m, 2H), 4.10–4.13 (m, 1H), 5.59 (d, J ¼ 8.0 Hz, 1H), 6.55
(d, J ¼ 8.0 Hz, 1H), 6.67 (t, J ¼ 7.4 Hz, 1H), 7.02 (d, J ¼ 7.1 Hz, 1H), 7.08 (t,
J ¼ 7.4 Hz, 1H), 7.23 (d, J ¼ 8.0 Hz, 2H), 7.70 (d, J ¼ 8.0 Hz, 2H); 13C NMR
(150 MHz, CDCl3): d ¼ 13.9, 17.3, 21.5, 46.3, 55.3, 62.3, 110.1, 117.9, 122.9, 127.0,
127.2, 129.7, 130.3, 136.4, 143.9, 144.9, 170.4; ESIMS (positive mode) m=z: 399

3410
X.-Y. HU ET AL.
[M þ Na]þ; HRESIMS (positive ion) m=z: 399.1366 [M þ Na]þ (calcd. for C19H24
N2Na1O4S1, 399.1349).
Ethyl
3-(p-toluidino)-2-(4-methylphenylsulfonamido)propanoate
1
(Table 3, Entries 5 and 2e). Colorless oil; H NMR (600 MHz, CDCl3): d ¼ 1.12
(t, J ¼ 7.0 Hz, 3H), 2.23 (s, 3H), 2.40 (s, 3H), 3.40 (dd, J1 ¼ 13.4 Hz, J2 ¼ 5.8 Hz,
1H), 3.50 (dd, J1 ¼ 13.4 Hz, J2 ¼ 4.7 Hz, 1H), 3.97–4.02 (m, 2H), 4.05–4.08 (m, 1H),
5.45 (d, J ¼ 7.8 Hz, 1H), 6.50 (d, J ¼ 8.2 Hz, 2H), 6.92 (d, J ¼ 8.2 Hz, 2H), 7.25 (d,
J ¼ 8.2 Hz, 2H), 7.70 (d, J ¼ 8.2 Hz, 2H); 13C NMR (150 MHz, CDCl3): d ¼ 13.9,
20.4, 21.5, 47.0, 55.4, 62.2, 113.8, 127.3, 127.7, 129.7, 129.8, 136.5, 143.9, 144.6,
170.3; ESIMS (positive mode) m=z: 377 [M þ H]þ, 399 [M þ Na]þ; HRESIMS
(positive ion) m=z: 399.1348 [M þ Na]þ (calcd. for C19H24N2Na1O4S1, 399.1349).
Ethyl
2-(p-toluidino)-3-(4-methylphenylsulfonamido)propanoate
1
(Table 3, Entries 5 and 3e). Colorless oil; H NMR (600 MHz, CDCl3): d ¼ 1.24
(t, J ¼ 7.3 Hz, 3H), 2.23 (s, 3H), 2.43 (s, 3H), 3.25–3.29 (m, 1H), 3.36–3.40 (m, 1H),
4.08–4.10 (m, 1H), 4.16–4.18 (m, 2H), 4.89 (t, J ¼ 6.0 Hz, 1H), 6.48 (d, J ¼ 7.9 Hz,
2H), 6.96 (d, J ¼ 7.9 Hz, 2H), 7.29 (d, J ¼ 7.9 Hz, 2H), 7.72 (d, J ¼ 7.7 Hz, 2H); 13C
NMR (150 MHz, CDCl3): d ¼ 14.1, 20.4, 21.5, 44.5, 56.9, 62.0, 114.3, 127.1, 128.7,
129.8, 129.9, 136.7, 143.6, 143.7, 171.5; ESIMS (positive mode) m=z: 377 [M þ H]þ,
399 [M þ Na]þ; HRESIMS (positive ion) m=z: 399.1358 [M þ Na]þ (calcd. for
C19H24N2Na1O4S1, 399.1349).
Ethyl
2-(4-fluorophenylamino)-3-(4-methylphenylsulfonamido)pro-
1
panoate (Table 3, Entries 6 and 2f). Colorless oil; H NMR (600 MHz, CDCl3):
d ¼ 1.12 (t, J ¼ 7.1 Hz, 3H), 2.40 (s, 3H), 3.38 (dd, J1 ¼ 13.3 Hz, J2 ¼ 6.0 Hz, 1H), 3.49
(dd, J1 ¼ 13.3 Hz, J2 ¼ 4.4 Hz, 1H), 3.99–4.05 (m, 3H), 5.47 (d, J ¼ 7.6 Hz, 1H),
6.51–6.53 (m, 2H), 6.86 (t, J ¼ 8.7 Hz, 2H), 7.26 (d, J ¼ 7.9 Hz, 2H), 7.69 (d,
J ¼ 7.9 Hz, 2H); 13C NMR (150 MHz, CDCl3): d ¼ 13.9, 21.5, 47.3, 55.3, 62.2,
114.5, 114.6, 115.6, 115.8, 127.3, 129.8, 136.3, 143.3, 144.0, 155.5, 170.2; ESIMS
(positive mode) m=z: 381 [M þ H]þ, 403 [M þ Na]þ; HRESIMS (positive ion) m=z:
403.1116 [M þ Na]þ (calcd. for C18H21F1N2Na1O4S1, 403.1098).
Ethyl 3-(4-methylphenylsulfonamido)-2-(4-nitrophenylamino) propano-
ate (Table 3, Entries 7 and 2g). Yellow oil; 1H NMR (600 MHz, CDCl3): d ¼ 1.15
(t, J ¼ 7.1 Hz, 3H), 2.42 (s, 3H), 3.50–3.54 (m, 1H), 3.65–3.69 (m, 1H), 4.03–4.08 (m,
3H), 4.92 (br s, 1H), 5.49 (d, J ¼ 7.2 Hz, 1H), 6.56 (d, J ¼ 9.0 Hz, 2H), 7.29 (d,
J ¼ 8.0 Hz, 2H), 7.71 (d, J ¼ 8.0 Hz, 2H), 8.08 (d, J ¼ 9.0 Hz, 2H); 13C NMR
(150 MHz, CDCl3): d ¼ 13.9, 21.5, 45.7, 55.1, 62.8, 111.7, 126.3, 127.3, 129.9,
135.8, 139.0, 144.4, 152.3, 169.4; ESIMS (positive mode) m=z: 408 [M þ H]þ, 430
[M þ Na]þ; HRESIMS (positive ion) m=z: 408.1210 [M þ H]þ (calcd. for C18H22
N3Na1O6S1, 408.1224).
Ethyl 2-(2,4-dimethoxyphenylamino)-3-(4-methylphenylsulfonamido)-
1
propanoate (Table 3, Entries 8 and 2h). Light-yellow oil; H NMR (600 MHz,
CDCl3): d ¼ 1.12 (t, J ¼ 7.1 Hz, 3H), 2.40 (s, 3H), 3.45 (d, J ¼ 4.8 Hz, 2H), 3.74 (s,
3H), 3.80 (s, 3H), 3.96–4.00 (m, 2H), 4.07–4.11 (m, 1H), 4.17 (br s, 1H), 5.42 (d,
J ¼ 8.3 Hz, 1H), 6.36 (dd, J1 ¼ 8.6 Hz, J2 ¼ 2.5 Hz, 1H), 6.42 (d, J ¼ 2.5 Hz, 1H),
6.50 (d, J ¼ 8.6 Hz, 1H), 7.25 (d, J ¼ 8.1 Hz, 2H), 7.70 (d, J ¼ 8.1 Hz, 2H);

CATALYTIC SYNTHESIS OF a,b-DIAMINO ACIDS
3411
13C NMR (150 MHz, CDCl3): d ¼ 13.9, 21.5, 47.3, 55.3, 55.5, 55.8, 62.0, 99.3, 103.8,
111.3, 127.3, 129.6, 131.0, 136.6, 143.7, 148.4, 152.7, 170.5; ESIMS (positive mode)
m=z: 445 [M þ Na]þ; HRESIMS (positive ion) m=z: 445.1388 [M þ Na]þ (calcd. for
C20H26N2Na1O6S1, 445.1404).
Ethyl 3-(2,4-dimethoxyphenylamino)-2-(4-methylphenylsulfonamido)-
1
propanoate (Table 3, Entries 8 and 3h). Light-yellow oil; H NMR (600 MHz,
CDCl3): d ¼ 1.23 (t, J ¼ 7.0 Hz, 3H), 2.42 (s, 3H), 3.23–3.27 (m, 1H), 3.36–3.40
(m, 1H), 3.74 (s, 3H), 3.83 (s, 3H), 4.05 (t, J ¼ 5.3, 1H), 4.12–4.17 (m, 2H), 5.01
(t, J ¼ 6.2 Hz, 1H), 6.31 (dd, J1 ¼ 8.6 Hz, J2 ¼ 2.6 Hz, 1H), 6.41 (d, J ¼ 8.6 Hz, 1H),
6.44 (d, J ¼ 2.6 Hz, 1H), 7.28 (d, J ¼ 8.0 Hz, 2H), 7.72 (d, J ¼ 8.0 Hz, 2H); 13C
NMR (150 MHz, CDCl3): d ¼ 14.1, 21.5, 44.6, 55.6, 55.7, 57.2, 61.8, 99.4, 103.8,
112.5, 127.1, 129.7, 129.8, 136.8, 143.5, 148.9, 153.5, 171.6; ESIMS (positive mode)
m=z: 445 [M þ Na]þ; HRESIMS (positive ion) m=z: 445.1381 [M þ Na]þ (calcd. for
C20H26N2Na1O6S1, 445.1404).
Ethyl
2-(benzylamino)-3-(4-methylphenylsulfonamido)propanoate
1
(Table 3, Entries 9 and 2i). Colorless oil; H NMR (600 MHz, CDCl3): d ¼ 1.10
(t, J ¼ 7.2 Hz, 3H), 2.40 (s, 3H), 2.87–2.93 (m, 2H), 3.66 (d, J ¼ 13.3 Hz, 1H), 3.75
(d, J ¼ 13.3 Hz, 1H), 3.96–4.02 (m, 3H), 7.23–7.32 (m, 7H), 7.72 (d, J ¼ 8.0 Hz,
2H); 13C NMR (150 MHz, CDCl3): d ¼ 13.9, 21.5, 50.5, 53.1, 55.6, 61.8, 127.1,
127.3, 128.1, 128.4, 129.7, 136.8, 139.7, 143.6, 170.7; ESIMS (positive mode) m=z:
377 [M þ H]þ, 399 [M þ Na]þ; HRESIMS (positive ion) m=z: 377.1516 [M þ H]þ
(calcd. for C19H25N2O4S1, 399.1530).
Ethyl
3-(4-methylphenylsulfonamido)-2-morpholinopropanoate
(Table 3, Entries 10 and 2j). Colorless oil; 1H NMR (600 MHz, CDCl3):
d ¼ 1.17 (t, J ¼ 7.0 Hz, 3H), 2.32–2.39 (m, 4H), 2.42 (s, 3H), 2.60 (dd, J1 ¼ 12.8 Hz,
J2 ¼ 5.5 Hz, 1H), 2.66 (dd, J1 ¼ 12.8 Hz, J2 ¼ 7.3 Hz, 1H), 3.57 (br t, J ¼ 4.4 Hz,
4H), 3.95 (br s, 1H), 3.99–4.07 (m, 2H), 5.51 (br s, 1H), 7.30 (d, J ¼ 8.0 Hz, 2H),
7.75 (d, J ¼ 8.0 Hz, 2H); 13C NMR (150 MHz, CDCl3): d ¼ 14.0, 21.5, 53.5, 53.9,
59.3, 61.6, 66.8, 127.3, 129.6, 136.8, 143.7, 170.7; ESIMS (positive mode) m=z: 357
[M þ H]þ, 379 [M þ Na]þ; HRESIMS (positive ion) m=z: 357.1487 [M þ H]þ (calcd.
for C16H25N2O5S1, 357.1479).
Ethyl
2-(4-methylphenylsulfonamido)-3-morpholinopropanoate
(Table 3, Entries 10 and 3j). Colorless oil; 1H NMR (600 MHz, CDCl3):
d ¼ 1.28 (t, J ¼ 7.3 Hz, 3H), 2.38–2.41 (m, 2H), 2.43 (s, 3H), 2.60 (br s, 2H),
3.04–3.08 (m, 1H), 3.22–3.26 (m, 2H), 3.57-3.65 (m, 4H), 4.11–4.22 (m, 2H), 5.07
(br d, J ¼ 5.5 Hz, 1H), 7.31 (d, J ¼ 8.1 Hz, 2H), 7.76 (d, J ¼ 8.1 Hz, 2H); 13C NMR
(150 MHz, CDCl3): d ¼ 14.4, 21.5, 40.3, 49.5, 60.9, 65.6, 67.2, 127.1, 129.8, 136.8,
143.7, 169.4; ESIMS (positive mode) m=z: 357 [M þ H]þ, 379 [M þ Na]þ; HRESIMS
(positive ion) m=z: 357.1483 [M þ H]þ (calcd. for C16H25N2O5S1, 357.1479).
ACKNOWLEDGMENT
We are grateful for the financial support from the National Science Foun-
dation of China (20802072).

3412
X.-Y. HU ET AL.
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