Three-component reactions based on trapping ammonium ylides with N-sulfonyl aldimines via cooperative catalysis of squaramides and Rh2(OAc) 4

Article abstract of DOI:10.1016/j.tet.2013.12.082

Three-component reactions of aryl diazoacetates, arylamines and N-sulfonyl aldimines cooperatively catalyzed by squaramides and dirhodium acetate are reported to afford N-sulfonyl α,β-diamino acid derivatives in moderate to good yields and diastereoselect

Full text of DOI:10.1016/j.tet.2013.12.082

Tetrahedron 70 (2014) 1471e1477
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Three-component reactions based on trapping ammonium ylides
with N-sulfonyl aldimines via cooperative catalysis of squaramides
and Rh2(OAc)4
*
Lin Qiu, Dongwei Wang, Fengping Lv, Xin Guo, Wenhao Hu, Liping Yang, Shunying Liu
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai 200062, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Three-component reactions of aryl diazoacetates, arylamines and N-sulfonyl aldimines cooperatively
Received 1 November 2013
Received in revised form 18 December 2013
Accepted 28 December 2013
Available online 3 January 2014
catalyzed by squaramides and dirhodium acetate are reported to afford N-sulfonyl
derivatives in moderate to good yields and diastereoselectivity.
a,b-diamino acid
Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.
Keywords:
Ammonium ylide
Multicomponent reaction
Cooperative catalysis
Squaramides
1. Introduction
While due to the poor reactivity of N-sulfonyl imine substrates in
that reaction, which PPAs used as co-catalyst, only aryl imines can
be used as electrophiles to provide a,b-diamino acid derivatives.
With the collection of our continuous efforts in multicomponent
reactions through active intermediate trapping process, here we
extended the trapping electrophiles to N-sulfonyl aldimine sub-
strates by using squaramide derivatives as co-catalysts to furnish N-
Multicomponent reactions1 offer significant advantages over
traditional approaches for the rapid construction of complex mul-
tifunctionalized molecular architectures in a single synthetic op-
eration. To develop novel multicomponent reactions, the main
challenges coming from the compatibility of catalysts to substrates
and the stereoselectivity control urgently need to be settled. Co-
operative catalysis, especially the combination of transition metal
catalysis and organocatalysis, has attracted much attention because
it is more powerful to enable the unprecedented transformation,
which catalyzed by single catalytic system alone.2,3 For this pur-
pose, cooperative catalysis strategy is considered as a practically
useful strategy to develop new multicomponent reactions.4
sulfonyl
a,b-diamino acid derivatives in one pot from simple
starting materials.
Both sulfamide moieties6 and -diamino acid derivatives6b,7
a,b
are key structural motifs of biologically active compounds and
have attracted a great deal of attention in pharmaceuticals and
organic synthesis. N-Sulfonyl
a,
b-diamino acid derivatives, con-
taining sulfamide motifs and a,b-diamino acid scaffolds, will pro-
Recent years, our research interesting has been focused on
a novel three-component reaction based on trapping the protic
ammonium ylides.5 In 2011, we developed a multicomponent
vide complex molecules with more biological potentials as well as
possible chemical synthons. Double hydrogen bond catalysts
(DHB), including thio(urea) and squaramide derivatives (Fig. 1), are
transformation to install a,b-diamino acid derivatives with an ex-
cellent diastereoselectivity and enantioselectivity by using BINOL-
derived chiral phosphoric acids (PPAs) and Rh2(OAc)4 co-catalysis.
In this transformation, the highly reactive protic carbamate am-
monium ylides were successfully trapped by imine electrophiles.5c
* Corresponding author. Tel./fax: þ86 21 62221237; e-mail address: syliu@sist.
ecnu.edu.cn (S. Liu).
Fig. 1. Double HB catalysts and chiral PPAs.
0040-4020/$ e see front matter Crown Copyright Ó 2014 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.12.082

1472
L. Qiu et al. / Tetrahedron 70 (2014) 1471e1477
Table 2
playing an increasingly important role in the development of
organocatalysis.8 To activate N-sulfonyl aldimine, double hydrogen
bond catalysts were considered to be used as co-catalysts instead of
PPAs. N-Sulfonyl aldimines have been reported to be activated with
PPAs or thiourea to develop asymmetric FriedeleCrafts reaction of
indoles by You9 and Deng10a groups, respectively. Zhou group used
to report N-sulfonyl aldimines activated by Cu(OTf) possible
through 1,3-coordination in FriedeleCrafts reaction.11a In 2010,
pioneered by the seminal works of Rawal, N-sulfonyl aldimines
were activated by squaramide to perform the same reaction.11b
Herein, squaramide 1 and thio(urea) 2, were used to activate N-
sulfonyl aldimines to promote the desired Mannich-type multi-
component reaction. PPAs 3 were employed for the control
research.
Screening substrates of the three-component reaction of 4, 5 and 6, 8 or 9a
Entry
4
5
Ar3/R
7
Yieldb drc
2. Results and discussion
(%)
(anti/syn)
1
2
3
4
5
6
7
8
4a 5a 4-BrC6H4/Ts/6a
4a 5b 4-BrC6H4/Ts/6a
4a 5c 4-BrC6H4/Ts/6a
4a 5d 4-BrC6H4/Ts/6a
4a 5e 4-BrC6H4/Ts/6a
4a 5f 4-BrC6H4/Ts/6a
4a 5g 4-BrC6H4/Ts/6a
4a 5h 4-BrC6H4/Ts/6a
4a 5g 4-NO2C6H4/Ts/6b
4a 5g 3-NO2C6H4/Ts/6c
4a 5g 2-NO2C6H4/Ts/6d
4a 5g 4-CNC6H4/Ts/6e
4a 5g 4-CF3C6H4/Ts/6f
4a 5g 4-ClC6H4/Ts/6g
4a 5d 4-ClC6H4/Ts/6g
4a 5d 4-MeC6H4/Ts/6h
4a 5g 4-BrC6H4/Ns/8a
4a 5g 4-BrC6H4/2-thiophenesulfonyl/9a
4a 5g 3-NO2C6H4/Ns/8b
7a
7b
7c
7d
7e
7f
7g
7h
7i
53
50
64
64
47
53
54
43
70
52
<5
52
40
<5
50:50
69:31
64:36
51:49
71:29
49:51
82:18
57:43
68:32
76:24
n.d.d
The preliminary reaction of methyl phenyldiazoacetate 4a,
phenylamine 5a and N-4-methylbenzenesulfonyl (Ts) aldimines 6a
was firstly ignited with a catalytic amount of Rh2(OAc)4 and co-
catalyst DHB in dichloromethane (DCM) over 1 h at room tem-
perature, and the results were tabulated in Table 1. Gratifyingly,
squaramides 1a and 1b were found to be effective to give the de-
sired product 7a in moderate isolated yield (50% and 53%, re-
spectively) but with no diastereoselectivity (entries 1 and 2). Even
though urea 2a and thiourea 2b were demonstrated as effective
hydrogen bond donors for N-sulfonyl aldimines,10 they gave only
side NeH insertion product 10a (entries 3 and 4). This presumably
is attributed to the deficient acidity of thioureas in the reaction.15c
Similar results were observed when using PPAs 3a and 3b9 as co-
catalysts, and only NeH insertion products were afforded (entries
5 and 6), which suggested that PPAs possibly served as a single
hydrogen bond catalyst in this process. The poor reactivity seen
with PPAs is consistent with the expectation that DHB catalyst is
required to promote the reaction. In the absence of all these co-
catalysts, only NeH insertion product was obtained (entry 7). Due
to the poor solubility of squaramides, the reaction yield had no
notable increase when the catalyst loading was increased to
20 mol % (entry 8). However, the yield dramatically decreased to
20% when decreasing the catalyst loading of squaramide from
10 mol % to 5 mol % (entry 9).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
7j
d
7k
7l
73:27
71:29
n.d.d
d
7m 40
45:55
69:31
70:30
81:19
80:20
79:21
80:20
77:36
79:21
76:24
85:15
7n
7o
7p
7q
15
48
56
58
56
57
36
55
52
4a 5g 3-NO2C6H4/2-thiophenesulfonyl/9b 7r
4b 5g 3-NO2C6H4/Ts/6c
4c 5g 3-NO2C6H4/Ts/6c
4d 5g 3-NO2C6H4/Ts/6c
4b 5g 3-NO2C6H4/Ns/8b
4e 5g 3-NO2C6H4/Ns/8b
7s
7t
7u
7v
7w 54
a
Reaction conditions: unless otherwise noted, the reaction was carry out in
CH2Cl2 with 4/5/6, 8 or 9¼1.5:1.5:1.0, catalyzed by 1 mol % of Rh2(OAc)4 and
10 mol % of 1a.
b
Isolated yield of 7 based on 6, 8 or 9.
c
Determined by 1H NMR analysis.
To demonstrate the generality of this squaramide-promoted
method, the substrate scope for the reaction was investigated,
and the results are summarized in Table 2. The chem- and
d
n.d.: not detected.
stereoselectivity of the reactions were found to be dependent on
electronic and steric features of the substrates. The reaction was
tolerant to several anilines (entries 1e8). In the reactions of methyl
aryl diazoacetates (4a) with anilines (5aeg) and N-sulfonyl aldi-
mines (6a), the halogen substituents on the N-aryl group of aniline
5 increased the diastereoselectivity from 50:50 dr up to 82:18 dr
(entry 1 vs 7). The steric variations of 5 had notable effect on the
diastereoselectivity (entry 2 vs 3 and 4). The ortho-substituted
aniline 5 gave a higher diastereoselectivity of the product (entry 2
vs 4, entry 5 vs 6, entry 7). In all these cases, both steric and elec-
tronic features had no notable effect on the yields. While for the
ortho electron-donating methoxy substituent 5h, both the yield and
the diastereoselectivity presented an observed decrease to 43% and
57:43, respectively (entry 8).
A number of substituted N-sulfonyl aldimines were evaluated in
this reaction with methyl phenyldiazoacetate (4a) and arylamine
(5g). The reaction proceeded smoothly to give the three-
component products 7 with strong electron-withdrawing sub-
stituents in the 3- and 4-positions of aryl group of 6 (entries 9e13).
While possible due to the steric hindrance, the 2-nitro substituent
6d gave the desired product in a yield of less than 5% (entry 11). The
weak electron-withdrawing substituent in the aryl group of 6g also
Table 1
Screening co-catalysts for the three-component reaction of 4a, 5a and 6aa
Entry
Cocat. (mol %)
Yieldb (%)
drc (anti/syn)
1
2
3
4
5
6
7
8
9
1a (10)
1b (10)
2a (10)
2b (10)
3a (10)
3b (10)
d
53
50
0d
0d
0d
0d
0d
55
20
50:50
50:50
n.d.e
n.d.e
n.d.e
n.d.e
n.d.e
1a (20)
1a (5)
50:50
50:50
a
Reaction conditions: unless otherwise noted, the reaction was carry out in
CH2Cl2 with 4a/5a/6a¼1.5:1.5:1.0, catalyzed by 1 mol % of Rh2(OAc)4.
b
Isolated yield of 7a based on 6a.
c
Determined by 1H NMR analysis.
d
Only NeH insertion product.
n.d.: not detected.
e

L. Qiu et al. / Tetrahedron 70 (2014) 1471e1477
1473
gave a very low yield (<5%, entry 14) when 5g was used as aniline.
Interestingly, when ortho-substituted 5g was replaced with para-
substituted 5d, this reaction proceeded smoothly again to produce
7m in 40% yield (entry 15). And even the electron-donating methyl
substituent 6h was used, the reaction can also give the multicom-
ponent product 7n in 69:31 dr, albeit in 15% yield (entry 16). These
results further confirmed that the steric feature played an impor-
tant role in this reaction. We were pleased to find that the trapping
electrophiles were easily extended to 4-nitrobenzenesulfonyl (Ns)
obtained when 1 equiv of 1a was added to the solution of 6a, the
maximum absorption of 6a at 293 nm was also blue shift to 288 nm
with 40% decrease in absorption. With the addition of 5a (1 equiv)
to the mixture solution of 6a and 1a, the maximum absorption of 6a
continuously decreased. Compared with the maximum absorption
of 6a with addition of 1a and 5a, the maximum absorption of 6a
with only addition of 5a presented a much less decrease with 5 nm
blue shift. These results suggested that squaramide 1a had reacted
with both N-sulfonyl aldimine and aniline through hydrogen
bondings.15
aldimines
8 and 2-thiophenesulfonyl imines 9 with no de-
terioration in yields and even better diastereoselectivity from 70:30
to 81:19 dr (entries 17e20). The reaction proceeded well with 3-
and 4-substituted phenyldiazoacetates when either Ts or Ns aldi-
mines were used and afforded the corresponding products in
moderate yields with diastereoselectivity up to 85:15 dr (entries
21e25). Stereochemical assignments were determined on the basis
of X-ray crystal structures for major product of anti-7g (Fig. 2).12
Since Rawal first developed a novel chiral squaramide derivative
to promote the Michael addition of 1,3-dicarbonyl compounds to
nitroalkenes in 2008,13e a series of chiral squaramide organo-
catalysts were developed and successfully applied in various
asymmetric reactions as DHB catalysts.13e14 Here, we developed
a squaramide and Rh2(OAc)4 co-catalyzed system to activate N-
sulfonyl imine to promote the multicomponent reaction. The N-
sulfonyl imine was hypothesized to be activated by squaramide 1a
through 1,3-coordiated hydrogen bonding.
On the basis of the above results, a plausible mechanism for the
Rh2(OAc)4 and squaramides co-catalyzed three-component re-
actions is illustrated in Scheme 1. N-Sulfonyl aldimine 6 was pro-
gressively activated by squaramide and arylamine 5 to form
intermediate III by hydrogen bonding. The in situ generated am-
monium ylides intermediate II are trapped by the intermediate III
to undergo a Mannich-type reaction to afford the desired product 7.
The observed anti-7 and syn-7 arised via the transition state TS-1
and TS-2, respectively. Possibly due to the less steric hindrance of
TS-1, anti-7 was obtained as the major product.
Fig. 2. X-ray crystal structure of anti-7g.
To probe the reaction mechanism, we conducted UV spectro-
photometric analyses to identify the abilities of catalyst 1a as hy-
drogen bonding donor in this reaction (Fig. 3).15 The free aniline 5a
exhibited a maximum absorption at 240 nm. When 1 equiv of
squaramide 1a was added, the maximum absorption of 5a at
240 nm was slightly blue shift to 235 nm with nearly 50% decrease
in absorption, which indicated that 1a possibly reacted with 5a
through 1,3-coordiated hydrogen bonding. Similar observation was
Scheme 1. Plausible reaction mechanism of Rh2(OAc)4 and squaramide co-catalyzed
three-component reactions.
3. Conclusion
In summary, we have developed an efficient squaramide and
dirhodium(II)-co-catalyzed methodology for N-sulfonyl
a,b-dia-
mino acid derivatives starting from aryl diazoacetates, arylamines
and N-sulfonyl aldimines under mild conditions with a consider-
able diastereoselectivity. With the co-catalysis strategy, the trap-
ping electrophiles for active ammonium ylides are readily
extended to N-sulfonyl imines, which facilitate the construction of
complex molecules with more biological potentials as well as
possible synthetic value. To the best of our knowledge, this is the
first example of squaramide-involved co-catalyzed multicompo-
nent reactions. A plausible mechanism is proposed on the basis of
mechanistic studies. Further studies to clearly understand the
reaction mechanism and its asymmetric variation are ongoing in
our laboratory.
Fig. 3. Absorption spectra taken over the course of 5.0ꢀ10ꢁ5 M in CH2Cl2.

1474
L. Qiu et al. / Tetrahedron 70 (2014) 1471e1477
4. Experimental section
134.12, 131.15, 130.05, 129.25, 129.13, 128.72, 128.54, 128.35, 127.07,
126.90, 126.72, 122.59, 120.73, 118.66, 115.18, 70.17, 63.83, 53.00,
4.1. General
21.41; ESCI-HRMS calcd for
635.0377; Found: 635.0358.
C
29H26BrClN2NaO4S [MþNa]þ
All moisture sensitive reactions were performed under an argon
atmosphere in
a
well-dried reaction flask. Dichloromethane
4.2.4. Methyl 3-(4-bromophenyl)-2-(3-chlorophenylamino)-3-(4-
(CH2Cl2), 1,2-dichloroethene (CH2Cl)2 and chloroform (CHCl3) were
freshly distilled over calcium hydride, toluene from sodium benzo-
phenone ketyl, respectively, prior to use. Solvents for the column
chromatography were distilled before use. 1H and 13C NMR spectra
were recorded on a Brucker-400 MHz spectrometer. Chemical shifts
are reported in parts per million relative to the internal standard
methylphenyl-sulfonamido)-2-phenylpropanoate (7c). Yield: 64%;
1H NMR (400 MHz, CDCl3)
d (anti) 7.40e7.23 (m, 2H), 7.18 (d,
J¼3.1 Hz, 2H), 7.07 (d, J¼8.3 Hz, 2H), 6.92 (dd, J¼21.7, 8.1 Hz, 3H),
6.77 (d, J¼7.7 Hz, 1H), 6.53 (d, J¼7.9 Hz, 1H), 6.43 (d, J¼8.3 Hz, 2H),
6.34 (d, J¼8.3 Hz, 2H), 6.21 (s, 1H), 5.98 (d, J¼8.2 Hz, 1H), 5.48 (d,
J¼9.8 Hz,1H), 5.10 (d, J¼9.8 Hz,1H), 4.99 (s, 1H), 3.58 (s, 3H), 2.26 (s,
3H); (syn) 7.40e7.23 (m, 2H), 7.18 (d, J¼3.1 Hz, 2H), 7.07 (d, J¼8.3 Hz,
2H), 6.92 (dd, J¼21.7, 8.1 Hz, 3H), 6.77 (d, J¼7.7 Hz, 1H), 6.53 (d,
J¼7.9 Hz, 1H), 6.43 (d, J¼8.3 Hz, 2H), 6.34 (d, J¼8.3 Hz, 2H), 6.21 (s,
1H), 5.98 (d, J¼8.2 Hz, 1H), 5.33 (s, 1H), 4.74 (d, J¼11.0 Hz, 1H), 3.49
tetramethylsilane (
d
¼0 ppm) for 1H NMR and deuterochloroform
(
d
¼77.00 ppm) for 13C NMR spectroscopy. The following abbrevia-
tions were used to designate chemical shift multiplicities: s¼singlet,
d¼doublet, t¼triplet, q¼quartet, h¼heptet, m¼multiplet, br¼broad.
HRMS spectra were recorded on a GCT Premier instrument.
(s, 3H), 2.24 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 171.51, 171.14,
145.52, 145.34, 143.72, 136.70, 136.55, 134.92, 134.31, 134.27, 133.98,
133.63, 133.08, 131.01, 130.80, 130.29, 130.13, 129.65, 129.42, 129.35,
129.31, 128.65, 128.40, 128.24, 128.12, 127.03, 126.94, 122.58, 122.16,
118.86, 118.55, 116.39, 115.58, 114.19, 113.26, 70.34, 70.12, 65.22,
63.08, 52.91, 52.71, 21.43, 21.42; ESCI-HRMS calcd for
4.2. General procedure for the three-component reaction of
diazo compounds with arylamine and N-sulfonyl aldimines
To a stirred solution of Rh2(OAc)4 (0.002 mmol), arylamine 5
(0.3 mmol), N-sulfonyl aldimines 6, 8 or 9 (0.2 mmol) and squar-
amide 1 in dichloromethane (1.5 mL) at room temperature for
10 min, then added diazo compounds 4 (0.3 mmol) in dichloro-
methane (0.5 mL) over 1 h. After completion of the addition, the
reaction mixture was stirred for another 1 h. Solvent was removed,
and a portion of crude product was subjected to 1H NMR analysis
for determination of diastereoselectivity. The crude product was
purified by flash chromatography on silica gel (ethyl acetate/pe-
troleum ether¼1:20w1:3) to give the corresponding three-
component products 7.
C
29H26BrClN2NaO4S, [MþNa]þ 635.0377; Found: 635.038.
4.2.5. Methyl 3-(4-bromophenyl)-2-(4-chlorophenylamino)-3-(4-
methylphenyl sulfonamido)-2-phenylpropanoate (7d). Yield: 64%;
1H NMR (400 MHz, CDCl3)
d (anti) 7.41e7.28 (m, 3H), 7.28e7.17 (m,
3H), 7.14 (d, J¼8.4 Hz, 2H), 7.01 (m, 3H), 6.93 (dd, J¼13.4, 8.8 Hz, 2H),
6.48 (d, J¼8.4 Hz, 2H), 6.19 (d, J¼8.9 Hz, 2H), 5.46 (d, J¼9.6 Hz, 1H),
5.18 (d, J¼9.7 Hz, 1H), 5.03 (s, 1H), 3.65 (s, 3H), 2.32 (s, 3H); (syn)
7.41e7.28 (m, 3H), 7.28e7.17 (m, 3H), 7.14 (d, J¼8.4 Hz, 2H), 7.01 (m,
3H), 6.93 (dd, J¼13.4, 8.8 Hz, 2H), 6.39 (dd, J¼11.3, 8.7 Hz, 4H), 6.05
(d, J¼11.0 Hz, 1H), 5.38 (s, 1H), 4.84 (d, J¼11.0 Hz, 1H), 3.55 (s, 1H),
4.2.1. Methyl 3-(4-bromophenyl)-3-(4-methylphenylsulfonamido)-2-
2.31 (s, 1H); 13C NMR (101 MHz, CDCl3)
d 171.61, 171.21, 143.67,
phenyl-2-(phenyl-amino)
propanoate
(anti-7a). 1H
NMR
143.38, 143.19, 136.67, 136.48, 134.95, 133.94, 133.58, 133.15, 131.46,
131.43, 130.97, 130.78, 130.29, 130.14, 129.39, 129.36, 129.25, 128.66,
128.63, 128.38, 128.25, 128.10, 127.03, 126.92, 122.52, 122.13, 117.94,
117.05, 110.93, 110.56, 70.36, 70.20, 65.11, 63.02, 52.89, 52.70, 21.43,
(400 MHz, CDCl3) 7.35e7.26 (m, 4H), 7.26e7.13 (m, 3H), 7.07 (m,
d
2H), 7.00e6.84 (m, 4H), 6.60 (m, 1H), 6.44 (d, J¼8.5 Hz, 2H), 6.20 (d,
J¼7.8 Hz, 2H), 5.36 (d, J¼9.1 Hz, 1H), 5.15 (d, J¼9.2 Hz, 1H), 4.83 (s,
1H), 3.56 (s, 3H), 2.26 (s, 3H). 13C NMR (101 MHz, CDCl3)
d
170.47,
21.41; ESCI-HRMS calcd for
635.0377; Found: 635.0376.
C
29H26BrClN2NaO4S, [MþNa]þ
143.21, 142.52, 135.81, 133.21, 132.76, 129.87, 129.20, 128.38, 128.32,
127.70, 127.47, 127.02, 125.91, 121.41, 117.71, 114.55, 69.38, 61.96,
51.74, 20.40; ESCI-HRMS calcd for C29H27BrN2NaO4S, [MþNa]þ
601.0767; Found: 601.0787.
4.2.6. Methyl 3-(4-bromophenyl)-2-(2-bromophenylamino)-3-(4-
methylphenyl-sulfonamido)-2-phenylpropanoate (anti-7e). Yield:
47%; 1H NMR (400 MHz, CDCl3)
7.33 (d, J¼8.0 Hz, 3H), 7.24 (d,
d
4.2.2. Methyl 3-(4-bromophenyl)-3-(4-methylphenylsulfonamido)-
J¼8.0 Hz, 2H), 7.16 (d, J¼7.6 Hz, 3H), 7.08 (d, J¼8.2 Hz, 2H), 6.88 (d,
J¼8.0 Hz, 2H), 6.66 (d, J¼7.8 Hz, 1H), 6.56 (d, J¼8.2 Hz, 2H), 6.42 (t,
J¼7.6 Hz, 1H), 5.85e5.81 (m, 2H), 5.43 (s, 1H), 5.11 (d, J¼9.3 Hz, 1H),
2-phenyl-2-(phenyl-amino)
(400 MHz, CDCl3)
propanoate
(syn-7a). 1H
NMR
d
7.25 (dd, J¼12.3, 7.8 Hz, 4H), 7.17 (dd, J¼13.6,
5.8 Hz, 3H), 6.95 (dd, J¼12.4, 7.8 Hz, 4H), 6.88 (d, J¼7.8 Hz, 2H), 6.63
(t, J¼7.3 Hz, 1H), 6.39 (t, J¼6.8 Hz, 4H), 5.90 (d, J¼10.9 Hz, 1H), 5.23
(s, 1H), 4.90 (d, J¼10.5 Hz, 1H), 3.47 (s, 3H), 2.25 (s, 3H); 13C NMR
3.58 (s, 3H), 2.23 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 171.47, 143.32,
141.49, 136.96, 134.34, 134.04, 132.47, 131.14, 130.13, 129.23, 128.69,
128.52, 128.37, 127.37, 126.92, 122.57, 119.18, 115.33, 111.41, 70.38,
63.88, 53.02, 21.41; ESCI-HRMS calcd for C29H26Br2ClN2NaO4S,
[MþNa]þ 678.9872; Found: 678.9850.
(101 MHz, CDCl3)
d 170.96, 143.09, 142.48, 135.70, 134.36, 132.89,
129.76, 129.27, 128.18, 127.71, 127.17, 125.95, 121.06, 117.91, 115.37,
69.29, 63.62, 51.65, 20.38; ESCI-HRMS calcd for C29H27BrN2NaO4S,
[MþNa]þ 601.0767; Found: 601.0787.
4.2.7. Methyl 3-(4-bromophenyl)-2-(4-bromophenylamino)-3-(4-
methylphenyl-sulfonamido)-2-phenylpropanoate (7f). Yield: 53%;
4.2.3. Methyl 3-(4-bromophenyl)-2-(2-chlorophenylamino)-3-(4-
1H NMR (400 MHz, CDCl3)
d
(anti) 7.28 (dd, J¼15.1, 7.9 Hz, 3H), 7.15
methylphenyl-sulfonamido)-2-phenylpropanoate (7b). Yield: 50%;
(dd, J¼20.1, 5.2 Hz, 6H), 6.96e6.78 (m, 4H), 6.39 (d, J¼8.2 Hz, 2H),
5.97 (d, J¼8.6 Hz, 2H), 5.68 (d, J¼9.9 Hz, 1H), 5.06 (s, 1H), 3.56 (s,
3H), 2.22 (s, 3H); (syn) 7.28 (dd, J¼15.1, 7.9 Hz, 2H), 7.15 (dd, J¼20.1,
5.2 Hz, 5H), 7.03 (d, J¼8.2 Hz, 1H), 6.97e6.77 (m, 5H), 6.32 (d,
J¼8.2 Hz, 2H), 6.14 (d, J¼8.4 Hz, 2H), 5.35 (s, 1H), 5.11 (d, J¼9.9 Hz,
1H), 4.73 (d, J¼11.1 Hz, 1H), 3.46 (s, 3H), 2.22 (s, 3H); 13C NMR
1H NMR (400 MHz, CDCl3)
d
(anti) 7.41 (d, J¼7.2 Hz, 2H), 7.36e7.19
(m, 6H), 7.16 (d, J¼8.4 Hz, 1H), 7.01e6.93 (m, 2H), 6.70 (d, J¼7.3 Hz,
2H), 6.63 (d, J¼8.4 Hz, 1H), 6.56 (dd, J¼11.9, 4.4 Hz, 2H), 5.92 (d,
J¼8.2 Hz, 1H), 5.84 (d, J¼9.3 Hz, 1H), 5.52 (s, 1H), 5.18 (d, J¼9.4 Hz,
1H), 3.65 (s, 3H), 2.31 (s, 3H); (syn) 7.41 (d, J¼7.2 Hz, 2H), 7.36e7.19
(m, 6H), 7.16 (d, J¼8.4 Hz, 1H), 7.01e6.93 (m, 2H), 6.70 (d, J¼7.3 Hz,
2H), 6.63 (d, J¼8.4 Hz, 1H), 6.45 (d, J¼8.3 Hz, 1H), 6.18 (d, J¼8.2 Hz,
1H), 6.02 (m, 1H), 5.03 (d, J¼10.9 Hz, 1H), 3.54 (s, 3H), 2.30 (s, 3H);
(101 MHz, CDCl3)
d 171.47, 171.20, 144.07, 143.90, 143.69, 137.30,
136.61, 136.41, 134.95, 133.89, 133.55, 133.15, 130.95, 130.78, 130.32,
130.19, 129.40, 129.37, 129.27, 128.68, 128.58, 128.38, 128.24, 128.07,
127.08, 126.95, 122.48, 122.13, 118.46, 117.62, 80.39, 79.93, 70.29,
13C NMR (101 MHz, CDCl3)
d 171.46, 143.34, 140.49, 136.93, 134.25,

L. Qiu et al. / Tetrahedron 70 (2014) 1471e1477
1475
70.03, 65.19, 63.01, 52.94, 52.74, 21.46, 21.45. ESCI-HRMS calcd for
C
7.35e7.29 (m, 2H), 7.22 (m, 9H), 6.91 (d, J¼8.1 Hz, 2H), 6.86 (d,
J¼8.3 Hz, 2H), 6.73 (s, 1H), 6.33 (d, J¼0.9 Hz, 1H), 5.95 (t, J¼8.6 Hz,
1H), 5.84 (dd, J¼8.3, 1.1 Hz, 1H), 5.26 (d, J¼8.0 Hz, 1H), 5.19 (s, 1H),
29H26Br2ClN2O4S, [MþNa]þ 678.9872; Found: 678.9856.
4.2.8. Methyl 3-(4-bromophenyl)-2-(2-iodophenylamino)-3-(4-
methylphenyl-sulfonamido)-2-phenylpropanoate (anti-7g). Yield:
54%; 1H NMR (400 MHz, CDCl3)
7.56 (d, J¼7.8 Hz, 1H), 7.35 (d,
3.61 (s, 3H), 2.25 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 170.37,142.56,
142.45, 139.62, 138.31, 135.83, 133.55, 130.54, 128.45, 128.29, 127.71,
127.56, 127.41, 127.32, 125.92, 119.41, 117.16, 113.70, 111.03, 86.56,
69.78, 62.29, 52.26, 20.39; ESCI-HRMS calcd for C30H26IN3NaO4S,
[MþNa]þ 674.0581; Found: 674.0563.
d
J¼7.6 Hz, 2H), 7.27e7.10 (m, 5H), 7.06 (d, J¼8.1 Hz, 2H), 6.88 (d,
J¼8.0 Hz, 2H), 6.71 (m, 1H), 6.57 (d, J¼8.2 Hz, 2H), 6.30 (m, 1H), 5.81
(d, J¼8.5 Hz, 2H), 5.22 (d, J¼2.5 Hz, 1H), 5.14 (d, J¼9.1 Hz, 1H), 3.59
(s, 3H), 2.23 (s, 3H); 13C NMR (101 MHz, CDCl3)
d
171.52, 143.82,
4.2.13. Methyl
amido)-2-phenyl-3-(4-(trifluoromethyl)phenyl) propanoate (anti-
7l). Yield: 40%; 1H NMR (400 MHz, CDCl3)
2-(2-iodophenylamino)-3-(4-methylphenylsulfon-
143.30, 139.23, 137.02, 134.50, 133.93, 131.13, 130.28, 129.21, 128.65,
128.49, 128.39, 128.28, 126.92, 122.54, 120.04, 114.81, 87.30, 70.77,
d
7.57 (dd, J¼7.9, 1.4 Hz,
63.79, 53.06, 21.41; ESCI-HRMS calcd for
C
29H26BrIN2NaO4S,
1H), 7.42e7.31 (m, 2H), 7.25e7.10 (m, 7H), 6.80 (dd, J¼15.7, 8.1 Hz,
4H), 6.75e6.67 (m, 1H), 6.31 (td, J¼7.8, 1.3 Hz, 1H), 5.90 (d, J¼9.0 Hz,
1H), 5.84 (dd, J¼8.3, 1.2 Hz, 1H), 5.29 (d, J¼9.0 Hz, 1H), 5.27 (s, 1H),
[MþNa]þ 726.9734; Found: 726.9707.
4.2.9. Methyl 3-(4-bromophenyl)-2-(2-methoxyphenylamino)-3-(4-
3.62 (s, 3H), 2.17 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 170.44, 142.61,
methylphenyl-sulfonamido)-2-phenylpropanoate (7h). Yield: 43%;
142.31, 138.26, 137.91, 135.87, 133.50, 128.13, 128.07, 127.59, 127.56,
127.46, 127.35, 125.88, 123.78, 123.75, 119.13, 113.66, 86.38, 69.72,
1H NMR (400 MHz, CDCl3)
d (anti) 7.38e7.20 (m, 3H), 7.20e7.08 (m,
2H), 7.04e6.97 (m, 2H), 6.87 (dd, J¼14.1, 8.0 Hz, 2H), 6.67 (dd, J¼20.3,
8.0 Hz,1H), 6.53(d, J¼8.1 Hz, 2H), 6.42(d, J¼7.9 Hz, 2H), 5.97e5.85(m,
1H), 5.78 (d, J¼7.9 Hz, 2H), 5.47 (s, 1H), 5.13 (d, J¼8.8 Hz, 1H), 3.74 (s,
3H), 3.53 (s, 3H), 2.23 (s, 3H); (syn) 7.38e7.20 (m, 3H), 7.20e7.08 (m,
2H), 7.04e6.97 (m, 2H), 6.87 (dd, J¼14.1, 8.0 Hz, 2H), 6.67 (dd, J¼20.3,
8.0 Hz,1H), 6.53(d, J¼8.1 Hz, 2H), 6.42(d, J¼7.9 Hz, 2H), 5.97e5.85(m,
1H), 5.78 (d, J¼7.9 Hz, 2H), 5.19 (s,1H), 4.98 (d, J¼10.5 Hz,1H), 3.81 (s,
62.34, 52.18, 20.14; ESCI-HRMS calcd for C30H26F3IN2NaO4S,
[MþNa]þ 717.0502; Found: 717.0472.
4.2.14. Methyl 3-(4-chlorophenyl)-2-(4-chlorophenylamino)-3-(4-
methylphenyl-sulfonamido)-2-phenyl propanoate (7m). Yield: 40%;
1H NMR (400 MHz, CDCl3)
d
(anti) 7.25 (t, J¼7.1 Hz, 3H), 7.22e7.10
(m, 3H), 6.92 (dd, J¼8.2, 6.2 Hz, 2H), 6.89e6.81 (m, 4H), 6.79 (d,
J¼8.5 Hz, 1H), 6.48 (d, J¼8.5 Hz, 2H), 6.16e6.08 (m, 2H), 5.42 (d,
J¼9.7 Hz,1H), 5.12 (d, J¼9.7 Hz, 1H), 4.98 (s, 1H), 3.57 (s, 3H), 2.24 (s,
3H); (syn) 7.25 (t, J¼7.1 Hz, 4H), 7.22e7.10 (m, 3H), 6.92 (dd, J¼8.2,
6.2 Hz, 2H), 6.89e6.81 (m, 4H), 6.79 (d, J¼8.5 Hz, 1H), 6.40 (d,
J¼8.5 Hz, 2H), 6.34e6.26 (m, 2H), 5.42 (d, J¼9.7 Hz, 1H), 5.31 (s, 1H),
5.12 (d, J¼9.7 Hz, 1H), 4.77 (d, J¼11.0 Hz, 1H), 3.48 (s, 3H), 2.22 (s,
3H), 3.42 (s, 3H), 2.22 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 171.88,
171.84, 147.93, 147.49, 143.33, 143.24, 136.99, 136.88, 135.36, 134.93,
134.56, 134.22, 134.15, 134.01, 130.80, 130.73, 130.37, 130.33, 129.21,
129.15, 128.88, 128.80, 128.32, 128.14, 127.03, 126.98, 122.24, 122.06,
120.41, 120.36, 118.21, 117.88, 114.94, 113.78, 109.86, 109.67, 70.18,
64.44, 63.41, 55.86, 55.76, 52.79, 52.64, 21.42, 21.41; ESCI-HRMS calcd
for C30H29BrN2NaO5S, [MþNa]þ 631.0873; Found: 631.0878.
3H); 13C NMR (101 MHz, CDCl3)
d 170.65, 170.23, 142.59, 141.90,
141.71, 135.69, 135.52, 134.03, 133.33, 132.95, 132.47, 132.18, 132.12,
128.93, 128.79, 128.38, 128.32, 128.20, 127.65, 127.59, 127.55, 127.51,
127.33, 127.20, 127.06, 126.99, 126.79, 126.01, 125.89, 122.69, 122.36,
116.48, 115.58, 69.46, 69.32, 64.01, 61.95, 51.82, 51.64, 20.36, 20.32;
4.2.10. Methyl
amido)-3-(4-nitrophenyl)-2-phenylpropanoate (7i). Yield: 70%; 1H
NMR (400 MHz, CDCl3)
2-(2-iodophenylamino)-3-(4-methylphenylsulfon-
d
(anti) 7.79 (d, J¼8.8 Hz, 2H), 7.58 (dd,
J¼7.9, 1.4 Hz, 1H), 7.36e7.29 (m, 2H), 7.29e7.22 (m, 3H), 7.22e7.14
(m, 3H), 6.92 (dd, J¼8.2, 6.7 Hz, 2H), 6.86 (d, J¼8.1 Hz, 1H), 6.73 (d,
J¼8.7 Hz, 2H), 6.36 (d, J¼7.7 Hz, 1H), 5.97 (d, J¼7.9 Hz, 1H),
5.89e5.84 (m, 1H), 5.31 (d, J¼7.8 Hz, 1H), 5.19 (s, 1H), 3.62 (s, 3H),
ESCI-HRMS calcd for
Found: 591.0885.
C
29H26Cl2N2NaO4S, [MþNa]þ 591.0883;
4 . 2 . 1 5 . M e t h y l 2 - ( 4 - c h l o r o p h e n y l a m i n o ) - 3 - ( 4 -
methylphenylsulfonamido)-2-phenyl-3-p-tolylpropanoate
2.21 (s, 3H); (syn)
d
7.79 (d, J¼8.8 Hz, 2H), 7.58 (dd, J¼7.9,1.4 Hz,1H),
7.36e7.29 (m, 2H), 7.29e7.22 (m, 3H), 7.22e7.14 (m, 3H), 6.92 (dd,
J¼8.2, 6.7 Hz, 2H), 6.86 (d, J¼8.1 Hz, 1H), 6.73 (d, J¼8.7 Hz, 2H), 6.36
(d, J¼7.7 Hz, 1H), 6.06 (dd, J¼8.3, 1.2 Hz, 1H), 5.76 (s, 1H), 5.14 (d,
J¼10.6 Hz, 1H), 3.50 (s, 3H), 2.16 (s, 3H); 13C NMR (101 MHz, CDCl3)
(7n). Yield: 15%; 1H NMR (400 MHz, CDCl3)
d
(anti) 7.26 (dd, J¼17.0,
8.2 Hz, 4H), 7.20e7.10 (m, 3H), 6.93e6.87 (m, 2H), 6.87e6.80 (m,
4H), 6.65 (d, J¼7.9 Hz, 1H), 6.36 (d, J¼8.0 Hz, 2H), 6.29 (d, J¼8.9 Hz,
2H), 5.76 (d, J¼10.9 Hz,1H), 5.28 (s, 1H), 4.80 (d, J¼10.9 Hz,1H), 3.48
(s, 3H), 2.19 (s, 3H), 2.13 (s, 3H); (syn) 7.26 (dd, J¼17.0, 8.2 Hz, 3H),
7.20e7.10 (m, 3H), 6.93e6.87 (m, 2H), 6.87e6.80 (m, 3H), 6.78 (d,
J¼7.9 Hz, 2H), 6.44 (d, J¼8.1 Hz, 2H), 6.11 (d, J¼8.9 Hz, 2H), 5.25 (s,
1H), 5.05 (s, 1H), 5.04 (d, J¼8.3 Hz, 1H), 3.57 (s, 3H), 2.21 (s, 3H), 2.18
d
170.37, 146.50, 142.66, 142.39, 141.61, 138.45, 138.34, 135.79,
133.56, 128.79, 128.70, 128.31, 128.25, 127.79, 127.62, 127.55, 127.45,
127.25, 126.03, 125.93, 121.87, 121.61, 119.53, 114.34, 113.68, 86.68,
69.89, 69.78, 62.04, 52.30, 52.01, 20.34; ESCI-HRMS calcd for
C
29H26IN3NaO6S, [MþNa]þ 694.0479; Found: 694.0474.
(s, 3H); 13C NMR (101 MHz, CDCl3)
d 170.75, 170.41, 142.24, 142.09,
141.99, 137.25, 136.77, 135.96, 135.72, 134.26, 132.39, 130.79, 130.55,
128.59, 128.18, 128.02, 127.85, 127.62, 127.52, 127.47, 127.41, 127.36,
127.31, 127.14, 127.09, 127.03, 126.88, 126.04, 125.86, 122.43, 121.97,
116.28, 115.40, 69.31, 64.02, 62.93, 51.58, 20.31, 20.01, 19.93; ESCI-
HRMS calcd for C30H32ClN2NaO7S, [MþNa]þ 571.1552; Found:
571.1423.
4.2.11. Methyl
amido)-3-(3-nitrophenyl)-2-phenylpropanoate (anti-7j). Yield: 52%;
1H NMR (400 MHz, CDCl3)
2-(2-iodophenylamino)-3-(4-methylphenylsulfon-
d
7.88 (dd, J¼8.1, 1.0 Hz, 1H), 7.60e7.43
(m, 2H), 7.32 (d, J¼7.2 Hz, 2H), 7.29e7.19 (m, 3H), 7.13 (m, 4H),
6.91e6.69 (m, 3H), 6.38e6.29 (m, 1H), 6.13 (d, J¼8.1 Hz, 1H), 5.91
(dd, J¼8.2, 1.0 Hz, 1H), 5.34 (d, J¼8.1 Hz, 1H), 5.25 (s, 1H), 3.64 (s,
3H), 2.16 (s, 3H); 13C NMR (101 MHz, CDCl3)
d
170.32, 146.51, 142.48,
4.2.16. Methyl 3-(4-bromophenyl)-2-(2-iodophenylamino)-3-(4-
142.38, 138.33, 136.18, 135.78, 133.91, 133.47, 128.31, 127.85, 127.74,
127.56, 127.49, 127.37, 126.04, 125.89, 122.54, 121.96, 119.40, 113.53,
86.58, 76.38, 76.06, 75.74, 69.70, 61.76, 52.38, 20.25; ESCI-HRMS
calcd for C29H26IN3NaO6S, [MþNa]þ 694.0466; Found: 694.0463.
nitrophenyl sulfonamido)-2-phenylpropanoate (anti-7o). Yield:
48%; 1H NMR (400 MHz, CDCl3)
d
7.97e7.89 (m, 2H), 7.55 (dd, J¼7.8,
1.4 Hz, 1H), 7.51e7.43 (m, 2H), 7.38 (dd, J¼7.8, 1.6 Hz, 2H), 7.16e7.23
(m, 5H), 6.84 (d, J¼8.4 Hz, 2H), 6.72e6.61 (m, 1H), 6.37 (s, 1H),
6.34e6.25 (m,1H), 5.74 (dd, J¼8.3,1.1 Hz,1H), 5.03 (d, J¼4.5 Hz,1H),
4.2.12. Methyl 3-(4-cyanophenyl)-2-(2-iodophenylamino)-3-(4-
4.91 (s,1H), 3.61 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 170.89,148.50,
methylphenyl sulfonamido)-2-phenylpropanoate (anti-7k). Yield:
144.79, 142.59, 138.19, 134.14, 133.12, 130.73, 129.21, 127.77, 127.72,
127.15, 126.93, 126.85, 122.82, 122.36, 119.42, 114.31, 86.75, 69.55,
52%; 1H NMR (400 MHz, CDCl3)
d
7.57 (dd, J¼7.9, 1.3 Hz, 1H),

1476
L. Qiu et al. / Tetrahedron 70 (2014) 1471e1477
63.95, 52.17; ESCI-HRMS calcd for C28H23BrIN3NaO6S, [MþNa]þ
(dd, J¼8.3,1.2 Hz,1H), 5.26 (d, J¼7.4 Hz,1H), 5.16 (s,1H), 3.72 (s, 3H),
3.64 (s, 3H), 2.19 (s, 3H); (syn) 7.94e7.88 (m, 1H), 7.52 (m, 2H),
7.32e7.22 (m, 2H), 7.22e7.05 (m, 4H), 6.85 (t, J¼19.6 Hz, 3H), 6.74
(dd, J¼33.1, 8.7 Hz, 3H), 6.38e6.31 (m, 1H), 6.10 (dd, J¼8.3, 1.3 Hz,
1H), 5.90e5.86 (m, 1H), 5.64 (s, 1H), 3.73 (s, 3H), 3.52 (s, 3H), 2.15 (s,
757.9433; Found: 757.9421.
4.2.17. Methyl 3-(4-bromophenyl)-2-(2-iodophenylamino)-2-
phenyl-3-(thiophe-ne-2-sulfonamido)propanoate (anti-7p). Yield:
56%; 1H NMR (400 MHz, CDCl3)
d
(anti) 7.64 (dd, J¼7.8, 1.4 Hz, 1H),
3H);13C NMR (101 MHz, CDCl3)
d 170.53, 158.70, 146.60, 142.44,
7.43 (dd, J¼7.9, 1.5 Hz, 2H), 7.33 (dd, J¼5.0, 1.3 Hz, 1H), 7.30e7.17 (m,
6H), 7.12 (dt, J¼3.8, 2.1 Hz, 1H), 6.82e6.70 (m, 4H), 6.38 (td, J¼7.8,
1.3 Hz,1H), 6.07 (d, J¼8.8 Hz,1H), 5.88 (dd, J¼8.3,1.2 Hz,1H), 5.27 (s,
1H), 5.24 (d, J¼2.9 Hz, 1H), 3.68 (s, 3H); 13C NMR (101 MHz, CDCl3)
138.31, 136.39, 135.90, 133.93, 128.61, 128.28, 127.86, 127.53, 125.85,
122.48, 122.02, 119.40, 113.58, 112.93, 86.61, 69.26, 62.02, 54.23,
52.30, 20.26; ESCI-HRMS calcd for C30H28IN3NaO7S, [MþNa]þ
724.0585; Found: 724.0562.
d
171.51, 143.78, 141.01, 139.26, 134.49, 133.95, 132.33, 131.99, 131.31,
130.10, 128.61, 128.55, 128.50, 128.28, 127.09, 122.82, 120.16, 114.91,
87.40, 70.77, 64.04, 53.12; ESCI-HRMS calcd for C26H22BrIN2NaO4S2,
[MþNa]þ 718.9141; Found: 718.9106.
4.2.22. Methyl 2-(4-bromophenyl)-2-(2-iodophenylamino)-3-(4-
methylphenyl sulfonamido)-3-(3-nitrophenyl)propanoate (7u).
Yield: 55%; 1H NMR (400 MHz, CDCl3)
d
(anti) 7.96 (dd, J¼8.1,
1.1 Hz, 1H), 7.66 (s, 1H), 7.57 (dd, J¼7.9, 1.3 Hz, 1H), 7.35e7.22 (m,
6H), 7.22e7.09 (m, 2H), 6.91 (d, J¼8.1 Hz, 2H), 6.76 (dd, J¼11.3,
4.2 Hz, 1H), 6.35 (td, J¼7.8, 1.2 Hz, 1H), 6.08 (d, J¼8.3 Hz, 1H), 5.80
(dd, J¼8.3, 1.1 Hz, 1H), 5.17 (d, J¼8.3 Hz, 1H), 5.12 (s, 1H), 3.64 (s,
3H), 2.21 (s, 3H); (syn) 7.96 (dd, J¼8.1, 1.1 Hz, 1H), 7.66 (s, 1H), 7.57
(dd, J¼7.9, 1.3 Hz, 1H), 7.35e7.22 (m, 6H), 7.22e7.09 (m, 2H), 6.91
(d, J¼8.1 Hz, 2H), 6.76 (dd, J¼11.3, 4.2 Hz, 1H), 6.39 (t, J¼5.7 Hz,
1H), 5.98 (dt, J¼14.9, 7.5 Hz, 1H), 5.85 (t, J¼10.9 Hz, 1H), 5.68 (s,
1H), 5.08 (d, J¼10.5 Hz, 1H), 3.50 (s, 3H), 2.15 (s, 3H); 13C NMR
4.2.18. Methyl 2-(2-iodophenylamino)-3-(3-nitrophenyl)-3-(4-
nitrophenylsulfonamido)-2-phenylpropanoate (7q). Yield: 58%; 1H
NMR (400 MHz, CDCl3)
d
(anti) 8.04 (d, J¼7.5 Hz, 1H), 8.00e7.89 (m,
2H), 7.86 (s, 1H), 7.62e7.50 (m, 3H), 7.34 (t, J¼7.4 Hz, 2H), 7.21 (s,
2H), 7.18 (d, J¼10.1 Hz, 3H), 6.75e6.65 (m, 1H), 6.53 (s, 1H), 6.34 (td,
J¼7.8, 1.3 Hz, 1H), 5.81 (dd, J¼8.3, 1.1 Hz, 1H), 5.18 (s, 1H), 4.87 (s,
1H), 3.64 (s, 3H); (syn) 8.04 (d, J¼7.5 Hz, 1H), 8.00e7.89 (m, 2H),
7.86 (s, 1H), 7.62e7.50 (m, 3H), 7.34 (t, J¼7.4 Hz, 2H), 7.21 (s, 2H),
7.18 (d, J¼10.1 Hz, 3H), 6.79 (s,1H), 6.40 (s,1H), 6.23 (s,1H), 6.04 (dd,
J¼8.3, 1.2 Hz, 1H), 5.63 (s, 1H), 5.25e5.19 (m, 1H), 3.52 (s, 3H); 13C
(101 MHz, CDCl3)
d 170.10, 146.77, 142.65, 142.13, 138.42, 136.21,
135.59, 133.70, 132.81, 130.70, 129.00, 128.39, 128.22, 127.51,
125.82, 122.38, 122.34, 122.19, 119.66, 113.60, 86.60, 69.18, 62.39,
52.50, 20.34; ESCI-HRMS calcd for C29H25BrIN3NaO6S, [MþNa]þ
771.9584; Found: 771.9581.
NMR (101 MHz, CDCl3)
d 170.77, 148.69, 146.99, 144.46, 142.21,
138.32, 136.82, 134.05, 133.67, 128.54, 128.02, 127.96, 127.73, 127.37,
127.21, 126.94, 126.61, 122.95, 122.84, 122.63, 119.88, 114.03, 87.03,
69.56, 63.22, 52.44; ESCI-HRMS calcd for
C28H23IN4NaO8S,
[MþNa]þ 725.0173; Found: 725.0152.
4.2.23. Methyl 2-(2-iodophenylamino)-3-(3-nitrophenyl)-3-(4-
nitrophenylsulfonamido)-2-p-tolylpropanoate (anti-7v). Yield: 52%;
4.2.19. Methyl 2-(2-iodophenylamino)-3-(3-nitrophenyl)-2-phenyl-
1H NMR (400 MHz, CDCl3)
d 7.96 (m, 1H), 7.66e7.47 (m, 4H),
3-(thiophene-2-sulfonamido) propanoate (anti-7r). Yield: 56%; 1H
7.44e7.29 (m, 2H), 7.20e7.08 (m, 4H), 6.94 (d, J¼8.1 Hz, 2H), 6.72
(dd, J¼11.4, 4.1 Hz, 1H), 6.54 (s, 1H), 6.33 (td, J¼7.8, 1.3 Hz, 1H), 5.80
(dd, J¼8.3, 1.1 Hz, 1H), 5.13 (s, 1H), 4.83 (s, 1H), 3.62 (s, 3H), 2.22 (s,
NMR (400 MHz, CDCl3)
d 8.00e7.93 (m, 1H), 7.69 (s, 1H), 7.58 (m,
1H), 7.40e7.29 (m, 2H), 7.29e7.17 (m, 5H), 7.17e7.05 (m, 2H), 6.77
(dt, J¼8.3, 2.8 Hz, 1H), 6.66 (s, 1H), 6.35 (td, J¼7.7, 1.3 Hz, 1H), 6.19 (s,
1H), 5.91 (dd, J¼8.3,1.1 Hz,1H), 5.38 (s, 1H), 5.19 (s, 1H), 3.67 (s, 3H);
3H); 13C NMR (101 MHz, CDCl3)
d 170.86, 148.60, 146.99, 144.44,
142.32, 138.26, 138.11, 137.03, 135.87, 133.69, 130.95,128.59, 128.55,
127.95, 127.34, 127.22, 127.09, 126.99, 126.40, 122.85, 122.81, 119.76,
114.05, 86.99, 69.37, 63.30, 52.35, 19.93; ESCI-HRMS calcd for
13C NMR (101 MHz, CDCl3)
d 170.32, 146.67, 142.32, 139.76, 138.37,
136.23, 133.70, 133.48, 131.47, 131.28, 128.02, 127.89, 127.70, 127.60,
127.51, 127.25, 126.12, 122.36, 122.33, 119.56, 113.60, 86.69, 69.71,
62.00, 52.44; ESCI-HRMS calcd for C28H22IN3NaO6S2, [MþNa]þ
685.9887; Found: 685.9866.
C
29H25IN4NaO8S, [MþNa]þ 739.0436; Found: 739.0347.
4.2.24. Methyl 2-(3-bromophenyl)-2-(2-iodophenylamino)-3-(3-
nitrophenyl)-3-(4-nitrophenylsulfonamido) propanoate (anti-7w).
4.2.20. Methyl
amido)-3-(3-nitrophenyl)-2-p-tolylpropanoate (7s). Yield: 57%; 1H
NMR (400 MHz, CDCl3)
(anti) 7.94e7.87 (m, 1H), 7.57 (dd, J¼7.9,
2-(2-iodophenylamino)-3-(4-methylphenylsulfon-
Yield: 54%; 1H NMR (400 MHz, CDCl3)
d 8.17e8.03 (m, 1H),
8.03e7.87 (m, 3H), 7.68e7.48 (m, 4H), 7.45e7.31 (m, 3H), 7.31e7.24
(m, 1H), 7.19 (s, 1H), 7.01 (t, J¼8.0 Hz, 1H), 6.72 (d, J¼7.1 Hz, 1H),
6.59 (s, 1H) 6.35 (td, J¼7.7, 1.3 Hz, 1H), 5.70 (dd, J¼8.3, 1.2 Hz, 1H),
5.06 (s, 1H), 4.80 (s, 1H), 3.63 (s, 3H); 13C NMR (101 MHz, CDCl3)
d
1.4 Hz, 1H), 7.49 (s, 1H), 7.26 (dd, J¼8.2, 5.2 Hz, 2H), 7.23e7.05 (m,
4H), 6.97 (d, J¼8.2 Hz, 2H), 6.87 (d, J¼8.1 Hz, 2H), 6.76 (dd, J¼11.3,
4.1 Hz, 1H), 6.33 (dd, J¼11.9, 4.5 Hz, 1H), 5.99 (d, J¼7.7 Hz, 1H), 5.93
(dd, J¼8.3,1.1 Hz,1H), 5.30 (d, J¼7.7 Hz,1H), 5.19 (s,1H), 3.63 (s, 3H),
2.24 (s, 3H), 2.18 (s, 3H); (syn) 7.94e7.87 (m, 1H), 7.57 (dd, J¼7.9,
1.4 Hz, 1H), 7.49 (s, 1H), 7.26 (dd, J¼8.2, 5.2 Hz, 2H), 7.23e7.05 (m,
4H), 6.97 (d, J¼8.2 Hz, 2H), 6.87 (d, J¼8.1 Hz, 2H), 6.76 (dd, J¼11.3,
4.1 Hz, 1H), 6.33 (dd, J¼11.9, 4.5 Hz, 1H), 6.08 (dt, J¼8.3, 4.1 Hz, 1H),
5.83 (dd, J¼18.3, 8.6 Hz, 1H), 5.67 (s, 1H), 5.14 (t, J¼8.6 Hz, 1H), 3.50
d
170.36, 148.80, 147.15, 144.22, 141.96, 138.38, 136.59, 136.53,
133.43, 131.08, 129.83, 129.40, 128.90, 127.41, 126.82, 125.18, 123.17,
123.08, 122.48, 122.17, 120.08, 114.12, 86.92, 68.98, 63.93, 52.61;
ESCI-HRMS calcd for C28H23IN4O8S, [MþNa]þ 802.9284; Found:
802.9265.
Acknowledgements
(s, 3H), 2.26 (s, 3H), 2.14 (s, 3H); 13C NMR (101 MHz, CDCl3)
d 170.45,
146.55, 142.47, 142.40, 138.31, 137.73, 136.40, 135.88, 133.98, 130.44,
128.31, 128.26, 127.82, 127.50, 127.14, 126.00, 125.87, 122.56, 121.97,
119.38, 113.55, 86.62, 69.55, 61.77, 52.31, 20.27, 20.02; ESCI-HRMS
calcd for C30H28IN3NaO6S, [MþNa]þ 708.0636; Found: 708.0627.
We wish to thank the National Science Foundation of China
(21125209, 21332003), the MOST of China (2011CB808600), STCSM
(12JC1403800) and Minhang District Government in Shanghai for
financial support.
4.2.21. Methyl 2-(2-iodophenylamino)-2-(4-methoxyphenyl)-3-(4-
methylphenyl
sulfonamido)-3-(3-nitrophenyl)propanoate
(anti) 7.94e7.88 (m,
Supplementary data
(7t). Yield: 36%; 1H NMR (400 MHz, CDCl3)
d
1H), 7.52 (m, 2H), 7.32e7.22 (m, 2H), 7.22e7.05 (m, 4H), 6.85 (t,
J¼19.6 Hz, 3H), 6.74 (dd, J¼33.1, 8.7 Hz, 3H), 6.38e6.31 (m, 1H), 5.93
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.12.082.

L. Qiu et al. / Tetrahedron 70 (2014) 1471e1477
1477
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