Rh2(OAc)4 catalyzed highly diastereoselective synthesis of 2,4,5-triaryl-1,3-oxazolidines and spirooxindolyl oxazolidines

Article abstract of DOI:10.1016/j.tet.2016.02.055

A three-component coupling (3CC) of aryldiazoacetate, aldehyde and N-tosylimine has been achieved using 1 mol % of Rh₂(OAc)₄ for the synthesis of highly substituted triaryl-1,3-oxazolidines in good yields with high diastereoselectivi

Full text of DOI:10.1016/j.tet.2016.02.055

Accepted Manuscript
Rh (OAc) catalyzed highly diastereoselective synthesis of 2,4,5-triaryl-1,3-
2
4
oxazolidines and spirooxindolyl oxazolidines
T. Rajasekaran, B. Sridhar, B.V. Subba Reddy
PII:
S0040-4020(16)30117-X
10.1016/j.tet.2016.02.055
TET 27525
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 October 2015
Revised Date: 9 February 2016
Accepted Date: 25 February 2016
Please cite this article as: Rajasekaran T, Sridhar B, Subba Reddy BV, Rh (OAc) catalyzed
2
4
highly diastereoselective synthesis of 2,4,5-triaryl-1,3-oxazolidines and spirooxindolyl oxazolidines,
Tetrahedron (2016), doi: 10.1016/j.tet.2016.02.055.
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Rh2(OAc)4 catalyzed highly
diastereoselective synthesis of 2,4,5-triaryl-
1,3-oxazolidines and spirooxindolyl
oxazolidines
Leave this area blank for abstract info.
T. Rajasekaran,a B. Sridhar,b B. V. Subba Reddy*a
N2
R
Ts
Ph
Ts
N
N
O
N2
R
O
N
Bn
Ts
Ph
CO2Me
N
O
Ph
Ph CHO
+
N
3 mol%
Rh2(OAc)4
CH2Cl2, rt
1 mol%
Rh2(OAc)4
CH2Cl2, rt
Ph
O
MeO2C
Bn
R
5 examples
dr >95:5
Yield 68-75%
18 examples
dr >95:5
Yield 72-86%
R = NO2,CN

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Rh2(OAc)4 catalyzed highly diastereoselective synthesis of 2,4,5-triaryl-1,3-
oxazolidines and spirooxindolyl oxazolidines
T. Rajasekaran,a B. Sridhar,b B. V. Subba Reddy*a
aNatural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India. E-mail:basireddy@iict.res.in
bLaboratory of X-ray Crystallography, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A three-component coupling (3CC) of aryl diazoacetate, aldehyde and N-tosylimine has been
achieved using 1 mol% of Rh2(OAc)4 for the synthesis of highly substituted triaryl-1,3-
oxazolidines in good yields with high diastereoselectivity. This protocol has been successfully
extended to cyclic diazoamide, i.e. 3-diazooxindole for the synthesis of fully substituted
spirooxindolyl oxazolidines using 3 mol% of Rh2(OAc)4 under similar reaction conditions.
Available online
2009 Elsevier Ltd. All rights reserved
.
Keywords:
Diazoester
Three component reaction
1,3-Oxazolidine
Spirooxazolidine
Rhodium(II) acetate
Introduction
Recently, we developed a method for the synthesis of
spirooxindolyl oxazolines using 1,3-dipolar cycloaddition of
carbonyl ylides with ketimines derived from isatin, without
the formation of side products.9
Oxazolidines are common structural units in many
biologically active natural products and designed molecules of
pharmaceutical importance.1 In particular, 1,3-oxazolidines
act as pro-drugs for β-blockers, β3-adrenoreceptor agonists
and precursors for α-hydroxy-β-amino esters which are
frequently found in a wide range of biologically active
molecules and used as building blocks in natural product
synthesis.2,3 On the other hand, spirooxindoles are often found
in medicinally important natural products and pharmaceutical
agents. As a result, a myriad of catalytic methods have been
developed for their synthesis.4, However, the development of
a three component strategy to generate the novel series of
oxazolidines and spirooxindoles is highly desirable as they
offer rapid access to highly functionalized biologically
relevant scaffolds with wide structural diversity and excellent
bond forming efficiency in a single step process. Furthermore,
transition metal catalyzed reactions of α-diazocarbonyl
compounds have emerged as powerful synthetic tools in
organic synthesis. They have been extensively used in the
synthesis of highly functionalized five-membered heterocyclic
compounds such as dihydrofurans, tetrahydrofurans,5
pyrrolidines,6 and dioxolanes.7 In particular, the synthesis of
1,3-oxazolidines using diazo chemistry is one of the most
useful protocols but less studied when compared to furans and
dioxolanes due to the competitive side reactions such as
epoxidation and dioxolane formation, which diminish the
efficiency of three component reaction of diazo compounds,
aldehydes and imines. In 2005, Somfai et al. reported the
three component reaction of diazoester, aldehyde and
aldimine for the synthesis of syn-α-hydroxy-β-amino esters.8
Following our interest on diazo chemistry,10 we herein report
the three component reaction of aryldiazoacetate, aldehyde
and imine to produce the highly functionalized triaryl
oxazolidines, which could easily be converted into α-hydroxy-
β-amino esters with a quaternary carbon centre by hydrolysis.
In general, the coupling of 2-diazo-2-arylacetate with
aldehyde generates the epoxide exclusively, whereas imines
furnish the aziridines (Scheme 1).11 Hu et al. reported the
chemoselective synthesis of 2,4,5-triaryl-1,3-dioxolane from
2-diazo-2-arylacetate and aryl aldehydes without the
formation of epoxide.12 To the best of our knowledge, there
have been no reports on the synthesis of 2,4,5-triaryl-1,3-
oxazolidines from 2-diazo-2-arylacetate and spirooxindolyl
oxazolidines from 3-diazooxindole.
In 2001, Doyle et al
Ph
N
O
Ph
N
O
Ph
H
CO2Me
Ph
H
Ph
H
H
CO2Me
Ph
N2
Ph
Rh2(OAc)4
79%
Ph
only
MeO2C
Rh2(OAc)4
66%
Ph
only
This work
Ar2
Ar1
Ar2
1 mol%
Rh2(OAc)4
N2
N
N
Ph
MeO2C
+
CO2Me
Ph CHO
+
Ar1
Ph
Ph
CH2Cl2, rt
O
Ar1 = p-NO2-C6H4 or p-CN-C6H4
Ar2 = p-CH3-C6H4-SO2

2
Tetrahedron
ACCEPTED MANUSCRIPT
Scheme 1. Rh(II) catalyzed reaction of aryl diazoacetate
deficient aldimine 3d. To our delight, the formation of desired
1
with aldehyde and imine.
1,3-oxazolidinde 4a was observed from H NMR analysis of
the crude reaction mixture, which was then purified by
column chromatography to afford the pure 1,3-oxazolidinde
4a in 68% yield along with epoxide 5a in 10% yield (entry 5,
Table 1). The results are summarized in Table 1.
Results and Discussion
To find an efficient imine as a dipolarophile, we initially
performed the three component reaction (3CR) of methyl
phenyldiazoacetate 1a, benzaldehyde 2a and aldimines 3a and
3b that are derived from benzyl amine and aniline (entries 1
and 2, Table 1) respectively.
With a suitable aldimine in hand, we were curious to
further optimize the reaction conditions to improve the yield
and diastereoselectivity. Interestingly, the yield was increased
considerably to 81% when aldehyde and aryldiazoacetate
were used in 1.3 equiv with slow addition of aryldiazoacetate.
To optimize the catalyst loading, we further performed this
3CR reaction by varying the amount of catalyst from 1 mol%
to 5 mol%. The reaction was quite successful even with 1
mol% of the catalyst affording the desired product in 81%
yield with excellent diastereoselectivity (entry 6, Table 1).
Further increase in catalyst loading did not improve the yield.
The structure of 4f was confirmed by NMR, IR and mass
spectrometry. The relative configuration of 4f was
Me
Br
MeO
Br
O
N
N
F
O
O
R
NH
X
H
N
O
N
NH2
NH
O
O
N
H
H
R = NHAc
R
Synoxoxazolidinone A, X = Cl
Synoxoxazolidinone B, X = H
Linezolid
(Zyvox)
Horsfiline R = MeO
Coerulescine R = H
SCH3
Ts
N
N
SCH3
N
R
N
Ar1
Ar2
unambiguously confirmed by
a single crystal X-ray
O
S
O
O
diffraction studies.13
O
O
N
N
H
H
R
Spirobrassinin
Spirobrassinin's analogs
for antipyretic activity
(Wang's work)
This work
Figure 1. Biologically active oxazolidinone and
spirooxindoles
To our surprise, no desired 1,3-oxazolidine was formed
with these aldimines instead the formation of complex
mixture was observed from 1H NMR analysis of crude
reaction mixture. Similar results were also observed with
electron-deficient aldimine 3c derived from tosylamine and
ketimine 6 derived from aniline and N-methylisatin (entries 3
and 4, Table 1).
Table 1. Optimization of the reaction in the formation of 4/5a
N2
CHO
Ar2
N
Ar2
1 mol%
Rh2(OAc)4
Ar1
Ph
MeO2C
O
Ph
N
CO2Me
+
+
+
Ph
Ph
Ar1
CH2Cl2
O
CO2Me
1a
2a
3
4
5
Yield (%)b Yield (%)c
Ar1
Ph
Ar2
drd
-
Entry
Imine
Solvent
CH2Cl2
4
5
Figure 2. ORTEP structure of 4f
1
Bn
3a
-
-
2
3
Ph
Ph
Ph
Ts
3b
3c
CH2Cl2
CH2Cl2
-
-
-
-
-
-
With optimized reaction conditions in hand, we further
studied the electronic effect of substituents on aromatic ring
of the diazoacetate. In all cases, the reactions proceeded
smoothly at room temperature under mild conditions and no
significant change in yield or diastereoselectivity was
observed with substituted aryldiazoacetates (entries 1-7, Table
2). Notably, halo substituted aryldiazoacetates such as bromo-
, chloro- and fluoro- gave the products in good yields (entries
N-Methyl
oxindole
4
Ph
Ts
Ts
6
CH2Cl2
CH2Cl2
CH2Cl2
-
60
10
-
-
p-NO2Ph
p-NO2Ph
5
3d
3d
68
81
>95:5
>95:5
6e
2,
3 and 4, Table 2). In deed, fluoro substituted
aAll the reactions were performed using 1 mol% Rh2(OAc)4 with imine (1 equiv),
aldehyde 2a (1 equiv) and diazoester 1a (1 equiv) in dry dichloromethane at 25 °C.
bYield refers to pure products after column chromatography. cMixture of epoxide and
imine (entries 1,2 and 3). ddr was determined by 1H NMR analysis of crude reaction
mixture. eReaction was performed using 1 mol% Rh2(OAc)4 with imine (1 equiv),
aldehyde 2a (1.3 equiv) and diazoester 1a (1.3 equiv) in dry dichloromethane at 25 °C.
aryldiazoacetate gave the product in higher yield than chloro
substituted aryldiazoacetate (entry 4, Table 2). Furthermore,
dichloro substitued aryldiazoacetate afforded the product in
higher yield than mono-chloro derivative (entry 5, Table 2).
We have also studied the effect of electron releasing groups
such as methyl- and methoxy- on the aromatic ring of
aryldiazoacetate. Interestingly, these substrates gave the
expected products 4f and 4g in 82% and 85% yields
respectively (entries 6 and 7, Table 2). However, nitro
subtituted aryldiazoacetate failed to undergo three component
Next we examined the electronic effect of substituents that are
present on aromatic ring of the aldehyde part of the imine.
Accordingly, we performed the 3CR reaction of methyl
phenyldiazoacetate 1a, benzaldehyde 2a and electron-

3
c
reaction under the identical reaction conditions (entry 8, Table
2). We further performed the 3CR reaction of aryldiazoacetate
with aryl aldehyde bearing electron releasing and electron
withdrawing groups.
refers to pure products after column chromatography. dr was determined by 1H NMR
analysis of crude reaction mixture. dno data.
ACCEPTED MANUSCRIPT
Furthermore, we examined the effect of p-cyano- and p-
trifluoromethyl- groups that are present on aromatic ring of
the aldehyde part of the imine. It is interesting to note that the
cyano substituted aldimine underwent a smooth cycloaddition
with carbonyl ylide (entries 19 and 20, Table 2) as efficient as
nitro substituted aldimine (entries 1-7, 9-12, and 14-18, Table
2), but trifluoromethyl substituted aldimine afforded the
product as a complex mixture (entry 21, Table 2). To our
surprize, no product formation was observed with aryl
aldehydes bearing electron-withdrawing groups such as p-
nitro- and p-cyano- on the aromatic ring (entries 22 and 23,
Table 2).
Interestingly, aryl aldehydes with electron releasing groups
such as p-methyl- and p-methoxy- on aromatic ring gave the
product in 81% and 84% yields respectively without the loss
of diastereoselectivity (entries 9 and 10, Table 2). It is worth
mentioning that di- and tri-methoxybenzaldehydes also gave
the products in 84% and 86% yields respectively with good
diastereoselectivity (entries 11 and 12, Table 2). Although no
product
formation
was
observed
with
ortho-
chlorobenzaldehyde (entry 13, Table 2), para-bromo, chloro
and fluoro substituted aryl aldehydes participated well in the
reaction (entries 14, 15 and 16, Table 2), In addition, β-
naphthaldehyde was also effective for this conversion (entry
17, Table 2). It is noteworthy to mention that the reaction also
proceeded effectively with heterocyclic aldehyde such as
furan-2-carboxaldehyde (entry 18, Table 2).
Due to the importance of spirooxindoles in drug discovery,
we further extended this method to cyclic diazoamide (7)
(Table 3). The reaction was successful only with electron-
deficient aldimine 3d. Accordingly, the coupling of 7 with 3d
in the presence of 3 mol% Rh2(OAc)4 gave the expected
spirocycle 8a in 68% yield with >95:5 diastereoselectivity.
The structure of the product was unambiguously confirmed by
NMR, IR and mass spectrometry.
Table 2. Three component reaction of aryldiazoacetate, aryl
aldehyde and N-tosyliminea
Ar3
1 mol%
Rh2(OAc)4
Ts
Ts
N2
N
N
Ar1
Table 3. Three-component reaction of diazooxindole, aryl
Ar2CHO
2a-j
+
CO2Me
+
Ar1
Ar2
O
aldehyde and N-tosyliminea
Ar3
dry CH2Cl2
rt
MeOOC
Ar1
1a-h
3d-f
4a-t
Ts
N
N2
3 mol%
Rh2(OAc)4
Ts
N
O
Ar1
Ar2
Ar3
Yield (%)b
drc
Entry
Ar2
O
Ar1CHO
+
O
+
CH2Cl2, r.t.
Ar2
N
N
1
2
3
C6H5
C6H5
C6H5
C6H5
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
81 (4a)
78 (4b)
80 (4c)
>95:5
>95:5
>95:5
Bn
Ar2 = p-NO2C6H4
Bn
p-BrC6H4
p-ClC6H4
7
3d
8
H3C
4
5
6
7
p-FC6H4
C6H5
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
86 (4d)
>95:5
>95:5
>95:5
>95:5
H3CO
4e
84 (
m,p-(Cl)2C6H3 C6H5
)
Ts
Ts
Ts
p-MeC6H4
C6H5
C6H5
82 (4f)
4g
N
N
N
O
O
Ar2
O
O
Ar2
O
p-MeOC6H4
85 (
-(4h)
)
Ar2
O
8d
9
p-NO2C6H4
C6H5
C6H5
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
n.d
N
Bn
N
N
Bn
Bn
p-MeC6H4
81 (4i)
84 (4j)
>95:5
>95:5
yield = 68% (8a)
dr ratio = >95:5
yield = 74% (8b)
dr ratio = >95:5
yield = 75% (8c)
dr ratio = >95:5
10
C6H5
p-MeOC6H4
F
Br
4k
84 (
11
C6H5
m,p-(CH3O)2C6H3
p-NO2C6H4
)
>95:5
Ts
Ts
12
C6H5
C6H5
3,4,5-(CH3O)3C6H2
p-NO2C6H4
p-NO2C6H4
86 (4l)
-(4m)
>95:5
n.d
N
N
13d
o-ClC6H4
Ar2
O
Ar2
O
O
O
4n
)
14
15
C6H5
C6H5
p-BrC6H4
p-ClC6H4
p-NO2C6H4
p-NO2C6H4
80 (
>95:5
>95:5
N
N
81 (4o)
80 (4p)
Bn
Bn
yield = 71% (8d)
yield = 74% (8e)
dr ratio = >95:5
16
17
18
19
C6H5
C6H5
C6H5
C6H5
p-FC6H4
2-Napthyl
2-Furyl
C6H5
p-NO2C6H4
p-NO2C6H4
p-NO2C6H4
p-CNC6H4
>95:5
>95:5
>95:5
>95:5
dr ratio = >95:5
4q
82 (
)
)
4r
72 (
76 (
aAll the reactions were performed using 3 mol% Rh2(OAc)4 with imine 3d (1 equiv),
aldehyde (1.1 equiv) and diazoamide 7 (1.1 equiv) in dry dichloromethane at 25 °C.
bYield refers to pure products after column chromatography. cdr was determined by 1H
NMR analysis of crude reaction mixture.
4s
)
20
21d
22d
23d
p-FC6H4
C6H5
C6H5
p-CNC6H4
p-CF3C6H4
p-NO2C6H4
p-NO2C6H4
75 (4t)
>95:5
n.d
4u
)
C6H5
-(
Similar yield and selectivity were achieved even with 3
mol% of the catalyst. But further decrease in catalyst loading
drastically reduces the yield to 40%. This 3CR was further
extended to various aryl aldehydes bearing electron releasing
and electron withdrawing groups on aromatic ring. It was
observed that the aldehydes with electron releasing groups
such as p-methyl- and p-methoxy- afforded the desired
C6H5
p-NO2C6H4
p-CNC6H4
-(4v)
-(4w)
n.d
C6H5
n.d
aAll the reactions were performed using 1 mol% Rh2(OAc)4 with imine (1 equiv),
aldehyde (1.3 equiv) and diazoester (1.3 equiv) in dry dichloromethane at 25 °C. bYield

4
Tetrahedron
spirooxazolidines 8b and 8c in 74% and 75% yields
To study the diastereoselectivity of this reaction, we have
ACCEPTED MANUSCRIPT
respectively with excellent diastereoselectivity. However, the
aldehydes with electron withdrawing groups such as p-nitro-
and p-cyano- failed to give the desired product. It is worth
mentioning that halo substituted aryl aldehydes such as p-
bromo- and p-fluoro- gave the products 8d and 8e in 71% and
74% yields respectively without any significant change in the
diastereoselectivity.
carried out three component coupling of ethyl diazoacetate,
benzaldehyde and imine 3d (Scheme 6).
Ts
O2N
N
1 mol%
Ts
Rh2(OAc)4
N
+
CO2Et + Ph-CHO
N2
dry DCM
rt
O
EtO2C
O2N
3d
Mechanistically, the reaction was assumed to proceed via the
Huisgen's cycloaddition of tosylimine with carbonyl ylide (A)
formed in situ from aryldiazoacetate and aromatic aldehyde.
9
10
yield 65%
dr ratio 75:25
Scheme 6. 3CC of ethyl diazoacetate 9, benzaldehyde and
imine 3d
As shown in scheme 3, the carbonyl ylide (A) can undergo
[3+2] cycloaddition with tosylimine (via endo attack as shown
in concerted transition state B) to give the expected
oxazolidine (C). The presence of π-π interaction between aryl
group of diazoester (Ar1) and aryl group of imine (Ar3)
attributes to the exclusive formation of trans-4,5-oxazolidine
(C).
In the above reaction, the desired oxazolidine was obtained in
65% yield with moderate dr ratio 75:25. It shows that the
presence of aryl ring in the diazoester enhances the
diastereoselectivity via π-π interaction. Further, the reaction of
diazo compound 1a with benzaldehyde and imine 3d was
carried out using 1 mol% of the catalyst with bulky ligands
such as Rh2(cap)4, and Rh2(esp)2 to address if ylide A is metal
associated. Preliminary result supports metal-free ylide
intermediate. Product 4a was obtained in similar yield and dr
ratio with both catalysts. In addition, no enantioselectivity
was observed with the chiral catalyst Rh2(S-DOSP)4 or Rh2(S-
TCPTTL)4.
CO2Me
Rh(II)
Ar1
O
Ar2
Ar2-CHO
Ar1
N2
+
MeO
O
A
Ts
Ar2
H
N
MeO2C
Ar1
Ar3
Ts
O
Ar3
endo attack
N
N
Ar1
MeOOC
Conclusion
Ar2
Ts
Ar3
O
C
B
In summary, we have developed a highly efficient protocol
for the synthesis of a novel class of highly substituted 1,3-
oxazolidines via a 1,3-dipolar cycloaddition of carbonyl
ylides with N-tosylimines. This protocol was also extended to
cyclic diazoamide for the synthesis of spirooxindolyl
oxazolidines. Due to a broad range of biological activities of
both oxazolidines and spirooxindolyl oxazolidines, this
method will find significant application in medicinal
chemistry.
Scheme 3. A plausible reaction mechanism
Ts
N
1 mol%
Rh2(OAc)4
O
H
Ph
4a
not observed
+
MeO2C
CH2Cl2, rt
Ph
NO2
Experimental
5
3d
Procedure for Synthesis of 4(a-u)
Scheme 4. Reaction of epoxide 5 with imine 3d
To know the actual reaction pathway, a controlled experiment
was performed between epoxide 5 and imine 3d using 1
mol% of Rh2(OAc)4 (Scheme 4). The reaction is expected to
proceed through the cycloaddition of epoxide with imine.14
However, in the present case, no oxazolidine (4a) formation
was observed by cycloaddition of epoxide with imine and
therefore unreacted starting materials were recovered.
Alternatively, the reaction of methyl phenyldiazoacetate 1a
with imine 3d did not afford the aziridine (Scheme 5). Thus
we have excluded the formation of oxazolidine via the
epoxide or aziridine.15
To a suspension of N-tosylimine 3a (200 mg, 0.66 mmol),
benzaldehyde 2a (90 mg, 0.86 mmol) and Rh2(OAc)4 (3.8 mg,
0.0085 mmol) in dry DCM (10 mL) under argon atmosphere at
room temperature was added slowly a solution of methyl 2-
diazo-2-phenylacetate 1a (150 mg, 0.86 mmol) in dry DCM (5
mL) through a syringe pump for a period of 3 h. After complete
addition, the mixture was stirred for another 30 min. After
complete consumption of the diazo compound as monitored by
TLC, the solvent was removed under reduced pressure.
Purification by flash column chromatography on silica gel (4:1
hexane/EtOAc) afforded the oxazolidine 4a (298 mg, 81%) as a
colourless solid. The above procedure was followed for the
synthesis of remaining products (4b-u).
Ts
Ts
N
N
CO2Me
N2
Ph
Rh2(OAc)4
+
Ph
1a
MeO2C
Procedure for Synthesis of 8a-e
O2N
NO2
not observed
3d
To a suspension of N-tosylimine 3a (200 mg, 0.66 mmol),
benzaldehyde 2a (90 mg, 0.86 mmol) and Rh2(OAc)4 (9 mg, 0.02
mmol) in dry DCM (10 mL) under argon atmosphere at room
temperature was added slowly a solution of N-benzyl-3-
diazooxindole 7 (180 mg, 0.72 mmol) in dry DCM (5 mL)
through a syringe pump for a period of 4 h. After complete
addition, the mixture was stirred for another 30 min. After
Scheme 5. Reaction of diazoester 1a with imine 3d

5
complete consumption of the diazo compound as monitored by
1252, 1160, 1092, 1025, 816, 665 cm-1; HRMS (ESI) calcd for
C30H25N2O7Cl2S, 627.0754 (M+H)+; Found, 627.0736.
ACCEPTED MANUSCRIPT
TLC, the solvent was removed under reduced pressure.
Purification by flash column chromatography on silica gel (4:1
hexane/EtOAc) afforded the product 8a (282 mg, 68%) as a
colourless solid. The above procedure was followed for the
synthesis of compounds 8b-e
Methyl
4-(4-nitrophenyl)-2-phenyl-5-(p-tolyl)-3-
tosyloxazolidine-5-carboxylate (4f): Colorless solid. mp: 174–
175 °C; H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 8.9 Hz, 2H),
1
7.64 – 7.59 (m, 2H), 7.48 – 7.38 (m, 5H), 7.33 (d, J = 8.9 Hz,
2H), 7.19 (d, J = 8.4 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 6.86 (d, J
= 8.3 Hz, 2H), 6.18 (s, 1H), 6.03 (s, 1H), 3.59 (s, 3H), 2.39 (s,
3H), 2.15 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 170.9, 147.1,
144.9, 144.3, 138.4, 135.7, 134.8, 130.7, 130.0, 129.84, 129.5,
128.9, 128.4, 128.3, 127.9, 125.8, 122.9, 91.7, 89.9, 67.2, 53.5,
21.5, 21.0; IR (neat) νmax 2854, 2840, 1735, 1615, 1510, 1348,
1293, 1160, 1092, 1025, 831, 670 cm-1; HRMS (ESI) calcd for
C31H29O7N2S 573.1690 (M+H)+; Found, 573.1691.
Methyl
4-(4-nitrophenyl)-2,5-diphenyl-3-tosyloxazolidine-5-
carboxylate (4a): Colorless solid. mp: 168–169 °C; 1H NMR
(300 MHz, CDCl3) δ 7.90 (d, J = 8.7 Hz, 2H), 7.62 (d, J = 7.7
Hz, 2H), 7.48 – 7.37 (m, 5H), 7.32 (d, J = 8.7 Hz, 2H), 7.24 –
7.13 (m, 4H), 7.10 – 7.02 (m, 3H), 6.20 (s, 1H), 6.06 (s, 1H),
3.61 (s, 3H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.6,
146.9, 144.7, 144.3, 135.5, 134.3, 133.5, 129.8, 129.7, 129.4,
128.4, 128.3, 128.1, 128.0, 127.8, 125.7, 122.8, 91.6, 89.7, 67.1,
53.4, 21.3. IR (neat) νmax 2925, 2856, 1746, 1609, 1519, 1349,
1243, 1164, 728 cm-1; ESI-MS m/z 559 (M+H)+; HRMS (ESI)
calcd for C30H27N2O7S, 559.15335 (M+H)+; Found, 559.15328.
Methyl
5-(4-methoxyphenyl)-4-(4-nitrophenyl)-2-phenyl-3-
tosyloxazolidine-5-carboxylate (4g): Colorless solid. mp: 174–
1
175 °C; H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 8.7 Hz, 2H),
Methyl
5-(4-bromophenyl)-4-(4-nitrophenyl)-2-phenyl-3-
7.46 (d, J = 8.1 Hz, 2H), 7.38 – 7.29 (m, 3H), 7.24 – 7.15 (m,
5H), 7.12 – 7.03 (m, 4H), 7.00 – 6.94 (m, 1H), 6.18 (s, 1H), 6.07
(s, 1H), 3.78 (s, 3H), 3.62 (s, 3H), 2.39 (s, 3H); 13C NMR (101
MHz, CDCl3) δ 13C NMR (101 MHz, CDCl3) δ 170.7, 159.5,
147.1, 144.8, 144.3, 137.0, 134.7, 133.6, 130.0, 129.4, 128.5,
128.1, 127.9, 125.9, 122.9, 120.5, 115.4, 113.7, 91.5, 89.9, 67.2,
55.2, 53.5, 21.4; IR (neat) νmax 2858, 2842, 1734, 1618, 1515,
1354, 1342, 1290, 1252, 1092, 1021, 816, 665 cm-1; HRMS (ESI)
calcd for C31H29N2O8S, 589.16391 (M+H)+; Found, 589.16391.
tosyloxazolidine-5-carboxylate (4b): Colorless solid. mp: 166–
167 °C; H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 8.8 Hz, 2H),
1
7.63 - 7.55 (m, 2H), 7.49 – 7.37 (m, 5H), 7.34 (d, J = 8.7 Hz,
2H), 7.24 – 7.15 (m, 4H), 7.09 (d, J = 8.7 Hz, 2H), 6.21 (s, 1H),
6.02 (s, 1H), 3.60 (s, 3H), 2.39 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 170.4, 147.2, 144.4, 135.4, 134.4, 132.8, 131.3, 129.9,
129.9, 129.5, 128.4, 128.1, 127.9, 127.6, 123.2, 122.8, 91.7, 89.4,
77.3, 67.1, 53.7, 21.5; IR (neat) νmax 3073, 2954, 2841, 1744,
1610, 1517, 1355, 1345, 1293, 1252, 1092, 1025, 831, 816, 665
cm-1; HRMS (ESI) calcd for C30H26O7N2BrS 637.06386 (M)+;
Found, 637.06212.
Methyl
4-(4-nitrophenyl)-5-phenyl-2-(p-tolyl)-3-
tosyloxazolidine-5-carboxylate (4i): Colorless solid. mp: 158–
1
159 °C; H NMR (300 MHz, CDCl3) δ 7.90 (d, J = 8.8 Hz, 2H),
Methyl
5-(4-chlorophenyl)-4-(4-nitrophenyl)-2-phenyl-3-
7.55 – 7.43 (m, 4H), 7.34 (d, J = 8.8 Hz, 2H), 7.29 – 7.14 (m,
6H), 7.12 – 6.99 (m, 3H), 6.15 (s, 1H), 6.02 (s, 1H), 3.58 (s, 3H),
2.41 (s, 3H), 2.40 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 170.9,
147.1, 144.9, 144.3, 139.9, 134.7, 133.7, 132.7, 129.9, 129.46,
129.1, 128.5, 128.2, 128.1, 127.9, 125.9, 122.91\, 91.7, 89.8,
67.3, 53.5, 21.5, 21.3; IR (neat) νmax 3074, 2949, 2921, 1745,
1597, 1515, 1450, 1346, 1243, 1162, 1019, 1009, 734, 674 cm-1;
ESI-MS m/z 595 (M+Na)+; HRMS (ESI) calcd for
C31H28N2O7SNa, 595.1509 (M+Na)+; Found, 595.1511.
tosyloxazolidine-5-carboxylate (4c): Colorless solid. mp: 176–
177 °C; H NMR (300 MHz, CDCl3) δ 7.95 (d, J = 8.7 Hz, 2H),
1
7.60 (dd, J = 7.5, 1.8 Hz, 2H), 7.49 – 7.38 (m, 5H), 7.33 (d, J =
8.7 Hz, 2H), 7.23 – 7.11 (m, 4H), 7.05 (d, J = 8.7 Hz, 2H), 6.21
(s, 1H), 6.02 (s, 1H), 3.61 (s, 3H), 2.39 (s, 3H); 13C NMR (126
MHz, CDCl3) δ 170.4, 147.2, 144.4, 135.3, 134.4, 132.8, 131.3,
129.9, 129.9, 129.5, 128.4, 128.1, 127.9, 127.6, 123.1, 122.8,
91.7, 89.4, 77.2, 67.1, 53.7, 21.5; IR (neat) νmax 2954, 2841,
1740, 1610, 1520, 1345, 1293, 1252, 1166, 1092, 1025, 816 cm-1;
ESI-MS m/z 593 (M+H)+; HRMS (ESI) calcd for
C30H26ClN2O7S, 593.1143 (M+H)+; Found, 593.1123
Methyl
2-(4-methoxyphenyl)-4-(4-nitrophenyl)-5-phenyl-3-
tosyloxazolidine-5-carboxylate (4j): Colorless solid. mp: 165–
1
166 °C; H NMR (300 MHz, CDCl3) δ 7.91 (d, J = 8.8 Hz, 2H),
Methyl
5-(4-fluorophenyl)-4-(4-nitrophenyl)-2-phenyl-3-
7.54 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.8
Hz, 2H), 7.23 – 7.16 (m, 4H), 7.10 – 7.02 (m, 3H), 6.93 (d, J =
8.8 Hz, 2H), 6.13 (s, 1H), 6.04 (s, 1H), 3.86 (s, 3H), 3.60 (s, 3H),
2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.9, 160.8, 147.0,
144.9, 144.2, 134.8, 133.7, 129.9, 129.7, 129.4, 128.5, 128.2,
127.9, 127.6, 125.9, 122.9, 113.8, 91.5, 89.7, 67.2, 55.3, 53.6,
21.5; IR (neat) νmax 3073, 2954, 2841, 1757, 1744, 1610, 1517,
1355, 1345, 1293, 1252, 1166, 1092, 1025, 831, 816, 665 cm-1;
ESI-MS m/z 611 (M+Na)+; HRMS (ESI) calcd for
C31H28N2O8SNa, 611.14586 (M+Na)+; Found, 611.14590.
tosyloxazolidine-5-carboxylate (4d): Colorless solid. mp: 169–
170 °C; H NMR (300 MHz, CDCl3) δ 7.94 (d, J = 8.8 Hz, 2H),
1
7.64 – 7.58 (m, 2H), 7.48 – 7.40 (m, 5H), 7.34 (d, J = 8.7 Hz,
2H), 7.24 – 7.15 (m, 4H), 6.76 (t, J = 8.6 Hz, 2H), 6.21 (s, 1H),
6.02 (s, 1H), 3.62 (s, 3H), 2.39 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 170.7, 147.2, 144.6, 144.4, 135.5, 134.5, 129.9, 129.5,
128.5, 128.2, 127.9, 123.1, 115.4, 115.1, 91.7, 89.4, 67.3, 53.6,
21.5; IR (neat) νmax 3073, 2954, 2841, 1740, 1610, 1517, 1350,
1292, 1250, 1166, 1092, 1025, 816, 665 cm-1; HRMS (ESI) calcd
for C30H26O7N2FS, 577.14393 (M+H)+; Found, 577.14398.
Methyl 2-(3,4-dimethoxyphenyl)-4-(4-nitrophenyl)-5-phenyl-3-
Methyl
5-(3,4-dichlorophenyl)-4-(4-nitrophenyl)-2-phenyl-3-
tosyloxazolidine-5-carboxylate (4k): Colorless solid. mp: 180–
181 °C; H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 8.7 Hz, 2H),
1
tosyloxazolidine-5-carboxylate (4e): Colorless solid. mp: 178–
179 °C; H NMR (300 MHz, CDCl3) δ 7.98 (d, J = 8.9 Hz, 2H),
1
7.41 – 7.34 (m, 4H), 7.24 – 7.20 (m, 2H), 7.18 – 7.13 (m, 3H),
7.10 – 7.05 (m, 3H), 7.01 (d, J = 2.0 Hz, 1H), 6.88 (d, J = 8.3 Hz,
1H), 6.19 (s, 1H), 6.12 (s, 1H), 3.93 (s, 3H), 3.77 (s, 3H), 3.65 (s,
3H), 2.37 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 170.7, 150.1,
148.7, 147.0, 144.9, 144.2, 134.9, 133.7, 130.0, 129.3, 128.5,
128.1, 127.7, 125.8, 122.8, 121.2, 110.9, 110.6, 91.6, 89.7, 66.99,
55.9, 55.7, 53.5, 21.4; IR (neat) νmax 3072, 2958, 2841, 1757,
7.62 - 7.56 (m, 2H), 7.48 – 7.31 (m, 8H), 7.22 – 7.10 (m, 3H),
7.04 – 6-98 (m, 1H), 6.22 (s, 1H), 5.99 (s, 1H), 3.62 (s, 3H), 2.39
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 170.1, 147.4, 144.5,
144.2, 135.2, 134.4, 133.9, 132.9, 132.6, 130.1, 129.9, 129.9,
129.5, 128.5, 128.1, 128.0, 127.9, 125.4, 123.3, 91.9, 88.7, 67.2,
53.8, 21.5; IR (neat) νmax 2954, 2941, 1736, 1517, 1350, 1342,

6
Tetrahedron
1744, 1610, 1517, 1345, 1293, 1252, 1167, 1092, 1025, 816,
Methyl
2-(furan-2-yl)-4-(4-nitrophenyl)-5-phenyl-3-
ACCEPTED MANUSCRIPT
665 cm-1; HRMS (ESI) calcd for C32H30N2O9NaS, 641.1564
(M+Na)+; Found, 641.1565.
tosyloxazolidine-5-carboxylate (4r): Colorless solid. mp: 137–
1
138 °C; H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 8.7 Hz, 2H),
7.54 – 7.44 (m, 3H), 7.32 – 7.19 (m, 5H), 7.14 – 7.04 (m, 5H),
6.7 (d, J = 3.2 Hz, 1H), 6.45 – 6.41 (m, 1H), 6.23 (s, 1H), 6.07 (s,
1H), 3.72 (s, 3H), 2.36 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
170.7, 147.9, 147.2, 144.7, 144.1, 144.0, 135.4, 133.3, 129.9,
129.3, 128.6, 128.2, 127.5, 125.8, 122.8, 113.3, 110.6, 90.3, 84.4,
66.8, 53.7, 21.5; IR (neat) νmax 2954, 2841, 1757, 1742, 1518,
1345, 1290, 1160, 1092, 836, 670 cm-1; HRMS (ESI) calcd for
C28H24N2O8NaS, 571.1145 (M+Na)+; Found, 571.1140.
Methyl
4-(4-nitrophenyl)-5-phenyl-3-tosyl-2-(3,4,5-
trimethoxyphenyl)oxazolidine-5-carboxylate (4l): Colorless
solid. mp: 188–189 °C; H NMR (500 MHz, CDCl3) δ 7.92 (d, J
1
= 8.8 Hz, 2H), 7.44 – 7.35 (m, 4H), 7.25 – 7.21 (m, 2H), 7.15 (d,
J = 8.0 Hz, 2H), 7.11 – 7.04 (m, 3H), 6.71 (s, 2H), 6.20 (s, 1H),
6.17 (s, 1H), 3.88 (s, 3H), 3.75 (s, 6H), 3.68 (s, 3H), 2.36 (s, 3H);
13C NMR (125 MHz, CDCl3) δ 170.7, 153.0, 147.1, 144.8, 144.3,
139.0, 135.2, 133.7, 130.6, 130.2, 129.3, 128.5, 128.2, 127.7,
125.9, 122.8, 105.4, 91.7, 89.8, 66.9, 60.8, 55.9, 53.6, 21.4; IR
(neat) νmax 3073, 2954, 2841, 1757, 1744, 1610, 1517, 1355,
1345, 1293, 1252, 1166, 1092, 1025, 831, 665 cm-1; HRMS
(ESI) calcd for C33H32N2O10NaS, 671.1670 (M+Na)+; Found,
671.1673.
Methyl
4-(4-cyanophenyl)-2,5-diphenyl-3-tosyloxazolidine-5-
carboxylate (4s): Colorless solid. mp: 172–173 °C; 1H NMR (300
MHz, CDCl3) δ 7.64-7.59 (m, 2H), 7.42 (d, J = 8.1 Hz. 4H),
7.37-7.31 (m, 2H), 7.28-7.24 (m, 2H), 7.21-7.15 (m, 4H), 7.09-
7.04 (m, 2H), 6.18 (s, 1H), 5.99 (s, 1H), 3.60 (s, 3H), 2.39 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 170.7, 144.2, 142.7, 135.6,
134.5, 133.6, 131.4, 129.7, 129.6, 129.4, 128.4, 128.3, 128.2,
128.0, 127.8, 125.8, 118.4, 111.3, 91.5, 89.8, 67.5, 53.4, 21.4; IR
(neat) νmax 3005, 2974, 2231, 1746, 1609, 1509, 1355, 1251,
1163, 1012, 754, 669 cm-1; HRMS (ESI) calcd for
C31H26N2O5NaS, 561.1454 (M+Na)+; Found, 561.1449.
Methyl
2-(4-bromophenyl)-4-(4-nitrophenyl)-5-phenyl-3-
tosyloxazolidine-5-carboxylate (4n): Colorless solid. mp: 185–
186 °C; H NMR (500 MHz, CDCl3) δ 7.91 (d, J = 8.8 Hz, 2H),
1
7.56 (d, J = 8.4 Hz, 2H), 7.51 - 7.46 (m, 4H), 7.30 – 7.25 (m,
3H), 7.23 (d, J = 8.1 Hz, 2H), 7.20 – 7.16 (m, 2H), 7.09 – 7.05
(m, 3H), 6.16 (s, 1H), 6.01 (s, 1H), 3.59 (s, 3H), 2.42 (s, 3H): 13
C
NMR (126 MHz, CDCl3) δ 170.6, 147.2, 144.6, 144.6, 134.8,
134.5, 133.5, 131.7, 129.9, 129.8, 129.6, 128.6, 128.2, 127.9,
125.9 124.1, 123.0, 91.0, 90.02, 67.3, 53.6, 21.5. IR (neat) νmax
3070, 298, 1758, 1746, 1610, 1517, 1358, 1290, 1166, 758, 685
cm-1.
Methyl
4-(4-cyanophenyl)-5-(4-fluorophenyl)-2-phenyl-3-
tosyloxazolidine-5-carboxylate (4t): Colorless solid. mp: 158–
159 °C; 1H NMR (300 MHz, CDCl3) δ 7.67 – 7.58 (m, 2H), 7.46
(d, J = 8.3 Hz, 2H), 7.32 – 7.39 (m, 2H), 7.29 – 7.03 (m, 11H),
6.18 (s, 1H), 5.98 (s, 1H), 3.59 (s, 3H), 2.41 (s, 3H). 13C NMR
(75 MHz, CDCl3) δ 170.7, 165.1, 161.8, 144.4, 142.6, 134.4,
133.6, 131.6, 131.6, 131.5, 130.2, 130.1, 129.6, 129.5, 128.9,
128.5, 128.1, 127.8, 125.8, 118.4, 115.5, 115.2, 111.5, 90.9,
89.8,67.5, 53.5, 21.4. IR (neat) νmax 3010, 2974, 2230, 1746,
1610, 1509, 1355, 1251, 1163, 1012, 836, 754, 669 cm-1; HRMS
(ESI) calcd for C31H25O5N2FNaS, 579.1360 (M+Na)+; Found,
579.1359.
Methyl
2-(4-chlorophenyl)-4-(4-nitrophenyl)-5-phenyl-3-
tosyloxazolidine-5-carboxylate (4o): Colorless solid. mp: 172–
1
173 °C; H NMR (300 MHz, CDCl3) δ 7.91 (d, J = 8.6 Hz, 2H),
7.57 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.40 (d, J = 8.4
Hz, 2H), 7.32 – 7.13 (m, 7H), 7.11 – 7.02 (m, 3H), 6.18 (s, 1H),
6.01 (s, 1H), 3.59 (s, 3H), 2.41 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 170.6, 147.2, 144.6, 144.6, 135.9, 134.5, 134.3, 133.5,
129.9, 129.6, 129.6, 128.7, 128.6, 128.2, 127.9, 125.9, 123.0,
90.9, 90.0, 67.3, 53.6, 21.5; HRMS (ESI) calcd for
C30H25O7N2ClS, 593.1143 (M+H)+; Found, 593.1127.
1-Benzyl-4'-(4-nitrophenyl)-2'-phenyl-3'-tosylspiro[indoline-3,5'-
oxazolidin]-2-one (8a): Colorless solid. mp: 188–189 °C; 1H
NMR (300 MHz, CDCl3) δ 8.05 (d, J = 7.1 Hz, 2H), 7.78 (dd, J =
6.3, 2.9 Hz, 2H), 7.58 – 7.01 (m, 15H), 6.89 (s, 1H), 6.70 – 6.51
(m, 2H), 6.13 (d, J = 7.4 Hz, 1H), 5.50 (s, 1H), 4.87 (s, 2H), 2.43
(s, 3H). 13C NMR (75 MHz, CDCl3) δ 174.7, 147.4, 144.9, 144.4,
143.1, 136.3, 134.9, 134.6, 130.9, 130.0, 129.5, 128.9, 128.5,
128.4, 127.9, 127.2, 126.9, 123.2, 122.6, 122.5, 109.5, 92.0, 84.7,
66.8, 43.7, 21.6. IR (neat) νmax 3062, 2917, 1725, 1609, 1524,
1470, 1358, 1170, 1029, 744, 668 cm-1; HRMS (ESI) calcd for
C36H29O6N3NaS = 654.1669 (M+Na)+; Found, 654.1660.
Methyl
2-(4-fluorophenyl)-4-(4-nitrophenyl)-5-phenyl-3-
tosyloxazolidine-5-carboxylate (4p): Colorless solid. mp: 161–
1
162 °C; H NMR (300 MHz, CDCl3) δ 7.92 (d, J = 8.7 Hz, 2H),
7.61 (dd, J = 8.5, 5.4 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 7.31 (d, J
= 8.7 Hz, 2H), 7.25 - 7.15 (m, 4H), 7.15 – 7.03 (m, 5H), 6.17 (s,
1H), 6.03 (s, 1H), 3.60 (s, 3H), 2.40 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 170.6, 164.5, 162.5, 147.1, 144.6, 144.5, 134.5, 133.5,
131.6, 130.2, 130.1, 129.9, 129.5, 128.6, 128.2, 127.9, 125.8,
122.9, 115.5, 115.4, 90.9, 89.9, 67.2, 53.6, 21.47. ESI-MS m/z
594 (M+NH4)+; HRMS (ESI) calcd for C30H25FN2O7SNH4,
594.1705 (M+NH4)+; Found, 594.1705.
1-Benzyl-4'-(4-nitrophenyl)-2'-(p-tolyl)-3'-tosylspiro[indoline-
3,5'-oxazolidin]-2-one (8b): Colorless solid. mp: 182–183 °C; 1H
NMR (300 MHz, CDCl3) δ 7.94 (d, J = 7.0 Hz, 2H), 7.57 (d, J =
8.1 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.31 – 7.10 (m, 10H), 7.01
– 6.90 (m, 2H), 6.74 (s, 1H), 6.58 – 6.44 (m, 2H), 6.12 – 5.98 (m,
1H), 5.37 (s, 1H), 4.82 – 4.70 (m, 2H). 13C NMR (75 MHz,
CDCl3) δ 174.8, 147.4, 145.1, 144.3, 143.1, 140.0, 135.0, 134.5,
133.3, 130.8, 129.4, 129.2, 128.9, 128.5, 128.2, 128.0, 127.9,
127.2, 126.9, 123.2, 122.6, 122.6, 109.4, 92.0, 84.5, 66.8, 43.6,
21.6, 21.4. . IR (neat) νmax 3061, 2920, 1716, 1613, 1523, 1368,
1171, 1104, 1034. 668 cm-1; HRMS (ESI) calcd for
C37H31O6N3NaS = 668.1825 (M+Na)+; Found, 668.1820.
Methyl
2-(naphthalen-2-yl)-4-(4-nitrophenyl)-5-phenyl-3-
tosyloxazolidine-5-carboxylate (4q): Colorless solid. mp: 176–
1
177 °C; H NMR (300 MHz, CDCl3) δ 8.02 (s, 1H), 7.97- 7.80
(m, 5H), 7.68 (dd, J = 8.5, 1.6 Hz, 1H), 7.61 – 7.51 (m, 2H), 7.47
– 7.36 (m, 4H), 7.25 – 7.19 (m, 2H), 7.13 – 7.03 (m, 5H), 6.37 (s,
1H), 6.14 (s, 1H), 3.65 (s, 3H), 2.31 (s, 3H); 13C NMR (126 MHz,
CDCl3) δ 170.8, 147.1, 144.8, 144.3, 134.5, 133.9, 133.7, 132.8,
132.6, 130.0, 129.4, 128.6, 128.5, 128.4, 128.1, 127.9, 127.6,
126.9, 126.4, 125.9, 124.6, 122.9, 91.9, 89.9, 77.3, 67.2, 53.5,
21.3; IR (neat) νmax 3057, 2950, 1743, 1599, 1523, 1347, 1242,
1167, 1133, 1011, 733, 674 cm-1; HRMS (ESI) calcd for
C34H28N2O7NaS, 631.1512 (M+Na)+; Found, 631.1509.
1-Benzyl-2'-(4-methoxyphenyl)-4'-(4-nitrophenyl)-3'-
tosylspiro[indoline-3,5'-oxazolidin]-2-one (8c): Colorless solid.
mp: 201–202 °C; H NMR (300 MHz, CDCl3) δ 7.97 (d, J = 7.0
1
Hz, 2H), 7.60 (d, J = 8.7 Hz, 2H), 7.42 – 6.83 (m, 14H), 6.74 (s,

7
Angew. Chem., Int. Ed. 1994, 33, 15. (h) Jefford, C. W.;
1H), 6.52 (dd, J = 15.8, 7.9 Hz, 2H), 6.06 (d, J = 6.9 Hz, 1H),
5.39 (s, 1H), 4.77 (d, J = 1.5 Hz, 2H), 3.81 (s, 3H), 2.35 (s, 3H).
13C NMR (75 MHz, CDCl3) δ 174.8, 160.9, 147.4, 145.1, 144.3,
143.1, 134.9, 134.6, 130.8, 129.7, 129.4, 128.9, 128.5, 128.1,
127.9, 127.9, 127.2, 126.9, 123.2, 122.6, 122.6, 113.9, 109.5,
91.8, 84.3, 66.6, 55.4, 43.6, 21.6. IR (neat) νmax 3059, 2900,
1719, 1611, 1515, 1347, 1251, 1170, 1101, 1023, 669 cm-1;
HRMS (ESI) C37H31O7N3NaS Found, 684.1758 (M+Na)+
ACCEPTED MANUSCRIPT
McNulty, J.; Lu, Z. H.; Wang, J. B. Helv. Chim. Acta. 1996, 79,
1203. (i) Makino, K.; Goto, T.; Hiroki, Y.; Hamada, Y. Angew.
Chem. Int. Ed. 2004, 43, 882. (j) Goodman, C. G.; Do, D. T.;
Johnson, J. S. Org Lett. 2013, 15, 2446.
4. Recent reviews on spirooxindoles: (a) Galliford, C. V.; Scheidt, K.
A. Angew. Chem. Int. Ed. 2007, 46, 8748. (b) Singh, G. S.; Desta,
Z. Y. Chem. Rev. 2012, 112, 6104. (c) Cheng, D.; Ishihara, Y.;
Tan, B.; Barbas III, C. F. ACS Catal. 2014, 4, 743 and references
therein. (d) Santos, M. M. M. Tetrahedron 2014, 70, 9735 and
references therein.
1-Benzyl-2'-(4-bromophenyl)-4'-(4-nitrophenyl)-3'-
5. For dihydro- and tetrahydrofurans see (a) Doyle, M. P.;
McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; Wiley & Sons: New York,
1998. (b) Huisgen, R.; de March, P. J. Am. Chem. Soc.1982, 104,
4953. (c) Alt, M.; Maas, G. Tetrahedron 1994, 50, 7435. (d)
Doyle, M. P.; Forbes, D. C.; Protopopova, M. N.; Stanley, S. A.;
Vasbinder, M. M.; Xavier, K. R. J. Org. Chem. 1997, 62, 7210. (e)
Hamaguchi, M.; Matsubara, H.; Nagai, T. J. Org. Chem. 2001, 66,
5395. (f) Johnson, T.; Cheshire, D. R.; Stocks, M. J.; Thurston, V.
T. Synlett 2001, 646. (g) Skaggs, A. J.; Lin, E. Y.; Jamison, T. F.
Org. Lett. 2002, 4, 2277. (h) Doyle, M. P.; Lu, C. D.; Chen, Z. Y.;
Liu, H.; Hu, W.; Mi, A. Q. J. Org. Chem. 2004, 69, 4856. (i) Nair,
V.; Mathai, S.; Varma, L. R. J. Org. Chem. 2004, 69, 1413. (j) De-
Angelis, A.; Taylor, M. T.; Fox, J. M. J. Am. Chem. Soc. 2009,
131, 1101.(k) Hashimoto, Y.; Itoh, K.; Kakehi, A.; Shiro, M.;
Suga, H. J. Org. Chem.2013, 78, 6182.
6. For dioxolanes see (a) de March, P.; Huisgen, R. J. Am. Chem.
Soc. 1982, 104, 4952. (b) Jiang, B.; Zhang, X.; Luo, Z. Org. Lett.
2002, 4, 2453. (c) Nair, V.; Mathai, S.; Nair, S. M.; Rath, N. P.
Tetrahedron Lett. 2003, 44, 8407. (d) Russell, A. E.; Brekan, J.;
Gronenberg, L.; Doyle, M. P. J. Org. Chem. 2004, 69, 5269. (e)
DeAngelis, A.; Panne, P.; Yap, G. P. A.; Fox, J. M. J. Org. Chem.
2008, 73, 1435.
tosylspiro[indoline-3,5'-oxazolidin]-2-one (8d): Colorless solid.
1
mp: 196–197 °C; H NMR (300 MHz, CDCl3) δ 7.94 (d, J = 7.1
Hz, 2H), 7.62 – 7.46 (m, 4H), 7.43 – 6.91 (m, 13H), 6.74 (s, 1H),
6.59 – 6.43 (m, 2H), 6.03 (d, J = 7.6 Hz, 1H), 5.36 (s, 1H), 4.75
(d, J = 3.4 Hz, 2H), 2.34 (s, 3H).13C NMR (75 MHz, CDCl3) δ
174.6, 147.4, 144.7, 143.1, 135.4, 134.9, 134.2, 131.7, 130.9,
129.9, 129.6, 128.9, 128.4, 128.0, 127.2, 126.8, 124.2, 123.2,
122.7, 122.2, 109.6, 91.3, 84.7, 66.7, 43.7, 21.6. IR (neat) νmax
2927, 1724, 1523, 1346, 1162, 1103, 673 cm-1; HRMS (ESI)
C36H28O6N3BrS Found, 734.0735 (M+2+Na)+
1-Benzyl-2'-(4-fluorophenyl)-4'-(4-nitrophenyl)-3'-
tosylspiro[indoline-3,5'-oxazolidin]-2-one (8e): Colorless solid.
1
mp: 178–179 °C; H NMR (300 MHz, CDCl3) δ 7.94 (d, J = 7.0
Hz, 2H), 7.74 – 7.61 (m, 2H), 7.42 – 6.93 (m, 15H), 6.78 (s, 1H),
6.63 – 6.45 (m, 2H), 6.04 (d, J = 6.9 Hz, 1H), 5.39 (s, 1H), 4.77
(s, 2H), 2.35 (s, 3H).13C NMR (75 MHz, CDCl3) δ 174.6, 165.3,
161.9, 147., 144.8, 144.6, 143.2, 134.9, 134.4, 132.3, 132.2,
130.9, 130.4, 130.2, 129.5, 128.9, 128.4, 127.9, 127.2, 126.8,
123.2, 122.7, 122.3, 115.7, 115.4, 109.6, 91.2, 84.6, 66.7, 43.7,
21.6. IR (neat) νmax 2927, 1725, 1610, 1519, 1347, 1162, 1036,
674 cm-1; HRMS (ESI) calcd for C36H28O6N3FNaS = 672.1575
(M+Na)+; Found, 672.1568.
7. For pyrrolidines see: (a) Bartnik, R.; Mloston, G. Tetrahedron
1984, 40, 2569. (b) Hansen, K. B.; Finney, N. S.; Jacobsen, E. N.
Angew. Chem., Int. Ed. 1995, 34, 676. (c) Doyle, M. P.; Yan , M.;
Hu, W.; Gronenberg, L. S. J. Am. Chem. Soc. 2003, 125, 4692. (d)
Li, G. Y.; Chen, J.; Yu, W. Y.; Hong, W.; Che, C. M. Org. Lett.
2003, 5, 2153.
8. (a) Torssell, S.; Kienle, M.; Somfai, P. Angew. Chem. Int. Ed.
2005, 44, 3096. (b) Torssell, S.; Somfai, P. Adv. Synth. Catal.
2006, 348, 24214.
Acknowledgments
9. Rajasekaran, T.; Karthik, G.; Sridhar, B.; Reddy, B. V. S. Org.
Lett. 2013, 15, 1512.
TRS thanks UGC, New Delhi for the award of fellowship
Supplementary data
10. (a) Reddy, B. V. S.; Rajasekaran, T.; Karthik, G.; Rao, T. P.
Tetrahedron Lett. 2012, 53, 3416. (b) Rajasekaran, T.; Karthik,
G.; Sridhar, B.; Reddy, B. V. S. Eur. J. Org. Chem. 2014, 2221.
(c) Karthik, G.; Rajasekaran, T.; Sridhar, B.; Reddy, B. V. S.
Tetrahedron 2014, 70, 8148.
11. Doyle, M. P.; Hu, W.; Timmons, D. J. Org. Lett. 2001, 3, 933.
12. Lu, C. D.; Chen, Z. Y.; Liu, H.; Hu, W. H.; Mi, A. Q. Org. Lett.
2004, 6, 3071.
Supplementary data (Copies of 1H and 13C NMR spectra of
products) related to this article can be found at
References and notes
13. CCDC 1029020
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Lazzell, C. L.; Collett, A. R. J. Am. Chem. Soc. 1950, 72, 2866.
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