Reagent-switch controlled metal-free intermolecular geminal diamination and aminooxygenation of vinylarenes

Article abstract of DOI:10.1016/j.tet.2016.01.005

We report here the first general method for the geminal diamination and an intermolecular metal-free, geminal aminooxygenation of vinylarenes using hypervalent iodine reagent. A new m-CPBA mediated geminal aminooxygenation is also reported. A novel reagent-switch for the control of migrating group by controlling the two independent geminal addition paths is developed. Deuterium labelling studies and the control studies have provided unambiguous evidences for the phenyl migration and hydride migration in the oxidative geminal difunctionalization process mediated by PhI(OCOCF₃)₂and m-CPBA, respectively through a semi-pinacol rearrangement.

Full text of DOI:10.1016/j.tet.2016.01.005

Tetrahedron 72 (2016) 1095e1104
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Reagent-switch controlled metal-free intermolecular geminal
diamination and aminooxygenation of vinylarenes
*
Pandur Venkatesan Balaji, Srinivasan Chandrasekaran
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We report here the first general method for the geminal diamination and an intermolecular metal-free,
geminal aminooxygenation of vinylarenes using hypervalent iodine reagent. A new m-CPBA mediated
geminal aminooxygenation is also reported. A novel reagent-switch for the control of migrating group by
controlling the two independent geminal addition paths is developed. Deuterium labelling studies and
the control studies have provided unambiguous evidences for the phenyl migration and hydride mi-
gration in the oxidative geminal difunctionalization process mediated by PhI(OCOCF3)2 and m-CPBA,
respectively through a semi-pinacol rearrangement.
Received 15 November 2015
Received in revised form 1 January 2016
Accepted 5 January 2016
Available online 7 January 2016
Keywords:
Geminal diamination
Geminal aminooxygenation
Hypervalent iodine
Ó 2016 Elsevier Ltd. All rights reserved.
Metal-free conditions
Semi-pinacol rearrangement
1. Introduction
Wacker process are rather limited as an oxidation reaction and in
the annulation reactions using a tethered heteroatom.8 In this
To have perfect control over the closely competitive reaction
pathways by selection of appropriate reagent systems is always
desirable and is highly challenging in the field of organic synthesis
for the installation of bonds with high precision and greater effi-
ciency.1 The difunctionalization of alkenes is a prominent tool in
organic chemistry, which has been extensively employed and
widely studied with renewed interest through many decades, due
to its great potential.2 This provides a rapid access to diversely
functionalized compounds with very high step-economy. A range
of methods have been developed and are much investigated for
the vicinal difunctionalization of alkenes, which utilizes the
unsaturation of the olefin moiety for the simple addition across
C]C bond.3
In contrast, the methods available for the geminal difunction-
alization of alkenes are really very scarce. This is due to its intricate
nature, of being a process, involving the transposition of atom/
group in addition to the formation of two new bonds.4 Especially,
the geminal diamination and geminal aminooxygenation pose
formidable challenge and are performed through arduous multi-
step sequence involving condensations and addition of tethered
nucleophile,5 through the conjugate addition to Michael acceptors6
and by cycloaddition reactions.7 The studies of the well-known
context, we have recently reported a bromonium ion mediated
geminal aminooxygenation of vinylarenes.9 More recently, the
metal-free methods, which provide an environmentally benign
alternative to toxic and precious metals have received significant
attention from organic chemists. In particular, the utility of hyper-
valent iodine reagents has increased tremendously in the metal-
free oxidations, a-functionalization of carbonyl compounds, cycli-
zation reactions, vicinal difunctionalization of alkenes and in
rearrangement reactions.10
The geminal heterodifunctionalized moieties such as imidazo-
lidines, and oxazolidines are widely present as key structural units
in a variety of bioactive natural products11 and have found use as
chiral ligands in asymmetric synthesis.12 In spite of their greater
potential, the access to these class of compounds are often ham-
pered due to the paucity of methods available. Hence, the de-
velopment of a new method for the geminal difunctionalization of
alkenes, especially under the metal-free conditions would be of
high significance and of greater practical utility.
To the best of our knowledge, there is no method available at
present for the geminal diamination and intermolecular, metal-
free geminal aminooxygenation of unfunctionalized alkene-
s.6a,10u Herein, we wish to present the first report for such
a transformation on vinylarenes via semi-pinacol rearrangement
using electrophilic activation strategy in a one-pot operation
(Fig. 1).
* Corresponding author. Tel.: þ91 80 2293 2404; fax: þ91 80 2360 2423; e-mail
address: scn@orgchem.iisc.ernet.in (S. Chandrasekaran).
http://dx.doi.org/10.1016/j.tet.2016.01.005
0040-4020/Ó 2016 Elsevier Ltd. All rights reserved.

1096
P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
them are essential for mediating this reaction efficiently (entries
12 and 13, Table 1).
While, the use of anhyd. PTSA was also found to mediate this
addition with same efficiency as that of PTSA$H2O (entry 14, Table
1). The use of hydrated activator PTSA$H2O makes this geminal
difunctionalization conditions practically very attractive, in addi-
tion to that of being highly efficient. Encouraged by the novelty and
potency of this method, we set out to study the scope and mech-
anistic details of this process further.
First, the effect of substituents on the N-Ts-aminoalcohol on the
stereoselectivity and the efficiency of the addition were studied.
The enantiopure aminoalcohols containing different substituents at
the nitrogen bearing carbon (entries 1e5, Table 2) were found to
Table 2
Effect of substituent of the aminoalcohol on the stereoselectivity and regioselectivity
Fig. 1. Synthesis of geminally heterodifunctionalized compounds.
2. Results and discussion
In continuation of our interest9 to find practically useful
methods for the straightforward synthesis of 1,4-heterocycles
directly from alkenes by the intermolecular vicinal difunctionali-
zation/annulation strategy, we have examined the feasibility of
the addition of a 1,2-aminoalcohol as a nucleophile [N-Ts-phe-
nylalaninol, 1a] to styrene 2a, by the electrophilic activation of
alkene using halogens (entries 1e4, Table 1) and no expected
addition product formation was observed.13 The activation using
the hypervalent iodine reagents (entries 5 and 6, Table 1) also did
not provide any addition product. When we attempted the addi-
tion in the presence of TMSOTf activated hypervalent iodine re-
agent, PhI(OCOCF3)2 (1.5 equiv) (CH2Cl2, 24 h, rt), we were
surprised to find the formation of the geminally difunctionalized
product, oxazolidine 3a (entry 8, Table 1) as a single diastereomer
in 40% yield. This turns out to be the first metal-free in-
termolecular geminal aminooxygenation of an alkene. To improve
the efficiency of this reaction the activation of hypervalent iodine
was performed using different acids (entries 7e11, Table 1). It was
found that the most optimal activator for the PhI(OCOCF3)2 was
PTSA$H2O for this addition reaction conditions (entry 11, Table 1).
However, the yield of the products formed was found to decrease
proportionally on decreasing either the hypervalent iodine re-
agent or the activator, suggesting stoichiometric amount of both
Entry
Amino alcohol
Oxazolidine
Yield (%)b
1)
2)
3)
86
89
72
4)
5)
80
81
6)
94
70
7)
8)
Table 1
Representative optimization
58c
9)
90d
65e
71
Entry Eþ(Electrophile source) Activator/Base Solvent Time Yield (%)b
1)
2)
3)
4)
5)
6)
7)
8)
NBS
NIS
PTAB
I2
d
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
CH2CI2
24 h N.R.
24 h N.R.
24 h N.R.
24 h N.R.
24 h N.R.
24 h N.R.
24 h 33
24 h 40
24 h 60
4 h 67
d
10)
11)
d
d
Phl(OAc)2
Phl(OCOCF3)2
Phl(OAc)2
Phl(OCOCF3)2
Phl(OCOCF3)2
Phl(OCOCF3)2
Phl(OCOCF3)2
Phl(OCOCF3)2
Phl(OCOCF3)2(cat.)
Phl(OCOCF3)2
d
d
TMSOTf
TMSOTf
CF3COOH
HCIO4(60%)
PTSA
PTSA(cat.)
PTSA
anhyd. PTSA
9)
10)
11)
12)
13)
14)
12)
75
4 h 86
4 h 25
4 h 15
4 h 82
aReaction conditions: 1 equiv (0.33 mmol) of corresponding aminoalcohol 1aeI,
1.1 equiv of 2a, 1.5 equiv of Phl(OCOCF3)2, 1.1 equiv of PTSA$H2O, 3 mL of solvent.
b
Isolated yield.
The bold faces are refer to the best or the significant result.
c
aReaction conditions: 1 equiv (0.33 mmol) of 1a, 1.1 equiv of 2a 1.5 equiv of
Ratio of 3ha:3hb¼4.4:1.0.
d
d.r.¼1.1:1.0.
electrophile source, 1.1 equiv of activator/base, 3 mL of solvent.
e
b
d.r.¼1.0:1.0.
Isolated yield.

P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
1097
render the corresponding oxazolidines with excellent stereo-
selectivity under the metal-free addition conditions (styrene 2a,
PhI(OCOCF3)2, PTSA$H2O, CH2Cl2, 4 h, rt). When norepinephrine
derived N-Ts-aminoalcohol 1f was reacted with the styrene 2a
under the metal-free conditions (styrene 2a, PhI(OCOCF3)2,
PTSA$H2O, CH2Cl2, 4 h, rt), a fully substituted oxazolidine 3f was
formed (94%) as a single diastereomer.
Linearly fused tricyclic oxazolidine 3g was obtained as single
diastereomer under the same conditions upon the addition of
indanol derived N-Ts aminoalcohol 1g to syrene 2a. Intriguingly,
in the reaction of unsubstituted N-Ts-2-aminoethanol 1h with
2a, in addition to the expected geminal addition product, oxa-
zolidine 3ha, formation of the vicinal addition product, mor-
pholine 3hb was also observed (3ha: 3hb¼4.4: 1.0). This
demonstrates the steering role of substituents on the amino-
alcohol in controlling the regioselectivity of the addition, in
addition to controlling the stereoselectivity. The aminoalcohol
ortho (2x, 2y) and para position (2per) were found to react
more efficiently than the meta substituted styrenes (2z, 2aa)
to give the corresponding oxazolidines. These results may be
attributed to the ability of the substituents to stabilize the
carbocationic intermediates formed in the geminal difunc-
tionalization reaction.
The styrenes (2uew, 2af) having acid-labile substituents,
having bulkier 2,4,6-trimethyl substituent 2ab and with chlor-
omethyl substituent 2ac were also found to react smoothly to
provide the corresponding oxazolidines in good yields. In-
triguingly, when the reaction was performed with either trans-
b-
methyl styrene 2ad or cis- -methyl styrene 2ae, the same prod-
b
uct (3ad) with the same stereoidentity was formed in good
yields. This implies stereoconvergence of the intermediates
formed from the two distinct diastereomeric styrenes under the
conditions of addition of 1b.
Motivated by the attractive results obtained from the geminal
aminooxygenation, we then decided to investigate the feasibility
of a more challenging and the unprecedented geminal diamination
of styrenes under metal-free conditions. When we attempted to
add the 1,2-diamine derivative 4a to styrene 2a, we were pleased
to find that the product formed in very good yield (79%) was the
geminal diaminated imidazolidine 5a as a single diastereomer
under the metal-free conditions (PhI(OCOCF3)2, PTSA$H2O, CH2Cl2,
8 h, rt) (entry 1, Table 4). The enantiopure diamine derivatives
(4bed) derived from the corresponding aminoacids with different
substituents were also found to react with styrene 2a smoothly to
give the corresponding imidazolidines (5bed) in good yields with
very high diastereoselectivity. Interestingly, the unsubstituted
diamine derivative 4e provided the geminal addition product 5e
almost exclusively with traces of vicinal addition product (imida-
zolidine: piperazine¼97: 3.0). It is important to note that the ex-
tent of geminal addition of diamine 4e to 2a is quite significant
derivatives, 1i and 1j having a substituent on the
a-carbon
adjacent to hydroxyl group, on reaction with 2a under the same
conditions provided the corresponding oxazolidines 3i and 3j
with low diastereoselectivity (entries 9 and 10, Table 2). This
result illustrates the importance of the effect of substituent at
the carbon bearing the amine or the hydroxyl group of the
aminoalcohol on the stereochemical course of the reaction. The
methodology was then applied to a rapid, straightforward, and
one-pot synthesis of pseudoprolines 3k and 3l by the reaction
of serine derived N-Ts-aminoalcohol 1k and threonine derived
N-Ts-aminoalcohol 1l, respectively with styrene 2a (entries 11
and 12, Table 2).
It was then decided to study the role of substituents on
styrenes in the geminal aminooxygenation reaction. A variety
of substituted styrenes (2me2af) on reaction with N-Ts-vali-
nol 1b (PhI(OCOCF3)2, PTSA$H2O, CH2Cl2, 4 h, rt) gave the
corresponding difunctionalized product, oxazolidines 3me3af
as a single diastereomer in good to excellent yields (Table 3).
Various alkyl (3meo, 3t) and aryl 3s substituted oxazolidines
were efficiently obtained by the addition of N-Ts-amino-
alcohol 1b to the corresponding styrenes (2meo, 2s, 2t). The
styrenes having electron withdrawing substituents at the
Table 4
Geminal diamination of vinylarenes
Table 3
Effect of substituent on the styrene in the geminal aminooxygenation
Entry
1)
Diamine
Imidazolidine
Yield (%)b
79
2)
3)
92
84
4)
5)
71
78c
aconditions: same as Table 2.
b
Isolated yield.
Imidazolidine: piperazine¼97.0: 3.0.
c

1098
P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
compared to the geminal addition of aminoalcohol 1h to 2a (cf.
entry 8, Table 2).
The control studies were then conducted to confirm the for-
mation of epoxide as the intermediate in the m-CPBA mediated
geminal aminooxygenation (Scheme 3). When the N-Ts amino-
alcohol 1b was added to styrene 2a in the absence of m-CPBA no
addition product was observed (entry 1, Scheme 3). The anticipated
epoxide 6a was formed and not the oxazolidine 3b, when the
aminoalcohol 1b was added with styrene 2a in the absence of
PTSA$H2O (entry 2, Scheme 3). The epoxide 6a (styrene oxide) on
reaction with N-Ts aminoalcohol 1b provided the oxazolidine 3b
(entry 3, Scheme 3) in the presence of PTSA$H2O. The product 3b
formed from the addition of N-Ts aminoalcohol 1b to epoxide 6a
(3b, Scheme 3) and the one formed from the addition to amino-
alcohol 1b to styrene 2a (3b, Scheme 1) were found to be spec-
troscopically the same. These results prove that the epoxide is the
actual intermediate formed in the m-CPBA mediated geminal
aminooxygenation.
After the successful geminal diamination and aminooxygenation,
we decided to develop a catalytic version of the reaction using only
a catalytic amount of hypervalent iodine.14 In the preliminary
experiments (entries 1e6, Table 5), we were pleased to find that,
using a catalytic amount of PhI(OCOCF3)2 (5 mol %) and m-CPBA14 as
an oxidant, the aminoalcohol 1b could be added geminally to
styrene 2a (entry 6, Table 5), (PTSA$H2O, CH2Cl2, 24 h, rt) to give
oxazolidine 3a smoothly in good yield (74%). In the course of
optimization studies, intriguingly, the formation of oxazolidines as
the sole product was observed even in the absence of PhI(OCOCF3)2
indicating that m-CPBA alone mediates, and also competes
preferentially in the geminal difunctionalization process rather than
the oxidation of hypervalent iodine(III) species (entries 7 and 8,
Table 5).
Table 5
H
H
NHTs
CH2Cl2
24 h, rt
Optimization of m-CPBA mediated geminal aminooxygenation
PTSA
1.
2.
3.
N.R.
+
+
+
+
+
+
2a H
Ph
H
1b
OH
H
O
NHTs
CH2Cl2
24 h, rt
H
H
H
m-CPBA
PTSA
6a
Ph
H
2a
Ph
1b
OH
Ts
N
O
NHTs
CH2Cl2
24 h, rt
H
H
H
Entry Styrene (equiv) Phl(OCOCF3)2 (mol %) m-CPBA (equiv) Yield (%)b
Ph
1b
6a
H
Ph
O
OH
3b, 75%
H
H
1)
2)
3)
4)
5)
6)
7)
1.1
1.1
1.1
2.5
1.1
2.5
2.5
20
10
05
05
05
05
1.5
1.5
1.5
1.5
2.0
2.0
1.5
41
48
45
56
48
74
50
Scheme 3. Control studies for the m-CPBA mediated geminal aminooxygenation of
vinylarenes.
Aroused by the curiosity to understand the mechanistic details
of this two intriguing oxidative geminal addition reactions medi-
ated by PhI(OCOCF3)2 and m-CPBA, deuterated styrene was used as
a probing tool to delineate the reaction pathways (Table 6). In-
8)
2.5
3.0
78
The bold faces are refer to the best or the significant result.
Table 6
Deuterium labelling studies
aReaction conditions: 1 equiv (0.33 mmol) of 1b, 1.1 equiv of PTSA$H2O, 3 mL of
solvent.
b
Isolated yield.
It is worth pointing out that, in addition to the hypervalent io-
dine mediated geminal addition process, we have also developed
an unprecedented m-CPBA mediated intermolecular geminal ami-
nooxygenation of vinlyarenes (Scheme 1).
Entry Phl(OCOCF3)2
(equiv)
m-CPBA
(equiv)
Product ratio (3ag: 3ah) Yield (%)b
1)
2)
3)
4)
1.1
0
0.05
0.50
0
100: 0
0:100
79
67
72
74
3.0
2.0
2.0
3.5: 96.5
44: 56
Ts
N
H
H
H
NHTs
OH
m-CPBA
The bold faces are refer to the best or the significant result.
H
Ph
2a
Ph
aReaction conditions: 1 equiv (0.33 mmol) of 1b, 1.1, 2.5, 2.0 and 2.0 equiv of 2ag for
entries 1, 2, 3 & 4, respectively. 1.1 equiv of PTSA$H2O, 3 mL of solvent.
+
PTSA.H2O,
CH2Cl2, 24 h, rt
O
, 78%
1b
H
H
3b
b
Isolated yield.
Scheme 1. m-CPBA mediated geminal aminooxygenation of vinylarenes.
We were interested to understand the path of oxidative acti-
vation of styrene by m-CPBA and PTSA$H2O in mediating the
geminal addition process to form the oxazolidine as the sole
product. We supposed that the epoxide 6a is the intermediate
formed in the m-CPBA mediated geminal aminooxygenation. The
epoxide 6a thus formed upon ring opening by the aminoalcohol 1b
leads to the formation of oxazolidine 3b (Scheme 2).
terestingly, when the aminoalcohol 1b was reacted with the b,b-
dideuterated styrene 2ag using only PhI(OCOCF3)2 as the reagent
(entry 1, Table 6) it was found to furnish the dideuterated phenyl-
methylene (-CD2Ph) substituted oxazolidine 3ag as the sole prod-
uct (79%). This would be the result of phenyl migration pathway
(vide infra path-A1, Scheme 4). However, when the same reaction
was performed using only m-CPBA as the reagent (entry 2, Table 6),
it provided exclusively a diastereomeric mixture of oxazolidine 3ah
having deuterium attached at the hemiaminal carbon (-CDNO) with
the stereogenic monodeuterohydrophenylmethylene (-CHDPh)
substituent as the sole product. The formation of 3ah could be
deduced as the product obtained from the deuterium migration
pathway (vide infra path-B, Scheme 4).
Scheme 2. Supposed pathway for the m-CPBA mediated geminal aminooxygenation of
vinylarenes.

P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
1099
Scheme 3) [cf. int B, Scheme 4] to give the dideuteromethylene ether
F. The alkoxonium ion G formed upon the attack of acid (PTSA$H2O)
on intermediate F gives rise to the benzylic carbocation H, which
after the deuterium shift forms a more stable oxonium ion I. The
oxonium ion eventually gets cyclized to give the oxazolidine 3ah, in
which one of the deuteriums of the parent styrene has migrated to
the adjacent carbon in the course of the reaction. It is interesting to
note that the geminal aminooxygenation of styrene 2ag occurs
through two independent, distinct oxidative difunctionalization
pathways mediated by PhI(OCOCF3)2 and m-CPBA, respectively,
thereby fulfilling the essential features of a reagent-switch.
3. Conclusions
In summary, in this article development of two new methods for
the geminal oxyamination of vinylarenes and their detailed study
to understand its mechanism are presented. We have developed
the first general method for the geminal diamination and the first
intermolecular metal-free geminal aminooxygenation of vinyl-
arenes with excellent stereoselectivity mediated by hypervalent
iodine reagent. In addition, a new m-CPBA mediated geminal
aminooxygenation has also been developed. A novel reagent-
switch for the control of migrating group by controlling the two
independent, distinct pathways of the two reagent systems has
been reported for this geminal addition. The control studies have
clearly demonstrated the intermediacy of epoxide in the m-CPBA
mediated geminal aminooxygenation. Deuterium labelling studies
have provided unambiguous evidences for the phenyl migration
and hydride migration in the semi-pinacol rearrangement and also
for the unusual ring-opening at methylene site of epoxide in-
termediate formed.
Scheme 4. Proposed mechanism for the metal-free geminal difunctionalization.
4. Experimental section
4.1. General
It is worth noting that in this case, the epoxide actually got
opened up at the methylene site (vide infra int-F, Scheme 4), which
is rather unusual, than the generally observed benzylic site.15 Ad-
ditionally, it was also observed that the ratio of phenyl migrated
product 3ag increases proportionally with added amount of
PhI(OCOCF3)2 (entries 3 and 4, Table 6). These results indicate that
the two oxazolidines 3ag and 3ah are the products obtained from
two independently competing pathways mediated by PhI(O-
COCF3)2 and m-CPBA, respectively.
In light of these observations, we propose a mechanism for the
geminal addition pathway mediated by PhI(OCOCF3)2 and m-CPBA as
shown in Scheme 4. In the PhI(OCOCF3)2 mediated pathway (Path-
A1), at first the highly electrophilic hypervalent iodine species acti-
All reactions were carried out in oven-dried apparatus using dry
solvents under anhydrous conditions, unless otherwise noted. Re-
action mixtures were stirred magnetically, unless otherwise stated.
Analytical grade solvents were distilled and dried according to lit-
erature procedures.17 Analytical TLC was performed on commercial
plates coated with silica gel GF254 (0.25 mm). Visualization of TLC
was accomplished using UV light or PMA stain. Silica gel
(230e400 mesh) was used for column chromatography. NMR
spectra were recorded on 400 MHz spectrometer. The chemical
shifts (d, ppm) are reported with reference to; either internal
vated by PTSA$H2O reacts with the p-bond of styrene 2ag to form the
standard SiMe4 (for 1H) or the central line (77.0 ppm) of CDCl3 (for
13C) for CDCl3; either solvent residual peak (2.05 ppm) of Acetone-
d6 (for 1H) or the central line (29.84 ppm) of Acetone-d6 (for 13C) for
Acetone-d6; either solvent residual peak (2.50 ppm) of DMSO-d6
(for 1H) or the central line (39.52 ppm) of DMSO-d6 (for 13C) for
DMSO-d6. The following abbreviations explain the multiplicity
s¼singlet, d¼doublet, t¼triplet, q¼quartet, dd¼doublet of a dou-
blet, quint¼quintet, m¼multiplet, and br¼broad. IR spectra were
recorded as thin films on NaCl plates on an FT-IR spectrometer.
High-resolution mass spectra (HRMS) were recorded on a Micro-
mass Q-TOF mass spectrometer. Isolated yields refer to chromato-
graphically and spectroscopically (1H NMR) homogeneous
materials, unless otherwise stated.
hypervalent iodonium intermediate A. This highly active hypervalent
iodonium ring gets opened up at the more reactive benzylic position
by the attack of hydroxyl nucleophile of aminoalcohol 1b to form the
acylic benzylether B. The reduction of hypervalent iodonium species
is facilitated by the anchimeric assistance rendered by the phenyl
group, forming the phenonium ion16 C. This species upon subsequent
phenyl migration leads to the formation of the more stable oxonium
ion D. The oxonium ion thus formed undergoes a 5-endo-trig cycli-
zation to furnish the oxazolidine 3ag (vide supra, entry 1, Table 6), in
which the two deuterium atoms are intact with the carbon attached
to them in the parent styrene throughout the process and the phenyl
group has migrated to the adjacent carbon. When the aminoalcohol
or the diamine is unsubstituted (entry 8, Table 2; entry 5, Table 4), the
6-endo-tet pathway (Path-A2) also competes with the phenyl mi-
gration pathway (Path-A1).
All commercially available reagent grade styrenes 2ae2af,
PhI(OCOCF3)2, m-CPBA and PTSA$H2O were used as received,
without further purification. The anhyd. PTSA was prepared by the
dehydration of PTSA$H2O according to the literature procedure.17
The N-Ts amino alcohols 1a, 1fel were prepared according to the
reported procedure.9 The amino alcohols such as (S)-(þ)-valinol,
(R)-(ꢀ)-phenylglycinol and (S)-(þ)-isoleucinol were synthesized by
In the m-CPBA mediated reaction (Path-B), the epoxide E is first
formed as a result oxidation of styrene by m-CPBA (entry 2, Scheme
3). The acid, PTSA$H2O activates the epoxide, which gets opened up
at the less hindered methylene site by the aminoalcohol (entry 3,

1100
P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
the reduction of the corresponding
L-amino acid according to the
13C NMR (100 MHz, CDCl3)
d 144.1, 136.1, 134.2, 130.2, 129.9, 128.1,
reported literature procedure.18 The 1,2-diamine precursors for
4bed were synthesized from corresponding amino acids according
to the reported literature procedure.19 Experimental procedure and
the complete characterization data for the starting materials 1be1e
(Table 2), 4ae4d (Table 4) can be found in the Supplementary
data.13 N-Ts-aminoalchols 1a, 1fel were prepared as previously
described.13
127.9, 126.7, 92.6, 69.7, 60.8, 42.6, 27.5, 21.5, 10.4; HRMS (ESI-
QTOF) m/z: [MþNa]þ calcd for C19H23NO3SNa, 368.1296; found,
368.1294.
4.2.6. (2S,4S,6S)-2-Benzyl-4-2-butyl-3-tosyloxazolidine
(3e). Colorless oil (102 mg, 81%); Rf 0.50 (pet. ether: EtOAc, 9:1);
[a
]
21 ꢀ53.8 (c 2.0, CHCl3); IR (cmꢀ1): 2964, 2930, 2873, 1599, 1495,
D
1456, 1350, 1164, 1089, 997, 972; 1H NMR (400 MHz, CDCl3)
d 7.73
4.2. PhI(OCOCF3)2 Mediated synthesis of oxazolidines 3ae3ag:
Method A
(d, J¼7.9 Hz, 2H), 7.33e7.23 (m, 7H), 5.02 (d, J¼7.7 Hz, 1H), 3.76 (d,
J¼8.9 Hz, 1H), 3.43 (t, J¼5.7 Hz, 1H), 3.31 (d, J¼13.9 Hz, 1H),
3.08e2.99 (m, 2H), 2.42 (s, 3H), 1.65e1.55 (m, 1H), 1.53e1.46 (m,
1H), 1.15e1.03 (m, 1H), 0.87 (s, 3H), 0.86 (s, 3H); 13C NMR (100 MHz,
4.2.1. General procedure for the PhI(OCOCF3)2 mediated synthesis of
oxazolidines 3ae3ag: Method A. To a colorless solution of corre-
sponding N-Ts aminoalcohol (0.33 mmol) and styrene (0.36 mmol)
in CH2Cl2 (3 mL) in a well dried Schlenk flask under argon atmo-
sphere was added PhI(OCOCF3)2 (0.50 mmol) and PTSA$H2O
(0.36 mmol) at room temperature [25 ꢁC]. The progress of the re-
action was monitored by TLC. After stirring the reaction mixture for
4 h at room temperature 5 mL of satd soln of aq NaHCO3 was added
and extracted with CH2Cl2. The combined organic layers were dried
(anhyd. Na2SO4), filtered and concentrated in vacuo. The crude
product obtained was purified by flash chromatography (pet. ether:
Et2O, 8:1) to furnish oxazolidines in pure form.
CDCl3)
d 144.1, 136.4, 133.9, 129.94, 129.87, 128.3, 128.0, 126.7, 92.9,
67.3, 64.0, 42.4, 37.4, 26.1, 21.5, 14.8, 11.7; HRMS (ESI-QTOF) m/z:
[MþNa]þ calcd for C21H27NO3SNa, 396.1609; found, 396.1607.
4.2.7. (2R,4R,5S)-2-Benzyl-4-methyl-5-phenyl-3-tosyloxazolidine
(3f).9 Colorless solid (126 mg, 94%); Rf 0.50 (pet. ether: EtOAc, 9:1);
mp 112e114 ꢁC (lit.9 mp 123e124 ꢁC); [
a]
21 þ2.4 (c 1.0, CHCl3) [lit.9
D
21
[a
]
þ2.8 (c 2.0, CHCl3)]; 1H NMR (400 MHz, CDCl3)
d 7.84 (d,
D
J¼8.0 Hz, 2H), 7.45e7.22 (m, 10H). 7.07 (d, J¼7.1 Hz, 2H), 5.21 (d,
J¼4.8 Hz, 1H), 4.18 (d, J¼5.4 Hz, 1H), 3.92e3.86 (m, 1H), 3.42 (d,
J¼13.9 Hz, 1H), 3.25 (dd, J¼14.0, 6.0, Hz, 1H), 2.46 (s, 3H), 0.40 (d,
J¼6.7 Hz, 3H).
4.2.2. (2S,4S)-2,4-Dibenzyl-3-tosyloxazolidine (3a).9 White solid
(115 mg, 86%); Rf 0.50 (pet. ether: EtOAc, 9:1); mp 80e81 ꢁC (lit.9
4.2.8. (2S,3aS,8aR)-2-Benzyl-3-tosyl-indanooxazolidine
21
mp 76e79 ꢁC); [
a
]
þ23.9 (c 1.0, CHCl3) [lit.9
[
a
]
2D1þ23.5 (c 1.0,
(3g).9 Colorless crystals (94 mg, 70%); Rf 0.50 (pet. ether: EtOAc,
D
21
CHCl3)]; 1H NMR (400 MHz, CDCl3)
d
; 7.76 (d, J¼8.1 Hz, 2H),
9:1); mp 120e122 ꢁC (lit.9 mp 123e124 ꢁC); [
a
]
D
ꢀ46.6 (c 1.0,
21
7.33e7.18 (m, 10H), 7.09 (d, J¼7.3 Hz, 2H), 5.09, (dd, J¼6.8, 1.6 Hz
1H), 3.78e3.74 (m, 1H), 3.61 (dd, J¼9.0, 2.3 Hz, 1H), 3.28 (dd, J¼14.0,
1.5 Hz, 1H), 3.08e2.99 (m, 2H), 2.92 (dd, J¼13.6, 3.5 Hz, 1H), 2.41 (s,
3H), 2.25 (dd, J¼13.3, 10.9 Hz, 1H).
CHCl3) [lit.9
[
a]
ꢀ38.8 (c 1.0, CHCl3)]; 1H NMR (400 MHz, CDCl3)
D
d
7.80 (d, J¼8.0 Hz, 2H), 7.49 (d, J¼6.3 Hz, 1H), 7.35e7.03 (m, 10H),
5.33 (dd, J¼7.7, 2.9 Hz, 1H), 5.24 (d, J¼5.4 Hz, 1H), 4.17 (t, J¼5.1 Hz,
1H), 3.10e2.90 (m, 3H), 2.49 (dd, J¼14.0, 8.0 Hz, 1H), 2.44 (s, 3H).
4.2.3. (2S,4S)-2-Benzyl-4-isopropyl-3-tosyloxazolidine
4.2.9. Mixture of 2-phenyl-4-tosylmorpholine (3ha9) and 2-benzyl-3-
tosyloxazolidine (3hb9). Mixture of oxazolidine A9 and morpholine
B9 (4.4:1.0): white solid (61 mg, 58%); R 0.30 (pet. ether: EtOAc,
(3b). Colorless oil (76 mg, 89%); Rf 0.50 (pet. ether: EtOAc, 9:1);
[
a]
21 ꢀ63.0 (c 1.0, CHCl3); IR (cmꢀ1): 3030, 2962, 2874, 1599, 1493,
D
1467, 1455, 1351, 1158, 1090, 1009, 816, 755, 706, 668; 1H NMR
9:1); 1H NMR (400 MHz, CDCl3)
d
7.73 (d, J¼7.8 Hz, 2H, 2A), 7.62 (d,
(400 MHz, CDCl3)
d
7.73 (d, J¼8.1 Hz, 2H), 7.33e7.22 (m, 7H), 5.03
J¼8.1 Hz, 0.44H, 2B), 7.33e7.14 (m, 8.6H, 7Aþ7B), 5.27 (d, J¼5.5 Hz,
1H, 1A), 4.6 (d, J¼10.1 Hz, 0.23H, 1B), 4.1 (d, J¼11.4 Hz, 0.24H, 1B),
3.89e3.72 (m, 1.52H, 1Aþ2B), 3.64 (d, J¼11.3 Hz, 0.24H, 1B),
3.43e3.38 (m, 1H, 1A), 3.26 (dd, J¼14.5, 7.2 Hz, 1H, 1A), 3.20e3.14
(m, 2H, 2A), 3.0 (dd, J¼13.9, 6.8 Hz, 1H, 1A), 2.54e2.43 (m, 3.9H,
3Aþ3Bþ1B), 2.24 (t, J¼10.9 Hz, 0.26H, 1B).
(dd, J¼8.2, 2.3 Hz, 1H), 3.75 (dd, J¼8.9, 1.8 Hz, 1H), 3.37e3.30 (m,
2H), 3.03e2.96 (m, 2H), 2.42 (s, 3H), 1.70e1.61 (m, 1H), 0.98 (d,
J¼6.8 Hz, 3H), 0.89 (d, J¼6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
144.1, 136.4, 134.1, 129.90, 129.85, 128.2, 128.0, 126.7, 92.9, 67.7,
65.2, 42.6, 31.1, 21.5, 19.7, 18.7; HRMS (ESI-QTOF) m/z: [MþNa]þ
calcd for C20H25NO3SNa, 382.1453; found, 382.1454.
4.2.10. (5R)-2-Benzyl-5-phenyl-3-tosyloxazolidine (3i).9 [Mixture of
diastereomers; d.r.¼1.0: 1.0] white solid (117 mg, 90%); Rf 0.50 (pet.
4.2.4. (2S,4S)-2-Benzyl-4-phenyl-3-tosyloxazolidine
(3c). White
solid (94 mg, 72%); Rf 0.50 (pet. ether: EtOAc, 9:1); mp 81e82 ꢁC;
ether: EtOAc, 9:1); 1H NMR (400 MHz, CDCl3)
d
7.79 (d, J¼8.1 Hz,
[
a]
21 þ20.8 (c 2.0, CHCl3); IR (cmꢀ1): 3783, 3702, 3661, 3432, 3031,
1H), 7.66 (d, J¼8.1 Hz, 1H), 7.39e7.14 (m, 10H), 7.02e7.0 (m, 1H),
6.85 (d, J¼7.2 Hz, 1H), 5.5 (t, J¼4.9 Hz, 0.5H), 5.43 (dd, J¼5.4, 2.9 Hz,
0.5H), 4.94 (t, J¼7.1 Hz, 0.5H), 4.05 (dd, J¼10.2, 5.4 Hz, 0.5H), 3.79
(dd, J¼11.9, 5.4 Hz, 0.5H), 3.70 (dd, J¼9.6, 6.3 Hz, 0.5H), 3.29e3.16
(m, 2H), 3.08 (t, J¼8.8 Hz, 0.5H), 2.83 (t, J¼11.0 Hz, 0.5H), 2.45 (s,
1.5H), 2.4 (s, 1.5H).
D
2925, 2871, 1597, 1351, 1161, 1089, 1000, 770, 701, 669; 1H NMR
(400 MHz, CDCl3)
d
7.72 (d, J¼8.1 Hz, 2H), 7.31e7.24 (m, 12H), 5.31
(dd, J¼8.4, 2.1 Hz, 1H), 4.69 (dd, J¼6.3, 5.0 Hz, 1H), 3.93 (dd, J¼8.9,
4.6 Hz, 1H), 3.77 (dd, J¼8.8, 6.9 Hz, 1H), 3.39 (dd, J¼14.0, 2.1 Hz, 1H),
3.11 (dd, J¼14.0, 8.5 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
144.2, 139.2, 136.3, 133.9, 129.90, 129.87, 128.5, 128.4, 128.0, 127.8,
126.8, 126.6, 93.6, 72.6, 62.2, 42.3, 21.5; HRMS (ESI-QTOF) m/z:
4.2.11. (5R)-2-Benzyl-5-methyl-3-tosyloxazolidine (3j).9 [Mix of di-
astereomers; d.r.¼1.0: 1.0]: colorless oil (72 mg, 65%); Rf 0.50 (pet.
[MþNa]þ calcd for C23H23NO3SNa, 416.1296; found, 416.1295.
ether: EtOAc, 9:1); 1H NMR (400 MHz, CDCl3)
d
7.72 (dd, J¼8.2,
4.2.5. (2S,4R)-2-Benzyl-4-ethyl-3-tosyloxazolidine (3d). White solid
2.3 Hz, 2H), 7.40e7.22 (m, 7H), 5.28 (dd, J¼7.1, 3.0 Hz, 0.5H), 5.24
(dd, J¼6.0, 2.5 Hz, 0.5H), 4.16e1.09 (m, 0.5H), 3.51 (dd, J¼11.6,
5.3 Hz, 0.5H), 3.45 (dd, J¼9.3, 5.7 Hz, 0.5H), 3.25e2.98 (m, 2.5H),
2.75 (dd, J¼9.0, 8.0 Hz, 0.5H), 2.47 (t, J¼10.9 Hz, 0.5H), 2.42 (s, 3H),
1.02 (d, J¼5.9 Hz, 1.5H), 0.92 (d, J¼6.1 Hz, 3H).
21
(91 mg, 80%); Rf 0.50 (pet. ether: EtOAc, 9:1); mp 81e83 ꢁC; [
a
]
D
þ39.8 (c 1.0, CHCl3); IR (cmꢀ1): 2871, 1598, 1494, 1455, 1347, 1215,
1187, 1163, 1088, 1005; 1H NMR (400 MHz, CDCl3)
d 7.74 (d,
J¼8.2 Hz, 2H), 7.33e7.21 (m, 7H), 5.07 (dd, J¼7.4, 2.2 Hz, 1H), 3.58
(dd, J¼8.7, 2.5 Hz, 1H), 3.54e3.49 (m, 1H), 3.28 (dd, J¼14.0, 2.2 Hz,
1H), 3.17 (dd, J¼8.6, 6.0 Hz, 1H), 3.03 (dd, J¼14.0, 7.4 Hz, 1H), 2.42
(s, 3H), 1.54e1.44 (m, 1H), 1.36e1.25 (m, 1H), 0.85 (t, J¼7.4 Hz, 3H);
4.2.12. (2R,4S)-Methyl-2-benzyl-3-tosyloxazolidine-4-carboxylate
(3k).9 Colorless oil (88 mg, 71%); Rf 0.40 (pet. ether: EtOAc, 4:1);

P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
1101
21
21
[
a
]
þ12.8 (c 1.0, CHCl3) [lit.9
[
a
]
D
þ11.1 (c 1.0, CHCl3)]; 1H NMR
7.34e7.20 (m, 6H), 4.98 (d, J¼6.1 Hz, 1H), 3.75 (d, J¼8.9 Hz, 1H), 3.34
(t, J¼6.8 Hz, 1H), 3.26 (d, J¼12.9 Hz, 1H), 3.03e2.95 (m, 2H), 2.43 (s,
3H),1.64e1.55 (m,1H), 0.96 (d, J¼6.8 Hz, 3H), 0.87 (d, J¼6.6 Hz, 3H);
D
(400 MHz, CDCl3)
d
7.75 (d, J¼8.2 Hz, 2H), 7.34e7.21 (m, 7H), 5.25
(dd, J¼8.3, 2.9 Hz, 1H), 4.38 (dd, J¼7.0, 3.4 Hz, 1H), 4.16 (dd, J¼9.0,
3.4 Hz, 1H), 3.73 (s, 3H), 3.60 (dd, J¼8.9, 7.1 Hz, 1H), 3.27 (dd, J¼14.1,
2.9 Hz, 1H), 3.05 (dd, J¼14.1, 8.3 Hz, 1H), 2.43 (s, 3H).
13C NMR (100 MHz, CDCl3)
d 144.2, 134.7, 134.0, 132.6, 131.4, 129.9,
128.3, 128.0, 92.6, 67.8, 65.2, 41.3, 31.1, 21.5, 19.7, 18.7; HRMS (ESI-
QTOF) m/z: [MþNa]þ calcd for C20H24ClNO3SNa, 416.1063; found,
416.1060.
4.2.13. (2R,4S,5R)-Methyl-2-benzyl-5-methyl-3-tosyloxazolidine-4-
carboxylate9 (3l). Colorless oil (97 mg, 75%); Rf 0.40 (pet. ether:
EtOAc, 4:1); [
a]
21 ꢀ3.7 (c 3.0, CHCl3) [lit.9 [
a]
21 ꢀ4.4 (c 1.0, CHCl3)];
4.2.19. (2S,4S)-4-Isopropyl-2-(4-bromobenzyl)-3-tosyloxazolidine
(3r). Colorless oil (136 mg, 94%); Rf 0.50 (pet. ether: EtOAc, 9:1);
D
D
1H NMR (400 MHz, CDCl3)
d
7.73 (d, J¼8.2 Hz, 2H), 7.33e7.21 (m,
21
7H), 5.41 (dd, J¼8.2, 3.9 Hz, 1H), 4.93e4.36 (m, 1H), 3.84 (d,
J¼6.2 Hz, 1H), 3.78 (s, 3H), 3.18e3.06 (m, 2H), 2.43 (s, 3H), 1.09 (d,
J¼6.1 Hz, 3H).
[a
]
ꢀ61.5 (c 1.0, CHCl3); IR (cmꢀ1): 2961, 2872, 1488, 1348, 1163,
D
1010; 1H NMR (400 MHz, CDCl3)
d
7.71 (d, J¼8.2 Hz, 2H), 7.42 (d,
J¼8.2 Hz, 1H), 7.33 (d, J¼8.0 Hz, 2H), 7.16 (d, J¼8.2 Hz, 2H), 4.97 (dd,
J¼7.7, 2.2 Hz,1H), 3.73 (dd, J¼8.9,1.5 Hz,1H), 3.36e3.32 (m,1H), 3.25
(dd, J¼14.0, 2.0 Hz,1H), 3.02e2.94 (m, 2H), 2.43 (s, 3H),1.64e1.55 (m,
1H), 0.96 (d, J¼6.8 Hz, 3H), 0.88 (d, J¼6.6 Hz, 3H); 13C NMR (100 MHz,
4.2.14. (2S,4S)-4-Isopropyl-2-(2-methylbenzyl)-3-tosyloxazolidine
(3m). Colorless oil (110 mg, 89%); Rf 0.50 (pet. ether: EtOAc, 9:1);
[
a]
21 ꢀ72.1 (c 1.0, CHCl3); IR (cmꢀ1): 2962, 2871,1349,1163; 1H NMR
CDCl3) d 144.2,135.2,134.0,131.8,131.3,129.9,128.0,120.7, 92.5, 67.8,
D
(400 MHz, CDCl3)
d
7.73 (d, J¼8.2 Hz, 2H), 7.32e7.12 (m, 6H), 5.03
65.2, 41.9, 31.1, 21.5,19.7,18.7; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd
(dd, J¼8.8, 2.0 Hz, 1H), 3.75 (dd, J¼9.0, 1.8 Hz, 1H), 3.42e3.37 (m,
2H), 3.00e0.8.93 (m, 2H), 2.42 (s, 6H), 1.83e1.4 (m, 1H), 1.04 (d,
J¼6.8 Hz, 3H), 0.95 (d, J¼6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3)
for C20H24BrNO3SNa, 460.0558; found, 460.0560.
4.2.20. (2S,4S)-4-Isopropyl-2-(4-phenylbenzyl)-3-tosyloxazolidine
(3s). White solid (94 mg, 65%); Rf 0.50 (pet. ether: EtOAc, 9:1); mp
d
144.1, 136.9, 134.9, 134.1, 130.7, 130.2, 129.9, 127.9, 126.9, 125.8,
ꢀ94.5 (c 1.0, CHCl3); IR (cmꢀ1): 2961, 1348, 1187,
21
92.4, 67.6, 65.2, 40.1, 31.2, 21.5, 19.8, 19.7, 18.7; HRMS (ESI-QTOF) m/
93e96 ꢁC; [
a
]
D
z: [MþNa]þ calcd for C21H27NO3SNa, 396.1609; found, 396.1620.
1163; 1H NMR (400 MHz, CDCl3)
d
7.75 (d, J¼8.0 Hz, 2H), 7.58e7.31
(m,11H), 5.06 (d, J¼6.4 Hz,1H), 3.77 (d, J¼8.7 Hz,1H), 3.38e3.35 (m,
2H), 3.05e3.00 (m, 2H), 2.42 (s, 3H), 1.73e1.65 (m, 1H), 1.0 (d,
J¼6.7 Hz, 3H), 0.90 (d, J¼6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
4.2.15. (2S,4S)-4-Isopropyl-2-(3-methylbenzyl)-3-tosyloxazolidine
(3n). Colorless oil (100 mg, 81%); Rf 0.50 (pet. ether: EtOAc, 9:1);
21
[
a]
ꢀ66.8 (c 2.0, CHCl3); IR (cmꢀ1): 2961, 2870, 1350, 1162; 1H
d 144.1, 141.0, 139.7, 135.5, 134.1, 130.3, 129.9, 128.7, 128.0, 127.1,
D
NMR (400 MHz, CDCl3)
d
7.73 (d, J¼8.0 Hz, 2H), 7.33e7.04 (m, 6H),
127.0; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for C26H29NO3SNa,
5.03 (d, J¼8.2 Hz,1H), 3.75 (d, J¼8.9 Hz,1H), 3.37e3.27 (m, 2H), 3.02
(dd, J¼8.7, 6.2 Hz,1H), 2.93 (dd, J¼13.9, 8.4 Hz,1H), 2.42 (s, 3H), 2.34
(s, 3H), 1.73e1.64 (m, 1H), 1.0 (d, J¼6.8 Hz, 3H), 0.90 (d, J¼6.6 Hz,
458.1766; found, 458.1766.
4.2.21. (2S,4S)-4-Isopropyl-2-(4-tert-butylbenzyl)-3-tosyloxazolidine
3H); 13C NMR (100 MHz, CDCl3)
d
144.1, 137.8, 136.3, 134.2, 130.6,
(3t). Colorless oil (114 mg, 83%); Rf 0.50 (pet. ether: EtOAc, 9:1);
21
129.9, 128.2, 128.0, 127.4, 126.8, 93.0, 67.7, 65.2, 42.7, 31.1, 21.5, 21.4,
19.7, 18.8; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for C21H27NO3SNa,
396.1609; found, 396.1608.
[a
]
ꢀ60.9 (c 1.0, CHCl3); IR (cmꢀ1) 2961, 2871, 1598, 1514, 1468,
D
1351, 1164, 1091, 1009, 888;1H NMR (400 MHz, CDCl3)
d 7.73 (d,
J¼8.0 Hz, 2H), 7.33e7.20 (m, 6H), 5.02 (d, J¼8.0 Hz, 1H), 3.74 (d,
J¼8.9 Hz, 1H), 3.36e3.27 (m, 2H), 3.02e2.91 (m, 2H), 2.41 (s, 3H),
1.67e1.59 (m, 1H), 1.30 (s, 9H), 0.97 (d, J¼6.8 Hz, 3H), 0.89 (d,
4.2.16. (2S,4S)-4-Isopropyl-2-(4-methylbenzyl)-3-tosyloxazolidine
(3o). Colorless oil (93 mg, 75%); Rf 0.50 (pet. ether: EtOAc, 9:1);
J¼6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 149.4, 144.0, 134.2,
133.3, 129.9, 129.5, 128.0, 125.2, 92.9, 67.7, 65.2, 42.1, 34.4, 31.3, 31.1,
[
a]
21 ꢀ70.0 (c 1.0, CHCl3); IR (cmꢀ1): 2961,1348,1163,1090,1012; 1H
D
NMR (400 MHz, CDCl3)
d
7.22 (d, J¼8.2 Hz, 2H), 7.31 (d, J¼8.0 Hz,
21.5, 19.8, 18.7; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for
2H), 7.17 (d, J¼7.9 Hz, 2H), 7.11 (d, J¼7.8 Hz, 2H), 5.0 (dd, J¼8.5,
2.3 Hz,1H), 3.74 (dd, J¼8.9, 1.8 Hz, 1H), 3.28e3.34 (m, 1H), 3.29 (dd,
J¼13.9, 2.0 Hz, 1H), 3.0 (dd, J¼8.9, 6.0 Hz, 1H), 2.92 (dd, J¼13.9,
8.5 Hz, 1H), 2.41 (s, 3H), 2.32 (s, 3H), 1.78e1.70 (m, 1H), 1.0 (d,
J¼6.8 Hz, 3H), 0.91 (d, J¼6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3)
C24H33NO3SNa, 438.2079; found, 438.2079.
4.2.22. (2S,4S)-4-Isopropyl-2-(4-acetylbenzyl)-3-tosyloxazolidine
(3u). Pale yellow oil (117 mg, 85%); Rf 0.45 (pet. ether: EtOAc, 4:1);
[
a
]
21 ꢀ54.7 (c 2.0, CHCl3); IR (cmꢀ1): 3462, 3310, 3026, 2963, 2930,
D
d
144.0, 136.2, 134.2, 133.4, 129.8, 129.7, 129.0, 128.0, 93.1, 67.7, 65.2,
2873, 1757, 1598, 1512, 1468, 1442, 1346, 1219, 1164, 1090, 1010, 971,
42.4, 31.2, 21.5, 21.0,19.7, 18.7; HRMS (ESI-QTOF) m/z: [MþNa]þ
913; 1H NMR (400 MHz, CDCl3)
d
7.72 (d, J¼7.9 Hz, 2H), 734e7.26
calcd for C21H27NO3SNa, 396.1609; found, 396.1609.
(m, 5H), 7.0 (d, J¼8.2 Hz, 2H), 5.0 (d, J¼7.4 Hz, 1H), 3.73 (d, J¼8.8 Hz,
1H), 3.35e3.27; (m, 2H), 3.02e2.98 (m, 2H), 2.43 (s, 3H), 2.29 (s,
3H),1.63e1.56 (m, 1H), 0.96 (d, J¼6.7 Hz, 3H), 0.87 (d, J¼6.6 Hz, 3H);
4.2.17. (2S,4S)-4-Isopropyl-2-(4-fluorobenzyl)-3-tosyloxazolidine
21
(3p). Colorless oil (110 mg, 88%); Rf 0.50 (pet. ether: EtOAc, 9:1); [
a]
13C NMR (100 MHz, CDCl3)
d 169.6, 149.5, 144.1, 134.0, 133.9, 131.0,
ꢀ52.5 (c 1.0, CHCl3); IR (cmꢀ1): 1510, 1348, 1222, 1163, 1093, 1013; 1DH
129.9, 128.0, 121.3, 92.7, 65.7, 65.2, 41.8, 31.0, 21.5, 21.1, 19.7, 18.7;
HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for C22H27NO5SNa,
440.1508; found, 440.1507.
NMR (400 MHz, CDCl3)
d
7.73 (d, J¼7.9 Hz, 2H), 7.33e7.23 (m, 4H), 6.98
(t, J¼8.4 Hz, 2H), 4.98 (d, J¼6.2 Hz, 1H), 3.73 (d, J¼8.7 Hz, 1H),
3.35e3.24 (m, 2H), 3.02e2.96 (m, 2H), 2.43 (s, 3H),1.59e1.54 (m,1H),
0.95 (d, J¼6.7 Hz, 3H), 0.86 (d, J¼6.5 Hz, 3H); 13C NMR (100 MHz,
4.2.23. (2S,4S)-4-Isopropyl-2-(4-methoxybenzyl)-3-tosyloxazolidine
CDCl3)
d
161.9 (d, 1JCeF¼243.2Hz),144.2,134.1,131.93(d, 4JCeF¼3.4Hz),
(3v). Colorless oil (102 mg, 79%); Rf 0.35 (pet. ether: EtOAc, 9:1);
3
2
21
131.56 (d, JCeF¼7.7 Hz), 129.9, 128.0, 115.2 (d, JCeF¼21.2 Hz), 92.8,
67.8, 65.2, 41.6, 31.1, 21.5, 19.7, 18.8; HRMS (ESI-QTOF) m/z: [MþNa]þ
calcd for C20H24FNO3SNa, 400.1359; found, 400.1357.
[a
]
ꢀ61.2 (c 1.5, CHCl3); IR (cmꢀ1): 3439, 1611, 1513, 1465, 1348,
D
1300, 1248, 1163, 1090, 1036; 1H NMR (400 MHz, CDCl3)
d 7.72 (d,
J¼8.2 Hz, 2H), 7.32 (d, J¼8.0 Hz, 2H), 7.20 (d, J¼8.5 Hz, 2H), 6.84 (d,
J¼8.5 Hz, 2H), 4.98 (dd, J¼8.1, 2.2 Hz,1H), 3.78 (s, 3H), 3.74 (dd, J¼8.9,
1.7 Hz,1H), 3.37e3.33 (m, 2H), 3.25 (dd, J¼14.1, 2.0 Hz,1H), 3.02 (dd,
J¼8.9, 6.1 Hz,1H), 2.93 (dd, J¼14.1, 8.1 Hz,1H), 2.42 (s, 3H),1.72e1.61
(m, 1H), 0.98 (d, J¼6.8 Hz, 3H), 0.89 (d, J¼56.7 Hz, 3H); 13C NMR
4.2.18. (2S,4S)-4-Isopropyl-2-(4-chlorobenzyl)-3-tosyloxazolidine
(3q). Colorless oil (112 mg, 86%); Rf 0.50 (pet. ether: EtOAc, 9:1);
[
a]
21 ꢀ62.5 (c 2.0, CHCl3); IR (cmꢀ1): 2963, 2872, 1598, 1493, 1349,
D
1163, 1090, 1012; 1H NMR (400 MHz, CDCl3)
d
7.2 (d, J¼8.0 Hz, 2H),
(100 MHz, CDCl3) d 158.4, 144.0, 134.2, 130.9, 129.8, 128.5, 128.0,

1102
P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
113.7, 93.1, 67.7, 65.2, 55.2, 41.7, 31.1, 21.5,19.7,18.7; HRMS(ESI-QTOF)
(d, J¼8.2 Hz, 2H), 7.30 (d, J¼8.0 Hz, 2H), 6.85 (s, 2H), 5.0 (dd, J¼9.9,
2.0 Hz, 1H), 3.73 (dd, J¼9.0, 1.72 Hz, 1H), 3.44e3.41 (m, 1H), 3.37
(dd, J¼14.1,1.6 Hz,1H), 3.03 (dd, J¼14.0,10.0 Hz,1H), 2.94 (dd, J¼8.9,
1.6 Hz, 1H), 2.41 (s, 3H), 2.38 (s, 6H), 2.23 (s, 3H),1.99e1.90 (m, 1H),
1.1 (d, J¼6.8 Hz, 3H), 1.01 (d, J¼6.7 Hz, 3H); 13C NMR (100 MHz,
m/z: [MþNa]þ calcd for C21H27NO4SNa, 412.1558; found, 412.1556.
4.2.24. (2S,4S)-4-Isopropyl-2-(4-ethoxybenzyl)-3-tosyloxazolidine
(3w). Colorless oil (111 mg, 83%); Rf 0.35 (pet. ether: EtOAc, 9:1);
21
[
a]
ꢀ68.7 (c 1.0, CHCl3); IR (cmꢀ1): 2963, 2927, 2872, 1609, 1512,
CDCl3) d 144.1, 137.3, 136.1, 134.2, 130.5, 129.8, 129.0, 127.9, 92.2,
D
1348, 1245, 1215, 1187, 1115, 1089, 1047, 1014; 1H NMR (400 MHz,
67.5, 65.2, 36.5, 31.5, 21.5, 20.8, 20.6,19.7, 18.7; HRMS (ESI-QTOF) m/
CDCl3)
d
7.73 (d, J¼8.1 Hz, 2H), 7.3 (d, J¼8.0 Hz, 2H), 7.19 (d, J¼8.4 Hz,
z: [MþNa]þ calcd for C23H31NO3SNa, 424.1922; found, 424.1922.
2H), 6.83 (d, J¼8.5 Hz, 2H), 4.98 (dd, J¼8.1, 2.2 Hz, 1H). 4.01 (q,
J¼7.0 Hz, 2H), 3.74 (dd, J¼8.9,1.7 Hz,1H), 3.37e3.3 (m,1H), 3.24 (dd,
J¼14.1, 2.1 Hz, 1H), 3.01 (dd, J¼8.9, 6.0 Hz, 1H), 2.92 (dd, J¼14.1,
8.2 Hz, 1H), 2.42 (s, 3H), 1.71e1.60 (m, 1H), 1.40 (t, J¼7.0 Hz, 3H),
0.98 (d, J¼6.8 Hz, 3H), 0.89 (d, J¼6.7 Hz, 3H); 13C NMR (100 MHz,
4.2.30. (2S,4S)-4-Isopropyl-2-(2-choromethylbenzyl)-3-
tosyloxazolidine (3ac). White solid (103 mg, 76%); mp 136e140 ꢁC;
Rf 0.50 (pet. ether: EtOAc, 9:1); [
a
]
21 ꢀ76.1 (c 1.0, CHCl3); IR (cmꢀ1):
D
2961, 2928, 1348, 1216, 1187, 1163, 1013; 1H NMR (400 MHz, CDCl3)
CDCl3)
d
157.8, 144.0, 134.2, 130.9, 129.8, 128.3, 128.0, 114.3, 93.1,
d
7.73 (d, J¼8.1 Hz, 2H), 7.40e7.21 (m, 6H), 5.0 (dd, J¼7.9, 2.0 Hz,1H),
67.1, 65.2, 63.4, 41.7, 31.1, 21.5, 19.8, 18.8, 14.8; HRMS (ESI-QTOF) m/
4.57 (s, 2H), 3.75e3.70 (m, 1H), 3.35e3.29 (m, 2H), 303e3.00 (m,
2H), 2.42 (s, 3H), 1.64e1.58 (m, 1H), 0.96 (d, J¼6.8 Hz, 3H), 0.88 (d,
z: [MþNa]þ calcd for C22H29NO4SNa, 426.1715; found, 426.1715.
J¼6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 144.2, 136.7, 135.9,134.1,
4.2.25. (2S,4S)-4-Isopropyl-2-(2-chlorobenzyl)-3-tosyloxazolidine
(3x). Colorless oil (92 mg, 71%); Rf 0.50 (pet. ether: EtOAc, 9:1);
130.4, 129.9, 128.5, 128.0, 92.7, 67.8, 65.2,46.1, 42.3, 31.1, 21.5, 19.7,
18.7; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for C21H26ClNO3SNa,
430.1220; found, 430.1220.
21
[
a]
ꢀ68.7 (c 1.0, CHCl3); IR (cmꢀ1): 2963, 1474, 1350, 1164, 1090,
D
1058; 1H NMR (400 MHz, CDCl3)
d
7.75 (d, J¼7.8 Hz, 2H), 7.37e7.19
(m, 6H), 5.16 (d, J¼8.6 Hz, 1H), 3.77 (d, J¼8.8 Hz, 1H), 3.55 (d,
J¼13.8 Hz, 1H), 3.44 (t, J¼11.4 Hz, 1H), 3.08e3.01 (m, 2H), 2.42 (s,
3H), 1.91e1.83 (m, 1H), 1.06 (d, J¼6.7 Hz, 3H), 0.97 (d, J¼6.5 Hz, 3H);
4.2.31. (2S,4S)-4-Isopropyl-2-(1-phenylethyl)-3-tosyloxazolidine
(3ad). [Mixture of diastereomers A and B; d.r.¼1.2: 1.0]: colorless oil
(100 mg, 81%); Rf 0.50 (pet. ether: EtOAc, 9:1); IR (cmꢀ1): 1451,1440,
13C NMR (100 MHz, CDCl3)
d 144.1, 134.4, 134.3, 134.0, 132.2, 130.0,
1355,1163,1090,1021; 1H NMR (400 MHz, CDCl3)
d
7.74 (d, J¼8.0 Hz,
129.4, 128.2, 128.0, 126.6; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for
2H, 2A), 7.67 (d, J¼8.0 Hz, 1.7H, 2B), 7.33e7.21 (m, 13H, 7Aþ7B), 5.07
(d, J¼6.2 Hz, 1H, 1A), 4.90 (d, J¼3.0 Hz, 0.86H, 1B), 3.76 (d, J¼8.8 Hz,
0.86H, 1B), 3.61 (dd, J¼8.6, 2.3 Hz, 1H, 1A), 3.49e3.43 (m, 0.86H, 1B),
3.31 (d, J¼9.8, 5.8 Hz, 0.86H, 1B), 3.24e3.13 (m, 2H, 2A), 3.04 (t,
J¼7.5 Hz, 1H, 1A), 2.96 (dd, J¼8.6, 6.0 Hz, 0.86H, 1B), 2.42e2.40 (s,
5.6H, 3Aþ3B),1.88e1.79 (m, 0.86H,1B),1.46 (d, J¼7.3 Hz, 3H, 3A),1.35
(d, J¼7.1 Hz, 2.6H, 3B), 1.19e1.12 (m, 3.6H, 1Aþ3B), 0.93 (d, J¼6.5 Hz,
C
20H24ClNO3SNa, 416.1063; found, 416.1064.
4.2.26. (2S,4S)-4-Isopropyl-2-(2-bromobenzyl)-3-tosyloxazolidine
(3y). Colorless oil (120 mg, 83%); Rf 0.50 (pet. ether: EtOAc, 9:1);
21
[
a]
ꢀ62.5 (c 1.0 CHCl3); IR (cmꢀ1): 2963, 2873, 1598, 1472, 1439,
D
1351, 1164, 1091; 1H NMR (400 MHz, CDCl3)
d
7.77 (d, J¼8.2 Hz, 2H),
7.55 (d, J¼7.9 Hz,1H), 7.33e7.23 (m, 4H), 7.12e7.08 (m,1H), 5.17 (dd,
J¼8.8, 2.9 Hz, 1H), 3.78 (dd, J¼8.9, 2.3 Hz, 1H), 3.56 (dd, J¼13.8,
2.9 Hz, 1H), 3.46e3.42 (m, 1H), 3.09e303 (m, 2H), 2.41 (s, 3H),
2.6H, 3B), 0.84 (d, J¼6.6 Hz, 3H, 3A), 0.72 (d, J¼6.5 Hz, 3H, 3A); 13
C
NMR (100 MHz, CDCl3)
d 144.0, 142.6, 141.3, 134.4, 134.2, 129.83,
129.80,128.9,128.3,128.2,128.14,128.07,127.99,126.74,126.71, 96.2,
95.9, 68.5, 68.0, 65.8, 65.7, 44.3, 43.7, 31.2, 31.0, 21.51, 21.49, 20.04,
19.8, 19.6, 19.2, 17.7, 13.2; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for
1.94e1.85 (m, 1H), 1.07 (d, J¼6.8 Hz, 3H), 0.98 (d, J¼6.7 Hz, 3H); 13
C
NMR (100 MHz, CDCl3)
d 144.1, 136.1, 134.0, 132.8, 132.3, 129.9,
128.5, 128.0, 127.3, 124.8, 96.2, 67.7, 65.3, 42.7, 31.4, 21.5, 19.8, 18.7;
HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for C20H24BrNO3SNa,
460.0558; found, 460.0557.
C21H27NO3SNa, 396.1609; found, 396.1609.
4.2.32. (2S,4S)-4-Isopropyl-2-(1-(p-acetoxy-phenyl)-ethyl)-3-
tosyloxazolidine (3af). [Mixture of diastereomers A and B; d.r.¼1.0:
1.2]: colorless oil (104 mg, 78%); Rf 0.50 (pet. ether: EtOAc, 9:1); IR
(cmꢀ1): 2963, 2873, 1610, 1513, 1464, 1349, 1247, 1165, 1120, 1066,
4.2.27. (2S,4S)-4-Isopropyl-2-(3-chorobenzyl)-3-tosyloxazolidine
(3z). Colorless oil (57 mg, 44%); Rf 0.50 (pet. ether: EtOAc, 9:1);
[
a
]
21 ꢀ61.6 (c 1.0, CHCl3); IR (cmꢀ1): 1349, 1163; 1H NMR (400 MHz,
D
1030, 946; 1H NMR (400 MHz, CDCl3)
d
7.73 (d, J¼8.1 Hz, 2H, 2A),
CDCl3)
d
7.73 (d, J¼8.0 Hz, 1H), 7.34e7.18 (m, 6H), 5.0 (d, J¼6.2 Hz,
7.67 (d, J¼8.1 Hz, 2.4H, 2B), 7.32e7.20 (m, 8.8H, 4Aþ4B), 6.88e6.28
(m, 4.4H, 2Aþ2B), 5.02 (d, J¼6.2 Hz, 1H, 1A), 4.86 (d, J¼3.2 Hz, 1.2H.
1B), 3.79e3.74 (m, 7.8H, 3Aþ3Bþ1B), 3.6 (dd, J¼9.1, 3.0 Hz,1.2H,1B),
3.43e3.37 (m, 1.2H, 1B), 3.30 (dd, J¼9.9, 5.7 Hz, 1.2H, 1B), 3.24e3.19
(m, 1H, 1A) 3.16e3.09 (m, 1H, 1A), 3.03 (dd, J¼8.4, 6.6 Hz, 1H, 1A),
2.95 (dd, J¼8.8, 6.0 Hz, 1H, 1A), 2.41 (s, 3H, 3A), 2.40 (s, 3.6H, 3B),
1.88e1.78 (m, 1.2H, 1B), 1.43 (d, J¼7.2 Hz, 3H, 3A), 1.32 (d, J¼7.1 Hz,
3.6H, 3B), 1.21e1.12 (m, 4.6H, 3Bþ1A), 0.93 (d, J¼6.5 Hz, 3.6H, 3B),
0.88 (d, J¼6.7 Hz, 3A), 0.73 (d, J¼6.6 Hz, 3H, 3A); 13C NMR (100 MHz,
1H), 3.75 (d, J¼8.9 Hz, 1H), 3.36e3.25 (m, 2H), 3.64e2.96 (m, 2H),
2.43 (s, 3H), 1.62e1.53 (m, 1H), 0.96 (d, J¼6.8 Hz, 3H), 0.88 (d,
J¼6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 144.2, 138.2, 134.0,
133.9, 130.1, 129.9, 129.4, 128.3, 128.0, 126.9, 92.4, 67.8, 65.2, 42.1,
31.1, 21.5, 19.7, 18.8; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for
C
20H24ClO3SNa, 416.1063; found, 416.1065.
4.2.28. (2S,4S)-4-Isopropyl-2-(3-bromobenzyl)-3-tosyloxazolidine
(3aa). Colorless oil (59 mg, 41%); Rf 0.50 (pet. ether: EtOAc, 9:1);
21
[
a]
ꢀ54.0 (c 1.0, CHCl3); IR (cmꢀ1): 2962, 2872, 1597, 1349, 1163;
D
CDCl3)
d 158.4, 158.3, 144.0, 134.6, 134.4, 134.1, 133.3, 130.4, 129.80,
1H NMR (400 MHz, CDCl3)
d
7.73 (d, J¼8.1 Hz, 2H), 7.44e7.14 (m,
129.79, 129.15, 129.14, 128.06, 113.7, 113.4, 96.3, 96.0, 68.4, 68.0,
65.8, 65.7, 55.24, 55.18, 43.4, 42.8, 31.2, 31.0, 21.51, 21.49, 20.0, 19.9,
19.6, 19.2, 17.8, 13.2; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for
6H), 5.0 (dd, J¼7.6 Hz, 1.7 Hz, 1H), 3.75 (d, J¼8.9 Hz, 1H), 3.35e3.24
(m, 2H), 3.04e2.95 (m, 2H), 2.43 (s, 3H), 1.60e1.53 (m, 1H), 0.96 (d,
J¼6.8 Hz, 3H), 0.87 (d, J¼6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3)
C22H29NO4SNa, 426.1715; found, 426.1715.
d
144.2, 138.6, 134.0, 133.0, 129.9, 129.8, 129.7, 128.8, 128.0, 122.2,
92.4, 67.8, 65.2, 42.1, 31.1, 21.5, 19.7, 18.8; HRMS (ESI-QTOF) m/z:
[MþNa]þ calcd for C20H24BrNO3SNa, 460.0558; found, 460.0552.
4.2.33. (2S,4S)-4-Isopropyl-2-(phenylmethyl-d2)-3-tosyloxazolidine
21
(3 ag). Colorlessoil(94mg, 79%);Rf 0.50(pet. ether:EtOAc,9:1);[a]
D
ꢀ25.1 (c 1.0, CHCl3); IR (cmꢀ1): 1349, 1163, 1098, 1015; 1H NMR
4.2.29. (2S,4S)-4-Isopropyl-2-(2,4,6-trimethylbenzyl)-3-
(400 MHz, CDCl3)
d
7.73 (d, J¼8.0 Hz, 2H), 7.33e7.24 (m, 7H), 5.02 (s,
tosyloxazolidine (3 ab). Colorless oil (111 mg, 84%); Rf 0.60 (pet.
1H, HC-CD2Ph), 3.75 (d, J¼8.9 Hz, 1H), 3.35 (t, J¼6.7 Hz, 1H), 3.02 (dd,
ether: EtOAc, 9:1); [
a
]
21 ꢀ74.1 (c 1.0, CHCl3); IR (cmꢀ1): 2961, 2872,
D
J¼8.7, 6.2 Hz, 1H), 2.42 (s, 3H), 1.69e1.62 (m, 1H), 0.98 (d, J¼6.8 Hz,
1350, 1163, 1090, 1073, 1031, 1004; 1H NMR (400 MHz, CDCl3)
d
7.73
3H), 0.89 (d, J¼6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 144.1, 136.3,

P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
1103
134.2, 129.90, 129.86, 128.2, 128.0, 126.7, 92.8, 67.7, 65.2, 42.0 (quint,
1JCeD¼19.45Hz), 31.1, 21.5,19.7,18.7; HRMS (ESI-QTOF) m/z: [MþNa]þ
calcd for C20H23D2NO3SNa, 384.1578; found, 384.1578.
157e159 ꢁC; IR (cmꢀ1): 3029, 2930, 2870, 1598, 1494, 1453, 1347,
1212, 1165, 1092; 1H NMR (400 MHz, CDCl3)
d
7.64 (d, J¼8.0 Hz, 2H),
7.33e7.26 (m, 9H), 7.14 (d, J¼8.0 Hz, 2H), 5.50 (t, J¼9.0 Hz, 1H),
3.33e3.25 (m, 3H), 3.14 (dd, J¼13.8, 5.5 Hz, 1H), 2.44 (t, J¼5.8 Hz,
1H), 2.44 (s, 3H), 2.41 (s, 3H), 0.97 (d, J¼5.6 Hz, 3H) 13C NMR
4.3. m-CPBA mediated geminal oxyamination: Method B
(100 MHz, CDCl3)
d 144.0, 143.9, 135.2, 134.7, 133.7, 131.1, 129.7,
4.3.1. Synthesis of oxazolidine 3b through the m-CPBA mediated
geminal oxyamination: Method B. To a colorless solution of N-Ts
valinol 1b (84 mg, 0.33 mmol) and styrene 2a (85 mg, 0.82 mmol) in
CH2Cl2 (3 mL) in a well dried Schlenk flask under argon atmosphere
was added m-CPBA (173 mg, 1.0 mmol) and PTSA$H2O (69 mg,
0.36 mmol) at room temperature [25 ꢁC]. The progress of the re-
action was monitored by TLC. After stirring the reaction mixture for
24 h at room temperature 5 mL of satd soln of aq NaHCO3 and 5 mL of
satd soln of aq Na2S2O3 were added in succession and extracted with
CH2Cl2. The combined organic layers were dried (anhyd. Na2SO4),
filtered and concentrated in vacuo. The crude product obtained was
purified by flash chromatography (pet. ether: Et2O, 8:1) to furnish
oxazolidine 3b as a colorless oil (93 mg, 78%) in pure form.
129.6, 128.1, 127.9, 127.5, 126.9, 76.4, 55.1, 52.8, 43.3, 21.62, 21.57,
19.5; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for C25H28N2O4S2Na,
507.1388; found, 507.1384.
4.5.3. (2R,4S)-2,4-Dibenzyl-1,3-ditosylimidazolidine
(5b). White
solid (170 mg, 92%); Rf 0.45 (pet. ether: EtOAc, 4:1); mp
219e220 ꢁC; [
a]
21 þ1.8 (c 0.5, Acetone); IR (cmꢀ1): 3639 (br), 3381
D
(br), 3080 (br), 3020 (br), 1514 (br), 1351, 1271, 1177, 1129, 1068,
1021; 1H NMR (400 MHz, Acetone-d6)
d
7.68 (d, J¼8.1 Hz, 2H),
7.38e7.18 (m, 14H), 7.0 (d, J¼7.2 Hz, 2H), 5.27 (dd, J¼5.0, 3.6 Hz, 1H),
3.65e3.58 (m, 1H), 3.42 (dd, J¼13.8, 3.3 Hz, 2H), 3.11 (dd, J¼13.8,
5.3 Hz, 1H), 2.93e2.71 (m, 3H), 2.45 (s, 3H), 2.43 (s, 3H), 1.90 (dd,
J¼13.5, 10.7 Hz, 1H); 13C NMR (100 MHz, Acetone-d6)
d 145.10,
145.06, 138.08, 136.6, 135.0, 134.7, 132.3, 130.8, 130.6, 130.0, 129.5,
129.0, 128.7, 128.6, 127.8, 127.6, 77.3, 60.6, 51.2, 43.2, 40.9, 21.6;
HRMS (ESI-QTOF) m/z: [MþNa]þ calcd for C31H32N2O4S2Na,
583.1701; found, 583.1705.
4.3.2. (2S,4S)-4-Isopropyl-2-(phenylmethyl-d)-3-tosyloxazolidine-2-
d (3ah): Method B. [Mixture of diastereomers]: colorless oil (80 mg,
21
67%); Rf 0.50 (pet. ether: EtOAc, 9:1); [
a]
ꢀ64.7 (c 1.0, CHCl3); IR
D
(cmꢀ1): 2961, 2871, 1350, 1163, 1088; 1H NMR (400 MHz, CDCl3)
d
7.74 (d, J¼8.1 Hz, 4H, 2Aþ2B), 7.33e7.22 (m, 14H, 7Aþ7B), 3.75 (d,
4.5.4. (2R,4S)-2-Benzyl-4-isobutyl-1,3-ditosylimidazolidine
J¼9.0 Hz, 2H, 1Aþ1B), 3.38e3.33 (m, 2H, 1Aþ1B), 3.29 (s, 1H, 1A,
HCDPh), 3.05e3.00 (m, 2H, 1Aþ1B), 2.97 (s, 1H, 1B, HCDPh), 2.42 (s,
6H, 3Aþ3B), 1.72e1.60 (m, 2H, 1Aþ1B), 0.98 (d, J¼6.6 Hz, 6H,
3Aþ3B), 0.90 (d, J¼6.6 Hz, 6H, 3Aþ3B); 13C NMR (100 MHz, CDCl3)
(5c). White solid (146 mg, 84%); Rf 0.45 (pet. ether: EtOAc, 4:1);
mp 171e173 ꢁC; [
a
]
D
ꢀ0.80 (c 1.0, Acetone); IR (cmꢀ1): 3634 (br),
21
3383 (br), 3080 (br), 3017 (br), 2822, 1512 (br), 1485, 1352, 1271,
1176, 1030, 1069; 1H NMR (400 MHz, Acetone-d6)
d 7.52 (d,
d
144.07, 144.04, 136.40, 136.37, 136.35, 134.3, 129.90, 129.85, 128.2,
J¼8.2 Hz, 2H), 7.49 (d, J¼8.2 Hz, 2H), 7.38e7.24 (m, 9H), 5.10 (t,
J¼4.0 Hz, 1H), 3.48e3.41 (m, 2H), 3.24 (dd, J¼13.8, 4.6 Hz, 1H),
2.85e2.81 (m, 2H), 2.56 (s, 3H), 2.42 (s, 3H), 1.39e1.29 (m, 1H),
1.23e1.17 (m, 1H), 0.74e0.67 (m, 7H); 13C NMR (100 MHz, Ace-
1
128.0, 126.6, 92.5 (t, JCeD¼24.0 Hz, CDNO), 67.7, 65.2, 42.22 (t,
1JCeD¼19.5 Hz, CHDPh of diast. A), 42.17 (t, 1JCeD¼19.6 Hz, CHDPh of
diast. B), 31.1, 21.5, 19.7, 18.7; HRMS (ESI-QTOF) m/z: [MþNa]þ calcd
for C20H23D2NO3SNa, 384.1579; found, 384.1578.
tone-d6)
d 145.1, 144.8, 136.5, 135.1, 134.2, 132.3, 130.7, 128.8, 128.5,
127.6, 77.0, 57.8, 52.9, 44.2, 42.9, 25.4, 23.3, 22.2, 21.7, 21.6; HRMS
(ESI-QTOF) m/z: [MþNa]þ calcd for C28H34N2O4S2Na, 549.1858;
found, 549.1856.
4.4. Synthesis of oxazolidine 3b by the addition of N-Ts-ami-
noalcohol and epoxide 6a: Method C
PTSA$H2O (69 mg, 0.36 mmol) was added to a colorless solution
of N-Ts valinol 1b (85 mg, 0.33 mmol) and styrene oxide 6a (52 mg,
0.43 mmol) in CH2Cl2 (3 mL) in a well dried Schlenk flask under
argon atmosphere at room temperature [25 ꢁC]. The progress of the
reaction was monitored by TLC. After stirring the reaction mixture
for 24 h at room temperature 5 mL of satd soln of aq NaHCO3 was
added and extracted with CH2Cl2. The combined organic layers
were dried (anhyd. Na2SO4), filtered and concentrated in vacuo. The
crude product obtained was purified by flash chromatography (pet.
ether: Et2O, 8:1) to furnish oxazolidine 3b as a colorless oil (89 mg,
75%) in pure form.
4.5.5. (2R,4S)-2-Benzyl-4-phenyl-1,3-ditosylimidazolidine
(5d). White solid (129 mg, 71%); Rf 0.45 (pet. ether: EtOAc, 4:1); mp
65e67 ꢁC; [
a
]
D
21 ꢀ23.3 (c 1.0, Acetone); IR (cmꢀ1): 3670, 3382, 3080,
3015, 2832, 1512, 1484, 1357, 1131, 1067; 1H NMR (400 MHz, Ace-
tone-d6)
d
7.53 (d, J¼8.2 Hz, 2H), 7.44 (d, J¼8.2 Hz, 2H), 7.34e7.21
(m, 12H), 7.08e7.06 (m, 2H), 5.70 (dd, J¼10.6, 4.0 Hz, 1H), 4.20 (dd,
J¼9.4, 7.1 Hz, 1H), 3.90 (dd, J¼12.7, 6.9 Hz, 1H), 3.40e3.29 (m, 2H),
3.12 (dd, J¼12.6, 9.5 Hz, 1H), 2.45 (s, 3H), 2.43 (s, 3H); 13C NMR
(100 MHz, Acetone-d6)
d 145.6, 145.0, 138.6, 136.8, 136.2, 135.2,
131.6, 130.7, 130.6, 129.13, 129.09, 129.01, 128.7, 128.4, 128.3, 127.7,
77.6, 64.2, 54.8, 44.0, 21.59, 21.56; HRMS (ESI-QTOF) m/z: [MþNa]þ
calcd for C30H30N2O4S2Na, 569.1545; found, 569.1544.
4.5. Synthesis of imidazolidines 5ae5e
4.5.1. General procedure for the synthesis of imidazolidines
5ae5e. To a colorless solution of corresponding N, N0-di Ts-diamine
(0.33 mmol) and styrene (0.36 mmol) in CH2Cl2 (3 mL) in a well
dried Schlenk flask under argon atmosphere was added PhI(O-
COCF3)2 (0.50 mmol) and PTSA$H2O (0.36 mmol) at room tem-
perature [25 ꢁC]. The progress of the reaction was monitored by
TLC. After stirring the reaction mixture for 8 h at room temperature
5 mL of satd soln of aq NaHCO3 was added and extracted with
CH2Cl2. The combined organic layers were dried (anhyd. Na2SO4),
filtered and concentrated in vacuo. The crude product obtained was
purified by flash chromatography (pet. ether: EtOAc, 7:1) to furnish
imidazolidines in pure form.
4.5.6. 2-Benzyl-1,3-ditosylimidazolidine (5e). [Contains 3% of piper-
azine]: white solid (121 mg, 78%); Rf 0.45 (pet. ether: EtOAc, 4:1);
mp 157e159 ꢁC; IR (cmꢀ1): 3031, 1580, 1348, 1162, 1091, 1028; 1H
NMR (400 MHz, Acetone-d6)
9H), 5.25 (t, J¼4.0 Hz, 1H), 3.27 (d, J¼4.0 Hz, 2H), 3.03e2.90 (m, 4H),
2.46 (s, 6H); 13C NMR (100 MHz, Acetone-d6)
145.0, 136.5, 135.4,
d
7.51 (d, J¼8.1 Hz, 4H), 7.36e7.28 (m,
d
132.0, 130.9, 129.0, 128.5, 127.7, 75.8, 47.3, 43.5, 21.7; HRMS (ESI-
QTOF) m/z: [MþNa]þ calcd for C24H26N2O4S2Na, 493.1232; found,
493.1235.
Acknowledgements
4.5.2. (ꢂ)-2-Benzyl-4-methyl-1,3-ditosylimidazolidine (5a). White
solid (126 mg, 79%); Rf 0.45 (pet. ether: EtOAc, 4:1); mp
P.V.B. thanks IISc, CSIR-India and JNCASR for research fellow-
ships. S.C.N thanks DST, India for a SERB Distinguished Fellowship.

1104
P. Venkatesan Balaji, S. Chandrasekaran / Tetrahedron 72 (2016) 1095e1104
9. Balaji, P. V.; Chandrasekaran, S. Chem. Commun. 2014, 70.
Supplementary data
10. For reviews: (a) Singh, F. V.; Wirth, T. In Comprehensive Organic Synthesis II;
Knochel, P., Ed.; Elsevier: Amsterdam, 2014; Vol. 7, p 880; (b) Romero, R. M.;
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the online version, at http://dx.doi.org/10.1016/j.tet.2016.01.005.
€
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