Tandem aziridine ring opening-disulfide formation-reduction-Michael addition in one-pot mediated by tetrathiomolybdate

Article abstract of DOI:10.1016/j.tet.2015.04.003

Abstract A detailed study of tetrathiomolybdate mediated tandem regio- and stereoselective ring opening of aziridine, disulfide formation, reduction of disulfide bond and Michael reaction in a one-pot operation is reported. This constitutes four reactions

Full text of DOI:10.1016/j.tet.2015.04.003

Tetrahedron xxx (2015) 1e15
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Tetrahedron
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Tandem aziridine ring opening-disulfide formation-reduction-
Michael addition in one-pot mediated by tetrathiomolybdate
*
Devarajulu Sureshkumar, Thanikachalam Gunasundari, 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:
A detailed study of tetrathiomolybdate mediated tandem regio- and stereoselective ring opening of
aziridine, disulfide formation, reduction of disulfide bond and Michael reaction in a one-pot operation is
reported. This constitutes four reactions that take place in one-pot operation. In the reaction of
[BnEt3N]4MoS4 with an aziridine derived from cyclohexene and in the absence of Michael acceptor in-
termediates sulfonamidodisulfide and sulfonamidothiol were isolated and fully characterized. It has also
been shown that it is possible to carry out selective opening of the aziridine ring in the presence of an
epoxide. By incorporating a suitable Michael acceptor as part of the substrate, intramolecular 1,4-
addition could be performed, to achieve the synthesis of sulfur containing acyclic, cyclic amino acid
ester derivatives and thia-bicyclo[3.3.1]nonane derivatives in good yields.
Received 31 January 2015
Received in revised form 19 March 2015
Accepted 2 April 2015
Available online xxx
Keywords:
Aziridines
Epoxides
Ring opening
Tetrathiomolybdate
Sulfur transfer
Tandem reactions
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
can mediate not only the aziridine ring opening to form a disulfide
bond but can also cleave the disulfide bond under appropriate re-
After the discovery of the Ugi four-component four-center re-
action, multicomponent reactions (MCR) involving tandem pro-
cesses with at least three different simple substrates have emerged
as an extremely powerful synthetic tool in organic synthesis es-
pecially in the field of combinatorial chemistry and drug discovery.1
This methodology allows facile formation of several new covalent
CeC and CeX (X¼O, N, S, Se) bonds in a one-pot operation with
high levels of molecular complexity and diversity. This would be
quite close to the concept of an ideal synthesis and is particularly
well adapted for parallel synthesis. To synthesize sulfur containing
organic compounds by MCR approach, very few reports are avail-
able in the literature due to the lack of efficient sulfur transfer re-
agents.2 In earlier reports, we presented results on the nucleophilic
ring opening of various aziridines with benzyltriethylammonium
tetrathiomolybdate3 [BnEt3N]2MoS4, 1 and demonstrated the util-
ity of this methodology for the synthesis of ß-sulfonamidodi-
sulfides,4 ß-sulfonamidosulfides5 and a number of interesting
sulfur heterocycles with high regio- and stereocontrol.
action conditions.7 Herein, we report a systematic study of tetra-
thiomolybdate mediated tandem regio- and stereoselective ring
opening of aziridine, disulfide formation, in situ reduction of
disulfide bond followed by Michael reaction to give a variety of
ß-sulfonamidosulfide derivatives in good yields. The main advan-
tage of this methodology is that four reactions involving three
components take place in a tandem fashion in one-pot.
2. Results and discussion
Our investigation began with the study of nucleophilic ring
opening of optically pure N-tosyl-2-benzyl aziridine8 2 with 1
[2.2 equiv, CH3CN, 28 ꢀC, 3e8 h] in the presence of different Michael
acceptors 3, which underwent smooth aziridine ring opening fol-
lowed by disulfide formation, in situ reduction of disulfide bond
and Michael reaction in a tandem fashion to afford ß-sulfonami-
dosulfides 4 in good yields with full regiocontrol (Scheme 1). This
reaction was tested with different Michael acceptors such as methyl
acrylate 3a, phenyl vinyl sulfone 3b, methyl methacrylate 3c,
methyl 2-acetamidoacrylate 3d, acrylonitrile 3e, ethyl vinyl ketone
3f and benzyl acrylate 3g (Table 1). In all cases the reaction worked
very well resulting in good yields of the products. Reaction of 3c
and 3d led to the formation of 1:1 diastereomeric mixture of thia-
amino acid derivatives 4c and 4d, respectively in good yields.
In continuing our studies to explore the redox chemistry asso-
ciated with MoeS systems,6 we found that tetrathiomolybdate 1
* Corresponding author. Jawaharlal Nehru Center for Advanced Scientific
Research, Jakkur, Bangalore. 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.2015.04.003
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
Scheme 1. Tandem aziridine opening, disulfide formation, reduction and Michael reaction.
Results of this investigation with different Michael acceptors are
summarized in Table 1.
2.2. Ring opening of carbohydrate derived aziridines followed
by Michael reaction with 3a in the presence of 1
In order to expand the scope of this methodology and to study
the reactivity of other aziridines having different functionality and
Table 1
Synthesis of thio-amino acids by tandem multi-step reactions
complexity, D-glucose and D
-mannitol derived aziridines 7a9 and
Entry Michael acceptor
Product
Time Yield
7b10 were treated with 1 [2.2 equiv, CH3CN, 28 ꢀC, 4e5 h] in the
presence of 3a to afford the corresponding sulfur-containing sugar
amino acid conjugates 8a and 8b, respectively in good yields. This
tandem multi-step reaction worked equally well in the case of
complex aziridine derived from carbohydrates to give the desired
products in good yields (Scheme 3).
(h)
(%)
1
3
85
2
3
4
7
74
66
2.3. Ring opening of 2,2-disubstituted aziridines with 1 fol-
lowed by Michael reaction
Having successfully demonstrated the efficiency of ring opening
reactions with 1 the stage was set for carrying out the reaction of
2,2-disubstituted aziridines. Treatment of 9 with 1 [2.2 equiv,
CH3CN, 28 ꢀC, 3e6 h] in the presence of 3a furnished the
substituted sulfur-containing amino-acid derivatives 10 in good
yields (Scheme 4). Although it has been reported in the literature
that 9a can undergo ring opening from the less hindered as well as
the more hindered side with sulfur nucleophiles,11 in our case
aziridine ring opening with 1 took place exclusively from the ste-
rically less substituted carbon centre with full regiocontrol. This
methodology has been extended to the synthesis of ß-methyl
cystinol derived.
4
5
8
5
60
50
ß-sulfonamidosulfides 10c and ß-methyl homo cystinol derived
ß-sulfonamidosulfide 10d in a single step from the corresponding
aziridines 9c and 9d, respectively in good yields (Table 3, entry 3
and 4).
6
7
4
6
78
55
2.4. Regio- and stereoselective ring opening of 2,3-
disubstituted aziridines 11 followed by Michael reaction with
3a in the presence of 1
To demonstrate the stereoselectivity in the ring opening of
*compounds 4c and 4d were isolates as 1:1 mixture of diastereomers.
2,3-disubstituted
aziridines
with
1,
meso-N-tosyl-2,3-
diethylaziridine 11a12 was treated with 1 (2.2 equiv; CH3CN,
28 ꢀC, 10 h) in the presence of 3a to afford exclusively the sulfur-
containing amino-acid derivative 12a (anti-isomer; 68% yield). In
the case of (ꢁ)-trans-N-tosyl-2,3-diethylaziridine 11b,12 sulfur-
containing amino-acid derivative 12b (syn-isomer) was obtained
in 70% yield under the same reaction conditions (Scheme 5,
Table 4).
In order to assess the regio- and stereoselectivity together in the
same substrate, (ꢁ)-cis-N-tosyl-2-isopropyl-3-methylaziridine 11c4
was treated with 1 (2.2 equiv; CH3CN, 28 ꢀC, 12 h) in presence of 3a
to afford exclusively the anti-amino-acid derivative 12c in 65%
2.1. Ring opening of mono-substituted aziridines 5 followed
by Michael reaction with 3a in the presence of 1
To study the scope of this methodology further, reactions were
carried out with different aziridines and methyl acrylate 3a was
chosen as the Michael acceptor. First we treated enantiomerically
pure mono-substituted aziridines8 5 with 1 [2.2 equiv, CH3CN,
28 ꢀC, 2e8 h] in the presence of 3a to afford sulfur-containing
amino-acid (ß-sulfonamidosulfides) derivatives 6 in good yields
(Scheme 2). Changing the substituents on the aziridine ring from
a methyl to tertiary butyl group did not affect the reactivity profile
of the aziridine. In fact, in all cases the reaction worked very well
with very good regioselectivity. In the case of methionine derived
aziridine 5g and tryptophan derived aziridine 5i, the reaction
proceeded very well without affecting the additional functional
groups (CH3Se and eNH) present in the molecules (Table 2, entry 7
and 9). The results are summarized in Table 2.
yield.
In
the
case
of
(ꢁ)-trans-N-tosyl-2-isopropyl-3-
methylaziridine 11d,4 the syn-amino-acid derivative 12d was ob-
tained in 68% yield under the same reaction conditions. Here, tet-
rathiomolybdate 1 attacks the aziridines 11c and 11d at the less
hindered C2 carbon site in a SN2 fashion with regio- and stereo-
control and with complete inversion (Table 4, entry 3 and 4) fol-
lowed by 1,4-addition to form 12c and 12d, respectively.
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
3
NHTs
Ts
N
[BnEt3N]2MoS4 1 (2.2 equiv)
OMe
S
OMe
+
R
O
CH3CN, rt, 2 - 8 h
60 - 82%
R
6
O
5
3a
Scheme 2. Tandem multi-step reaction of mono-substituted aziridines with methyl acrylate 3a.
Table 2
Synthesis of
b
-aminosulfides by tandem multi-step reaction
Optically pure aziridines
Entry
1
Product
Time (h)
2
Yield (%)
82
2
3
80
3
4
5
5
78
76
5
6
70
6
7
8
9
8
4
3
8
75
63
72
60
2.5. Ring opening of aziridines derived from cyclic system
followed by Michael addition with 3a in the presence of 1
[2.2 equiv, CH3CN, 28 ꢀC, 4e24 h] in the presence of 3a led to facile
ring opening in a stereoselective manner to afford amino-acid de-
rivatives 14 (trans-isomer) in very good yields (Scheme 6 and
Table 5). It is interesting to note that the reaction can be performed
efficiently with substrate 13c containing two free hydroxy groups.
The reaction in the case of aziridine 13e was considerably slower
and it gave the ring-opened product 14e in only 40% yield. When
Next, this methodology was extended to study the reaction of
aziridines derived from cyclic systems. The aziridines 13 were
synthesized starting from the corresponding cyclic olefins using
sharpless aziridination protocol.13 Reaction of aziridines 13 with 1
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
Scheme 3. Tandem multi-step reaction of carbohydrate derived aziridines 7a and 7b with 1.
Ts
N
NHTs
R1
R2
[BnEt3N]2MoS4 1 (2.2 equiv)
R1
R2
OMe
S
OMe
+
CH3CN, rt, 3 - 6 h
64 - 78%
O
3a
O
10
9
Scheme 4. Tandem multi-step reaction of 2,2-disubstituted aziridines 9 with methyl acrylate 3a.
Table 3
Ring opening of 2,2-disubstituted aziridines 9 with 1 followed by Michael reaction with 3a
Entry
1
2,2-Disubstituted aziridines
b
-Substituted
b-aminodisulfide
Time (h)
3
Yield (%)
78
2
4
75
3
4
5
6
68
64
Ts
NHTs
[BnEt3N]2MoS4 1 (2.2 equiv)
N
R2
+
OMe
S
OMe
R1
CH3CN, rt, 8 - 12 h
65 - 70%
R1
O
3a
R2
O
11
12
Scheme 5. Tetrathiomolybdate 1 mediated regio- and stereoselective ring opening of 2,3-disubstituted aziridines 11 and Michael reaction with 3a in tandem multi-step reaction.
the reaction was extended to aziridine 13f with 1 it failed to un-
dergo the reaction even after 24 h and the aziridine 13f was re-
covered unchanged. The failure of the reaction may be attributed to
the puckered nature of the cyclooctane conformation.
aziridine 13b with 1 occurs first followed by disulfide formation14
to furnish 13g, which undergoes reduction of the disulfide bond
in the presence of second equivalent of 1 to form the thiolate 13h in
situ,7 which finally undergoes 1,4-addition to Michael acceptor 3a
to form ß-sulfonamidosulfide derivative 14b as shown in Scheme 7.
To gain further insight into the reaction pathway and mechanism
that has been postulated, the aziridine 13b was treated with excess
tetrathiomolybdate 1 [2.2 equiv, CH3CN, 28 ꢀC] in the absence of
Michael acceptor and was allowed to react for a longer time (24 h).
Under these conditions the intermediates trans-ß-sulfonamidodi-
sulfide4 13g and thiol 13h0 were isolated in approximately 1:1 ratio
2.6. Tentative mechanism of tandem multi-step reactions
with aziridines mediated by tetrathiomolybdate 1
It is reasonable to visualize the nucleophilic attack of tetra-
thiomolybdate 1 on the aziridine 13b in a SN2 fashion with regio-
and stereocontrol and with complete inversion. The ring opening of
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
5
Table 4
Regio- and stereoselective ring opening of 2,3-disubstituted aziridines with 1 followed by Michael reaction with 3a
Entry
2,3-Disubstituted aziridines
b
-Aminodisulfides
Time (h)
10
Yield (%)
68
1
2
3
4
9
12
8
70
65
68
Scheme 6. Multi-step reaction of 2,3-disubstituted cyclic-aziridines 13 with 3a in the presence of 1.
after work up. The structure of intermediate 13h0 was further
confirmed by X-ray crystallography15 (Fig. 1).
Table 5
Synthesis of cyclic trans- thia-amino acid esters 14
Entry
Aziridines
Product
Time Yield
(h)
(%)
2.7. Selective ring opening of aziridines with 1 in the presence
of epoxides followed by Michael reaction with 3a
1
4
78
To demonstrate the selective ring opening of aziridines in the
presence of epoxides, aziridino-epoxides16 15be15e were synthe-
sized from the corresponding 1,4-cyclic dienes using Sharpless
aziridination protocol [1,4-diene, 3 mmol; CAT (Chloramine-T),
3.3 mmol; PTAB (PhMe3NþBr3e), 0.3 mmol; 15 mL CH3CN, 28 ꢀC,
12 h] followed by epoxidation using m-CPBA as the reagent.17
2
3
4
6
6
6
72
62
70
Treatment of aziridino-epoxides 15ae15e with
1 (2.2 equiv,
CH3CN, 28 ꢀC) in the presence of 3a resulted in the exclusive for-
mation of products 16ae16e, respectively in good yields (Scheme 8
and Table 6). In all the cases epoxide ring remained unaffected
under the reaction conditions.
2.8. Ring opening of aziridines followed by intramolecular
Michael reaction mediated by 1
By incorporating a suitable Michael acceptor in the same azir-
idine, intramolecular 1,4 addition could be performed in a single
pot operation. Selective aziridination at the electron rich olefin of
(R)-carvone using Sharpless aziridination protocol afforded the
carvone derived aziridine 17 as a diastereomeric mixture (dr¼1:1)
in good yield. Treatment of the diastereomeric mixture of aziridine
17 with tetrathiomolybdate 1 (2.2 equiv; CH3CN, 28 ꢀC, 10 h) yiel-
ded two diastereomers of thia-bicyclo[3.3.1]nonane derivatives 18a
5
6
24
24
40
No reaction
d
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
Scheme 7. Tentative mechanism for tetrathiomolybdate 1 mediated tandem multi-step ring opening of aziridine, disulfide formation, disulfide bond cleavage followed by Michael
reaction.
and 18b (1:1), respectively in 88% yield (Scheme 9). These di-
astereomers were easily separated using column chromatography
[using ethyl acetate and hexanes (2:8) as an eluant]. Compound 18a
was isolated as very good quality crystals with a melting point of
174 ꢀC, whereas compound 18b was isolated as fluffy, colorless solid
with the melting point of 223 ꢀC. The solid-state structure of 18a
was confirmed by single crystal X-ray analysis18 (Fig. 2). The same
methodology was extended to (S)-carvone derived aziridine to
synthesize the opposite enantiomer.
Next, this methodology was extended to study the reaction of
aziridine derived from (ꢂ)-perillaldehyde. Reaction of aziridines 19
with 1 [2.2 equiv, CH3CN, 28 ꢀC 10 h] led to facile aziridine ring
opening in a regioselective manner and subsequent intramolecular
Michael reaction to afford an inseparable diastereomeric mixture of
thia-bicyclo[3.3.1]nonane derivatives 20a and 20b (1:1) in 81%
Fig. 1. Molecular structure of 13h0.
yield (Scheme 10).
R3
O
R2
R3
NHTs
OMe
[BnEt3N]2MoS4 1 (2.2 equiv)
O
NTs
R1
+
O
R2
O
3
CH3CN, rt, 4 - 9 h
65 - 80%
OMe
S
R1
15
16
Scheme 8. Tandem multi-step reaction of aziridino-epoxides 15 with 1 in the presence of 3a.
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
7
Table 6
Selective aziridine ring opening in presence of epoxides followed by Michael reaction
Entry
trans-Aziridino-epoxides
Product
Time (h)
4
Yield (%)
65
1
2
3
6
8
80
70
4
9
77
5
6
5
6
70
72
* compounds 15* and 16* are 1:1 mixture of diastereomers.
Scheme 9. Tandem intramolecular multi-step reaction in the synthesis of thiabicyclo[3.3.1]nonane derivative 18.
2.9. Application of this methodology for the synthesis of
tetrahydrothiophane derived amino ester derivatives
by Wittig reaction at ꢂ78 ꢀC in one-pot gave trans-
a,b-unsaturated
aziridino ester 23 in 62% yield.19 The formation of Z-isomer of 23
was detected as a minor product during the course of reaction, but
it could not be isolated in pure form by column chromatography
due to its instability.20
By incorporating an
a,b-unsaturated ester in the aziridine
backbone in an appropriate fashion, it is possible to synthesize
sulfur containing unnatural amino acids. Aziridination of homo
allylic alcohol 21 using Sharpless aziridination protocol gave
aziridino-alcohol 22 in 56% yield. Swern oxidation of 22 followed
Treatment of aziridine 23 with 1 [2.2 equiv, CH3CN, 28 ꢀC, 5 h]
led to facile aziridine ring opening in a regioselective manner to
afford a single diastereomer of tetrahydrothiophane derived cis-u-
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
diastereomer during the reaction can be explained as shown in
Scheme 12. Reaction of 23 with 1 furnishes intermediate disulfide
X, which further undergoes reductive cleavage of disulfide bond7 in
the presence of excess reagent 1 to give thiolate intermediates X1
and X2. In the chair-like intermediate21 X1 the eNHTs group exists
in an axial position whereas in the case of chair-like intermediate
X2 the eNHTs group exists in the equatorial position. We hypoth-
esize that the faster rate of 5-exo-trig thia-cyclization of the pseudo-
equatorial intermediate X2 could lead to the formation of single
diastereomer 24 as shown in Scheme 12. The structure of com-
pound 24 was confirmed by 1H, 13C, DEPT, 1He1H, 1He13C and
NOESY studies. Recrystallization of 24 in ethyl acetate and hexane
mixture provided good quality crystals, which were subjected to X-
ray crystallographic investigation in order to determine the stereo
chemical outcome of the reaction. The X-ray structure of 2622
shown in Fig. 3 clearly confirms that amido and ester groups are
cis to each other.
Fig. 2. X-ray CAMERON structure of compound 18a.
amido ester 24 in 70% yield (Scheme 11). In order to confirm the
formation of a single diastereomer during the reaction, 1H NMR of
24 was recorded on the crude product, which clearly indicates the
formation of a single diastereomer. The formation of only one
Scheme 10. Tandem intramolecular multi-step reaction in the synthesis of amido-thiabicyclo[3.3.1]nonanal derivative 20.
Scheme 11. Synthesis of sulfur containing unnatural amino acid derivative 24.
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
9
Scheme 12. Proposed mechanism for the formation of single diastereomer 24.
and 28b (dr¼1:1) in good yields. Diastereomers 28a and 28b were
formed in equal ratio due to the similar sizes of Me/NHTs.
3. Conclusion
In summary, we have demonstrated the efficiency of tandem
multi-step aziridine/epoxide ring opening, disulfide formation,
reductive cleavage of disulfide bond and Michael addition in a one-
pot operation using tetrathiomolybdate 1 resulting in interesting
and unusual molecular structures. The intermediacy of thiolate in
the multi-step reaction was established by isolation of the thiol
intermediate 13h0 in the absence of Michael acceptor and the
compound was fully characterized by X-ray structure analysis. Us-
ing this methodology, a number of ß-sulfonamidosulfides were
synthesized in good yields. It has been shown that selective azir-
idine ring opening followed by Michael reaction can be performed
in the case of aziridino-epoxides. Tetrahydrothiophene based
Fig. 3. X-ray CAMERON structure of compound 24.
In the next stage, 3-methy-3-buten-1-ol 25 was converted to
2,2-disubstituted aziridine having trans-a,b-unsaturated ester 27 as
shown in Scheme 13. As expected, treatment of aziridine 27 with
tetrathiomolybdate 1 furnished the mixture of diastereomers 28a
Scheme 13. Synthesis of sulfur containing unnatural amino acid derivatives 30a and 30b.
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D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
amino acid derivatives 24 and 28 have also been synthesized in
good yields. Further, this methodology has been used for the con-
struction of thiabicyclo[3.3.1]nonane system in high yield with
good regio- and diastereoselectivity.
21.5; HRMS m/z: calcd for C20H25NO4S2Naþ[MþNaþ]: 430.1123;
found: 430.1134.
4.2.2. (S)-4-Methyl-N-(1-phenyl-3-((2-(phenylsulfonyl)ethyl)thio)
propan-2-yl)benzenesulfonamide 4b. Colorless liquid; Rf¼0.40
(EtOAc/hexane, 3:7); Yield: 0.180 g, 74%; ½a D27
þ54.00 (c¼1.0,
ꢄ
4. Experimental section
CHCl3); IR (neat) nmax: 3282, 1321, 1150, 1085, 813, 738, 665 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
7.94 (d, J¼8.1 Hz, 2H), 7.72e7.51 (m,
4.1. General procedure for sharpless aziridination
5H), 7.21e7.17 (m, 5H), 6.95e6.93 (m, 2H), 4.70 (d, J¼6.6 Hz, 1H),
3.49e3.41 (m, 1H), 3.38e3.22 (m, 2H), 2.87e2.51 (m, 6H), 2.42 (s,
To
a mixture of an appropriate olefin (3 mmol) and
3H); 13C NMR (75 MHz, CDCl3):
d 143.5, 138.8, 136.5, 136.1, 134.0,
TsNClNa.3H2O (CAT) (0.930 g, 3.3 mmol) in CH3CN (15 mL), was
added phenyltrimethylammonium tribromide, (PTAB) (0.113 g,
0.3 mmol) at 28 ꢀC. After 12 h of vigorous stirring, the reaction
mixture was concentrated and filtered through a short column of
silica gel and eluted with 10% EtOAc in hexanes. After evaporation
of solvent, the resultant solid was purified by flash column
chromatography to yield the corresponding aziridines in good
yield.
129.7, 129.1, 128.7, 128.1, 126.9, 126.8, 55.9, 54.1, 39.5, 36.6, 24.6,
21.5; HRMS m/z: calcd for C24H27NO4S3Naþ[MþNaþ]: 512.1000;
found: 512.1011.
4.2.3. Methyl-2-methyl-3-(((S)-2-((4-methylphenyl)sulfonamido)-3-
phenylpropyl)thio)propanoate 4c. Colorless liquid; Rf¼0.40 (EtOAc/
hexane, 3:7); Yield: 0.139 g, 66%; IR (neat) nmax: 3282, 1734,
1455, 1329, 1158, 814, 746, 701, 665 cmꢂ1
;
1H NMR (300 MHz,
CDCl3, 1:1 mixture of diastereomers):
d
7.61 (d, J¼8.1 Hz, 2H),
4.1.1. (R)-2-Methyl-5-(2-methyl-1-tosylaziridin-2-yl)cyclohex-2-en-
1-one 17. Colorless liquid; Rf¼0.40 (EtOAc/hexanes, 3:7); Yield:
0.689 g, 72%; IR (neat) nmax: 1671, 1451, 1320, 1159, 959, 847, 713,
696 cmꢂ1; 1H NMR (300 MHz, CDCl3, 1:1 mixture of diastereomers):
7.23e7.19 (m, 5H), 7.02e7.01 (m, 2H), 4.92 (d, J¼7.5 Hz, 1H), 3.71
(s, 3H), 3.57e3.48 (m, 1H), 2.85 (dd, J¼13.8, 6.6 Hz, 1H),
2.77e2.45 (m, 6H), 2.41 (s, 3H), 1.19 (d, J¼7.2 Hz, 3H); 13C NMR
(75 MHz, CDCl3, 1:1 mixture of diastereomers):
d 175.4, 175.3,
d
7.81 (d, J¼8.4 Hz, 2H), 7.32 (d, J¼8.4 Hz, 2H), 6.72 (br s,1H), 2.63 (s,
143.3, 137.1, 136.6, 136.5, 129.6, 129.3, 129.2, 128.6, 127.0, 126.7,
54.4, 54.2, 51.9, 40.1, 40.0, 39.7, 39.6, 37.2, 37.1, 36.1, 21.5, 16.9,
16.8; HRMS m/z: calcd for C21H27NO4S2Naþ[MþNaþ]: 444.1279;
found: 444.1287.
1H), 2.44 (s, 3H), 2.28 (m, 3H), 2.17 (s, 2H), 1.76 (s, 3H), 1.74 (s, 3H),
1.69 (s, 1H); 13C NMR (75 MHz, CDCl3, 1:1 mixture of di-
astereomers):
d 198.5, 198.4, 144.1, 144.0, 143.9, 143.6, 137.6, 137.5,
135.5, 135.3, 129.4, 127.2, 51.4, 51.1, 42.8, 41.9, 40.2, 40.1, 39.6, 39.5,
28.2, 27.9, 21.5, 15.8, 15.5, 15.0; HRMS m/z: calcd for C17H21
NO3SNaþ[MþNaþ]: 342.1140; found: 342.1145.
4.2.4. Methyl N-acetyl-S-((S)-2-((4-methylphenyl)sulfonamido)-3-
phenylpropyl)cysteinate 4d. Colorless liquid; Rf¼0.40 (EtOAc/hex-
ane, 3:7); Yield: 0.139 g, 60%; IR (neat) nmax: 3287, 1744, 1656, 1534,
1436, 1322, 1156, 1091, 813, 743, 702, 665 cmꢂ1; 1H NMR (300 MHz,
4.1.2. 2-(2-Methyl-1-tosylaziridin-2-yl)ethan-1-ol 28. Colorless liq-
uid; Rf¼0.65 (silica gel, EtOAc/hexanes, 1:1); Yield: 0.489 g, 64%;
CDCl3, 1:1 mixture of diastereomers):
d
7.59 (d, J¼8.1 Hz, 2H),
IR (neat) nmax: 3525, 1597, 1318, 1158, 943, 818, 709 cmꢂ1 1H
;
7.23e7.19 (m, 10H), 6.98 (br s, 4H), 6.47 (d, J¼7.2 Hz, 1H), 6.39 (d,
J¼8.1 Hz, 1H), 5.37 (d, J¼7.8 Hz, 1H), 4.92e4.89 (m, 2H), 4.80e4.78
(m,1H), 3.78 (m, 3H), 3.75 (s, 3H), 3.58e3.52 (m, 2H), 3.00e2.84 (m,
4H), 2.80e2.57 (m, 7H), 2.41 (s, 3H), 2.08 (s, 3H), 2.03 (s, 3H); 13C
NMR (300 MHz, CDCl3):
d
7.81 (d, J¼8.3 Hz, 2H), 7.32 (d,
J¼8.3 Hz, 2H), 3.78 (m, 2H), 2.61 (s, 1H), 2.43 (s, 3H), 2.38 (s,
1H), 2.03 (m, 1H), 1.76 (m, 1H), 1.72 (s, 3H); 13C NMR (75 MHz,
CDCl3):
d 144.0, 137.4, 129.5, 127.2, 59.2, 48.8, 40.9, 39.5, 21.5,
NMR (75 MHz, CDCl3, 1:1 mixture of diastereomers): d 171.2, 170.3,
18.9; HRMS. m/z: calcd for C12H17NO3SNaþ [MþNaþ]: 278.0827;
143.4, 143.2, 136.9, 136.6, 136.4, 129.6, 129.2, 128.7, 128.6, 126.9,
126.8, 126.7, 54.4, 54.3, 52.8, 52.7, 52.4, 52.1, 39.8, 39.6, 38.3, 37.4,
35.7, 34.9, 23.2, 23.0, 21.5; HRMS m/z: calcd for
found: 278.0836.
4.2. General procedure for ring opening of monosubstituted
aziridines followed by Michael reaction in the presence of 1
C
22H28N2O5S2Naþ[MþNaþ]: 487.1337; found: 487.1331.
4.2.5. (S)-N-(1-((2-Cyanoethyl)thio)-3-phenylpropan-2-yl)-4-
Tetrathiomolybdate 1 (0.670, 1.00 mmol) was added to a well-
stirred solution of appropriate monosubstituted aziridine
(0.50 mmol) and methyl acrylate 3a (0.054 mL, 0.6 mmol) in CH3CN
(3 mL). The reaction mixture was stirred at room temperature
(28 ꢀC) for 2e8 h. The solvent was evaporated under reduced
pressure, the black residue was extracted with CH2Cl2:Et2O (1:5, 3ꢃ
10 mL) and filtered through a Celite pad. The filtrate was concen-
trated and the residue was purified by flash column chromatogra-
methylbenzenesulfonamide 4e. Colorless liquid; Rf¼0.50 (EtOAc/
hexane, 3:7); Yield: 0.94 g, 50%; ½a D27
þ42.00 (c¼1.0, CHCl3); IR
ꢄ
(neat) nmax: 3288, 2261, 1741, 1334, 1160, 810, 741, 703, 668 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
7.61 (d, J¼8.1 Hz, 2H), 7.28e7.22 (m,
5H), 7.21 (m, 2H), 4.91 (d, J¼6.9 Hz,1H), 3.50e3.48 (m,1H), 2.87 (dd,
J¼13.5, 6.5 Hz, 1H), 2.78 (dd, J¼14.2, 7.1 Hz, 1H), 2.70e2.68 (m, 2H),
2.64e2.50 (m, 4H), 2.43 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 144.3,
137.0, 136.6, 130.0, 129.6, 128.3, 126.5, 126.7, 121.2, 48.4, 40.2, 36.6,
34.7, 28.3, 22.3; HRMS m/z: calcd for C19H22N2O2S2Naþ[MþNaþ]:
397.1020; found: 397.1026.
phy on silica gel to give corresponding
derivatives in good yields.
b-sulfonamidosulfide
4.2.1. Methyl-(S)-3-((2-((4-methylphenyl)sulfonamido)-3-
4.2.6. (S)-4-Methyl-N-(1-((3-oxopentyl)thio)-3-phenylpropan-2-yl)
phenylpropyl)thio)propanoate 4a. Colorless
liquid;
þ32.00 (c¼1.0,
Rf¼0.40
benzenesulfonamide 4f. Colorless liquid; Rf¼0.45 (EtOAc/hexane,
(EtOAc/hexane, 3:7); Yield: 0.173 g, 85%; ½a D27
ꢄ
3:7); Yield: 0.173 g, 78%; ½a D27
þ56.00 (c¼1.0, CHCl3); IR (neat)
ꢄ
CHCl3); IR (neat) nmax: 3284, 1735, 1330, 1157, 813, 745, 701,
nmax: 3285, 1706, 1334, 1154, 816, 742, 702, 667 cmꢂ1 1H NMR
;
665 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
7.60 (d, J¼8.1 Hz, 2H),
(300 MHz, CDCl3):
d
7.61 (d, J¼8.2 Hz, 2H), 7.25e7.20 (m, 5H), 7.02
7.23e7.20 (m, 5H), 7.01 (m, 2H), 4.88 (d, J¼6.9 Hz, 1H), 3.71 (s,
3H), 3.55e3.53 (m, 1H), 2.86 (dd, J¼13.5, 6.6 Hz, 1H), 2.74 (dd,
J¼14.4, 7.2 Hz, 1H), 2.69e2.65 (m, 2H), 2.61e2.52 (m, 4H), 2.41
(m, 2H), 4.81 (d, J¼6.8 Hz, 1H), 3.58e3.54 (m, 1H), 2.84 (dd, J¼13.4,
6.5 Hz, 1H), 2.72 (dd, J¼13.4, 7.3 Hz, 1H), 2.71e2.67 (m, 2H),
2.60e2.51 (m, 4H), 2.42 (s, 3H) 2.2 (q, J¼7.2 Hz, 2H), 1.42 (t,
(s, 3H); 13C NMR (75 MHz, CDCl3):
d
172.2, 143.3, 136.9, 136.5,
J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 210.2, 143.1, 136.6,
129.6, 129.3, 128.6, 126.9, 126.7, 54.3, 51.9, 39.6, 36.7, 34.3, 27.7,
136.5, 129.5, 129.4, 128.2, 126.6, 126.6, 52.0, 46.4, 39.4, 36.9, 34.5,
Please cite this article in press as: Sureshkumar, D.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.04.003

D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
11
27.8, 21.5, 19.2; HRMS m/z: calcd for C21H27NO3S2Naþ[MþNaþ]:
(m, 1H), 0.82 (t, J¼7.2 Hz, 3H), 0.80 (t, J¼6.6 Hz, 3H); 13C NMR
428.1330; found: 428.1336.
(75 MHz, CDCl3): d 172.1, 143.3, 137.6, 129.5, 127.1, 57.0, 51.8, 36.9,
34.2, 34.1, 27.3, 24.5, 21.4, 14.8, 11.4; HRMS m/z: calcd for
4.2.7. Benzyl-(S)-3-((2-((4-methylphenyl)sulfonamido)-3-
C
17H27NO4S2[MþNaþ]: 396.1279; found: 396.1269.
phenylpropyl)thio)propanoate 4g. Colorless liquid; Rf¼0.5 0 (EtOAc/
hexane, 3:7); Yield: 0.133 g, 55%; ½a D27
ꢄ
þ32.00 (c¼1.0, CHCl3); IR
4.2.13. (S)-Methyl-3-(3,3-dimethyl-2-(4-methylphenylsulfonamido)
(neat) nmax: 3292, 1732, 1330, 1154, 812, 743, 698, 661 cmꢂ1
;
1H
butylthio)propanoate 6f. Colorless liquid; Rf¼0.50 (EtOAc/hexanes,
NMR (300 MHz, CDCl3):
d
7.58 (d, J¼8.1 Hz, 2H), 7.36e7.34 (m, 5H),
3:7); Yield: 0.140 g, 75%; ½a D27
ꢄ
ꢂ71.00 (c¼1.0, CHCl3); IR (neat) nmax
:
7.18e7.16 (m, 5H), 7.01e6.98 (m, 2H), 5.15 (s, 2H), 4.88 (d, J¼7.2 Hz,
1H), 3.56e3.49 (m, 1H), 2.84 (dd, J¼13.8, 6.9 Hz, 1H), 2.75e2.68 (m,
3H), 2.65e2.52 (m, 4H), 2.38 (s, 3H); 13C NMR (75 MHz, CDCl3):
3295, 1736, 1331, 1155, 1019, 814, 665 cmꢂ1 1H NMR (300 MHz,
;
CDCl3):
d
7.79 (d, J¼8.1 Hz, 2H), 7.29 (d, J¼8.1 Hz, 2H), 5.04 (d,
J¼9.6 Hz, 1H), 3.69 (s, 3H), 3.32e3.25 (m, 1H), 2.72 (dd, J¼13.5,
d
171.6, 143.3, 137.0, 136.5, 135.7, 129.6, 129.3, 128.6, 128.3, 127.0,
5.7 Hz, 1H), 2.58e2.45 (m, 5H), 2.43 (s, 3H), 0.86 (s, 9H); 13C NMR
126.7, 66.6, 54.3, 39.7, 36.8, 34.6, 27.6, 21.5; HRMS m/z: calcd for
C
(75 MHz, CDCl3): d 172.2, 143.2, 138.4, 129.4, 127.1, 61.5, 51.8, 35.4,
26H29NO4S2Naþ[MþNaþ]: 506.1436; found: 506.1432.
34.6, 34.2, 28.6, 26.9, 21.5; HRMS m/z: calcd for
C
17H27NO4S2[MþNaþ]: 396.1279; found: 396.1288.
4.2.8. Methyl-(S)-3-(2-(4-methylphenylsulfonamido)propylthio)
propanoate 6a. Colorless liquid; Rf¼0.40 (EtOAc/hexanes, 3:7);
4.2.14. (S)-Methyl-3-((2-((4-methylphenyl)sulfonamido)-4-(methyl-
Yield: 0.138 g, 80%; ½a D27
ꢄ
þ16.00 (c¼1.0, CHCl3); IR (neat) nmax: 3276,
thio)butyl)thio 6g. Colorless liquid; Rf¼0.55 (EtOAc/hexane, 3:7);
1736, 1436, 1331, 1160, 1093, 664 cmꢂ1; 1H NMR (300 MHz, CDCl3):
Yield: 0.123 g, 63%; ½a D27
ꢄ
ꢂ132.08 (c¼1.0, CHCl3); IR (neat) nmax
:
d
7.78 (d, J¼8.1 Hz, 2H), 7.31 (d, J¼8.1 Hz, 2H), 4.97 (d, J¼6.6 Hz, 1H),
3242, 1746, 1346, 1162, 825, 745, 668 cmꢂ1 1H NMR (300 MHz,
;
3.71 (s, 3H), 3.48e3.40 (m, 1H), 2.65e2.48 (m, 6H), 2.43 (s, 3H), 1.14
CDCl3):
d
7.79 (d, J¼8.1 Hz, 2H), 7.32 (d, J¼8.1 Hz, 2H), 5.31 (d,
(d, J¼6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d
172.1, 143.4, 137.5,
J¼8.1 Hz, 1H), 3.68 (s, 3H), 3.77e3.63 (m, 1H), 3.02 (dd, J¼14.2,
4.3 Hz, 1H), 2.76 (dd, J¼14.2, 6.7 Hz, 1H), 2.45 (s, 3H), 2.38e2.17 (m,
4H), 1.95 (s, 3H), 1.90e1.82 (m, 3H), 1.71e1.69 (m, 1H); 13C NMR
129.7, 127.1, 51.9, 48.9, 39.3, 34.3, 27.4, 21.5, 20.6; HRMS m/z: calcd
for C14H21NO4S2[MþNaþ]: 354.0810; found: 354.0815.
(75 MHz, CDCl3):
d 171.8, 143.5, 137.6, 129.9, 127.3, 62.1, 52.5, 44.4,
4.2.9. Methyl-(S)-3-(2-(4-methylphenylsulfonamido)butylthio)prop-
35.6, 34.2, 32.2, 30.3, 21.7, 15.3; HRMS m/z: calcd for
C
anoate 6b. Colorless liquid; Rf¼0.40 (EtOAc/hexanes, 3:7); Yield:
16H25NO4S3Naþ[MþNaþ]: 414.0843; found: 414.0846.
0.138 g, 80%; ½a 2D7
þ29.20 (c¼1.0, CH2Cl2); IR (neat) nmax: 3283,
ꢄ
1737, 1436, 1326, 1157, 1093, 816, 665 cmꢂ1
;
1H NMR (300 MHz,
4.2.15. (S)-Methyl-3-(2-(4-methylphenylsulfonamido)-3-(4-(tosy-
CDCl3):
d
7.79 (d, J¼8.4 Hz, 2H), 7.31 (d, J¼8.4 Hz, 2H), 5.21 (d,
loxy)phenyl)propylthio)propanoate 6h. Colorless liquid; Rf¼0.60
J¼7.5 Hz, 1H), 3.70 (s, 3H), 3.32e3.22 (m, 2H), 2.69e2.62 (m, 2H),
(EtOAc/hexanes, 3:7); Yield: 0.208 g, 72%; ½a D27
ꢂ54.00 (c¼1.0,
ꢄ
2.54e2.49 (m, 3H), 2.43 (s, 3H), 1.67e1.53 (m, 1H), 1.49e1.36 (m,
CHCl3); IR (neat) nmax: 3277, 1742, 1434, 1335, 1169, 821, 667 cmꢂ1
;
1H), 0.77 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d
172.1, 143.3,
1H NMR (300 MHz, CDCl3):
d
7.69 (d, J¼7.8 Hz, 2H), 7.57 (d, J¼7.8 Hz,
137.7, 129.5, 126.9, 54.5, 51.7, 37.0, 34.3, 27.6, 26.6, 21.4, 9.8; HRMS
2H), 7.32 (d, J¼8.1 Hz, 2H), 7.22 (d, J¼8.1 Hz, 2H), 6.93 (d, J¼8.4 Hz,
2H), 6.79 (d, J¼8.4 Hz, 2H), 4.94 (d, J¼7.2 Hz, 1H), 3.71 (s, 3H),
3.56e3.45 (m, 1H), 2.84 (dd, J¼14.0, 6.4 Hz, 1H), 2.71e2.60 (m, 2H),
2.84 (dd, J¼14.7, 6.9 Hz, 1H), 2.71e2.60 (m, 4H), 2.54 (s, 3H), 2.42 (s,
m/z: calcd for C15H23NO4S2[MþNaþ]: 368.0966; found: 368.0976.
4.2.10. Methyl-(S)-3-(3-methyl-2-(4-methylphenylsulfonamido)bu-
tylthio)propanoate 6c. Colorless liquid; Rf¼0.40 (EtOAc/hexanes,
3H); 13C NMR (75 MHz, CDCl3):
d 172.3, 148.4, 145.4, 143.6, 136.9,
3:7); Yield: 0.140 g, 78%; ½a D27
ꢄ
ꢂ25.00 (c¼1.0, CHCl3); IR (neat) nmax
:
135.7, 132.3, 130.4, 130.0, 129.8, 129.7, 128.4, 126.9, 122.4, 54.2, 51.9,
3285, 1737, 1437, 1327, 1159, 1093, 815, 665 cmꢂ1
;
1H NMR
39.1, 36.8, 34.3, 27.7, 21.7, 21.5; HRMS m/z: calcd for
(300 MHz, CDCl3):
d
7.79 (d, J¼8.1 Hz, 2H), 7.31 (d, J¼8.1 Hz, 2H),
C
27H31NO7S3[MþNaþ]: 600.1160; found: 600.1165.
5.01 (d, J¼8.4 Hz, 1H), 3.70 (s, 3H), 3.19e3.12 (m, 1H), 2.69e2.45 (m,
6H), 2.43 (s, 3H), 1.98e1.84 (m, 1H), 0.80 (d, J¼7.2 Hz, 3H), 0.66 (dd,
4.2.16. (S)-Methyl-3-(3-(1H-indol-2-yl)-2-(4-methylphenylsulfo-
J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d
172.1, 143.3, 137.7, 129.6,
namido)propylthio)propanoate 6i. Colorless liquid; Rf¼0.40 (EtOAc/
127.1, 58.3, 51.8, 34.8, 29.9, 27.6, 21.5, 18.9, 17.5; HRMS m/z: calcd for
hexane, 1:1); Yield: 0.134 g, 60%; ½a D27
ꢂ25.41 (c¼1.0, CHCl3); IR
ꢄ
C
16H25NO4S2[MþNaþ]: 382.1123; found: 382.1125.
(neat) nmax: 3274, 1741, 1431, 1336, 1163, 811, 661 cmꢂ1 1H NMR
;
(300 MHz, CDCl3):
d
8.09 (br s, 1H), 7.81 (d, J¼8.4 Hz, 2H), 7.51 (d,
4.2.11. Methyl-(S)-3-(4-methyl-2-(4-methylphenylsulfonamido)pen-
J¼8.4 Hz, 2H), 7.29 (s, 1H), 7.19e7.14 (m, 1H), 7.07e6.95 (m, 4H),
4.92 (d, J¼6.6 Hz, 1H), 3.71 (s, 3H), 3.60e3.52 (m, 1H), 3.06 (dd,
J¼14.7, 6.3 Hz, 1H), 2.89 (dd, J¼14.7, 6.9 Hz, 1H), 2.78e2.71 (m, 3H),
tylthio)propanoate 6d. Colorless liquid; Rf¼0.40 (EtOAc/hexanes,
3:7); Yield: 0.142 g, 76%; ½a D27
ꢂ76.05 (c¼1.0, CH2Cl2); IR (neat)
ꢄ
nmax: 3282, 1738, 1436, 1332, 1159, 1093, 815, 665 cmꢂ1
;
1H NMR
2.66e2.51 (m, 3H), 2.33 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 172.3,
(300 MHz, CDCl3):
d
7.78 (d, J¼8.1 Hz, 2H), 7.31 (d, J¼8.1 Hz, 2H),
143.2, 136.5, 136.2, 129.4, 127.1, 126.8, 123.1, 122.1, 119.6, 118.6, 111.1,
4.94 (d, J¼8.4 Hz,1H), 3.71 (s, 3H), 3.49e3.37 (m, 1H), 2.71e2.64 (m,
3H), 2.55e2.47 (m, 3H), 2.43 (s, 3H), 1.57e1.30 (m, 3H), 0.81 (d,
J¼6.6 Hz, 3H), 0.67 (d, J¼6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3):
110.5, 53.2, 51.9, 36.9, 34.4, 29.4, 27.7, 21.5; HRMS m/z: calcd for
C
22H26N2O4S2Naþ[MþNaþ]: 469.1232; found: 469.1244.
d
172.2, 143.4, 137.8, 129.6, 127.1, 51.8, 51.3, 43.2, 38.2, 34.4, 27.9,
4.2.17. Methyl-3-(((R)-2-((3aR,5R,6S,6aR)-6-(benzyloxy)-2,2-
dimethyltetrahydrofuro[2,3-d][1,3] dioxol-5-yl)-2-((4-methylphenyl)
sulfonamido)ethyl)thio)propanoate 8a. Colorless liquid; Rf¼0.50
(EtOAc/hexane, 1:1); Yield: 0.192 g, 68%; IR (neat) nmax: 3279, 1737,
1331, 1215, 1162, 1075, 1026, 665 cmꢂ1; 1H NMR (300 MHz, CDCl3):
24.3, 22.8, 21.6, 21.5; HRMS m/z: calcd for C17H27NO4S2[MþNaþ]:
396.1279; found: 396.1299.
4.2.12. Methyl-3-((2S,3S)-3-methyl-2-(4-methylphenylsulfonamido)
pentylthio)propanoate 6e. Colorless liquid; Rf¼0.50 (EtOAc/hex-
d
7.73 (d, J¼8.1 Hz, 2H), 7.37 (d, J¼8.1 Hz, 2H), 7.26e7.22 (m, 5H),
anes, 3:7); Yield: 0.131 g, 70%; ½a D27
ꢄ
þ22.36 (c¼1.0, CH2Cl2); IR
5.72 (d, J¼3.9 Hz, 1H), 5.15 (d, J¼5.1 Hz, 1H), 4.52 (dd, J¼56.4,
11.7 Hz, 2H), 4.53 (d, J¼3.6 Hz, 1H), 4.28 (dd, J¼7.5, 3.0 Hz, 1H), 3.89
(d, J¼3.0 Hz, 1H), 3.80e3.73 (m, 1H), 3.69 (s, 3H), 2.84 (dd, J¼14.4,
6.3 Hz, 1H), 2.72 (m, 3H), 2.52 (t, J¼6.9 Hz, 2H), 2.39 (s, 3H), 1.45 (s,
(neat) nmax: 3286, 1738, 1437, 1332, 1158, 816, 665 cmꢂ1 1H NMR
;
(300 MHz, CDCl3):
5.09 (d, J¼8.1 Hz, 1H), 3.69 (s, 3H), 3.26e3.18 (m, 1H), 2.84e2.45 (m,
6H), 2.43 (s, 3H), 1.72e1.61 (m, 1H), 1.48e1.35 (m, 1H), 1.07e0.92
d
7.78 (d, J¼8.1 Hz, 2H), 7.30 (d, J¼8.1 Hz, 2H),
3H), 1.28 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 172.2, 137.2, 136.8,
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12
D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
129.4, 128.6, 128.2, 127.8, 127.4, 111.9, 104.5, 81.9, 81.4, 79.1, 71.4,
hexanes, 1:1); Yield: 0.120 g, 64%; IR (neat) nmax: 3505, 3284, 1736,
52.3, 51.8, 34.4, 34.1, 27.8, 26.7, 26.2, 21.5; HRMS m/z: calcd for
1439, 1325, 1154, 1092, 815, 664 cmꢂ1; 1H NMR (300 MHz, CDCl3):
C
27H35NO8S2Naþ[MþNaþ]: 588.1702; found: 588.1704.
d
7.78 (d, J¼8.1 Hz, 2H), 7.28 (d, J¼8.1 Hz, 2H), 5.93 (s, 1H), 3.77 (br s,
1H), 3.72 (s, 3H), 2.89 (s, 2H), 2.82 (t, J¼7.2 Hz, 2H), 2.60 (t, J¼7.2 Hz,
4.2.18. Methyl-3-(((R)-2-((4-methylphenyl)sulfonamido)-2-
((4S,40R,5R)-2,2,20,20-tetramethyl-[4,40-bi(1,3-dioxolan)]-5-yl)ethyl)
thio)propanoate 8b. Colorless liquid; Rf¼0.50 (EtOAc/hexane, 1:1);
Yield: 0.168 g, 65%; IR (neat) nmax: 3291, 2986, 1739, 1159, 1070,
2H), 2.42 (s, 3H), 1.98e1.71 (m, 4H), 1.24 (s, 3H); 13C NMR (75 MHz,
CDCl3):
d 172.3, 143.0, 140.4, 129.7, 129.5, 127.0, 126.8, 59.4, 59.1,
51.9, 43.8, 41.0, 34.6, 28.9, 23.7, 21.5; HRMS m/z: calcd for
C
16H25NO5S2[MþNaþ]: 398.1072; found: 398.1086.
669 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.77 (d, J¼8.1 Hz, 2H), 7.31
(d, J¼8.1 Hz, 2H), 5.13 (d, J¼9.9 Hz, 1H), 4.21 (dd, J¼7.8, 1.2 Hz, 1H),
4.11 (dd, J¼8.4, 6.3 Hz, 1H), 4.01e3.94 (m, 1H), 3.74e3.55 (m, 3H),
3.71 (s, 3H), 2.73e2.59 (m, 3H), 2.56e2.43 (m, 3H), 2.43 (s, 3H), 1.40
(s, 3H), 1.38 (s, 3H), 1.36 (s, 3H), 1.33 (s, 3H); 13C NMR (75 MHz,
4.3.5. Methyl-3-(((3R*,4R*)-4-((4-methylphenyl)sulfonamido)hexan-
3-yl)thio)propanoate 12a. Colorless liquid; Rf¼0.40 (EtOAc/hexane,
3:7); Yield: 0.127 g, 68%; IR (neat) nmax: 3286, 1738, 1332, 1160,
816, 665 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.77 (d, J¼8.1 Hz, 2H),
CDCl3):
d
172.1,143.7,138.1,129.8,127.0,109.8,100.5, 78.3, 77.5, 76.9,
7.29 (d, J¼8.1 Hz, 2H), 4.95 (d, J¼8.1 Hz, 1H), 3.71 (s, 3H), 3.33e3.27
(m, 1H), 2.81e2.75 (m, 3H), 2.59 (t, J¼7.5 Hz, 2H), 2.43 (s, 3H),
1.72e1.55 (m, 2H), 1.32e1.22 (m, 2H), 0.95 (t, J¼7.5 Hz, 3H), 0.68 (t,
67.9, 52.3, 51.8, 34.9, 34.3, 26.9, 26.8, 26.7, 26.2, 25.1, 21.5; HRMS m/
z: calcd for C23H35NO8S2Naþ[MþNaþ]: 540.1702; found: 540.1718.
J¼7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 172.3, 143.2, 138.1,
4.3. General procedure for regio- and stereoselective ring
opening of 2,2-disubstituted and 2,3-disubstituted aziridines
followed by Michael reaction in the presence of 1
129.6, 126.9, 59.3, 52.4, 51.8, 34.7, 26.9, 24.6, 23.9, 21.5, 12.3, 10.7;
HRMS m/z: calcd for C17H27NO4S2Naþ[MþNaþ]: 396.1279; found:
396.1279.
Tetrathiomolybdate 1 (0.670, 1.00 mmol) was added to a well-
stirred solution of appropriate 2,2-disubstituted or 2,3- di-
substituted aziridine (0.50 mmol) and methyl acrylate 3a
(0.054 mL, 0.6 mmol) in CH3CN (3 mL). The reaction mixture was
stirred at room temperature (28 ꢀC) for 3e12 h. The solvent was
evaporated under reduced pressure, the black residue was extrac-
ted with CH2Cl2:Et2O (1:5, 3ꢃ 10 mL) and filtered through a Celite
pad. The filtrate was concentrated and the residue was purified by
flash column chromatography on silica gel to give corresponding
amino acid derivatives in good yields.
4.3.6. Methyl-3-(((3S*,4R*)-4-((4-methylphenyl)sulfonamido)hexan-
3-yl)thio)propanoate 12b. Colorless liquid; Rf¼0.50 (EtOAc/hexane,
3:7); Yield: 0.131 g, 70%; IR (neat) nmax: 3293, 1737, 1437, 1337, 1161,
1092, 816, 666 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.79 (d, J¼8.1 Hz,
2H), 7.30 (d, J¼8.1 Hz, 2H), 5.21 (d, J¼9.3 Hz, 1H), 3.73 (s, 3H),
3.30e3.25 (m, 1H), 2.83e2.58 (m, 3H), 2.51 (t, J¼7.2 Hz, 2H), 2.43 (s,
3H),1.53e1.37 (m, 2H),1.29e1.17 (m, 2H), 0.95 (t, J¼7.2 Hz, 3H), 0.75
(t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 172.2, 143.2, 138.3,
129.5, 127.0, 57.9, 55.6, 51.9, 34.5, 33.8, 28.2, 27.3, 22.5, 21.5, 12.3,
10.6; HRMS m/z: calcd for C17H27NO4S2Naþ[MþNaþ]: 396.1279;
found: 396.1264.
4.3.1. Methyl-3-((2-methyl-2-((4-methylphenyl)sulfonamido)propyl)
thio)propanoate 10a. Colorless liquid; Rf¼0.40 (EtOAc/hexane, 3:7);
Yield: 0.135 g, 78%; IR (neat) nmax: 3282,1737,1436,1323,1151,1093,
4.3.7. Methyl-3-((2R*,3R*)-4-methyl-3-(4-methylphenylsulfo-
namido)pentan-2-ylthio)propanoate 12c. Colorless liquid; Rf¼0.60
(EtOAc/hexanes, 3:7); Yield: 0.121 g, 65%; IR (neat) nmax: 3291, 1737,
998, 815, 663 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
7.79 (d, J¼8.1 Hz,
2H), 7.29 (d, J¼8.1 Hz, 2H), 5.25 (s, 1H), 3.71 (s, 3H), 2.84 (t, J¼7.2 Hz,
1437, 1329, 1159, 1093, 666 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d 7.75
2H), 2.73 (m, 2H), 2.61 (t, J¼7.2 Hz, 2H), 2.42 (s, 3H), 1.22 (s, 6H); 13
C
(d, J¼8.1 Hz, 2H), 7.28 (d, J¼8.1 Hz, 2H), 4.90 (d, J¼9.3 Hz, 1H), 3.70
(s, 3H), 3.17e3.01 (m, 2H), 2.99e2.64 (m, 2H), 2.56 (d, J¼7.2 Hz, 2H),
2.41 (s, 3H), 1.92e1.77 (m, 1H), 1.18 (d, J¼6.9 Hz, 3H), 0.86 (t,
J¼7.2 Hz, 3H), 0.78 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
NMR (75 MHz, CDCl3):
d 172.2, 142.9, 140.1, 129.4, 126.9, 56.8, 51.8,
45.9, 34.6, 28.9, 26.9, 21.4; HRMS m/z: calcd for
C
15H23NO4S2Naþ[MþNaþ]: 368.0966; found: 368.0976.
d
172.3, 143.0, 139.0, 129.4, 126.9, 64.7, 51.8, 43.2, 34.5, 30.9, 25.6,
4.3.2. Methyl-3-(2-methyl-2-(4-methylphenylsulfonamido)pen-
tylthio)propanoate 10b. Colorless liquid; Rf¼0.6 (EtOAc/hexanes,
3:7); Yield: 0.140 g, 75%; IR (neat) nmax: 3286,1736, 1437, 1326, 1152,
21.4, 20.6, 19.6; HRMS m/z: calcd for
396.1279; found: 396.1279.
C
17H27NO4S2[MþNaþ]:
1093, 663 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.78 (d, J¼8.1 Hz, 2H),
4.3.8. Methyl-3-((2S*,3R*)-4-methyl-3-(4-methylphenylsulfo-
namido)pentan-2-ylthio)propanoate 12d. Colorless liquid; Rf¼0.60
(EtOAc/hexanes, 3:7); Yield: 0.127 g, 68%; IR (neat) nmax: 3296,1738,
7.28 (d, J¼8.1 Hz, 2H), 5.06 (s,1H), 3.71 (s, 3H), 2.82 (t, J¼6.9 Hz, 2H),
2.75 (s, 2H), 2.61 (t, J¼6.9 Hz, 2H), 2.42 (s, 3H), 1.56e1.37 (m, 2H),
1.28e1.16 (m, 2H), 1.16 (s, 3H), 0.81 (t, J¼6.9 Hz, 3H); 13C NMR
1439, 1326, 1159, 1093, 667 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d 7.78
(75 MHz, CDCl3):
d
172.2, 143.0, 140.1, 129.4, 126.9, 59.5, 51.8, 44.0,
(d, J¼8.1 Hz, 2H), 7.28 (d, J¼8.1 Hz, 2H), 4.93 (d, J¼9.9 Hz, 1H), 3.70
(s, 3H), 3.38e3.35 (m, 1H), 3.32e3.25 (m, 1H), 2.75e2.54 (m, 2H),
2.48 (t, J¼6.9 Hz, 2H), 2.42 (s, 3H), 1.99e1.91 (m, 1H), 1.23 (d,
J¼6.9 Hz, 3H), 0.82 (t, J¼6.9 Hz, 3H), 0.78 (t, J¼6.6 Hz, 3H); 13C NMR
42.1, 34.7, 28.8, 23.4, 21.4, 16.8, 14.1; HRMS m/z: calcd for
C
17H27NO4S2[MþNaþ]: 396.1279; found: 396.1279.
4.3.3. Methyl-3-(3-hydroxy-2-methyl-2-(4-methylphenylsulfo-
namido)propylthio)propanoate 10c. Colorless liquid; Rf¼0.40
(EtOAc/hexanes, 1:1); Yield: 0.123 g, 68%; IR (neat) nmax: 3515, 3274,
(75 MHz, CDCl3): d 172.2, 143.1, 138.6, 129.5, 127.0, 62.2, 51.8, 45.6,
34.4, 28.9, 27.1, 21.5, 21.1, 19.4, 17.5; HRMS m/z: calcd for
C
17H27NO4S2[MþNaþ]: 396.1279; found: 396.1286.
1735, 1437, 1321, 1154, 1092, 815, 665 cmꢂ1 1H NMR (400 MHz,
;
CDCl3):
d
7.79 (d, J¼8.4 Hz, 2H), 7.30 (d, J¼8.4 Hz, 2H), 5.34 (s, 1H),
4.3.9. Methyl-3-(((1R*,2R*)-2-((4-methylphenyl)sulfonamido)cyclo-
pentyl)thio)propanoate 14a. Colorless liquid; Rf¼0.60 (EtOAc/hex-
ane, 3:7); Yield: 0.139 g, 78%; IR (neat) nmax: 3272, 1737, 1437, 1330,
3.71 (s, 3H), 3.58 (d, J¼6.6 Hz, 2H), 2.87e2.68 (m, 4H), 2.60 (t,
J¼7.2 Hz, 2H), 2.43 (s, 3H), 1.06 (s, 3H); 13C NMR (75 MHz, CDCl3):
d
172.3, 143.5, 139.5, 129.7, 126.9, 67.3, 60.3, 51.9, 41.1, 34.5, 28.7,
1159, 1093, 815, 665 cmꢂ1 1H NMR (300 MHz, CDCl3):
; d 7.78 (d,
21.5, 20.9; HRMS m/z: calcd for C15H23NO4S2[MþNaþ]: 384.0915;
J¼8.1 Hz, 2H), 7.32 (d, J¼8.1 Hz, 2H), 5.08 (d, J¼8.4 Hz, 1H), 3.71 (s,
3H), 3.34e3.28 (m, 1H), 2.98e2.91 (m, 1H), 2.70 (t, J¼6.9 Hz, 2H),
2.55 (t, J¼6.9 Hz, 2H), 2.44 (s, 3H), 2.13e1.96 (m, 2H), 1.71e1.61 (m,
found: 384.0928.
4.3.4. Methyl-3-(4-hydroxy-2-methyl-2-(4-methylphenylsulfo-
2H), 1.54e1.38 (m, 2H); 13C NMR (75 MHz, CDCl3):
d 172.3, 143.5,
namido)butylthio)propanoate 10d. Colorless liquid; Rf¼0.45 (EtOAc/
137.1, 129.7, 127.2, 60.4, 51.8, 50.0, 34.5, 31.9, 31.0, 26.1, 21.9, 21.5;
Please cite this article in press as: Sureshkumar, D.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.04.003

D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
13
HRMS m/z: calcd for C16H23NO4S2Naþ[MþNaþ]: 380.0966; found:
Yield: 0.097 g, 68%; mp: 112 ꢀC; IR (neat) nmax: 3275, 1321, 1157, 811,
664 cmꢂ1; 1H NMR (300 MHz, CDCl3):
(d, J¼8.1 Hz, 2H), 4.93 (d, J¼6.4 Hz, 1H), 2.84e2.79 (m, 1H),
2.64e2.55 (m, 1H), 2.43 (s, 3H), 2.22e2.09 (m, 2H), 1.67e1.63 (m,
3H), 1.42e1.35 (m, 2H), 1.28e1.13 (m, 2H); 13C NMR (75 MHz,
380.0970.
d
7.77 (d, J¼8.1 Hz, 2H), 7.30
4.3.10. Methyl-3-(((1R*,2R*)-2-((4-methylphenyl)sulfonamido)cyclo-
hexyl)thio)propanoate 14b. Colorless liquid; Rf¼0.65 (EtOAc/hex-
ane, 3:7); Yield: 0.134 g, 72%; IR (neat) nmax: 3278, 1745, 1438, 1334,
CDCl3):
d 143.4, 137.4, 129.6, 127.3, 60.3, 43.8, 36.7, 34.0, 25.7, 24.5,
1161, 1096, 816, 667 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
7.75 (d,
21.6; HRMS m/z: calcd for C13H19NO2S2Naþ[MþNaþ]: 308.0755;
J¼8.2 Hz, 2H), 7.36 (d, J¼8.2 Hz, 2H), 5.34 (d, J¼8.4 Hz, 1H), 3.73 (s,
3H), 3.34e3.28 (m, 1H), 2.93e2.90 (m, 1H), 2.71 (t, J¼6.9 Hz, 2H),
2.56 (t, J¼6.9 Hz, 2H), 2.47 (s, 3H), 2.14e1.97 (m, 2H), 1.70e1.62 (m,
found: 308.0757.
4.4. General procedure for selective ring opening of aziridine
followed by Michael reaction of aziridino-epoxides in the
presence of 1
4H), 1.56e1.35 (m, 2H); 13C NMR (75 MHz, CDCl3):
d 172.6, 143.4,
137.2, 129.8, 127.1, 61.5, 52.0, 50.5, 35.1, 32.1, 31.2, 26.3, 21.8, 21.6,
21.5; HRMS m/z: calcd for C17H25NO4S2Naþ[MþNaþ]: 394.1123;
found: 394.1120.
Tetrathiomolybdate 1 (0.670, 1.00 mmol) was added to a well-
stirred solution of appropriate aziridino-epoxide (0.50 mmol) and
methyl acrylate 3a (0.054 mL, 0.6 mmol) in CH3CN (3 mL). The
reaction mixture was stirred at room temperature (28 ꢀC) for 4e9 h.
The solvent was evaporated under reduced pressure, the black
residue was extracted with CH2Cl2:Et2O (1:5, 3ꢃ 10 mL) and filtered
through a Celite pad. The filtrate was concentrated and the residue
was purified by flash column chromatography on silica gel to give
corresponding epoxy amino acid derivatives in good yields.
4.3.11. Methyl-3-((1R*,2R*,4S*,5R*)-4,5-dihydroxy-2-(4-methyl-
phenylsulfonamido)cyclohexylthio) pro-panoate 14c. Colorless liq-
uid; Rf¼0.30 (EtOAc/hexanes, 1:1); Yield: 0.125 g, 62%; IR (neat)
nmax: 3480, 3304, 1732, 1436, 1157, 1092, 815, 664 cmꢂ1 1H NMR
;
(300 MHz, CDCl3):
d
7.76 (d, J¼8.4 Hz, 2H), 7.31 (d, J¼8.4 Hz, 2H),
6.34 (br s, 1H), 3.88e3.82 (m, 2H), 3.71 (s, 3H), 3.29 (br s, 1H),
3.09e3.08 (m, 2H), 2.98 (br s, 1H), 2.81e2.71 (m, 2H), 2.67e2.55 (m,
2H), 2.43 (s, 3H), 2.35e2.25 (m, 1H), 2.08e2.00 (m, 1H), 1.75e1.60
(m, 2H); 13C NMR (75 MHz, CDCl3):
d
172.3,143.4,137.6,129.7,126.9,
4.4.1. Methyl-3-(2-(4-methylphenylsulfonamido)-3-(oxiran-2-yl-me-
thoxy)propylthio)propanoate 16a. Colorless liquid; Rf¼0.40 (EtOAc/
hexane, 3:7); Yield: 0.196 g, 65%; IR (neat) nmax: 3277, 1735, 1437,
69.6, 67.3, 51.9, 51.8, 45.7, 34.4, 30.3, 30.2, 26.7, 21.5; HRMS m/z:
calcd for C17H25NO6S2[MþNaþ]: 426.1021; found: 426.1040.
1334, 1159, 1092, 816, 666 cmꢂ1
mixture of diastereomers):
J¼8.4 Hz, 4H), 5.32 (d, J¼7.2 Hz, 1H), 5.27 (d, J¼7.5 Hz, 1H), 3.69 (s,
6H), 3.68e3.59 (m, 4H), 3.50e3.22 (m, 6H), 3.08e3.03 (m, 2H), 2.78
(m, 2H), 2.69e2.63 (m, 8H), 2.56e2.51 (m, 6H), 2.39 (s, 6H); 13C
;
1H NMR (300 MHz, CDCl3, 1:1
7.78 (d, J¼8.4 Hz, 4H), 7.31 (d,
4.3.12. (1S*,2R*,4R*,5R*)-4-(3-Methoxy-3-oxopropylthio)-5-(4-
d
methylphenylsulfonamido)cyclo
hexane-1,2-diyl
diacetate
14d. Colorless liquid; Rf¼0.80 (EtOAc/hexanes, 1:1); Yield: 0.170 g,
70%; IR (neat) nmax: 3281, 1739, 1437, 1247, 1158, 1038, 1019, 815,
665 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.77 (d, J¼8.1 Hz, 2H), 7.33
NMR (75 MHz, CDCl3, 1:1 mixture of diastereomers): d 172.1, 143.5,
(d, J¼8.1 Hz, 2H), 5.42 (d, J¼4.8 Hz, 1H), 5.18 (bt, J¼3.0 Hz, 1H),
4.94e4.91 (m, 1H), 3.72 (s, 3H), 3.11e2.98 (m, 1H), 2.98e2.80 (m,
1H), 2.65e2.56 (m, 1H), 2.51e2.46 (m, 4H), 2.43 (s, 3H), 2.37e2.22
(m, 1H), 2.07 (s, 3H), 2.05 (s, 3H), 1.87e1.68 (m, 2H); 13C NMR
137.5, 129.7, 127.1, 71.8, 71.7, 70.7, 52.8, 51.8, 50.5, 44.0, 34.3, 33.7,
27.4, 21.5; HRMS m/z: calcd for
426.1021; found: 426.1036.
C
17H25NO6S2Naþ[MþNaþ]:
(75 MHz, CDCl3):
d
171.9, 169.9, 169.7, 143.8, 136.5, 129.8,127.2, 68.9,
4.4.2. Methyl-3-((1S*,3R*,4R*,6R*)-4-(4-methylphenylsulfonamido)-
67.8, 43.9, 34.2, 31.7, 24.9, 21.5, 20.9; HRMS m/z: calcd for
C
7-oxabicyclo[4.1.0]heptan-3-ylthio)propanoate 16b. Colorless liquid;
21H29NO8S2[MþNaþ]: 510.1232; found: 510.1220.
Rf¼0.45 (EtOAc/hexanes, 1:1); Yield: 0.540 g, 80%; IR (neat) nmax
3273, 1735, 1435, 1328, 1159, 1091, 815, 669 cmꢂ1 1H NMR
(300 MHz, CDCl3):
:
;
4.3.13. Methyl-3-(((1R*,2R*)-2-((4-methylphenyl)sulfonamido)cyclo-
heptyl)thio)propanoate 14e. Colorless liquid; Rf¼0.70 (EtOAc/hex-
ane, 3:7); Yield: 0.77 g, 40%; IR (neat) nmax: 3282, 1750, 1435, 1332,
d
7.77 (d, J¼8.4 Hz, 2H), 7.31 (d, J¼8.4 Hz, 2H),
5.27 (d, J¼3.6 Hz, 1H), 3.71 (s, 3H), 3.17 (br s, 1H), 3.11 (t, J¼4.2 Hz,
1H), 3.03 (m, 1H), 2.87e2.81 (m, 1H), 2.58e2.26 (m, 6H), 2.42 (s,
3H), 2.12e2.02 (m, 1H), 1.77 (dq, J¼9.6, 5.4, 1.8 Hz, 1H); 13C NMR
1165, 1101, 814, 669 cmꢂ1 1H NMR (300 MHz, CDCl3):
; d 7.77 (d,
J¼8.1 Hz, 2H), 7.34 (d, J¼8.1 Hz, 2H), 5.34 (d, J¼8.4 Hz, 1H), 3.72 (s,
3H), 3.35e3.26 (m, 1H), 2.93e2.90 (m, 1H), 2.72 (t, J¼6.9 Hz, 2H),
2.58 (t, J¼6.9 Hz, 2H), 2.46 (s, 3H), 2.13e1.96 (m, 2H), 1.72e1.61 (m,
(75 MHz, CDCl3): d 171.8, 143.7, 136.5, 129.7, 127.2, 52.4, 51.9, 50.9,
49.5, 44.2, 34.1, 32.6, 31.1, 24.2, 21.5; HRMS m/z: calcd for C17H23
NO5S2Naþ[MþNaþ]: 408.0915; found: 408.0921.
6H), 1.56e1.35 (m, 2H); 13C NMR (75 MHz, CDCl3):
d 172.4, 143.4,
137.2, 129.5, 127.3, 60.3, 51.7, 50.1, 34.6, 31.9, 31.1, 26.2, 21.9, 21.6, 1.4,
21.5; HRMS m/z: calcd for C18H27NO4S2Naþ[MþNaþ]: 408.1279;
found: 408.1281.
4.4.3. Methyl-3-(((1S*,3R*,4R*,6R*)-1,6-dimethyl-4-((4-
methylphenyl)sulfonamido)-7-oxabicyclo
[4.1.0]heptan-3-yl)thio)
propanoate 16c. Colorless liquid; Rf¼0.40 (EtOAc/hexane, 3:7);
Yield: 0.159 g, 77%; IR (neat) nmax: 3264, 1735, 1438, 1330, 1160,
4.3.14. N,N0-((1R*,10R*,2R*,20R*)-Disulfanediylbis(cyclohexane-2,1-
diyl))bis(4-methylbenzene sulfonamide) 13g. Colorless solid;
Rf¼0.60 (EtOAc/hexane, 3:7); Yield: 0.097 g, 68%; mp: 160 ꢀC; IR
1091, 906, 815, 663 cmꢂ1 1H NMR (300 MHz, CDCl3):
; d 7.77 (d,
J¼8.1 Hz, 2H), 7.31 (d, J¼8.1 Hz, 2H), 5.35 (d, J¼3.6 Hz, 1H), 3.70 (s,
3H), 3.05e2.96 (m, 1H), 2.73 (dd, J¼15.0, 4.8 Hz, 1H), 2.56e2.47 (m,
2H), 2.42 (s, 3H), 2.41e2.38 (m, 2H), 2.99e2.25 (m, 1H), 2.26 (dd,
J¼15.3, 6.9 Hz, 1H), 2.08 (dd, J¼15.3, 10.5 Hz, 1H), 1.73 (dd, J¼15.0,
(neat) nmax: 3289, 1323, 1157, 811, 664 cmꢂ1 1H NMR (300 MHz,
;
CDCl3, 1: 1 mixture of diastereomers):
d
7.78 (d, J¼8.1 Hz, 2H), 7.31
(d, J¼8.1 Hz, 2H), 5.36 (d, J¼6.9 Hz, 1H), 3.49e3.47 (m, 1H),
2.73e2.68 (m, 1H), 2.43 (s, 3H), 2.13e2.09 (m, 1H), 1.69e1.68 (m,
1H), 1.66e1.56 (m, 2H), 1.40e1.19 (m, 4H); 13C NMR (75 MHz, CDCl3,
9.9 Hz, 1H), 1.26 (s, 6H); 13C NMR (75 MHz, CDCl3):
d 171.9, 143.6,
136.5, 129.7, 127.2, 62.6, 61.4, 51.9, 50.4, 44.9, 39.0, 37.4, 34.2, 24.0,
21.5, 20.4, 19.2; HRMS m/z: calcd for C19H27NO5S2Naþ[MþNaþ]:
436.1228; found: 436.1230.
1:1 mixture of diastereomers): d 143.3,138.3,129.7,127.0, 56.8, 55.7,
33.3, 32.3, 25.0, 23.9, 21.6; HRMS m/z: calcd for
C
26H36N2O4S4Naþ[MþNaþ]: 591.1456; found: 591.1462.
4.4.4. Methyl-3-(((3aS*,5R*,6R*,7aR*)-6-((4-methylphenyl)sulfona-
mido)hexahydro-1H-3a,7a-epoxyinden-5-yl)thio)propanoate
16d. Colorless liquid; Rf¼0.50 (EtOAc/hexane, 3:7); Yield: 0.149 g,
70%; IR (neat) nmax: 3265, 1737, 1436, 1333, 1160, 1091, 664 cmꢂ1; 1H
4.3.15. N-((1R*,2R*)-2-Mercaptocyclohexyl)-4-methylbenzene-
sulfonamide 13h0. Colorless slid; Rf¼0.75 (EtOAc/hexane, 3:7);
Please cite this article in press as: Sureshkumar, D.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.04.003

14
D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
NMR (300 MHz, CDCl3):
d
7.78 (d, J¼8.1 Hz, 2H), 7.32 (d, J¼8.1 Hz,
J¼6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 211.1, 143.1, 140.4, 129.6,
126.7, 56.0, 49.7, 43.5, 41.7, 40.5, 33.5, 31.7, 23.9, 21.5, 12.8; HRMS m/
2H), 5.52 (d, J¼3.9 Hz, 1H), 3.70 (s, 3H), 3.15e3.08 (m, 1H), 2.79 (dd,
J¼14.7, 4.8 Hz, 1H), 2.61e2.51 (m, 2H), 2.43 (s, 3H), 2.37e2.29 (m,
4H), 2.15 (dd, J¼15.0, 9.3 Hz,1H),1.97e1.86 (m, 2H),1.75 (dd, J¼15.0,
z: calcd for C17H23NO3S2[MþNaþ]: 376.1017; found: 376.1030.
8.7 Hz, 1H), 1.56e1.32 (m, 4H); 13C NMR (75 MHz, CDCl3):
d
171.9,
4.5.4. N-((1S,4S,5R,8R)-4,8-Dimethyl-7-oxo-2-thiabicyclo[3.3.1]
143.6, 136.5, 129.7, 127.2, 67.1, 66.2, 51.8, 50.6, 44.7, 34.1, 33.8, 32.6,
nonan-4-yl)-4-methylbenzenesulfon-amide
enant-18b. Colorless
31.3, 30.9, 24.7, 21.5, 19.7; HRMS m/z: calcd for
C
solid; Rf¼0.40 (EtOAc/hexanes, 3:7); Yield: 0.077 g, 44%; mp:
20H27NO5S2Naþ[MþNaþ]: 448.1228; found: 448.1248.
225 ꢀC; ½a 2D7
ꢄ
ꢂ138.00 (c¼1.0, CHCl3); IR (neat) nmax: 3255, 1690,
1437, 1329, 1156, 1092, 816, 666 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
4.4.5. Methyl-3-(((2R*,3R*,4aR*,8aS*)-3-((4-methylphenyl)sulfona-
mido)octahydro-4a,8a-epoxy naphthalen-2-yl)thio)propanoate
d
7.75 (d, J¼8.1 Hz, 2H), 7.29 (d, J¼8.1 Hz, 2H), 4.83 (s, 1H),
2.99e2.84 (m, 2H), 2.72e2.38 (m, 5H), 2.42 (s, 3H), 2.31 (td, J¼14.4,
3.6 Hz, 1H), 2.06 (d, J¼14.4 Hz, 1H), 1.60 (s, 3H), 1.19 (d, J¼6.6 Hz,
16e. Colorless liquid; Rf¼0.50 (EtOAc/hexanes, 3:7); Yield: 0.158 g,
72%; IR (neat) nmax: 3269, 2934, 1737, 1437, 1328, 1159, 1092,
3H); 13C NMR (75 MHz, CDCl3):
d 211.3, 143.3, 129.7, 126.8, 58.9,
664 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.77 (d, J¼8.4 Hz, 2H), 7.31
50.0, 42.6, 41.9, 41.4, 32.9, 31.5, 23.0, 21.5, 12.6; HRMS m/z: calcd for
C
(d, J¼8.4 Hz, 2H), 5.22 (d, J¼3.0 Hz, 1H), 3.71 (s, 3H), 3.10e2.96 (m,
1H), 2.79 (dd, J¼14.7, 4.5 Hz, 1H), 2.57 (dd, J¼11.1, 6.9 Hz, 1H),
2.51e2.44 (m, 2H), 2.42 (s, 3H), 2.40e2.37 (m, 2H), 2.26e2.03 (m,
3H), 1.93e1.63 (m, 4H), 1.57 -1.19 (m, 4H); 13C NMR (75 MHz,
17H23NO3S2[MþNaþ]: 376.1017; found: 376.1025.
4.5.5. N-((1S,4R,5R,8R)-8-Formyl-4-methyl-7-oxo-2-thiabicyclo
[3.3.1]nonan-4-yl)-4-methyl-benzene sulfonamide 20a and N-
((1S,4S,5R,8R)-8-formyl-4-methyl-7-oxo-2-thiabicyclo[3.3.1] nonan-
4-yl)-4-methylbenzenesulfonamide 20b. Colorless liquid; Rf¼0.50
(EtOAc/hexanes, 3:7); Yield: 0.138 g, 81%; IR (neat) nmax: 3277, 1723,
CDCl3):
d 171.8, 143.7, 136.3, 129.7, 127.3, 62.7, 61.4, 51.9, 50.0, 45.0,
38.8, 37.4, 34.2, 30.8, 28.9, 23.7, 21.5, 20.3, 19.6; HRMS m/z: calcd for
C
21H29NO5S2Naþ[MþNaþ]: 462.1385; found: 462.1382.
1321, 1155, 1092, 980, 815, 735, 663 cmꢂ1
CDCl3,1:1 mixture of diastereomers):
;
1H NMR (300 MHz,
d 9.64 (s,1H), 9.61 (s,1H), 7.77
4.5. Synthesis of thia-bicyclononane derivatives 18a and 18b
(d, J¼8.1 Hz, 4H), 7.29 (d, J¼8.1 Hz, 4H), 5.63 (s, 1H), 5.01 (s, 1H),
3.21e3.02 (m, 4H), 2.77e2.61 (m, 4H), 2.43 (s, 3H), 2.42 (s, 3H),
2.33e2.24 (m, 2H), 2.09e1.51 (m, 14H), 1.31 (s, 6H); 13C NMR
Tetrathiomolybdate 1 (0.670, 1.00 mmol) was added to a well-
stirred solution of aziridine 17 (0.160 g, 0.50 mmol) in CH3CN
(3 mL) and it was stirred at room temperature (28 ꢀC) for 3 h. The
solvent was evaporated under reduced pressure, the black residue
was extracted with CH2Cl2:Et2O (1:5, 3ꢃ 10 mL) and filtered
through a Celite pad. The filtrate was concentrated and the residue
was purified by flash column chromatography on silica gel to give
thia-bicyclononane derivatives 18a and 18b as white solids.
(75 MHz, CDCl3, 1:1 mixture of diastereomers):
d 203.3, 202.9,
143.2, 142.9, 140.5, 140.4, 129.6, 129.5, 126.8, 126.7, 58.6, 56.4, 54.6,
54.5, 38.6, 36.9,36.4, 35.6, 32.4, 32.3, 32.2, 31.0, 24.9, 24.5, 24.4, 24.2,
21.5, 21.4, 20.3; HRMS m/z: calcd for C17H23NO3S2Naþ[MþNaþ]:
376.1017; found: 376.1028.
4.6. Synthesis of ethyl-(E)-4-(1-tosylaziridin-2-yl)but-2-
4.5.1. N-((1R,4S,5S,8S)-4,8-Dimethyl-7-oxo-2-thiabicyclo[3.3.1]
enoate 23
nonan-4-yl)-4-methylbenzenesulfon-amide 18a. Colorless solid;
27
Rf¼0.40 (EtOAc/hexanes, 3:7); Yield: 0.077 g, 44%; mp: 174 ꢀC; [
a
]
To a stirred solution of oxalyl chloride (0.26 mL, 3.0 mmol) in dry
CH2Cl2 (20 mL) at ꢂ78 ꢀC under argon was added drop wise a so-
lution of DMSO (0.71 mL, 10.0 mmol) in dry CH2Cl2 (2 mL). After
20 min, a solution of the aziridino-alcohol 22 (0.482 g, 2.0 mmol) in
CH2Cl2 (2 mL) was added to the above reagent at ꢂ78 ꢀC, and the
mixture was stirred for 30 min when diisopropylethylamine
(0.7 mL, 40 mmol) was added drop wise to the above solution at
ꢂ78 ꢀC, and the mixture was stirred for 0.5 h at that temperature.
(Ethoxycarbonymethylene)triphenylphosphate (1.34 g, 4 mmol)
was added to the mixture at ꢂ78 ꢀC, and the mixture was stirred for
2 h during, which time it was allowed to warm to 0. ꢀC. The mixture
was extracted with Et2O and the extract was washed successively
with water, 10% aqueous citric acid, water, saturated aqueous
NaHCO3 and water, and dried over MgSO4. After concentration
under reduced pressure an oily residue was isolated, which was
flash chromatographed on silica gel, eluting with hexanes-EtOAc
(3:1) to give the trans-ester 23 (383 mg, 62%) as colorless oil. The
cis-isomer of 23 could not be isolated in a pure state due to its in-
stability. Colorless liquid; Rf¼0.60 (EtOAc/hexanes, 3:7); IR (neat)
nmax: 1730, 1724, 1661, 1582, 1326, 1162, 1042, 951, 832, 712, 670,
D
þ97.00 (c¼1.0, CHCl3); IR (neat) nmax: 3284, 1706, 1420, 1316, 1152,
1018, 667 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.76 (d, J¼8.4 Hz, 2H),
7.28 (d, J¼8.4 Hz, 2H), 5.82 (s, 1H), 2.97 (br s, 1H), 2.86 (br s, 2H),
2.71 (m, 1H), 2.58 (s, 1H), 2.54 (d, J¼5.0 Hz, 2H), 2.41 (s, 3H), 2.23
(td, J¼7.2, 3.3 Hz, 1H), 1.96 (d, J¼15.0 Hz, 1H), 1.24 (s, 3H), 1.23 (d,
J¼6.0Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 211.1, 143.2, 140.2, 129.3,
126.9, 56.1, 49.6, 43.5, 41.8, 40.6, 33.6, 31.6, 23.8, 21.4, 12.8; HRMS
m/z: calcd for
C
17H23 NO3S2Naþ[MþNaþ]: 376.1017, found:
376.1033.
4.5.2. N-((1R,4R,5S,8S)-4,8-Dimethyl-7-oxo-2-thiabicyclo[3.3.1]
nonan-4-yl)-4-methylbenzenesulfon-amide 18b. Colorless solid;
Rf¼0.30 (EtOAc/hexanes, 3:7); Yield: 0.078 g, 44%; mp: 223 ꢀC; ½a D27
ꢄ
þ137.00 (c¼1.0, CHCl3); IR (neat) nmax: 3274, 1704, 1332, 1159, 1091,
909, 815, 732, 663 cmꢂ1 1H NMR (300 MHz, CDCl3):
; d 7.74 (d,
J¼8.4 Hz, 2H), 7.29 (d, J¼8.4 Hz, 2H), 4.74 (s, 1H), 2.92 (m, 2H),
2.71e2.45 (m, 5H), 2.42 (s, 3H), 2.31 (td, J¼13.8, 3.6 Hz, 1H), 2.05 (d,
J¼13.8 Hz,1H), 1.64 (s, 3H), 1.19 (d, J¼6.6 Hz, 3H); 13C NMR (75 MHz,
CDCl3):
d 211.1, 143.3, 140.1, 129.6, 126.8, 58.9, 50.0, 42.6, 41.9, 41.4,
32.9, 31.5, 22.9, 21.5, 12.6; HRMS m/z: calcd for
651 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.81 (d, J¼8.4 Hz, 2H), 7.34
C
17H23NO3S2Naþ[MþNaþ]: 376.1017; found: 376.1030.
(d, J¼8.4 Hz, 2H), 6.67 (td, J¼15.6, 6.2 Hz, 1H), 5.82 (td, J¼15.6,
1.5 Hz, 1H), 4.16 (q, J¼7.2 Hz, 2H), 2.86e2.79 (m, 1H), 2.69 (d,
J¼6.6 Hz, 1H), 2.45 (s, 3H), 2.35e2.17 (m, 2H), 2.12 (d, J¼4.5 Hz, 1H),
4.5.3. N-((1S,4R,5R,8R)-4,8-Dimethyl-7-oxo-2-thiabicyclo[3.3.1]
nonan-4-yl)-4-methylbenzenesulfon-amide enant-18a. Colorless
1.28 (t, J¼7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 165.7, 144.7,
solid; Rf¼0.50 (EtOAc/hexanes, 3:7); Yield: 0.078 g, 44%; mp:
142.3, 129.7, 127.9, 127.4, 123.9, 60.3, 38.0, 33.5, 32.9, 21.6, 14.2;
HRMS m/z: calcd for C15H19NO4SNaþ[MþNaþ]: 332.0932; found:
332.0939.
176 ꢀC; ½a 2D7
ꢄ
ꢂ96.00 (c¼1.0, CHCl3); IR (neat) nmax: 3289, 1705, 1316,
1154, 1092, 818, 665 cmꢂ1
;
1H NMR (300 MHz, CDCl3):
d
7.77 (d,
J¼8.1 Hz, 2H), 7.28 (d, J¼8.1 Hz, 2H), 5.83 (s, 1H), 2.99e2.97 (m, 1H),
2.92e2.86 (m, 2H), 2.76e2.67 (m, 1H), 2.58e2.53 (m, 3H), 2.42 (s,
3H), 2.27e2.19 (m, 1H), 1.97 (d, J¼15.0 Hz, 1H), 1.24 (s, 3H), 1.23 (d,
4.6.1. Ethyl-(E)-4-(2-methyl-1-tosylaziridin-2-yl)but-2-enoate
27. Colorless liquid; Rf¼0.60 (EtOAc/hexanes, 3:7); Yield: 0.388 g,
Please cite this article in press as: Sureshkumar, D.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.04.003

D. Sureshkumar et al. / Tetrahedron xxx (2015) 1e15
15
60%; IR (neat) nmax: 1722, 1715, 1656, 1597, 1324, 1159, 1038, 946,
830, 709, 669, 647 cmꢂ1 1H NMR (300 MHz, CDCl3):
7.83 (d,
References and notes
;
d
1. (a) Domling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168e3210 and refer-
ences cited therein; (b) Zhu, A.; Bienayme, H.; Domling, A. Multicomponent
J¼8.4 Hz, 2H), 7.32 (d, J¼8.4 Hz, 2H), 6.90e6.80 (m, 1H), 5.91 (d,
J¼15.3 Hz, 1H), 4.19 (q, J¼7.2 Hz, 2H), 2.61 (s, 1H), 2.59 (dd, J¼13.5,
7.5 Hz, 2H), 2.43 (s, 3H), 2.36 (s, 1H), 1.63 (s, 3H), 1.29 (t, J¼7.2 Hz,
€
Reactions; Wiley-VCH: Weinheim, Germany, 2005; pp 76e94.
2. (a) Kamimura, A.; Mitsudera, H.; Asano, S.; Kidera, S.; Kakehi, A. J. Org. Chem.
1999, 64, 6353e6360; (b) Miyata, O.; Shinada, T.; Ninomiya, I.; Naito, T.; Date,
T.; Okamura, K.; Inagaki, S. J. Org. Chem. 1991, 56, 6556e6564; (c) Clauss, R.;
Hinz, W.; Hunter, R. Synlett 1997, 57e58.
3H); 13C NMR (75 MHz, CDCl3):
d 165.8, 143.9, 142.7, 137.3, 129.4,
127.2, 124.6, 60.2, 48.6, 40.1, 40.0, 21.4, 18.8, 14.1; HRMS m/z: calcd
for C16H21NO4SNaþ[MþNaþ]: 346.1089; found: 346.1096.
3. Sureshkumar, D.; Koutha, S.; Chandrasekaran, S. J. Am. Chem. Soc. 2005, 127,
12760e12761.
4. Sureshkumar, D.; Gunasundari, T.; Ganesh, V.; Chandrasekaran, S. J. Org. Chem.
2007, 72, 2106e2117.
5. Sureshkumar, D.; Ganesh, V.; Vidyarini, R. S.; Chandrasekaran, S. J. Org. Chem.
2009, 74, 7958e7961.
4.7. General procedure for synthesis of tetrahydrothiophane
derivatives
6. Prabhu, K. R.; Devan, N.; Chandrasekaran, S. Synlett 2002, 1762e1778.
7. (a) Pan, W. H.; Harmer, M. A.; Halbert, T. R.; Stiefel, E. I. J. Am. Chem. Soc. 1984,
106, 459e460; (b) Coyle, C. L.; Harmer, M. A.; George, G. N.; Daage, M.; Stiefel,
E. I. Inorg. Chem. 1990, 29, 14e19 and references therein; (c) Prabhu, K. R.; Si-
vanand, P.; Chandrasekaran, S. Angew. Chem., Int. Ed. 2000, 39, 4316e4319; (d)
Sridhar, P. R.; Prabhu, K. R.; Sivanand, P.; Chandrasekaran, S. Eur. J. Org. Chem.
2004, 4809e4815.
8. (a) Berry, M. B.; Craig, D. Synlett 1992, 41e44; (b) Bieber, L. W.; De Araujo, M. C.
F. Molecules 2002, 7, 902e906.
9. (a) Methods in Carbohydrate Chemistry; Academic: New York, NY, 1963, Vol. II,
pp 190e205; (b) Atsushi, E.; Toshiyuki, K.; Tohru, F. Synlett 1999, 7, 1103e1105.
10. Mao, H.; Joly, G. J.; Peters, K.; Hoornaert, G. J.; Compernolle, F. Tetrahedron 2001,
57, 6955e6967.
11. Stamm, H.; Assithianakis, P.; Buchholz, B.; Weib, R. Tetrahedron Lett. 1982, 23,
5021e5024.
12. Iwamoto, K.; Kajima, M.; Chatani, N.; Murai, S. J. Org. Chem. 2001, 66, 169e174.
13. Jeong, J. U.; Tao, B.; Sagasser, I.; Henniges, H.; Sharpless, K. B. J. Am. Chem. Soc.
1998, 120, 6844e6845.
14. (a) Kruhlak, N. L.; Wang, M.; Boorman, P. M.; Parvez, M. Inorg. Chem. 2001, 40,
3141e3148; (b) Boorman, P. M.; Wang, M.; Parvez, M. J. Chem. Soc., Chem.
Commun. 1995, 999e1000.
Tetrathiomolybdate 1 (0.670, 1.00 mmol) was added to a well-
stirred solution of aziridine 23/27 (0.50 mmol) in CH3CN (3 mL)
and it was stirred at room temperature (28 ꢀC) for 5e6 h. The
solvent was evaporated under reduced pressure, the black residue
was extracted with CH2Cl2:Et2O (1:5, 3ꢃ 10 mL) and filtered
through a Celite pad. The filtrate was concentrated and the residue
was purified by flash column chromatography on silica gel to give
tetrahydrothiophane derivatives in good yields.
4.7.1. Ethyl-2-((2S*,4S*)-4-((4-methylphenyl)sulfonamido)tetrahy-
drothiophen-2-yl)acetate 24. Colorless liquid; Rf¼0.40 (EtOAc/hex-
ane, 3:7); Yield: 0.113 g, 66%; IR (neat) nmax: 3266, 1731, 1330, 1159,
1093, 815, 665 cmꢂ1; 1H NMR (300 MHz, CDCl3):
d
7.77 (d, J¼8.4 Hz,
2H), 7.32 (d, J¼8.4 Hz, 2H), 5.02 (d, J¼8.1 Hz, 1H), 4.12 (q, J¼7.2 Hz,
2H), 3.94 (m, 1H), 3.71e3.58 (m, 1H), 2.88 (dd, J¼11.1, 6.3 Hz, 1H),
2.68e2.52 (m, 3H), 2.44 (s, 3H), 2.42e2.31 (m, 1H), 1.59e1.49 (m,
15. The structure was solved by direct methods (SIR92). Refinement was by full-
1H), 2.42 (t, J¼6.9 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 171.2, 143.8,
matrix least-squares procedures on F2 by using SHELXL-97. CCDC No. 631953.
Crystal system: Orthorhombic, space group: P212121, cell parameters: a¼6.
137.2, 129.9, 127.0, 60.7, 57.0, 41.9, 41.8, 39.5, 36.8, 21.5, 14.1; HRMS
ꢀ
219(2), b¼11.053(3), c¼21.344(6) A,
a
¼90.00ꢀ,
b
m
¼90.00ꢀ,
g
¼90.00ꢀ, V¼1467.
m/z: calcd for
366.0825.
C
15H21NO4S2Naþ[MþNaþ]: 366.0810; found:
17(7) A , Z¼4, rcalcd¼1.29 g cmꢂ3, F(000)¼608,
¼0.36 mmꢂ1
,
l
¼0.71073 A.
3
ꢀ
ꢀ
Total number l.s. parameters¼172. R1¼0.052 for 2586 Fo>4
s(Fo) and 0.061 for
all 10609 data. wR2¼0.126, GOF¼1.075, restrained GOF¼1.075 for all data.
16. Sureshkumar, D.; Maity, S.; Chandrasekaran, S. J. Org. Chem. 2006, 71,
1653e1657.
4.7.2. Ethyl-2-((2R*,4S*)-4-methyl-4-((4-methylphenyl)sulfonamido)
tetrahydrothiophen-2-yl)acetate 28a and ethyl-2-((2S*,4S*)-4-
methyl-4-((4-methylphenyl)sulfonamido)tetrahydrothiophen-2-yl)
acetate 28b. Colorless liquid; Rf¼0.40 (EtOAc/hexane, 3:7); Yield:
0.121 g, 68%; IR (neat) nmax: 3273, 1731, 1328, 1157, 1093, 1022, 815,
17. (a) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 23, 1973e1976;
(b) VanRheenen, V.; Cha, D. Y.; Hartley, W. M. Organic SynthesisCollect. Vol. 6;
Wiley: New York, NY, 1988, Collect. Vol. 6, pp 342e347; (c) Maras, A.; Secen, H.;
Sutbeyaz, Y.; Balci, M. J. Org. Chem. 1998, 63, 2039e2041; (d) Mehta, G.; Ramesh,
S. S.; Bera, M. K. Chem.dEur. J. 2003, 9, 2264e2272.
667 cmꢂ1
;
1H NMR (300 MHz, CDCl3, 1:1 mixture of di-
18. The structure was solved by direct methods (SIR92). Refinement was by full-
matrix least-squares procedures on F2 by using SHELXL-97. CCDC No. 631953.
astereomers):
d
7.79 (d, J¼8.4 Hz, 2H), 7.29 (d, J¼8.4 Hz, 2H), 5.53 (s,
Crystal system: Orthorhombic, space group: P21, cell parameters: a¼10.879(8),
3
1H), 5.38 (s, 1H), 4.17e4.09 (m, 2H), 3.78e3.54 (m, 1H), 3.01 (d,
J¼10.5 Hz, 1H), 2.86e2.50 (m, 3H), 2.43 (s, 3H), 2.17 (dd, J¼12.9,
6.9 Hz,1H),1.90e1.83 (m,1H),1.28e1.22 (m, 3H); 13C NMR (75 MHz,
ꢀ
ꢀ
ꢀ
b¼6.214(4), c¼13.814(9) A,
a
¼90.00ꢀ,
b
¼106.64(1)ꢀ,
g
¼90.00 , V¼894.7(3) A ,
Z¼2, rcalcd¼1.31 g cmꢂ3, F(000)¼376,
m
¼0.31 mmꢂ1
¼0.71073 A. Total number
,
l
ꢀ
l.s. parameters¼208. R1¼0.031 for 3145 Fo>4
a(Fo) and 0.032 for all 6441 data.
wR2¼0.085, GOF¼1.132, restrained GOF¼1.132 for all data.
CDCl3, 1:1 mixture of diastereomers):
d 171.4, 171.2, 143.3, 143.2,
19. (a) Ney, J. E.; Wolfe, J. P. J. Am. Chem. Soc. 2006, 128, 15415e15422; (b) Ibuka, T.;
Nakai, K.; Habashita, H.; Hotta, Y.; Fujii, N.; Mimura, N.; Miwa, Y.; Taga, T.;
Yamamoto, Y. Angew. Chem., Int. Ed. Engl. 1994, 33, 652e654.
139.8, 139.7, 129.6, 129.5, 126.9, 126.8, 67.1, 65.3, 60.7, 48.4, 47.7,
44.5, 420.7, 41.7, 41.6, 41.5, 39.8, 23.8, 23.7, 21.5, 14.1; HRMS m/z:
calcd for C16H23NO4S2Naþ[MþNaþ]: 380.0966; found: 380.0977.
20. Fujii, N.; Nakai, K.; Tamamura, H.; Otaka, A.; Mimura, N.; Miwa, Y.; Taga, T.;
Yamamoto, Y.; Ibuka, T. J. Chem. Soc., Perkin Trans. 1 1995, 1359e1371.
21. Ren, X. F.; Turos, E.; Lake, C. H.; Churchill, M. R. J. Org. Chem. 1995, 60,
6468e6483.
Acknowledgements
22. The structure was solved by direct methods (SIR92). Refinement was by full-
matrix least-squares procedures on F2 by using SHELXL-97. CCDC No. 631953.
Crystal system: Orthorhombic, space group: P212121, cell parameters: a¼7.
We thank the Department of Science and Technology, New Delhi
for financial support of this investigation and the award of a SERB
Distinguished Fellowship to SCN. TG thanks JNCASR, Jakkur for
support in the form of a postdoctoral fellowship.
¼90.00ꢀ,
b
¼90.00ꢀ,
g
¼90.00ꢀ, V¼1673.5(2)
ꢀ
061(5), b¼8.740(6), c¼27.116(1) A,
a
3
A , Z¼4, rcalcd¼1.36 g cmꢂ3, F(000)¼728,
m
¼0.33 mmꢂ1
,
l
¼0.71073 A. Total
ꢀ
ꢀ
number l.s. parameters¼201. R1¼0.124 for 2962 Fo>
4a(Fo) and 0.0.148 for all
11803 data. wR2¼0.27, GOF¼1.256, restrained GOF¼1.256 for all data.
Please cite this article in press as: Sureshkumar, D.; et al., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.04.003