Facile synthesis of various substituted taurines, especially syn- and anti-1,2-disubstituted taurines, from nitroolefins

Article abstract of DOI:10.1016/j.tet.2012.01.031

Taurine and substituted taurines present a group of important structural elements in many natural products. Various substituted taurines, including 1- and 2-substituted, 1,1-, syn-1,2-, and anti-1,2-disubstituted taurines, were synthesized from the corresponding nitroolefins via Michael addition with thioacetic acid, oxidation with peroxyformic acid, and the catalytic hydrogenation under the catalysis of palladium on carbon or platinum dioxide. It is a general, versatile, and salt-free method for the preparation of substituted taurines, especially for syn- and anti-1,2-disubstituted taurines and some taurines with more bulky substituents. The stereostructures of both syn- and anti-1,2-disubstituted taurines were deduced from the nitroalkyl thioacetates in the Michael addition, which were identified via the Karplus equation analysis and computational analysis, and finally confirmed by the XRD single crystal analysis. The diastereoselectivity in the Michael addition was rationalized with the Cram rule.

Full text of DOI:10.1016/j.tet.2012.01.031

Tetrahedron 68 (2012) 2513e2522
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Facile synthesis of various substituted taurines, especially
syn- and anti-1,2-disubstituted taurines, from nitroolefins
*
Ning Chen, Jiaxi Xu
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing 100029, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Taurine and substituted taurines present a group of important structural elements in many natural
products. Various substituted taurines, including 1- and 2-substituted, 1,1-, syn-1,2-, and anti-1,2-
disubstituted taurines, were synthesized from the corresponding nitroolefins via Michael addition
with thioacetic acid, oxidation with peroxyformic acid, and the catalytic hydrogenation under the ca-
talysis of palladium on carbon or platinum dioxide. It is a general, versatile, and salt-free method for the
preparation of substituted taurines, especially for syn- and anti-1,2-disubstituted taurines and some
taurines with more bulky substituents. The stereostructures of both syn- and anti-1,2-disubstituted
taurines were deduced from the nitroalkyl thioacetates in the Michael addition, which were identified
via the Karplus equation analysis and computational analysis, and finally confirmed by the XRD single
crystal analysis. The diastereoselectivity in the Michael addition was rationalized with the Cram rule.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 21 November 2011
Received in revised form 30 December 2011
Accepted 13 January 2012
Available online 28 January 2012
Keywords:
Taurine
2-Aminoalkanesulfonic acid
Nitroolefin
Nitroalkylthioacetate
Diastereoselectivity
1. Introduction
acid (ASPA) and cysteic acid (CA) (Fig. 1), as representatives
of 1-substituted and 2-substituted taurines, show some anti-
As very important sulfur-containing analogs of amino carboxylic
acids, aminoalkanesulfonic acids, especially taurines and their de-
rivatives,1 have been found in many mammals, marine algae, fishes,
and shellfishes.2 Taurine, the simplest 2-aminoalkanesulfonic acid,
was first isolated from ox bile.3 However, for the next century and
a half, it was labeled as non-essential, biologically inert, and the end
product of sulfur metabolism.4 During recent half century, taurine
has been rediscovered and its beneficial effects in processes like
epilepsy, hypertension, congestive heart failure, and diabetes have
been well-documented.4 Besides these discoveries, substituted tau-
rines that are taurine analogs attracted more and more attention in
their biological actions and potential therapeutic applications.4,5 For
example, some cyclic analogs, trans-2-aminocyclopentanesulfonic
acid (TAPS) and piperidine-3-sulfonic acid (PSA) show different ef-
fects on ATP-dependent calcium ion uptake,6 while cis-2-
aminocyclohexanesulfonic acid (CAHS) and trans-2-amino-
cyclohexanesulfonic acid (TAHS) have the thermoregulation ability
via interaction with the central serotonergic system7 (Fig. 1). As an N-
substituted taurine derivative, phthalimidoethanesulfonamide
(PIESA), which was found in the cerebral spinal fluid, is very effective
against maximal electroshock seizure and pentylentetrazole seizure
threshold (PST) test in mice (Fig. 1). 3-Amino-2-sulfopropionic
inflammatory activity.4
A number of taurine derivatives have been found in natural
products to date. For example, (þ)-agelasidine C (Fig. 2), which was
isolated from Agelas nakamurai, is antimicrobial that inhibits
smooth muscle contraction and enzyme activity of Naþ/Kþ.8 Its
analogs (ꢀ)-agelasidines C and D, isolated from the Caribbean sea
sponge Agelas clathrodes, also show similar antimicrobial func-
tions.9 2-Substituted taurine derivatives have also been found as
moieties in some natural products. Flavocristamides A and B were
obtained from the marine bacterium Flavobacterium sp. that was
isolated from the marine bivalve Cristaria plicata,10 and 2-amino-3-
[5-deoxy-5-(dimethylarsinoyl)-b-D-ribofuranosyloxy]-propene-1-
sulfonic acid (I) was isolated from Sargassum lacerifolium.11 Taurine
H2
+
+
-
+
NH3
NH3
NH3
N
-
-
SO3
SO3
CAHS
SO3
-
SO3
TAPS
PSA
TAHS
O
COOH
SO3H
ASPA
H2N
O
S
NH2
N
SO3H
COOH
CA
H2N
O
O
PIESA
* Corresponding author. Tel./fax: þ86 10 64435565; e-mail address: jxxu@
mail.buct.edu.cn (J. Xu).
Fig. 1. Taurine derivatives.
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.01.031

2514
N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
products would be obtained. Enders and co-workers used ethyl b-
aminoalkanesulfonates (2-substituted taurine derivatives) as sub-
strates to react with haloalkanes in the presence of lithium diiso-
R
H
N
NH2
NH
S
propylamide (LDA), giving the
a-alkylation products (1,2-
O
O
disubstituted taurine derivatives).18b Enders’ group has also syn-
thesized some protected 1,2-disubstituted taurine derivatives from
(+)-agelasidine C, R = H
(-)-agelasidine C, R = H
sulfonates and a
-amino sulfones.27 1,2-Disubstituted taurines were
(-)-agelasidine D, R = OH
also prepared from the ring-opening of 3,4-disubstituted
b-sul-
O
OH
5
tams28 derived from [2þ2] cycloaddition of sulfonyl chlorides with
O
As
(CH2)10
imines29 and an intramolecular cyclization of N-substituted
a-
HN
O
SO3H
hydroxyalkanesulfonamides.30 Although several methods for
preparation of 1,2-disubstituted taurines have been reported, the
general and efficient synthetic methods are still in demand, espe-
cially for 1,2-disubstituted taurines with different 1,2-substituents
and configurations. Herein, we report a versatile and salt-free
method for the preparation of various substituted taurines, espe-
cially syn- and anti-1,2-disubstituted taurines.
O
4
NH2
HO3S
(CH2)8
OH OH
OH
I
flavocristamide A: 4,5-ene
flavocristamide B: 4,5-ane
H
N
CONH2
SO3H
O
O
O
O
O
H
N
H
H
N
N
N
H
N
H
N
H
N
Ph
NH
2. Results and discussion
2.1. Synthesis
N
O
O
O
O
O
O
R1
CHO
O
O
H
N
OH
O
HN
O
N
H
NH
CONH2
N
R2
HN
NH2
b
-Substituted and
b,b-disubstituted nitroolefins were prepared
according to our reported method.25a
a
-Substituted nitroolefins
Halicylindramides
were synthesized from paraformaldehyde and nitroalkanes.31
Paraformaldehyde reacted with nitroalkanes to generate vicinal
nitroalkyl alcohols, which were dehydrated with phthalic anhy-
II R1 = H, R2 = Me
III
Br
R
1 = Me, R2 = H
R
IV
1 = Me, R2 = Me
NH2
O
N
dride to afford a-substituted nitroolefins in good yields. Sodium
HO3S
N
N
sulfite and sodium ethylxanthate have been used as sulfur nucle-
ophiles in the Michael addition with nitroolefins.25 Herein, we tried
to use other sulfur nucleophiles as the Michael addition donors,
hoping to develop a general method for the preparation of various
substituted taurines, especially syn- and anti-1,2-disubstituted
taurines. Commercially available thiolacetic acid and potassium
N
N
NH
H
H
O
N
O
R
S
P
N
HO
5
X
O
O
O
O
O OH
R
OH
Tau-dAMP: R = H
L-Cys-dAMP: R = COOH
OH OH
m U: X = O
m s U: X = S
τ
τ
5
2
isocyanate were considered as the desired nucleophiles. Initially,
nitrostyrene (1a) was selected as a model substrate to react with
the sulfur nucleophiles. McCarthy and co-workers reported that
b-
Fig. 2. Taurine derivatives in natural products.
b
-
nitrostyrene (1a) reacted with thiolacetic acid in benzene to give
rise to S-2-nitro-1-phenylethyl thioacetate (2a) in 87% yield under
the catalysis of tributylamine.32 We repeated the reaction, and
found that the yield reached 98% because another 11% yield of 2a
can be obtained from the mother liquor (Table 1, entry 1). When the
solvent was changed to diethyl ether, 2a was also obtained in
a quantitative yield of 99% (Table 1, entry 2). However, when po-
tassium isocyanate was applied as a sulfur nucleophile, the corre-
sponding adduct was not observed in different solvents (Table 1,
entries 3e5).
derivatives also participate in the constitution of peptides. Hal-
icylindramides (IIeIV) are antifungal and cytotoxic depsipeptides
from Halichondria cylindrata.9a,b,12 Recently, some taurine uridine
derivatives, 5-taurinomethyluridine (
2-thiouridine (
m5s2U), were discovered in mammalian mito-
chondrial tRNAs.13 In addition, Tau-dAMP and
-Cys-dAMP were
s
m5U) and 5-taurinomethyl-
s
L
recently developed by Hedewijn and co-workers as potential sub-
strates for the HIV-1 reverse transcriptase.14
Several methods have already been developed for the prepara-
tion of substituted taurine derivatives. 2-Substituted taurines have
It was delighted to find that 2a was colorless crystals. Compared
with liquid product S-nitroalkyl xanthate from sodium ethyl-
xanthate,25a it is convenient to purify 2a via recrystallization, which
been synthesized from
aziridines,16 2-arylthiiranes,17
substituted thiazolidine-2-thiones,19 and terminal olefins.20 2,2-
b
-amino primary alcohols,15 2-substituted
a,b
-unsaturated sulfonates,18 4-
Table 1
Disubstituted taurines were obtained from b,b-disubstituted amino
Reaction of 2-nitro-1-phenylpropene (1a) with sulfur-containing nucleophiles
ethanols,15h,21 terminal olefins,20 aliphatic 2,2-disubstitued azir-
idines,22 and aromatic 2,2-disubstituted thiiranes.17 1-Substituted
O
O
taurines have been generated from b
-amino secondary alcohols,23
solvent
S
NO2
+
2-substituted aliphatic thirranes,17,24 and
b-substituted nitroolefins
Ph
HS
NO2
1a
Ph
and sodium ethylxanthate.25 1,1-Disubstituted taurines have been
yielded from aliphatic 2,2-disubstituted thiiranes,17,26 aromatic 2,2-
or KSCN
2a
disubstituted aziridines,22 and
b,b-disubstituted nitroolefins and
Entry
S-Nucleophile
Solvent
Product
Yielda (%)
sodium ethylxanthate.25
1
2
3
4
5
HSAc
HSAc
KSCN
KSCN
KSCN
PhH
Et2O
Acetone
DMF
AcOH
2a
2a
98
99
0
0
0
Some cyclic taurines, as a class of 1,2-disubhstituted taurines,
were prepared from the corresponding vicinal amino cyclic alco-
hols or cyclic alkenes.15h,16b,17,19,20,24,26 However, these methods can
only be applied in the preparation of 1,2-disubstituted taurines
with the same substituents, otherwise a regiomeric mixture of
a
Isolated yield

N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
2515
is an important skill to separate syn- and anti-nitroalkyl thio-
acetates for the following preparation of syn- and anti-1,2-
disubstituted taurines (for the discussions, vide post).
and reduced under hydrogenation to generate substituted taurines
4 in excellent yields in each of cases (Table 2, the last column,
entries 1e7).
The adduct S-2-nitro-1-phenylethyl thioacetate (2a) was then
oxidized with peroxyformic acid generated in situ from 98% formic
acid and 30% hydrogen peroxide, giving rise to 2-nitro-1-
phenylethanesulfonic acid (3a) in a quantitative yield of 98%. Fur-
ther hydrogenation of 3a under the catalysis of palladium on car-
bon powder afforded 2-amino-1-phenylethanesulfonic acid (4a) in
an excellent yield (90%) (Scheme 1).
2.1.2. Synthesis of 2-substituted taurines. The current method can
also be used in the synthesis of 2-substituted taurines with
a-
substituted nitroolefins as the starting materials. -Substituted
a
nitroolefins 1h,i reacted with thiolacetic acid to afford S-2-alkyl-2-
nitroethyl thioacetates 2h,i in excellent yields after distillation
under reduced pressure. Further oxidation and reduction gave rise
to 2-substituted taurines 4h,i in good yields (Scheme 2).
O
O
R3
R3
H2O2,
R3
HCO3H Pd/C H2
S
HSAc
S
HCOOH
99%
NO2
SH
97%
O3S
NO2
NH3
Ph
Ph
NO2
NO2
O
Ph
2
4
1
3 = Me, 75%
4i R3 = Et, 78%
1a
2a
-( )
3 = Me, 94%
2i R3 = Et, 89%
4h
R
2h
R
SO3H
SO3
Pd/C, H2 (g)
90%
Scheme 2. Synthesis of 2-substituted taurines.
NO2
NH3
Ph
3a
-( )
4a-( )
2.1.3. Synthesis of 1,2-disubstitued taurines. After successful syn-
thesis of 1- and 2-monosubstituted, and 1,1-disubstituted taurines,
we focused on the preparation of syn- and anti-1,2-disubstituted
Scheme 1. Synthesis of 2-phenyltaurine (4a) from thiolacetic acid and b-nitrostyrene (1a).
taurines with a,b-disubstituted nitroolefins as starting materials,
2.1.1. Synthesis of 1-substituted and 1,1-disubstituted taur-
ines. Inspired by the successful synthesis of 1-phenyltaurine (4a),
we expanded the method to other 1-substituted and 1,1-
disubstituted taurines (Table 2). From Table 2, it can be found
that all monosubstituted nitroolefins 1aec afforded the Michael
adducts in excellent yields (Table 2, entries 1e3). However, for di-
substituted nitroolefins 1deg, the yields decrease along with the
increase of the steric hindrance (Table 2, entries 4e7). Compared
with the Michael addition of nitroolefins with sodium O-ethyl
xanthate,25a the yields of adducts increased obviously due to the
less steric hindrance of the nucleophile thioacetate anion. Thus, the
thioacetate anion attacks nitroolefins favorably to produce the
adducts in higher yields. Especially, for the more steric nitroolefin
1f, it cannot react with sodium O-ethyl xanthate,25a while it reacted
with thiolacetic acid to give rise to the corresponding adduct in 41%
which were synthesized from the corresponding aldehydes and
nitroalkanes via the Henry reaction.33 We first synthesized 2-nitro-
1-phenylpropene (1j) from benzaldehyde and nitroethane. Sub-
jected to McCarthy’s conditions,31 1j reacted with thiolacetic acid
under the catalysis of tributylamine in benzene, affording colorless
crystals 2j in 83% yield with a diastereomeric ratio (dr) of 90:10 on
the basis of 1H NMR analysis. 15% Yield of 2j was further obtained
from the mother liquor, reaching a total yield of 98%. However, the
dr value of the combined product 2j dropped to 64:36 (Table 3,
entry 1), revealing that crystallization can enrich one of di-
astereomers as major products. Further optimization of the re-
action conditions, including temperature, solvent, and catalyst, was
carried out and the results are summarized in Table 3. Yields change
yield (Table 2, entry 6). Moreover, when b,b-diphenylnitroolefin 1g
Table 3
was applied in the reaction, the yield with thiolacetic acid (34%,
Table 2, entry 7) was notably greater than that with sodium O-
ethylalkylxanthate (5%),25a revealing that the nucleophilic ability of
thioacetate anion is stronger than that of the xanthate anion. Re-
sultant nitroalkylthiolacetates 2 were oxidized with performic acid
Optimization on the reaction of 2-nitro-1-phenylpropene (1a) and thiolacetic acid
SAc
SAc
NO2
AcSH
Ph
Ph
+
Ph
conditions
NO2
-anti-( )
NO2
-syn-( )
1j
2j
2j
Table 2
Entry
Reaction conditions
Yielda (%)
dra syn/anti
Synthesis of 1-substituted and 1,1-disubstituted taurines
Temp
Solv.
Cat.
Time (h)
1
2
3
4
5
6
7
8
20
0
80
0
0
0
0
0
0
0
ꢀ78
ꢀ78
ꢀ78
ꢀ35
20
PhH
PhH
PhH
CHCl3
Et2O
Bu3N
Bu3N
Bu3N
Bu3N
Bu3N
Bu3N
Bu3N
Et3N
DMAP
Bu3N
Bu3N
DMAP
DMAP
Bu3N
d
1
1
1
1
1
1
1
1
1
5
1
1
5
1
4
98
98
98
99
98
99
99
90
75
98
51
13
18
98
82
64:36b
68:32
48:52
72:28
55:45
50:50
60:40
60:40
55:45
63:37
71:29
66:34
65:35
71:29
75:25
THF
Entry
Nitroolefin 1
Thioacetate
Taurine
2 yielda (%)
4 yieldb (%)
CH2Cl2
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
AcOH
1
R1
R2
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
Ph
4-ClPh
i-Pr
Ph
Et
H
H
H
Me
Me
Me
Ph
97
97
98
94
71
41
34
90
93c
94
97
91
98
90
9
10
11
12
13
14
15c
t-BuCH2
Ph
1g
a
a
Yield and dr value were determined by 1H NMR.
After filtering, 87% of 4a was obtained with the dr value of 90:10.
Reaction with sodium ethylxanthate instead of thiolacetic acid.
Isolated yield.
b
c
b
c
Isolated overall yields from 2.
PtO2 was used as the catalyst instead of Pd/C. For the discussions, vide post.

2516
N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
Table 4
slightly under the catalysis of tributylamine under different con-
ditions (Table 3, entries 1e7). So, we focused on the variation of the
dr value. The reaction at the lower temperature (0 ꢁC) resulted in
the increase of the dr value (68:32), while the decrease (48:52) in
the dr value was observed at higher temperature (Table 3, entries 2
and 3). It seems that the lower temperature is beneficial for im-
proving the dr value. However, further decreasing the temperature
to below 0 ꢁC would freeze benzene. So, the scope of solvents was
screened and the chloroform turns out to be the most appropriate
(dr: 72:28, Table 3, entry 4). Catalysts were also evaluated and
tributylamine (TBA) shows better activity than triethylamine (TEA)
and N,N-dimethylaminopyridine (DMAP) (Table 3, entries 4, 8, and
9). Prolonging the reaction time results in the decrease of the dr
value (55:45, Table 3, entry 10) because the chiral carbon bearing
the strong electron-withdrawing nitro group slowly racemized
under the basic environment. When the reaction was conducted at
ꢀ78 ꢁC, the yield dropped to 51% under TBA catalysis and 13% under
the catalysis of DMAP (Table 3, entries 11 and 12). Even the reaction
time was prolonged to 5 h, the yield did not increase (Table 3, entry
13). Allowing the reaction mixture to warm slowly to ꢀ35 ꢁC under
the catalysis of TBA, the reaction proceeded smoothly, but the dr
value was similar with that at 0 ꢁC (Table 3, entries 4 and 14).
After optimizing the conditions, intermediate thioacetate 2j was
obtained as a couple of diastereoisomers with very close polarities
[Fig. 3, cucurbit-like dots in TLC, silica gel plate, PE/EA (petroleum
ether/ethyl acetate)¼10:1, v/v], which is inconvenient to isolate and
to obtain its pure syn- and anti-isomers in large scale by column
chromatography. After many attempts, we delightedly validate that
the pure major diastereomer with the higher melting point was
isolated via recrystallization from benzene or petroleum ether.
Considering the harmfulness to health, petroleum ether with little
ethyl acetate is the best choice. The pure minor diastereomer with
relatively lower melting point was obtained from the concentrated
mother liquor via silica gel column chromatography [eluted with
PE/EA¼20:1, v/v].
Synthesis of syn- and anti-S-2-nitroalkyl thiolacetates 2 from
nitroolefins
a,b-disubstituted
R3
NO2
O
NO2
Bu3N, CHCl3
0 o
R1
R1
+
HS
R3
C
1
syn- and anti-2
Entry
1
Nitroolefins
Yield (%)
dr (syn/anti)
NO2
Ph
Ph
99
99
28:72
40:60
1j
NO2
2
Et
1k
NO2
p-ClC6H4
p-ClC6H4
3
4
5
99
99
99
30:70
42:58
1:99
1l
NO2
Et
Ph
NO2
1m
Ph
1n
The purified syn- and anti-S-nitroalkyl thiolacetates 2jen were
oxidized with peroxyformic acid to give rise to the corresponding
vicinal syn- and anti-nitroalkanesulfonic acids 3jen, which were
subsequently hydrogenated without purification in the presence of
palladium on carbon powder to afford the final products vicinal
syn- and anti-aminoalkanesulfonic acids 4jen in good to excellent
yields (Table 5). Although 2-nitro-1-phenylethanesulfonic acid (3a)
Table 5
Synthesis of 1,2-disubstituted taurines 4 from S-nitroalkyl thiolacetate 2
Entry
1
2
syn/anti-2
syn-2j
4
Yielda (%)
88
syn-4j
Fig. 3. Reaction of a,b-disubstituted nitroolefins and thioacetic acid.
2
3
4
anti-2j
syn-2k
anti-2k
anti-4j
syn-4k
anti-4k
83
87
87
The reaction of nitroolefin 1j and potassium ethylxanthate was
also carried out, giving rise to 5j in 82% yield with the dr value of
75:25 (Table 3, entry 15). However, 5j is a liquid product with very
close polarity of the diastereoisomers (only one dot was de-
termined on TLC, silica gel plate, PE/EA¼10:1 to 100:1, v/v). Its di-
astereomers were hardly separated through either column
chromatography or recrystallization. Thus, nitroalkyl thioacetates
are the best precursors for the preparation of syn- and anti-1,2-
disubstituted taurines.
40b
92c
82c
SAc
5
6
7
syn-2l
syn-2l
anti-2l
syn-4l
anti-4l
pClPh
NO2
)
(
Under the optimized conditions (Table 3, entry 4), thiolacetic
acid reacted with other nitroolefins 1ken to afford the corre-
sponding thioacetates 2ken in excellent yields and their anti-iso-
mers are always the major products. The results are shown in
Table 4. The results also demonstrated that the ratio of anti-products
increases with the increase of the steric hindrance. The product 2n
(phenyl as R3) (Table 4, entry 5) shows a greatly better dr value
(99:1) than 2jem (methyl and ethyl as R3) (Table 4, entries 1e4).
syn- and anti-Isomers of 2 were obtained following the method for
the preparation of syn- and anti-2j. The identification of the ster-
eostructures of diastereoisomers will be discussed, vide post.
8
syn-2m
anti-2m
anti-2m
syn-4m
anti-4m
80c
41b
83c
9
10
11
anti-2n
anti-4n
88
a
Overall yield from 2.
b
c
Pd/C as the catalyst and dechlorination was unavoidable.
PtO2 as the catalyst at 64 ꢁC under 10 atm of hydrogen for 1 h.

N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
2517
was reduced to 1-phenyltaurine (4a) in 90% yield during a day, syn-
and anti-1-aryl-2-nitroalkanesulfonic acids 3jen were reduced for
2e3 days to afford the desired taurines 4jen in satisfactory to ex-
cellent yields due to the steric hindrance around the nitro group,
which decreased the reaction rate and prolonged the reaction time
(Scheme 3).
cases. To shorten the reaction time, the reaction temperature and
hydrogen pressure were increased. anti-4l was obtained in the yield
of 5% at 64 ꢁC for 1 d under 1 atm of hydrogen and in the yield of
92% at 64 ꢁC for 1 h under 10 atm of hydrogen, respectively (Table 6,
entries 4 and 5). Thus,10 atm of hydrogen at 64 ꢁC is the best choice
for the catalyst of PtO2.
2.2. Determination of the relative configuration
-
SO3H
NO2
SO3
Pd/C, H2 (g)
1 day, 90%
+
NH3
Ph
The relative configurations of diastereomeric compounds 2jen
were deduced via the analysis of the coupling constants between the
protons attached on the carbon atoms with nitro and acetylthio
groups with the Karplus equation.36 According to the Karplus
equation, the closer the dihedral angle approaches to 180ꢁ, the
greater of the coupling constant will be. For our system, the stable
conformations of syn- and anti-S-1,2-disubstituted nitroethyl thio-
acetates 2jen can be shown in the Newman projection as follows
(Fig. 4). On the basis of the Karplus equation, the coupling constant is
dominated by the dihedral angle between HA and HB. As for the steric
hindrance, alkyl is greater than the planar nitro group and aryl is
greater than the acetylthio group. The two bulky groups R1 (Me and
Et) and R3 (Ar) are in anti positions in the anti-isomers and in
gauche positions in the syn-isomers (For detailed discussion, see
Supplementary data, Fig. S2). Thus, the dihedral angle between HA
and HB in syn-isomers would have a more obvious difference from
180ꢁ than that in anti-isomers due to steric hindrance in the gauche
positions, indicating that the coupling constants between HA and HB
in syn-isomers would be smaller than those in anti-isomers. The
observed coupling constants between HA and HB in major isomers
are bigger than those in the minor isomers (see Supplementary data,
Figs. S1 and S2). For example, compound 2m, the observed coupling
constant is 10.3 Hz in its major isomer and 9.4 Hz in its minor isomer.
Ph
( )-3a
( )-4a
-
SO3
SO3H
R3
R3
Pd/C, H2 (g)
R1
R1
+
2-3 days, > 80%
R1 = Ph, 4-ClPh
NH3
( )-4j-n
NO2
( )-3j-n
R
3 = Me, Et, Ph
Scheme 3. Effect of the steric hindrance in the reduction of the nitro group.
When R1 is the phenyl group, the corresponding taurines were
successfully synthesized in good to excellent yields (Table 5, entries
1e4 and 11). Nevertheless, when R1 is 4-chlorophenyl, the results
are more complicated. Taking anti-31 as an example, after re-
duction for 2 days, TLC indicated that substrate anti-3l was con-
sumed completely and 1H NMR showed that two products were
obtained. Besides the desired reduction product (anti-4l), the
dechlorinated product (anti-4j) was also generated through the 1H
NMR analysis. The ratio of the dechlorinated product (anti-4j) in-
creased via prolonging the reduction time. After reduction for 3
days, product anti-4j became sole product. The results reveal that
the chlorine atom on phenyl can be hydrogenated to afford dech-
lorinated products under the catalysis of palladium. We attempted
to shorten the reaction time, hoping to obtain the desired product
anti-4l. Unfortunately, even though the reaction time was short-
ened to 10 h, the yield of anti-4l dropped to 10%, but the de-
chlorination still occurred. It has been reported that in the presence
of formic acid or formate salts, the aldehyde group in formate
would prompt the dechlorination.34 Thus, we used the high vac-
uum pump to remove residual formic acid after the oxidation.
However, the dechlorination was still unavoidable in further re-
duction under the hydrogen atmosphere.35 We had to give up
palladium and looked for other catalysts.
HA
HA
Ar
SAc
R3
AcS
O2N
Ar
R3
O2N
HB
2
anti-
HB
2
syn-
Fig. 4. Stable conformations of syn- and anti-S-1,2-disubstituted nitroethyl thio-
lacetates 2jen in the Newman projection.
Platinum dioxide (PtO2) is also a good catalyst in the catalytic
hydrogenation and was selected as the catalyst in the reduction.
However, none of anti-4l was detected in the reaction mixture after
reduction for 3 days at room temperature under its catalysis (Table
6, entry 1). anti-4l was obtained in yields of 40% and 90% at room
temperature for 7 and 10 days of reduction, respectively (Table 6,
entries 2 and 3). No dechlorinated product was detected in each of
We then calculated the dihedral angles in syn-2m and anti-2m
with the DFT (the density functional theory) method at B3LYP
theory lever, and found the angle is 172.2ꢁ in syn-2m and 174.5ꢁ in
anti-2m (see Supplementary data, Fig. S3). The calculated results
support the above analysis and identification.
Compared with the reported spectral data of syn- and anti-1,2-
diphenyltaurines,20,28 the major isomer of product 4n was identi-
fied as anti-1,2-diphenyltaurine (anti-4n). According to the chem-
ical correlation, both the major isomer of product 2n in the Michael
addition and its oxidized product 3n are in anti-configuration
(Scheme 4).
Table 6
Optimization on the reduction of anti-3l with PtO2 as the catalyst
-
SO3
SO3H
PtO2, H2(g)
cond.
+
NH3
O
NO2
Cl
Cl
3l
anti- -( )
SO3
3l
anti- -( )
SO3
S
H2
HCO3H
Ph
Ph
Ph
NO2
Ph
Entry
Temp
Pressure (atm)
Time
Yield (%)
Ph
Ph
Pd/C
NH3
1
2
3
4
5
rt
rt
rt
1
1
1
1
10
3 d
7 d
10 d
1 d
1 h
0
40
90
5
NO2
( )
( )
( )
3n
anti-
anti-2n
4n
anti-
64 ꢁC
64 ꢁ
C
92
Scheme 4. Determination on the relative configuration of major isomer of 2n by the
chemical correlation.

2518
N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
Finally, the crystals of major isomers of compounds 2l and 2m
and AcS groups in the conformation I. Thus, the conformation I
exists predominantly in the reaction mixture and was used to ex-
plain the diastereoselectivity in the Michael addition with the Cram
rule (Fig. 7). As the steric hindrance of R1 is greater than that of AcS
group, the protonation occurred favorably from the less steric AcS
side (the right side in Fig. 7), resulting in the formation of the anti-
isomers as major products.
were selected and subjected to the X-ray single crystal diffraction
analysis. The results reveal that both of them are anti-configuration
(2l in Fig. 5 and 2m in Fig. 6).37 It can be seen from the crystal
structures that two bulky groups R1 and R3 are in anti-positions,
agreeing with our previous analysis. The relative configurations of
products 3jem and 4jem can be deduced from their starting
materials.
R3
NO2
R1
R1
SAc
SAc
O
N
SAc
H+
&
Less steric
anti-
R1
O
3
H
H
R3
( )
R
NO2
I
II
-( )
-( )
7-
Fig. 7. Explanation on the configuration of the major products in the Michael addition
by the Cram rule.
With the increase of the steric hindrance of the R3 group, the
concentration of the conformation I increased generally, so the ratio
of anti-products increased. Although the ratios are not obviously
different when R3 is methyl and ethyl due to their similar steric
effect, but the ratio increased remarkably when R3 is phenyl,
reaching to 99:1 for the anti-/syn- ratio.
Fig. 5. Crystal structure of anti-2l.
2.3.3. Mechanism in the formation of nitroalkanesulfonic acids 3 via
oxidation of S-nitroalkyl thiolacetates 2. To investigate the oxidation
mechanism, S-nitroalkyl thioacetates 2a and anti-2j were selected
as examples and dissolved in formic acid. After the resulting solu-
tions were stirred for 1 day, none hydrolyzed products, nitro-
alkanethiols, were observed in each of the cases studied. As for the
oxidation mechanism, taking into accounting for the reported ox-
idation of thiazolidine-2-thiones,19 we assumed that thioacetates 2
were first oxidized to thioacetate S,S-dioxides 8, sulfur analogs of a-
oxo sulfones.38 They were unstable because the carbonyl group was
a stronger electrophile than that in the corresponding ketones and
esters due to the existence of the vicinal sulfone group. They
readily underwent acid-catalyzed hydrolysis to generate 2-
nitroalkanesulfinic acids 9 and protonated acetic acid, which fur-
ther decomposed to acetic acid. The 2-nitroalkanesulfinic acids
were further oxidized to 2-nitroalkanesulfonic acids 3 with per-
formic acid (Scheme 6).
Fig. 6. Crystal structure of anti-2m.
2.3. Mechanisms and diastereoselectivity
2.3.1. Mechanisms in the Michael addition of nitroolefins and thiol-
acetic acid. Under the catalysis of TBA, thiolacetic acid was first
deprotonated and then attacked nitroolefins
1 to form in-
termediates 7, which abstracted a proton from ammonium to give
rise to S-nitroalkyl thioacetate 2 (Scheme 5).
O
OH
HO
O
O
S
OH2
NO2
O
S
O
O
R1
H+
O
R1
O
R1
S
S
HCO3H
H2O
NO2
R1
R2
NO2
NO2
R2
R2
R2
R3
R3
R3
R3
HSAc
H+ transfer
2
8
-+HNBu3
NBu3
R1
R1
R2
O
O
N
R2
R3
O
R2
R3
HO
S
-SAc
OH
NO2
O
HO
H
NBu3
OH
NO2
O
R1
OH
S
O
O
S
HCO3H
OH
S
S
+
O
R3
7
R1
R2
NO2
NO2
R1
2
NO2
R1
1
OH
R2
R2
R3
R3
R3
Scheme 5. Mechanism of the Michael addition of nitroolefins and thiolacetic acid.
3
9
Scheme 6. Oxidation mechanism of nitrothiolacetates 2 to nitroalkanesulfonic acids 3.
2.3.2. Diastereoselectivity in the reaction of a,b-disubstituted nitro-
olefins and thiolacetic acid. According to the experimental results,
we can conclude that whether R3 is alkyl or aryl group, the major
products are always anti-isomers. In the Michael addition process,
the final step is the protonation of intermediates 7, which exist in
conformations I and II in the Newman projections. Since the con-
formation II shows more steric hindrance than the conformation I
due to more bulky R3 in gauche position with R1 and AcS groups in
the conformation II and less bulky NO2 in gauche position with R1
3. Conclusion
Various substituted taurines, including 1- and 2-
monosubstituted, 1,1-, syn-1,2-, and anti-1,2-disubstituted tau-
rines, were synthesized from the corresponding nitroolefins via the
Michael addition with thiolacetic acid, oxidation with peroxyformic
acid, and the catalytic hydrogenation under the catalysis of

N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
2519
palladium on carbon or platinum dioxide. The current method can
be applied to synthesize taurines with steric bulky substituents and
both syn- and anti-1,2-disubstituted taurines with two different
substituents. Thus, it is a general, versatile, and salt-free method for
the preparation of various mono- and disubstituted taurines. Ad-
ditionally, the relative configurations of syn- and anti-1,2-
disubstituted taurines were deduced from the products in the Mi-
chael addition, which were identified by the Karplus equation
analysis, computational analysis, and confirmed by the XRD single
crystal analysis. The diastereoselectivity in the Michael addition
was rationalized with the Cram rule.
4.2.4. S-2-Nitro-1-methyl-1-phenylethyl thiolacetate (2d). Colorless
liquid, yield: 94%. 1H NMR (300 MHz, CDCl3)
: 7.50e7.43 (m, 2H,
d
ArH), 7.40e7.31 (m, 3H, ArH), 5.46 (d, J¼12.2 Hz, 1H in CH2N), 5.21
(d, J¼12.2 Hz, 1H in CH2N), 2.27 (s, 3H, CH3Ar), 2.15 (s, 3H, CH3); 13
C
NMR (75 MHz, CDCl3) d: 195.1, 138.9, 128.7, 128.4, 126.2, 81.6, 53.6,
30.8, 23.6. IR (CH2Cl2),
n
(cmꢀ1): 1694 (C]O), 1553 (NO2). HRMS
(ESI) calcd for C11H13NO3SNaþ [MþNa]þ m/z: 262.0508; found:
262.0512.
4.2.5. S-1-Methyl-1-nitromethylpropyl thiolacetate (2e). Colorless
liquid, yield: 71%. 1H NMR (300 MHz, CDCl3)
d
: 4.97 (d, J¼11.1 Hz,1H
in CH2N), 4.85 (d, J¼11.1 Hz, 1H in CH2N), 2.30 (s, 3H, CH3CO), 2.00
(dq, J¼14.6, 7.4 Hz, 1H in CH2 in Et), 1.74 (dq, J¼14.6, 7.4 Hz, 1H in
CH2 in Et),1.52 (s, 3H, CH3), 1.01 (t, J¼7.4 Hz, 3H, CH3 in Et); 13C NMR
4. Experimental section
4.1. General
(75 MHz, CDCl3) d: 195.9, 80.7, 52.5, 31.3, 30.2, 22.5, 8.3. IR (CH2Cl2),
n
(cmꢀ1): 1691 (C]O), 1553 (NO2). HRMS (ESI) calcd for
C7H13NO3Sþ [MþH]þ m/z: 192.0689; found: 192.0695.
Melting points were determined on a melting point apparatus
and are uncorrected. 1H NMR spectra were recorded at 200, 300, or
400 MHz in CDCl3 with TMS as the internal standard, in DMSO-d6
with TMS as the internal standard, or in D2O with HDO as the in-
ternal standard at 4.67 ppm. 13C NMR spectra were recorded at
50.3, 75.5, or 100.6 MHz in CDCl3 with CDCl3 as the internal stan-
dard at 77.0 ppm, in DMSO-d6 with DMSO-d6 as the internal stan-
dard at 39.5 ppm, or D2O with HCOOH as the internal standard at
166.3 ppm. IR spectra were determined directly. HRMS spectra
were performed on an LC/MSD TOF mass spectrometer. Column
chromatography was carried out with silica gel (200e300 mesh)
with petroleum ether and ethyl acetate as the eluent.
4.2.6. S-1,3,3-Trimethyl-1-nitromethylbutyl thiolacetate (2f). Colorless
liquid, yield: 41%. 1H NMR (300 MHz, CDCl3)
d: 5.01 (d, J¼11.1 Hz,1H
in CH2N), 4.88 (d, J¼11.1 Hz, 1H in CH2N), 2.29 (s, 3H, CH3CO), 2.02
(d, J¼15.2 Hz, 1H in CH2), 1.82 (d, J¼15.2 Hz, 1H in CH2), 1.66 (s, 3H,
CH3), 1.06 (s, 9H, 3CH3 in t-Bu); 13C NMR (75 MHz, CDCl3)
d
: 196.0,
82.5, 52.8, 49.0, 32.4, 31.6, 31.2, 24.4. IR (CH2Cl2),
n
(cmꢀ1): 1700
(C]O),1557 (NO2). HRMS (ESI) calcd for C10H19NO3Sþ [MþH]þ m/z:
234.1158; found: 234.1153.
4.2.7. S-2-Nitro-1,1-diphenylethyl thiolacetate (2g). Colorless liquid,
yield 34%. 1H NMR (300 MHz, CDCl3)
d: 7.34e7.27 (m, 10H, ArH),
5.79 (s, 2H, CH2N), 2.26 (s, 3H, CH3); 13C NMR (101 MHz, CDCl3)
193.5, 140.5, 128.20, 128.16, 128.0, 81.0, 61.0, 31.0. IR (CH2Cl2),
d:
n
4.2. General procedure for the preparation of S-2-nitroalkyl
thiolacetates 2aei
(cmꢀ1): 1695 (C]O), 1557 (NO2). HRMS (ESI) calcd for
C14H15NO3SNaþ [MþNa]þ m/z: 324.0665; found: 324.0667.
To a solution of nitroolefins (5 mmol) in 10 mL of diethyl ether
solution in an ice-water bath was added thiolacetic acid (385 mg,
5 mmol) and tributylamine (46 mg, 0.25 mmol). The resulting so-
lution was stirred for 1 h. Diethyl ether (10 mL) was then added and
the whole mixture was washed with 10 mL of hydrochloric acid
(1 M) and water, and then dried over anhydrous Na2SO4. After re-
moval of the solvent in vaccum, the residue was purified with re-
crystallization (2a and 2b), or silica gel column chromatography
eluent with petroleum ether (60e90 ꢁC)/ethyl acetate (2cei).
4.2.8. S-2-Nitropropyl thiolacetate (2h). Colorless liquid, yield: 94%.
1H NMR (300 MHz, CDCl3)
d
: 4.66 (ddq, J¼7.1, 6.0, 6.8 Hz, 1H, CHN),
3.35 (dd, J¼14.4, 7.1 Hz, 1H in CH2S), 3.33 (dd, J¼14.4, 6.0 Hz, 1H in
CH2S), 2.38 (s, 3H, CH3CO), 1.64 (d, J¼6.8 Hz, 3H, CH3); 13C NMR
(50 MHz, CDCl3) d: 194.4, 82.3, 32.0, 30.4, 18.9. IR (CH2Cl2), n
(cmꢀ1):
1698 (C]O), 1556 (NO2). HRMS (ESI) calcd for C5H10NO3Sþ [MþH]þ
m/z: 164.0376; found: 164.0383.
4.2.9. S-2-Nitrobutyl thiolacetate (2i). Colorless liquid, yield: 89%.
1H NMR (300 MHz, CDCl3)
d
: 4.49 (dddd, J¼9.6, 8.8, 5.0, 4.7 Hz, 1H,
4.2.1. S-2-Nitro-1-phenylethyl thiolacetate (2a).32 Colorless crys-
tals, yield: 97%. Mp 126e127 ꢁC, lit.32 mp 126e127 ꢁC. 1H NMR
CHN), 3.37 (dd, J¼14.4, 4.7 Hz, 1H in CH2S), 3.27 (dd, J¼14.4, 8.8 Hz,
1H in CH2S), 2.37 (s, 3H, CH3CO), 2.14e1.99 (m, 1H in CH2 in Et),
1.98e1.84 (m, 1H in CH2 in Et), 1.01 (t, J¼7.4 Hz, 3H, CH3); 13C NMR
(300 MHz, CDCl3)
d
: 7.34e7.29 (m, 5H, ArH), 5.29 (t, J¼7.5 Hz, 1H,
CHS), 4.84 (d, J¼7.5 Hz, 2H, CH2N), 2.36 (s, 3H, CH3); 13C NMR
(75 MHz, DMSO-d6) d: 194.4, 88.8, 30.8, 30.4, 27.0, 9.9. IR (CDCl3), n
(75.5 MHz, CDCl3)
d: 193.3, 135.6, 129.2, 128.8, 127.7, 77.9, 44.4, 30.3.
(cmꢀ1): 1704 (C]O), 1547 (NO2). HRMS (ESI) calcd for C6H12NO3Sþ
[MþH]þ m/z: 178.0532; found: 178.0538.
IR (CHCl3),
n
(cmꢀ1): 1685 (C]O), 1550 (NO2).
4.2.2. S-1-(4-Chlorophenyl)-2-nitroethyl thiolacetate (2b).39 Colorless
4.3. General procedure for the preparation of vicinal anti-
and syn-S-nitroalkyl thiolacetates 2jen
crystals, yield: 97%. Mp 67e68 ꢁC. 1H NMR (300 MHz, CDCl3)
: 7.33
d
(d, J¼8.6 Hz, 2H, ArH), 7.26 (d, J¼8.6 Hz, 2H, ArH), 5.25 (dd, J¼9.0,
6.6 Hz, 1H, CHD), 4.84 (dd, J¼13.4, 6.6 Hz, 1H in CH2N), 4.79 (dd,
J¼13.4, 9.0 Hz, 1H in CH2N), 2.36 (s, 3H, CH3); 13C NMR (50 MHz,
To a solution of nitroolefins (5 mmol) in 10 mL of CHCl3 in an
ice-water bath were added thiolacetic acid (385 mg, 5 mmol) and
tributylamine (145 mg, 0.25 mmol). The resulting solution was
stirred for 1 h. Dichloromethane (10 mL) was then added and the
whole mixture was washed with hydrochloric acid (1 M, 10 mL)
and water (10 mL), and then dried over anhydrous Na2SO4. After
removal of the solvent in vaccum, the residue was first purified
with recrystallization from a mixture of petroleum ether and ethyl
acetate to afford the anti-products. After filtering the anti-products,
the residue was purified via silica gel column chromatography el-
uent with petroleum ether (60e90 ꢁC)/ethyl acetate to give rise to
syn-products.
CDCl3)
d: 193.1, 134.8, 134.3, 129.4, 129.2, 43.7, 30.3. IR (CHCl3), n
(cmꢀ1): 1698 (C]O), 1556 (NO2).
4.2.3. S-2-Methyl-1-nitromethylpropyl thiolacetate (2c).39 Colorless
liquid, yield: 98%. 1H NMR (300 MHz, CDCl3)
d: 4.58 (dd, J¼13.0,
7.5 Hz, 1H in CH2N), 4.53 (dd, J¼13.0, 7.0 Hz, 1H in CH2N), 4.17 (ddd,
J¼7.5, 7.0, 4.5 Hz, 1H, CHS), 2.38 (s, 3H, CH3), 2.07 (dhept, J¼4.5,
6.8 Hz,1H, CH), 1.03 (d, J¼6.8 Hz, 3H, 1CH3 in i-Pr), 0.97 (d, J¼6.8 Hz,
3H, 1CH3 in i-Pr); 13C NMR (50 MHz, CDCl3)
d: 193.8, 76.4, 47.4, 30.6,
29.2, 20.1, 18.3. IR (CHCl3),
n
(cmꢀ1): 1698 (C]O), 1555 (NO2).

2520
N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
4.3.1. syn-S-2-Nitro-1-phenylpropyl thiolacetate (syn-2j). Colorless
4.3.8. anti-S-1-(4-Chlorophenyl)-2-nitrobutyl thiolacetate (anti-
crystals, NMR yield: 28% (CHCl3), 50% (THF), isolated yield: 25%
2m). Colorless crystals, NMR yield: 58%, isolated yield: 50%. Mp
(THF). Mp 51e53 ꢁC. 1H NMR (300 MHz, CDCl3)
d
: 7.36e7.26 (m, 5H,
79e81 ꢁC. 1H NMR (300 MHz, CDCl3)
d
: 7.28 (d, J¼8.6 Hz, 2H, ArH),
ArH), 5.10 (d, J¼9.0 Hz, 1H, CHS), 4.96 (dq, J¼9.0, 6.6 Hz, 1H, CHN),
7.20 (d, J¼8.6 Hz, 2H, ArH), 5.03 (d, J¼10.3 Hz, 1H, CHS), 4.77 (ddd,
2.32 (s, 3H, CH3), 1.48 (d, J¼6.6 Hz, 3H, CH3); 13C NMR (75.5 MHz,
J¼10.3, 9.8, 4.1 Hz, 1H, CHN), 2.36 (s, 3H, CH3CO), 2.09 (m, 2H, CH2),
CDCl3)
(CHCl3),
d
: 192.4, 136.8, 129.0, 128.5, 128.2, 86.0, 50.2, 30.4, 18.0. IR
n
0.99 (t, J¼7.4 Hz, 3H, CH3); 13C NMR
d: 192.0, 135.6, 134.4, 129.3,
(cmꢀ1) : 1700 (C]O), 1550 (NO2). HRMS (ESI), calcd for
129.1, 93.0, 48.7, 30.4, 25.3, 10.2. IR (CHCl3), n
(cmꢀ1): 1701 (C]O),
C11H13NO3NaS [MþNa]þ m/z: 262.0508; found: 262.0518.
1551 (NO2). HRMS (ESI) calcd for C12H14NO3NaSCl [MþNa]þ m/z:
310.0275; found: 310.0285.
4.3.2. anti-S-2-Nitro-1-phenylpropyl thiolacetate (anti-2j). Colorless
crystals, NMR yield: 72%, isolated yield: 55%. Mp 83e84.5 ꢁC. 1H
4.3.9. anti-S-2-Nitro-1,2-diphenylethyl
Colorless crystals, NMR yield: 99%, isolated yield: 96%. Mp
165e168 ꢁC. 1H NMR (300 MHz, CDCl3)
: 7.60 (dd, J¼2.0, 7.6 Hz, 2H,
thiolacetate
(anti-2n).
NMR (300 MHz, CDCl3)
d
: 7.36e7.26 (m, 5H, ArH), 5.14 (d, J¼9.2 Hz,
1H, CH), 4.97 (dq, J¼9.2, 6.6 Hz, 1H, CHS), 2.35 (s, 3H, CH3), 1.67 (d,
d
J¼6.6 Hz, 3H, CH3); 13C NMR (75.5 MHz, CDCl3)
d
: 192.3, 136.9,
ArH), 7.45e7.31 (m, 8H, ArH), 5.92 (d, J¼12.3 Hz, 1H, CHN), 5.68 (d,
128.9, 128.5, 128.0, 85.6, 50.3, 30.4, 17.5. IR (CHCl3),
n
(cmꢀ1): 1699
J¼12.3 Hz, 1H, CHS), 2.10 (s, 3H, CH3); 13C NMR (75.5 MHz, CDCl3)
d:
(C]O), 1553 (NO2). HRMS (ESI) calcd for C11H13NO3NaS [MþNa]þ
m/z: 262.0508; found: 262.0509.
191.3, 137.6, 132.0, 130.5, 129.0, 128.9, 128.5, 128.4, 128.0, 94.0, 49.2,
30.2. IR (CDCl3), n
(cmꢀ1): 1690 (C]O),1551(NO2). HRMS (ESI) calcd
for C16H15NO3NaSþ [MþNa]þ m/z: 324.0670; found. 324.0671.
4.3.10. syn-S-2-Nitro-1,2-diphenylethyl thiolacetate (syn-2n).40
4.3.3. syn-S-2-Nitro-1-phenylbutyl thiolacetate (syn-2k). Colorless
crystals, NMR yield: 40%, isolated yield: 21%. Mp 59e61 ꢁC. 1H NMR
(300 MHz, CDCl3)
d
: 7.38e7.26 (m, 5H, ArH), 5.06 (d, J¼9.7 Hz, 1H,
Colorless crystals, NMR yield: 1%. 1H NMR (300 MHz, CDCl3)
d:
CHS), 4.79 (ddd, J¼3.6, 9.7, 10.4 Hz, 1H, CHN), 2.30 (s, 3H), 1.94 (ddq,
J¼10.4, 14.8, 7.4 Hz, 1H in CH2), 1.61 (ddq, J¼3.6, 14.8, 7.4 Hz, 1H in
7.41e7.15 (m, 10H, ArH), 5.86 (d, J¼11.7 Hz, 1H, CHN), 5.64 (d,
J¼11.7 Hz, 1H, CHS), 2.33 (s, 3H, Me). HRMS (ESI) calcd for
C16H15NO3NaSþ [MþNa]þ m/z: 324.0670; Found. 324.0667.
CH2), 0.91 (t, J¼7.4 Hz, 3H, CH3); 13C NMR (75.5 MHz, CDCl3)
d:
192.3, 137.4, 129.1, 128.4, 128.0, 92.8, 49.4, 30.4, 26.0, 10.3. IR
(CHCl3),
n
(cmꢀ1): 1699 (C]O), 1553 (NO2). HRMS (ESI) calcd for
C12H15NO3NaS [MþNa]þ m/z: 276.0665; found: 276.0676.
4.4. General procedure for the preparation of various
substituted taurines (4ae4n)20
4.3.4. anti-S-2-Nitro-1-phenylbutyl thiolacetate (anti-2k). Colorless
crystals, NMR yield: 60%, isolated yield: 50%. Mp 102e103 ꢁC. 1H
To peroxyformic acid solution, generated in situ from formic
acid (98%, 5 mL) and hydrogen peroxide (30%, 1 mL) at 0 ꢁC for
0.5 h, was added a solution of nitroalkylthiolacetate 2 (1 mmol) in
1e2 mL of THF. After stirring overnight, 10 mL of deionized
water was added and the mixture was washed with diethyl
ether (5 mL) and dichloromethane (5 mL). After concentration, 2-
nitroalkylsulfonic acid 3 was obtained. It was used directly in the
subsequent hydrogenation without any further purification.
2-Nitroalkanesulfonic acid 3 (3ae3k and 3l) prepared above
was dissolved in MeOH (10 mL), and 10% Pd on carbon powder
(30 mg) was added. The suspension was stirred under the atmo-
sphere of hydrogen at rt for 2e3 days. Methanol 20 mL was added
to dissolve the precipitate. The catalyst was removed by filtration
through a filter paper and was washed twice with formic acid
(5 mL). After evaporation of the solvent, the crude product was
purified by recrystallization from methanol or a mixture of meth-
anol and diethyl ether to afford colorless crystals.
NMR (300 MHz, CDCl3)
d: 7.33e7.24 (m, 5H, ArH), 5.77 (d,
J¼10.2 Hz, 1H, CHS), 4.81 (dt, J¼10.2, 4.5 Hz, 1H, CHN), 2.36 (s, 3H),
2.09 (m, 2H, CH2), 0.99 (t, J¼4.5 Hz, 3H, CH3); 13C NMR (50 MHz,
CDCl3)
IR (CHCl3),
d: 192.3, 137.0, 128.9, 128.5, 127.9, 93.3, 49.4, 30.4, 25.2, 10.3.
n
(cmꢀ1) : 1697 (C]O), 1554 (NO2). HRMS (ESI) calcd for
C12H15NO3NaS [MþNa]þ m/z: 276.0665; found: 276.0666.
4.3.5. syn-S-1-(4-Chlorophenyl)-2-nitropropyl thiolacetate (syn-2l).
Colorless crystals, NMR yield: 30%, isolated yield: 16%. Mp
55e57 ꢁC. 1H NMR (300 MHz, CDCl3)
d
: 7.32 (d, J¼8.6 Hz, 2H), 7.22
(d, J¼8.6 Hz, 2H), 5.07 (d, J¼8.7 Hz, 1H), 4.93 (dq, J¼8.7, 6.6 Hz, 1H),
2.33 (s, 3H), 1.48 (d, J¼6.6 Hz, 3H); 13C NMR(75.5 MHz, CDCl3)
d:
192.2, 135.4, 134.4, 129.6, 129.2, 85.7, 49.6, 30.4, 17.8. IR (CHCl3),
n
(cmꢀ1
) : 1701 (C]O), 1555 (NO2). HRMS (ESI) calcd for
C11H12NO3NaSCl [MþNa]þ m/z: 296.0119; found: 296.0120.
4.3.6. anti-S-1-(4-Chlorophenyl)-2-nitropropyl thiolacetate (anti-2l).
Colorless crystals, NMR yield: 70%, isolated yield: 51%. Mp
2-Nitroalkanesulfonic acids 3 (3lem) prepared above was dis-
solved in MeOH (10 mL), and PtO2$H2O (9 mg, 5 mmol %) was
added. The suspension was stirred under the atmosphere of hy-
drogen at rt for 10 days, or at 10 atm in refluxing for 1 h. After fil-
tered off PtO2 and washed with formic acid, the filtrate was
concentrated and the residue was recrystallized from MeOH to
afford the colorless crystals 4lem.
84e86 ꢁC. 1H NMR (300 MHz, CDCl3)
d
: 7.29 (d, J¼8.4 Hz, 2H, ArH),
7.21 (d, J¼8.4 Hz, 2H, ArH), 5.08 (d, J¼9.4 Hz, 1H), 4.93 (dq, J¼9.4,
6.6 Hz, 1H), 2.37 (s, 3H, CH3CO), 1.68 (d, J¼6.6 Hz, 3H, CH3); 13C
NMR (75.5 MHz, CDCl3) d: 192.1, 135.5, 134.4, 129.4, 129.1, 86.3,
49.7, 30.4, 17.6. IR (CHCl3),
n
(cmꢀ1): 1702 (C]O), 1554 (NO2).
HRMS (ESI) calcd for C11H12NO3NaSCl [MþNa]þ m/z: 296.0119;
found: 296.0129.
4.4.1. 2-Amino-1-phenylethanesulfonic acid (4a).25a Colorless crys-
tals, yield: 90%. Mp >330 ꢁC, lit. mp 352 ꢁC.25a 1H NMR (200 MHz,
4.3.7. syn-S-1-(4-Chlorophenyl)-2-nitrobutyl thiolacetate (syn-2m).
DMSO-d6)
d: 7.82 (br s, 3H, ArH), 7.44e7.18 (m, 5H, ArH), 3.88 (dd,
Colorless liquid, NMR yield: 42%, isolated yield: 19%. 1H NMR
J¼9.8, 4.4,1H, CHS), 3.64e3.42 (m,1H in CH2N), 3.29e2.94 (m,1H in
(300 MHz, CDCl3)
d
: 7.32 (d, J¼8.6 Hz, 2H, ArH), 7.22 (d, J¼8.6 Hz,
CH2N); 13C NMR (50 MHz, DMSO-d6)
d: 136.1, 129.0, 127.9, 127.2,
2H, ArH), 5.02 (d, J¼9.4 Hz, 1H, CHS), 4.75 (ddd, J¼10.4, 9.4, 3.6 Hz,
1H, CHN), 2.31 (s, 3H, CH3CO), 1.94 (ddq, J¼14.6, 10.4, 7.4 Hz, 1H in
CH2), 1.62 (ddq, J¼14.6, 3.6, 7.4 Hz, 1H in CH2), 0.92 (t, J¼7.4 Hz, 3H,
61.5, 40.9; 13C NMR (50 MHz, D2OeHCOOH)
d: 132.7, 129.94, 129.75,
63.4, 40.8.
CH3); 13C NMR
d: 192.3, 136.0, 134.4, 129.4, 129.3, 92.5, 48.9, 30.4,
4.4.2. 2-Amino-1-(4-chlorophenyl)ethanesulfonic
Colorless crystals, yield: 93%. Mp >330 ꢁC (dec). 1H NMR (D2O,
300 MHz)
: 3.47 (dd, J¼13.4, 8.6 Hz, 1H in CH2N), 3.76 (dd, J¼13.4,
6.9 Hz, 1H in CH2N), 4.27 (dd, J¼8.6, 6.9 Hz, 1H, CHS), 7.38 (m, 4H,
acid
(4b).25a
26.0, 10.3. IR (CHCl3),
n
(cmꢀ1) : 1699 (C]O), 1556 (NO2). HRMS
(ESI) calcd for C12H14NO3NaSCl [MþNa]þ m/z: 310.0275; found:
d
310.0271.

N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
2521
ArH); 13C NMR (D2OeHCOOH, 75.5 MHz)
130.9, 134.9.
d
: 41.1, 61.9, 129.2, 129.4,
4.4.11. syn-2-Amino-1-phenylpropane-1-sulfonic
acid
(syn-4j).
Colorless crystals, yield: 88%. Mp >310 ꢁC. 1H NMR (300 MHz, D2O)
d
: 7.34 (s, 5H, ArH), 4.12e4.01 (m, 2H, CHN and CHS), 1.06 (d,
4.4.3. 1-Amino-3-methylbutane-2-sulfonic acid (4c).25a Colorless
crystals, yield: 94%. Mp >330 ꢁC (dec). 1H NMR (D2O, 300 MHz)
J¼6.3 Hz, 3H, CH3); 13C NMR (125 MHz, D2OeHCOOH)
d: 133.1,
d:
130.2, 129.52, 129.47, 68.5, 48.8, 17.4. HRMS (ESI) calcd for
3.26 (dd, J¼13.8, 2.9 Hz, 1H in CH2N), 3.18 (dd, J¼13.8, 10.1 Hz, 1H in
CH2N), 2.87 (ddd, J¼10.1, 3.3, 2.9 Hz, 1H, CHS), 2.22 (dhept, J¼3.3,
7.0 Hz, 1H, CH), 0.97 (d, J¼7.0 Hz, 3H, CH3), 0.89 (d, J¼7.0 Hz, 3H,
C9H14NO3S [MþH]þ m/z: 216.0689; found: 216.0690.
4.4.12. anti-2-Amino-1-phenylbutane-1-sulfonic acid (anti-4k).
Colorless crystals, yield: 87%. Mp >310 ꢁC. 1H NMR (300 MHz, D2O)
CH3); 13C NMR (75 MHz, D2OeHCOOH)
d: 62.8, 37.4, 28.0, 21.1, 17.2.
d
: 7.42e7.27 (m, 5H, ArH), 4.25 (d, J¼4.4 Hz, 1H, CHN), 3.89e3.83
4.4.4. 1-Amino-2-phenylpropane-2-sulfonic acid (4d).25a Colorless
crystals, yield: 97%. Mp 288e289 ꢁC (MeOH), lit.21 mp 285e287 ꢁC.
(m, 1H, CHN),1.75e1.43 (m, 2H, CH2), 0.92 (t, J¼7.4 Hz, 3H, CH3); 13
C
NMR (75 MHz, DMSO-d6) d: 133.5, 130.0, 128.1, 127.4, 63.6, 53.5,
1H NMR (D2O, 200 MHz)
d: 7.38e7.45 (m, 2H, Ar), 7.23e7.31 (m, 3H,
24.1, 10.2. HRMS (ESI) calcd for C10H15NO3SNaþ [MþNa]þ m/z:
ArH), 3.68 (d, J¼13.4 Hz, 1H in CH2), 3.51 (d, J¼13.4 Hz, 1H in CH2),
252.0665; found: 252.0667.
1.67 (s, 3H, CH3); 13C NMR (D2O, 75 MHz)
d: 134.8, 128.9, 128.8,
129.9, 61.6, 44.7, 18.2. HRMS (ESI) calcd for C9H14NO3Sþ [MþH]þ m/
z: 216.0689; found 216.0693.
4.4.13. syn-2-Amino-1-phenylbutane-1-sulfonic
Colorless crystals, yield: 87%. Mp >310 ꢁC. 1H NMR (400 MHz,
DMSO-d6) : 8.17 (br s, 3H), 7.33e7.27 (m, 5H, ArH), 3.75 (d,
acid
(syn-4k).
d
4.4.5. 1-Amino-2-methylbutane-2-sulfonic acid (4e).25a Colorless
J¼10.9 Hz, 1H, CHS), 3.68e3.62 (m, 1H, CHN), 1.45e1.16 (m, 2H,
crystals, yield: 91%. Mp 324e327 ꢁC. 1H NMR (300 MHz, D2O)
d:
CH2), 0.76 (t, J¼7.3 Hz, 3H, CH3); 13C NMR (101 MHz, DMSO-d6)
d:
3.21 (d, J¼15.1 Hz, 1H in CH2N), 3.15 (d, J¼15.1 Hz, 1H in CH2N), 1.78
(dq, J¼14.4, 7.6 Hz, 1H in CH2), 1.69 (dq, J¼14.4, 7.6 Hz, 1H in CH2),
1.25 (s, 3H, CH3), 0.89 (t, J¼7.6 Hz, 3H, CH3); 13C NMR (125 MHz,
135.4, 129.6, 127.9, 127.2, 66.0, 53.1, 23.9, 8.7. HRMS (ESI) calcd for
C10H15NO3SNaþ [MþNa]þ m/z: 252.0665; found, 252.0659.
D2OeHCOOH)
d
: 58.0, 42.8, 25.6, 16.6, 7.1. HRMS (ESI) calcd for
4.4.14. anti-2-Amino-1-(4-chlorophenyl)propane-1-sulfonic
(anti-4l). Colorless crystals, yield: 82% (PtO2 as the catalyst.). Mp
>10 ꢁC. 1H NMR (300 MHz, D2O)
: 7.43e7.35 (m, 4H, ArH), 4.18 (d,
acid
C5H14NO3S [MþH]þ m/z: 168.0689; found 168.0690.
d
4.4.6. 1-Amino-2,4,4-trimethylpentane-2-sulfonic acid (4f). Colorless
J¼6.3 Hz, 1H, CHS), 4.06 (dq, J¼6.3, 6.6 Hz, 1H, CHN), 1.39 (d,
crystals, yield: 98%. Mp 329 ꢁC (dec). 1H NMR (300 MHz, D2O)
d:
J¼6.6 Hz, 3H, CH3); 13C NMR (75 MHz, DMSO-d6)
d: 134.0, 132.5,
3.37 (d, J¼14.2 Hz, 1H in CH2N), 3.25 (d, J¼14.2 Hz, 1H in CH2N), 1.76
131.7, 127.9, 66.4, 47.9, 17.2. HRMS (ESI) calcd for C9H13ClNO3Sþ
(d, J¼15.0 Hz, 1H in CH2), 1.63 (d, J¼15.0 Hz, 1H in CH2), 1.40 (s, 3H,
[MþH]þ m/z: 250.0299; found: 250.0311.
CH3), 0.91 (s, 9H, 3CH3 in t-Bu); 13C NMR (101 MHz, DMSO-d6)
d:
56.8, 43.9, 43.8, 31.6, 31.5, 18.2. HRMS (ESI) calcd for C8H19NNaO3Sþ
4.4.15. syn-2-Amino-1-(4-chlorophenyl)propane-1-sulfonic
(syn-4l). Colorless crystals, yield: 92% (PtO2 as the catalyst). Mp
>310 ꢁC. 1H NMR (300 MHz, DMSO-d6)
: 8.05 (br s, 3H, NH3), 7.38
acid
[MþNa]þ m/z: 232.0978; found: 232.0984.
d
4.4.7. 2-Amino-1,1-diphenylethanesulfonic acid (4g).22 Colorless
crystals, yield 90%. Mp 196e198 ꢁC (dec). 1H NMR (300 MHz,
(d, J¼8.6 Hz, 2H, ArH), 7.35 (d, J¼8.6 Hz, 2H, ArH), 4.05 (dq, J¼10.4,
5.6 Hz, 1H, CHN), 3.97 (d, J¼10.4 Hz, 1H, CHS), 0.92 (d, J¼5.6 Hz, 3H,
DMSO-d6)
d
: 7.28e7.11 (m, 10H, ArH), 3.69 (s, 2H, CH2); 13C NMR
CH3); 13C NMR (75 MHz, DMSO-d6)
d: 134.6, 132.0, 131.4, 127.9, 66.7,
(75.5 MHz, HCO2H)
d
: 143.1, 128.9, 128.5, 126.0, 75.9, 49.5. IR,
n
48.0, 17.4. HRMS (ESI) calcd for C9H13ClNO3Sþ [MþH]þ m/z:
(cmꢀ1): 3424.2 (br, NH and OH), 1178.6 (SO2). MS (ESI) m/z: 276
[MꢀH]ꢀ. HRMS (ESI) calcd for C14H16NO3S [MþH]þ m/z: 278.0845;
found: 278.0835.
250.0299; found: 250.0303.
4.4.16. anti-2-Amino-1-(4-chlorophenyl)butane-1-sulfonic
(anti-4m). Colorless crystals, yield: 83% (PtO2 as the catalyst).
Mp 307e310 ꢁC (dec). 1H NMR (300 MHz, DMSO-d6)
: 7.88 (s,
acid
4.4.8. 2-Aminopropane-1-sulfonic acid (4h).25b Colorless crystals,
yield: 75%. Mp >330 ꢁC, lit.25b mp 318e320 ꢁC. 1H NMR (300 MHz,
d
3H, NH3), 7.50 (d, J¼8.6 Hz, 2H, ArH), 7.42 (d, J¼8.6 Hz, 2H,
ArH), 4.07 (d, J¼2.8 Hz, 1H, CHS), 3.63 (m, 1H, CHN), 1.42e1.35
(m, 2H, CH2), 0.91 (t, J¼7.4 Hz, 3H, CH3); 13C NMR (75 MHz,
D2O)
d
: 5.56 (ddq, J¼3.0, 8.1, 6.5 Hz, 1H, CHN), 3.12 (dd, J¼3.6,
13.7 Hz, 1H in CH2S), 2.96 (dd, J¼8.1, 13.7 Hz, 1H in CH2S), 1.24
(d, J¼6.5 Hz, 3H, CH3); 13C NMR (75.5 MHz, D2OeHCO2H)
d
: 73.5,
DMSO-d6) d: 132.6, 132.3, 131.9, 128.1, 62.8, 53.4, 24.1, 10.1.
44.3, 18.0.
HRMS (ESI) calcd for C10H14ClNO3SNaþ [MþNa]þ m/z: 286.0275;
found: 286.0278.
4.4.9. 2-Aminobutane-1-sulfonic acid (4i).41 Colorless crystals,
yield: 78%. Mp 306e307 ꢁC (dec), lit.41 mp 303e306 ꢁC. 1H NMR
4.4.17. syn-2-Amino-1-(4-chlorophenyl)butane-1-sulfonic acid (syn-
(300 MHz, D2O)
d
: 3.50 (ddt, J¼9.4, 3.1, 6.7 Hz, 1H, CHN), 3.15 (dd,
4m). Colorless crystals, yield: 80% (PtO2 as the catalyst.). Mp
J¼15.0, 3.1 Hz, 1H in CH2S), 3.00 (dd, J¼15.0, 9.4 Hz, 1H in CH2S),
>310 ꢁC (dec). 1H NMR (300 MHz, DMSO-d6)
d: 8.25 (br s, 3H,
1.67 (dq, J¼6.7, 7.5 Hz, 2H, CH2), 0.88 (t, J¼7.5 Hz, 3H, CH3); 13C NMR
NHþ3 ), 7.45 (d, J¼8.6 Hz, 2H, ArH), 7.33 (d, J¼8.6 Hz, 2H, ArH),
3.75 (d, J¼10.6 Hz, 1H, CHS), 3.74e3.71 (m, 1H, CHN), 1.44e1.13
(m, 2H, CH2), 0.77 (d, J¼7.4 Hz, 3H, CH3); 13C NMR (75 MHz,
(300 MHz, D2OeHCOOH) d: 51.9, 50.5, 25.9, 9.2. HRMS (ESI) calcd
for C4H11NO3SNaþ [MþNa]þ m/z: 176.0352; found: 176.0357.
DMSO-d6)
d: 134.6, 132.8, 130.9, 128.2, 63.5, 53.1, 24.0, 10.2.
4.4.10. anti-2-Amino-1-phenylpropane-1-sulfonic acid (anti-4j).
Colorless crystals, yield: 83%. Mp 291e293 ꢁC. 1H NMR
HRMS (ESI) calcd for C10H14ClNO3SNaþ [MþH]þ m/z: 286.0275;
found: 286.0265.
(300 MHz, D2O)
d
: 7.40e7.34 (m, 5H, ArH), 4.16 (d, J¼6.3 Hz, 1H,
CHS), 4.06 (dq, J¼6.3, 6.6, 1H, CHN), 1.40 (d, J¼6.6 Hz, 3H, CH3);
4.4.18. anti-2-Amino-1,2-diphenylethanesulfonic acid (anti-4n).20
Colorless crystals, yield, 88%. Mp 288e290 ꢁC, lit.20 mp 306e308 ꢁC.
13C NMR (75 MHz, D2OeHCOOH)
d: 132.0, 130.03, 129.99, 68.2,
49.5, 17.7. HRMS (ESI) calcd for C9H14NO3S [MþH]þ m/z:
216.0689; found: 216.0680. Anal. Calcd for C9H14NO3S$1/4H2O:
C, 50.21; H, 6.09; N, 6.51; S, 14.90; Found: C, 49.08; H, 6.14; N,
6.50; S, 14.47.
1H NMR (300 M)
d: 8.01 (br s, 3H), 7.24e7.07 (m, 10H, ArH), 4.99 (d,
J¼3.1 Hz, 1H, CHN), 4.09 (d, J¼3.1 Hz, 1H, CHS); 13C NMR (75 MHz,
DMSO)
56.09.
d: 135.87,132.84,130.38,128.13,128.07,127.73,127.41, 67.38,

2522
N. Chen, J. Xu / Tetrahedron 68 (2012) 2513e2522
Marijne, M. F.; Brouwer, A. J.; Liskamp, R. M. J. Tetrahedron Lett. 2000, 41,
Acknowledgements
7991e7995; (h) Zhang, W.; Wang, B. Y.; Chen, N.; Du, D. M.; Xu, J. X. Synthesis
2008, 197e200; (i) Brouwer, A. J.; Ceylan, T.; van der Linden, T.; Liskamp, R. M. J.
Tetrahedron Lett. 2009, 50, 3391e3393.
This work was supported by the National Natural Science
Foundation of China (20973013) and the Beijing Natural Science
Foundation (2092022).
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Supplementary data
19. Chen, N.; Jia, W. Y.; Xu, J. X. Eur. J. Org. Chem. 2009, 5841e5846.
20. Cordero, F. M.; Cacciarini, M.; Machetti, F.; De Darlo, F. Eur. J. Org. Chem. 2002,
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Copies of 1H and 13C NMR spectra. Supplementary data associated
with this article can be found in the online version, at doi:10.1016/
j.tet.2011.11.020. These data include MOL files and InChiKeys of the
most important compounds described in this article.
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