Asymmetric synthesis of 1,2-anti-disubstituted taurine derivatives

Article abstract of DOI:10.1055/s-0029-1216643

An efficient asymmetric synthesis of anti-1,2-disubstituted taurine derivatives through nucleophilic addition of phenylmethanesulfonate to various N-acylimines in the presence of 1,2:5,6-di-O-isopropylidene-α-D- allofuranose as a chiral auxiliary is descr

Full text of DOI:10.1055/s-0029-1216643

PAPER
1683
Asymmetric Synthesis of 1,2-anti-Disubstituted Taurine Derivatives
1
, 2-anti-Disubstitu
i
ted Tau
e
rine
D
eriv
t
atives er Enders,* Dirk Iffland, Gerhard Raabe
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Fax +49(241)8092127; E-mail: enders@rwth-aachen.de
Received 12 February 2009
hols,4 and from epoxides.5 2-Substituted taurines have
been prepared from b-amino primary alcohols,6 from azir-
idines,7 and from 2-nitroalkanesulfonic acids.8 1,1-Disub-
stituted taurines are available from ketones through
Abstract: An efficient asymmetric synthesis of anti-1,2-disubsti-
tuted taurine derivatives through nucleophilic addition of phenyl-
methanesulfonate to various N-acylimines in the presence of
1,2:5,6-di-O-isopropylidene-a-D-allofuranose as a chiral auxiliary
is described. The taurine derivatives were obtained in three steps Corey–Chaykovsky epoxidation, episulfidation, and
with good overall yields (36–61%) and excellent enantiomeric ex-
ammonia-induced ring cleavage, followed by oxidation
with performic acid.9 1,2-Disubstituted taurines have been
cesses (83–98%). The diastereomeric excesses of 15–91% could be
improved to 90–98% by column chromatography or recrystalliza-
prepared from olefins9,10 and from epoxides.5 2,2-Disub-
tion. The relative and absolute configurations of the products were
stituted taurines have been synthesized from aziridines,11
determined by means of an X-ray crystal structure analysis.
from amino alcohols,6f and from ketones through the
Key words: taurine, asymmetric synthesis, sugar auxiliary, N-
Strecker amino acid synthesis.12
acylimines, a-amido sulfones, chiral auxiliary
Our group has described an efficient asymmetric synthe-
sis of 2-substituted and 1,2-disubstituted taurine deriva-
tives through aza-Michael addition of the enantiopure
hydrazines (2S)-2-(methoxymethyl)pyrrolidin-1-amine
(SAMP) or (2R,3aR,6aR)-2-(methoxymethyl)hexahydro-
cyclopenta[b]pyrrol-1(2H)-amine (RAMBO) to a,b-un-
saturated sulfonates in the presence of a Lewis acid
catalyst.13
Sulfonic acids and their derivatives are important biolog-
ically active constituents of mammals, marine algae, fish,
and shellfish.1 The best known are 2-aminoethanesulfonic
acid (taurine) and related compounds such as 3-aminopro-
panesulfonic acid (homotaurine), 2-carbamimidamido-
ethanesulfonic acid (N-guanidinotaurine), cysteic acid,
and 2-hydroxyethanesulfonic acid (isethionic acid)
(Figure 1). Taurine is found in relatively high concentra-
tions in the central nervous system, brain, heart, retina,
and muscles, and is involved in various physiological pro-
cesses such as brain development, neurotransmission, and
immunomodulation.2
In our ongoing research on the asymmetric synthesis of
sulfonic acid derivatives, we planned to gain access to
1,2-disubstituted taurine derivatives through nucleophilic
addition to an N-acylimine of a chiral phenylmethane-
sulfonate bearing an enantiopure sugar auxiliary.
In previous communications and a full paper,14 we report-
ed on efficient asymmetric electrophilic a-substitution re-
actions of various alkyl halides and nitroalkenes with
benzyl sulfonates bearing 1,2:5,6-di-O-isopropylidene-a-
D-allofuranose as a chiral auxiliary. In subsequent inves-
tigations, we extended this method by using allylic halides
as electrophiles to give a,g-substituted g-sultones diaste-
reo- and enantioselectively.15 We also used this method in
a highly efficient asymmetric synthesis of a,g-substituted
g-amino sulfonates through diastereoselective ring-open-
ing of the g-sultones.16
In view of the important physiological effects of these nat-
urally occurring aminosulfonic acids, which can be re-
garded as sulfur analogues of amino acids, the
development of new diastereo- and enantioselective
methods for their synthesis is highly desirable.
Several reports have already been devoted to the synthesis
of taurine derivatives. 1-Substituted taurines have been
synthesized from olefins,3 from b-amino secondary alco-
H
N
NH2
NH2
HO3S
NH2
HO3S
HO3S
Moreover, in our synthesis of various optically active a,g-
substituted sulfonates from the sultones,17 we have shown
that the ring-opening reaction of the g-sultones proceeds
by an SN2 mechanism with inversion of configuration at
the attacked g-carbon. Very recently, the method has been
extended to alkyl bromoacetates18 and aldehydes19 as
electrophiles.
NH
taurine
homotaurine
N-guanidino taurine
NH2
CO2H
cysteic acid
OH
HO3S
HO3S
isethionic acid
We now wish to describe a short three-step asymmetric
synthesis of anti-configured 1,2-disubstituted taurine de-
rivatives through addition of phenylmethanesulfonate to
various N-acylimines using 1,2:5,6-di-O-isopropylidene-
a-D-allofuranose as a chiral auxiliary.
Figure 1 Taurine and related compounds
SYNTHESIS 2009, No. 10, pp 1683–1688
x
x.
x
x
.
2
0
0
9
Advanced online publication: 14.04.2009
DOI: 10.1055/s-0029-1216643; Art ID: Z02409SS
© Georg Thieme Verlag Stuttgart · New York

1684
D. Enders et al.
PAPER
Because of their high electrophilicity, N-acylimines are
much more reactive than the corresponding N-alkyl and
N-aryl analogues. N-Acylimines can be generated in situ
from the corresponding a-amido sulfones 2, which serve
as stable precursors, by elimination with a suitable base.
We used the benzyloxycarbonyl (Cbz) group as an acti-
vating N-acyl substituent to obtain the final 1,2-disubsti-
tuted taurine derivatives in a protected form that can
easily be cleaved under mild conditions.
CbzHN
R
a
SO3R*
SO3R*
76–94%
1
3a–e
36–61%
(3 steps)
b
CbzHN
R
CbzHN
R
First, we investigated the reaction between a-amido sul-
fone 2a and the enantiopure sulfonate 1 (Figure 2). One
equivalent of sulfonate 1 was deprotonated with one
equivalent of butyllithium at –100 °C and then treated
with 0.5 equivalents of a-amido sulfone 2a at –100 °C for
2 h and then overnight at –78 °C. After aqueous workup,
the 1,2-disubstituted taurine derivative 3a was obtained in
very good yield (82%). In this method, 0.5 equivalents of
the enantiopure sulfonate 1 are regenerated in the elimina-
tion step that forms the corresponding acylimine from 2a,
and can be separated and recovered by flash column chro-
matography.
c
SO3i-Pr
SO3H
48–71%
(2 steps)
5a–e
4a–e
R = aryl ,alkyl
ee = 83–98%
de = 15–91% (90–98%
after column chromatography
or recrystallization)
Scheme 1 Synthesis of the protected 1,2-disubstituted taurine deri-
vatives 5a–e from the enantiopure sulfonate 1. Reagents and condi-
tions: (a) BuLi (1.0 equiv), THF, –100 °C, 1 h, then a-amido sulfone
2a–e (0.5 equiv), –100 °C, 2 h, then –78 °C, overnight; (b) 2% TFA
in EtOH, reflux; (c) (i-PrO)3CH, CH2Cl2, rt.
ArO2S
SO3R*
R
NHCbz
Table 1 Asymmetric Syntheses of Protected Taurine Derivatives
5a–e
1
2a: R = Ph, Ar = Ph
2b: R = 4-ClC6H4, Ar = Ph.
2c: R = Ar = Tol
2d: R = i-Pr, Ar = Tol
2e: R = Et, Ar = Tol
Product
5a
R
Yield (%)a de (%)b
ee (%)b
97
Ph
58
36
61
49
46
66 (98)c
35 (98)d
37 (90)d
91 (98)d
15
O
Me
Me
O
O
5b
4-ClC6H4
4-Tol
i-Pr
93
O
R* =
Me
O
5c
98
Me
Figure 2 Enantiopure sulfonate 1 and a-amido sulfones 2a–e
5d
98
5e
Et
83
Cleavage of the chiral auxiliary was accomplished by
treatment with trifluoroacetic acid in refluxing ethanol.
Subsequent treatment of the resulting sulfonic acid 4a
with triisopropyl orthoformate in dichloromethane gave
the final protected 1,2-disubstituted taurine derivative 5a
in good overall yield (58%, three steps) and high stereose-
lectivities [ee = 97%; de = 66% (98% after recrystalliza-
tion)] (Scheme 1).
a Overall yield of the three-step synthesis.
b Determined by HPLC on a chiral stationary phase.
c The value in parentheses is after recrystallization.
d The values in parentheses is after flash column chromatography.
We then applied these conditions to various a-amido sul-
fones 2. Thus, the enantiopure sulfonate 1 was deprotonat-
ed with butyllithium in tetrahydrofuran at –100 °C, the a-
amido sulfone was added at –100 °C, and the mixture was
kept for 2 h at –100 °C and then overnight at –78 °C to
give the final 1,2-disubstituted taurine derivative 5a–e in
good overall yields and high stereoselectivities. The re-
sults are summarized in Table 1.
A single crystal X-ray structure analysis carried out on
compound 5d provided unambiguous proof of the struc-
ture (Figure 3).20 The configuration of the stereogenic
center at the a-position is S and that at the b-position is R.
Therefore, on the assumption that the reaction mechanism
is uniform, all the 1,2-disubstituted taurine derivatives
5a–e are expected to have a (1S,2R)-configuration.
Figure 3 X-ray crystal structure of 5d
In summary, we have developed an efficient three-step
asymmetric synthesis of protected 1,2-disubstituted tau-
rine derivatives starting from the sulfonate 1. The result-
ing anti-configured b-amino sulfonates 5a–e were
Synthesis 2009, No. 10, 1683–1688 © Thieme Stuttgart · New York

PAPER
1,2-anti-Disubstituted Taurine Derivatives
1685
1,2:5,6-Di-O-isopropylidene-a-d-allofuranos-3-yl (1S, 2R)-2-
[(Benzyloxycarbonyl)amino]-2-(4-chlorophenyl)-1-phenyl-
ethanesulfonate (3b)
According to the general procedure, the sulfonate 1 (928 mg, 2.24
mmol) was deprotonated with a 1.6 M solution of BuLi in hexane
(1.40 mL) and allowed to react with a-amido sulfone 2b (465 mg,
1.12 mmol). Workup and flash column chromatography gave 3b as
a colourless solid; yield: 581 mg (76%); mp 135 °C.
obtained in moderate-to-good overall yields (36–61%)
and good-to-excellent stereoselectivities [ee = 83–98%,
de = 15–91% (90–98% after column chromatography or
recrystallization)]. The relative and absolute configura-
tion of the compounds was determined by X-ray crystal
structure analysis on a typical example.
IR (KBr): 3373, 2988, 2932, 1720, 1528, 1497, 1455, 1375, 1244,
1168, 1022, 877, 832, 758, 698, 517 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.29 (s, 3 H, CH3), 1.36 (s, 3 H,
CH3), 1.45 (s, 3 H, CH3), 1.56 (s, 3 H, CH3), 3.78 (dd, J = 7.3, 8.5
All solvents were dried by conventional methods. Starting materials
and reagents were purchased from commercial suppliers and used
without further purification. THF was freshly distilled from Na/Pb
alloy under argon. Preparative column chromatography: Merck sil-
ica gel 60, particle size 0.040–0.063 mm (230–240 mesh, flash).
Analytical TLC: silica gel 60, F254 plates (Merck, Darmstadt). Op-
tical rotation values were measured on a PerkinElmer P241 pola-
rimeter. IR spectra were recorded on a PerkinElmer 1760 FT-IR
Hz,
1
H, CHHOC), 3.94–4.02 (m,
2
H, CHHOC,
H,
SO3CHCHCHCH2O), 4.16 [dd, J = 4.0, 6.0 Hz,
1
SO3CHCHOC(CH3)2], 4.25–4.31 (m, 1 H, SO3CHCHCHO), 4.71–
4.79 (m, 2 H, PhCHSO3CH, PhCHSO3), 5.09 [s, 2 H, C(O)CH2Ph],
5.61 (d, J = 9.3 Hz, 1 H, NH), 5.65 [d, J = 3.7 Hz, 1 H,
SO3CHCHCH(O)2], 5.79 (dd, J = 4.7, 9.2 Hz, 1 H, PhCHNH),
7.06–7.42 (m, 14 H, PhH).
13C NMR (75 MHz, CDCl3): d = 25.1 (CH3), 26.2 (CH3), 26.6
(CH3), 26.7 (CH3), 54.9 (PhCHNH), 65.1 (CH2OC), 67.3
(OCH2Ph), 71.8 (PhCHSO3), 74.6 (CHO), 76.8 (CHO), 77.6
(CHO), 77.7 (CHO), 103.6 [CH(OC)2], 110.2 [(O)2C(CH3)2], 113.6
[(O)2C(CH3)2], 128.1, 128.2, 128.5, 128.6, 129.0, 129.7, 130.2
(CHarom), 134.0, 136.0, 136.9 (Carom), 155.1 (NHCO).
1
spectrophotometer. H and 13C NMR spectra were recorded on a
Gemini 300 or a Varian Inova 400, and all measurements were per-
formed with tetramethylsilane as the internal standard. Mass spectra
were acquired on a Finnigan SSQ 7000 spectrometer (EI: 70 eV).
Microanalyses were obtained with a Vario EL element analyzer.
1,2-Disubstituted Taurine Derivatives 3a–e; General Procedure
The enantiopure sulfonate 1 (1.0 equiv) was dissolved in anhyd
THF (20 mL) and the solution was cooled to –100 °C. After 20 min,
BuLi (1.0 equiv) was added dropwise. The solution was stirred for
1 h, after which the a-amido sulfone 2 (0.5 equiv) was added. The
mixture was stirred for 2 h at –100 °C, and then at –78 °C to r.t.
overnight. The mixture was quenched with H2O (5 mL) and evapo-
rated to dryness. The crude product was purified by flash column
chromatography (silica gel, Et2O–pentane 1:1) to yield the sulfonate
esters 3a–e.
MS (EI, 70 eV): m/z (%) = 672 (5), 274 (59), 230 (26), 214 (11), 179
(14), 166 (19), 127 (6), 108 (9), 91 (100), 65 (5).
Anal. Calcd for C34H38NO10SCl: C, 59.34; H, 5.57; N, 2.04. Found:
C, 59.44; H, 5.83; N, 1.90.
1,2:5,6-Di-O-isopropylidene-a-d-allofuranos-3-yl (1S, 2R)-2-
[(Benzyloxycarbonyl)amino]-1-phenyl-2-(4-tolyl)ethane-
sulfonate (3c)
According to the general procedure, the sulfonate 1 (900 mg, 2.17
mmol) was deprotonated with a 1.6 M solution of BuLi in hexane
(1.36 mL) and allowed to react with a-amido sulfone 2c (445 mg,
1.09 mmol). Workup and flash column chromatography gave 3c as
a colourless solid; yield: 685 mg (94%); mp 84 °C.
1,2:5,6-Di-O-isopropylidene-a-d-allofuranos-3-yl (1S, 2R)-2-
[(Benzyloxycarbonyl)amino]-1,2-diphenylethanesulfonate (3a)
According to the general procedure, the sulfonate 1 (400 mg, 0.97
mmol) was deprotonated with a 1.6 M solution of BuLi in hexane
(0.60 mL) and allowed to react with a-amido sulfone 2a (185 mg,
0.49 mmol). Workup and flash column chromatography gave 3a as
a colourless solid; yield: 262 mg (82%); mp 123 °C.
IR (KBr): 3852, 3742, 3620, 3364, 2986, 2361, 2340, 2329, 1720,
1522, 1459, 1373, 1243, 1168, 1024, 836, 739, 698, 601, 518 cm–1.
IR (KBr): 3350, 2987, 2937, 2361, 1718, 1522, 1455, 1373, 1244,
1168, 1121, 1025, 922, 878, 834, 756, 699, 606, 512 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.30 (s, 3 H, CH3), 1.34 (s, 3 H,
CH3), 1.46 (s, 3 H, CH3), 1.56 (s, 3 H, CH3), 2.32 (s, 3 H, PhCH3),
3.77 (dd, J = 7.2, 9.0 Hz, 1 H, CHHOC), 3.97 (dd J = 7.4, 9.0 Hz, 1
H, CHHOC), 4.04 (d, J = 4.9 Hz, 1 H, SO3CHCHCHCH2O), 4.17
[br s, 1 H, SO3CHCHOC(CH3)2], 4.29 (br s, 1 H, SO3CHCHCHO),
4.73 (dd, J = 4.9, 8.7 Hz, 1 H, PhCHSO3CH), 4.80 (br s, 1 H,
PhCHSO3), 5.05 [d, J = 12.3 Hz, 1 H, C(O)CHHPh], 5.09 [d,
J = 12.2 Hz, 1 H, C(O)CHHPh], 5.47 (br s, 1 H, NH), 5.66 [d,
J = 3.7 Hz, 1 H, SO3CHCHCH(O)2], 5.85 (dd, J = 4.4, 9.7 Hz, 1 H,
PhCHNH), 6.99–7.40 (m, 14 H, PhH).
13C NMR (100 MHz, CDCl3): d = 21.2 (PhCH3), 25.3 (CH3), 26.4
(CH3), 26.7 (CH3), 26.8 (CH3), 55.0 (CH3PhCHNH), 65.1
(CH2OC), 67.1 (OCH2Ph), 72.1 (PhCHSO3), 74.4 (CHO), 76.7
(CHO), 77.6 (CHO), 103.6 [CH(OC)2], 110.1 [(O)2C(CH3)2], 113.6
[(O)2C(CH3)2], 126.6, 127.8, 128.1, 128.4, 128.7, 129.1, 130.0
(CHarom), 135.3, 136.1, 137.8 (Carom), 155.1 (NHCO).
1H NMR (400 MHz, CDCl3): d = 1.30 (s, 3 H, CH3), 1.33 (s, 3 H,
CH3), 1.46 (s, 3 H, CH3), 1.57 (s, 3 H, CH3), 3.77 (dd, J = 7.1, 9.0
Hz, 1 H, CHHOC), 3.97 (dd, J = 7.3, 9.0 Hz, 1 H, CHHOC), 4.03
(d, J = 5.7 Hz, 1 H, SO3CHCHCHCH2O), 4.18 [br s, 1 H, SO3
CHCHOC(CH3)2], 4.30 (br s, 1 H, SO3CHCHCHO), 4.76 (dd,
J = 4.6, 8.5 Hz, 1 H, PhCHSO3CH), 4.81 (br s, 1 H, PhCHSO3),
5.06 [d, J = 12.3 Hz, 1 H, C(O)CHHPh], 5.10 [d, J = 12.2 Hz, 1H,
C(O)CHHPh], 5.48 (br s, 1 H, NH), 5.66 [d, J = 3.7 Hz, 1 H,
SO3CHCHCH(O)2], 5.90 (dd, J = 4.3, 9.6 Hz, 1 H, PhCHNH),
7.10–7.20 (m, 15 H, PhH).
13C NMR (100 MHz, CDCl3): d = 25.2 (CH3), 26.4 (CH3), 26.7
(CH3), 26.8 (CH3), 55.1 (PhCHNH), 65.2 (CH2OC), 67.2
(OCH2Ph), 72.1 (PhCHSO3), 74.5 (CHO), 76.8 (CHO), 77.7
(CHO), 103.6 [CH(OC)2], 110.1 [(O)2C(CH3)2], 113.6
[(O)2C(CH3)2], 127.0, 128.0, 128.3, 128.4, 128.8, 129.4, 130.3
(CHarom), 136.1, 138.3 (Carom), 155.1 (NHCO).
MS (EI, 70 eV): m/z (%) = 652 (5), 544 (5), 300 (5), 254 (71), 236
(13), 210 (44), 193 (7), 146 (55), 107 (9), 101 (23), 91 (100), 55
(16).
MS (EI, 70 eV): m/z (%) = 638 (12), 286 (6), 240 (68), 196 (43), 180
(5), 113 (5), 101 (10), 91 (100), 56 (6).
Anal. Calcd for C34H39NO10S: C, 62.47; H, 6.01; N, 2.14. Found: C,
62.39; H, 6.26; N, 2.17.
Anal. Calcd for C35H41NO10S: C, 62.95; H, 6.19; N, 2.10. Found: C,
62.79; H, 6.22; N, 2.21.
Synthesis 2009, No. 10, 1683–1688 © Thieme Stuttgart · New York

1686
D. Enders et al.
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1,2:5,6-Di-O-isopropylidene-a-d-allofuranos-3-yl (1S, 2R)-2-
[(Benzyloxycarbonyl)amino]-3-methyl-1-phenylbutane-1-sul-
fonate (3d)
According to the general procedure, the sulfonate 1 (1030 mg, 2.49
mmol) was deprotonated with a 1.6 M solution of BuLi in hexane
(1.55 mL) and allowed to react with a-amido sulfone 2d (449 mg,
1.24 mmol). Workup and flash column chromatography gave 3d as
a colourless solid; yield: 615 mg, (80%); mp 151 °C.
Anal. Calcd for C30H39NO10S: C, 59.49; H, 6.49; N, 2.31. Found: C,
59.73; H, 6.58; N, 2.52.
Isopropyl Sulfonates 5a–e; General Procedure
The taurine derivative 3 was dissolved in a solution of TFA in
EtOH. The solution was refluxed for 16 h and then evaporated to
dryness. The resulting oil was dissolved in CH2Cl2, (i-PrO)3CH was
added dropwise and the mixture was stirred at r.t.. The solvent was
removed in vacuo and the crude product was purified by flash col-
umn chromatography (SiO2, Et2O-pentane 1:1) to yield the final
products 5a-e.
IR (KBr): 3361, 3034, 2979, 1712, 1533, 1457, 1362, 1246, 1169,
1115, 1018, 872, 840, 741, 700, 597, 462 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.89 [d, J = 6.7 Hz, 3 H, PhCH-
CHCH(CH3)CH3], 1.05 [d, J = 6.6 Hz,
3
H, PhCH-
Isopropyl (1S, 2R)-2-[(Benzyloxycarbonyl)amino]-1,2-diphe-
nylethanesulfonate (5a)
CHCH(CH3)CH3], 1.26 (s, 3 H, CH3), 1.36 (s, 3 H, CH3), 1.47 (s, 3
H, CH3), 1.52 (s, 3 H, CH3), 1.85 [sept, J = 6.6 Hz, 1 H, PhCH-
CHCH(CH3)2], 3.87 (dd, J = 6.1, 8.6 Hz, 1 H, CHHOC), 3.97–4.03
[m, 2 H, CHHOC, SO3CHCHCHCH(O)2], 4.10 (dd, J = 4.0, 8.7 Hz,
1 H, SO3CHCHCHCH2), 4.29–4.33 (m, 1 H, SO3CHCHCHCH2),
4.56–4.65 (m, 2 H, PhCHCHNH, PhCHCHNH), 4.67 [dd, J = 4.6,
8.7 Hz, 1 H, PhCHSO3CH], 4.99 [s, 2 H, C(O)CHHPh], 5.61 (d,
J = 3.7 Hz, 1 H, SO3CHCHCH(O)2], 7.21–7.52 (m, 10 H, PhH).
13C NMR (100 MHz, CDCl3): d = 17.5 [CH(CH3)CH3)], 20.3
[CH(CH3)CH3)], 25.3 (CH3), 26.4 (CH3), 26.7 (CH3), 26.8 (CH3),
31.2 [CH(CH3)CH3)], 55.9 (PhCHNH), 65.1 (CH2OC), 66.9
(OCH2Ph), 68.8 (PhCHSO3), 74.4 (CHO), 77.6 (CHO), 77.7
(CHO), 103.4 [CH(OC)2], 110.1 [(O)2C(CH3)2], 113.5
[(O)2C(CH3)2], 127.9, 128.0, 128.4, 128.9, 129.3, 130.0 (Carom),
130.3 (CHarom), 136.4 (Carom), 155.7 (NHCO).
According to the general procedure, the sulfonic acid ester 3a (271
mg, 0.42 mmol) was refluxed in EtOH (10 mL) containing TFA (0.2
mL) for 17 h. The resulting oil was dissolved in CH2Cl2 (10 mL) and
(i-PrO)3CH (1.0 mL, 4.5 mmol) was added dropwise. The mixture
was stirred at r.t. for 4 h. Workup and flash column chromatography
gave 5a as a colourless solid; yield: 133 mg (71%); de = 66%
(HPLC, Daicel Chiralpak IA, heptane–i-PrOH, 7:3) (de ≥ 98% after
recrystallization from i-PrOH); ee = 97% (HPLC, Daicel Chiralpak
IA, heptane–EtOH, 7:3); mp 121 °C; [a]D25 +13.8 (c 1.0, CHCl3).
IR (KBr): 3341, 3064, 3036, 2932, 1698, 1542, 1456, 1343, 1282,
1251, 1166, 1091, 1026 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.08 [d, J = 6.0 Hz, 3 H,
SO3CH(CH3)CH3], 1.26 [d, J = 6.0 Hz, 3 H, SO3CH(CH3)CH3],
4.57 (br s, 1 H, PhCHSO3), 4.76 [sept, J = 6.2, 1 H, (CH3)2CHO3S],
5.05 [d, J = 12.3 Hz, 1 H, C(O)OCHHPh], 5.09 [d, J = 12.3 Hz, 1
H, C(O)OCHHPh], 5.47 (br s, 1 H, NH), 5.78 (dd, J = 4.4, 9.5 Hz,
1 H, PhCHNH), 7.08–7.39 (m, 15 H, PhH).
13C NMR (100 MHz, CDCl3): d = 22.7 (CH3), 23.3 (CH3), 55.2
(PhCHNH), 67.2 (CH2), 71.8 (PhCHSO3), 78.6 [SO3CH(CH3)2],
126.9, 128.1, 128.4, 128.5, 128.8, 129.3, 130.2 (CHarom), 136.1,
138.8 (Carom), 155.1 (NHCO).
MS (EI, 70 eV): m/z (%) = 604 (7), 206 (35), 162 (52), 113 (5), 101
(15), 91 (100).
Anal. Calcd for C31H41NO10S: C, 60.08; H, 6.67; N, 2.26. Found: C,
60.23; H, 6.59; N, 2.27.
1,2:5,6-Di-O-isopropylidene-a-d-allofuranos-3-yl (1S, 2R)-2-
[(Benzyloxycarbonyl)amino]-1-phenylbutane-1-sulfonate (3e)
According to the general procedure, the sulfonate 1 (915 mg, 2.21
mmol) was deprotonated with a 1.6 M solution of BuLi in hexane
(1.38 mL) and allowed to react with a-amido sulfone 2e (385 mg,
1.11 mmol). Workup and flash column chromatography gave 3e as
a colourless solid; yield: 517 mg (77%); mp 132 °C.
MS (EI, 70 eV): m/z (%) = 240 (32), 196 (26), 180 (6), 91 (100).
Anal. Calcd for C25H27NO5S: C, 66.20; H, 6.00; N, 3.09. Found: C,
66.39; H, 6.34; N, 2.88.
Isopropyl (1S, 2R)-2-[(Benzyloxycarbonyl)amino]-2-(4-chlo-
rophenyl)-1-phenylethanesulfonate (5b)
IR (KBr): 3854, 3744, 3673, 3648, 3398, 2982, 2362, 2342, 2330,
1717, 1647, 1534, 1458, 1377, 1237, 1168, 1021, 930, 843, 742,
699, 599, 514, 464 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.91 (t, J = 7.3 Hz, 3 H, CH3CH2),
1.33 (s, 3 H, CH3), 1.35 (s, 3 H, CH3), 1.42 (s, 3 H, CH3), 1.44–1.49
(m, 1 H, CH3CH2), 1.52 (s, 3 H, CH3), 1.70–1.76 (m, 1 H, CH3CH2),
3.68 (dd, J = 6.9, 8.6 Hz, 1 H, CHHOC), 3.90 (dd, J = 6.7, 8.6 Hz,
1 H, CHHOC), 4.02 (dd, J = 4.4, 8.5 Hz, 1 H, SO3CHCHCHCH2O),
4.10–4.14 (m, 1 H, SO3CHCHCHCH2O), 4.32–4.40 (m, 1 H, Ph-
According to the general procedure, the sulfonic acid ester 3b (360
mg, 0.52 mmol) was refluxed in EtOH (20 mL) containing TFA (0.2
mL) for 3 d. The resulting oil was dissolved in CH2Cl2 (10 mL) and
(i-PrO)3CH (1.4 mL, 6.3 mmol) was added dropwise. The mixture
was stirred at r.t. for 20 h. Workup and flash column chromatogra-
phy gave 3b as a colourless solid; yield: 122 mg (48%); de = 35%
(HPLC, Daicel Chiralpak IA, heptane–EtOH 3:1) (de ≥ 98% after
flash column chromatography); ee = 93% (HPLC, Daicel Chiralpak
IA, heptane–EtOH, 3:1); mp 132 °C; [a]D25 +4.9 (c 1.1, CHCl3).
CHCHNH),
4.64–4.69
(m,
2
H,
PhCHCHNH,
H,
SO3CHCHCHCH2O), 4.78 (dd, J = 4.3, 5.0 Hz,
1
IR (KBr): 2250, 3064, 2934, 2863, 1699, 1537, 1457, 1339, 1249,
1163, 1089, 1017, 915, 836, 739, 700, 585, 535 cm–1.
SO3CHCHCHO2), 5.11 [d, J = 12.2 Hz, 1 H, C(O)CHHPh], 5.15 [d,
J = 12.2 Hz, 1 H, C(O)CHHPh], 5.38 (d, J = 8.9 Hz, 1 H, NH), 5.76
[d, J = 3.7 Hz, 1 H, SO3CHCHCH(O)2], 7.29–7.45 (m, 10 H, PhH).
13C NMR (100 MHz, CDCl3): d = 10.3 (CH3CH2), 25.5 (CH3), 25.6
(CH3CH2), 26.2 (CH3), 26.7 (CH3), 54.4 (PhCHCHNH), 65.5
(CH2OC), 66.8 (OCH2Ph), 70.2 (PhCHSO3), 74.8 (CHO), 78.0
(CHO), 103.8 [CH(OC)2], 110.2 [(O)2C(CH3)2], 113.7
[(O)2C(CH3)2], 127.9, 128.0, 128.4, 128.8, 129.2, 129.8 (CHarom),
131.0 (Carom), 136.5 (Carom), 155.7 (NHCO).
1H NMR (300 MHz, CDCl3): d = 1.06 [d, J = 6.2 Hz, 3 H,
SO3CH(CH3)CH3], 1.26 [d, J = 6.2 Hz, 3 H, SO3CH(CH3)CH3],
4.50 (d, J = 4.2 Hz, 1 H, PhCHSO3), 4.74 [sept, J = 6.2, 1 H,
(CH3)2CHO3S], 5.04 [d, J = 12.2 Hz, 1 H, C(O)OCHHPh], 5.08 [d,
J = 12.4 Hz, 1 H, C(O)OCHHPh], 5.53 (br s, 1 H, NH), 5.69 (dd,
J = 4.6, 9.0 Hz, 1 H, PhCHNH), 7.03–7.42 (m, 14 H, PhH).
13C NMR (100 MHz, CDCl3): d = 22.5 (CH3), 23.3 (CH3), 55.0
(PhCHNH), 67.2 (CH2), 71.5 (PhCHSO3), 78.8 [SO3CH(CH3)2],
128.1, 128.2, 128.5, 128.6, 128.7, 128.9, 129.3, 129.5, 130.1
(CHarom), 134.0, 136.0, 137.3 (Carom), 155.2 (NHCO).
MS (EI, 70 eV): m/z (%) = 605 (3), 590 (29), 547 (6), 414 (8), 356
(7), 320 (6), 282 (13), 238 (7), 192 (53), 148 (55), 113 (6), 101 (16),
91 (100).
MS (EI, 70 eV): m/z (%) = 274 (40), 230 (21), 226 (8), 91 (100), 65
(8).
Synthesis 2009, No. 10, 1683–1688 © Thieme Stuttgart · New York

PAPER
1,2-anti-Disubstituted Taurine Derivatives
1687
Anal. Calcd for C25H26NO5SCl: C, 61.53; H, 5.37; N, 2.87. Found:
C, 61.40; H, 5.33; N, 2.96.
Isopropyl (1S, 2R)-2-[(Benzyloxycarbonyl)amino]-1-phenyl-
butane 1-sulfonate (5e)
According to the general procedure, the sulfonic acid ester 3e (488
mg, 0.81 mmol) was refluxed in EtOH (12 mL) containing TFA (0.3
mL) for 16 h. The resulting oil was dissolved in CH2Cl2 (10 mL) and
(i-PrO)3CH (1.8 mL, 8.1 mmol) was added dropwise. The mixture
was stirred at r.t. for 23 h. Workup and flash column chromatogra-
phy gave 5e as a colourless solid; yield: 198 mg (60%); de = 15%
(HPLC, Daicel Chiralpak IA, heptane–EtOH, 9:1); ee = 83%
(HPLC, Daicel Chiralpak IA, heptane–EtOH, 9:1); mp 97 °C.
Isopropyl (1S, 2R)-2-[(Benzyloxycarbonyl)amino]-1-phenyl-2-
(4-tolyl)ethanesulfonate (5c)
According to the general procedure, the sulfonic acid ester 3c (771
mg, 1.16 mmol) was refluxed in EtOH (28 mL) containing TFA
(0.56 mL) for 15 h. The resulting oil was dissolved in CH2Cl2 (28
mL) and (i-PrO)3CH (2.8 mL, 12.6 mmol) was added dropwise. The
mixture was stirred at r.t. for 4 h. Workup and flash column chro-
matography gave 5c as a colourless solid; yield: 352 mg (65%);
de = 37% (HPLC, Daicel Chiralpak IA, heptane–EtOH, 9:1)
(de = 90% after flash column chromatography); ee = 98% (HPLC,
Daicel Chiralpak IA, heptane–EtOH, 9:1); mp 119 °C; [a]D25 +5.6
(c 1.2, CHCl3).
IR (KBr): 3382, 3063, 3038, 2977, 2873, 1709, 1533, 1457, 1343,
1285, 1235, 1165, 1085, 977, 908, 755, 698, 638, 594, 526, 469 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.91 (t, J = 7.4 Hz, 3 H, CH3CH2),
1.07 [d, J = 6.2 Hz, 3 H, SO3CH(CH3)CH3], 1.25 [d, J = 6.2 Hz, 3
H, CHCH(CH3)CH3], 1.78–1.94 (m, 2 H, CH3CH2), 4.26–4.33 (m,
1 H, PhCHCHNH), 4.52 (d, J = 7.0 Hz, 1 H, PhCHSO3), 4.69 [sept,
J = 6.2 Hz, 1 H, SO3CH(CH3)2], 5.05–5.17 [m, 3 H, C(O)OCH2Ph,
NH], 7.30–7.48 (m, 10 H, PhH).
13C NMR (100 MHz, CDCl3): d = 10.3 [CH3CH2], 22.5 (CH3), 23.5
(CH3), 25.3 (CH3CH2), 54.4 (PhCHCHNH), 66.8 (CH2), 69.9
(PhCHSO3), 78.5 [SO3CH(CH3)2], 127.4, 128.1, 128.4, 128.7,
129.0, 130.9 (CHarom), 130.7, 136.5 (Carom), 155.7 (NHCO).
IR (KBr): 3388, 3333, 3032, 2977, 2934, 1728, 1691, 1530, 1455,
1344, 1247, 1165, 1090, 1020, 913, 815, 739, 697, 595, 533 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.06 [d, J = 6.1 Hz, 3 H,
SO3CH(CH3)CH3], 1.25 [d, J = 6.1 Hz, 3 H, SO3CH(CH3)CH3],
2.31 (s, 3 H, PhCH3), 4.53 (br s, 1 H, PhCHSO3), 4.73 [sept, J = 6.2,
1 H, (CH3)2CHO3S], 5.02 [d, J = 12.4 Hz, 1 H, C(O)OCHHPh],
5.06 [d, J = 12.3 Hz, 1 H, C(O)OCHHPh], 5.49 (br s, 1 H, NH), 5.73
(dd, J = 4.6, 9.6 Hz, 1 H, PhCHNH), 6.97–7.38 (m, 14 H, PhH).
13C NMR (100 MHz, CDCl3): d = 21.3 (PhCH3), 22.7 (CH3), 23.3
(CH3), 55.1 (CHNH), 67.1 (CH2), 71.9 (PhCHSO3), 78.5
[SO3CH(CH3)2], 126.9, 128.0, 128.4, 128.7, 129.1, 129.2, 130.2
(CHarom), 135.7, 136.2, 137.8 (Carom), 155.1 (NHCO).
MS (EI, 70 eV): m/z (%) = 405 (5), 192 (73), 181 (25), 148 (84), 117
(7), 107 (9), 91 (100), 65 (13).
Anal. Calcd for C21H27NO5S: C, 62.20; H, 6.71; N, 3.45. Found: C,
61.76; H, 6.53; N, 3.41.
MS (EI, 70 eV): m/z (%) = 254 (54), 210 (48), 91 (100), 65 (5).
Acknowledgment
Anal. Calcd for C26H29NO5S: C, 66.79; H, 6.25; N, 3.00. Found: C,
66.74; H, 6.65; N, 3.05.
This work was supported by the Fonds der Chemischen Industrie.
We thank BASF AG and Bayer AG for the donation of chemicals.
Isopropyl (1S, 2R)-2-[(Benzyloxycarbonyl)amino]-3-methyl-1-
phenylbutane-1-sulfonate (5d)
According to the general procedure, the sulfonic acid ester 3d (404
mg, 0.65 mmol) was refluxed in EtOH (23 mL) containing TFA
(0.46 mL) for 16 h. The resulting oil was dissolved in CH2Cl2 (24
mL) and (i-PrO)3CH (2.3 mL, 10.4 mmol) was added dropwise. The
mixture was stirred at r.t. for 22 h. Workup and flash column chro-
matography gave 5d as a colourless solid; yield: 166 mg (61%);
de = 91% (HPLC, Daicel Chiralpak IA, heptane–i-PrOH, 9:1) (de ≥
98% after flash column chromatography); ee = 98% (HPLC, Daicel
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25
Chiralpak IA, heptane–i-PrOH, 9:1); mp 118 °C; [a]D +67.6 (c
1.0, CHCl3).
IR (KBr): 3386, 2870, 2877, 1724, 1537, 1500, 1458, 1384, 1347,
1304, 1250, 1168, 1093, 1051, 990, 905, 746, 699, 627, 602, 549
cm–1.
1H NMR (400 MHz, CDCl3): d = 0.90 [d, J = 6.7 Hz, 3 H,
CHCH(CH3)CH3], 1.06 [d, J = 6.7 Hz, 3 H, CHCH(CH3)CH3], 1.06
[d, J = 6.2 Hz, 3 H, SO3CH(CH3)CH3], 1.32 [d, J = 6.2 Hz, 3 H,
SO3CH(CH3)CH3], 1.90–1.97 [m, 1 H, CHCH(CH3)2], 4.37 (d,
J = 5.1 Hz, 1 H, PhCHSO3), 4.49–4.62 [m, 1 H, PhCHCHNH], 4.74
[sept, J = 6.2 Hz, 1 H, SO3CH(CH3)2], 5.05 [s, 2 H, C(O)OCH2Ph],
7.22–7.47 (m, 10 H, PhH).
13C NMR (100 MHz, CDCl3): d = 17.2 [PhCHCH(CH3)CH3], 20.4
[PhCHCH(CH3)CH3], 22.6 (CH3), 23.5 (CH3), 31.1 [Ph-
CHCH(CH3)2], 55.9 (PhCHNH), 66.8 (CH2), 68.5 (PhCHSO3), 78.4
[SO3CH(CH3)2], 127.9, 128.0, 128.4, 128.8, 129.0, 130.0 (CHarom),
130.8, 136.4 (Carom), 155.8 (NHCO).
(11) (a) Koller, W.; Linkies, A.; Rehling, H.; Reuschling, D.
Tetrahedron Lett. 1983, 24, 2131. (b) Hu, L. B.; Zhu, H.;
Du, D. M.; Xu, J. X. J. Org. Chem. 2007, 72, 4543.
(12) Wang, B.; Zhang, W.; Zhang, L.; Du, D.-M.; Liu, G.; Xu, J.
Eur. J. Org. Chem. 2008, 350.
MS (EI, 70 eV): m/z (%) = 290 (8), 209 (5), 206 (26), 162 (32), 91
(100), 65 (5).
Anal. Calcd for C22H29NO5S: C, 62.98; H, 6.97; N, 3.34. Found: C,
63.05; H, 6.97; N, 3.19.
(13) (a) Enders, D.; Wallert, S. Synlett 2002, 304. (b) Enders,
D.; Wallert, S.; Runsink, J. Synthesis 2003, 1856.
Synthesis 2009, No. 10, 1683–1688 © Thieme Stuttgart · New York

1688
D. Enders et al.
PAPER
(14) (a) Enders, D.; Vignola, N.; Berner, O. M. Angew. Chem.
Int. Ed. 2002, 41, 109; Angew. Chem. 2002, 114, 116.
(b) Enders, D.; Berner, O. M.; Vignola, N. Chem. Commun.
2001, 2498. (c) Enders, D.; Berner, O. M.; Vignola, N.;
Harnying, W. Synthesis 2002, 1945.
(15) (a) Enders, D.; Harnying, W.; Vignola, N. Synlett 2002,
1727. (b) Enders, D.; Harnying, W.; Vignola, N. Eur. J. Org.
Chem. 2003, 20, 3939.
(16) Enders, D.; Harnying, W. Synthesis 2004, 2910.
(17) (a) Enders, D.; Harnying, W. ARKIVOC 2004, (ii), 181;
available online at www.arkat-usa.org. (b) Enders, D.;
Harnying, W.; Raabe, G. Synthesis 2004, 590. (c) Enders,
D.; Iffland, D. Synthesis 2007, 1837.
(18) Enders, D.; Adelbrecht, J.-C.; Harnying, W. Synthesis 2005,
2962.
(19) Harnying, W.; Kitisriworaphan, W.; Pohmakotr, M.; Enders,
D. Synlett 2007, 2529.
(20) CCDC 713539 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from www.ccdc.cam.ac.uk/data_request/cif or by contacting
the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK: fax: +44(1223)336033.
Synthesis 2009, No. 10, 1683–1688 © Thieme Stuttgart · New York