An efficient synthesis of N-protected β-aminoethanesulfonyl chlorides: Versatile building blocks for the synthesis of oligopeptidosulfonamides

Article abstract of DOI:10.1055/s-2000-7615

A very efficient method for the synthesis of β-aminoethanesulfonyl chlorides is described. These aliphatic functionalized sulfonyl chlorides are accessible starting from a variety of protected amino acids, including those having functionalized side chains

Full text of DOI:10.1055/s-2000-7615

PAPER
1579
An Efficient Synthesis of N-Protected b-Aminoethanesulfonyl Chlorides:
Versatile Building Blocks for the Synthesis of Oligopeptidosulfonamides
Arwin J. Brouwer, Menno C. F. Monnee, Rob M. J. Liskamp*
Department of Medicinal Chemistry, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht,
The Netherlands
Fax (+31)302536655; E-mail: R.M.J.Liskamp@pharm.uu.nl
Received 19 April 2000; revised 30 May 2000
de/reprotection step. Therefore, the idea was to avoid the
Abstract: A very efficient method for the synthesis of b-amino-
substitution step in water by preparation of a thioacetate
precursor of the sulfonate.
ethanesulfonyl chlorides is described. These aliphatic functional-
ized sulfonyl chlorides are accessible starting from a variety of pro-
tected amino acids, including those having functionalized side
chains.
To this end, Fmoc-protected amino acids (Ala, Val, Leu,
Phe) were reduced to the corresponding alcohols 1a-d
Key words: sulfonamides, sulfonyl chloride, amino acid, thio-
acetate, oxidation
(Scheme 1) using a method described by Rodriguez et
al.10 The alcohols were obtained as pure solids in high
yields and did not require further purification. The mesy-
lates 2a-d were obtained in high yields (Table) by reac-
There is still a growing interest in easily accessible build-
ing blocks, especially for combinatorial chemistry appli-
cations. We are interested in building blocks for the
synthesis of peptoid-1, urea-,2 peptoidsulfonamide-,3 and
peptidosulfonamide-4peptidomimetics. Building blocks
for peptidosulfonamides have been successfully applied
to the synthesis of receptor molecules,5 catalysts6 and oli-
gopeptidosulfonamides.7 For combinatorial chemistry
purposes, in which libraries of considerable size and puri-
ty are required, convenient and efficient syntheses of
building blocks are indispensable. This is also a require-
ment for the solid phase synthesis of oligopeptidosulfon-
amides of considerable length,7 perhaps ultimately lead-
ing to proteinosulfonamides. Originally, peptidosulfon-
amides were synthesized by the reaction of a b-amino-
ethanesulfinyl chloride with an amine, and subsequent
oxidation to the sulfonamide.4a-f The oxidation step did
not always result in high yields and was difficult to opti-
mize for use in solid phase synthesis.4f This problem
was circumvented by the b-aminoethanesulfonyl chloride
approach in which Boc-4g,8 or Fmoc-protected4g b-amino-
ethanesulfonyl chlorides have been employed. Using
these Fmoc-protected aminoethanesulfonyl chlorides, we
were able to synthesize oligopeptidosulfonamides on the
solid phase as well as peptide-peptidosulfonamide hy-
brids.4h However, the route leading to these Boc- and
Fmoc-protected sulfonyl chlorides was very cumbersome
and only afforded impure compounds. Fmoc-protected
sulfonyl chlorides are especially attractive for solid phase
synthesis, because the efficiency of the synthesis can be
monitored by formation of the dibenzofulvene-adduct af-
ter Fmoc-cleavage.9 In the previously reported sulfonyl
chloride syntheses,4g,8 the Boc-group had to be cleaved in
order to generate a soluble intermediate for the introduc-
tion of the sulfonate using aqueous sodium sulfite. Clearly
the aim was to eliminate this tedious substitution step, of
which the success was very much dependent on the solu-
bility of the intermediate and which required an additional
tion of alcohols 1a-d with methanesulfonyl chloride in
1) NMM, DME
iBuOC(O)Cl
O
2) NaBH4, H2O
-15 °C
H
PN
H
PN
OH
OH
R
R
1a-f
MsCl, Et3N
CH2Cl2, 0 °C
Cs2CO3, HSAc
DMF, r.t.
H
PN
H
PN
OMs
SAc
R
R
2a-f
3a-f
1) H2O2, HOAc
Pd/C
H
PN
Cl
S
2) COCl2/Toluene
CH2Cl2, DMF, r.t.
O
O
R
4a-f
4 P
a Fmoc CH3
b Fmoc CH(CH3)2
R
Amino Acid
Ala
Val
c Fmoc CH2CH(CH3)2 Leu
d Fmoc CH2Ph
e Cbz CH2Ph
Fmoc CH2OtBu
Phe
Phe
Ser
f
Scheme 1
Table Yields of Compounds 2–4
Yield (%)
Amino Acid
2
3
4
FmocAlaOH (a)
FmocValOH (b)
FmocLeuOH (c)
FmocPheOH (d)
CbzPheOH (e)
86
92
91
94
80
97
72
58
60
64
86
54
62
60
59
68
87a
82a
FmocSer(t-Bu) (f)
a Yields obtained using the sodium acetate method.
Synthesis 2000, No. 11, 1579–1584 ISSN 0039-7881 © Thieme Stuttgart · New York

1580
A. J. Brouwer et al.
PAPER
dichloromethane and Et3N (Table) and could be purified (vide supra). The synthesis of sulfonyl chloride 4e pro-
by crystallization. The next three steps were crucial for the ceeded as expected, showing, albeit not surprising, that
success of this approach. The first step was the introduc- our new method for the synthesis of Fmoc-protected b-
tion of the thioacetate group, which was carried out by aminoethanesulfonyl chlorides is even better for Cbz-pro-
adding the mesylates 2a-d to a mixture of thioacetic acid tected amino acids.
(HSAc) and Cs2CO3 in DMF. Although a slight excess of
For the preparation of oligopeptidosulfonamides with
Cs2CO3 is needed for overnight completion and a clean
functional side chains and peptidomimetic libraries of
conversion, a large excess of Cs2CO3 had to be avoided to
considerable diversity, b-aminoethanesulfonyl chlorides
derived from functionalized amino acids are needed. So
far, virtually only nonfunctionalized b-aminoethane-sul-
prevent cleavage of the Fmoc-group. Nevertheless, the
slight basicity of the mixture was sufficient for cleavage
of a small amount of the Fmoc-groups. After stirring over-
fonyl chlorides4-8 are reported. To our knowledge, only
night followed by workup and column chromatography,
the synthesis of a sulfonyl chloride having an ethyl-ester
thioacetates 3a-d were obtained in 58-72% yield on a
14-31 mmol scale.
in the side chain was reported.11 Chiral vinylogous sulfo-
nyl chlorides have been described12 starting from serine
Originally, it was attempted to synthesize the thioacetates and tyrosine, but these are not compatible with solid phase
3a-d directly from alcohols 1a-d by a Mitsunobu reac- synthesis using the Fmoc strategy. We envisioned that by
tion. It was found that this reaction was faster than the carefully adjusting the conditions, the above described
substitution reaction using the mesylate. However, purifi- method could be adapted to the preparation of functional-
cation was usually very tedious, and not reproducible on a ized b-aminoethanesulfonyl chlorides, i.e., containing
larger scale (>10 mmol), due to formation of the Michael acid labile protecting groups. As a test case, the synthesis
adduct of thioacetic acid and DIAD in addition to tri- of the sulfonyl chloride derived from Fmoc-Ser(t-Bu)-OH
phenyl phosphinoxide. Next, thioacetates 3a-d were oxi- was undertaken. It was assumed that if it was possible to
dized to the corresponding sulfonic acids using aqueous convert this amino acid with the acid labile tert-butyl
hydrogen peroxide (30% w/w) and acetic acid. After stir- ether to the corresponding sulfonyl chloride, then it
ring overnight, the excess of peroxide was destroyed by should also be possible to synthesize other functionalized
addition of 10% Pd/C, followed by filtration, evaporation b-aminoethanesulfonyl chlorides.
to dryness, and removal of residual water in the crude sul-
fonic acids by co-evaporation with toluene. The third and
most crucial step is the conversion of the sulfonic acid to
Reduction of Fmoc-Ser(t-Bu)-OH to the corresponding
alcohol 1f followed by conversion to mesylate 2f, and
synthesis of the thioacetate afforded 3f in a good yield
the corresponding sulfonyl chloride. Originally triphos-
(overall: 47%, Table) without any problems. As more or
gene was used but this was difficult to remove during pu-
less anticipated, a problem occurred during the oxidation
rification. The sulfonyl chlorides that were prepared in
step. After completion of the reaction and destruction of
this way invariably contained some unreacted triphos-
excess of peroxide, it was found that during the evapora-
tion of the solvents (acetic acid, water), part of the tert-bu-
tyl groups were cleaved. Probably, the mixture became
gene, which was not detectable on 13C NMR and TLC.
This residual triphosgene caused serious problems in the
couplings reactions. Apart from incomplete coupling, iso-
too acidic due to concentration of the sulfonic acid. This
cyanates were formed, which upon reaction with the
problem was solved by addition, after completion of the
amine gave urea byproducts (dimers). Although almost all
oxidation, of solid sodium acetate,13 in order to convert
triphosgene could be removed using ethyl acetate/hexanes
the sulfonic acid in situ to its sodium-salt, thus preventing
mixtures instead of dichloromethane over a silica plug,
the reaction mixture from becoming too acidic. As a re-
the yields of the sulfonyl chlorides were reduced as well.
sult, the thioacetate derived from serine, i.e., 3f, could be
easily converted to the desired sulfonyl chloride 4f in a
yield of 82%.
This problem was completely remedied by using a phos-
gene solution in toluene instead of triphosgene. Excess of
phosgene can easily be removed by evaporation in vacuo,
In order to investigate if the addition of sodium acetate
which simplifies the purification. The phosgene reactions
could improve the yields of other sulfonyl chlorides as
well, Cbz-protected sulfonyl chloride 4e was synthesized
from 3e using sodium acetate. Indeed the yield of sulfonyl
chloride 4e was increased from 50% to 87%, thus showing
that reducing the acidity by addition of sodium acetate
was also favorable for the preparation of a sulfonyl chlo-
proceeded similar to the triphosgene reactions, and after
completion, the reaction mixture was concentrated, fol-
lowed by a short silica plug (CH2Cl2) affording the sulfo-
nyl chlorides 4a-d in 59-68% yield at a 6-18 mmol
scale, starting from thioacetates 3a-d.
This procedure was also suitable for the preparation of
ride containing the more stable Cbz-group when com-
sulfonyl chlorides containing the Cbz-protecting group,
pared to a t-Bu-.
e.g., 4e, which were required for a different project. Re-
duction to the alcohol 1e and synthesis of the mesylate 2e
proceeded similar to 1d and 2d, respectively. However,
the Cbz-protected thioacetate 3e was obtained in a yield of
86% as compared to 64% for 3d. This difference is prob-
ably due to some Fmoc cleavage in the latter compound
The simplest aminoethanesulfonyl chloride, i.e., tauryl-
sulfonyl chloride is derived from taurine and was earlier
synthesized14 by treatment of N-protected taurine with
triphosgene.4g It was assumed that the above described
method using phosgene might be also efficient for the
Synthesis 2000, No. 11, 1579–1584 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Efficient Synthesis of N-Protected b-Aminoethanesulfonyl Chlorides
1581
Alcohols 1a-f; General Procedure:
synthesis of N-protected taurylsulfonyl chlorides. Indeed,
the phosgene method was very high yielding and repro-
ducible, even on a large scale (100 mmol) (Scheme 2).
Thus after N-protection sulfonyl chlorides 5 and 6 were
obtained in high yields (60-85%).
Alcohols 1a-f were synthesized according to Rodriguez et al.10 The
described method afforded the alcohols 1a-f in high yields (85-
95%). Reactions were carried out up to 150 mmol scale.
Mesylates 2a-f; General Procedure16
To a solution of alcohol 1a-f (18 mmol) in CH2Cl2 (60 mL) was
added Et3N (3.0 mL, 21.6 mmol). After cooling to 0 ∞C, methane-
sulfonyl chloride (MsCl, 1.67 mL, 21.6 mmol) was added dropwise.
Stirring was continued for 1-4.5 h at r.t., followed by addition of
CH2Cl2 (60 mL). The mixture was washed with a KHSO4 (1 M, 60
mL), H2O (60 mL), and brine (30 mL). After drying (Na2SO4) and
evaporating the solvent in vacuo, the mesylate was crystallized
from CH2Cl2/hexanes.
COCl2/Toluene
CH2Cl2, DMF, r.t.
O
O
O
O
S
S
CbzN
ONa
CbzN
Cl
H
H
5
60-85%, 2 steps
Cbz-Cl, NaOH
Dioxane, H2O, rt
O
O
+
H3N
S
-
O
2a
Fmoc-Cl, NaOH
CH3CN, H2O, rt
The reaction was carried out on a 37 mmol scale using 2.5 times the
amount of solvent of the general procedure due to the poor solubil-
ity of Fmoc-alaninol in CH2Cl2. Crystallization (EtOAc/hexanes)
afforded white crystals. Rf = 0.24 (EtOAc/Hexanes, 1:1);
mp = 139 °C.
1H NMR (CDCl3): d = 1.27 (d, J = 6.6 Hz, 3H, CHCH3), 3.00 (s, 3H,
SO2CH3), 4.05 (m, 1H, CHCH3), 4.22 [m, 3H, MsOCH2, CH
(Fmoc)], 4.43 [m, 2H, CH2 (Fmoc)], 4.86 (br s, 1H, NH), 7.19-7.78
[m, 8H, Ar-CH (Fmoc)].
COCl2/Toluene
CH2Cl2, DMF, r.t.
O
O
O
O
S
S
FmocN
Cl
FmocN
ONa
H
H
6
83%, 2 steps
Scheme 2
13C NMR (CDCl3): d = 17.1 (CHCH3), 37.4 (SO2CH3), 46.1 (NCH),
47.2 [CH (Fmoc)], 66.8 [CH2 (Fmoc)], 71.7 (MsOCH2), 120.0,
125.0, 127.1, 127.7, 141.3, 143.8 [Ar-C (Fmoc)], 155.8 [C=O
(Fmoc)].
In conclusion, we have developed a highly efficient meth-
od for the convenient synthesis of b-aminoethanesulfonyl
chlorides, in principle starting from any conceivable
Fmoc- and Cbz-protected amino acid, including those
having functionalized side chains. The method features
ESI MS: m/z = 398.05 [M+Na]+.
Anal. Calcd for C19H21NO5S: C, 60.78; H, 5.64; N, 3.73. Found: C,
the synthesis of a sodium sulfonate from a thioacetate, 60.76; H, 5.38; N, 3.74.
which is followed by synthesis of the sulfonyl chloride us-
ing phosgene.
2b
Scale: 18 mmol; white crystals; Rf = 0.45 (EtOAc/Hexanes, 1:1);
mp = 141 °C.
1H NMR (CDCl3): d = 0.97 [2d, J = 6.6 and 7.0 Hz, 6H, CH(CH3)2],
1.87 [m, 1H, CH(CH3)2], 2.98 (s, 3H, SO2CH3), 3.69 (m, 1H, NCH),
4.27 [m, 3H, MsOCH2, CH (Fmoc)], 4.46 [d, 2H, CH2 (Fmoc)],
4.85 (br d, 1H, NH), 7.19-7.78 [m, 8H, Ar-CH (Fmoc)].
Under present investigation is extension of the scope to-
wards other functionalized amino acids, and to evaluate if
this procedure could be fully applied to tryptophane, his-
tidine, etc., which might be sensitive to the oxidation step.
13C NMR (CDCl3): d = 18.6, 19.3 [CH(CH3)2], 29.0 [CH(CH3)2],
37.4 (SO2CH3), 47.2 [CH (Fmoc)], 55.5, 55.6 (NCH), 67.0 [CH2
(Fmoc)], 69.4 (MsOCH2), 120.0, 125.0, 127.1, 127.7, 141.3, 143.8
[Ar-C (Fmoc)], 156.1 [C=O (Fmoc)].
Fmoc-protected amino acids were purchased from Alexis Corpora-
tion (Läufelfingen, Switzerland) and Cbz-protected amino acids
from Advanced Chemtech Europe (Machelen, Belgium). Peptide
grade solvents for synthesis were purchased from Biosolve (The
Netherlands). N-methylmorpholine (NMM) was distilled from
CaH2. Reactions were carried out at ambient temperature unless
stated otherwise. TLC analysis was performed on Merck pre-coated
silica gel 60 F-254 (0.25 mm) plates. Spots were visualized with UV
light, ninhydrin, or Cl2-TDM15. Solvents were evaporated under re-
duced pressure at 40 °C. Column chromatography was performed
on Merck Kieselgel 60 (40-63 µm). Mps were determined using a
Gallenkamp melting point apparatus no. 889339, and were uncor-
rected. Electrospray mass spectra were recorded on a Shimadzu
LCMS-QP-8000 spectrometer. Elemental analyses were carried out
at Kolbe Mikroanalytisches Laboratorium (Mülheim an der Ruhr,
ESI MS: m/z = 426.15 [M+Na]+.
Anal. Calcd for C21H25NO5S: C, 62.51; H, 6.24; N, 3.47. Found: C,
62.54; H, 5.88; N, 3.43.
2c
Scale: 18 mmol; white crystals; Rf = 0.51 (EtOAc/Hexanes, 1:1);
mp = 119 °C.
1H NMR (CDCl3): d = 0.93 [2d, J = 6.6 Hz, 6H, CH(CH3)2], 1.40
[m, 2H, CH2CH (CH3)2], 1.64 [m, 1H, CH(CH3)2], 3.00 (s, 3H,
SO2CH3), 3.99 (m, 1H, NCH), 4.22 [m, 3H, MsOCH2, CH (Fmoc)],
4.45 [d, 2H, CH2 (Fmoc)], 4.78 (br d, 1H, NH), 7.29-7.78 [m, 8H,
Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 21.9, 22.9 [CH(CH3)2], 24.6 [CH(CH3)2],
37.3 (SO2CH3), 40.0 [CH2CH(CH3)2], 47.2 [CH (Fmoc)], 48.5
(NCH), 66.6 [CH2 (Fmoc)], 71.4 (MsOCH2), 120.0, 125.0, 127.1,
127.7, 141.3, 143.7 [Ar-C (Fmoc)], 155.8 [C=O (Fmoc)].
1
Germany). H NMR (300 MHz) and 13C NMR (75 MHz) spectra
were recorded on a Varian G-300 spectrometer. Chemical shifts are
1
reported in ppm relative to TMS (0 ppm) for the H NMR and to
CDCl3 (77 ppm) for the 13C NMR as internal standards. 13C NMR
spectra were recorded using the attached proton test (APT) pulse se-
quence.
ESI MS: m/z = 440.00 [M+Na]+.
Anal. Calcd for C22H27NO5S: C, 63.29; H, 6.52; N, 3.35. Found: C,
63.08; H, 6.12; N, 3.34.
Synthesis 2000, No. 11, 1579–1584 ISSN 0039-7881 © Thieme Stuttgart · New York

1582
2d
A. J. Brouwer et al.
PAPER
ESI MS: m/z = 378.05 [M+Na]+.
Scale: 78.3 mmol; white crystals; Rf = 0.11 (CH2Cl2); mp = 149 °C.
Anal Calcd for C20H21NO3S: C, 67.58; H, 5.95; N, 3.94. Found: C,
67.51; H, 6.04; N, 3.79.
1H NMR (CDCl3): d = 2.93 (m, 2H, CH2Ph), 2.99 (s, 3H, SO2CH3),
4.22 [m, 4H, MsOCH2, CH (Fmoc), NCH], 4.39 [d, J = 6.6 Hz, 2H,
CH2 (Fmoc)], 5.02 (br d, 1H, NH), 7.20-7.78 [m, 13H, Ar-CH (Ph,
Fmoc)].
13C NMR (CDCl3): d = 37.1 (CH2Ph), 37.3 (SO2CH3), 47.1 [CH
(Fmoc)], 51.4 (NCH), 66.8 [CH2 (Fmoc)], 69.6 (MsOCH2), 120.0,
125.0, 127.1, 127.7, 128.8, 129.2, 136.3, 141.3, 143.7 [Ar-C (Ph,
Fmoc)], 155.6 [C=O (Fmoc)].
3b
Scale: 14 mmol; white solid; Rf = 0.20 (CH2Cl2); mp = 121 °C.
1H NMR (CDCl3): d = 0.96 (2d, J = 6.6 Hz, 6H, CHCH3)2), 1.81 [m,
1H, CH(CH3)2], 2.32 [s, 3H, C(O)CH3], 3.04 (m, 2H, SCH2), 3.64
(m, 1H, NCH), 4.21 [t, J = 7.0 Hz, 1H, CH (Fmoc)], 4.37 [m, 2H,
CH2 (Fmoc)], 4.82 (br d, 1H, NH), 7.28-7.77 [m, 8H, Ar-CH
(Fmoc)].
13C NMR (CDCl3): d = 18.0, 19.2 [CH(CH3)2], 30.6 [CH(CH3)2],
31.6 (SCH2), 32.2 [C(O)CH3], 47.2 [CH (Fmoc)], 56.7 (NCH), 66.6
[CH2 (Fmoc)], 119.9, 125.0, 125.1, 127.0, 127.6, 141.2, 143.9,
144.0 [Ar-C (Fmoc)], 156.3 [C=O (Fmoc)], 196.3 (SC=O).
ESI MS: m/z = 474.35 [M+Na]+.
Anal. Calcd for C25H25NO5S: C, 66.50; H, 5.58; N, 3.10. Found: C,
66.39; H, 5.65; N, 2.96.
2e
Scale: 83.4 mmol; white crystals, Rf = 0.67 (5% MeOH/CH2Cl2);
ESI MS: m/z = 406.10 [M+Na]+.
mp = 101 °C.
Anal. Calcd for C22H25NO3S: C, 68.90; H, 6.57; N, 3.65. Found: C,
68.96; H, 6.58; N, 3.59.
1H NMR (CDCl3): d = 2.96 (m, 5H, SO2CH3, CHCH2Ph), 4.15 (m,
3H, MsOCH2, NCH), 5.08 (m, 3H, OCH2Ph, NH), 7.33 [m, 10H,
Ar-CH (Ph, Cbz)].
13C NMR (CDCl3): d = 37.0 (CHCH2Ph), 37.2 (SO2CH3), 51.3
(NCH), 66.9 (OCH2Ph), 69.4 (MsOCH2), 127.0, 128.1, 128.2,
128.5, 128.8, 129.2, 136.3 [Ar-C (Ph, Cbz)], 155.6 [C=O (Cbz)].
3c
Scale: 15 mmol; white solid; Rf = 0.21 (CH2Cl2), mp = 79 °C.
1H NMR (CDCl3): d = 0.91 [d, J = 6.6 Hz, 6H, CH(CH3)2], 1.36 [m,
2H, CH2CH(CH3)2], 1.64 [m, 1H, CH(CH3)2], 2.33 [s, 3H,
C(O)CH3], 2.98 (dd, Jgem = 13.9 Hz, Jvic = 7.3 Hz, 1H, SCHa), 3.09
(dd, Jgem = 13.9 Hz, Jvic = 4.8 Hz, 1H, SCHb), 3.90 (m, 1H, NCH),
4.21 [t, J = 7.0 Hz, 1H, CH (Fmoc)], 4.39 [m, 2H, CH2 (Fmoc)],
4.70 (br d, 1H, NH), 7.28-7.77 [m, 8H, Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 22.1, 23.0 [CH(CH3)2], 24.8 [CH(CH3)2],
30.6 [C(O)CH3], 34.2 (SCH2), 43.6 [CH2CH(CH3)2], 47.2 [CH
(Fmoc)], 49.3 (NCH), 66.5 [CH2 (Fmoc)], 119.9, 125.0, 127.0,
127.6, 141.3, 143.8, 144.0 [Ar-C (Fmoc)], 155.9 [C=O (Fmoc)],
195.8 (SC=O).
ESI MS: m/z = 386.15 [M+Na]+.
Anal. Calcd for C18H21NO5S: C, 59.49; H, 5.82; N, 3.85. Found: C,
59.38; H, 5.89; N, 3.76.
2f
Scale: 42.5 mmol; colorless oil; Rf = 0.11 (CH2Cl2).
1H NMR (CDCl3): d = 1.19 [s, 9H, C(CH3)3], 3.01 (s, 3H, SO2CH3),
3.41 (dd, Jgem = 8.8 Hz, Jvic = 5.5 Hz, 1H, t-BuOCHa), 3.54 (dd,
J
gem = 9.2 Hz, Jvic = 3.3 Hz, 1H, t-BuOCHb), 4.06 (m, 1H, NCH),
ESI MS: m/z = 420.20 [M+Na]+.
4.26 [m, 3H, MsOCH2, CH (Fmoc)], 4.42 [m, 2H, CH2 (Fmoc)],
5.23 (br d, 1H, NH), 7.30-7.78 [m, 8H, Ar-CH (Fmoc)].
Anal. Calcd for C23H27NO3S: C, 69.49; H, 6.85; N, 3.52. Found: C,
69.26; H, 6.80; N, 3.38.
13C NMR (CDCl3): d = 27.3 [C(CH3)3], 37.2 (SO2CH3), 47.1 [CH
(Fmoc)], 50.0 (NCH), 59.5 (t-BuOCH2), 66.9 [CH2 (Fmoc)], 67.9
(MsOCH2), 73.5 [C(CH3)3], 120.0, 125.0, 127.0, 127.7, 141.3,
143.7 [Ar-C (Fmoc)], 155.8 [C=O (Fmoc)].
3d
Scale: 31 mmol; white solid, Rf = 0.23 (CH2Cl2); mp = 83 °C.
1H NMR (CDCl3): d = 2.33 [s, 3H, C(O)CH3], 2.78-3.09 (m, 4H,
SCH2, CH2Ph), 4.04 (m, 1H, NCH), 4.17 [t, J = 7.0 Hz 1H, CH
(Fmoc)], 4.32 [m, 2H, CH2 (Fmoc)], 4.95 (br s, 1H, NH), 7.16-7.76
[m, 13H, Ar-CH (Fmoc, Ph)].
ESI MS: m/z = 470.35 [M+Na]+.
Thioacetates 3a-f; General Procedure16
13C NMR (CDCl3): d = 30.6 [C(O)CH3], 32.6 (SCH2), 40.5
(CH2Ph), 47.2 [CH (Fmoc)], 52.6 (NCH), 66.6 [CH2 (Fmoc)],
119.9, 125.0, 126.7, 127.0, 127.6, 128.6, 129.3, 137.0, 141.2, 143.8
[Ar-C (Fmoc, Ph)], 155.7 [C=O (Fmoc)], 195.7 (SC=O).
HSAc (1.18 mL, 16.8 mmol) was added to a suspension of Cs2CO3
(2.96 g, 9.1 mmol) in DMF (70 mL). The mesylate 2a-f (14 mmol)
was added in one portion to the formed solution and stirring was
continued at r.t. for 18 h, during which the reaction flask was cov-
ered with aluminium foil. The mixture was poured into distilled
H2O (300 mL), and extracted with EtOAc (3 ¥ 300 mL). The com-
bined organic layers were washed with H2O (400 mL), NaHCO3
(5% w/w, 400 mL), and brine (200 mL). Drying (Na2SO4) followed
by concentration in vacuo afforded the crude product, which was
purified by column chromatography (CH2Cl2).
ESI MS: m/z = 454.15 [M+Na]+.
Anal. Calcd for C26H25NO3S: C, 72.36; H, 5.84; N, 3.25. Found: C,
72.28; H, 5.92; N, 3.16.
3e
Scale: 20 mmol; purified by crystallization (CH2Cl2/hexanes);
3a
white needles; Rf = 0.59 (EtOAc/hexanes, 1:1); mp = 85 °C.
Scale: 30 mmol; white solid; Rf = 0.73 (EtOAc/hexanes, 1:1);
mp = 134 °C.
1H NMR (CDCl3): d = 2.33 [s, 3H, C(O)CH3], 2.95 (m, 4H,
CHCH2Ph, SCH2), 4.06 (m, 1H, NCH), 4.92 (br d, 1H, NH), 5.07
[s, 2H, CH2 (Cbz)], 7.33 [m, 10H, Ar-CH (Ph, Cbz)].
13C NMR (CDCl3): d = 30.5 [C(O)CH3], 32.6 (SCH2), 40.3
(CHCH2Ph), 52.5 (NCH), 66.5 [CH2 (Cbz)], 126.7, 127.9, 128.0,
128.4, 128.5, 129.3, 136.5, 137.0 [Ar-C (Ph, Cbz)], 155.7 [C=O
(Cbz)], 195.9 (SC=O).
1H NMR (CDCl3): d = 1.20 (d, J = 6.6 Hz, 3H, CHCH3), 2.34 [s, 3H,
C(O)CH3], 3.04 (d, J = 6.2 Hz, 2H, SCH2), 3.93 (m, 1H, NCH), 4.20
[t, J = 7.0 Hz, 1H, CH (Fmoc)], 4.36 [m, 2H, CH2 (Fmoc)], 4.94 (br
d, 1H, NH), 7.27-7.76 [m, 8H, Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 20.2 (CHCH3), 30.5 [C(O)CH3], 34.7
(SCH2), 47.1 [NCH, CH (Fmoc)], 66.5 [CH2 (Fmoc)], 119.9, 125.0,
126.9, 127.6, 141.2, 143.8 [Ar-C (Fmoc)], 155.6 [C=O (Fmoc)],
195.8 (SC=O).
ESI MS: m/z = 366.10 [M+Na]+.
Anal. Calcd for C19H21NO3S: C, 66.45; H, 6.16; N, 4.08. Found: C,
66.55; H, 6.23; N, 3.96.
Synthesis 2000, No. 11, 1579–1584 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
An Efficient Synthesis of N-Protected b-Aminoethanesulfonyl Chlorides
1583
3f
1H NMR (CDCl3): d = 0.94 [m, 6H, CH(CH3)2], 1.43-1.78 [m, 3H,
CH2CH(CH3)2], 3.85 (dd, 1H, Jgem = 14.3 Hz, Jvic = 4.0 Hz,
SO2CHa), 4.07 (dd, Jgem = 14.3 Hz, Jvic = 6.1 Hz, 1H, SO2CHb), 4.21
[m, 2H, NCH, CH (Fmoc)], 4.46 [m, 2H, CH2 (Fmoc)], 5.01 (d, 1H,
NH), 7.29-7.78 [m, 8H, Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 21.5, 22.8 [CH(CH3)2], 24.7 [CH(CH3)2],
42.1 [CH2CH(CH3)2], 47.0 (NCH), 47.2 [CH (Fmoc)], 66.7 [CH2
(Fmoc)], 69.0 (SO2CH2), 120.0, 125.0, 127.1, 127.8, 141.3, 143.6
[Ar-C (Fmoc)], 155.3 [C=O (Fmoc)].
Scale: 35 mmol; white crystalline solid; Rf = 0.18 (CH2Cl2);
mp = 78 °C.
1H NMR (CDCl3): d = 1.19 [s, 9H, C(CH3)3], 2.35 [s, 3H,
C(O)CH3], 3.37 (d, J = 6.6 Hz, 2H, SCH2), 3.44 (m, 2H, t-
BuOCH2), 3.92 (m, 1H, NCH), 4.25 [m, 1H, CH (Fmoc)], 4.38 [m,
2H, OCH2 (Fmoc)], 5.25 (br d, 1H, NH), 7.30-7.78 [m, 8H, Ar-CH
(Fmoc)].
13C NMR (CDCl3): d = 27.4 [C(CH3)3], 30.6 [C(O)CH3], 31.0
(SCH2), 47.2 [CH (Fmoc)], 51.3 (NCH), 62.5 (t BuOCH2), 66.8
[CH2 (Fmoc)], 73.2 [C(CH3)3], 120.0, 125.1, 127.0, 127.6, 141.3,
143.9 [Ar-C (Fmoc)], 155.9 [C=O (Fmoc)], 196.0 (SC=O).
ESI MS: m/z = 444.00, 446.15 [M+Na]+: due to chlorine isotopes.
Anal. Calcd for C21H24ClNO4S: C, 59.78; H, 5.73; N, 3.32. Found:
C, 60.20; H, 5.83; N, 3.18.
ESI MS: m/z = 450.25 [M+Na]+.
4d
Anal. Calcd for C24H29NO4S: C, 67.42; H, 6.84; N, 3.28. Found: C,
67.65; H, 6.61; N, 3.08.
Scale: 5.6 mmol; white solid; Rf = 0.21 (CH2Cl2); mp = 175 °C
(dec.).
1H NMR (THF-d8): d = 2.87 (dd, Jgem = 13.6 Hz, Jvic = 5.1 Hz, 1H,
CHaPh), 2.98 (dd, Jgem = 13.6 Hz, Jvic = 8.1 Hz, 1H, CHbPh), 4.05-
4.33 [m, 6H, SO2CH2, NCH, CH (Fmoc), CH2 (Fmoc)], 6.96 (d, 1H,
NH), 7.06-7.68 [m, 13H, Ar-CH (Fmoc, Ph)].
13C NMR (THF-d8, Int. ref. = 67.4 ppm): d = 39.8 (CH2Ph), 48.3,
50.9 [NCH, CH (Fmoc)], 66.7, 68.3 [SO2CH2, CH2 (Fmoc)], 120.7,
126.0, 126.0, 127.6, 127.8, 128.4, 129.4, 130.3, 138.4, 143.4 [Ar-C
(Fmoc, Ph)], 145.4 [C=O (Fmoc)].
Sulfonyl Chlorides 4a-f; General Procedure16
A mixture of H2O2 [30% w/w in H2O (5 mL)] and HOAc (10 mL)
was added to a solution of thioacetate 3a-f (4.9 mmol) in HOAc (5
mL). After stirring overnight at r.t., 10% Pd/C (25 mg) was added
to destroy the excess of peroxide. For synthesis of the sodium sul-
fonate, NaOAc (1.1 equiv) was added before adding the Pd/C, fol-
lowed by 1 h of stirring at r.t. Filtration over Hyflo, concentration,
and co-evaporation with toluene (3 ¥ 30 mL) afforded the crude sul-
fonic acid or sodium sulfonate. Under a N2 atm, CH2Cl2 (30 mL)
was added followed by a phosgene solution in toluene (20% m/m, 4
mL) and DMF (0.6 mL). If necessary, after 1 h additional phosgene
solution (1-2 mL) was added for completion of the reaction. After
stirring for 2 h at r.t., the mixture was concentrated and the product
was purified through a silica plug (CH2Cl2), followed by precipita-
tion in CH2Cl2/hexanes, and filtration. The product was dried (P2O5)
and stored under Ar.
ESI MS: m/z = 478.05, 480.25 [M+Na]+: due to chlorine isotopes.
Anal. Calcd for C24H22ClNO4S: C, 63.22; H, 4.86; N, 3.07. Found:
C, 63.16; H, 4.61; N, 2.94.
4e
Scale: 11.4 mmol; white solid; Rf = 0.30 (CH2Cl2); mp = 126 °C.
1H NMR (CDCl3): d = 3.09 (m, 2H, CHCH2Ph), 3.87 (dd,
J
J
gem = 14.3 Hz, Jvic = 4.0 Hz, 1H, SO2CHa), 4.13 (dd, Jgem = 14.3 Hz,
vic = 7.0 Hz, 1H, SO2CHb), 4.39 (m, 1H, NCH), 5.09 (dd, J = 14.1
4a
Hz, 2H, OCH2Ph), 5.22 (br d, 1H, NH), 7.15-7.39 [m, 10H, Ar-CH
(Ph, Cbz)].
13C NMR (CDCl3): d = 39.1 (CHCH2Ph), 49.8 (NCH), 67.1
(OCH2Ph), 69.0 (SO2CH2), 127.4, 128.1, 128.3, 128.5, 129.0,
129.2, 135.7, 135.9 [Ar-C (Ph, Cbz)], 155.3 [C=O (Cbz)].
Scale: 9.1 mmol; white solid; Rf = 0.20 (CH2Cl2); mp = 149 °C.
1H NMR (CDCl3): d = 1.48 (d, J = 6.2 Hz, 3H, CHCH3), 3.86 (dd,
1H, SO2CHa), 4.14 (dd, 1H, SO2CHb), 4.22 [t, 1H, CH (Fmoc)],
4.32 (m, 1H, NCH), 4.46 [m, 2H, CH2 (Fmoc)], 5.09 (d, 1H, NH),
7.30-7.78 [m, 8H, Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 19.6 (CH3), 44.4 (NCH), 47.1 [CH (Fmoc)],
66.8 [CH2 (Fmoc)], 69.4 (SO2CH2), 120.0, 125.0, 127.1, 127.8,
141.3, 143.6 [Ar-C (Fmoc)], 155.2 [C=O (Fmoc)].
ESI MS: m/z = 390.10, 392.05 [M+Na]+: due to chlorine isotopes.
Anal. Calcd for C17H18ClNO4S: C, 55.51; H, 4.93; N, 3.81. Found:
C, 55.38; H, 5.06; N, 3.74.
ESI MS: m/z = 402.10, 404.15 [M+Na]+: due to chlorine isotopes.
4f
The thioacetate 3f was first dissolved in THF (8 mL), before adding
HOAc. NaOAc (8.8 mmol) was added after completion of the oxi-
dation. The chloride was purified by column chromatography, and
was not precipitated. Scale: 8.0 mmol; white solid. Rf = 0.29
(CH2Cl2); mp = 119 °C.
1H NMR (CDCl3): d = 1.21 [s, 9H, C(CH3)3], 3.52 (dd, Jgem = 9.2
Hz, Jvic = 4.4 Hz, 1H, t-BuOCHa), 3.67 (dd, Jgem = 9.2 Hz, Jvic = 2.9
Hz, 1H, t-BuOCHb), 4.02 (m, 2H, SO2CH2), 4.24 [m, 1H, CH
(Fmoc)], 4.47 [m, 3H, OCH2 (Fmoc), NCH], 5.42 (br d, 1H, NH),
7.31-7.79 [m, 8H, Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 27.3 [C(CH3)3], 47.1 [NH (Fmoc)], 48.1
(NCH), 61.4 (t-BuOCH2), 65.3 (SO2CH2), 66.9 [CH2 (Fmoc)], 73.9
[C(CH3)3], 120.0, 124.9, 125.0, 127.0, 127.7, 141.2, 143.6 [Ar-C
(Fmoc)], 155.3 [C=O (Fmoc)].
Anal. Calcd for C18H18ClNO4S: C, 56.92; H, 4.78; N, 3.69. Found:
C, 56.90; H, 4.42; N, 3.75.
4b
Scale: 16.3 mmol; white solid; Rf = 0.56 (EtOAc/hexanes, 1:2);
mp = 168 °C.
1H NMR (CDCl3, 50 ∞C): d = 0.96 [m, 6H, CH(CH3)2], 2.09 [m, 1H,
CH(CH3)2], 3.87-4.06 (m, 3H, SO2CH2CH), 4.22 [t, 1H, CH
(Fmoc)], 4.46 [m, 2H, CH2 (Fmoc)], 5.04 (br s, 1H, NH), 7.28-7.77
[m, 8H, Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 18.2, 19.3 [CH(CH3)2], 31.3 [CH(CH3)2],
47.2 [CH (Fmoc)], 53.8 (NCH), 66.8 [CH2 (Fmoc)], 67.0 (SO2CH2),
120.0, 125.0, 127.1, 127.7, 141.3, 143.6, 143.7 [Ar-C (Fmoc)],
155.6 [C=O (Fmoc)].
ESI MS: m/z = 430.05, 432.05 [M+Na]+: due to chlorine isotopes.
ESI MS: m/z = 474.15, 475.90 [M+Na]+: due to chlorine isotopes.
Anal. Calcd for C20H22ClNO4S: C, 58.89; H, 5.44; N, 3.43. Found:
C, 58.82; H, 5.54; N, 3.33.
Anal. Calcd for C22H26ClNO5S: C, 58.47; H, 5.80; N, 3.10. Found:
C, 58.26; H, 5.91; N, 2.97.
4c
Scale: 18.2 mmol; white solid; Rf = 0.26 (CH2Cl2); mp = 144 °C.
Synthesis 2000, No. 11, 1579–1584 ISSN 0039-7881 © Thieme Stuttgart · New York

1584
A. J. Brouwer et al.
PAPER
Cbz-taurylsulfonyl Chloride (5)
References
Taurine (6.26 g, 50 mmol) was dissolved in a solution of NaOH (1
M, 50 mL) in H2O. Then simultaneously, under vigorous stirring, a
solution of Cbz-chloride (10.6 mL, 75 mmol) in dioxane (65 mL)
and a solution of NaOH (1 M, 75 mL) in H2O were added dropwise.
After stirring for 1 h, the reaction mixture was extracted with EtOAc
(2 ¥ 200 mL) to remove excess of Cbz-chloride. Concentration of
the aqueous layer in vacuo followed by co-evaporation with toluene
(150 mL), EtOH (150 mL), and CH2Cl2 (3 ¥ 150 mL) afforded the
crude sodium sulfonate salt, which was dried (P2O5). Subsequently,
a phosgene solution in toluene (20% w/w, 50 mL) and DMF (4 mL)
were added to a suspension of the sodium sulfonate in CH2Cl2 (350
mL). The reaction mixture was concentrated after stirring for 1 h at
r.t. Purification by silica gel column chromatography (CH2Cl2) af-
forded Cbz-taurylsulfonyl chloride as a white solid in 60% yield (2
steps). On a larger scale (150 mmol) yields up to 85% were reached.
(1) Kruijtzer, J. A. W.; Liskamp, R. M. J. Tetrahedron Lett. 1995,
36, 6969.
Kruijtzer, J. A. W.; Hofmeyer, L. J. F.; Heerma, W.; Versluis,
C.; Liskamp, R. M. J. Chem. Eur. J. 1998, 4, 1570.
(2) Boeijen, A.; Liskamp, R. M. J. Eur. J. Org. Chem. 1999, 2127.
(3) van Ameijde, J.; Liskamp, R. M. J. Tetrahedron Lett. 2000,
41, 1103.
(4) a) Moree, W. J.; van der Marel, G. A.; Liskamp, R. M. J.
Tetrahedron Lett. 1991, 32, 409.
b) Moree, W. J.; van der Marel, G. A.; Liskamp, R. M. J.
Tetrahedron Lett. 1992, 33, 6389.
c) Moree, W. J.; van der Marel, G. A.; Liskamp, R. M. J.
Tetrahedron 1993, 49, 1133.
d) Moree, W. J.; Schouten, A.; Kroon, J.; Liskamp, R. M. J.
Int. J. Pept. Protein Res. 1995, 45, 501.
e) Moree, W. J.; van der Marel, G. A.; Liskamp, R. M. J. J.
Org. Chem. 1995, 60, 5157.
Rf = 0.27 (CH2Cl2); mp = 47 °C.
1H NMR (CDCl3): d = 3.85 (m, 4H, SO2CH2CH2), 5.12 (br s, 2H,
CH2Ph), 5.44 (br s, 1H, NH), 7.35 (s, 5H, Ar-CH).
13C NMR (CDCl3): d = 36.3 (NCH2), 64.6 (SO2CH2), 67.3 (CH2Ph),
128.1, 128.4, 128.6, 135.8 (Ar-C), 156.1 [C = O (Cbz)].
ESI MS: m/z = 278.01, 280.01 [M+H]+, 299.94, 301.97 [M+Na]+:
due to chlorine isotopes.
f) de Bont, D. B. A.; Moree, W. J.; Liskamp, R. M. J. Bioorg.
Med. Chem. 1996, 4, 667.
g) de Bont, D. B. A.; Dijkstra, G. D. H.; den Hartog, J. A. J.;
Liskamp, R. M. J. Bioorg. Med. Chem. Lett. 1996, 24, 3035.
h) de Bont, D. B. A.; Sliedrecht-Bol, K. M.; Hofmeyer, L. J.
F.; Liskamp, R. M. J. Bioorg. Med. Chem. 1999, 7, 1043.
(5) Löwik, D. W. P. M.; Mulders, S. J. E.; Cheng, Y.; Shao, Y.;
Liskamp, R. M. J. Tetrahedron Lett. 1996, 37, 8253.
Löwik, D. W. P. M.; Weingarten, M. D.; Broekema, M.;
Brouwer, A. J.; Still, W. C.; Liskamp, R. M. J. Angew. Chem.,
Int. Ed. Engl. 1998, 37, 1846.
Anal. Calcd for C10H12ClNO4S: C, 43.25; H, 4.36; N, 5.04; S, 11.54.
Found: C, 43.33; H, 4.37; N, 5.01; S, 11.42.
Fmoc-taurylsulfonyl Chloride (6)
A solution of taurine (3.13 g, 25 mmol) in H2O (50 mL) was adjust-
ed to pH 8.5 by the addition of NaOH (1 M) in H2O. Subsequently,
a solution of Fmoc-chloride (7.75 g, 30 mmol) in CH3CN (100 mL)
was added, during which the pH was kept at 8-8.5 by addition of
small amounts of 1 M NaOH. The reaction mixture was stirred for
approximately 1 h. After addition of H2O (150 mL), excess of
Fmoc-chloride was removed by washing with EtOAc (2 ¥ 150 mL).
Concentration of the aqueous layer under reduced pressure fol-
lowed by co-evaporation with toluene (3 ¥ 150 mL), EtOH (3 ¥ 150
mL), and CH2Cl2 (3 ¥ 150 mL) afforded the crude sodium sulfonate
salt, which was dried (P2O5). Subsequently, a phosgene solution in
toluene (20% m/m, 20 mL) and DMF (3 mL) were added to a sus-
pension of the sodium sulfonate in CH2Cl2 (200 mL). If necessary,
more phosgene solution (5 mL) was added after 1 h to complete the
reaction. The reaction mixture was concentrated after stirring for 2
h at r.t. Purification by silica gel column chromatography (CH2Cl2)
under an elevated N2 pressure afforded Fmoc-taurylsulfonyl chlo-
ride as a white solid in 83% yield (2 steps).
(6) Brouwer, A. J.; van der Linden, H. J.; Liskamp, R. M. J. J.
Org. Chem. 2000, 65, 1750.
Gennari, C.; Ceccarelli, S.; Piariulli, P.; Montalbetti, C. A. G.
N.; Jackson. R. F. W. J. Org. Chem. 1998, 63, 5312.
(7) Monnee, M. C. F.; Marijne, M. F.; Brouwer, A. J.; Liskamp,
R. M. J. Manuscript in preparation.
(8) Gude, M.; Piariulli, U.; Potenza, D.; Salom, B.; Gennari, C.
Tetrahedron Lett. 1996, 37, 8589.
(9) Meienhofer, J.; Waki, M.; Heimer, E. P.; Lambros, T. J.;
Makofske, R. C.; Chang, C. -D. Int. J. Pept. Protein Res. 1979,
13, 35.
(10) Rodriguez, M.; Llinares, M.; Doulut, S.; Heitz, A.; Martinez,
J. Tetrahedron Lett. 1991, 32, 923.
(11) Luisi, G.; Calcagni, A.; Pinnen, F. Tetrahedron Lett. 1993, 34,
2391.
(12) Gennari, C.; Longari, C.; Ressel, S.; Salom, B.; Mielgo, A.
Eur. J. Org. Chem. 1998, 945.
(13) Fernandez-Bolaños, J.; Castilla, I. M.; Fernandez-Bolaños
Guzman, J. Carbohydr. Res. 1988, 173, 33.
Rf = 0.16 (CH2Cl2); mp = 95 °C.
1H NMR (CDCl3): d = 3.84 (m, 4H, SO2CH2CH2), 4.20 [t, 1H, CH
(Fmoc)], 4.44 [d, 2H, CH2 (Fmoc)], 5.35 (br s, 1H, NH), 7.28-7.77
[m, 8H, Ar-CH (Fmoc)].
13C NMR (CDCl3): d = 36.3 (NCH2), 47.1 [CH (Fmoc)], 64.6
(SO2CH2), 67.1 [CH2 (Fmoc)], 128.1, 128.4, 128.6, 135.8 (Ar-C),
156.1 [C=O (Fmoc)].
(14) For the preparation of Cbz-taurylsulfonyl chloride from Cbz-
taurine by treatment with PCl5: Bricas, E.; Kieffer, F.;
Fromageot, C. Biochim. Biophys. Acta 1955, 18, 358.
(15) Arx, E. von; Faupel, M.; Bruggen, M., J. Chromatogr. 1976,
120, 224.
(16) In the NMR spectra, broad, low intensity signals were also
present presumably of the minor Fmoc-rotamer.
ESI MS: m/z = 388.03, 390.03 [M+Na]+: due to chlorine isotopes.
Anal. Calcd for C17H16ClNO4S: C, 55.81; H, 4.41; N, 3.83; S, 8.76.
Found: C, 55.91; H, 4.28; N, 3.66; S, 8.55.
Article Identifier:
1437-210X,E;2000,0,11,1579,1584,ftx,en;Z03000SS.pdf
Acknowledgement
We thank Mrs. Lovina Hofmeyer for preliminary experiments and
Michael Marijne for reproducing some of the experiments.
Synthesis 2000, No. 11, 1579–1584 ISSN 0039-7881 © Thieme Stuttgart · New York