Amino-sulfonation of alkenes in a three-component reaction

Article abstract of DOI:10.1002/1099-0690(200204)2002:8<1407::AID-EJOC1407>3.0.CO;2-I

2-Aminoalkanesulfonic acids have been synthesized by a three-component alkene/SO₃·-DMF/acetonitrile reaction, followed by hydrolysis. Trifluoromethanesulfonic acid was added to the amino-sulfonation mixture to accelerate the reaction and prevent the competitive formation of by-products. The reported two-step procedure provided a concise and versatile approach to new analogues of the natural amino acid taurine. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Full text of DOI:10.1002/1099-0690(200204)2002:8<1407::AID-EJOC1407>3.0.CO;2-I

FULL PAPER
Amino-Sulfonation of Alkenes in a Three-Component Reaction[‡]
Franca M. Cordero,*[a] Martina Cacciarini,[a] Fabrizio Machetti,[a] and
Francesco De Sarlo[a]
Keywords: Amino-sulfonation / Electrophilic additions / Multicomponent reactions / Sulfur trioxide complexes / Taurine
2-Aminoalkanesulfonic acids have been synthesized by a
three-component alkene/SO3·DMF/acetonitrile reaction, fol-
The reported two-step procedure provided a concise and ver-
satile approach to new analogues of the natural amino acid
lowed by hydrolysis. Trifluoromethanesulfonic acid was ad- taurine.
ded to the amino-sulfonation mixture to accelerate the reac-
tion and prevent the competitive formation of by-products.
(
Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
We now report some examples of a practical two-step
conversion of mono-, di-, and trisubstituted alkenes into 2-
aminoalkanesulfonic acids, based on the use of the com-
mercially available, solid, and easily handled SO3·DMF
complex.
Taurine (2-aminoethanesulfonic acid) is a conditionally
essential amino acid found in very high concentrations in
excitable tissues, where it plays key roles in the regulation
of several biological processes.[1] The mechanism and site
of taurine polyvalent functions are basically unknown.
Taurine is a conformationally flexible molecule with only Results and Discussion
small steric demand, and its analogues are very useful for
study of its biological activity and receptor-bound con-
Cyclohexene (1a; Scheme 1) has been reported[2d] to af-
formations.
ford 41% of trans-2-aminocyclohexanesulfonic acid (3a) on
treatment with 0.5 equiv. of liquid SO3 and 1 equiv. of
CH3CN in 1,2-dichloroethane, followed by hydrolysis.
When we applied the same procedure with the SO3·DMF
complex in place of liquid SO3, only 7% of 3a was obtained,
probably due to the low solubility of SO3·DMF. When the
reaction was carried out in CH3CN as a solvent, 3a was
afforded in 36% overall yield.
The need for new 2-aminosulfonic acids as taurine sur-
rogates prompted us to search for a rapid and general syn-
thetic approach to these compounds.
The amino-sulfonation (AS) of alkenes was an appealing
strategy because of the introduction of both the amino and
the sulfonic acid moieties in the same step, and also because
of the potential to obtain a large assortment of products
starting from easily available substrates.
The three-component alkene/SO3/nitrile reaction has to
date been reported in very few papers,[2] its scope being lim-
ited because of the poor yields and chemoselectivity.
One practical problem in running the AS reaction, espe-
cially in a research laboratory, concerned the use of liquid
SO3 or oleum, because of their high reactivity and difficulty
in handling. To the best of our knowledge, none of the more
stable SO3 complexes had yet been used in the AS of al-
kenes, despite their well-known effectiveness and conveni-
ence as sulfating and sulfonating reagents.[3]
Other commercially available SO3 complexes with
stronger bases, such as SO3·Py and SO3·TMA, did not react
at all under the same reaction conditions.
[‡]
Synthesis of Taurine Analogues, 2. Ϫ Part 1: Ref.[11]
[a]
Dipartimento di Chimica Organica ‘‘Ugo Schiff’’, and Centro
di Studio sulla Chimica e la Struttura dei Composti Eterociclici
`
e loro Applicazioni Ϫ CNR, Universita degli Studi di Firenze,
Polo Scientifico,
Via della Lastruccia 13, 50019 Sesto Fiorentino, Italy
Fax: (internat.) ϩ 39-055/457-3531
E-mail: franca.cordero@unifi.it
Scheme 1
Eur. J. Org. Chem. 2002, 1407Ϫ1411
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 1434Ϫ193X/02/0408Ϫ1407 $ 20.00ϩ.50/0
1407

F. M. Cordero, M. Cacciarini, F. Machetti, F. De Sarlo
FULL PAPER
The progress of the AS reaction of an equimolecular
Styrene (1d) and 1-methylcyclohexene (1e) were trans-
(0.35 mmol) mixture of cyclohexene (1a) and SO3·DMF in formed into the corresponding 2-amidosulfonic acids 2d
CD3CN (0.7 mL) (method A) at room temp. was monitored and 2e, respectively, only in the presence of CF3SO3H. The
by 1H NMR. Analysis of the spectra showed that the degree reaction mixtures obtained in the absence of the acid were
of conversion of 1a after 5 d was only partial. When 1 mol- not resolved, but the amides 2 were absent, as clearly shown
1
equiv. of CF3SO3H (0.35 mmol) was added to the original by the H NMR spectrum analyses.
mixture (method B), however, it was complete after only
2 h.
Cyclopentene (1b) and 1-hexene (1c) showed lower react-
ivities than cyclohexene (1a), and required 22 h and 6 d,
The AS reactions of different alkenes (1aϪ1f) with respectively, to be completely consumed even in the pres-
SO3·DMF (A) and with SO3·DMF/CF3SO3H (B) in ence of the CF3SO3H. In contrast, the reactions with styr-
CD3CN were similarly compared, and a considerable in- ene (1d) and 1-methylcyclohexene (1e) were very fast, as
crease in the reaction rate upon addition of CF3SO3H was they completely reacted in 15 and 10 min, respectively. Fi-
in general observed. In fact, analysis of the reaction mix- nally, the electron-poor 1-nitrocyclohexene (1f) was unaf-
1
tures B by H NMR at regular intervals showed that the fected under the reaction conditions after 1 month, in
reaction times reported in Table 1 were largely sufficient for agreement with the electrophilic character of the addition.
the complete disappearance of the olefinic signals, except in
The cyclic and acyclic alkenes 1 were subjected to AS
the case of 1f, which did not react at all (Entry 6, Table 1). under our optimized reaction conditions (Table 1). Upon
Without addition of the acid (A) the olefinic signals never completion of the AS reaction and aqueous workup, the
completely disappeared, even after reaction times twice (1b, 2-acetamidosulfonic acids 2 could be isolated by standard
1c) or 100 times (1a, 1d, 1e) those reported.
techniques. Alternatively, the crude compounds 2 could be
directly hydrolyzed to the corresponding amino derivatives
3 in refluxing aqueous 10% HCl[2d] or NH2NH2.[5] The AS
reaction of alkenes 1 directly followed by acid hydrolysis
gave the 2-aminosulfonic acids 3 in moderate to good over-
all yields (36Ϫ73%) (Table 1). The aminosulfonic acid 3 was
the only product detected in the reaction mixture in all the
reported examples, except in the case of ethylene (1i), which
afforded a 4:1 mixture of 3i and the corresponding 2-hydro-
xysulfonic acid.
The cyclic 2-aminosulfonic acids 3a and 3b were thus pre-
pared in yields significantly higher than those previously
obtained with liquid SO3 and 2 equiv. of alkene[2d] (3a: 65
vs. 41%; 3b: 56 vs. 12%) (Entries 1 and 2, Table 1). The AS
of 1-methylcyclohexene (1e) was completely regioselective
and stereoselective, solely giving the aminosulfonic acid 3e
in 30% yield (30 min, room temp.). An improved yield
(50%) of 3e was obtained when the AS step was run at 0
°C for 1.5 h (Entry 5, Table 1).
Table 1. Synthesis of 2-aminosulfonic acids 3 by AS of alkenes 1,
followed by hydrolysis
Entry
Alkene
AS reaction time[a]
Product
Yield[b] [%]
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
1g
1h
1i
1 h 40 min
23 h
6 d
1 h
1.5 h
30 d
3a
3b
3c
3d
3e
Ϫ
65
56
62
48
50
Ϫ
3 h
5
57
16 h
3h[c]
3i
43[d]
40[f]
12 d[e]
[a]
Reaction conditions: i) AS: 10 mmol of 1, SO3·DMF and
CF3SO3H in 20 mL of CH3CN, room temp. (Entry 5: 0 °C); ii)
H2O or H2O/MeOH, room temp., overnight; iii) 10% HCl, reflux,
12Ϫ24 h. [b] Yield of analytically pure product. [c] Only the erythro-
[d]
3h isomer was formed.
In this case 52% of starting material 1h
was also recovered. [e] The AS was performed in autoclave with an
[f]
The assignment of the structure of 3e could be achieved
indirectly by X-ray analysis[6,7] of a single crystal of the cor-
responding amide 2e (Scheme 3). The addition of the sul-
fonic group had occurred exclusively at the less substituted
carbon atom and in a cis relationship to the methyl group.
excess of ethylene at a pressure of 50 atm. Yield of analytically
pure taurine (3i) relative to SO3·DMF.
The presence of CF3SO3H also affected the chemoselec-
tivity of the reaction, since it prevented the competitive
formation of by-products. In particular, 1-hexene (1c)
slowly reacted with SO3·DMF in CD3CN to give, after
aqueous workup, an almost equimolecular mixture of 2c
and 2-hydroxysulfonic acid 4c.[4] In the presence of
CF3SO3H, however, 1c exclusively afforded the 2-acetamido
acid 2c (Scheme 2).
Scheme 3
The study of the structure of the 2e crystal established
that it existed as an inner salt. The amide moiety was pro-
tonated at the oxygen atom, in agreement with what has
been reported for amides in strongly acidic media and for
amide hydrofluoroborates.[8] The observed identical in-
˚
Scheme 2
1408
teratomic distances (1.29 A) between the carbamidic carbon
Eur. J. Org. Chem. 2002, 1407Ϫ1411

Amino-Sulfonation of Alkenes in a Three-Component Reaction
FULL PAPER
atom and the vicinal nitrogen and oxygen atoms are consist- vered in 40% yield after hydrolysis and crystallization. Al-
ent with a partial double bond character of the two bonds though this methodology is less convenient than the current
and a sharing of the positive charge between the two het- production processes of taurine (3i), it represents a new syn-
eroatoms (Scheme 3).
thetic approach to valuable isotopically labeled taurine. For
Pent-4-enyl benzoate (1g) reacted much more rapidly example, [13C]- and [2H]taurine, useful tools in the investi-
than the analogous terminal alkene 1-hexene (1c), conver- gation of biological processes such as taurine metabol-
sion being complete after only 3 h (Entry 7, Table 1). After ism,[10] can directly be obtained by AS of commercially
acid hydrolysis the highly water-soluble 5-hydroxyamino- available [13C2]- and [2H4]ethylene.
sulfonic acid 5 was recovered in 57% yield (Scheme 4).
Conclusion
This study has demonstrated a broader synthetic utility
of the multiple-component AS reaction. The method starts
from inexpensive and readily available alkenes and gives ac-
cess to a highly diverse range of natural and nonnatural 2-
aminosulfonic acids in only two steps.
The new modified conditions allow the reaction to be
run with greater simplicity and efficiency than previously
reported, through the use of a commercially available com-
plex of SO3 and inclusion of a stoichiometric amount of
Scheme 4
The two-step process of AS and hydrolysis on trans-stil-
bene (1h) exclusively afforded the known erythro-2-amino-
sulfonic acid[9] 3h (Scheme 5). The lower yield (43%) relative
CF3SO3H. This process appears to be quite general for elec-
to that obtained with SO3·DMF may possibly be attribut-
tron-rich carbonϪcarbon double bonds, and the wide cho-
able to the poorer reactivity of the 1,2-disubstituted alkene
ice of starting olefin provides a useful opportunity for diver-
1h, which was recovered unchanged to the extent of 52%
after the AS (thus the actual yield with respect to alkene
converted was 90%, Entry 8, Table 1).
sification of substituents on the basic 2-aminosulfonic sys-
tem. A structure-activity relationship study on the nonnat-
ural analogues of taurine by both in vitro and in vivo
experiments is currently underway and will be published
elsewhere.
Experimental Section
Scheme 5
General Remarks: All reactions that required dry conditions were
run under nitrogen with anhydrous solvents. Melting points (M.p.)
The stereochemical outcome of the AS, namely the anti
addition of the amino and sulfonic group both on cyclic
1
are uncorrected. H and 13C NMR spectra (in D2O, unless other-
wise stated) were recorded with a Varian Gemini (1H 200 MHz) or
and on acyclic olefins, was consistent with the mechanism
a Bruker DRX 500 (1H 500 MHz). Chemical shifts are given in
previously proposed.[2] In particular, the β-sultone 6 was
considered to be the primary intermediate, followed by nu-
cleophilic attack of CH3CN to afford the oxathiazine 7,
which was converted into the 2-amidosulfonic acid on hy-
ppm from TMS. The notation s, d, t, q, m and br indicates singlet,
doublet, triplet, quadruplet, multiplet, and broad, respectively. IR
spectra (in KBr, unless otherwise stated) were recorded with
PerkinϪElmer 881 or BX II spectrophotometers. Mass spectra
drolysis (Scheme 6). At present there is no evidence con-
(MS) were recorded with QMD 1000 Carlo Erba (EI, 70 eV) or PE
cerning the role played by CF3SO3H in the three-compon- SCIEX API 365 (ESI) instruments. Microanalyses were measured
with a PerkinϪElmer 2400 C instrument.
ent reaction, but the experimental results suggested its in-
volvement in promoting the addition of SO3 to the double
bond and enhancing the reactivity of 6 toward acetonitrile.
General Procedure: The appropriate alkene (10 mmol) was added
dropwise at room temp. (unless otherwise specified in Table 1) to a
solution of SO3·DMF complex (1.532 g, 10 mmol) and CF3SO3H
(875 mL, 10 mmol) in CH3CN (20 mL). The reaction mixture was
stirred at room temp. for the time reported in Table 1; H2O or H2O/
CH3OH (10 mL) was then added, and stirring was continued over-
night. Concentration in vacuo afforded the crude acetylaminosul-
fonic acid 2, which could be directly used for subsequent hydrolysis.
Small amounts of the intermediate 2 were filtered through ion-
exchange resins and characterized spectroscopically. The crude
product 2 was dissolved in 10% aqueous HCl solution (10 mL) and
then heated at a vigorous reflux overnight. The solution was then
partially concentrated in vacuo and diluted with CH3CN to precip-
itate the aminosulfonic acid, which was filtered, washed, and
Scheme 6
The last alkene studied was ethylene (1i). The AS reac-
tion was carried out in an autoclave under an ethylene pres-
sure of 50 atm, and the resulting amino acid 3i was reco- recrystallized when necessary (overall yields as reported in Table 1).
Eur. J. Org. Chem. 2002, 1407Ϫ1411 1409

F. M. Cordero, M. Cacciarini, F. Machetti, F. De Sarlo
FULL PAPER
trans-2-Acetylaminocyclohexanesulfonic Acid (2a): M.p. Ͼ 330 °C. H, Ph), 5.19Ϫ5.02 (m, 1 H, 2-H), 3.13Ϫ2.96 (AB system, 2 H, 1-
1H NMR: δ ϭ 3.88 (td, J ϭ 11.0, 4.4 Hz, 1 H, 2-H), 2.82 (td, J ϭ H2), 1.80 (s, 3 H, CH3).
11.0, 4.0 Hz, 1 H, 1-H), 2.31Ϫ2.15 (m, 1 H), 1.96 (s, 3 H, CH3CO),
2-Amino-2-phenylethanesulfonic Acid (3d): M.p. 314Ϫ315 °C (eth-
1.99Ϫ1.68 (m, 3 H), 1.55Ϫ1.20 (m, 4 H). 13C NMR: δ ϭ 173.2 (s),
anol/H2O) (ref.[12] 306Ϫ308 °C). 1H NMR ([D6]DMSO): δ ϭ
7.63Ϫ7.29 (m, 5 H, Ph), 4.66Ϫ4.41 (m, 1 H, H-2), 3.26Ϫ3.05 (m,
62.0 (d), 50.4 (d), 33.2 (t), 28.2 (t), 24.8 (t), 24.7 (t), 22.8 (q). IR
(CHCl3): ν ϭ 3674, 3001, 1707, 1413, 1356 cmϪ1. MS: m/z (%) ϭ
˜
1 H, 1-H), 2.92Ϫ2.78 (m, 1 H, 1-H). 13C NMR ([D6]DMSO): δ ϭ
137.2 (s, ipso C), 128.9 (d, 2 CAr), 128.8 (d, CAr), 127.4 (d, 2 CAr),
54.0 (t, C-1), 52.2 (d, C-2). IR:[13] ν˜ ϭ 3206Ϫ2864, 1246Ϫ1128,
1049 cmϪ1. MS (ESI): 240 [M ϩ K]ϩ, 224 [M ϩ Na]ϩ, 202 [M ϩ
H]ϩ. C8H11NO3S (201.24): calcd. C 47.75, H 5.51, N 6.96; found
C 47.66, H 5.30, N 6.76.
221 (7) [M]ϩ, 178 (7), 140 (22), 98 (21), 81 (40), 60 (100).
trans-2-Aminocyclohexanesulfonic Acid (3a): M.p. 408 °C (CH3CN/
H2O) (ref.[11] 410 °C, dec.). 1H NMR: δ ϭ 3.41 (dt, J ϭ 4.0,
11.4 Hz, 1 H, 2-H), 2.96 (dt, J ϭ 4.0, 11.4 Hz, 1 H, 1-H), 2.36Ϫ2.10
(m, 2 H), 1.94Ϫ1.74 (m, 2 H), 1.64Ϫ1.24 (m, 4 H). 13C NMR: δ ϭ
˜
62.3 (d), 52.9 (d), 32.7 (t), 28.9 (t), 26.0 (t), 25.9 (t). IR: ν ϭ
(1R*,2R*)-2-Acetylamino-2-methylcyclohexanesulfonic Acid (2e):
M.p. 194Ϫ197 °C. H NMR ([D6]DMSO): δ ϭ 10.60Ϫ9.90 (br. s,
3400Ϫ2800, 1501, 1240Ϫ1105, 1029 cmϪ1. MS (ESI): 202 [M ϩ
Na]ϩ, 180 [M ϩ H]ϩ. C6H13NO3S (179.20): calcd. C 40.21, H 7.31,
N 7.81; found C 40.52, H 7.59, N 7.65.
1
SO3 H), 8.60Ϫ8.40 (br. s, NH), 2.76 (dd, J ϭ 12.2, 3.0 Hz, 1 H, 1-
H), 2.44 (d, J ϭ 15.4 Hz, 1 H), 1.99 (dd, J ϭ 13.3, 2.7 Hz, 1 H),
1.70 (s, 3 H, CH3CO), 1.63 (d, J ϭ 12.8 Hz, 1 H), 1.48Ϫ1.43 (m,
3 H), 1.34 (s, 3 H, CH3), 1.32Ϫ1.05 (m, 3 H). 13C NMR: δ ϭ 173.7
(s, CϭO), 62.3 (d, C-1), 56.6 (s, C-2), 37.8 (t), 25.6 (t) 25.2 (t), 24.0
1
trans-2-Acetylaminocyclopentanesulfonic Acid (2b): H NMR: δ ϭ
4.37 (q, J ϭ 6.9 Hz, 1 H, 2-H), 3.23 (dt, J ϭ 9.1, 6.9 Hz, 1 H, 1-
H), 2.22Ϫ1.42 (m, 6 H), 1.96 (s, 3 H, CH3CO). 13C NMR: δ ϭ
175.7 (s), 66.6 (d), 55.7 (d), 35.9 (t), 30.1 (t) 25.6 (t), 24.6 (q).
˜
(q), 22.5 (t), 19.6 (q). IR: ν ϭ 3265, 3185, 3098, 2941, 2852, 2377,
1661, 1544, 1428, 1247, 1110, 993 cmϪ1. MS: m/z (%) ϭ 192 (3)
[M Ϫ COMe]ϩ, 178 (3), 154 (39), 112 (31), 95 (65), 81 (18), 70 (64),
60 (100). C9H17NO4S (235.30): calcd. C 45.94, H 7.28, N 5.95;
found C 46.29, H 7.16, N 5.99.
trans-2-Aminocyclopentanesulfonic Acid (3b): M.p. 324 °C (H2O/
ethanol) (ref.[11] 330 °C, dec.). H NMR: δ ϭ 3.84 (m, 1 H, 2-H),
1
3.40 (ddd, J ϭ 9.2, 7.3, 7.0 Hz, 1 H, 1-H), 2.31Ϫ2.14 (m, 2 H),
2.07Ϫ1.72 (m, 4 H). 13C NMR: δ ϭ 63.4 (d), 54.6 (d), 31.4 (t), 27.8
(t), 23.1 (t). IR: ν ϭ 3180Ϫ3050, 1220Ϫ1160, 1040 cmϪ1. MS (ESI):
(1R*,2R*)-2-Amino-2-methylcyclohexanesulfonic Acid (3e): M.p. Ͼ
˜
1
204 [M ϩ K]ϩ, 188 [M ϩ Na]ϩ, 166 [M ϩ H]ϩ. C5H11NO3S
(165.20): calcd. C 36.35, H 6.71, N 8.48; found C 36.49, H 7.09,
N 8.71.
340 °C (CH3CN/CH3OH/H2O). H NMR: δ ϭ 3.09 (dd, J ϭ 12.1,
3.7 Hz, 1 H, 1-H), 2.19Ϫ2.14 (m, 1 H), 1.94Ϫ1.80 (m, 2 H),
1.80Ϫ1.59 (m, 3 H), 1.53 (s, 3 H, CH3), 1.47Ϫ1.31 (m, 2 H). 13C
NMR: δ ϭ 63.7 (d, C-1), 56.2 (s, C-2), 38.7 (t), 25.1 (t), 24.9 (t),
2-Acetylaminohexanesulfonic Acid (2c): 1H NMR (CD3OD): δ ϭ
4.39 (m, 1 H, 2-H), 3.00 (d, J ϭ 6.3 Hz, 2 H, 1-H2), 2.20 (s, 3 H,
CH3CO), 1.79Ϫ1.58 (m, 2 H, 3-H2), 1.38Ϫ1.25 (m, 4 H, 4-H2, 5-
H2), 0.96Ϫ0.89 (m, 3 H, CH3). 13C NMR (CD3OD): δ ϭ 175.2 (s,
CϭO), 54.8 (t, C-1), 50.6 (d, C-2), 34.6 (t, C-3), 28.9 (t, C-4) 23.3
(t, C-5), 20.6 (q, CH3CO), 14.2 (q, CH3). MS: m/z (%) ϭ 224 (3)
[M]ϩ, 208 (3), 194 (2), 166 (13), 142 (32), 124 (100), 86 (69), 60
(45). C8H17NO4S (223.29): calcd. C 43.03, H 7.67, N 6.27; found
C 43.24, H 8.07, N 6.11.
˜
21.9 (t), 18.0 (q, CH3). IR: ν ϭ 3466, 2951, 2360, 1240Ϫ1147, 1032
cmϪ1. MS (ESI): 232 [M ϩ K]ϩ,216 [M ϩ Na]ϩ, 194 [M ϩ H]ϩ.
C7H15NO3S (193.26): calcd. C 43.501, H 7.82, N 7.25; found C
43.28, H 7.87, N 7.03.
2-Amino-5-hydroxypentanesulfonic Acid (5): 1H NMR:
δ ϭ
3.84Ϫ3.62 (m, 3 H, 2-H and 5-H2), 3.32 (A part of an ABX system,
JAB ϭ 14.7 Hz, JAX ϭ 3.5 Hz, 1 H, 1-H), 3.17 (B part of an ABX
system, JAB ϭ 14.7 Hz, JBX ϭ 8.8 Hz, 1 H, 1-H), 1.97Ϫ1.61 (m, 4
H, 3-H2 and 4-H2). 13C NMR: δ ϭ 51.0 (t), 47.7 (d, C-2), 43.9 (t),
29.0 (t), 26.9 (t). MS (ESI): 222 [M ϩ K]ϩ, 206 [M ϩ Na]ϩ, 184
[M ϩ H]ϩ.
2-Aminohexanesulfonic Acid (3c): M.p. Ͼ 300 °C (CH3CN/H2O).
1H NMR: δ ϭ 3.69 (m, 1 H, 2-H), 3.30 (A part of an ABX system,
JAB ϭ 15.0 Hz, JAX ϭ 3.3 Hz, 1 H, 1-H), 3.13 (B part of an ABX
system, JAB ϭ 15.0 Hz, JBX ϭ 9.5 Hz, 1 H, 1-H), 1.84Ϫ1.72 (m, 2
(1R*,2S*)-2-Amino-1,2-diphenylethanesulfonic Acid (3h): M.p. Ͼ
255 °C dec. (EtOH/H2O) (ref.[9] 306Ϫ308 °C). 1H NMR
([D6]DMSO): δ ϭ 8.60Ϫ8.20 (br. s), 7.38Ϫ7.01 (m, 10 H, 2 Ph),
5.00 (m, 1 H, 2-H), 4.11 (d, J ϭ 2.9 Hz, 1 H, 1-H). 13C NMR
([D6]DMSO): δ ϭ 135.2 (s, ipso C), 132.7 (s, ipso C), 130.3 (d, 2
CAr), 128.3 (d), 128.1 (d, 2 CAr), 127.8 (d, 2 CAr), 127.6 (d), 127.5
(d, 2 CAr), 67.1 (d, C-1), 56.1 (d, C-2).
H, 3-H2), 1.47Ϫ1.27 (m, 4 H, 4-H2, 5-H2), 0.90 (m, 3 H, CH3). 13
C
NMR: δ ϭ 52.2 (t, C-1), 49.3 (d, C-2), 32.3 (t, C-3), 26.9 (t, C-4),
22.2 (t, C-5), 13.6 (q, CH3). IR: ν˜ ϭ 1250Ϫ1190, 1041 cmϪ1. MS
(ESI): 220 [M ϩ K]ϩ, 204 [M ϩ Na]ϩ, 182 [M ϩ H]ϩ. C6H15NO3S
(181.25): calcd. C 39.75, H 8.34, N 7.73; found C 40.05, H 8.11,
N 7.63.
Taurine (3i): The AS was performed in a autoclave with an excess
of ethylene at a pressure of 50 atm. The spectroscopic data were
identical with those of a commercial sample of taurine.
2-Hydroxyhexanesulfonic Acid (4c): M.p. 218Ϫ220 °C (ethyl acet-
ate/CH3OH). H NMR: δ ϭ 4.09 (m, 1 H, 2-H), 3.09 (A part of
an ABX system, JAB ϭ 14.9 Hz, JAX ϭ 4.7 Hz, 1 H, 1-H), 3.00 (B
part of an ABX system, JAB ϭ 14.9 Hz, JBX ϭ 7.4 Hz, 1 H, 1-H),
1.69Ϫ1.50 (m, 2 H, 3-H2), 1.49Ϫ1.34 (m, 4 H, 4-H2, 5-H2),
0.91Ϫ0.81 (m, 3 H, CH3). 13C NMR: δ ϭ 68.2 (d, C-2), 57.6 (t, C-
1
[1]
For example see: [1a] S. W. Schaffer, J. B. Lombardini, J. Azuma,
Amino Acids 2000, 18, 305Ϫ318. [1b] J. D. Militante, J. B. Lom-
bardini, S. W. Schaffer, Cardiovasc. Res. 2000, 46, 393Ϫ402.
[1c] H. Satoh, N. Sperelakis, Gen. Pharmac. 1998, 30, 451Ϫ463.
˜
1), 36.1 (t, C-3), 27.2 (t, C-4) 22.4 (t, C-5), 13.8 (q, CH3). IR: ν ϭ
3387, 2955, 2924, 2517, 1227, 1170, 1051 cmϪ1. MS (ESI): 431 [2 M
ϩ 3 Na]ϩ, 227 [M ϩ 2 Na]ϩ, 182 [M]ϩ, 163 [M Ϫ H2O]ϩ, 95
(CH2SO3H), 80 (SO3H). C6H14O4S (182.20): calcd. C 39.55, H
7.74; found C 39.94, H 7.63.
[1d]
R. J. Huxtable, Physiol. Rev. 1992, 72, 101Ϫ163.
[2] [2a]
G. L. Broussalian, U. S. Patent 3,303,137, 1967; Chem.
[2b]
Abstr. 1966, 66, 67063d.
I. D. Khalistova, V. A. Podgor-
[2c]
nova, Russ. J. Appl. Chem. 1994, 67, 1185Ϫ1188.
V. A .
2-Acetylamino-2-phenylethanesulfonic Acid (2d): 1H NMR
([D6]DMSO): δ ϭ 8.60Ϫ8.45 (m, 1 H, NHCO), 7.38Ϫ7.15 (m, 5
Podgornova, I. D. Khalistova, B. F. Ustavshchikov, Russ. J.
[2d]
Appl. Chem. 1996, 69, 110Ϫ113.
S. M. Liebowitz, J. B.
1410
Eur. J. Org. Chem. 2002, 1407Ϫ1411

Amino-Sulfonation of Alkenes in a Three-Component Reaction
FULL PAPER
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Similarly, long-chain terminal alkenes gave mixtures of 2-acyl-
Centre, 12 Union Road, Cambridge, CB2 1EZ, UK [Fax: (in-
ternat.) ϩ 44-1223/336-033; E-mail: deposit@ccdc.cam.ac.uk].
[3]
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[8b]
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[9]
and an alkanenitrile (ref.[2a]).
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[5]
[10]
D. D. Keith, J. A. Tortora, R. Yang, J. Org. Chem. 1978, 43,
3711Ϫ3713.
Dr. Cristina Faggi is acknowledged for carrying out the X-
ray analysis.
[6]
[11]
[7]
[12]
[13]
The authors have deposited atomic coordinates for this struc-
ture with the Cambridge Crystallographic Data Centre; depos-
itory number CCDC-167422. The data can be obtained free of
charge on application to Cambridge Crystallographic Data
Received August 13, 2001
[O01396]
Eur. J. Org. Chem. 2002, 1407Ϫ1411
1411