Development of a mild procedure for the addition of bisulfite to electrophilic olefins

Article abstract of DOI:10.1002/adsc.201000543

The sulfonylation of activated alkenes is an important yet unexplored reaction due to the harshness of conditions required. We have identified a procedure which allowed the reaction of alkenes with equimolar amounts of bisulfite at room temperature. Copyr

Full text of DOI:10.1002/adsc.201000543

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DOI: 10.1002/adsc.201000543
Development of a Mild Procedure for the Addition of Bisulfite to
Electrophilic Olefins
Francesco Fini,a Murali Nagabelli,a and Mauro F. A. Adamoa,*
a
Centre for Synthesis and Chemical Biology (CSCB), Department of Pharmaceutical and Medicinal Chemistry, The Royal
College of Surgeons in Ireland, 123 St. Stephenꢀs Green, Dublin 2, Dublin, Ireland
Fax : (+353)-1-402-2168; phone: (+353)-1-402-2208; e-mail: madamo@rcsi.ie
Received: July 10, 2010; Revised: October 5, 2010; Published online: December 1, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000543.
Abstract: The sulfonylation of activated alkenes is
an important yet unexplored reaction due to the
harshness of conditions required. We have identi-
fied a procedure which allowed the reaction of al-
kenes with equimolar amounts of bisulfite at room
temperature.
alkylation of sulfonic acid esters with alkyl halides or
with b-nitroalkenes using a chiral auxiliary strategy[10]
and the nucleophilic addition of chiral nitrogen nucle-
ophiles such as (S)-1-amino-2-methoxymethylpyrroli-
dine (SAMP) to a,b-unsaturated sulfonic acid
esters.[11] The same group reported an organocatalyt-
ic-mediated addition of a sulfur nucleophile to a,b-un-
saturated sulfonic acid esters.[12] Despite all these ef-
forts, the simple addition of bisulfite to olefins, discov-
ered over a century ago,[13] still remains the most
straight-forward access to aliphatic sulfonic acids. This
reaction employs large excesses of reactants and re-
quires high temperatures. The harsh conditions effec-
Keywords: alkenes; amine catalysis; sulfonic acids;
thia-Mchael addition; triethylamine
Herein we report a mild, amine-promoted, room tem- tively limited the synthetic utility of this reaction with
perature procedure for the addition of aqueous the reports of Kellogg[4] and Crowley[14] being the
sodium bisulfite to activated olefins to give organic only variant described recently. Kellogg reported the
sulfonic acids. Sulfonic acids are among the strongest addition of solid sodium bisulfite to chalcones in etha-
acids in organic chemistry with a pKa (DMSO) of nol at reflux;[4] Crawley and co-workers have success-
1.6.[1] For this reason, they have been often used as re- fully optimized a microwave-assisted sulfonylation of
solving agents for chiral racemic amines,[2] and fami- cinnamic acid ester derivatives using aqueous sodium
lies of sulfonic acids were prepared and used in bisulfite.[14] Both these procedures required the use of
“Dutch resolution” experiments.[3,4] Sulfonic acids and high temperature and a large excess of bisulfite reac-
sulfonamides are isosteric with carboxylates which tant. The need for forcing conditions could be under-
justifies their popularity in medicinal chemistry.[5] stood when considering the behaviour of bisulfite in
Taurine and some of its derivatives (e.g., homotaur- aqueous solutions (Scheme 1).
ine, guanidotaurine) have repeatedly being found to
have activity on the central nervous system (CNS).[6]
The sulfonic acid functionality is also present in
some naturally occurring compounds, for example, in
6-gingesulfonic acid, extracted from ginger (Zingiberis
Rhizoma) which is used as an anti-ulcer drug.[7] Due
to the biological activity of sulfonic acids, several mul-
tistep syntheses have been reported. For example,
Corey prepared chiral sulfonic acids via a synthetic
sequence in which acetophenone reduction was the
key enantio-determining step.[8] Di Bella and co-
workers successfully synthesized some enantiopure
amino sulfonic acids starting from chiral amino
Scheme 1. Different equilibria existing in a bisulfite solu-
acids.[9] Enders and co-workers have reported the a- tion.
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Francesco Fini et al.
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chalcone 1 was reacted with 10 equivalents of bisulfite
and 10 equivalents of triethylamine, the reaction pro-
ceeded to full conversion within an hour (Table 1,
entry 2). Use of lower amounts of triethylamine gave
incomplete conversions or longer reaction times. This
procedure allowed the reaction of a few alkenes at
room temperature although in order to get high con-
Scheme 2. The addition of bisulfite to chalcone.
Bisulfite establishes two equilibria, the first one be- versions and yields large excesses of both reagents
tween its forms A and B and a second one involving were needed.[17] Secondary amines such as piperidine
interaction of A plus B to give C. Pertinent to this and pyrrolidine gave equally a full conversion at
discussion, form
A
is the active nucleophile room temperature but required longer reaction times.
(Scheme 1).[15] It has been reported that at high con- Having established that amines had an effect on the
centration, e.g., commercial 38% w/v aqueous bisul- reaction rate we then investigated the role of bisulfite
fite, the two forms A and B interact by hydrogen concentration. Importantly, the use of a diluted solu-
bonding to form mainly the non-nucleophilic dimer tion of bisulfite (0.5M) allowed us to obtain a 50%
C; conversely at low concentrations (<10À2 M) dimer conversion of chalcone 1 in 18 h using only 1.2 equiv-
C decomposes to give isomeric forms A and B alents of bisulfite and 0.2 equivalents of triethylamine
(Scheme 1). From this report, commercial concentrat- (Table 1, entry 3). The reaction efficiency increased
ed solutions of bisulfite, which mostly contain dimeric when THF was replaced by methanol. Hence, reac-
C, could not add to alkenes at room temperature, but tion of chalcone 1 with 1.2 equivalents of bisulfite and
rather require heating in order to dissolve dimeric C. 0.2 equivalents of triethylamine (Table 1, entry 4) pro-
Considering that faster sulfonylation occurs when the ceeded to full conversion in 18 h. Significantly, the
concentration of A is maximised, we hyphothesised same reaction excluding triethylamine (Table 1,
that addition of bisulfite to alkenes could be promot- entry 5) gave negligible conversion after 360 hours
ed by: (i) using diluted solutions to move equilibrium (15 days), demonstrating the rate acceleration impart-
from dimeric C to monomeric A and B; (ii) using ed by triethylamine. The novel procedure identified
Brønsted bases, for example an amine, to shift the was complemented by a straight-forward method of
equilibrium from unreactive B to reactive A.
purification. The pure sulfonic acid was therefore ob-
In analogy with the phosphonate–phosphite tauto- tained by passing the crude material through a plug
merism,[16] it was thought that triethylamine may have of freshly activated acidic ion exchange resin. With
an effect on the A–B equilibrium towards the most the optimised reaction conditions in hand, the reactiv-
reactive species A, increasing therefore the reaction ity of other electrophilic olefins was explored
rate with electrophilic alkenes. With this in mind, we (Table 2). The new conditions were highly effective
have tested the effect of bisulfite concentration and and sulfonylation of strong electrophilic alkenes, for
basic catalysis independently (Scheme 2 and Table 1). instance, b-nitrostyrene 3, was complete in minutes in
Initial studies run using commercial aqueous sodium the presence of only 10 mol% of triethylamine
bisulfite (5M) showed that amines accelerated the re- (Table 2, entry 1). Noteworthy, the sulfonylation of
action rate. Reaction of chalcone 1 (Scheme 2) with a substrates 5 and 7 arose from a nucleophilic process
large excess of bisulfite at room temperature gave rather than an electrophilic substitution (Table 2, en-
limited conversion (Table 1, entry 1), however, when tries 2 and 3).[18] Less reactive electrophiles (Table 2,
entries 4–7) reacted equally well proceeding to a full
conversion in 18–24 h, using 20 mol% of triethylamine
(entries 4–7). Less activated olefins showed a signifi-
Table 1. Optimization of the reactions conditions for the
direct sulfonylation of chalcone 1.[a]
cantly lower reactivity (entry 8–12), not achieving a
full conversion after four days (entries 8–12) under
the conditions used.[19] 4-Methyl-3-penten-2-one 15
(entry 8) and methylvinylketone 21 (entry 11) reacted
at room temperature with bisulfite (1.2 equiv.) in the
Entry Equiv of NaHSO3 Equiv of Et3N t [h] Conv.[b] [%]
1[c]
2[c]
3[c]
4[d]
5[d]
6[d]
10 (5M)
10 (5M)
1.2 (0.5M)
1.2 (0.5M)
1.2 (0.5M)
1.2 (0.5M)
–
6
1
18
18
<10%
>98%
<50%
>98%
10
0.2
0.2
–
presence of
a
slight excess of triethylamine
(1.2 equiv.) giving the corresponding sulfonic acids 16
and 22 in high yields.[19] However, when the catalyst
loading was limited to 0.2 equiv., the reaction rate
was significantly slower and sulfonic acids 16 and 22
were obtained in poor yields (Table 2, entries 8 and
11).
360 <10%
18 >98%
0.2
[a]
[b]
Reactions carried out in a test tube on a 0.1-mmol scale.
Conversion evaluated by 1H NMR analysis run on the
crude reaction mixture.
THF used as solvent.
MeOH used as solvent.
[c]
[d]
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Development of a Mild Procedure for the Addition of Bisulfite to Electrophilic Olefins
Table 2. Screening of the olefins for the catalytic sulfonylation reaction.[a,b]
Entry
1[d]
Reagent
Product
t
Yield [%][c]
89
3
5
4
6
10 min
2[d]
10 min
87
3[d]
7
9
8
10 min
21 h
86
96
4
10
5
6
1
2
21 h
24 h
85
96
11
12
7
13
15
17
19
21
14
16
18
20
22
40 h
4d
84
18
15
16
18
8
9
4d
10
11
4d
4d
12
23
24
4d
15
[a]
Reactions carried out in a test tube without any precautions to exclude moisture and air, by means of 0.1 mmol of
alkene, 0.12 mmol of aqueous sodium bisulfite (0.5M) and 0.04 mmol of Et3N in 2 mL of MeOH at 228C.
A full characterisation of the pure sulfonic acids obtained is included in the Supporting Information.
Isolated yield after passing the crude through freshly activated acidic ion exchange resin.
Reaction performed with 10 mol% of Et3N.
[b]
[c]
[d]
The scope of the catalytic sulfonylation reaction strong electron-donating or electron-withdrawing
was therefore demonstrated by reacting several chal- group on the aromatic ring (Table 3, entries 2 and 3).
cones 1 and styryl nitroisoxazole 2.[4,20]
Styryl nitroisoxazole 11 and derivatives showed
Compounds 1, 25 and 27 showed an excellent reac- slower reactivity compared to chalcones,[21] neverthe-
tivity furnishing the corresponding products 2, 26 and less giving the corresponding sulfonic acid in excellent
28 in good yields (83–87%, Table 3, entries 1–3) and yields (Table 3, entries 4–12). The reaction conditions
in 18–36 h regardless of the presence of either a were tolerable to a great variety of functional groups.
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Table 3. Catalytic sulfonylation reactions of chalcones 1 and styryl nitroisoxazole 2.[a]
Entry
Reagent
Product
t [h]
Yield [%][b]
85
1
1
2
21
2
3
4
5
25
27
11
29
26
28
12
30
36
87
36
83
42 (36)[c]
90
97 (99)[c]
97
6
31
32
75
99
7
8
33
35
34
36
36
36
98
99
9
37
38
42
93
10
11
39
41
40
42
48
36
99
91
12
43
44
75
88
[a]
Unless otherwise noted, the reactions were carried out in a test tube without any precautions to exclude moisture and air,
by means of 0.2 mmol of alkene, 0.3 mmol of aqueous sodium bisulfite (0.5M) and 0.04 mmol of Et3N in 2 mL of MeOH
at 178C.
Isolated yield after passing the crude material through freshly activated acidic ion exchange resin.
Value in brackets refers to the reaction carried out on a 7-mmol scale.
[b]
[c]
Alkenes 11 bearing either an electron-donating or corresponding products were obtained in 91% and
an electron-withdrawing group reacted equally well 88% yields (Table 3, entries 11 and 12). The robust
furnishing high yields of the desired sulfonic acid (97– protocol introduced was further supported in a prepa-
99%, Table 3, entries 5 and 6); alkenes 11 carrying an rative-scale reaction, where 11 was obtained in 99%
halogen-substituted aromatic ring or an heteroaro- yields on a 7-mmol scale-reaction producing 2 grams
matic group, for example 35 and 39 gave the corre- of pure sulfonic acid after 36 h (Table 3, entry 4,
sponding sulfonic acids in excellent yields (93–99%, values in brackets).
Table 3, entries 7–10). Remarkably, also acidic or
In conclusion, we have established a procedure
basic functional groups were well tolerated and the which allowed the preparation of complex sulfonic
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Development of a Mild Procedure for the Addition of Bisulfite to Electrophilic Olefins
(s, 3H); 13C NMR (100 MHz, MeOD): d=173.4, 156.7,
acids by the direct sulfonylation of activated olefins.[22]
The procedure herein reported is significant for the
following reasons: (i) it runs at room temperature; (ii)
makes use of only slight excesses of bisulfite; (iii) it is
catalysed by simple amines, for example, triethyla-
mine; (iv) it is complemented by an easy purification
method; (v) the method allows for the multi-gram
preparation of sulfonic acids.
136.6, 131.7, 130.3, 129.2, 129.1, 64.0, 31.1, 11.5; HR-MS:
m/z=311.0329, C12H11N2O6S [MÀH]À requires 311.0338.
1-(4-Methoxyphenyl)-2-(3-methyl-4-nitroisoxazol-5-yl)eth-
anesulfonic acid (30): Pale brown solid; yield. 66 mg (97%);
mp 191–1938C; 1H NMR (400 MHz, MeOD): d=7.34 (d,
J=8.8 Hz, 2H), 6.82 (d, J=8.8 Hz, 2H), 4.50 (dd, J=10.1,
6.0 Hz, 1H), 4.09 (dd, J=15.3, 6.0 Hz, 1H), 4.02 (dd, J=
15.3, 10.2 Hz, 1H), 3.74 (s, 3H), 2.41 (s, 3H); 13C NMR
(100 MHz, MeOD): d=173.5, 161.0, 156.8, 131.7, 131.4,
128.3, 114.6, 63.3, 55.6, 31.1, 11.5; HR-MS: m/z=341.0430,
C13H13N2O7S [MÀH]À requires 341.0443.
Further studies on the enantioselective version of
this process are currently in process.
2-(3-Methyl-4-nitroisoxazol-5-yl)-1-(4-nitrophenyl)ethane-
sulfonic acid (32): Pale brown solid; yield: 71 mg (99%); mp
193–1958C; 1H NMR (400 MHz, MeOD): d=8.17 (d, J=
8.9 Hz, 2H), 7.72 (d, J=8.8 Hz, 2H), 4.70 (dd, J=10.1,
5.7 Hz, 1H), 4.21 (dd, J=15.7, 5.7 Hz, 1H), 4.05 (dd, J=
15.6, 10.1 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz,
MeOD): d=172.9, 156.9, 149.0, 144.6, 131.6, 124.2, 63.3,
31.0, 11.5; HR-MS: m/z=356.0202, C12H10N3O8S [MÀH]À
requires 356.0189.
Experimental Section
General Procedure
In a test tube equipped with a magnetic stirring bar were
added in sequence olefins 1, 11, 25, 27, 29, 31, 33, 35, 37, 39,
41 or 42 (0.20 mmol), MeOH (2.0 mL), triethylamine
(5.5 mL, 0.04 mmol), and 0.5M aqueous sodium bisulfite
(0.6 mL, 0.3 mmol). The reaction mixture was vigorously
stirred at 178C for the stated time. The crude mixture was
filtered off over a celite pad and then dried under reduced
pressure. The crude product was then passed through a plug
of freshly activated acidic ion exchange resin and washed
with deionized water (3ꢂ3 mL).[23] Finally, pure sulfonic
acid was obtained by drying the aqueous solution under re-
duced pressure and in high vacuum.
3-Oxo-1,3-diphenylpropane-1-sulfonic acid (2): Off white
solid; yield: 49.3 mg (85% ); mp 175–1778C; 1H NMR
(400 MHz, MeOD): d=7.96–7.92 (m, 2H), 7.60–7.53 (m,
1H), 7.51–7.42 (m, 4H), 7.30–7.19 (m, 3H), 4.69 (dd, J=9.5,
4.3 Hz, 1H), 3.97 (dd, J=17.4, 4.3 Hz, 1H), 3.88 (dd, J=
17.5, 9.5 Hz, 1H); 13C NMR (100 MHz, MeOD): d=198.8,
138.1, 138.0, 134.4, 130.5, 129.7, 129.1, 129.0, 128.5, 63.2,
41.6; HR-MS: m/z=291.0700, C15H15O4S [M+H]+ requires
291.0691.
1-(4-Methoxyphenyl)-3-oxo-3-phenylpropane-1-sulfonic
acid (26): Yellow solid; yield: 55.7 mg (87%); mp 186–
1888C; 1H NMR (400 MHz, CD3OD): d=7.97–7.89 (m,
2H), 7.60–7.52 (m, 1H), 7.50–7.41 (m, 2H), 7.39 (d, J=
8.8 Hz, 2H), 6.82 (d, J=8.8 Hz, 2H), 4.64 (dd, J=9.6,
4.2 Hz, 1H), 3.93 (dd, J=17.3, 4.2 Hz, 1H), 3.83 (dd, J=
17.3, 9.6 Hz, 1H), 3.72 (s, 3H); 13C NMR (100 MHz,
MeOD): d=198.0, 160.7, 138.2, 134.5, 131.6, 129.9, 129.8,
129.2, 114.6, 62.7, 55.7, 41.8; HR-MS: m/z= 319.0646,
C16H15O5S [MÀH]À requires 319.0640.
1-(4-Fluorophenyl)-2-(3-methyl-4-nitroisoxazol-5-yl)eth-
anesulfonic acid (34): Off white solid; yield: 64.7 mg (98%);
1
mp 165–1688C; H NMR (400 MHz, MeOD): d=7.50–7.40
(m, 2H), 7.05–6.94 (m, 2H), 4.55 (dd, J=10.24, 5.76 Hz,
1H), 4.12 (dd, J=15.41, 5.76 Hz, 1H), 4.01 (dd, J=15.4,
10.2 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, MeOD):
d=173.3, 163.9 (d, J=245 Hz), 156.8, 132.8 (d, J=3 Hz),
132.2 (d, J=8 Hz), 131.7, 115.9 (d, J=22 Hz), 63.1, 31.1,
11.5; HR-MS: m/z=329.0233, C12H10FN2O6S [MÀH]À re-
quires 329.0244.
1-(3-Chlorophenyl)-2-(3-methyl-4-nitroisoxazol-5-yl)eth-
anesulfonic acid (36): Off white solid; yield: 68.6 mg (99%);
1
mp 118–1208C; H NMR (400 MHz, MeOD): d=7.57–7.43
(m, 1H), 7.41–7.30 (m, 1H), 7.29–7.19 (m, 2H), 4.54 (dd, J=
10.1, 5.8 Hz, 1H), 4.13 (dd, J=15.5, 5.8 Hz, 1H), 4.00 (dd,
J=15.4, 10.1 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz,
MeOD): d=173.1, 156.8, 139.1, 135.0, 131.7, 130.7, 130.3,
129.1, 128.8, 63.4, 31.0, 11.5; HR-MS: m/z=344.9940,
C12H10ClN2O6S [MÀH]À requires 344.9948.
1-(2,3-Dichlorophenyl)-2-(3-methyl-4-nitroisoxazol-5-yl)-
ethanesulfonic acid (38): Pale yellow solid; yield: 71 mg
(93%); 1H NMR (400 MHz, MeOD): d=7.77 (dd, J=7.9,
1.5 Hz, 1H), 7.4 (dd, J=8.0, 1.5 Hz, 1H), 7.29 (t, J=8.0 Hz,
1H), 5.36 (dd, J=10.4, 5.5 Hz, 1H), 4.17 (dd, J=15.4,
5.5 Hz, 1H), 3.97 (dd, J=15.4, 10.4 Hz, 1H), 2.43 (s, 3H);
13C NMR (100 MHz, MeOD): d=172.8, 156.9, 137.3, 134.4,
133.9, 131.7, 131.1, 128.9, 128.5, 59.4, 31.4, 11.5; HR-MS: m/
z=378.9551, C12H9Cl2N2O6S [MÀH]À requires 378.9558.
2-(3-Methyl-4-nitroisoxazol-5-yl)-1-(thiophen-2-yl)ethane-
sulfonic acid (40): Pale brown solid; yield after 48 h: 63 mg
1-(4-Nitrophenyl)-3-oxo-3-phenylpropane-1-sulfonic acid
(28): Pale yellow solid ; yield: 55.6 mg (83%); mp 173–
1758C; 1H NMR [400 MHz, (CD3)2SO]: d=8.09 (d, J=
8.8 Hz, 2H), 7.92 (d, J=8.4 Hz, 2H), 7.66–7.58 (m, 3H),
7.51 (t, J=7.7, 7.7 Hz, 2H), 4.34 (dd, J=9.9, 3.9 Hz, 1H),
3.9 (dd, J=17.9, 4.0 Hz, 1H), 3.75 (dd, J=17.8, 9.9 Hz, 1H);
13C NMR [100 MHz, (CD3)2SO]: d=197.5, 147.3, 146.0,
136.4, 133.2, 130.4, 128.7, 127.9, 122.5, 61.0, 40.8; HR-MS:
m/z=334.0374, C15H12NO6S [MÀH]À requires 334.0385.
2-(3-Methyl-4-nitroisoxazol-5-yl)-1-phenylethanesulfonic
acid (12): Off white solid; yield: 60.6 mg (97%); mp 176–
1
(99%); mp 128–1308C; H NMR (400 MHz, CD3OD): d=
7.33–7.24 (m, 1H), 7.10–7.03 (m, 1H), 6.92 (dd, J=5.1,
3.6 Hz, 1H), 4.84 (dd, J=10.2, 5.6 Hz, 1H), 4.13 (dd, J=
15.3, 5.6 Hz, 1H), 3.98 (dd, J=15.3, 10.3 Hz, 1H), 2.44 (s,
3H); 13C NMR (100 MHz, MeOD): d=173.0, 156.8, 138.5,
131.8, 128.7, 127.4, 126.7, 59.4, 32.6, 11.5; HR-MS: m/z=
316.9912, C10H9N2O6S2 [MÀH]À requires 316.9902.
2-(3-Methyl-4-nitroisoxazol-5-yl)-1-(pyridin-2-yl)ethane-
sulfonic acid (42): White solid; yield: 57 mg (91%); mp
2508C (dec.); 1H NMR (400 MHz, D2O): d=8.72 (d, J=
4.9 Hz, 1H), 8.45 (t, J=8.0 Hz, 1H), 8.10 (d, J=8.1 Hz,
1
1788C; H NMR (400 MHz, MeOD): d=7.47–7.39 (m, 2H),
7.31–7.20 (m, 3H), 4.55 (dd, J=10.0, 6.0 Hz, 1H), 4.12 (dd,
J=15.4, 6.0 Hz, 1H), 4.05 (dd, J=15.4, 10.0 Hz, 1H), 2.40
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Francesco Fini et al.
COMMUNICATIONS
1H), 5.08 (dd, J=8.3, 6.8 Hz, 1H), 4.35 (dd, J=16.1, 6.7 Hz,
1H), 4.13 (dd, J=16.1, 8.6 Hz, 1H), 2.48 (s, 3H); 13C NMR
(100 MHz, D2O): d=173.6, 159.8, 152.7, 148.1, 146.8, 133.7,
129.7,129.3, 63.4, 31.0, 13.6; HR-MS: m/z=312.0296,
C11H10N3O6S [MÀH]À requires 312.0290.
[7] M. Yoshikawa, S. Yamaguchi, K. Kunimi, H. Matsuda,
J. Yamahara, N. Murakami, Chem. Pharm. Bull. 1994,
42, 1226.
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Angew. Chem. 2002, 114, 116; Angew. Chem. Int. Ed.
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J. W. Bats, Chem. Commun. 2001, 2489; D. Enders,
O. M. Berner, N. Vignola, W. Harnying, Synthesis 2002,
1945.
1-(2-Hydroxyphenyl)-2-(3-methyl-4-nitroisoxazol-5-yl)eth-
anesulfonic acid (44): Pale brown solid; yield: 58 mg (88%);
mp 150–1528C; 1H NMR (400 MHz, CD3OD): d=7.52 (d,
J=7.8 Hz, 1H), 7.0 (t, J=7.3 Hz, 1H), 6.78 (t, J=7.5 Hz,
1H), 6.70 (d, J=8.1 Hz, 1H), 5.19 (dd, J=10.7, 5.4 Hz, 1H),
4.12 (dd, J=14.8, 5.4 Hz, 1H), 3.94 (dd, J=14.8, 10.7 Hz,
1H), 2.41 (s, 3H); 13C NMR (100 MHz, CD3OD): d=173.5,
156.9, 156.6, 131.7, 130.1, 130.0, 122.9, 120.5, 116.6, 56.4,
31.0, 11.5; HR-MS: m/z=327.0285, C12H11N2O7S [MÀH]À
requires 327.0287.
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Acknowledgements
We would like to acknowledge Enterprise-Ireland for a grant
to F.F. and PTRLI cycle III for a grant to M.F.A.A.
[14] M. L. Crawley, E. McLaughlin, W. Zhu, A. Combs,
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[23] A 5-mL syringe packed with acidic ion exchange resin
(3 mL, ca. 2.2 g) was washed with 6M HCl (4ꢂ3 mL)
and then with deionized water (4ꢂ3 mL). After that
the resin pad was ready to be used.
3168
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Adv. Synth. Catal. 2010, 352, 3163 – 3168