Synthesis of N-Acyl Sulfamates from Fluorosulfates and Amides

Article abstract of DOI:10.1021/acs.joc.8b02785

A novel synthetic strategy toward N-acyl sulfamates was developed. Interestingly, fluorosulfates, a new emerging class of electrophiles, were used to construct the sulfamate core. This precludes handling of chlorosulfonyl isocyanate and sulfamoyl chloride

Full text of DOI:10.1021/acs.joc.8b02785

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Note
Synthesis of N-Acyl Sulfamates from Fluorosulfates and Amides
Philippe Gilles, Cedrick Veryser, Sarah Vangrunderbeeck, Sam
Ceusters, Luc Van Meervelt, and Wim Michel De Borggraeve
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02785 • Publication Date (Web): 24 Dec 2018
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Synthesis of N-Acyl Sulfamates from Fluorosulfates and Amides
Philippe Gilles,† Cedrick Veryser,† Sarah Vangrunderbeeck,† Sam Ceusters,† Luc Van Meervelt,‡ Wim
M. De Borggraeve.*,†
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†Molecular Design and Synthesis, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, box 2404, 3001 Leuven,
Belgium.
‡Biochemistry, Molecular and Structural Biology, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, box 2404,
3001 Leuven, Belgium
Supporting Information Placeholder
ABSTRACT: A novel synthetic strategy towards N-acyl sulfamates was developed. Interestingly, fluorosulfates, a new emerging
class of electrophiles, were used to construct the sulfamate core. This precludes handling of chlorosulfonyl isocyanate and sulfamoyl
chloride. In combination with amides, a wide and diverse set of N-acyl sulfamates was synthesized, including functionalized bioactive
compounds. Furthermore, initial results showed that this method is also amenable to access N-thioacyl sulfamates.
Sulfur-based functional groups are encountered in numerous
biologically relevant molecules.1 In particular sulfonamides and
thioesters are virtually essential in our daily therapeutics.2 Re-
cently, sulfamates have gained more attention by the scientific
community as this functional group has bioactive properties.3-5
Despite the presence of N-acyl sulfamates in biologically rel-
evant molecules, only limited synthetic methodologies for their
synthesis exist (Scheme 1). Current strategies rely on the use of
chlorosulfonyl isocyanate or its unstable derivative, sulfamoyl
chloride. Syntheses involve highly exothermic reaction proce-
dures that release stoichiometric amounts of carbon monoxide
and carbon dioxide.13-16 Both agents are classified as reactive,
toxic and hence require storage at low temperatures. In addition,
the established pathways are susceptible to extensive purifica-
tions and variable yields.
Scheme 1. Strategies for the synthesis of N-acyl sulfamates.
Figure 1. Sulfamate-containing bioactive molecules.
In particular the N-acylated sulfamate analogs exhibit inter-
esting biological activities with Avasimibe and Ascamycin as
two archetypal examples (Figure 1). The former is an Acyl-co-
enzyme A:Cholesterol Acyl Transferase (ACAT) inhibitor that
reached clinical phase III as an anti-hyperlipidemic and anti-
atherosclerotic agent. The latter, Ascamycin, is a natural nucle-
otide antibiotic produced by Strepromyces sp. and is identified
as a potent inhibitor of aminoacyl-tRNA synthetases (aaRSs).6,7
Moreover, the N-acyl sulfamate moiety serves as a good bio-
isoster for the labile acylphosphate functional group.8-10 N-acyl
sulfamates are not only endowed with therapeutic applications,
e.g. Acesulfam-K is a well known artificial sweetener and is
widely used in the food industry.11 Other applications of the
N-acyl sulfamate functionality can be found in ruthenium catal-
ysis as it acts as an oxidizing directing group.12
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Here, we propose an alternative and straightforward strategy
Scheme 2. Synthesis of N-acyl sulfamates from fluorosul-
fates and amides using sodium hydride as base.a, b
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starting from fluorosulfates as the sulfate core. This newly
emerging class of electrophiles are excellent substrates for var-
ious transformations including Sharpless’ click sulfur(VI) fluo-
ride exchange (SuFEx) chemistry17-19 and cross-coupling reac-
tions.20-24
5
For a long time, fluorosulfates have been rather hard to syn-
thesize given the requirement of using lecture bottles of pres-
surized SO2F2 or inefficient protocols. Recently, these problems
have been overcome by the development of general fluorosul-
fation procedures either by using an ex situ SO2F2 precursor in
a two-chamber reactor25 or in situ surrogates.26,27 With this
methodology at hand we now report on the synthesis of N-acyl
sulfamates starting from aryl fluorosulfates and amides.
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We hypothesized that aryl fluorosulfates are able to react
with weak nucleophiles, amides in particular, under strong
basic conditions. After a thorough optimization study, the de-
sired N-acyl sulfamate 3a could be isolated in 85% yield (Table
1). The optimized reaction conditions consist of reacting
fluorosulfate 1a (1.0 equiv) and acetamide (1.2 equiv) in the
presence of sodium hydride (2.3 equiv) in THF at room temper-
ature for two hours (entry 1). Performing the reaction with less
equivalents of sodium hydride (1.5 instead of 2.3 equiv) dimin-
ished the yield to 64% (entry 2). This observation was expected
as formation of the N-acyl sulfamate generates a second acidic
proton that consumes the remaining unreacted base. On the
other hand, increasing the amount of sodium hydride had no
deterring effect on the reaction (entry 3). The reaction also
works using a higher boiling, aprotic solvent such as dioxane
(entry 4). Next, the applicability of organobases was examined.
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), which is widely
used in SuFEx chemistry as a catalytic base, was not able to
successfully couple the fluorosulfate with the amide as only
trace amounts of the product were observed (entry 6). The more
basic 1,5,7-triazabicyclo[4.4.0]dec-5-ene did furnish the de-
sired product, although in only 17% yield (entry 7). Potassium
tert-butoxide solidified the reaction mixture and hence was not
suitable for this reaction (entry 8). Unfortunately, NaNH2
yielded only 24% of the product (entry 9).
Table 1. Optimization of the reaction conditions
aReaction conditions: 1.0 mmol of 1, 1.2 mmol of amide 2, 2.3
b
mmol NaH, 2 mL THF (dry) under argon atmosphere. Isolated
yield. c0.5 mmol instead of 1.0 mmol fluorosulfate. dReaction was
stirred for 24 hours.
Deviation from standard condi-
tions
entry
Yielda (%)
Other bases such as sodium bis(trimethylsilyl)amide
(NaHMDS) and lithium bis(trimethylsilyl)amide (LiHMDS)
were evaluated as well but resulted in very complex reaction
mixtures with poor yields (results not shown). It is clear that the
use of sodium hydride is mandatory to convert the fluorosulfate
smoothly into the N-acyl sulfamate. Noteworthy is the ease of
purification of this reaction; extraction with 10% NaHCO3 and
subsequent acidification using 4 M HCl provided the desired
product in high purity. Throughout the optimization study, one
main side product was regularly observed and identified as the
phenol of the corresponding fluorosulfate. It is hypothesized
that traces of water might be able to hydrolyze either the
fluorosulfate or the N-acyl sulfamate during the progress of the
reaction.
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none
97 (85)b
64
1.5 equiv NaH
3.0 equiv NaH
30 min reaction time
Dioxane instead of THF
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87
2.3 equiv DBU instead of NaH, 24 h Traces
2.3 equiv TBD instead of NaH
2.3 equiv t-BuOK instead of NaH
2.3 equiv NaNH2 instead of NaH
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c
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aYield determined by 1H NMR using 1,3,5-trimethoxybenzene as
c
an internal standard. bIsolated yield. The reaction mixture instan-
taneously solidified upon addition of the solvent.
Next, the scope and functional group tolerance of the reaction
were investigated (Scheme 2). First, several mono-substituted
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fluorosulfates (including halide, ester and nitrile substituents)
were coupled and isolated in moderate to very good yields (3b-
1
3j). Gratifyingly, both the ester and nitrile group were tolerated
under the optimized reaction conditions (3c and 3g).
Additionally, ortho-substituents did not dramatically hamper
the reaction as seen with compounds 3i and 3j. Moreover, the
structure of 3j was confirmed via X-ray analysis. Bicyclic
compounds 3k and 3l were obtained successfully from their
corresponding fluorosulfates. The fluorosulfonyl analog of
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indole
(-NSO2F)
produced
the
corresponding
sulfonylacetamide in comparable yield (3m) suggesting similar
reactivity compared to fluorosulfates (-OSO2F). Substrates
containing two fluorosulfate groups formed the bifunctional N-
acylderivatives in fair yields (3n-3o). Next, it was investigated
whether naturally occurring phenols could be derivatized with
the N-acetyl sulfamate group. First, eugenol and D-α-
tocopherol were fluorosulfated in excellent yields (see SI) and
subsequently converted into the N-acyl sulfamate derivative (3p
and 3q). Interestingly, the developed procedure was amenable
to the synthesis of the N-acetylated sulfamate analog of estrone
(3r), a known bioactive compound that has been subject to
biological studies on the mechanism of irreversible estrone
sulphatase inhibitors.28
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Figure 2. Experimental plot of the decomposition of 3a in a pH 13
aqueous solution at 20 and 70 °C.
Gratifyingly, reaction of the fluorosulfated analog of sesamol
with thioacetamide yielded the desired compound (5); the struc-
ture was confirmed via X-ray analysis (Scheme 3a). To the best
of our knowledge, this is the first method to synthesize acyclic
N-thioacyl sulfamates.
Next, we were interested if secondary amides performed
equally well in the above outlined reaction. Unfortunately,
when reacting N-methyl benzamide with fluorosulfate 2a, the
N-substituted N-acyl sulfamate 6 was not formed (Scheme 3b).
Instead, the symmetric imide 7 derived from benzamide was
isolated. We hypothesize that the N-substituted N-acyl sulfa-
mate is formed in situ but instantaneously reacts with a second
equivalent of benzamide under the basic conditions. These find-
ings were not observed for the free N-acyl sulfamate; here the
remainder of the base directly deprotonates the newly created
acidic proton thus decreasing its reactivity towards an attack on
the carbonyl functionality.
We also briefly investigated the scope of various amides as
coupling partners. Both butyramide as well as methylacryla-
mide provided 3s and 3t in good yields. In addition, Boc-pro-
linamide was successfully converted into 3u. Benzamide
proved to be less reactive than alkylamides; after 24 hours of
reaction, 3v was isolated in 79% yield. When evaluating para-
substituted benzamides, however, the products 3w-3y were fur-
nished in significantly lower yield. We speculate that this can
be explained by the poor solubility of these benzamides. Fortu-
nately, performing the reaction at elevated temperatures (50 °C)
improved the yield significantly.
Lastly, we investigated whether the reaction could occur in-
tramolecularly and if we could hence cyclize ortho-amidesub-
stituted fluorosulfates, forming a 6-membered ring. Such cycli-
zations are interesting in e.g. late-stage functionalization of ac-
tive pharmaceutical ingredients (API’s). Niclosamide, an an-
thelmintic agent, was chosen as substrate. To our surprise, the
intramolecular cyclization already occurred during the
fluorosulfation reaction; compound 9 was furnished in 64%
yield by reacting Niclosamide 8 with SO2F2 under basic condi-
tions (Scheme 3c). A similar observation was reported earlier
by Hedayatullah.30
A few additional experiments were performed to further in-
vestigate the scope and limitations of the developed procedure.
Since thioamides are well-known isosters of amides, we won-
dered if they could be used in this transformation.29
Scheme 3. Additional experimentsa
The stability of the N-acyl sulfamate functionality towards
hydrolytic cleavage was assessed in basic medium. Compound
3a was dissolved in an aqueous solution at pH 13 and stored at
both 20 and 70 °C (Figure 2). The sample stored at 20 °C
showed slow degradation towards the corresponding phenol
with 88% of the N-acyl sulfamate still intact after an incubation
time of 200 hours (or approximately 8 days). In contrast, at
higher temperatures, 3a is more prone towards degradation: al-
ready 50% of the starting material is hydrolyzed after 24 hours.
After 200 hours, no remaining N-acyl sulfamate was detected
in the sample. The acidic stability had been assessed in earlier
work and N-acyl sulfamates showed higher lability under those
conditions with half-life values in the range of 0.6-1.5 hours at
70 °C.31
aIsolated yield. bReaction conditions: 1.0 mmol of 1l, 1.2 mmol of
thioamide 4, 2.3 mmol NaH, 2 mL THF (dry) under argon atmos-
phere. c1.3 mmol NaH was used. dThe reaction was conducted in a
two-chamber reactor, see Experimental Section for details.
In summary, we describe a novel route towards biologically
interesting N-acyl sulfamates. After a detailed optimization
study, it was found that sodium hydride exhibits a privileged
performance for the direct coupling of aryl fluorosulfates with
amides to afford N-acyl sulfamates. Interestingly, the developed
method relies on fluorosulfates, a newly emerging class of elec-
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trophiles and thereby omits the use of chlorosulfonyl isocya- mL, 10.0 mmol, 2.0 eq.) and dichloromethane (DCM, 4 mL).
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nate. Various fluorosulfates were prepared, including several
analogs of bioactive molecules, and subsequently coupled with
a variety of amides. Moreover, initial results suggest that this
method can be extended towards the synthesis of unpreceded
acyclic N-thioacyl sulfamates.
Finally, 15 mL of a trifluoroacetic acid (TFA)/water mixture
(1/1, v/v) was added by injection through the septum in cham-
ber A and instant gas formation was observed. After 18 hours
stirring at room temperature, one of the caps was carefully re-
moved to release the residual pressure. As sulfuryl fluoride is a
toxic gas, the reaction was stirred for another 15 minutes to en-
sure that all sulfuryl fluoride was extracted out of the fume
hood. Next, the content of chamber B was transferred to a 100
mL round-bottomed flask. Chamber B was rinsed five times
with 10 mL of dichloromethane and these fractions were added
to the same flask. After the addition of Celite®545, the solvent
was removed under reduced pressure. The crude product was
dry-loaded on a silica gel column for purification.
EXPERIMENTAL SECTION
General Experimental Information. All reagents were ob-
tained from commercially available sources and were used as
purchased without further purification. 1,1’-Sulfonyldiimidaz-
ole (SDI) was in house prepared using the procedure described
by Veryser et al.25 Chromatography solvents were distilled
prior to use. All moisture-sensitive reactions were carried out
under nitrogen atmosphere and in flame-dried glassware. Reac-
tions were magnetically stirred and monitored by using Ma-
cherey-Nagel SIL G-25 UV254 0.25 mm UV254 pre-coated sil-
ica gel glass-supported TLC plates. Compounds were visual-
ized by UV irradiation (254 nm). Column chromatography was
performed using either a MPLC apparatus or via standard col-
umn chromatography. Silica gel for MPLC: ACROS Silica gel,
for column chromatography, ultra pure, 40-60 µm, average pore
diameter of 60 Å. Silica gel for standard column chromatog-
raphy: ACROS Silica gel, for column chromatography, 60-200
µm, average pore diameter of 60 Å. The MPLC device is a Bu-
chi SepacoreTM flash apparatus, consisting of a C-660 Buchi
fraction collector, C-615 Pump manager, C-635 UV-
photometer, two C-605 pump modules and a Linseis D120S
plotter. Solvents were evaporated with a rotavapor at a temper-
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General procedure B for the synthesis of fluorosulfates.
Identical to general procedure A, except that N,N-diisopro-
pylethylamine (DIPEA, 2.67 mL, 15.0 mmol, 3.0 eq.) was used
as base in chamber A and acetonitrile (MeCN, 10 mL) as sol-
vent in chamber B.
3,5-dimethylphenyl sulfurofluoridate (1a): General proce-
dure A was followed using 611 mg of 3,5-dimethylphenol
(99 wt%, 5 mmol, 1 equiv). The crude reaction mixture was pu-
rified by column chromatography on silica gel (mixture of pe-
troleumether/diethylether 98/2 as the eluent). The title com-
1
pound was obtained as a white solid (930 mg, 91%). H NMR
(400 MHz, CDCl3) δ 7.03 (s, 1H), 6.94 (s, 2H), 2.36 (s, 6H);
19F{1H, 13C} NMR (377 MHz, CDCl3) δ 37.52; 13C{1H} NMR
(101 MHz, CDCl3) δ 150.1, 140.6, 130.2, 118.2, 21.2; FT-IR
(neat, cm-1): 3080, 2929, 1618, 1588, 1437, 1222; CHN Anal.
Calcd for C8H9FO3S: C, 47.05; H, 4.44; N, 0.00. Found: C,
46.73; H, 4.42; N, 0.00. Melting point: 43-46 °C
1
ature of 50 °C. H NMR spectra were recorded on Bruker
Avance 400 (400 MHz) and Bruker Avance II+ 600 (600 MHz)
spectrometers. Samples were dissolved in CDCl3 (7.26 ppm,
singlet) or DMSO-d6 (2.50 ppm, quintet) and tetramethylsilane
was used as an internal standard. 13C-NMR spectra were rec-
orded on Bruker Avance 400 (working at 101 MHz) and Bruker
Avance II+ 600 (working at 151 MHz) spectrometers. The deu-
terated solvents were used as internal standard (CDCl3: 77.16
ppm, triplet; DMSO-d6: 39.52 ppm, quintet). 19F NMR spectra
were recorded on Bruker Avance 400 (working at 376 MHz)
and Bruker Avance II+ 600 (working at 565 MHz) spectrome-
ters. Samples were dissolved in CDCl3 or DMSO-d6. All δ-val-
ues are expressed in ppm. HR-MS spectra were acquired on a
quadrupole orthogonal acceleration time-of-flight mass spec-
trometer (Synapt G2 HDMS, Waters, Milford, MA). Samples
were dissolved in a mixtrue of 1:1 (v/v) acetonitrile:water and
infused at 3uL/min. Spectra were obtained in negative ioniza-
tion mode with a resolution of 15000 (FWHM) using leucine
enkephalin as lock mass. Infrared spectra were recorded on a
Bruker Alpha-T FT-IR spectrometer with universal sampling
module and data was processed using the Opus software. Melt-
ing/decomposition points were determined on a Mettler-Toledo
DSC1 instrument, using a heating rate of 15ꢀ°Cꢀmin−1 under he-
lium atmosphere. CHN (carbon, hydrogen, nitrogen) elemental
analyses were obtained with the aid of a Thermo Scientific In-
terscience Flash 2000 Elemental analyser. Crystal structures for
3j and 5 (CCDC 1868893 and 1868894) were determined on an
Agilent SuperNova diffractometer (single source at offset, Eos
detector).
3-(trifluoromethyl)phenyl sulfurofluoridate (1b): General
procedure A was followed using 827 mg of 3-(trifluorome-
thyl)phenol (98 wt%, 5 mmol, 1 equiv). The crude reaction mix-
ture was purified by column chromatography on silica gel (mix-
ture of petroleumether/diethylether 98/2 as the eluent). The title
1
compound was obtained as a colorless oil (1010 mg, 83%). H
NMR (400 MHz, CDCl3) δ 7.74 – 7.68 (m, 1H), 7.67 – 7.60 (m,
2H), 7.58 – 7.54 (m, 1H); 19F{1H, 13C} NMR (377 MHz, CDCl3)
δ 38.13, -63.10; 13C{1H} NMR (151 MHz, CDCl3) δ 149.8 (s),
133.2 (q, J = 33.8 Hz), 131.3 (s), 125.6 (q, J = 3.6 Hz), 124.5
(s), 123.2 (q, J = 272.7 Hz), 118.4 (q, J = 3.6 Hz); FT-IR (neat,
cm-1): 3105, 2979, 2918, 1685, 1324, 1127; CHN Anal. Calcd
for C7H4F4O3S: C, 34.44; H, 1.65; N, 0.00. Found: C, 34.24; H,
1.88; N, 0.00.
ethyl 4-((fluorosulfonyl)oxy)benzoate (1c): General proce-
dure A was followed using 839 mg of ethyl 4-hydroxybenzoate
(99 wt%, 5 mmol, 1 equiv). The crude reaction mixture was pu-
rified by column chromatography on silica gel (mixture of pe-
troleumether/diethylether 98/2 as the eluent). The title com-
pound was obtained as a colorless oil (1199 mg, 97%). 1H NMR
(400 MHz, CDCl3) δ 8.25 – 8.05 (m, 2H), 7.46 – 7.35 (m, 2H),
4.40 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); 19F{1H, 13C}
NMR (377 MHz, CDCl3) δ 38.66; 13C{1H} NMR (101 MHz,
CDCl3) δ 164.9, 152.8, 132.0, 131.0, 120.9, 61.6, 14.3. These
data are in agreement with literature data.24
4-methoxyphenyl sulfurofluoridate (1d): General procedure
A was followed using 627 mg of 4-methoxyphenol (99 wt%, 5
mmol, 1 equiv). The crude reaction mixture was purified by col-
umn chromatography on silica gel (mixture of petroleume-
ther/diethylether 98/2 as the eluent). The title compound was
obtained as a colorless oil (989 mg, 96%). 1H NMR (400 MHz,
CDCl3) δ 7.31 – 7.19 (m, 2H), 6.98 – 6.88 (m, 2H), 3.82 (s, 3H);
General procedure A for the synthesis of fluorosulfates.
Chamber A of a flame-dried medium-sized two-chamber reac-
tor (Figure S1) was filled with 1,1’-sulfonyldiimidazole (SDI,
1.487 g, 7.5 mmol, 1.5 eq.) and potassium fluoride (KF, 1.162
g, 20.0 mmol, 4.0 equiv). Next, chamber B was charged with
the appropriate aryl alcohol (5.0 mmol), triethylamine (1.394
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19F{1H, 13C} NMR (377 MHz, CDCl3) δ 36.37; 13C{1H} NMR
7.25 (m, 1H); 19F{1H, 13C} NMR (377 MHz, CDCl3) δ 41.45;
13C{1H} NMR (101 MHz, CDCl3) δ 147.3, 134.6, 129.9, 129.2,
1
2
(101 MHz, CDCl3) δ 159.3, 143.6, 122.0, 115.2, 55.8. These
data are in agreement with literature data.24
122.6, 115.5. These data are in agreement with literature data.25
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5
6
7
8
9
3-iodophenyl sulfurofluoridate (1e): General procedure A
was followed using 1111 mg of 3-iodophenol (99 wt%, 5 mmol,
1 equiv). The crude reaction mixture was purified by column
chromatography on silica gel (mixture of petroleumether/dieth-
ylether 98/2 as the eluent). The title compound was obtained as
a colorless oil (1461 mg, 97%). 1H NMR (400 MHz, CDCl3) δ
7.76 (d, J = 7.9 Hz, 1H), 7.70 (s, 1H), 7.34 (dd, J = 8.4, 1.5 Hz,
1H), 7.21 (t, J = 8.1 Hz, 1H); 19F{1H, 13C} NMR (377 MHz,
CDCl3) δ 38.29; 13C{1H} NMR (101 MHz, CDCl3) δ 149.7,
137.9, 131.6, 130.0, 120.4, 93.9. These data are in agreement
with literature data.32
naphthalen-2-yl sulfurofluoridate (1k): General procedure A
was followed using 728 mg of naphthalen-2-ol (99 wt%, 5
mmol, 1 equiv). The crude reaction mixture was purified by col-
umn chromatography on silica gel (mixture of petroleume-
ther/diethylether 98/2 as the eluent). The title compound was
obtained as a white solid (1075 mg, 95%). 1H NMR (400 MHz,
CDCl3) δ 7.91 – 7.73 (m, 4H), 7.58 – 7.47 (m, 2H), 7.38 (dd, J
= 9.0, 2.0 Hz, 1H); 19F{1H, 13C} NMR (377 MHz, CDCl3) δ
37.80; 13C{1H} NMR (101 MHz, CDCl3) δ 147.6, 133.3, 132.5,
130.8, 128.1, 128.0, 127.6, 127.3, 119.0, 118.8. These data are
in agreement with literature data.18
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4-(methylsulfonyl)phenyl sulfurofluoridate (1f): General pro-
cedure A was followed using 888 mg of 4-(methylsulfonyl)phe-
nol (97 wt%, 5 mmol, 1 equiv). The crude reaction mixture was
purified by column chromatography on silica gel (mixture of
petroleumether/diethylether 5/5 as the eluent). The title com-
pound was obtained as white crystals (1177 mg, 93%). 1H NMR
(400 MHz, CDCl3) δ 8.11 (d, J = 8.5 Hz, 2H), 7.58 (d, J = 8.3
Hz, 2H), 3.10 (s, 3H); 19F{1H, 13C} NMR (377 MHz, CDCl3) δ
39.38; 13C{1H} NMR (101 MHz, CDCl3) δ 153.0, 141.1, 130.3,
122.2, 44.5. These data are in agreement with literature data.24
benzo[d][1,3]dioxol-5-yl sulfurofluoridate (1l): General pro-
cedure A was followed using 705 mg of benzo[d][1,3]dioxol-5-
ol (98 wt%, 5 mmol, 1 equiv). The crude reaction mixture was
purified by column chromatography on silica gel (mixture of
petroleumether/diethylether 98/2 as the eluent). The title com-
pound was obtained as a colorless oil (1078 mg, 98%). 1H NMR
(400 MHz, CDCl3) δ 6.82 (s, 1H), 6.06 (s, 1H); 19F{1H, 13C}
NMR (377 MHz, CDCl3) δ 36.58; 13C{1H} NMR (101 MHz,
CDCl3) δ 148.6, 147.7, 144.1, 114.0, 108.3, 103.0, 102.5. These
data are in agreement with literature data.18
4-cyanophenyl sulfurofluoridate (1g): General procedure A
was followed using 614 mg of 3-hydroxybenzonitrile (97 wt%,
5 mmol, 1 equiv). The crude reaction mixture was purified by
column chromatography on silica gel (mixture of petroleume-
ther/diethylether 98/2 as the eluent). The title compound was
obtained as a colorless oil (980 mg, 97%). 1H NMR (400 MHz,
CDCl3) δ 7.81 – 7.71 (m, 1H), 7.69 – 7.51 (m, 3H); 19F{1H, 13C}
NMR (377 MHz, CDCl3) δ 38.86; 13C{1H} NMR (101 MHz,
CDCl3) δ 149.6, 132.5, 131.6, 125.8, 124.8, 116.6, 114.8. These
data are in agreement with literature data.32
1H-indole-1-sulfonyl fluoride (1m): General procedure A
was followed using 592 mg of 1H-indole (99 wt%, 5 mmol, 1
equiv). The crude reaction mixture was purified by column
chromatography on silica gel (mixture of petroleumether/dieth-
ylether 98/2 as the eluent). The title compound was obtained as
1
a colorless oil (366 mg, 37%). H NMR (400 MHz, CDCl3) δ
7.91 (d, J = 8.3 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.52 – 7.31
(m, 3H), 6.81 (d, J = 3.7 Hz, 1H); 19F{1H, 13C} NMR (377 MHz,
CDCl3) δ 54.31; 13C{1H} NMR (101 MHz, CDCl3) δ 134.8,
130.3, 126.1, 125.8, 124.8, 121.9, 113.5, 111.0; FT-IR (neat,
cm-1): 3154, 3127, 3060, 2979, 1440, 1262, 1222; CHN Anal.
Calcd for C8H6FNO2S: C, 48.24; H, 3.04; N, 7.03. Found: C,
47.89; H, 3.10; N, 7.24.
4-bromophenyl sulfurofluoridate (1h): General procedure A
was followed using 874 mg of 4-bromophenol (99 wt%, 5
mmol, 1 equiv). The crude reaction mixture was purified by col-
umn chromatography on silica gel (mixture of petroleume-
ther/diethylether 98/2 as the eluent). The title compound was
obtained as a colorless oil (1213 mg, 95%). 1H NMR (400 MHz,
CDCl3) δ 7.65 – 7.56 (m, 2H), 7.29 – 7.19 (m, 2H); 19F{1H, 13C}
NMR (377 MHz, CDCl3) δ 37.80; 13C{1H} NMR (101 MHz,
CDCl3) δ 148.9, 133.6, 122.7, 122.4. These data are in agree-
ment with literature data.33
propane-2,2-diylbis(4,1-phenylene) bis(sulfurofluoridate)
(1n): General procedure A was followed using 588 mg of 4,4'-
(propane-2,2-diyl)diphenol (97 wt%, 2.5 mmol, 1 equiv). The
crude reaction mixture was purified by column chromatography
on silica gel (mixture of petroleumether/diethylether 95/5 as the
eluent). The title compound was obtained as a white solid (898
mg, 92%). 1H NMR (400 MHz, CDCl3) δ 7.36 – 7.19 (m, 8H),
1.70 (s, 6H); 19F{1H, 13C} NMR (377 MHz, CDCl3) δ 37.52;
13C{1H} NMR (101 MHz, CDCl3) δ 150.4, 148.2, 128.7, 120.6,
42.9, 30.8. These data are in agreement with literature data.18
2,6-dimethylphenyl sulfurofluoridate (1i): General procedure
A was followed using 617 mg of 2,6-dimethylphenyl sulfuro-
fluoridate (99 wt%, 5 mmol, 1 equiv). The crude reaction mix-
ture was purified by column chromatography on silica gel (mix-
ture of petroleumether/diethylether 98/2 as the eluent). The title
(3-oxo-1,3-dihydroisobenzofuran-1,1-diyl)bis(4,1-phe-
nylene) bis(sulfurofluoridate)(1o): General procedure A was
followed using 804 mg of (3-oxo-1,3-dihydroisobenzofuran-
1,1-diyl)bis(4,1-phenylene) bis(sulfurofluoridate) (99 wt%, 2.5
mmol, 1 equiv). The crude reaction mixture was purified by col-
umn chromatography on silica gel (mixture of petroleume-
ther/diethylether 5/5 as the eluent). The title compound was ob-
1
compound was obtained as a colorless oil (718 mg, 70%). H
NMR (400 MHz, CDCl3) δ 7.18 – 7.05 (m, 3H), 2.37 (s, 6H);
19F{1H, 13C} NMR (377 MHz, CDCl3) δ 43.27; 13C{1H} NMR
(101 MHz, CDCl3) δ 148.8, 131.0, 129.9, 128.2, 16.5; FT-IR
(neat, cm-1): 3050, 2969, 2937, 1439, 1267; CHN Anal. Calcd
for C8H9FO3S: C, 47.05; H, 4.44; N, 0.00. Found C, 47.05; H,
4.48; N, 0.00.
1
tained as a white solid (1052 mg, 87%). H NMR (400 MHz,
CDCl3) δ 8.00 (d, J = 7.6 Hz, 1H), 7.79 (t, J = 7.5 Hz, 1H), 7.65
(t, J = 7.5 Hz, 1H), 7.58 (d, J = 7.7 Hz, 1H), 7.47 (d, J = 8.8
Hz, 4H), 7.36 (d, J = 8.7 Hz, 4H); 19F{1H, 13C} NMR (377
MHz, CDCl3) δ 38.23; 13C{1H} NMR (101 MHz, CDCl3) δ
168.6, 150.3, 150.0, 141.0, 134.9, 130.3, 129.2, 126.7, 125.3,
123.9, 121.4, 89.6. These data are in agreement with literature
data.18
2-bromophenyl sulfurofluoridate (1j): General procedure A
was followed using 883 mg of 2-bromophenol (98 wt%, 5
mmol, 1 equiv). The crude reaction mixture was purified by col-
umn chromatography on silica gel (mixture of petroleume-
ther/diethylether 98/2 as the eluent). The title compound was
obtained as a colorless oil (1094 mg, 86%). 1H NMR (400 MHz,
CDCl3) δ 7.70 (d, J = 7.9 Hz, 1H), 7.47 – 7.40 (m, 2H), 7.32 –
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4-allyl-2-methoxyphenyl sulfurofluoridate (1p): General pro- cycles using a Schlenk line. Next, the fluorosulfate was dis-
1
2
3
4
5
6
7
8
cedure A was followed using 829 mg of 4-allyl-2-methoxyphe-
nol (99 wt%, 5 mmol, 1 equiv). The crude reaction mixture was
purified by column chromatography on silica gel (mixture of
petroleumether/diethylether 98/2 as the eluent). The title com-
pound was obtained as a colorless oil (1110 mg, 90%). 1H NMR
(400 MHz, CDCl3) δ 7.20 (d, J = 8.3 Hz, 1H), 6.86 (d, J = 1.5
Hz, 1H), 6.79 (dd, J = 8.3, 1.7 Hz, 1H), 6.03 – 5.82 (m, 1H),
5.21 – 5.01 (m, 2H), 3.87 (s, 3H), 3.38 (d, J = 6.7 Hz, 2H);
19F{1H, 13C} NMR (377 MHz, CDCl3) δ 39.32; 13C{1H} NMR
(101 MHz, CDCl3) δ 151.0, 142.4, 137.4, 136.3, 122.1, 120.9,
116.9, 113.7, 56.1, 40.1. These data are in agreement with liter-
ature data.18
solved in 2 mL THF (via two portions of 1 mL) and added to
the reaction tube (as described above) containing only the am-
ide and sodium hydride. Remark 2: In some cases, the
fluorosulfate could not be extracted into the aqueous layer. In
these cases, the reaction mixture was transferred into a separa-
tion funnel and diluted with DCM (the reaction tube was rinsed
3x). 4 M HCl was added and the aqueous layer was extracted 3
times with DCM. The combined DCM fractions were dried on
sodium sulfate and Celite® was added to the mixture prior to
evaporation. The solid was dry-loaded onto the medium-pres-
sure liquid chromatography system and eluted with the desig-
nated solvent system. Remark 3: Take care while adding the
solvent as H2 is produced. It is advised to capture the overpres-
sure using a balloon.
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(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-
tridecyl)chroman-6-yl sulfurofluoridate (1q): General proce-
dure A was followed using 2220 mg of (R)-2,5,7,8-tetramethyl-
2-((4R,8R)-4,8,12-trimethyltridecyl)chroman-6-ol (97 wt%, 5
mmol, 1 equiv). The crude reaction mixture was purified by col-
umn chromatography on silica gel (mixture of petroleume-
ther/diethylether 98/2 as the eluent). The title compound was
obtained as a colorless oil (2501 mg, 98%). 1H NMR (400 MHz,
CDCl3) δ 2.60 (t, J = 6.8 Hz, 2H), 2.23 (s, 3H), 2.20 (s, 3H),
2.10 (s, 3H), 1.89 – 1.72 (m, 2H), 1.60 – 1.00 (m, 24H), 0.90 –
0.80 (m, 12H); 19F{1H, 13C} NMR (377 MHz, CDCl3) δ 41.37;
13C{1H} NMR (101 MHz, CDCl3) δ 151.0, 141.9, 127.5, 126.1,
124.4, 118.4, 75.7, 39.9, 39.4, 37.5, 37.4, 37.3, 32.8, 32.7, 30.8,
28.0, 24.8, 24.4, 23.9, 22.7, 22.6, 21.0, 20.6, 19.8, 19.7, 13.5,
12.7, 11.9. These data are in agreement with literature data.18
3,5-dimethylphenyl acetylsulfamate (3a): General procedure
C was followed using 204 mg of 3,5-dimethylphenyl sulfuro-
fluoridate (1 mmol, 1 equiv). The title compound was obtained
as a white solid (207 mg, 85%). 1H NMR (400 MHz, CDCl3) δ
8.59 (bs, 1H), 6.96 (s, 1H), 6.86 (s, 2H), 2.31 (s, 6H), 2.20 (s,
3H); 13C{1H} NMR (101 MHz, CDCl3) δ 168.8, 149.6, 140.2,
129.6, 119.1, 23.0, 21.2; FT-IR (neat, cm-1): 3191, 3148, 2921,
2853, 1713, 1466; HR-MS (ESI) m/z: calculated for
C10H12NO4S- 242.0492 [M-H]-, found 242.0474; Decomposi-
tion: 95 °C.
3-(trifluoromethyl)phenyl acetylsulfamate (3b): General pro-
cedure C was followed using 244 mg of 3-(trifluoromethyl)phe-
nyl sulfurofluoridate (1 mmol, 1 equiv). The title compound
1
(8R,9S,13S,14S)-13-methyl-17-oxo-
was obtained as a white solid (170 mg, 60%). H NMR (400
7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phe-
nanthren-3-yl sulfurofluoridate (1r): General procedure B was
followed using 1366 mg of (8R,9S,13S,14S)-3-hydroxy-13-me-
thyl-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclo-
penta[a]phenanthren-17-one (99 wt%, 5 mmol, 1 equiv). The
crude reaction mixture was purified by column chromatography
on silica gel (mixture of petroleumether/diethylether 5/5 as the
eluent). The title compound was obtained as a white solid (1255
MHz, CDCl3) δ 7.99 (bs, 1H), 7.67 – 7.48 (m, 4H), 2.26 (s, 3H);
19F{1H, 13C} NMR (377 MHz, CDCl3) δ -62.77; 13C{1H} NMR
(101 MHz, CDCl3) δ 167.6 (s), 149.6 (s), 132.8 (q, J = 33.5 Hz),
130.9 (s), 125.5 (s), 124.8 (q, J = 3.7 Hz), 123.0 (q, J = 272.7),
119.2 (q, J = 3.8 Hz), 23.2 (s); FT-IR (neat, cm-1): 3144, 2914,
2839, 1709, 1461; HR-MS (ESI) m/z: calculated for
C9H7F3NO4S- 282.0053 [M-H]-, found 282.0038; Decomposi-
tion: 135 °C.
1
mg, 71%). H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.6 Hz,
ethyl 4-((N-acetylsulfamoyl)oxy)benzoate (3c): General pro-
cedure C was followed using 248 mg of ethyl 4-((fluorosul-
fonyl)oxy)benzoate (1 mmol, 1 equiv). The title compound was
1H), 7.14 – 7.03 (m, 2H), 3.02 – 2.88 (m, 2H), 2.52 (dd, J =
18.8, 8.6 Hz, 1H), 2.45 – 2.25 (m, 2H), 2.23 – 1.92 (m, 4H),
1.72 – 1.40 (m, 6H), 0.92 (s, 3H); 19F{1H, 13C} NMR (377 MHz,
CDCl3) δ 37.42; 13C{1H} NMR (101 MHz, CDCl3) δ 220.5,
148.3, 140.7, 139.6, 127.5, 120.8, 118.0, 50.5, 48.0, 44.2, 37.9,
35.9, 31.6, 29.5, 26.2, 25.8, 21.7, 13.9. These data are in agree-
ment with literature data.20
1
obtained as a white solid (201 mg, 70%). H NMR (400 MHz,
DMSO-d6) δ 8.08 (d, J = 8.7 Hz, 2H), 7.41 (d, J = 8.7 Hz, 2H),
4.33 (q, J = 7.1 Hz, 2H), 2.05 (s, 3H), 1.32 (t, J = 7.1 Hz, 3H);
13C{1H} NMR (101 MHz, DMSO-d6) δ 168.6, 164.7, 152.6,
131.4, 129.1, 122.2, 61.1, 23.3, 14.1; FT-IR (neat, cm-1): 3075,
2990, 2907, 2844, 1711, 1697; HR-MS (ESI) m/z: calculated
for C11H12NO6S- 286.0391 [M-H]-, found 286.0372; Decompo-
sition: 91 °C.
General procedure C for the synthesis of N-acylsulfa-
mates. To a flame-dried reaction tube (15 mL) was added sub-
sequently amide (1.2 equiv, 1.3 mmol), fluorosulfate (1.0 equiv,
1 mmol) and sodium hydride (2.3 equiv, 2.3 mmol). Next, the
tube was capped with a screw cap fitted with septum and
brought under argon atmosphere via three consecutive vacuum-
argon cycles using a Schlenk line. 2 mL of THF was added and
the reaction was stirred at 1000 rpm at room temperature. After
two hours, the reaction was diluted with ethyl acetate and trans-
ferred into a separation funnel. The sulfamate was extracted out
(4x) towards the aqueous layer using a 10% NaHCO3 solution.
The combined aqueous layers were acidified by adding 45 mL
of a 4 M HCl solution in small portions and the sulfamate was
extracted with DCM. The combined organic layers were dried
using sodium sulfate and evaporated in vacuo to afford the title
compound. Remark 1: When the fluorosulfate was a liquid, the
fluorosulfate was weighed in a separate flame-dried reaction
tube capped with a screw cap fitted with septum and brought
under argon atmosphere via three consecutive vacuum-argon
4-methoxyphenyl acetylsulfamate (3d): General procedure C
was followed using 206 mg of 4-methoxyphenyl sulfurofluori-
date (1 mmol, 1 equiv). The title compound was obtained as a
1
white solid (196 mg, 80%). H NMR (400 MHz, DMSO-d6) δ
12.33 (bs, 1H), 7.18 (d, J = 9.0 Hz, 2H), 7.03 (d, J = 9.0 Hz,
2H), 3.77 (s, 3H), 2.04 (s, 3H); 13C{1H} NMR (101 MHz,
DMSO-d6) δ 168.6, 158.2, 142.8, 122.9, 115.0, 55.6, 23.2; FT-
IR (neat, cm-1): 3109, 3014, 2915, 2847, 1710, 1470; HR-MS
(ESI) m/z: calculated for C9H10NO5S- 244.0285 [M-H]-, found
244.0263; Decomposition: 104 °C.
3-iodophenyl acetylsulfamate (3e): General procedure C was
followed using 302 mg of 3-iodophenyl sulfurofluoridate (1
mmol, 1 equiv). The title compound was obtained as a white
1
solid (233 mg, 68%). H NMR (400 MHz, DMSO-d6) δ 12.54
(bs, 1H), 7.79 (d, J = 6.8 Hz, 1H), 7.62 (s, 1H), 7.36 – 7.23 (m,
6
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The Journal of Organic Chemistry
(ESI) m/z: calculated for C12H10NO4S- 264.0336 [M-H]-, found
2H), 2.05 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
1
2
3
4
5
6
7
8
168.6, 149.5, 136.5, 132.0, 130.3, 121.4, 94.8, 23.3; FT-IR
(neat, cm-1): 3239, 2911, 1704, 1459; HR-MS (ESI) m/z: calcu-
lated for C8H7INO4S- 339.9148 [M-H]-, found 339.9135; De-
composition: 133 °C.
264.0319; Decomposition: 142 °C
benzo[d][1,3]dioxol-5-yl acetylsulfamate (3l): General pro-
cedure C was followed using 220 mg of benzo[d][1,3]dioxol-5-
yl sulfurofluoridate (1 mmol, 1 equiv). The title compound was
1
4-(methylsulfonyl)phenyl acetylsulfamate (3f): General pro-
cedure C was followed using 254 mg of 4-(methylsulfonyl)phe-
nyl sulfurofluoridate (1 mmol, 1 equiv). The title compound
obtained as a white solid (213 mg, 82%). H NMR (400 MHz,
DMSO-d6) δ 12.40 (bs, 1H), 6.99 (d, J = 8.5 Hz, 1H), 6.87 (d,
J = 1.9 Hz, 1H), 6.70 (dd, J = 8.4, 1.9 Hz, 1H), 6.10 (s, 2H),
2.04 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 168.6,
147.9, 146.4, 143.5, 114.7, 108.3, 103.7, 102.2, 23.3; FT-IR
(neat, cm-1): 3142, 2850, 1703, 1462; HR-MS (ESI) m/z: calcu-
lated for C9H8NO6S- 258.0078 [M-H]-, found 258.0062; De-
composition: 101 °C
1
was obtained as a white solid (181 mg, 62%). H NMR (400
MHz, DMSO-d6) δ 8.08 (d, J = 8.7 Hz, 2H), 7.54 (d, J = 8.7 Hz,
2H), 3.27 (s, 3H), 2.07 (s, 3H); 13C{1H} NMR (101 MHz,
DMSO-d6) δ 168.8, 152.7, 139.9, 129.6, 123.0, 43.4, 23.4; FT-
IR (neat, cm-1): 3195, 3161, 2922, 1695, 1469; HR-MS (ESI)
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13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
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59
60
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m/z: calculated for C9H10NO6S2 291.9955 [M-H]-, found
N-((1H-indol-1-yl)sulfonyl)acetamide (3m): General proce-
dure C was followed using 199 mg of 1H-indole-1-sulfonyl flu-
oride (1 mmol, 1 equiv). The title compound was obtained as
an off-white solid (158 mg, 67%). 1H NMR (400 MHz, DMSO-
d6) δ 12.93 (bs, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.65 (d, J = 7.8
Hz, 1H), 7.60 (d, J = 3.6 Hz, 1H), 7.32 (dt, J = 33.5, 7.4 Hz,
2H), 6.72 (d, J = 3.5 Hz, 1H), 1.91 (s, 3H); 13C{1H} NMR (101
MHz, DMSO-d6) δ 168.7, 133.6, 130.0, 128.4, 124.1, 123.1,
121.5, 112.7, 106.5, 23.1; FT-IR (neat, cm-1): 3115, 2919, 2854,
1705, 1446; HR-MS (ESI) m/z: calculated for C10H9N2O3S-
237.0339 [M-H]-, found 237.0318. Decomposition: 108 °C
291.9924; Decomposition: 139 °C.
3-cyanophenyl acetylsulfamate (3g): General procedure C
was followed using 201 mg of 3-cyanophenyl sulfurofluoridate
(1 mmol, 1 equiv). The title compound was obtained as a white
solid (172 mg, 72%); 1H NMR (400 MHz, DMSO-d6) δ 7.91 (d,
J = 7.6 Hz, 1H), 7.83 (s, 1H), 7.72 (t, J = 8.0 Hz, 1H), 7.68 –
7.57 (m, 1H), 2.06 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-
d6) δ 168.7, 149.4, 131.7, 131.7, 127.2, 125.6, 117.5, 112.9,
23.4; FT-IR (neat, cm-1): 3136, 2922, 2852, 2230 (C≡N stretch),
1707, 1465; HR-MS (ESI) m/z: calculated for C9H7N2O4S-
239.0132 [M-H]-, found 239.0112; Decomposition: 97 °C.
propane-2,2-diylbis(4,1-phenylene)
bis(acetylsulfamate)
4-bromophenyl acetylsulfamate (3h): General procedure C
was followed using 255 mg of 4-bromophenyl sulfurofluoridate
(1 mmol, 1 equiv). The title compound was obtained as a white
(3n): General procedure C was followed using 196 mg of pro-
pane-2,2-diylbis(4,1-phenylene) bis(sulfurofluoridate) (0.5
mmol, 1 equiv). The title compound was obtained as a white
solid (93 mg, 39%). 1H NMR (400 MHz, DMSO-d6) δ 12.41 (s,
2H), 7.34 (d, J = 8.7 Hz, 4H), 7.18 (d, J = 8.7 Hz, 4H), 2.04 (s,
6H), 1.65 (s, 6H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
168.5, 149.2, 147.4, 128.3, 121.5, 42.2, 30.3, 23.3; FT-IR (neat,
cm-1): 3207, 3162, 2965, 2918, 1709, 1456; HR-MS (ESI) m/z:
1
solid (228 mg, 78%). H NMR (400 MHz, DMSO-d6) δ 12.50
(bs, 1H), 7.71 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 9.0 Hz, 2H), 2.05
(s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 168.6, 148.6,
133.2, 124.1, 120.3, 23.3; FT-IR (neat, cm-1): 3083, 2919, 2851,
1699, 1477; HR-MS (ESI) m/z: calculated for C8H7BrNO4S-
291.9285 [M-H]-, found 291.9268; Decomposition: 140 °C.
-
calculated for C19H21N2O8S2 469.0745 [M-H]-, found
469.0732; Decomposition: 175 °C
2,6-dimethylphenyl acetylsulfamate (3i): General procedure
C was followed using 204 mg of 2,6-dimethylphenyl acetyl-
sulfamate (1 mmol, 1 equiv). The title compound was obtained
(3-oxo-1,3-dihydroisobenzofuran-1,1-diyl)bis(4,1-phe-
nylene) bis(acetylsulfamate) (3o): General procedure C was fol-
lowed using 241 mg of (3-oxo-1,3-dihydroisobenzofuran-1,1-
diyl)bis(4,1-phenylene) bis(sulfurofluoridate) (0.5 mmol, 1
equiv). The title compound was obtained as white solid (116
1
as a white solid (184 mg, 76%). H NMR (400 MHz, DMSO-
d6) δ 12.59 (bs, 1H), 7.15 (s, 3H), 2.29 (s, 6H), 2.09 (s, 3H);
13C{1H} NMR (101 MHz, DMSO-d6) δ 168.5, 147.4, 131.5,
129.3, 127.0, 23.4, 16.6; FT-IR (neat, cm-1): 3166, 2929, 2840,
1714, 1468; HR-MS (ESI) m/z: calculated for C10H12NO4S-
242.0492 [M-H]-, found 242.0466; Decomposition: 100 °C
1
mg, 39%). H NMR (400 MHz, DMSO-d6) δ 12.48 (bs, 2H),
8.03 – 7.89 (m, 3H), 7.73 (t, J = 7.5 Hz, 1H), 7.49 (d, J = 8.7
Hz, 4H), 7.32 (d, J = 8.7 Hz, 4H), 2.03 (s, 6H); 13C{1H} NMR
(101 MHz, DMSO-d6) δ 168.6, 168.3, 150.6, 149.4, 139.7,
135.5, 130.4, 128.6, 125.9, 124.6, 124.1, 122.4, 89.6, 23.3; FT-
IR (neat, cm-1): 3217, 3135, 1776, 1700, 1464; HR-MS (ESI)
2-bromophenyl acetylsulfamate (3j): General procedure C
was followed using 255 mg of 2-bromophenyl sulfurofluoridate
(1 mmol, 1 equiv). The title compound was obtained as a white
m/z: calculated for C24H19N2O10S2 559.0486 [M-H]-, found
-
1
solid (202 mg, 69%). H NMR (400 MHz, CDCl3) δ 8.13 (bs,
559.0488; Decomposition: 169 °C
1H), 7.65 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.2 Hz, 1H), 7.39 (t,
J = 7.8 Hz, 1H), 7.23 (t, J = 7.7 Hz, 1H), 2.34 (s, 3H); 13C{1H}
NMR (151 MHz, CDCl3) δ 168.2, 147.0, 134.2, 129.0, 129.0,
124.1, 115.6, 23.4; FT-IR (neat, cm-1): 3182, 2932, 2850, 1719,
1465; HR-MS (ESI) m/z: calculated for C8H7BrNO4S- 291.9285
[M-H]-, found 291.9267; Decomposition: 138 °C
4-allyl-2-methoxyphenyl acetylsulfamate (3p): General pro-
cedure C was followed using 246 mg of 4-allyl-2-methoxy-
phenyl sulfurofluoridate (1 mmol, 1 equiv). The title compound
1
was obtained as an off-white solid (197 mg, 69%). H NMR
(400 MHz, DMSO-d6) δ 12.25 (bs, 1H), 7.16 (d, J = 8.2 Hz,
1H), 7.03 (s, 1H), 6.82 (d, J = 8.1 Hz, 1H), 5.96 (ddt, J = 16.8,
9.9, 6.8 Hz, 1H), 5.20 – 5.00 (m, 2H), 3.78 (s, 3H), 3.38 (d, J =
6.7 Hz, 2H), 2.07 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-
d6) δ 168.3, 151.3, 140.7, 137.1, 136.2, 123.6, 120.5, 116.3,
113.6, 55.9, 39.2, 23.3; FT-IR (neat, cm-1): 3166, 2976, 1726,
1637, 1461; HR-MS (ESI) m/z: calculated for C12H14NO5S-
284.0598 [M-H]-, found 284.0576; Decomposition: 143 °C
naphthalen-2-yl acetylsulfamate (3k): General procedure C
was followed using 226 mg of naphthalen-2-yl sulfurofluori-
date (1 mmol, 1 equiv). The title compound was obtained as a
1
white solid (219 mg, 83%). H NMR (400 MHz, DMSO-d6) δ
12.45 (bs, 1H), 8.12 – 7.96 (m, 3H), 7.84 (d, J = 1.6 Hz, 1H),
7.65 – 7.55 (m, 2H), 7.40 (dd, J = 8.9, 2.2 Hz, 1H), 2.06 (s, 3H);
13C{1H} NMR (101 MHz, DMSO-d6) δ 168.7, 147.0, 133.1,
131.7, 130.3, 127.9, 127.7, 127.2, 126.7, 120.7, 119.2, 23.3;
FT-IR (neat, cm-1): 3213, 3161, 2921, 1716, 1471; HR-MS
(R)-2,5,7,8-tetramethyl-2-((4R,8R)-4,8,12-trimethyl-
tridecyl)chroman-6-yl acetylsulfamate (3q): General procedure
C was followed using 529 mg of (R)-2,5,7,8-tetramethyl-2-
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((4R,8R)-4,8,12-trimethyltridecyl)chroman-6-yl sulfurofluori- was followed using 204 mg of 3,5-dimethylphenyl sulfurofluor-
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5
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7
8
date (97 wt%, 1 mmol, 1 equiv). Purification was performed
according to remark 2. The resulting solid was dry-loaded onto
the MPLC system and eluted with following gradient: hep-
tane/ethyl acetate 95/5 - heptane/ethyl acetate 5/5. The title
compound was obtained as a pale yellow solid (381 mg, 69%).
1H NMR (400 MHz, DMSO-d6) δ 12.40 (bs, 1H), 2.55 (t, J =
6.4 Hz, 2H), 2.13 (s, 3H), 2.11 (s, 3H), 2.07 (s, 3H), 2.02 (s,
3H), 1.75 (t, J = 6.7 Hz, 2H), 1.54 – 0.98 (m, 24H), 0.88 – 0.78
(m, 12H); 13C{1H} NMR (151 MHz, DMSO-d6) δ 168.45,
149.48, 139.98, 128.20, 127.04, 122.62, 117.99, 75.09, 39.27,
38.77, 36.77, 36.76, 36.68, 36.62, 32.08, 31.94, 30.49, 27.37,
24.16, 23.75, 23.43, 23.37, 22.49, 22.40, 20.30, 19.95, 19.55,
19.47, 13.82, 12.96, 11.58; FT-IR (neat, cm-1): 3087, 2925,
2868, 1701, 1460; HR-MS (ESI) m/z: calculated for
C31H52NO5S- 550.3571 [M-H]-, found 550.3571; Decomposi-
tion: 74 °C
idate (1 mmol, 1 equiv) and 257 mg of tert-butyl (S)-2-car-
bamoylpyrrolidine-1-carboxylate (1.2 mmol, 1.2 equiv). The ti-
tle compound was obtained as a white solid (201 mg, 50%). 1H
NMR (400 MHz, CDCl3) δ 10.99 (bs, 1H), 6.94 (s, 1H), 6.88
(s, 2H), 4.29 (d, J = 6.4 Hz, 1H), 3.33 (s, 2H), 2.57 (s, 1H), 2.31
(s, 6H), 1.93 (s, 3H), 1.39 (s, 9H); 13C{1H} NMR (101 MHz,
CDCl3) δ 168.5, 157.2, 149.9, 139.7, 129.2, 119.2, 82.3, 60.1,
47.3, 28.2, 26.0, 24.5, 21.2; FT-IR (neat, cm-1): 3022, 2984,
2971, 2918, 2883, 2849, 2810, 1743, 1657, 1410; HR-MS (ESI)
m/z: calculated for C18H25N2O6S- 397.1439 [M-H]-, found
397.1426; Decomposition: 96 °C (thermal decomposition of
boc-group) and 173 °C
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3,5-dimethylphenyl benzoylsulfamate (3v): General proce-
dure C was followed using 204 mg of 3,5-dimethylphenyl sul-
furofluoridate (1 mmol, 1 equiv) and 148 mg benzamide (98
wt%, 1.2 mmol, 1.2 equiv). After 24 hours of reaction time, pu-
rification was performed according to remark 2. The resulting
solid was dry-loaded onto the MPLC system and eluted with
following gradient: DCM - DCM/AcOH 98/2. The title com-
(8R,9S,13S,14S)-13-methyl-17-oxo-
7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phe-
nanthren-3-yl acetylsulfamate (3r): General procedure C was
followed using 352 mg of (8R,9S,13S,14S)-13-methyl-17-oxo-
7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phe-
nanthren-3-yl sulfurofluoridate (1 mmol, 1 equiv). The title
1
pound was obtained as a white solid (242 mg, 79%). H NMR
(400 MHz, CDCl3) δ 8.53 (bs, 1H), 7.80 (d, J = 7.7 Hz, 2H),
7.64 (t, J = 7.4 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H), 6.93 (s, 3H),
2.26 (s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ 163.8, 149.8,
140.1, 133.9, 130.9, 129.5, 129.2, 127.8, 119.3, 21.2; FT-IR
(neat, cm-1): 3215, 3077, 2919, 1692, 1454. HR-MS (ESI) m/z:
calculated for C15H14NO4S- 304.0649 [M-H]-, found 304.0629;
Decomposition: 149 °C
1
compound was obtained as a white solid (285 mg, 73%). H
NMR (300 MHz, DMSO-d6) δ 12.36 (bs, 1H), 7.41 (d, J = 8.5
Hz, 1H), 7.02 – 6.95 (m, 2H), 2.94 – 2.82 (m, 2H), 2.49 – 2.19
(m, 3H), 2.16 – 1.89 (m, 6H), 1.83 – 1.74 (m, 1H), 1.66 – 1.30
(m, 6H), 0.84 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ
220.0, 169.0, 147.8, 139.7, 139.2, 127.6, 122.0, 119.2, 50.0,
47.7, 44.0, 37.8, 35.8, 31.7, 29.3, 26.1, 25.8, 23.7, 21.6, 14.0;
FT-IR (neat, cm-1): 3072, 2925, 2839, 1712, 1476; HR-MS
(ESI) m/z: calculated for C20H24NO5S- 390.1381 [M-H]-, found
390.1365; Decomposition: 219 °C
3,5-dimethylphenyl (4-fluorobenzoyl)sulfamate (3w): Gen-
eral procedure C was followed using 204 mg of 3,5-dime-
thylphenyl sulfurofluoridate (1 mmol, 1 equiv) and 170 mg 4-
fluorobenzamide (98 wt%, 1.2 mmol, 1.2 equiv). After 24 hours
of reaction time, purification was performed according to re-
mark 2. The resulting solid was dry-loaded onto the MPLC sys-
tem and eluted with following gradient: DCM - DCM/AcOH
98/2. The title compound was obtained as a white solid (201
3,5-dimethylphenyl butyrylsulfamate (3s): General procedure
C was followed using 204 mg of 3,5-dimethylphenyl sulfuro-
fluoridate (1 mmol, 1 equiv) and 106 mg butyramide (99 wt%,
1.2 mmol, 1.2 equiv). Purification was performed according to
remark 2. The resulting solid was dry-loaded onto the MPLC
system and eluted with following gradient: DCM - DCM/AcOH
98/2. The title compound was obtained as a white solid (187
mg, 69%). 1H NMR (400 MHz, CDCl3) δ 8.05 (bs, 1H), 6.96 (s,
1H), 6.88 (s, 2H), 2.38 (t, J = 7.3 Hz, 2H), 2.31 (s, 6H), 1.76 –
1.60 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H); 13C{1H} NMR (101 MHz,
CDCl3) δ 170.7, 149.7, 140.1, 129.5, 119.2, 37.8, 21.2, 17.9,
13.5; FT-IR (neat, cm-1): 3148, 3083, 3017, 2970, 2917, 2875;
HR-MS (ESI) m/z: calculated for C12H16NO4S- 270.0805
[M-H]-, found 270.0786; Decomposition: 94 °C
1
mg, 62%). H NMR (400 MHz, CDCl3) δ 8.52 (bs, 1H), 7.84
(dd, J = 8.7, 5.1 Hz, 2H), 7.18 (t, J = 8.5 Hz, 2H), 6.94 (s, 1H),
6.91 (s, 2H), 2.26 (s, 6H); 19F{1H, 13C} NMR (377 MHz,
CDCl3) δ -103.03; 13C{1H} NMR (101 MHz, CDCl3) δ 167.4
(s), 164.9 (s), 149.7 (s), 140.1 (s), 130.5 (d, J = 9.5 Hz), 129.6
(s), 127.0 (s), 119.2 (s), 116.5 (d, J = 22.3 Hz), 21.2 (s); FT-IR
(neat, cm-1): 3173, 3137, 3085, 2919; HR-MS (ESI) m/z: calcu-
lated for C15H13FNO4S- 322.0555 [M-H]-, found 322.0533; De-
composition: 124 °C
3,5-dimethylphenyl (4-nitrobenzoyl)sulfamate (3x): General
procedure C was followed using 204 mg of 3,5-dimethylphenyl
sulfurofluoridate (1 mmol, 1 equiv) and 203 mg 4-nitroben-
zamide (98 wt%, 1.2 mmol, 1.2 equiv). After 24 hours of reac-
tion time, purification was performed according to remark 2.
The resulting solid was dry-loaded onto the MPLC system and
eluted with following gradient: DCM - DCM/AcOH 98/2. The
title compound was obtained as a pale yellow solid (220 mg,
63%). 1H NMR (400 MHz, CDCl3) δ 8.95 (bs, 1H), 8.33 (d, J =
8.7 Hz, 2H), 8.01 (d, J = 8.6 Hz, 2H), 6.95 (s, 1H), 6.90 (s, 2H),
2.27 (s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ 162.4, 150.8,
149.7, 140.3, 136.2, 129.7, 129.2, 124.3, 119.1, 21.2; FT-IR
(neat, cm-1): 3213, 2918, 2853, 1716, 1523, 1448; HR-MS (ESI)
m/z: calculated for C15H13N2O6S- 349.0500 [M-H]-, found
349.0480; Decomposition: 163 °C
3,5-dimethylphenyl methacryloylsulfamate (3t): General pro-
cedure C was followed using 204 mg of 3,5-dimethylphenyl
sulfurofluoridate (1 mmol, 1 equiv) and 104 mg methacryla-
mide (98 wt%, 1.2 mmol, 1.2 equiv). Purification was per-
formed according to remark 2. The resulting solid was dry-
loaded onto the MPLC system and eluted with following gradi-
ent: DCM - DCM/AcOH 98/2. The title compound was ob-
1
tained as a white solid (186 mg, 69%). H NMR (400 MHz,
CDCl3) δ 8.26 (bs, 1H), 6.95 (s, 1H), 6.89 (s, 2H), 5.77 (s, 1H),
5.65 (d, J = 1.3 Hz, 1H), 2.31 (s, 6H), 1.99 (s, 3H); 13C{1H}
NMR (101 MHz, CDCl3) δ 164.4, 149.7, 140.0, 138.0, 129.5,
124.0, 119.2, 21.2, 18.2; FT-IR (neat, cm-1): 3193, 2922, 1684,
1453; HR-MS (ESI) m/z: calculated for C12H14NO4S- 268.0649
[M-H]-, found 268.0625; Decomposition: 104 °C
3,5-dimethylphenyl (4-methoxybenzoyl)sulfamate (3y): Gen-
eral procedure C was followed using 204 mg of 3,5-dime-
thylphenyl sulfurofluoridate (1 mmol, 1 equiv) and 185 mg 4-
tert-butyl
(S)-2-(((3,5-dimethylphenoxy)sulfonyl)car-
bamoyl)pyrrolidine-1-carboxylate (3u): General procedure C
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The Journal of Organic Chemistry
Supporting Information
methoxybenzamide (98 wt%, 1.2 mmol, 1.2 equiv). After 24
1
hours of reaction time, purification was performed according to
remark 2. The resulting solid was dry-loaded onto the MPLC
system and eluted with following gradient: DCM - DCM/AcOH
98/2. The title compound was obtained as a white solid (84 mg,
25%). 1H NMR (400 MHz, CDCl3) δ 8.46 (bs, 1H), 7.78 (d, J =
8.8 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 6.92 (s, 3H), 3.88 (s, 3H),
2.25 (s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ 164.2, 163.1,
149.8, 140.0, 130.1, 129.5, 122.8, 119.3, 114.4, 55.6, 21.2; FT-
IR (neat, cm-1): 3214, 2916, 2845, 1671, 1436; HR-MS (ESI)
m/z: calculated for C16H16NO5S- 334.0755 [M-H]-, found
334.0734; Decomposition: 97 °C
The Supporting Information is available free of charge on the ACS
Publications website.
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Optimization of the reaction conditions, stability study, X-ray anal-
ysis data for 3j and 5 and NMR spectra for all compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
* E-mail: wim.deborggraeve@kuleuven.be
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ORCID
benzo[d][1,3]dioxol-5-yl ethanethioylsulfamate (5): General
procedure C was followed using 204 mg of 3,5-dimethylphenyl
sulfurofluoridate (1 mmol, 1 equiv) and 90 mg thioacetamide
(98 wt%, 1.2 mmol, 1.2 equiv). After 24 hours of reaction time,
purification was performed according to remark 2. The result-
ing solid was dry-loaded onto the MPLC system and eluted with
following gradient: DCM - DCM/AcOH 98/2. The title com-
pound was obtained as a yellow solid (110 mg, 40%). 1H NMR
(400 MHz, CDCl3) δ 9.03 (bs, 1H), 6.83 – 6.66 (m, 3H), 6.03
(s, 2H), 2.81 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 205.8,
148.5, 147.3, 143.5, 114.8, 108.3, 103.9, 102.3, 32.6; FT-IR
(neat, cm-1): 3191, 3122, 2917, 2851, 1462, 1391; HR-MS (ESI)
m/z: calculated for C9H8NO5S2 273.9849 [M-H]-, found
273.9823; Decomposition: 86 °C
Philippe Gilles: 0000-0001-8382-8396
Cedrick Veryser: 0000-0001-9076-3623
Sarah Vangrunderbeeck: 0000-0001-6682-9936
Sam Ceusters: 0000-0002-8352-5608
Luc Van Meervelt: 0000-0003-2186-5209
Wim M. De Borggraeve: 0000-0001-7813-6192
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful to Karel Duerinckx (KU Leuven) for the assistance
with NMR measurements and to prof. dr. Jef Rozenski for HR-MS
measurements. P.G. and C.V. thank FWO (PhD Fellowship of the
N-benzoyl-N-methylbenzamide (7): General procedure C was
followed using 204 mg of 3,5-dimethylphenyl sulfurofluoridate
(1 mmol, 1 equiv). The title compound was obtained as a white
liquid after purification via column chromatography (56 mg,
47%). 1H NMR (300 MHz, CDCl3) δ 7.51 – 7.44 (m, 4H), 7.33
– 7.27 (m, 2H), 7.20 (tt, J = 6.8, 1.6 Hz, 4H), 3.52 (s, 1H). These
data are in agreement with literature data.34
Research Foundation
- Flanders) for fellowships received.
W.M.D.B. thanks KU Leuven for financial support via Project
OT/14/067. The Hercules Foundation of the Flemish Government
is acknowledged for making mass spectrometry possible (grant
20100225-7) and supporting the purchase of a 400 MHz NMR
spectrometer through project AKUL1311 and a diffractometer
through project AKUL/09/0035.
6-chloro-3-(2-chloro-4-nitrophenyl)benzo[e][1,2,3]oxathia-
zin-4(3H)-one 2,2-dioxide (9): Chamber A of a flame-dried 20
mL two-chamber reactor was filled with 1,1’-sulfonyldiimidaz-
ole (SDI, 297 mg, 1.5 mmol, 1.5 equiv) and potassium fluoride
(KF, 232 mg, 4 mmol, 4.0 equiv). Next, chamber B was charged
with Niclosamide (1 mmol, 1 equiv), DIPEA (0.7 mL, 4 mmol,
4.0 equiv) and acetonitrile (MeCN, 4 mL). Finally, 1 mL of a
trifluoroacetic acid (TFA) was added by injection through the
septum in chamber A and instant gas formation was observed.
After 18 hours stirring at room temperature, one of the caps was
carefully removed to release the residual pressure. As sulfuryl
fluoride is a toxic gas, the reaction was stirred for another 15
minutes to ensure that all sulfuryl fluoride was extracted out of
the fume hood. Next, the content of chamber B was transferred
to a 100 mL round-bottomed flask. Chamber B was rinsed five
times with 5 mL of dichloromethane and these fractions were
added to the same flask. After the addition of Celite®545, the
solvent was removed under reduced pressure. The crude prod-
uct was dry-loaded onto MPLC for purification (mixture of hep-
tane/ethyl acetate 9/1 as the eluent). The title compound was
REFERENCES
(1)
Minghao, F.; Bingqing, T.; Steven, H. L.;
Xuefeng, J. Sulfur Containing Scaffolds in Drugs: Synthesis and
Application in Medicinal Chemistry. Curr. Top. Med. Chem. 2016,
16, 1200-1216.
(2)
Ilardi, E. A.; Vitaku, E.; Njardarson, J. T. Data-
Mining for Sulfur and Fluorine: An Evaluation of Pharmaceuticals
To Reveal Opportunities for Drug Design and Discovery. J. Med.
Chem. 2014, 57, 2832-2842.
(3)
Substituted Derivatives. Chem. Rev. 2014, 114, 2507-2586.
(4) Winum, J. Y.; Scozzafava, A.; Montero, J. L.;
Spillane, W. Sulfamic Acid and Its N- and O-
Supuran, C. T. Sulfamates and their therapeutic potential. Med.
Res. Rev. 2005, 25, 186-228.
(5)
Atmaca, U.; Yildirim, A.; Taslimi, P.; Celik, S.
T.; Gulcin, I.; Supuran, C. T.; Celik, M. Intermolecular amination
of allylic and benzylic alcohols leads to effective inhibitions of
acetylcholinesterase enzyme and carbonic anhydrase I and II
isoenzymes. Journal of Biochemical and Molecular Toxicology
2018, 32.
1
obtained as an off-white solid (249 mg, 64%). H NMR (400
MHz, CDCl3) δ 8.49 (d, J = 2.1 Hz, 1H), 8.31 (dd, J = 8.7, 2.2
Hz, 1H), 8.18 (d, J = 2.3 Hz, 1H), 7.82 – 7.70 (m, 2H), 7.40 (d,
J = 8.8 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3) δ 158.2,
149.3, 148.8, 137.0, 136.2, 134.9, 133.7, 132.2, 130.5, 126.3,
123.1, 120.3, 118.0. FT-IR (neat, cm-1): 3105, 3083, 2925,
1724, 1530, 1408; CHN Anal. Calcd for C13H6Cl2N2O6S: C,
40.12; H, 1.55; N, 7.20. Found: C, 40.45; H, 1.75; N, 6.99. De-
composition: 190 °C
(6)
Isono, K.; Uramoto, M.; Kusakabe, H.; Miyata,
N.; Koyama, T.; Ubukata, M.; Sethi, S. K.; McCloskey, J. A.
Ascamycin and dealanylascamycin, nucleoside antibiotics from
Streptomyces sp. J. Antibiot. 1984, 37, 670-672.
(7)
selective toxicity of ascamycin,
Antimicrob. Agents Chemother. 1985, 27, 230-233.
Osada, H.; Isono, K. Mechanism of action and
a
nucleoside antibiotic.
(8)
Ferreras, J. A.; Ryu, J. S.; Di Lello, F.; Tan, D.
S.; Quadri, L. E. N. Small-molecule inhibition of siderophore
ASSOCIATED CONTENT
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Page 10 of 10
biosynthesis in Mycobacterium tuberculosis and Yersinia pestis.
Nat. Chem. Biol. 2005, 1, 29-32.
Ligand-Free Suzuki Reaction in Water Using Aryl Fluorosulfates.
Org. Lett. 2015, 17, 1942-1945.
(25) Veryser, C.; Demaerel, J.; Bieliunas, V.;
Gilles, P.; De Borggraeve, W. M. Ex Situ Generation of Sulfuryl
Fluoride for the Synthesis of Aryl Fluorosulfates. Org. Lett. 2017,
19, 5244-5247.
1
2
3
4
5
6
7
8
(9)
Somu, R. V.; Boshoff, H.; Qiao, C. H.;
̅
Bennett, E. M.; Barry, C. E.; Aldrich, C. C. Rationally designed
nucleoside antibiotics that inhibit siderophore biosynthesis of
Mycobacterium tuberculosis. J. Med. Chem. 2006, 49, 31-34.
(10)
Grimes, K. D.; Lu, Y. J.; Zhang, Y. M.; Luna,
(26)
Zhou, H.; Mukherjee, P.; Liu, R.; Evrard, E.;
V. A.; Hurdle, J. G.; Carson, E. I.; Qi, J.; Kudrimoti, S.; Rock, C.
O.; Lee, R. E. Novel Acyl Phosphate Mimics that Target PlsY, an
Wang, D.; Humphrey, J. M.; Butler, T. W.; Hoth, L. R.; Sperry, J.
B.; Sakata, S. K.; Helal, C. J.; am Ende, C. W. Introduction of a
Crystalline, Shelf-Stable Reagent for the Synthesis of Sulfur(VI)
Fluorides. Org. Lett. 2018, 20, 812-815.
Essential
Chemmedchem 2008, 3, 1936-1945.
(11) Chattopadhyay, S.; Raychaudhuri, U.;
Acyltransferase
in
Gram-Positive
Bacteria.
9
(27)
Guo, T.; Meng, G.; Zhan, X.; Yang, Q.; Ma,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Chakraborty, R. Artificial sweeteners - a review. J. Food Sci.
Technol. (New Delhi, India) 2014, 51, 611-621.
T.; Xu, L.; Sharpless, K. B.; Dong, J. A New Portal to SuFEx Click
Chemistry: A Stable Fluorosulfuryl Imidazolium Salt Emerging as
an “F−SO2+” Donor of Unprecedented Reactivity, Selectivity, and
Scope. Angew. Chem. Int. Ed. 2018, 57, 2605-2610.
(12)
Petrova, E.; Rasina, D.; Jirgensons, A. N-
Sulfonylcarboxamide as an Oxidizing Directing Group for
Ruthenium-Catalyzed C-H Activation/Annulation. Eur. J. Org.
Chem. 2017, 1773-1779.
(28)
Woo, L. W. L.; Purohit, A.; Reed, M. J.; Potter,
B. V. L. Oestrone 3-O-(N-acetyl)sulphamate, a potential molecular
probe of the active site of oestrone sulphatase. Bioorg. Med. Chem.
Lett. 1997, 7, 3075-3080.
(13)
Akrmi, A.; Beji, M.; Baklouti, A. Synthesis of
N-acylsulfamates. Phosphorus, Sulfur Silicon Relat. Elem. 2003,
178, 83-88.
(29)
Wang, F.; Langley, R.; Gulten, G.; Dover, L.
(14)
Sbihi, H.; Beji, M.; Baklouti, A. Reaction of
G.; Besra, G. S.; Jacobs, W. R.; Sacchettini, J. C. Mechanism of
thioamide drug action against tuberculosis and leprosy. J. Exp.
Med. 2007, 204, 73-78.
acids and diacids with aroxy(alcoxy)sulfonyl isocyanates:
Synthesis of N-acylsulfamates, disulfamates, and N,N '-
disulfonylureas. Synth. Commun. 2008, 38, 2490-2498.
(30)
Hedayatullah, M.; Guy, A.; Denivelle, L.
(15)
Cherian, P. T.; Yao, J. W.; Leonardi, R.;
Synthese von 3-Aryl-1,2,3-oxathiazin-4-on-2,2-dioxiden. Sci.
Chim 1975, 85-87.
Maddox, M. M.; Luna, V. A.; Rock, C. O.; Lee, R. E. Acyl-
sulfamates target the essential glycerol-phosphate acyltransferase
(PlsY) in Gram-positive bacteria. Bioorg. Med. Chem. 2012, 20,
4985-4994.
(31)
Spillane, W. J.; Malaubier, J. B. Mechanism of
the acid-catalyzed hydrolysis of N-acylsulfamates. Tetrahedron
Lett. 2007, 48, 7574-7577.
(16)
Kim, S. E.; Kim, S. Y.; Kim, S.; Kang, T.; Lee,
(32)
Schimler, S. D.; Cismesia, M. A.; Hanley, P.
J. Deoxyribosyl analogues of methionyl and isoleucyl sulfamate
adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA
synthetases. Bioorg. Med. Chem. Lett. 2005, 15, 3389-3393.
S.; Froese, R. D. J.; Jansma, M. J.; Bland, D. C.; Sanford, M. S.
Nucleophilic Deoxyfluorination of Phenols via Aryl
Fluorosulfonate Intermediates. J. Am. Chem. Soc. 2017, 139, 1452-
1455.
(17)
Revathi, L.; Ravindar, L.; Leng, J.; Rakesh, K.
P.; Qin, H. L. Synthesis and Chemical Transformations of
Fluorosulfates. Asian J. Org. Chem. 2018, 7, 662-682.
(33)
Roth, G. P.; Fuller, C. E. Palladium cross-
coupling reactions of aryl fluorosulfonates: an alternative to triflate
chemistry. J. Org. Chem. 1991, 56, 3493-3496.
(18)
Dong, J. J.; Krasnova, L.; Finn, M. G.;
Sharpless, K. B. Sulfur(VI) Fluoride Exchange (SuFEx): Another
Good Reaction for Click Chemistry. Angew. Chem. Int. Ed. 2014,
53, 9430-9448.
(34)
Yu, H.; Zhang, Y. H. Copper-Catalyzed
Synthesis of Imides from Aldehydes or Alcohols and Amine
Hydrochloride Salts. Eur. J. Org. Chem. 2015, 1824-1828.
(19)
Gao, B.; Zhang, L. D.; Zheng, Q. H.; Zhou, F.;
Klivansky, L. M.; Lu, J. M.; Liu, Y.; Dong, J. J.; Wu, P.; Sharpless,
K. B. Bifluoride-catalysed sulfur(VI) fluoride exchange reaction
for the synthesis of polysulfates and polysulfonates. Nat. Chem.
2017, 9, 1083-1088.
(20)
Domino, K.; Veryser, C.; Wahlqvist, B. A.;
Gaardbo, C.; Neumann, K. T.; Daasbjerg, K.; De Borggraeve, W.
M.;
Skrydstrup,
T.
Direct
from
Access
Aryl
to
Aryl
or
Bis(trifluoromethyl)carbinols
Bromides
Fluorosulfates: Palladium-Catalyzed Carbonylation. Angew.
Chem. Int. Ed. 2018, 57, 6858-6862.
(21)
Fang, W. Y.; Huang, Y. M.; Leng, J.; Qin, H.
L. Pd-Catalyzed One-Pot Dehydroxylative Coupling of Phenols
and Amines under a Carbon Monoxide Atmosphere: A Chemical-
Specific Discrimination for Arylcarboxylic Amide Synthesis.
Asian J. Org. Chem. 2018, 7, 751-756.
(22)
Hanley, P. S.; Clark, T. P.; Krasovskiy, A. L.;
Ober, M. S.; O'Brien, J. P.; Staton, T. S. Palladium- and Nickel-
Catalyzed Amination of Aryl Fluorosulfonates. ACS Catal. 2016,
6, 3515-3519.
(23)
Hanley, P. S.; Ober, M. S.; Krasovskiy, A. L.;
Whiteker, G. T.; Kruper, W. J. Nickel- and Palladium-Catalyzed
Coupling of Aryl Fluorosulfonates with Aryl Boronic Acids
Enabled by Sulfuryl Fluoride. ACS Catal. 2015, 5, 5041-5046.
(24)
Liang, Q. B.; Xing, P.; Huang, Z. G.; Dong, J.
J.; Sharpless, K. B.; Li, X. X.; Jiang, B. Palladium-Catalyzed,
10
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