A New Portal to SuFEx Click Chemistry: A Stable Fluorosulfuryl Imidazolium Salt Emerging as an “F?SO2+” Donor of Unprecedented Reactivity, Selectivity, and Scope

Article abstract of DOI:10.1002/anie.201712429

Sulfuryl fluoride, SO₂F₂, has been found to derivatize phenols in all kinds of environments, even those in highly functional molecules. We now report that a solid fluorosulfuryl imidazolium triflate salt delivers the same “F?SO₂+” fragment to Nu?H acceptor groups in the substrates. However, this triflate salt is a far more reactive fluorosulfurylating agent than SO₂F₂ and displays selectivity preferences of its own. Moreover, the new azolium triflate reagent reacts once with primary amines and anilines before the reaction stops. On the other hand, with triethylamine and two equivalents of the “F?SO₂+” donor present, it proceeds on to the bis(fluorosulfuryl)imides in good yield—two important conversions that we have never seen with sulfuryl fluoride as the electrophile.

Full text of DOI:10.1002/anie.201712429

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: A New Portal to SuFEx Click Chemistry: a Stable Fluorosulfuryl
Imidazolium Salt Emerging as an "F-SO2+" Donor of
Unprecedented Reactivity, Selectivity, and Scope
Authors: Taijie Guo, Genyi Meng, Xiongjie Zhan, Qian Yang,
Tiancheng Ma, Long Xu, Karl Barry Sharpless, and Jiajia
Dong
This manuscript has been accepted after peer review and appears as an
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of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
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content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201712429
Angew. Chem. 10.1002/ange.201712429
Link to VoR: http://dx.doi.org/10.1002/anie.201712429
http://dx.doi.org/10.1002/ange.201712429

10.1002/anie.201712429
Angewandte Chemie International Edition
COMMUNICATION
A New Portal to SuFEx Click Chemistry: a Stable Fluorosulfuryl
+
Imidazolium Salt Emerging as an “F-SO2 ” Donor of
Unprecedented Reactivity, Selectivity, and Scope
Taijie Guo†,§, Genyi Meng†,§, Xiongjie Zhan†,§, Qian Yang‡, Tiancheng Ma†, Long Xu†, K. Barry
Sharpless*,† and Jiajia Dong*,†
This paper is dedicated to Professor Li-Xin Dai on the occasion of his 93rd birthday
Abstract: Sulfuryl fluoride, SO2F2, has been found to derivatize
phenols of all kinds of environments, even those in highly
polyfunctional molecules. We now report that solid reagent 3-1
was further applied in the synthesis of polysulfates, analogs to
the well-known polycarbonates with promising mechanical
properties and chemical stability.[3,8] Fluorosulfates were also
utilized to discover novel warheads of irreversible inhibitors
which covalently capture protein side chains in a context-
dependent manner, providing a powerful tool to investigate
protein functions in complex biological environments.[5a,5i,5n] In
addition, SO2F2 participated in the fluorination of phenols[9] via
the formation of intermediates Ar-OSO2F, a pseudo halide with
incomparable balanced accessibility and reactivity that has been
+
delivers the same "F-SO2 " fragment to Nu-H acceptor groups in the
substrates. However, triflate salt 3-1 is
a far more reactive
fluorosulfating agent than SO2F2 and displays selectivity preferences of
its own. Moreover, the new azolium triflate reagent reacts once with
primary amines and anilines, and stops. But with TEA and two
equivalents of the FSO2-donor present it proceeds on to the bis-
fluorosulfuryl imide in good yield — two important conversions that we
have never seen with sulfuryl fluoride as the electrophile.
2
2
successfully applied in the construction of Csp -C and Csp -N
bonds.[10] SO2F2 was as well applied in the production of the
important yet expensive bis(fluorosulfuryl)imide anion for the
new generation of electrolyte in lithium ion batteries.[11]
Click chemistry features the modular assembly of organic
synthons through the formation of heteroatom linkages to
discover useful properties.[1] Focusing on reactions with strong
thermodynamic driving forces and consistent, well-controlled
pathways is an inherent and constant demand for the
advancement of click chemistry.[2] In 2014, by revisiting the
Previous work:
Excellent performance
with phenols
Ar OH
NH2
R1R2NH
Ar
O SO2F
Hard to operate in lab
unique properties of SVI-F bond, we encountered
a new
R
R
NH SO2F
No sulfamoyl fluoride
formed with primary amines
embodiment of click chemistry, Sulfur(VI) Fluoride Exchange
(SuFEx), to achieve efficient and reliable linkage via the fringe
acid base reactivity of SVI-F functional groups.[3] Numerous
investigations on SuFEx chemistry have since been sparked,
leading to a variety of intriguing discoveries that showcase the
distinctive reactivity of the SuFExable compounds towards
targets including small molecules,[3,4] biomacromolecules[5] and
polymers[6].
Sulfuryl fluoride (SO2F2) gas is a kiloton-scale industrial
product widely used as a fumigant (Vikane by Dow Chemical).[7]
It was recently identified by our SuFEx manifesto as a versatile
SuFEx hub. In the presence of trimethylamine[3] or a borax
buffer[5d], it reacts readily and selectively with a variety of
phenols at room temperature to quantitatively generate aryl
fluorosulfates (Scheme 1).[3] Since then, this SuFEx reaction
R1
N
R2
SO2F
Sluggish reactivity
towards secondary amines
This work:
Ar OH
Ar
O SO2F
i). N
NH
TfO
O
F
R
NH2
S
R
NH SO2F
SO2F2
N
N
O
ii). MeOTf
R1
R1R2NH
SO2F
N
R2
Fluorosulfonation
Gas
Solid
Easy to scale up
Surrogates to SO2F2
for the reaction with phenols
Scheme 1. SO2F2 as
Shelf-stable
Overwheming performance with
primary and secondary amines
a
versatile SuFEx hub and now the facile
fluorosulfonation of phenols and amines using the fluorosulfuryl imidazolium
salt.
[†] T. Guo, X. Zhan, T. Ma, Prof. Dr. J. Dong
Key Laboratory of Organofluorine Chemistry, Center for Excellence in
Molecular Synthesis, Shanghai Institute of Organic Chemistry, University
of Chinese Academy of Sciences, Chinese Academy of Sciences.
345 Ling-Ling Road, Shanghai 200032 (P.R. China)
E-mail: jiajia@sioc.ac.cn
Although SO2F2 possesses ideal reactivity and selectivity as
a SuFEx connector, it encountered several challenges as a
reagent used in the laboratories. Firstly, operations are
problematic for those laboratories without sufficient apparatus to
handle harmful gas or under strict regulations to acquire SO2F2.
Secondly, compared with phenols, SO2F2 reacted sluggishly with
secondary amines to generate sulfamoyl fluorides where limited
substrate scope and complicated reaction conditions were
applied.[3] Thirdly, for the reactions between SO2F2 and primary
amines, it was not successful to obtain the proposed sulfamoyl
fluorides which undergo facile elimination to the azasulfene
intermediates[12] under basic conditions by virtue of the acidic
nature of the N-sulfamoyl proton. Considering all the drawbacks
G. Meng, L. Xu, Prof. Dr. K. B. Sharpless
Key Laboratory of Organofluorine Chemistry, Center for Excellence in
Molecular Synthesis, Shanghai Institute of Organic Chemistry, University
of Chinese Academy of Sciences, Chinese Academy of Sciences.
345 Ling-Ling Road, Shanghai 200032 (P.R. China)
E-mail: sharples@scripps.edu
[‡] Q. Yang
No.187 Building, 1799 Yinchun Road, Shanghai 200032 (P. R. China)
E-mail:yangq430@tom.com
[§] T. Guo, G. Meng and X. Zhan contributed equally to this work.
Supporting information for this article can be found under:
This article is protected by copyright. All rights reserved.

10.1002/anie.201712429
Angewandte Chemie International Edition
COMMUNICATION
above, it would be of great value to develop an easy-to-access
and user-friendly reagent as an efficient and practical alternative
to the gaseous SO2F2, and more importantly, to facilitate the
fluorosulfonation of amines. Sulfuryl imidazolium salts have
been shown to be powerful reagents for the preparation of
sulfates and sulfonamides where the alkylated imidazoliums
served as good leaving groups.[13] What we are particularly
interested in is that they displayed unusally high reactivity
towards primary and secondary amines at base-free condition to
deliver sulfonamides.[13c,13d] This feature might help us
accomplish the pursuit since the birth of SuFEx click chemistry,
to synthesize a broad scope of sulfamoyl fluorides, especially
the R-NH-SO2F compounds.
O
O
Na2CO3 2.5 equiv.
MeOTf, 1.0 equiv.
O
O
F
F
S
S
N
NH
1-1
N
N
N
N
(a)
+
S
CH2Cl2, 0 oC to R.T., 1 h
O
O
TfO
F
F
CH3CN, R.T., overnight
2-1
3-1
(b)
(c)
(d)
To address the task above, herein we report the synthesis
and reactivity of a fluorosulfuryl imidazolium salt as a
fluorosulfuryl transfer reagent. We initially examined the SuFEx
reaction between SO2F2 and 2-methylimidazole to generate 2-1
(Figure 1a). The choice of the base was crucial for this
conversion as the subsequent N-methylation with methyl
trifluoromethanesulfonate would be interfered with organic bases
in the system. After careful screening of a series of inorganic
bases, sodium carbonate was found to be optimal due to its low
cost and convenient removal by water-organic extraction. The
procedure did not require the isolation of the intermediate 2-1;
instead, the organic layer containing 2-1 was treated with
Figure 1. a) Synthetic procedure of 3-1; b) large-scale preparation of 3-1; c)
Structure of 3-1 determined by single crystal X-ray diffraction; d) stability test
of 3-1 under different conditions.
dichloromethane and methyl trifluoromethanesulfonate at 0 ℃
under N2. The whole mixture was then gradually warmed to
room temperature and stirred for one hour, allowing us to obtain
the fluorosulfuryl imidazolium salt 3-1 as a white powder after a
O
S
Et3N , CH3CN
R.T. , 1 h
O
S
F
+
Ar-OH
N
N
Ar
O
F
O
TfO
OH
O
4
3-1
5
F
S
O
O
O
O
O
O
O
S
O
F
N
H
O
O
O
O
O
O
O
S
O
F
N
F
F
O
S
O
F
H
H
S
O
O
S
O
AcHN
O
O
O
HO
C
O
5-1[a]
61 %
m.p. 228-230 o
5-2
88 %
m.p. 45-48 o
C
5-6[b]
5-3
81 %
m.p. 164-165 o
5-4
90 %
5-5
98 %
O
86 %
C
m.p. 85-88 o
C
m.p. 150-152 o
C
O
O
O
O
O
F
O
F
F
O
F
F
O
S
S
S
S
S
O
O
O
O
O
O
O
Cl
O
O
N
N
O
H3CO
H3CO2C
H3CO
F
S
O
O
F
O
O
S
O
O
NO2
Cl
CHO
5-12
87 %
m.p. 80-81 o
5-13
82 %
m.p. 93-94 o
C
5-8
94 %
m.p. 51-52 o
5-11
5-7
5-9
81 %
5-10
96 %
97 %
m.p. 65-66 o
99 %
m.p. 87-88 o
C
C
C
C
O
O
O
O
O
I
F
F
F
O
O
O
S
O
S
F
S
S
F
F
O
O
O
O
N
N
S
O
O
S
S
O
O
S
O
O
Cl
O
O
O
N
O
O
O
Cl
S
Cl
Cl
N
N
O
I
O
O
N
S
S
N
O
F
O
O
O
5-18[d]
Cl
Cl
5-17[c]
5-19
94 %
5-14
67 %
5-20[e]
5-15
75 %
5-16
71 %
85 %
55 %
m.p. 183-184 o
56 %
m.p. 197-201 o
C
m.p. 117-118 oC
C
S
O
F
O
O
S
F
O
O
S
O
O
O
S
O
O
O
S
O
O
O
S
O
O
F
F
F
F
O
F
F
O
O
S
S
S
O
S
O
O
O
O
O
F
F
O
O
S
O
O
O
S
O
O
O
F
O
O
5-22[f]
77 %
m.p. 125-126 o
5-21[f]
82 %
m.p. 48-50 o
5-23
5-24
5-25
75 %
81 %
m.p. 95-97 o
C
57 %
m.p. 96-97 o
C
C
m.p. 123-124 o
C
C
Figure 2．Synthesis of fluorosulfates using 3-1. Reaction conditions: 1 mmol phenols, 1.2 mmol 3-1, 1.5 mmol Et3N, 2 ml CH3CN, R.T., 1 h; isolated yields.
Unless otherwise stated, the products were isolated by silica gel chromatography. [a] 0.5 mmol phenol, 2.5 mmol 3-1 and 3 mmol Et3N. [b] 20 mmol phenol, 25
mmol 3-1, 32 mmol Et3N, product 5-6 was isolated by water-EtOAc extraction, without silica gel chromatography. [c] 0.4 mmol phenol. [d] 0.6 mmol phenol. [e] 0.5
mmol phenol, 3.5 mmol 3-1 and 4.5 mmol Et3N. [f] 0.5 mmol phenol.
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10.1002/anie.201712429
Angewandte Chemie International Edition
COMMUNICATION
O
O
F
R1
CH3CN
R.T.
R1
S
F
S
NH
R2
6
N
N
+
N
O
O
TfO
R2
3-1
7
F
O
O
O
S
N
O
F
F
S
S
N
N
O
N
O
N
O
N
O
O
O
F
N
O
N
N
O
S
F
O
S
S
S
S
F
F
F
O
O
O
O
7-7[b]
7-8[b]
72 %
7-1
7-2
7-3[a]
7-4
7-5
82 %
7-6
92 %
94 %
85 %
81 %
83 %
76 %
O
m.p. 83-84 oC
m.p. 58-62 oC
O
F
S
N
O
S
O
F
O
O
O
O
N
F
N
N
S
S
O
N
O
O
H
O
F
F
N
F
O
O
N
S
O
S
O
N
N
N
N
O
O
Cl
S
O
H
O
O
F
F3C
O
F3C
7-12[d][e]
7-14[e][f]
7-9[b]
7-10[c][d]
7-11[d]
7-13[d][e]
95 %
92 %
70 %
85 %
81 %
98 %
m.p. 246-248 oC
m.p. 184-186 oC
m.p. 125-127 oC
m.p. 147-150 oC
m.p. 205-207 oC
Figure 3. Synthesis of sulfamoyl fluorides from 3-1 and secondary amines. Reaction conditions: 0.1-1.0 M amine in CH3CN, 1.0 equiv. 3-1, R.T., 1-2 h; isolated
yields. Unless otherwise stated, the products were isolated by water-EtOAc extraction. [a] 3-1 was added in ice bath. [b] The corresponding amine hydrochloride
was used. [c] THF was used. [d] The product was isolated by silica gel chromatography. [e] CH2Cl2 was used. [f] 2.0 equiv. 3-1.
simple wash with methyl tert-butyl ether. Due to the simplicity of
the procedure and the accessibility of the starting materials, the
synthesis of 3-1 can be easily scaled up, giving 0.6 mole (179
grams, 91% yield) of the product (Figure 1b).
excellent selectivity towards aromatic hydroxyl groups, leaving
other functional groups, such as aliphatic hydroxyl untouched
under basic reaction conditions. Formation of the cyclization
products 5-17 and 5-18 was observed when the SuFExable
hydroxyl group was adjacent to a secondary amide. Moreover,
the conversion of the starting phenols was complete within only
one hour, in contrast to a longer reaction time required (2-4
hours) for SO2F2. Our results identified 3-1 as a sibling reagent
to gaseous SO2F2 for the synthesis of fluorosulfates.
More surprisingly, unlike SO2F2, 3-1 reacted cleanly with
either primary or secondary amines. As shown in Figure 3, it
directly converted a broad scope of secondary amines to
sulfamoyl fluorides in an additive-free condition. In contrast,
trimethylamine and an additive (DMAP or DABCO) were
required when SO2F2 was used. Compared with the sluggish
reactivity of SO2F2 towards secondary amines which led to a
longer reaction time (8-18 hours) and lower yields, 3-1 showed a
superior performance, accomplishing the conversion within 2
hours with good to excellent yields. While SO2F2 showed a
limited substrate scope (cyclic and few symmetric secondary
amines), 3-1 reacted rapidly with the secondary amines bearing
alkyl or phenyl substituents to deliver the corresponding
sulfamoyl fluorides, such as 7-3 and 7-4 in Figure 3.
More impressive performances of 3-1 were displayed in the
reactions with primary amines which are totally incompatible with
sulfuryl fluoride. With 3-1, a variety of anilines or aliphatic
primary amines were successfully converted to NH-sulfamoyl
fluorides (Figure 4), a type of compound that has rarely
appeared in literatures[3,15] in spite of being a potentially useful
SuFEx hub. In the reactions between primary amines and 3-1
under base-free conditions, most sulfamoyl fluoride products
could survive the reaction environment (pH was around 2 after
completion), and were isolated by the simple water-EtOAc
extraction. To the best of our knowledge, this is the first example
showing the facile and rapid synthesis of R-NH-SO2F under
such mild conditions. What’s more, unlike the selectivity
To evaluate the stability of 3-1 for daily use, we first tested
its thermal stability data. It melted at 58-60 ℃ and decomposed
at 228 ℃. The half-life of 3-1 in deionized water was determined
to be 30 minutes, indicating the instability of 3-1 in the aqueous
solution (however we did find 3-1 could react smoothly with
some substrates under aqueous conditions, see supporting
information). We also checked the long-term stability of 3-1
considering its moderate hygroscopic nature. It was found that
after 231 days, the sample of 3-1 stored on bench turned to a
white sticky slurry while the samples stored in refrigerator (4 ℃)
or in desiccator (22 ℃) remained a white coarse powder (Figure
1d). NMR analysis of the resultant sample stored on bench
1
revealed miscellaneous peaks in both H and 19F NMR spectra
while those stored in refrigerator or desiccator had almost
unchanged NMR spectra. (For the NMR spectra and reactivity
tests of these three samples with 4-cumylphenol, see supporting
information). Interestingly, similar to a recently reported process
using
1,1’-sulfuryldiimidazole,
potassium
fluoride
and
trifluoracetic acid to produce sulfuryl fluoride,[14] we found that in
the presence of one equivalent of potassium fluoride, 3-1 would
release sulfuryl fluoride in an efficient and much safer way. The
in situ generated sulfuryl fluoride was transferred to another
flask containing 4-cumylphenol and trimethylamine to give the
corresponding fluorosulfate 5-6.
With the new reagent in-hand, we next explored its ability to
serve as a surrogate to SO2F2 for the synthesis of fluorosulfates.
To our delight, in the presence of triethylamine, 3-1 reacted
smoothly with a variety of phenols or heteroaryl hydroxides to
form fluorosulfates in good to excellent yields under ambient
conditions (Figure 2). Sterically hindered substrates or those
bearing electron-withdrawing or donating substituents were well-
tolerated in this transformation. Similar to SO2F2, 3-1 showed
This article is protected by copyright. All rights reserved.

10.1002/anie.201712429
Angewandte Chemie International Edition
COMMUNICATION
O
F
O
O
R
O
S
F
Solvent
F
N
R
S
S
O
R
NH2
N
N
+
N
or
S
F
O
O
0 oC to R.T.
O
H
TfO
9
8
3-1
10
O
O
O
O
H
H
O
F
F
O
S
F
F
F
O
N
S
N
S
S
O
S
S
N
N
N
N
O
S
O
O
O
O
F
F
H
H
H
H
N
O
O
O
H
F
HO
OH
O
9-5[a][b]
63 %
m.p. 90-92 oC
9-6[a][b]
9-7[a][d]
9-1
9-2
9-3
9-4[a]
84 %
92 %
47 %
94 %
90 %
91 %
m.p. 46-49 oC
m.p. 64-67 oC
O
H
N
H
O
OH
HN
O
N
S
S
CO2Et
O
O
O
F
F
F
F
O
O
O
S
O
S
N
H
MeO2C
NH
N
S
O
S
O
O
H
F
O
S
F
O
O
O
O
O
9-12[c]
9-8
9-9
9-10[a]
9-11[d]
9-13[a][d]
99 %
93 %
m.p. 68-71 oC
99 %
72 %
75 %
97 %
decomp. 136 oC
m.p. 81-84 oC
m.p. 69-71 oC
H
N
H
H
H
N
H
H
N
H
O
O
O
O
O
O
O
N
O
N
N
N
S
S
S
S
S
S
S
O
F
F
F
F
F
F
F
F
O
O
O
O
O
O
O
S
Cl
O
HO
O
9-15[b]
9-16[b]
9-17
9-18[e]
9-19
9-14
9-20[b][f]
88 %
89 %
88 %
88 %
88 %
91%
74 %
m.p. 44-48 oC
m.p. 106-111 oC
O O
F
F
F
F
F
F
S
S
O
O
S
N
O
O
S
N
O
O
S
N
O
O
S
N
O
N
F
O
O
O
O
O
O
O
S
F
O
O
N
S
F
S
S
S
S
O
F
F
F
F
O
O
O
O
O
O
10-1[g]
10-4[b][g]
10-2[b][g]
10-3[b][g]
10-5[b][g]
10-6[b][g]
81 %
64 %
53%
96 %
86 %
72 %
m.p. 41-43 oC
m.p. 49-51 oC
m.p. 53-56 oC
m.p. 110-114 oC
Figure 4. Synthesis of sulfamoyl fluorides from 3-1 and primary amines. Reaction conditions: for aliphatic amine substrates, 0.3-1.4 M amine in CH3CN, 1.0 equiv.
3-1, 0 ℃ to R.T., 0.2-4 h, isolated yields; for aniline substrates, 0.1 M aniline in CH2Cl2, 1.1 equiv. 3-1, 0 ℃ to R.T., 4 h, isolated yields. Unless otherwise stated,
the products were isolated by water-EtOAc extraction. [a] 3-1 was added at R.T.. [b] The product was isolated by silica gel chromatography. [c] 1.1 equiv. 3-1. [d]
amine hydrochloride was used. [e] EtOAc as solvent. [f] Yield of 9-20 was based on the reaction of isolated 4-aminophenyl fluorosulfonate with 3-1. [g] 1 equiv.
aniline, 2.5 equiv. 3-1, 0.5 equiv. Et3N, 0 ℃ to R.T., 1-12 h.
SVI-F
functionalization
N-H
we detected the formation of the imides R-N(SO2F)2 in the
fluorosulfonation of anilines (Figure 4). These bis-
fluorosulfonated compounds could also be prepared by adding
1.5 equivalent of 3-1 and 0.5 equivalent of Et3N to Ar-NH-SO2F
that also undergoes the sulfonation with amines (Scheme 2).
Undoubtedly, the protocol herein offers a new window for the
O
functionalization
F
S
F
N
N
N
H
O
O
S
N
O
TfO
H
O
O
6-4
3-1
O
N
N
S
S
S
N
F
F
Et3N, CH3CN
80 oC, 2h
O
Et3N, CH3CN
oC to R.T., 1h
O
O
H
0
11-1
9-14
10-1
82 %
89 %
m.p. 91-95 oC
systematic study of NH-sulfamoyl fluorides as
a diverse
Scheme 2. Bifunctionalization of NH-sulfamoyl fluoride.
connecting hub where either the N-H or the SVI-F can be further
decorated.
revealed in the cases of SO2F2 and phenols[3], a reversed priority
of amino groups over aromatic hydroxyls was observed,
enabling the formation 9-6 in Figure 4 without cyclization with
the adjacent hydroxyl group. Mono-fluorosulfonated product 9-
18 was obtained after the reaction between 3-1 and 4-
aminophenol in ethyl acetate. Stepwise fluorosulfonation of 4-
aminophenol could be achieved via sequentially reacting with
SO2F2 and then 3-1 to give 9-20. To unveil the mysteries of NH-
sulfamoyl fluorides, we monitored the stability of 9-2 and 9-15 in
aqueous solutions at different pH by LC-MS. We found that they
decomposed more rapidly at more basic pH. For instance, 9-2
was fully decomposed after 25 minutes at pH=5, whereas its full
decomposition took more than 13 hours at pH=0. Interestingly,
In conclusion, we have demonstrated the simplicity in the
synthesis of the fluorosulfuryl imidazolium salt 3-1 and its
unprecedented reactivity, selectivity, and scope. Being a more
+
reactive “F-SO2 ” donor than sulfuryl fluoride, 3-1 offers an
opportunity to add several new examples to the category of
sulfamoyl fluorides, especially NH-sulfamoyl fluorides. Further
exploration of these lack-of-study compounds is ongoing in our
lab.
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Acknowledgements
J.D. is grateful for the One Hundred Talents Program supported
by SIOC, CAS. J.D. is financially supported by the National
Natural Science Foundation of China (NSFC 21672240),
Chinese Academy of Sciences, Strategic Priority Research
Program (XDB200203) and Key Research Program of Frontier
Sciences (QYZDB-SSWSLH-028), Shanghai Pujiang Program
(16PJ1410800). K.B.S. is grateful to SIOC for its long-term
friendship and support. We thank Professor Jinbo Hu for helpful
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Conflict of interest
The authors declare the following competing financial interest(s):
Shanghai Institute of Organic Chemistry, CAS, has filed a patent
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Keywords: azolium salt • click chemistry • sulfamoyl fluoride •
SuFEx • sulfuryl fluoride
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SuFEx Click Chemistry
T. Guo, G. Meng, X. Zhan, Q. Yang, T. Ma, L. Xu,
K. B. Sharpless*, J. Dong* ________
A New Portal to SuFEx Click Chemistry:
a Stable Fluorosulfuryl Imidazolium Salt
Emerging as an “F-SO2 ” Donor of
Unprecedented Reactivity, Selectivity,
and Scope
A New Portal to SuFEx Click Chemistry:
with TEA and two equivalents of the FSO2-
donor present it proceeds on to the bis-
fluorosulfuryl imide in good yield — two
important conversions that we have never
seen with sulfuryl fluoride as the electrophile.
A fluorosulfuryl imidazolium salt delivers the
+
+
"F-SO2 " fragment to Nu-H acceptor groups
(phenols and amines) in the substrates. This
new azolium triflate reagent reacts once with
primary amines and anilines, and stops. But
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