Trifluoromethanesulfinyl Chloride for Electrophilic Trifluoromethythiolation and Bifunctional Chlorotrifluoromethythiolation

Article abstract of DOI:10.1002/chem.201804027

Trifluoromethanesulfinyl chloride (CF₃SOCl) has been introduced as a new reagent for C?H trifluoromethylthiolation of indoles, thiophenes, and ketones under catalyst-free conditions and in the absence of reductant. The disproportionation of CF<

Full text of DOI:10.1002/chem.201804027

A Journal of
Accepted Article
Title: Trifluoromethanesulfinyl Chloride for Electrophilic
Trifluoromethythiolation and Bifunctional
Chlorotrifluoromethythiolation
Authors: Lvqi Jiang, Qiang Yan, Rongkang Wang, Tianqi Ding, Webin
Yi, and Wei Zhang
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To be cited as: Chem. Eur. J. 10.1002/chem.201804027
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Trifluoromethanesulfinyl Chloride for Electrophilic Trifluoromethythiolation
and Bifunctional Chlorotrifluoromethythiolation
[a]
Lvqi Jiang‡ , Qiang Yan ‡ [a], Rongkang Wang[a], Tianqi Ding[a], Wenbin Yi*[a] and Wei Zhang*[b]
catalytic conditions for electrophilic trifluoromethylthiolation.[19]
Abstract: Trifluoromethanesulfinyl chloride (CF3SOCl) is introduced as
a new reagent for C-H trifluoromethylthiolation of indoles, thiophenes,
and ketones under catalyst-free conditions and in the absence of
reductant. The disproportionation of CF3SOCl to CF3SO2Cl and CF3SCl
provides two pathways for the trifluoromethylthiolation. Direct
trifluoromethylthiolation with CF3SCl or trifluoromethylsulfoxidation
with CF3SOCl followed by the reduction with CF3SOCl. This reagent
can be used to functionalize benzothiophenes, benzofurans and indenes
under the promotion of Ag2CO3. It can also be used for
trifluoromethylthiolation of thiols and benzeneselenols, and 1,2-
bifunctional chlorotrifluoromethylthiolation of indoles, styrenes, and
alkyens. The method can also be extended for difluorometylthiolation
CF3SO2Na has also been used to generate CF3S- for nucleophilic,
trifluoromethylthiolation of aryliodides.[20] More recently, CF3SO2Cl
was introduced for electrophilic trifluoromethylthiolation by using Ph3P
or (EtO)2P(O)H.[21] Even some progresses have been made, CF3SO2-
based trifluoromethylthiolation still has following limitations: 1)
requirement of stoichiometric amount of metal salts; 2) limited scope for
electron-rich heterocycles and alkenes such as indoles, pyrroles and
19-21]
enamines.[
During the trifluoromethylthiolation reactions with CF3SO2Na or
CF3SO2Cl, reactive species such as CF3SSCF3 and CF3SCl were
observed from the reaction process.[19-21] CF3SOCl, which could be
obtained from commercial suppliers or easily synthesiezd by the
treatment of readily available CF3SO2Na and SOCl2,[22] has been
reported for direct trifluoromethylsulfoxidations.[23] It was reported that
CF3SOCl could disproportionate into CF3SCl and CF3SO2Cl.[24] Thus,
we believe it is possible to develop CF3SOCl as a reagent for
trifluoromethylthiolation through dismutation without using an
additional reductant.
reactions using CF2HSOCl.
Introduction
Lipophilic trifluoromethylthio (CF3S) group could be introduced to
improve pharmacokinetic and physicochemical properties of
medicinally and agrochemically interested compounds,[1,2] such as
Fipronil,[3] Tiflorex,[4] Toltrazuril[5] and Cefazaflur[6] (Figure 1). Late
stage direct C-H trifluoromethylthiolation is a good approach for lead
optimization.[7] Over the years, highly reactive, but very toxic CF3S-
based reagents such as CF3SCl[8] and CF3SSCF3[9] have been introduced
as trifluoromethylthiolation reagents. Stable and use-friendly CF3SN-
and CF3SO-based reagents 1a-g[10-16] and CF3SO2-containing
hypervalent idonium ylides 2a-b have been developed for
trifluoromethylthiolation of CSP2-H bonds (Figure 2).[17,18] However,
they generally require several steps to prepare and involve reactions with
expensive reagents such as AgSCF3, (diethylamino)sulfur trifluoride
(DAST), or the Ruppert−Prakash reagent (CF3SiMe3).
Figure 2. Electrophilic trifluoromethylthiolation reagents.
Results and Discussion
Indole is a well-studied substrate for trifluoromethylthiolation.[19,21]
A
reaction of 1:1.5:1.5 indole/CF3SOCl/(EtO)2P(O)H in MeCN was
o
carried out at 90 C for 6 h. This condition is similar to our previous
reported for the CF3SO2Cl/(EtO)2P(O)H system.[21b] Product 4a was
obtained in 36% yield (Table 1, entry 1), together with 9% yield of
trifluoromethylsulfoxidation product 4a’. After testing other reductants
(Table 1, entries 2-4), it was found that the reaction with PPh3 gave a
good yield of 86%. Considering CF3SOCl has disproportionation
capability to generate CF3SCl by self reduction,[24] a reaction of
CF3SOCl (1.5 equiv) without using phosphorus as a reductant was
conducted (Table 1, entry 5). To our delight, 26% yield of 4a was
observed. Increased the amounts of CF3SOCl from 1.5 to 3 equiv, the
yield of 4a steadily increased from 26% to 83% (Table 1, entries 6-8).
Figure 1. SCF3-containing biologically active compounds.
Stable and readily available CF3SO2Na (Langlois reagent) was
recently introduced to generate CF3S+ in situ under reductive and
[a]Prof. Dr. W. Yi, L. Jiang, Q. Yan, R. Wang, T. Ding
School of Chemical Engineering, Nanjing University of Science and
Technology
It
is
worth
noting
that
a
significant
amount
of
200 Xiao Ling Wei Street, Nanjing 210094 (China)
E-mail: yiwb@njust.edu.cn
[b]Prof. Dr. W. Zhang
Department of Chemistry, University of Massachusetts Boston
100 Morrissey Boulevard, Boston, MA 02125 (USA)
E-mail: wei2.zhang@umb.edu
trifluoromethylsulfoxidation product 4a’ was observed from the
reaction mixture, especially from the reactions with a low loading of
CF3SOCl. The screening of solvents revealed that MeCN is better than
ClCH2CH2Cl (DCE), PhMe and DMF for the reaction of indole (Table
1, entries 9-11).
Supporting information for this article is given via a link at the end of the
document.
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Table 1: Optimization of trifluoromethylthiolation with CF3SOCl[a]
Entry
3 (equiv)
Solvent
Reductant
(1.5 equiv)
4a/4a’
(%)[b]
1
2
1.5
1.5
1.5
1.5
1.5
2
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DCE
(EtO)2P(O)H
36/9
31/10
66/8
(MeO)2P(O)H
3
PPh2Cl
4
PPh3
86/5
Scheme 2. Proposed Mechanism for trifluoromethylthiolation of indole
5
-
-
-
-
-
-
-
26/40
44/31
65/20
83/8
6
two thiophenes were conducted in DCE gave better results than in
MeCN to afford 4p and 4q in 72% and 64% yields, respectively.
7
2.5
3
8
9
3
32/10
44/21
trace
Table 2. Trifluoromethylthiolation of indoles and thiophenes
10
3
PhMe
11
3
DMF
[a] Reaction conditions: indole (0.2 mmol), solvent (1 mL), under N2 at 90 oC for
6 h; [b] Yield determined by 19F NMR using PhCF3 as an internal standard.
Results in Table 1 show that reactions using CF3SOCl (1.5
equiv)/PPh3 (1.5 equiv) or using CF3SOCl (3 equiv) without an
additional reductant gave similar results (Table 1, entries 4 and 8).
[21a]
Previously reported CF3SO2Cl/(EtO)2P(O)H[21b] and CF3SO2Cl/PPh3
reaction systems both generated CF3S+ as a reactive species for
trifluoromethylthiolation. To confirm if CF3SCl was generated from the
reaction of CF3SOCl in the absence of a reductant, a sample of CF3SOCl
o
in MeCN was heated at the reaction temperature of 90 C for 1 h. 19F
NMR analysis of the sample gave two new signals at δ -46.27 and -75.64
ppm for CF3SCl and CF3SO2Cl, respectively. A control reaction of
indole using only 1.0 equiv of CF3SOCl was also conducted (Scheme
1a). Trifluoromethylsulfoxidation product 4a’ was obtained in 63%
yield. Compound 4a’ was then reacted with 1 equiv of CF3SOCl at 90
oC for 1 h to afford trifluoromethylthiolation product 4a in 41% yield
(Scheme 1b). The yield of 4a was increased to 60% if 2 equiv of
CF3SOCl was used.
Reaction conditions: Indole (or thiophene) (0.2 mmol), 3 (0.6 mmol), in MeCN or
DCE (1 mL) under N2 at 90 oC for 6 h; isolated yields; [a] Yield was determined
by 19F NMR using PhCF3 as an internal standard.
A reaction of benzothiophene under the standard conditions only gave
product 4r in less than 10% yield (Table 2, entry 1). It was suggested
that a catalyst may needed for a better conversion. After screening of Cu
and Ag catalysts as well as solvents, it was found that the reaction with
0.2 equiv of Ag2CO3 in PhMe at 110 oC for 12 h resulted 4r in 84% yield
(Table 2, entry 7). We speculated that Ag2CO3 acts as a base to remove
the trace amount of HCl which could be generated from CF3SOCl or
SOCl2 by reacting with residual water in hygroscopic CF3SO2Na. Under
the siliver-promoted conditions, reactions of halogen-substituted
benzothiophenes, 2-butylbenzofuran, and indene gave the products 4s-v
in 63-78% yields (Table 3).
α-Trifluoromethylthiolated carbonyl compounds have gained
growing interest in recent years due to special properties imparted by the
trifluoromethylthio group.[25] Extension for the scope of CF3SOCl
reaction for ketones was attempted (Table 4). The synthesis of 5a-c from
indanone derivatives, 5d-e from tetralone derivatives, 5f from
Scheme 1. Formation of 4a’ and its reaction with CF3SOCl for 4a
Results from the control experiment and literature[21,24] allowed us to
propose two possible pathways for CF3SOCl trifluoromethylthiolation
(Scheme 2). Heating CF3SOCl with indole at the reaction temperature
o
of 90 C resulted trifluoromethylsulfoxylated compound 4a’. It is then
reduced with CF3SOCl to form product 4a. CF3SOCl could also undergo
disproportionation to form CF3SO2Cl and CF3SCl. The CF3SCl reacts
with indole to give the direct trifluoromethylthiolation product 4a.
Reactions of a series of substituted indoles under the optimized
conditions were conducted (Table 2). Reactions of indoles bearing Me,
MeO, halogen, or ester groups at the 5-position generated corresponding
products 4b-f in high yields. Reactions of indoles with Me or halogen
groups at 6- or 7-position gave 4g-m also in good yields. Reactions with
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Table 2: Metal-catalyzed trifluoromethylthiolation of benzothiophene
benzylacetones also processed smoothly to afford products 5o-p.
Trifluoromethylthiolation of ketones with CF3SOCl shown in Table 4
would not be achieved by previously reported reactions with CF3SO2Na
or CF3SO2Cl.[19,21]
We have previously reported CF3SO2Cl-based reaction of thiols in the
synthesis of trifluoromethylthiolated disulfides.[21b] CF3SOCl was also
able to react with thiols to generate disulfides in CH2Cl2 (Table 5). In
addition to the reaction of substituted thiophenols for 6a-i, benzyl thiol
and naphthalene-1-thiol also gave products 6j and 6k in good yields.
Under the same conditions, reaction of benzeneselenol afforded
trifluoromethylthiolated product 6l in 90% yield.
Entry
Cat. (0.2 equiv)
-
Yield[a]
<10%
22%
1
2
3
4
5
6
7
CuCl
CuI
26%
Cu2O
17%
AgNO3
AgF
78%
67%
Ag2CO3
84%
Table 5. Trifluoromethylthiolation of thiols and benzeneselenol
Conditions: benzothiophene (0.2 mmol), 3 (0.6 mmol), PhMe (1 mL), under N2; [a]
Yields were determined by 19F NMR using PhCF3 as an internal standard.
Table 3. Trifluoromethylthiolation of other aromatic compounds
Reaction conditions: benzothiophene, benzofuran or indene (0.2 mmol), 3 (0.6 mmol),
Ag2CO3 (0.04 mmol) in toluene (1 mL) under N2 at 110 oC for 12 h; Isolated yields
Table 4. Trifluoromethylthiolation of ketones
Reaction conditions: thiol or benzeneselenol (0.2 mmol), 3 (0.6 mmol), in DCE (1
mL) under N2 at 90 oC for 1 h; isolated yields.
Bifunctionalization is an atom economic way to introduce functional
groups to alkenes and alkynes.[26] Several CF3SO2Cl-initiated
bifunctionalization reactions have been reported in the literature.[27]
After successful trifluoromethylthiolation of heterocycles and thiols
with CF3SOCl, we explored CF3S-based bifunctionalization with this
reagent. To our surprise, by simply increasing the reaction time from 6
h to 20 h, 2-chloro-3-trifluoromethylthio-substituted indole 7a was
obtained in 52% yield. Reactions of various indoles under this condition
afforded 7b-k in good yields, except for 7l which has a NO2 group to
deactivate the indole ring (Table 6). The structure of bifunctionalized
product 7d was confirmed by single crystal x-ray analysis. Very recently,
the Liu group reported a similar transformation using POCl3 as
chlorination reagent.[28] We attempted to gain some insights into the
reaction mechanism. 19F NMR analysis of this reaction process showed
that 4a is an intermediate piror to the Chlorotrifluoromethylthiolated
product 7a, which means that 7a was formed by chlorination of 4a. To
gain more insights, especially for the chlorination of 4a, several control
experiments conducted (Scheme 3). The results showed that both
CF3SO2Cl and CF3SOCl contributed to the chlorination, and their
mixture were more efficient.
In addition to the bifunctionalization of indoles, we also explored
bifunctionalization of alkenes and alkynes through 1,2-addition. We
have noticed that Shen group’s report on formoxy-, acetoxy-, or
Reaction conditions: ketone (0.2 mmol), 3 (0.6 mmol), in toluene (1 mL) under N2 at
110 oC for 12 h, isolated yields; [a] 0.2 equiv Ag2CO3 was used.
hydroxy-trifluoromethylthiolation
of
styrenes
with
1-benzosuberone, and 5g from 1-phenyl-1,3-butanedione all gave >80%
yields, but only 49% yield for 5h from acetophenone. However, addition
of 0.2 equiv of Ag2CO3 increased the yield of 5h to 81%. Thus, under
the siliver-promoted conditions, reactions of seven acetophenone
derivatives afforded products 5h-n in >70% yields. Reactions of
N-trifluoromethylthiodibenzenesulfonimide 1d in different reaction
solvents.[13] It was determined that the solvent was crucial for the
reaction, and DMF is favorable for the chlorotrifluoromethylthiolation
reaction of styrene with CF3SOCl. Thus, reaction of a series of styrene
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Table 6. Bifuctional chlorotrifluoromethylthiolation of indoles
Table 7. Chlorotrifluoromethylthiolation of alkenes
Reaction conditions: styrene derivative (0.2 mmol), 3 (0.6 mmol), in DMF (1 mL) under
N2 at 90 oC for 1 h; isolated yields.
Table 8. Chlorotrifluoromethylthiolation of alkynes
Reaction conditions: Indole (0.2 mmol), 3 (0.6 mmol), in MeCN (1 mL) under N2 at 90
oC for 20 h; isolated yields.
Scheme 3. Chlorination of 4a under different conditions
derivatives with CF3SOCl in DMF at 90 oC for 1 h afforded 8a-k in good
yields (Table 7). Reaction of two nonstyrene-type alkenes afforded 8l
and 8m in >80% yields. The regiochemistry of the bifunctionalized
products was confirmed by 1H NMR analysis,[21e] 8a-8l were
Markovnikov products while 8m was produced in high anti-
Markovnikov selectivity. The regiochemistry was similar to our
previous CF3SO2Cl/PPh3/DMF system,[21e] which made us believe that
the process of bifunctionalization of alkenes is also an electrophilic
addition by the decomposition product CF3SCl.
Reaction conditions: alkyne (0.2 mmol), 3 (0.6 mmol), in DMF (1 mL) under N2 at 90
oC for 6 h, isolated yields.
The extension of the scope of bifunctionalization for alkynes was also
derivatives with CF2HSO2Cl afforded 10a-10f in good yields. Ketones
were also tested under similar conditions. Research on direct
difluoromethylthiolation of kentones are very limited up to now.
Reactions of a series of indanone derivatives with CF2HSO2Cl gave
difluoromethylthiolated 11a-10f in 73-90% yields. Other ketones like
1-tetralone and 1-acenaphthenone also afforded corresponding products
11g and 11h in 82% and 73% yields, respectively.
achieved using DMF as
a solvent. Reactions of a series of
phenylacetylenes and other alkynes with CF3SOCl under catalyst-free
conditions at 90 °C for 6 h afforded products 9a-o in 52-92% yields
(Table 8). It seems that the CF3SOCl system was more efficient than our
previously reported CF3SO2Cl/PPh3 system and higher yields were
obtained. Similar to alkenes, 9a-9l were found to be Markovnikov
products while 9m and 9n were anti-Markovnikov products by 1H NMR
analysis.[21e] Different from our previous report, internal alkyens, for
example, 1,2-diphenylethyne, was also applicable to give the product 9o
in 70% yield (9o).
Conclusions
The SCF2H-containing molecules have also shown to be uniquely
effective in bioactive compounds.[29] To our delight, CF2HSOCl was
successfully synthesized by using CF2HSO2Na (see Experimental
Section for details). Next, we sought to extended the reaction scope for
difluoromethylthiolation (Table 9). Reactions of a series of indole
In summary, CF3SOCl is introduced as a new reagent for electrophilic
trifluoromethylthiolation and bifunctionalization. The new reaction
process is different from previously reported methods using CF3SO2-
based reagents such as CF3SO2Na and CF3SO2Cl. The SOCF3
intermediate was first generated and then reduced by CF3SOCl to form
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Table 9. Difluoromethylthiolation using CF2HSOCl
General procedure for Trifluoromethylthiolation of Kentones
(5a-5p).
A 10 mL oven-dried reaction vessel was charged with a ketone (0.2
mmol), trifluoromethansulfinyl chloride (3, 0.6 mmol) (for 5i-5p, silver
carbonate (Ag2CO , 0.04 mmol) was also added). Toluene (1 mL) was
added to the sealed reaction vessel by syringe. The resulting solution was
0
stirred under N2 at 110 C for 12 h. After cooling to room temperature
the volatiles were removed under vacuum and the residue was purified
by column chromatography to give the corresponding
trifluoromethylthiolated product.
General Procedure for Reaction of Thiols and Benzeneselenol for
6a-l
A 10 mL oven-dried reaction vessel was charged with a thiol or
benzeneselenol (0.2 mmol) and trifluoromethansulfinyl chloride (3, 0.6
mmol). Dichloroethane (1 mL) was added to the sealed reaction vessel
by syringe. The resulting solution was stirred under N2 at 90 0C for 1 h.
After cooling to room temperature the volatiles were removed under
vacuum and the residue was purified by column chromatography to give
the corresponding trifluoromethylthiolated product.
Reaction conditions: indole or ketone (0.2 mmol), CF2HSOCl (0.6 mmol), in MeCN (1
mL) under N2 at 90 oC for 6 h (for indole) or in toluene (1 mL) under N2 at 110 oC for
12 h (for ketone), isolated yields; isolated yields.
General Procedure for Chlorotrifluoromethylthiolation of
Indoles for 7a-k
A 10 mL oven-dried reaction vessel was charged with an indole (0.2
mmol) and trifluoromethansulfinyl chloride (3, 0.6 mmol). Acetonitrile
(1 mL) was added to the sealed reaction vessel by syringe. The resulting
solution was stirred under N2 at 90 0C for 20 h. After cooling to room
temperature the volatiles were removed under vacuum and the residue
was purified by column chromatography to give the corresponding
chlorotrifluoromethylthiolated product.
SCF3 product. Meanwhile, CF3SOCl also generates reactive CF3S+
through self-disproportionation. Under catalyst-free conditions,
CF3SOCl is able to trifluoromethylthiolate indoles, ketones, thiols and
benzeneselenols effectively without an additiona reductant. In the
present of Ag2CO3 catalyst, CF3SOCl reacts with benzothiophenes,
benzofurans and indenes. In addition, by simply increasing the reaction
time or changing the reaction solvent, 1,2-bifunctional
chlorotrifluoromethylthiolation could be achieved for indoles, alkenes
and alkyens. CF2HSOCl was also successfully synthesized and used for
difluoromethylthiolation under the catalyst-free conditions.
General Procedure for Chlorotrifluoromethylthiolation of
Alkenes for 8a-m
A 10 mL oven-dried reaction vessel was charged with an alkene (0.2
mmol) and trifluoromethansulfinyl chloride (3, 0.6 mmol). DMF (1 mL)
was added to the sealed reaction vessel by syringe. The resulting solution
was stirred under N2 at 90 0C for 1 h. After cooling to room temperature
the volatiles were removed under vacuum and the residue was purified
by column chromatography to give the corresponding
chlorotrifluoromethylthiolated product.
Experimental Section
General Procedure for Reaction of Indoles for 4a-o
A 10 mL oven-dried reaction vessel was charged with an indole (0.2
mmol) and trifluoromethansulfinyl chloride (3, 0.6 mmol). Acetonitrile
(1 mL) was added to the sealed reaction vessel by syringe. The resulting
General Procedure for Chlorotrifluoromethylthiolation of
Alkynes for 9a-o
A 10 mL oven-dried reaction vessel was charged with an alkyne (0.2
mmol) and trifluoromethansulfinyl chloride (3, 0.6 mmol). DMF (1 mL)
was added to the sealed reaction vessel by syringe. The resulting solution
was stirred under N2 at 90 0C for 6 h. After cooling to room temperature
the volatiles were removed under vacuum and the residue was purified
by column chromatography to give the corresponding
chlorotrifluoromethylthiolated product.
0
solution was stirred under N2 at 90 C for 6 h. After cooling to room
temperature the volatiles were removed under vacuum and the residue
was purified by column chromatography to give the corresponding
trifluoromethylthiolation substituted products.
General Procedure for Reaction of Thiophenes for 4p, 4q
A 10 mL oven-dried reaction vessel was charged with a thiophene
(0.2 mmol) and trifluoromethansulfinyl chloride (3, 0.6 mmol).
Dichloroethane (1 mL) was added to the sealed reaction vessel by
syringe. The resulting solution was stirred under N2 at 90 0C for 6 h.
After cooling to room temperature the volatiles were removed under
vacuum and the residue was purified by column chromatography to give
the corresponding trifluoromethylthiolation substituted products.
General Procedure for the synthesis of 4r-v
Synthesis of CF2HSOCl
A 10 mL oven-dried reaction vessel was charged with CF2HSO2Na
(10g, 72.5 mmol) and benzyltriethylammonium chloride (0.5g, 2.2
mmol). Toluene (30 mL) was added to the sealed reaction vessel by
syringe. Thionyl chloride (SOCl2) was added dropwise under vigorous
stirring at room temperature, and the mixture was kept for 18 h. The 19
NMR showed that the conversion ratio was about 70%.
F
A
10 mL oven-dried reaction vessel was charged with
a
For the isolation of CF2HSOCl, the crude mixture was filtered by
Silica gel, and the residue was washed by toluene (20 ml). The collected
liquid contains CF2HSOCl and toluene, which cannot be separated by
small-scale distillation. The sample of CF2HSOCl containing traces of
toluene was obtained by fractional distillation through a 15-cm column
with glass filling.
benzothiophene, benzofuran or indene (0.2 mmol),
trifluoromethansulfinyl chloride (3, 0.6 mmol) and silver carbonate
(Ag2CO3, 0.04 mmol). Toluene (1 mL) was added to the sealed reaction
vessel by syringe. The resulting solution was stirred under N2 at 110 0C
for 12 h. After cooling to room temperature the volatiles were removed
under vacuum and the residue was purified by column chromatography
to give the corresponding trifluoromethylthiolated product.
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General Procedure for Difluoromethylthiolation of Indoles for
10a-f
A 10 mL oven-dried reaction vessel was charged with an indole (0.2
mmol) and difluoromethansulfinyl chloride (0.6 mmol). Acetonitrile (1
mL) was added to the sealed reaction vessel by syringe. The resulting
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0
solution was stirred under N2 at 90 C for 6 h. After cooling to room
temperature the volatiles were removed under vacuum and the residue
was purified by column chromatography to give the corresponding
difluoromethylthiolation substituted products.
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General Procedure for Difluoromethylthiolation of Kentones for
11a-h
A 10 mL oven-dried reaction vessel was charged with a ketone (0.2
mmol), difluoromethansulfinyl chloride (0.6 mmol). Toluene (1 mL)
was added to the sealed reaction vessel by syringe. The resulting solution
was stirred under N2 at 110 0C for 12 h. After cooling to room
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was purified by column chromatography to give the corresponding
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Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (21776138, 21476116), Fundamental Research
Funds for the Central Universities (30916011102, 30918011314),
Natural Science Foundation of Jiangsu Province (BK20180476),
Qing Lan and Six Talent Peaks in Jiangsu Province, Priority
Academic Program Development of Jiangsu Higher Education
Institutions, and the Centre for Green Chemistry at the University of
Massachusetts Boston and the Center for Advanced Materials and
Technology in Nanjing University of Science and Technology for
financial support. We also acknowledge the Bruker DRX 500 at
Analysis and Test Center Nanjing University of Science and
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Author Contributions
‡ L. Jiang and Q. Yan contributed equally
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Keywords: Trifluoromethanesulfinyl Chloride
• Reductant-free •
Trifluoromethythiolation• Bifunctional Chlorotrifluoromethythiolation
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10.1002/chem.201804027
Chemistry - A European Journal
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Lvqi Jiang, Qiang Yan, Rongkang Wang, Tianqi
Ding, Wenbin Yi* and Wei Zhang*
Page No. – Page No.
Trifluoromethanesulfinyl Chloride for
Electrophilic Trifluoromethythiolation and
Bifunctional Chlorotrifluoromethythiolation
Trifluoromethanesulfinyl chloride (CF3SOCl) is introduced as a new reagent for C-H
trifluoromethylthiolation of indoles, thiophenes, ketones, thiols and benzeneselenols, as
well as 1,2-chlorotrifluoromethylthiolation of indoles, styrenes, and alkyens.
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