Cu-mediated oxidative trifluoromethylthiolation of arylboronic acids with (bpy)CuSCF3

Article abstract of DOI:10.1016/j.jfluchem.2017.01.007

An efficient trifluoromethylthiolation reaction of arylboronic acids with (bpy)CuSCF₃in the presence of oxygen at room temperature is described. This method produces a variety of aryl trifluoromethylthioether derivatives in good to high yield. The mechanism of this trifluoromethylthiolation is discussed as well.

Full text of DOI:10.1016/j.jfluchem.2017.01.007

Accepted Manuscript
Title: Cu-Mediated Oxidative Trifluoromethylthiolation of
Arylboronic Acids with (bpy)CuSCF3
Author: <ce:author id="aut0005"
author-id="S0022113916304833-
b2f25a7498636c336534da0361705913"> Mingzhu
Zhao<ce:author id="aut0010"
author-id="S0022113916304833-
05079f887e326f7ffe4caa17e36b5bdb"> Xiaoming
Zhao<ce:author id="aut0015"
author-id="S0022113916304833-
6e002966fafb4921f9c90100809bd88f"> Purui
Zheng<ce:author id="aut0020"
author-id="S0022113916304833-
951c2e121f7ae73df7a850d1fc495755"> Yawei
Tian
PII:
S0022-1139(16)30483-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2017.01.007
FLUOR 8932
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
29-11-2016
7-1-2017
7-1-2017
Please cite this article as: Mingzhu Zhao, Xiaoming Zhao, Purui
Zheng, Yawei Tian, Cu-Mediated Oxidative Trifluoromethylthiolation of
Arylboronic Acids with (bpy)CuSCF3, Journal of Fluorine Chemistry
http://dx.doi.org/10.1016/j.jfluchem.2017.01.007
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

Journal
of
Fluorine
Chemistry
journal homepage: www.elsevier.com
Cu-Mediated Oxidative Trifluoromethylthiolation of Arylboronic Acids with
(bpy)CuSCF3
Mingzhu Zhao, Xiaoming Zhao*, Purui Zheng, and Yawei Tian
Shanghai Key Lab of Chemical Assessment and Sustainability, Department of Chemistry, Tongji University, 1239 Siping Road, Shanghai 200092, China

Graphical abstract
Cu-mediated oxidative trifluoromethylthiolation of aryl boronic acids with (bpy)CuSCF3 under mild
conditions is presented, giving aryl trifluoromethylthioethers in good to excellent yield.
O2 balloon
+
Ar
(bpy)CuSCF3
B(OH)2
Ar SCF3
NMP, rt, 1h
up to 98% yield
23 examples
Ar = aryl
Highlights:
 Use of aryl boronic acids and (bpy)CuSCF3.
 Tolerance a wide range of functional groups on the aryl ring.
 Under mild conditions.
ARTICLE INFO
ABSTRACT
Article history:
Received
An efficient trifluoromethylthiolation reaction of arylboronic acids with (bpy)CuSCF3 in the
presence of oxygen at room temperature is described. This method produces a variety of aryl
Received in revised form
Accepted
trifluoromethylthioether derivatives in good to high yield.
trifluoromethylthiolation is discussed as well.
The mechanism of this
Available online
2016 Elsevier B.V. All rights reserved.
Keywords:
Trifluoromethylthiolation
Arylboronic acid
(bpy)CuSCF3
Copper
Oxidation
1. Introduction
Trifluoromethylthiolated compounds have received incredible attention since SCF3 with strong electron-withdrawing character
makes organic compounds more lipophilic than that of trifluoromethyl group (the greatest Hansch constant π = 1.44 for SCF3 vs. 0.88
for CF3) [1]. These could enhance the drug molecule’s cell membrane permeability and improve the pharmacokinetics and efficacy [2].
SCF3-containing lead compounds have been increasing in medicinal chemistry during the recent decade [3]. Therefore, new practical
method for the synthesis of trifluoromethylthiolated compounds is highly desirable. There are four representative examples such as the
coccidiostatic Toltrazuril [4], the parenteral cephalosporin Cefazaflur [5], the Dopamine antagonists [6], and the inhibitor of ubiquitin-
activating enzyme for the treatment of cell proliferation disorders TAK-243 [7] (Fig. 1).
Several methods for C-SCF3 bond formation were reported [8]; for example, trifluoromethylthioethers were prepared through the
radical reaction and electrophilic of CF3SCl [9]. Indirect trifluoromethylthiolation strategies involved trifluoromethylation of sulfur-
containing compounds including thiols, thiolates, and disulfides [10]. The substitution of halogen atoms by fluorine in aryl
polyhalogenalkyl sulfides provided synthetic route toward aryl trifluoromethyl sulfides [11]. These methods required preformation of
the thiolated precursors and suffer from either harsh conditions or limited substrate scope [12]. Recently, several shelf-stable and
conveniently handled trifluoromethylthio reagents have been developed, which demonstrated potential in the electrophilic
trifluoromethylthiolation of alkenes, alkynes, and aromatic compounds [13]. In recent decade, either metal-mediated or metal-catalyzed
trifluoromethylthiolation has been withdrawing great attention [14]. Among these methods, trifluoromethylthiolations of arylboronic
acids with trifluoromethylthio reagent such as hypervalent iodine [15], N-(trifluoromethylthio)-phthalimide [16], Me4NSCF3 [17],
TMSCF3 and S8 have also been reported [18]. Although some trifluoromethylthiolation reactions proceed under mild conditions, they
need either long reaction time or excessive trifluoromethylthio reagent. Recently, Weng reported an elegant air-stable (bpy)CuSCF3
and its application in trifluoromethylthiolation with aryl halides [19] (eq 1 in Scheme 1), allylic bromides [20], and benzyl bromides
[21]. Nevertheless, use of (bpy)CuSCF3 in cross-coupling trifluoromethylthiolation has less reported. Herein, we report Cu-mediated
oxidative cross-coupling trifluoromethylthiolation of arylboronic acids with (bpy)CuSCF3, which provides trifluoromethylthiolated
products (eq 2 in Scheme 1).

2. Results and discussion
Initially, we conducted a model reaction of (bpy)CuSCF3 1 with 4-biphenylboronic acid 2a in DCM at room temperature for 1h
under air atmosphere. To our delight, the formation of biphenyl-4-yl(trifluoromethyl)sulfane 3a was observed in a 25% yield (entry 1).
The subsequent examination of additives such as 4Å MS, triethylamine (TEA) and Cs2CO3 indicated that the improvement in yield was
not achieved (entries 2-4). Interestingly, the reaction was carried out under oxygen atmosphere instead of air and the yield of 3a was
improved from 25 to 50% (entry 1 vs. entry 5). Under oxygen atmosphere, we further screened the solvents. For example, the
halogenated solvents (CHCl3 and DCE) gave 3a in comparable yields (entries 6-7). However, THF, dioxane, EtOAc, toluene, and
acetone gave acceptable to moderate yield (entries 8-12). Both diglyme and MeOH resulted in the similar yields (entries 13-14).
Notably, the protic solvent (iPrOH) was deleterious for this reaction (entry 15). More significantly, the aprotic polar solvents such as N-
methyl-2-pyrrolidone (NMP), MeCN, DMSO, DMF were examined. NMP gave the best result (entry 16), whereas others led to good
results (entries 17-19). We next tested the different reaction temperature (entries 20-21). When the reaction was conducted at 0 C and
it underwent slowly (entry 20). The reaction at 50 C resulted in a slight lowering yield (entry 21) Furthermore, (bpy)CuSCF3 (0.1
equiv) 1 was used and it gave a trace amount of 3a.
With the optimized conditions shown in entry 16 of Table 1 in hand, the scope of various arylboronic acids 2 with (bpy)CuSCF3 1
were explored and the results were summarized in Table 2. The benzeneboronic acid 2b and arylboronic acids 2b-2i with either
electron-rich (e.g., Ph, Me, o-OMe, p-OMe, m-OMe) or electron-poor (e.g., p-F, p-Cl and p-Br) group on the phenyl ring gave the
corresponding products 3a-3i in good to high yield, except for 2g, in which an ortho effect (a 52% yield of 3g) was observed (Table
2). Interestingly, the substrates with halogen (e.g., p-F, p-Cl and p-Br) on the phenyl ring were still tolerated. Moreover, the
trifluoromethylthiolation reaction of arylboronic acid 2j-2q was also tolerant of the varying functional groups such as hydroxy,
aldehyde, ketone, ester, cyano, nitro and sulfone (Table 2). It was noteworthy that 1-naphthylboronic acid 2r performed well in spite of
the ortho-effect (3r vs. 3s). In addition, both 9-anthraceneboronic acid 2t and 9-phenanthreneboronic acid 2u were suitable for this
trifluoromethylthiolation, giving more than 80% yields of 3t-3u. Furthermore, the heterocyclic boronic acids 1v-1w were compatible
with the reaction conditions and showed good reactivity (Table 2).
To gain insight into the trifluoromethylthiolation process, we carried out five control experiments. We found that the yields of
trifluoromethylthioether 3a decreased from 96% to 75% when the atmosphere was changed from O2 to air (eq 1 in Scheme 2). Trace
amount ArSCF3 3a was observed when the reaction performed under argon (eq 2). Under the optimal conditions, TEMPO (1.0 equiv),
a radical scavenger, was tested and 88 % of 3a was obtained (eq 3); a trace amount of 3a was observed under argon (eq 4). These results
suggest that the formation of free radical intermediates is unlikely, and that oxygen instead of TEMPO works as an oxidizing agent for
this trifluoromethylthiolation. 2-Phenylethylboronic acid 2w failed to take place this reaction, which was in consistent with the
oxidative coupling pathway supposition [22] (eq 5).
Given these observations, a cross coupling mechanism for this reaction is proposed (Fig. 2.). In the presence of O2, an oxidative
addition of (bpy)CuSCF3 1 to arylboronic acid 2 followed by a transmetallation gives Int A, which is in the equilibrium with Int B
oxidizing by O2. Both Int A and Int B could undergo reductive elimination to afford the aryl trifluoromethylthioether 3. The reductive
elimination rate of Int B undergoes faster than that of Int A. These give rational explanation on the effect of oxygen on this
transformation [23].
To illustrate the synthetic value of the trifluoromethylthioethers 3 generated by this method, the preparative scale reaction was
performed under the standard conditions.
The (bpy)CuSCF3
1
(1.28 g, 4.0 mmol) reaction with (4-
((methoxycarbonyl)amino)phenyl)boronic acid 4 (940 mg, 4.8 mmol) led to 5 (810 mg, in 81% isolated yield), the fungicide and
herbicide (Scheme 3), which was synthesized by thiophenol and suffered from the harsh conditions [24].
3. Conclusion
In conclusion, we developed a trifluoromethylthiolation of arylboronic acids with (bpy)CuSCF3 under the mild conditions, which
gave the corresponding trifluoromethylthioethers in fair to high yield. This method allows the use of oxygen atmosphere, tolerates
various functional groups, and provides a new way to aryl trifluoromethylthioethers.
4. Experimental
4.1. General
1H NMR (TMS as the internal standard), 19F NMR spectra and 13C NMR was recorded on Bruker AM400 spectrometer. 1H NMR
spectra were obtained at 400 MHz and recorded relative to tetramethylsilane signal (0 ppm) or residual protic solvent. 13C NMR spectra
1
were obtained at 100 MHz and chemical shifts were recorded relative to the solvent resonance (CDCl3, 77.0 ppm). Data for H NMR
are recorded as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, m = multiplet or unresolved, br =
broad singlet, coupling constant (s) in Hz, integration). 19F NMR spectra were obtained at 376 MHz. IR spectra were measured on
Thermo Nicolet spectrometer. GC-MS was conducted on Agilent 8453/5973N. Unless otherwise noted, all reagents and starting
materials were purchased from commercial sources and used without further purification
4.2. General procedure for trifluoromethylthiolation of arylboronic acids
Arylboronic acid 2 (0.12 mmol) and (bpy)Cu(SCF3) 1 (0.1 mmol) were added to a Schlenk flask fitted with magnetic stir bar and O2
balloon. The flask was evacuated and back filled with O2. The solvent NMP (2.0 mL) was added by syringe at room temperature and

the solution was stirred for 1h. For the products reported with isolated yields (3a, 3k, 3l, 3m, 3n, 3o, 3p, 3q, 3r, 3s, 3t, 3u and 3w), the
reaction mixture was diluted with EtOAc, then washed with water and brine. The organic phase was dried over anhydrous Na2SO4 and
filtered. The filtrate was concentrated under reduced pressure and the residue was purified by flash chromatography on silica gel (n-
hexane/ethyl acetate gradient) to afford the desired compounds. Gram-scale synthesis of compound 5 was prepared following the
similar procedure. The relatively volatile products (3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j and 3v) were not isolated and their yields were
determined by 19F NMR measurement in CDCl3 of the reaction mixture. For the products reported with 19F NMR yields, PhOCF3 (1.0
equiv) was added to the reaction mixture as internal standard added after the reaction completed. The reaction mixture was purified by
flash chromatography on silica gel (pentane/diethyl ether gradient) to afford the desired compounds.
4.2.1. 4-[(Trifluoromethyl)thio]biphenyl (3a)
Colorless solid (22.8 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 7.72 (d, J = 8.2 Hz, 2H), 7.66 – 7.62 (m, 2H), 7.60 (dd, J = 5.2, 3.3
Hz, 2H), 7.50 – 7.44 (m, 2H), 7.43 – 7.37 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 143.9 (s), 139.7 (s), 136.8 (s), 129.7 (q, J = 308.2
Hz), 129.0 (s), 128.2 (s), 127.3 (s), 123.1 (q, J = 2.0 Hz). 19F NMR (376 MHz, CDCl3) δ -42.7 (s, 3F). GC-MS (EI, 70eV): m/z (%) =
254 (M+, 79), 185 (M+-CF3, 100), 152 (47), 139 (14), 115 (19), 69 (30). The data corroborate with the literature report [18].
4.2.2. 4-(Trifluoromethylthio)benzene (3b)
1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 7.4 Hz, 2H), 7.49 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.4 Hz, 2H). 13C NMR (101 MHz,
CDCl3) δ 136.4 (s), 130.9 (s), 129.7 (q, J = 307.9 Hz), 129.5 (s), 124.5 (q, J = 1.9 Hz). 19F NMR (376 MHz, CDCl3) δ -42.8 (s, 3F). GC-
MS (EI, 70eV): m/z (%) = 178 (M+, 44), 109 (M+-CF3, 100), 69 (39), 51 (21). The data corroborate with the literature report [10j].
4.2.3. 1-Fluoro-4-[(trifluoromethyl)thio]benzene (3c)
1H NMR (400 MHz, CDCl3) δ 7.65 (dd, J = 8.5, 5.3 Hz, 2H), 7.12 (t, J = 8.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 164.6 (d, J =
252.6 Hz), 138.8 (d, J = 8.9 Hz,), 129.4 (q, J = 305.7 Hz), 119.70 (m), 116.8 (d, J = 22.3 Hz). 19F NMR (376 MHz, CDCl3) δ -43.4 (s,
3F), -108.6 (s, 1F). GC-MS (EI, 70eV): m/z (%) =196 (M+, 49), 127 (M+-CF3, 100), 83 (72), 69 (39), 57 (42). The data corroborate with
the literature report [25].
4.2.4. 1-Chloro-4-[(trifluoromethyl)thio]benzene (3d)
1H NMR (400 MHz, CDCl3) δ 7.58 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 137.7 (s), 137.6 (s),
129.8 (s), 129.4 (q, J = 308.2 Hz), 122.8 (q, J = 2.0 Hz). 19F NMR (376 MHz, CDCl3) δ -42.9 (s, 3F). GC-MS (EI, 70eV): m/z (%) =
214 (21), 212 (M+, 42), 145 (37), 143 (M+-CF3, 100), 108 (70), 69 (79), 63 (36), 50 (24). The data corroborate with the literature report
[10j].
4.2.5. 1-Bromo-4-[(trifluoromethyl)thio]benzene (3e)
1H NMR (400 MHz, CDCl3) δ 7.56 (d, J = 8.5 Hz, 2H), 7.51 (d, J = 8.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 137.8 (s), 132.8 (s),
129.3 (q, J = 308.3 Hz), 126.0 (s), 123.4 (q, J = 2.0 Hz). 19F NMR (376 MHz, CDCl3) δ -42.7 (s, 3F). GC-MS (EI, 70eV): m/z (%) =
258 (M+, 77), 256 (M+, 70), 189 (M+-CF3, 59), 187 (M+-CF3, 50), 108 (100), 69 (70), 63 (33). The data corroborate with the literature
report [18].
4.2.6. 4-(Trifluoromethylthio)toluene (3f)
1H NMR (400 MHz, CDCl3) δ 7.53 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 7.9 Hz, 2H), 2.38 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 141.4
(s), 136.4 (s), 130.3 (s), 129.7 (q, J = 307.9 Hz), 120.92 (q, J = 1.7 Hz), 21.32 (s). 19F NMR (376 MHz, CDCl3) δ -43.2 (s, 3F). GC-MS
(EI, 70eV): m/z (%) = 192 (M+, 82), 123 (M+-CF3, 100), 91 (63), 77 (36), 69 (65). The data corroborate with the literature report [8].
4.2.7. 1-(Methoxy)-2-[(trifluoromethyl)thio]benzene (3g)
1H NMR (400 MHz, CDCl3) δ 7.62 (d, J = 7.6 Hz, 1H), 7.46 (td, J = 8.2, 1.6 Hz, 1H), 7.01 – 6.96 (m, 2H), 3.91 (s, 3H). 13C NMR
(101 MHz, CDCl3) δ 160.6 (s), 138.6 (s), 132.9 (s), 129.6 (q, J = 308.8 Hz), 121.2 (s), 112.5 (q, J = 1.6 Hz), 111.76 (s), 56.05 (s). 19F
NMR (376 MHz, CDCl3) δ -42.4 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 208 (M+, 100), 139 (M+-CF3, 21), 96 (55), 95 (40), 69 (93). The
data corroborate with the literature report [13c].
4.2.8. 1-(Methoxy)-3-[(trifluoromethyl)thio]benzene (3h)
1H NMR (400 MHz, CDCl3) δ 7.32 (t, J = 8.0 Hz, 1H), 7.23 (d, J = 7.9 Hz, 1H), 7.18 (s, 1H), 7.01 (dd, J = 8.2, 1.6 Hz, 1H), 3.81 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 159.98 (s), 130.21 (s), 129.69 (q, J = 307.9 Hz), 128.43 (s), 125.25 (q, J = 1.9 Hz), 121.23 (s),
116.89 (s), 55.41 (s). 19F NMR (376 MHz, CDCl3) δ -42.6 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 208 (M+, 100), 139 (M+-CF3, 41), 124
(55), 96 (54), 95 (65), 69 (82). The data corroborate with the literature report [13c].
4.2.9. 1-(Methoxy)-4-[(trifluoromethyl)thio]benzene (3i)
1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.7 Hz, 2H), 3.83 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 161.9
(s), 138.3 (s), 129.7 (q, J = 308.0 Hz), 115.0 (s), 114.9 (d, J = 2.0 Hz), 55.40 (s).19F NMR (376 MHz, CDCl3) δ -44.0 (s, 3F). GC-MS
(EI, 70eV): m/z (%) = 208 (M+, 53), 139 (M+-CF3, 100), 124 (15), 95 (39), 69 (49). The data corroborate with the literature report [13c].

4.2.10. 4-((Trifluoromethyl)thio)phenol (3j)
1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.5 Hz, 2H), 5.22 (br, 1H). 13C NMR (101 MHz, CDCl3) δ 157.9
(s), 138.6 (s), 129.6 (q, J = 308.0 Hz), 116.6 (s), 115.4 (q, J = 2.1 Hz). 19F NMR (376 MHz, CDCl3) δ -43.9 (s, 3F). GC-MS (EI, 70eV):
m/z (%) = 194 (M+, 37), 125 (M+-CF3, 100), 97 (25), 81 (19), 69 (51), 53 (16). The data corroborate with the literature report [25].
4.2.11. 4-(Trifluoromethylthio)benzaldehyde (3k)
1
Colorless oil (16.4 mg, 80%). H NMR (400 MHz, CDCl3) δ 10.07 (s, 1H), 7.94 (d, J = 8.2 Hz, 2H), 7.82 (d, J = 8.1 Hz, 2H). 13C
NMR (101 MHz, CDCl3) δ 191.2 (s), 137.4 (s), 135.9 (s), 131.7 (q, J = 2.0 Hz), 129.2 (q, J = 308.5 Hz), 130.3 (s). 19F NMR (376 MHz,
CDCl3) δ -41.5 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 206 (M+, 100), 205 (87), 109 (56), 108 (50), 69 (87). The data corroborate with
the literature report [26].
4.2.12. 1-(4-((Trifluoromethyl)thio)phenyl)ethanone (3l)
1
Colorless oil (20.0 mg, 91%). H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.3 Hz, 2H), 7.75 (d, J = 8.2 Hz, 2H), 2.64 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 197.1 (s), 138.5 (s), 135.8 (s), 130.0 (q, J = 2.1 Hz), 129.3 (q, J = 308.4 Hz), 129.1 (s), 26.76 (s). 19F NMR
(376 MHz, CDCl3) δ -41.8 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 220 (M+, 42), 205 (M+-CH3, 100), 136 (27), 108 (45), 69 (78), 43 (72).
The data corroborate with the literature report [14g].
4.2.13. Methyl 4-[(trifluoromethyl)thio]benzoate (3m)
1
Colorless solid (16.7 mg, 71%). H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.3 Hz, 2H), 7.72 (d, J = 8.2 Hz, 1H), 3.95 (s, 1H). 13C
NMR (101 MHz, CDCl3) δ 166.1 (s), 135.6 (s), 132.2 (s), 130.4 (s), 129.9 (q, J = 2.1 Hz), 129.3 (q, J = 308.4 Hz), 52.5 (s). 19F NMR
(376 MHz, CDCl3) δ -41.8 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 236 (M+, 53), 205 (100), 177 (21), 108 (44), 69 (36). The data
corroborate with the literature report [18].
4.2.14. 4-[(Trifluoromethyl)thio]benzonitrile (3n)
Colorless oil (16.6 mg, 82%). 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 8.2 Hz, 2H), 7.72 (d, J = 8.3 Hz, 2H). 13C NMR (101 MHz,
CDCl3) δ 136.0 (s), 133.0 (s), 130.6 (q, J = 2.3 Hz), 129.1 (q, J = 308.7 Hz), 117.6(s), 114.7 (s). 19F NMR (376 MHz, CDCl3) δ -41.5 (s,
3F). GC-MS (EI, 70eV): m/z (%) = 203 (M+, 81), 134 (M+-CF3, 100), 107 (21), 90 (39), 69 (74). The data corroborate with the literature
report [18].
4.2.15. (3-Nitrophenyl)(trifluoromethyl)sulfane (3o)
Yellowish oil (16.7 mg, 75%). 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 8.38 (d, J = 8.3 Hz, 1H), 8.01 (d, J = 7.7 Hz, 1H), 7.67 (t,
J = 8.0 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 148.6 (s), 141.8 (s), 130.8 (s), 130.48 (s), 129.1 (q, J = 308.9 Hz), 126.7 (q, J = 2.2 Hz),
125.78 (s). 19F NMR (376 MHz, CDCl3) δ -42.0 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 223 (M+, 100), 177 (M+-NO2, 26), 127 (32), 108
(M+-NO2-CF3, 83), 95 (40), 69 (70). The data corroborate with the literature report [14a].
4.2.16. 1-(Methylsulfonyl)-4-[(trifluoromethyl)thio]benzene (3p)
1
Yellow solid (20.7 mg, 81%). H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 8.3 Hz, 2H), 7.86 (d, J = 8.2 Hz, 2H), 3.10 (s, 1H). 13C
NMR (101 MHz, CDCl3) δ 142.7 (s), 136.2 (s), 131.6 (q, J = 2.1 Hz), 129.1 (q, J = 308.7 Hz), 128.4 (s), 44.39 (s). 19F NMR (376 MHz,
CDCl3) δ -41.4 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 256 (M+, 100), 241 (M+-CH3, 44), 193 (69), 108 (87), 95 (55), 69 (100). The data
corroborate with the literature report [18].
4.2.17. tert-Butyl (4-((trifluoromethyl)thio)phenyl)carbamate (3q)
White solid (27.2 mg, 93%). 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.5 Hz, 2H), 7.43 (d, J = 8.5 Hz, 2H), 6.68 (s, 1H), 1.52 (s,
9H). 13C NMR (101 MHz, CDCl3), δ 152.3 (s), 141.2 (s), 137.6 (s), 129.6 (q, J = 308.1 Hz). 118.8 (s), 117.2 (q, J = 2.0 Hz), 81.3 (s),
28.3 (s). 19F NMR (376 MHz, CDCl3) δ -43.6 (s, 3F). IR (KBr): max (cm-1) = 3334, 2988, 1701, 1587, 1515, 1400, 1369, 1312, 1156,
1211, 826, 775, 519. GC-MS (EI, 70eV): m/z (%) = 293 (M+, 3), 237 (M+-tBu, 17), 193 (M+-Boc, 41), 124 (M+-Boc-CF3, 100), 80 (35),
57 (48). HRMS (ESI-TOF) m/z calcd. for C12H14F3NNaO2S [M+Na]+: 316.0590; found: 316.0590. The data corroborate with the
literature report [14b].
4.2.18. 1-[(Trifluoromethyl)thio]naphthalene (3r)
1
Colorless oil (19.3 mg, 85%). H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 8.5 Hz, 1H), 8.00 (dd, J = 17.3, 7.7 Hz, 2H), 7.91 (d, J =
8.1 Hz, 1H), 7.66 (m, 1H), 7.58 (m, 1H), 7.51 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 137.9 (s), 135.4 (s), 134.3 (s), 132.4 (s), 129.7 (q,
J = 309.4 Hz), 128.6 (s), 127.7 (s), 126.8 (s), 125.9 (s), 125.6 (s), 121.66 (q, J = 1.8 Hz). 19F NMR (376 MHz, CDCl3) δ -41.4 (s, 3F).
GC-MS (EI, 70eV): m/z (%) = 228 (M+, 100), 159 (M+-CF3, 77), 115 (97), 69 (39). The data corroborate with the literature report [19a].
4.2.19. 2-[(Trifluoromethyl)thio]naphthalene (3s)
Colorless oil (20.9 mg, 92%). 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.88 (d, J = 8.2 Hz, 3H), 7.67 (d, J = 8.0 Hz, 1H), 7.61 –
7.51 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 137.1 (s), 133.9 (s), 133.4 (s), 131.8 (s), 129.7 (q, J = 309.4 Hz), 129.3 (s), 128.2 (s),
128.0 (s), 127.8 (s), 127.0 (s), 121.5 (q, J = 1.9 Hz). 19F NMR (376 MHz, CDCl3) δ -42.5 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 228
(M+, 52), 159 (M+-CF3, 44), 115 (100), 69 (29). The data corroborate with the literature report [10j].
4.2.20. 9-[(Trifluoromethyl)thio]anthracene (3t)
Yellow solid (22.5 mg, 81%). 1H NMR (400 MHz, CDCl3) δ 8.86 (d, J = 8.8 Hz, 2H), 8.66 (s, 1H), 8.05 (d, J = 8.4 Hz, 2H), 7.69 –
7.65 (m, 2H), 7.57 – 7.53 (m, 2H). 13C NMR (101 MHz, CDCl3) δ 136.17 (s), 132.53 (s), 131.78 (s), 129.78 (q, J = 311.4 Hz), 128.92
(s), 127.87 (s), 126.53 (s), 125.69 (s), 117.2 (q, J = 2.1 Hz). 19F NMR (376 MHz, CDCl3) δ -41.2 (s, 3F). GC-MS (EI, 70eV): m/z (%) =
278 (M+, 89), 209 (M+-CF3, 55), 165 (100), 69 (59). The data corroborate with the literature report [14g].

4.2.21. .9-[(Trifluoromethyl)thio]phenanthrene (3u)
White solid (23.0 mg, 83%). mp: 98.3 – 99.8 °C. 1H NMR (400 MHz, CDCl3) δ 8.71 – 8.61 (m, 3H), 8.30 (s, 1H), 7.90 (d, J = 7.9
Hz, 1H), 7.76 – 7.69 (m, 3H), 7.63 (t, J = 7.1 Hz, 1H). 13C NMR (101 MHz, CDCl3) δ 140.2, 132.5, 131.8, 131.2, 131.1, 129.8 (q, J =
309.4 Hz), 129.3, 128.9, 127.5, 127.5, 127.3, 126.9, 123.0, 122.7, 120.6 (q, J = 1.8 Hz). 19F NMR (376 MHz, CDCl3) δ -42.0 (s, 3F). IR
(KBr): max (cm-1)= 3073, 3056, 2925, 1610, 1449, 1244, 1140, 1109, 895, 763, 750, 721. GC-MS (EI, 70eV): m/z (%) = 278 (M+, 65),
209 (M+-CF3, 100), 208 (30), 165 (58), 69 (58). HRMS (ESI-TOF) m/z calcd. for C15H8F3S [M-H]-: 277.0304; found: 277.0344.
4.2.22. 4-(Trifluoromethylthio)pyridine (3v)
1H NMR (400 MHz, CDCl3) δ 8.67 (d, J = 5.7 Hz, 2H), 7.51 (d, J = 5.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 150.6 (s), 135.8 (q,
J = 2.1 Hz), 129.0 (q, J = 308.7 Hz), 127.8 (s). 19F NMR (376 MHz, CDCl3) δ -40.6 (s, 3F). GC-MS (EI, 70eV): m/z (%) = 179 (M+,
100), 110 (M+-CF3, 45), 83 (27), 78 (33), 69 (81), 57 (24), 51(37). The data corroborate with the literature report [25].
4.2.23. 3-((Trifluoromethyl)thio)quinolone (3w)
Colorless solid (19.7 mg, 86%). 1H NMR (400 MHz, CDCl3) δ 9.04 (d, J = 1.5 Hz, 1H), 8.54 (d, J = 1.1 Hz, 1H), 8.17 (d, J = 8.5 Hz,
1H), 7.90 – 7.82 (m, 2H), 7.67 – 7.63 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 154.6 (s), 148.4 (s), 144.8 (s), 131.7 (s), 129.6 (s), 129.2
(q, J = 308.8 Hz), 128.2 (s), 127.9 (s), 118.3 (q, J = 1.9 Hz). 19F NMR (376 MHz, CDCl3) δ -42.3 (s, 3F). GC-MS (EI, 70eV): m/z (%) =
229 (M+, 100), 160 (M+-CF3, 96), 133 (19), 116 (25), 89 (76), 69 (61). The data corroborate with the literature report [25]
4.2.24. tert-Butyl(4-((trifluoromethyl)thio)phenyl)carbamate (5)
White solid (810 mg, 81%). 1H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 8.5 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 6.89 (s, 1H), 3.80 (s,
3H). 13C NMR (100 MHz, CDCl3) δ 153.7, 140.6, 137.6, 129.6 (q, J = 308.1 Hz), 119.0, 117.8 (q, J = 1.8 Hz), 52.7. 19F NMR (376
MHz, CDCl3) δ -43.5 (s, 3F). IR (KBr): max (cm-1)= 3333, 1708, 1598, 1540, 1402, 1314, 1239, 1151, 1110, 836, 769, 678, 520. GC-
MS (EI, 70eV): m/z (%) = 251 (M+, 100), 219 (30), 182 (M+-CF3, 56), 150 (M+-SCF3, 48), 138 (33), 96 (34), 69 (47), 59 (55). HRMS
(ESI-TOF) m/z calcd. for C9H8F3NNaO2S [M+Na]+: 274.0120; found: 274.0123. The data corroborate with the literature report [24].
Acknowledgments
We thank the NSFC (No. 21272175) and Shanghai science and technology commission (14DZ2261100) for generous financial
support.
References
[1] (a) A. Leo, C. Hansch, D. Elkins, Chem. Rev. 71 (1971) 525-616;
(b) C. Hansch, A. Leo, S.H. Unger, K.H. Kim, D. Nikaitani, E.J. Lien, J. Med. Chem. 16 (1973) 1207-1216;
(c) C. Hansch, A. Leo, R.W. Taft, Chem. Rev. 91 (1991) 165-195.
[2] (a) F. Leroux, P. Jeschke, M. Schlosser, Chem. Rev. 105 (2005) 827-856;
(b) F. Qing, Chin. J. Org. Chem. 32 (2012) 815-824;
(c) G. Landelle, A. Panossian, F.R. Leroux, Curr. Top. Med. Chem. 4 (2014) 941-951.
[3] (a) D.R. Langlois, T. Dillard, S. Large, N. Roques, Fluorinated Bio-Active Compounds in the Agricultural and Medical Fields; Brussels: Belgium, 1999;
(b) F. Leroux, P. Jeschke, M. Schlosser, Chem. Rev. 105 (2005) 827-856;
(c) B. Manteau, S. Pazenok, J.-P. Vors, F.R. Leroux, J. Fluorine Chem. 131 (2010) 140-158;
(d) V.N. Boiko, Beilstein J. Org. Chem. 6 (2010) 880-921;
(e) X.-H. Xu, K. Matsuzaki, N. Shibata, Chem. Rev. 115 (2015) 731-764.
[4] (a) P. Laczay, G. Vörös, G. Semjén, Int. J. Parasitol. 25 (1995) 753-756;
(b) P. Pommier, A. Keita, S. Wessel-Robert, B. Dellac, H. C. Mundt, Rev. Med. Vet. 154 (2003) 41-46.
[5] (a) G.W. Counts, D. Gregory, D. Zeleznik, M. Turck, Antimicrob. Agents Chemother. 11 (1977) 708-711;
(b) N. Aswapokee, H. C. Neu, Antimicrob. Agents Chemother. 15 (1979) 444-446.
[6] (a) K.J. Watling, J. Pharm. Pharmacol. 32 (1980) 778-779;
(b). D.C. Remy, S.F. Britcher, S.W. King, P.S. Anderson, C.A. Hunt, W.C. Randall, P. Bélanger, J.G. Atkinson, Y. Girard, C.S. Rooney, J.J. Fuentes, J.A. Totaro,
J.L. Robinson, E.A. Risley, M. Williams, J. Med. Chem. 26 (1983) 974-980.
[7] R. Afroze, I.T. Bharathan, J.P. Ciavarri, P.E. Fleming, J.L. Gaulin, M. Girard, Y. Ye, U.S. Patent 9 290 500, 2016.
[8] (a) G. Landelle, A. Panossian, S. Pazenok, J.-P. Vors, F.R. Leroux, Beilstein J. Org. Chem. 9 (2013) 2476-2536;
(b) T. Liang, C. N. Neumann, T. Ritter, Angew. Chem. Int. Ed. 52 (2013) 8214-8264;
(c) A. Tlili, T. Billard, Angew. Chem. Int. Ed. 52 (2013) 6818-6819;
(d) J. Zheng, L. Wang, J. H. Lin, J. C. Xiao, S.H. Liang, Angew. Chem. Int. Ed. 54 (2015) 13236-13240.
[9] (a) J.F. Harris J. Am. Chem. Soc. 84 (1962) 3148-3153;
(b) J.F. Harris Jr, J. Org. Chem. 31 (1966) 931-935;
(c) D.I. Rossman, A.J. Muller, E.O. Lewis, J. Fluorine Chem. 55 (1991) 221-224;
(d) S. Munavalli, D.K. Rohrbaugh, F.J. Berg, L.R. McMahon, F.R. Longo, H.D. Durst, Phosphorus Sulfur Silicon Relat. Elem. 177 (2002) 1117-1125;
(e) D.K. Rohrbaugh, H.D. Durst, F.R. Longo, S. Munavalli, Phosphorus Sulfur Silicon Relat. Elem. 177 (2002) 2639-2650;
(f) S. Munavalli, R.K. Rohrbaugh, G.W. Wagner, H.D. Durst, F.R. Longo, Phosphorus Sulfur Silicon Relat. Elem. 179 (2004) 1635-1643.
[10] (a) For the selected examples, see: M. Tordeux, C. Francese, C. Wakselman, J. Fluorine Chem. 43 (1989) 27-34;
(b) C.E. Granger, C.P. Fꢀlix, H.P. Parrot-Lopez, B.R. Langlois, Tetrahedron Lett. 41 (2000) 9257-9260;
(c) S. Large, N. Roques, B.R. Langlois, J. Org. Chem. 65 (2000) 8848-8856;
(d) A.M. Sipyagin, V.S. Enshov, A.T. Lebedev, N.K. Karakhanova, Chem. Heterocycl. Compd. 39 (2003) 1022-1028;
(e) C. Pooput, M. Medebielle, W.R. Dolbier, Org. Lett. 6 (2004) 301-303;

(f) M. Goenrich, F. Mahlert, E.C. Duin, C. Bauer, B. Jaun, R.K. Thauer, J. Biol. Inorg. Chem. 9 (2004) 691-705;
(g) L.V. Sokolenko, I.I. Maletina, L.M. Yagupolskii, R.-Y. Tang, P. Zhong, Q.-L. Lin, J. Fluorine Chem. 127 (2006) 948-953;
(h) S. Ebner, B. Jaun, M. Goenrich, R.K. Thauer, J. Harmer, J. Am. Chem. Soc. 132 (2010) 567-575;
(i) H. Yasui, T. Yamamoto, E. Tokunaga, N. Shibata, J. Fluorine Chem. 132 (2011) 186-189;
(j) A. Harsꢁnyi, ꢂ. Dorkꢃ, ꢄ. Csapꢃ, T. Bakꢃ, C. Peltz, J. Rꢁbai, J. Fluorine Chem. 132 (2011) 1241-1246.
[11] (a) For the selected examples, see: E.A. Nodiff, S. Lipschutz, P.N. Craig, M. Gordon, J. Org. Chem. 25 (1960) 60-65;
(b) M. Suda, C. Hino, Tetrahedron Lett. 22 (1981) 1997-2000;
(c) T. Umemoto, S. Ishihara, J. Fluorine Chem. 92 (1998) 181-187;
(d) L. Saint-Jalmes, J. Fluorine Chem. 127 (2006) 85-90;
(e) B.R. Langlois, T. Billard, J.-C. Mulatier, C. Yezeguelian, J. Fluorine Chem. 128 (2007) 851-856;
(f) J.M. Kremsner, M. Rack, C. Pilger, C.O. Kappe, Tetrahedron Lett. 50 (2009) 3665-3668;
(g) B. Gutmann, D. Obermayer, B. Reichart, B. Prekodravac, M. Irfan, J.M. Kremsner, C.O. Kappe, Chem. Eur. J. 16 (2010) 12182-12194.
[12] V.N. Boiko, Beilstein J. Org. Chem. 6 (2010) 880-921.
[13] (a) For the selected examples, see: A. Ferry, T. Billard, B.R. Langlois, E. Bacqué, Angew. Chem. Int. Ed. 48 (2009) 8551-8555;
(b) A. Ferry, T. Billard, E. Bacqué, B.R. Langlois, J. Fluorine Chem. 134 (2012) 160-163;
(c) F. Baert, J. Colomb, T. Billard, Angew. Chem. Int. Ed. 51 (2012) 10382-10385;
(d) X. Shao, X. Wang, T. Yang, L. Lu, Q. Shen, Angew. Chem. Int. Ed. 52 (2013) 3457-3460;
(e) Y.-D. Yang, A. Azuma, E. Tokunaga, M. Yamasaki, M. Shiro, N. Shibata, J. Am. Chem. Soc. 135 (2013) 8782-8785;
(f) X. Shao, C. Xu, L. Lu, Q. Shen, Acc. Chem. Res. 48 (2015) 1227-1326;
(g) S. Arimori, M. Takada, N. Shibata, Dalton Trans. 44 (2015) 19456-19459;
(h) M. Li, J. Guo, X.S. Xue, J.P. Cheng, Org. Lett. 18 (2016) 264-267.
[14] (a) For the selected examples, see: D.J. Adams, A. Goddard, J.H. Clark, D.J. Macquarrie, Chem. Commun. 11 (2000) 987-988;
(b) G. Teverovskiy, D.S. Surry, S.L. Buchwald, Angew. Chem. Int. Ed. 50 (2011) 7312-7314;
(c) C.-P. Zhang, D. A. Vicic, J. Am. Chem. Soc. 134 (2012) 183-185;
(d) J.-B. Xu, X. Mu, P.-H. Chen, J.-X. Ye, G.-S. Liu, Org. Lett. 16 (2014) 3942-3945;
(e) G. Danoun, B. Bayarmagnai, M.F. Grunberg, L.J. Goossen, Chem. Sci. 2014, 5, 1312-1316;
(f) G. Yin, I. Kalvet, U. Englert, F. Schoenebeck, J. Am. Chem. Soc. 137 (2015) 4164-4172;
(g) G. Yin, I. Kalvet, F. Schoenebeck, Angew. Chem. Int. Ed. 54 (2015) 6809-6813;
(h) Y. Yang, L. Xu, S. Yu, X. Liu, Y. Zhang, D.A. Vicic, Chem. Eur. J. 22 (2016) 858-863;
(i) C. Matheis, V. Wagner, L.J. Goossen, Chem. Eur. J. 22 (2016) 79-82.
[15] (a) X. Shao, X. Wang, T. Yang, L. Lu, Q. Shen, Angew. Chem. Int. Ed. 52 (2013) 3457-3460;
(b) X. Shao, C. Xu, L. Lu, Q. Shen, J. Org. Chem. 80 (2015) 3012-3021.
[16] (a) R. Pluta, P. Nikolaienko, M. Rueping, Angew. Chem. Int. Ed. 126 (2014) 1676-1679;
(b) K. Kang, C. Xu, Q. Shen, Org. Chem. Front. 1 (2014) 294-297.
[17] C.-P. Zhang, D.A. Vicic, Chem.-Asian J. 7 (2012) 1756-1758.
[18] C. Chen, Y. Xie, L. Chu, R.-W. Wang, X. Zhang, F.-L. Qing, Angew. Chem. Int. Ed. 51 (2012) 2492-2495.
[19] (a) Z. Weng, W. He, C. Chen, R. Lee, D. Dan, Z. Lai, D. Kong, Y. Yuan, K.-W. Huang, Angew. Chem. Int. Ed. 52 (2013) 1548-1552;
(b) M. Zhang, Z. Weng, Adv. Synth. Catal. 358 (2016) 386-394. (c) Y. Zhang, K. Gan, Z. Weng, Org. Process Res. Dev. 20 (2016) 799-802.
[20] J. Tan, G. Zhang, Y. Ou, Y. Yuan, Z. Weng, Chin. J. Chem. 31 (2013) 921-926.
[21] D. Kong, Z. Jiang, S. Xin, Z. Bai, Y. Yuan, Z. Weng, Tetrahedron 69 (2013) 6046-6050.
[22] (a) For the selected reviews of oxidative cross-coupling reactions, see: J.A. Ashenhurst, Chem. Soc. Rev. 39 (2010) 540-548;
(b) W. Shi, C. Liu, A. Lei, Chem. Soc. Rev. 40 (2011) 2761-2776;
(c) C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 111 (2011) 1780-1824.
[23] (a) For the selected review and papers about Chan-Lam cross coupling reaction, see: G. Evano, N. Blanchard, M. Toumi, Chem. Rev. 108 (2008) 3054-3131;
(b) P.Y.S. Lam, C.G. Clark, S. Saubern, J. Adams, K.M. Averill, D.M.T. Chan, A. Combs, Synlett 5 (2000) 674-676;
(c) A.E. King, L.M. Huffman, A. Casitas, M. Costas, X. Ribas, S.S. Stahl, J. Am. Chem. Soc. 132 (2010) 12068-12073;
(d) H.J. Xu, Y.Q. Zhao, T. Feng, Y.S. Feng, J. Org. Chem. 77 (2012) 2878-2884;
(e) S.Y. Moon, J. Nam, K. Rathwell, W.S. Kim, Org. Lett. 16 (2014) 338-341.
[24] (a) V.G. Koshechko, L.A. Kiprianova, L.I. Fileleeva, Tetrahedron Lett. 33 (1992) 6677-6678;
(b) V.N. Boiko, G.M. Shchupak, J. Fluorine Chem. 69 (1994) 207-212;
(c) V.G. Koshechko, L.A. Kiprianova, L.I. Fileleeva, Z.Z. Rozhkova, J. Fluorine Chem. 70 (1995) 277-278.
[25] B. Exner, B. Bayarmagnai, F. Jia, L.J. Goossen, Chemistry 21 (2015) 17220-17223.
[26] Y. Yang, L. Xu, S. Yu, X. Liu, Y. Zhang, D.A. Vicic, Chemistry 22 (2016) 858-863.

H
N
O
OH
O
O
N
N
N
O
N
N
SCF3
N
S
N
H
O
O
S
N
H
O
SCF3
Toltrazuril
Cefazaflur
OH
O
O
S
HO
HN
NH2
R
N
O
N
N
SCF3
R
N
SCF3
Dopamina antagonists
TAK-243
Fig. 1. Four representative CF3S-containing compounds.

Fig. 2. Plausible mechanism.

Scheme 1. Cu-mediated trifluoromethylthiolation with (bpy)CuSCF3.

B(OH)2
B(OH)2
SCF3
air
+ (bpy)CuSCF3
(eq 1)
(eq 2)
NMP, rt, 1h
Ph
Ph
1
Ph
Ph
2a
2a
3a
, 75%
SCF3
Ar
+ (bpy)CuSCF3
NMP, rt, 1h
1
3a
, trace
B(OH)2
B(OH)2
B(OH)2
SCF3
O2, TEMPO
NMP, rt, 1h
+ (bpy)CuSCF3
(eq 3)
(eq 4)
(eq 5)
Ph
Ph
1
Ph
Ph
2a
3a,
88%
SCF3
Ar, TEMPO
NMP, rt, 1h
+ (bpy)CuSCF3
1
2a
3a,
3w
trace
SCF3
O2
+ (bpy)CuSCF3
NMP, rt, 1h
1
2w
, 0%
Scheme 2. Control experiments.

Scheme 3. Gram-scale reaction.

Table 1
Optimization reaction conditions for a trifluoromethylthiolation of 4-biphenylboronic acid 2a with (bpy)CuSCF3 1a.
Entry Solvent
Additive Atmosphere Yield of 3a (%)b
1
DCM
-
air
4Å MS air
TEA air
Cs2CO3 air
25
2
DCM
18
3
DCM
15
4
DCM
10
5
DCM
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
O2
50
6
CHCl3
DCE
50
7
65
8
THF
65
9
Dioxane
EtOAc
Toluene
Aceton
Diglyme
MeOH
iPrOH
NMP
56
10
11
12
13
14
15
16
17
18
19
20d
21e
68
40
66
53
45
Trace
96 (90)c
67
MeCN
DMSO
DMF
68
70
NMP
90
NMP
93
aReaction conditions: 1 (0.1 mmol) and 2a (0.12 mmol) in solvent (2.0 mL) at a range of zero to 50 °C for 1h.
bDetermined by 19F NMR using 1.0 equiv of PhOCF3 as internal standard added after the reaction.
cIsolated yield in bracket.
dAt 0 °C.
eAt 50 °C.

Table 2
Scope of the trifluoromethylthiolation of arylboronic acid 2 with (bpy)CuSCF3 1a.
aReaction conditions: 1 (0.1 mmol) and 2 (0.12 mmol) in NMP (2.0 mL) at room temperature under O2 for 1h. Yields of isolated products are shown.
bYields were determined by 19F NMR using 1.0 equiv of PhOCF3 as internal standard added after the reaction.