Coupling of gem-difluorinated organozinc reagents with S-electrophiles

Article abstract of DOI:10.1016/j.jfluchem.2016.07.018

gem-Difluorinated organozinc reagents, which were prepared by insertion of CF₂-fragment into C[sbnd]Zn bond, couple with diethyl dixanthogen, di(benzothiazolyl) disulfide, and tetraethylthiuram disulfide. The reaction is promoted either by a copper(I) catalyst or by irradiation with blue light in the presence of Eosin Y disodium salt.

Full text of DOI:10.1016/j.jfluchem.2016.07.018

Accepted Manuscript
Title: Coupling of gem-difluorinated organozinc reagents with
S-electrophiles
Author: Salavat S. Ashirbaev Vitalij V. Levin Marina I.
Struchkova Alexander D. Dilman
PII:
S0022-1139(16)30207-X
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2016.07.018
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9-6-2016
21-7-2016
25-7-2016
Please cite this article as: Salavat S.Ashirbaev, Vitalij V.Levin, Marina
I.Struchkova, Alexander D.Dilman, Coupling of gem-difluorinated
organozinc reagents with S-electrophiles, Journal of Fluorine Chemistry
http://dx.doi.org/10.1016/j.jfluchem.2016.07.018
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1
Coupling of gem-difluorinated organozinc reagents with S-electrophiles
Salavat S. Ashirbaev,a,b Vitalij V. Levin,a Marina I. Struchkova,a Alexander D. Dilmana,*
aN. D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Leninsky prosp. 47, Russian
Federation, Fax: +7-499-1355328, E-mail: adil25@mail.ru
b
Moscow State University, Department of Chemistry, 119991, Moscow, Leninskie Gory 1-3,
Russian Federation

2
GRAPHICAL ABSTRACT
Cu(I) or LED/eosin Y
F
F
F F
Y
S
+
Y
S
Y
R
ZnX
R
S
Y = C(S)OEt, C(S)NEt2,
2-benzothyazolyl, Ph
Copper-catalyzed or light-promoted coupling of gem-difluorinated organozinc reagents with
disulfides is described.
HIGHLIGHT
Reactions of fluorinated organozinc reagents.
Copper-catalyzed copper-sulfur bond coupling.
Light-promoted reactions of disulfides.
Abstract gem-Difluorinated organozinc reagents, which were prepared by insertion of CF2-
fragment into C-Zn bond, couple with diethyl dixanthogen, di(benzothiazolyl) disulfide, and
tetraethylthiuram disulfide. The reaction is promoted either by a copper(I) catalyst or by irradiation
with blue light in the presence of Eosin Y disodium salt.
Keywords: Organozinc reagents, Difluorinated compounds, Difluorocarbene, Disulfides
1. Introduction
Fluorinated organometallics constitute important class of reagents for the introduction fluorine-
containing fragment into organic molecules [1]. In contrast to lithium and magnesium reagents,
which frequently possess limited stability, less polar organozincs [2] are notably more robust that
offers wider scope of possible reagents. On the other hand, decreased reactivity of carbon-zinc bond
narrows the scope of suitable electrophiles. Typically, fluorinated organozincs are prepared from

3
fluorinated bromides or iodides either by reaction with elemental zinc [3] or by halogen/zinc
exchange [4]. In some cases, direct zincation of C-H bonds by zinc amides is possible [5].
Recently, we proposed a concept for the generation of reagents 1 by insertion of CF2-fragment
into carbon-zinc bond [6]. These reagents were coupled with carbon [7], halogen [6,8] and nitrogen
[9] electrophiles. Herein we report our studies on the interaction of species 1 with S-electrophiles.
2. Results and discussion
Sulfenyl chlorides were first considered as typical sulfur electrophiles [10]. When reagent 1a
was treated with phenyl sulfenyl chloride, compound 2 bearing bromodifluoromethyl group was
observed, whereas no desired sulfenylation product was detected (Scheme 2). At the same time,
organozinc 1a was absolutely unreactive towards diphenyl disulfide. Correspondingly, we proposed
to employ thio-electrophiles of intermediate electrophilic activity, such as dixanthogens.
Reaction of organozinc 1a obtained in acetonitrile with 1.1 equivalent of diethyl dixanthogen 3a
provided product 4a in 24% yield (Table 1, entry 1). Addition of 2.5 mol % of copper
chloride/triphenylphosphine complex doubled the product yield (entry 2). Subsequent optimization
revealed that increase of amount of catalyst to 5 mol % and use of DMF as a co-solvent allowed to
obtain sulfenylation product 4a in 64% isolated yield (entry 4). Further variation of reaction
conditions did not lead to increase of yield. The accelerating role of copper in this process is likely
to generate fluorinated organocopper species, which undergoes oxidative addition into S-S bond of
the disulfide followed by reductive elimination from copper(III) intermediate.
Under optimized conditions a series of conventional organozinc reagents were subjected to the
difluoromethylene insertion using (bromodifluoromethyl)trimethylsilane followed by coupling with
disulfides (Table 2). Besides dixanthogene, di(benzothiazolyl) disulfide (3b) was also employed,
which typically gave slightly higher yields of products compared to those of dixanthogene. The
scalability of the reaction was demonstrated by coupling of 10 mmol of benzylzinc bromide with
disulfide 3b affording product 4b in 50% yield.

4
Surprisingly, when difluorinated reagents 1 were coupled with thiuram disulfide 3c under typical
conditions involving a copper catalyst, no sulfenylation products were formed. Extensive screening
of conditions demonstrated that irradiation of the mixture of 1 and 3с with blue light (strip of light
emitting diodes) in the presence of 2 mol % of Eosin Y disodium salt led to desired products 4l-n
(Table 3). No products were formed when the reaction was performed in the dark.
Concerning mechanism, we may propose that the reaction starts from the generation of thiyl
radical 5 by one electron reduction of disulfide 3c with light activated Eosin Y [11] (Schem 3).
Then, thiyl radical 5 may attack at the zinc of reagent 1 to effect radical substitution [12,13] with
the formation of fluorinated radical 6. The latter species reacts at the C=S bond of disulfide 3c in a
typical way [14] leading to the product with the regeneration of radical 5.
The key point of this mechanism is the intermediacy of thiyl radical 5. In fact, it is known that
the S-S bond can be homolytically cleaved under photochemical conditions [15]. Accordingly,
when reactions of 1 with disulfide 3c were performed without Eosin Y but with blue light
irradiation, expected products 4 were also formed in similar yields as with Eosin (for example, for
product 4l, 50% yield).
Encouraged by these results, we tested diphenyl disulfide under light mediated conditions
(Scheme 4). Thus, the reaction of organozinc 1a proceeded smoothly, and expected product 4o was
isolated in 53% yield, while in reaction without Eosin, the product was formed in 51% yield.
3. Conclusions

5
In summary, various disufide reagents were demonstrated to behave as competent electrophiles
towards gem-difluorinated organozinc reagents. The reactions were promoted either by copper(I)
catalyst or visible light in the presence of Eosin Y.
4. Experimental
4.1 General Experimental Procedures
All reactions were performed under an argon atmosphere. DMF and MeCN were distilled under
vacuum from P2O5 and stored over MS 4Å. 1,2-Dimethoxyethane (DME) was distilled from
LiAlH4. As light source, a strip of diodes SMD 2835 120 LED/m Blue was used. NMR spectra
were recorded on a Bruker AM-300 instrument. Starting organozinc reagents [6], Me3SiCF2Br [16]
were obtained according to literature procedures. Diphenyl disulfide was commercial.
4.2. Preparation of disulfides.
4.2.1. Dixanthogen (3a) [17].
Iodine (7 g, 27.5 mmol) was slowly added to a solution of potassium ethyl xanthogenate (8.8 g,
55 mmol) in water at room temperature, and the mixture was stirred for 2 hours. The mixture was
extracted with hexane (315 mL), the combined extracts were filtered through Na2SO4,
concentrated under vacuum, and the residue was recrystallized from petrol ether with cooling to –12
°C. Yield 4.7 g (70%). Mp 29–30 °C.
4.2.2. 2-(1,3-Benzothiazol-2-yldithio)-1,3-benzothiazole (3b) [18].
Hydrogen peroxide (5 mL of 12M aqueous solution, 60 mmol) was added to a solution of 2-
mercaptobenzothiazole (10 g, 60 mmol) in ethanol (100 mL). Then, iodine (20 mg) was added at
room temperature, and the mixture was heated at 55 °C for 30 min. The heating bath was removed,
and the mixture was allowed to stand overnight without stirring. The precipitate was filtered,
washed with ethanol, and dried under vacuum. Yield 10 g (98%). Mp 176–178 °C.
4.2.3. Tetraethylthiuram disulfide (3c) [19].

6
To a solution of diethylamine (7 mL, 67 mmol) in methanol (50 mL) upon cooling with room
temperature water bath was added dropwise CS2 (4.3 mL, 71 mmol), and then hydrogen peroxide
(3.1 mL of 12M aqueous solution, 37 mmol) which caused the formation of the precipitate. The
mixture was heated until dissolution of the precipitate. The mixture was allowed cool slowly to 5
°C. The crystals was filtered, washed with methanol, and dried under vacuum. Yield 5.5 g (55%).
Mp 69–71 °C.
4.3. Synthesis of compounds 4a-k (General Procedure).
A solution of organozinc reagent in THF (1 mmol) was concentrated under vacuum, the residue
was dissolved in DME (1.5 mL), and sodium acetate (99 mg, 1.2 mmol) was added at room
temperature. The mixture was cooled to –25 °C, Me3SiCF2Br (244 mg, 1.2 mmol) was added
dropwise, and the mixture was stirred for at –25 °C for 18 h. Then, DMF (0.5 mL) was added.
Disulfide (1.1 mmol) was added [dixanthogen 3a was added in one portion; for dibenzothiazolyl
disulfide 3b, half of the amount was added, the mixture was stirred for 30 min followed by addition
of the second half]. The reaction mixture was allowed to warm to room temperature during 6 h, and
stirred for additional 12 h. For the work-up, water (7 mL) was added, the mixture was extracted
with methyl tert-butyl ether/hexane, 1/1 (for 4a-j) or methyl tert-butyl ether (for 4k) (35 mL). The
combined organic layers were filtered through Na2SO4, concentrated under vacuum, and the residue
was purified by column chromatography.
4.3.1. S-(1,1-Difluoro-2-phenylethyl) O-ethyl (dithiocarbonate) (4a).
Yield 168 mg (64%). Yellow oil. Rf 0.23 (Hexanes/CH2Cl2, 10/1). 1H NMR (300 MHz, CDCl3),
δ: 1.54 (t, 3H, J = 7.3 Hz), 3.62 (t, 2H, J = 16.0 Hz), 4.75 (q, 2H, J = 7.3 Hz), 7.31–7.44 (m, 5H).
13
19F NMR (282 MHz, CDCl3), δ: –73.8 (t, J = 16.0 Hz). C{1H} NMR (75 MHz, CDCl3), δ: 13.7,
45.0 (t, J = 23.2 Hz), 70.6, 127.6 (t, J = 285.3 Hz), 128.1, 128.7, 130.7, 131.3 (t, J = 3.3 Hz), 205.9
(t, J = 2.9 Hz). HRMS (ESI): calcd for C11H12F2OS2Na [M+Na] 285.0190, found 285.0191.
4.3.2. 2-[(1,1-Difluoro-2-phenylethyl)thio]-1,3-benzothiazole (4b).

7
Yield 169 mg (55%). For the reaction performed on 10 mmol of benzylzinc bromide, the yield
1
was 1.58 g (50%). Colorless solid. Mp 57–60 °C. Rf 0.29 (Hexanes/EtOAc, 15/1). H NMR (300
MHz, CDCl3), δ: 3.68 (t, 3H, J = 15.4 Hz), 7.34–7.56 (m, 1H), 7.87 (d, 1H, J = 8.1 Hz), 8.12 (d,
13
1H, J = 8.1 Hz). C{1H} NMR (75 MHz, CDCl3), δ: 45.4 (t, J = 23.2 Hz), 121.2, 123.6, 126.0,
126.6, 128.2, 128.7, 128.8 (t, J = 284.7 Hz), 130.8, 131.2 (t, J = 3.3 Hz), 137.6, 153.2, 156.0 (t, J =
2.6 Hz). 19F NMR (282 MHz, CDCl3), δ: –70.0 (t, J = 14.1 Hz). HRMS (ESI): calcd for
C15H12F2NS2 [M+H] 308.0374, found 308.0368.
4.3.3. S-(1,1-Difluoro-2-methylpropyl) O-ethyl (dithiocarbonate) (4c).
Yield 107 mg (50%). Yellow oil. Rf 0.29 (Hexanes/CH2Cl2, 30/1). 1H NMR (300 MHz, CDCl3),
δ: 1.13 (d, 6H, J = 3.0 Hz), 1.48 (t, 3H, J = 7.3 Hz), 2.35–2.57 (m, 1H), 4.72(q, 2H, J = 7.3 Hz).
13C{1H} NMR (75 MHz, CDCl3), δ: 13.6, 16.1 (t, J = 3.8 Hz), 37.0 (t, J = 21.1 Hz), 70.5, 131.2 (t, J
= 287.5 Hz), 206.5 (t, J = 2.0 Hz). 19F NMR (282 MHz, CDCl3), δ: –81.9 (d, J = 11.3 Hz). HRMS
(ESI): calcd for C7H13F2OS2 [M+H] 215.0370, found 215.0373.
4.3.4. 2-[(1,1-Difluoro-2-methylpropyl)thio]-1,3-benzothiazole (4d).
Yield 155 mg (60%). Colorless oil. Rf 0.33(Hexanes/EtOAc, 12/1). 1H NMR (300 MHz, CDCl3),
δ: 1.22 (d, 6H, J = 6.9 Hz), 2.52 (sept, 1H, J = 6.9 Hz), 7.45 (m, 2H), 7.86 (d, 1H, J = 7.8 Hz), 8.08
(d, 1H, J = 7.8 Hz). 13C{1H} NMR (75 MHz, CDCl3), δ: 16.5 (t, J = 3.4 Hz), 37.6 (t, J = 21.5 Hz),
19
121.0, 123.6, 126.0, 126.5, 132.4 (t, J = 286.0 Hz), 137.8, 153.1, 155.9 (t, J = 2.3 Hz). F NMR
(282 MHz, CDCl3), δ: –77.5 (d, J = 12.7 Hz). HRMS (ESI): calcd for C11H12F2NS2 [M+H]
260.0374, found 260.0375.
4.3.5. S-(1,1-Difluoro-3-methylbutyl) O-ethyl (dithiocarbonate) (4e).
1
Yield 91 mg (40%). Yellow oil. Rf 0.33 (Hexanes/CH2Cl2, 40/1). H NMR (300 MHz, CDCl3),
δ: 1.03 (d, 6H, J = 6.5 Hz), 1.48 (t, 3H, J = 7.3 Hz), 1.96–2.12 (m, 1H), 2.18 (td, 2H, J = 17.0, 6.5
Hz), 4.71 (q, 2H, J = 7.3 Hz). 13C{1H} NMR (75 MHz, CDCl3), δ: 13.6, 23.2, 24.1 (t, J = 2.3 Hz),
19
47.0 (t, J = 21.9 Hz), 70.4, 129.0 (t, J = 284.5 Hz), 206.4 (t, J = 3.8 Hz). F NMR (282 MHz,

8
CDCl3), δ: –72.0 (t, J = 17.0 Hz). Calcd for C8H14F2OS2 (228.32): C 42.09, H 6.18 Found: C 42.04,
H 6.28.
4.3.6. 2-[(1,1-Difluoro-3-methylbutyl)thio]-1,3-benzothiazole (4f).
1
Yield 128 mg (47%). Colorless oil. Rf 0.33 (Hexanes/CH2Cl2, 25/1). H NMR (300 MHz,
CDCl3), δ: 1.05 (d, 6H, J = 6.4 Hz), 2.10–2.29(m, 3H Hz), 7.40–7.53(m, 2H), 7.86 (d, 1H, J = 8.2
Hz), 8.08 (d, 1H, J = 8.2 Hz). 13C{1H} NMR (75 MHz, CDCl3), δ: 23.2, 24.2 (t, J = 2.3 Hz), 47.2 (t,
J = 21.1 Hz), 121.2 , 123.6, 126.0, 126.6, 130.0 (t, J = 284.0 Hz), 137.7, 153.1, 156.0 (t, J = 3.0
19
Hz). F NMR (282 MHz, CDCl3), δ: –68.3(t, J = 15.5 Hz). HRMS (ESI): calcd for C12H14F2NS2
[M+H] 274.0530, found 274.0536.
4.3.7. 2-[(1,1-Difluoroethyl)thio]-1,3-benzothiazole (4g).
1
Yield 160 mg (61%). Colorless liquid. Rf 0.27 (Hexanes/EtOAc, 12/1). H NMR (300 MHz,
CDCl3), δ: 2.13(t, 3H, J = 16.5 Hz), 7.38–7.52(m, 2H Hz), 7.83(d, 1H, J = 8.2 Hz), 8.07(d, 1H, J =
8.2 Hz). 13C{1H} NMR (75 MHz, CDCl3), δ: 26.6 (t, J = 24.9 Hz), 121.1, 123.6, 126.0, 126.6, 128.0
19
(t, J = 280 Hz), 137.6, 153.1, 156.0 (t, J = 3.0 Hz). F NMR (282 MHz, CDCl3), δ: –64.6 (q, J =
16.9 Hz). HRMS (ESI): calcd for C9H8F2NS2 [M+H] 232.0061, found 232.0067.
4.3.8. S-[4-(Benzyloxy)-1,1-difluorobutyl] O-ethyl (dithiocarbonate) (4h).
1
Yield 112 mg (35%). Colorless oil. Rf 0.23 (Hexanes/EtOAc, 15/1). H NMR (300 MHz,
CDCl3), δ: 1.46 (t, 3H, J = 7.3 Hz), 1.85–1.95 (m, 2H), 2.36–2.52(m, 2H), 3.56 (t, 2H, J = 5.9 Hz),
4.53 (s, 2H), 4.70 (q, 2H, J = 7.3 Hz), 7.27–7.42 (m, 5H). 13C{1H} NMR (75 MHz, CDCl3), δ: 13.5,
23.1 (t, J = 3.8 Hz), 35.8 (t, J = 22.6 Hz), 68.8, 70.5, 73.0, 127.7, 127.8, 128.5, 128.9 (t, J = 284.5
19
Hz), 138.3, 206.1 (t, J = 3.8 Hz). F NMR (282 MHz, CDCl3), δ: –74.4 (t, J = 14.1 Hz). HRMS
(ESI): calcd for C14H19F2O2S2 [M+H] 321.0789, found 321.0797.
4.3.9. 2-{[4-(Benzyloxy)-1,1-difluorobutyl]thio}-1,3-benzothiazole (4i).
Yield 190 mg (52%). Colorless oil. Rf 0.23 (Hexanes/EtOAc, 4/1). 1H NMR (300 MHz, CDCl3),
δ: 1.96–2.05 (m, 2H), 2.42–2.58 (m, 2H), 3.56 (t, 2H, J = 5.5 Hz), 4.52 (s, 2H), 7.29–7.54 (m, 7H),
7.84 (d, 1H, J = 8.2 Hz), 8.10 (d, 1H, J = 8.2 Hz). 13C{1H} NMR (75 MHz, CDCl3), δ: 23.6 (t, J =

9
3.4 Hz), 36.2 (t, J = 22.6 Hz), 68.7, 73.0, 121.2, 123.7, 126.0, 126.6, 127.7, 127.8, 128.5, 130.0 (t, J
= 283.0 Hz), 137.3, 138.4, 153.2, 155.6 (t, J = 2.3 Hz). 19F NMR (282 MHz, CDCl3), δ:–68.3(t, J =
15.3 Hz). HRMS (ESI): calcd for C18H18F2NOS2 [M+H] 366.0792, found 366.0795.
4.3.10. Ethyl 5-(1,3-benzothiazol-2-ylthio)-5,5-difluoropentanoate (4j).
Yield 142 mg (43%). Colorless oil. Rf 0.28 (Hexanes/EtOAc, 4/1). 1H NMR (300 MHz, CDCl3),
δ: 1.24 (t, 3H, J = 7.3 Hz), 1.95–2.05 (m, 2H), 2.32–2.47 (m, 4H), 4.13 (q, 2H, J = 7.3 Hz), 7.40–
7.53 (m, 2H), 7.85(d, 1H, J = 8.1 Hz), 8.10 (d, 1H, J = 8.1 Hz). 13C{1H} NMR (75 MHz, CDCl3), δ:
14.0, 18.4 (t, J = 3.5 Hz), 32.9, 38.0 ( t, J = 22.6 Hz), 60.3, 121.0, 123.4, 125.8, 126.4, 129.3 (t, J =
283.3 Hz), 137.4, 152.9, 155.4 (t, J = 3.0 Hz), 172.2. 19F NMR (282 MHz, CDCl3), δ: –70.9 (t, J =
14.1 Hz). HRMS (ESI): calcd for C14H16F2NO2S2 [M+H] 332.0585, found 332.0572.
4.3.11. Diethyl 3-(1,3-benzothiazol-2-ylthio)-3,3-difluoropropylphosphonate (4k).
Yield 187 mg (49%). Colorless oil. Rf 0.33 (Hexanes/i-PrOH, 5/1). 1H NMR (300 MHz, CDCl3),
δ: 1.26 (t, 6H, J = 7.2 Hz), 1.98–2.10 (m, 2H), 2.48–2.68 (m, 2H), 4.01–4.17 (m, 4H), 7.37–7.49
13
(m, 2H), 7.81 (d, 1H, J = 8.2 Hz), 8.02 (d, 1H, J = 8.2 Hz). C{1H} NMR (75 MHz, CDCl3), δ:
16.4 (d, J = 5.3 Hz), 19.9 (dt, J = 145.3, 3.2 Hz), 32.9 (td, J = 24.1, 3.0 Hz), 62.1 (d, J = 6.8 Hz),
19
121.2, 123.7, 126.2, 126.7, 129.1 (t, J = 283.8 Hz), 137.6, 153.2, 155.0 (t, J = 3.0 Hz). F NMR
(282 MHz, CDCl3), δ: –72.8 (t, J = 14.1 Hz). HRMS (ESI): calcd for C14H19F2NO3PS2 [M+H]
382.0507, found 382.0502.
4.4. Synthesis of compounds 4l-n (General Procedure).
A solution of organozinc reagent in THF (1 mmol) was concentrated under vacuum, the residue
was dissolved in DME (1.5 mL), and sodium acetate (99 mg, 1.2 mmol) was added at room
temperature. The mixture was cooled to –25 °C, Me3SiCF2Br (244 mg, 1.2 mmol) was added
dropwise, and the mixture was stirred for at –25 °C for 18 h. Then, DMF (0.5 mL) was added. To
the resulting mixture were successively added disulfide 3c (311 mg, 1.05 mmol) and Eosin Y
disodium salt (15 mg, 0.02 mmol). The cooling bath was removed, and the reaction flask was
irradiated with blue LED at room temperature during 4 h. For the work-up, water (7 mL) was

10
added, the mixture was extracted with methyl tert-butyl ether/hexane (1/1, 35 mL). The combined
organic layers were filtered through Na2SO4, concentrated under vacuum, and the residue was
purified by column chromatography.
4.3.1. 1,1-Difluoro-2-phenylethyl diethyl-(dithiocarbamate) (4l).
1
Yield 147 mg (51%). Yellow oil. Rf 0.22 (Hexanes/EtOAc, 20/1). H NMR (300 MHz, CDCl3),
δ: 1.21 (t, 3H, J = 6.9 Hz), 1.32 (t, 3H, J = 6.9 Hz), 3.62 (q, 2H, J = 6.9 Hz), 4.01 (q, 2H, J = 6.9
13
Hz), 4.10 (t, 2H, J = 15.5 Hz), 7.28–7.41(m, 5H). C{1H} NMR (75 MHz, CDCl3), δ: 11.2, 12.7,
43.4(t, J = 22.1 Hz), 47.9, 48.3, 127.5, 128.1, 129.1 (t, J = 280.3 Hz), 130.6, 132.4 (t, J = 3.5 Hz),
186.7(t, J = 5.5 Hz). 19F NMR (282 MHz, CDCl3), δ: –71.1 (t, J = 15.5 Hz). HRMS (ESI): calcd for
C13H18F2NS2 [M+H] 290.0843, found 290.0847.
4.3.2. Methyl 4-(2-{[(diethylamino)carbonothioyl]thio}-2,2-difluoroethyl)benzoate (4m).
Yield 187 mg (54%). Yellow oil. Rf 0.28 (Hexanes/EtOAc, 6/1). 1H NMR (300 MHz, CDCl3), δ:
1.22 (t, 3H, J = 7.2 Hz), 1.30 (t, 3H, J = 7.2 Hz), 3.61 (q, 2H, J = 7.2 Hz), 3.90 (s, 3H), 3.98 (q, 2H,
13
J = 7.2 Hz), 4.16 (t, 2H, J = 16.5 Hz), 7.42 (d, 2H, J = 8.1 Hz), 7.98 (d, 2H, J = 8.1 Hz). C{1H}
NMR (75 MHz, CDCl3), δ: 11.4, 13.0, 43.5 (t, J = 22.7 Hz), 48.1, 48.6, 52.1, 128.9 (t, J = 280.6
Hz), 129.6, 130.9, 137.9 (t, J = 3.2 Hz), 166.9, 186.6 (t, J = 5.4 Hz). 19F NMR (282 MHz, CDCl3),
δ: –70.9 (t, J = 16.4 Hz). HRMS (ESI): calcd for C15H20F2NO2S2 [M+H] 348.0898, found 348.0890.
4.3.3. 1,1-Difluoro-2-methylpropyl diethyl-(dithiocarbamate) (4n).
Yield 77 mg (32%). Yellow oil. Rf 0.28 (Hexanes/EtOAc, 20/1). 1H NMR (300 MHz, CDCl3), δ:
1.12 (d, 6H, J = 6.9 Hz), 1.22–1.34 (m, 6H), 3.11–3.35 (m, 1H), 3.76 (q, 2H, J = 6.9 Hz), 3.97 (q,
13
2H, J = 6.9 Hz). C{1H} NMR (75 MHz, CDCl3), δ: 11.4, 13.1, 16.1 (t, J = 4.1 Hz), 36.0 (t, J =
21.3 Hz), 48.4, 132.3 (t, J = 284.6 Hz), 186.2 (t, J = 3.9 Hz). 19F NMR (282 MHz, CDCl3), δ: –81.7
(d, J = 15.0 Hz). HRMS (ESI): calcd for C9H18F2NS2 [M+H] 242.0843, found 242.0838.
4.4. [(1,1-Difluoro-2-phenylethyl)thio]benzene (4o) [20].
A solution of reagent 1a (4.2 mL of 0.45 M in DMF, 1.88 mmol, 1 equiv, prepared according to
a literature procedure [7c]) was treated diphenyl disulfide (436 mg, 2 mmol, 1.05 eqiuv) and Eosin

11
Y disodium salt (26 mg, 0.0375 mmol, 0.02 equiv) at room temperature. Then, the reaction flask
was irradiated with blue LED at room temperature during 4 h. For the work-up, water (7 mL) was
added, the mixture was extracted with methyl tert-butyl ether/hexane (1/1, 35 mL). The combined
organic layers were filtered through Na2SO4, concentrated under vacuum, and the residue was
purified by column chromatography. Yield 248 mg (53%). Colorless oil. Rf 0.10 (Hexanes/EtOAc,
40/1). 1H NMR (300 MHz, CDCl3), δ: 3.50 (t, 2H, J = 15 Hz), 7.39–7.49 (m, 8H), 7.66 (d, J = 2.4
13
Hz). C{1H} NMR (75 MHz, CDCl3), δ: 45.3 (t, J = 24.4 Hz), 127.2, 127.9, 128.6, 128.9(t, J =
282.2 Hz), 129.2, 129.8, 130.7, 132.2 (t, J = 3.2 Hz), 136.3. 19F NMR (282 MHz, CDCl3), δ: –
72.2(t, J = 14.7 Hz). Calcd for C14H12F2S (250.31): C 67.18, H 4.83. Found: C 67.15, H 4.98.
Acknowledgments
This work was supported by the Russian Science Foundation (project 14-23-00150).
References and Notes
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12
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Chem. 79 (2014) 11819–11823.
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13
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14
Me3SiCF2Br
F
F
F
F
or BrCF2CO2K
E
R
ZnBr
R
R
E
ZnBr
1
Previous work:
This work:
E = ''RS+'' (RSSR)
E = C (cross-coupling)
N (ArNO)
Hal+, H+
Scheme 1. Preparation of reagents 1.
F
F
PhSCl
Ph
F
F
Br
Ph
2
ZnBr
PhSSPh
1a
no reaction
Scheme 2. Attempted sufenylation reactions.
S
Et
N
Et
S
N
S
Et
S
S
Et
S
Et
Et
3c
N
S
+
N
S
Et
Et
h
5
EY
EY*
S
Et
N
SZnX
S
Et
N
F
F
Et
Et
S
F
F
N
S
Et
R
ZnX
S
1
Et
S
R
3c
6
Et
N
S
Et
5
S
Et
N
Et
S
N
S
Et
S
F
F
Et
S
R
Et
R
S
N
F
F
Et
Scheme 3. Proposed mechanism.

15
PhSSPh
F
F
F
F
Eosin Y-Na2 (2 mol %)
Ph
Ph
ZnBr
SPh
4o, 53%
blue LED, rt, 4 h
1a
Scheme 4. Synthesis of sulfide 4o.

16
Table 1. Reaction of organozinc 1a.
S
F
F
S
F
F
S
OEt –25°C to rt
18 h
Ph
Ph
EtO
S
+
ZnBr
S
OEt
S
1a
4a
3a, 1.1 equiv
Entry Solv.
Cat. (mol %)
–
Yield of 4a, %a
1
MeCN
24
2
MeCN CuCl·1.5PPh3 (2.5)
52
3
DME
DME
DME
DME
CuCl·1.5PPh3 (2.5)
CuCl·1.5PPh3 (5)
CuCN (2.5)
60
4b
5
65 (64c)
53
6
CuI·IMes (2.5)
61
a Determined by 19F NMR of crude material with 4-fluorotoluene as an internal standard.
b DMF was used as a co-solvent.
c Isolated yield.

17
Table 2. Synthesis of sulfides 4.
F
F
F
F
R1
ZnX
i
ii
R1
R1
ZnX
SR3
R2
R2
R2
4
i: Me3SiCF2Br (1.2 equiv)
AcONa (1.2 equiv)
ii: R3SSR3 (1.1 equiv)
CuCl·PPh3 (5 mol %)
DME, –25 °C, 18 h
DME/DMF, –25 °C to rt
Entry Reagent
R3SSR3
Product
Yield of 4, %a
4b 55
Ph
ZnBr
S
F
F
N
Ph
S
S
N
S
S
S
N
ZnI
S
S
F
F
F
4c 50
4d 60
S
OEt
S
OEt
EtO
S
S
S
F
N
S
S
N
S
S
S
S
N
S
F
F
4e 40
4f 47
ZnI
S
OEt
S
OEt
EtO
S
S
S
F
F
N
S
S
S
N
S
S
S
S
S
N
N
4g 61
Me ZnI
S
F
F
N
S
N
S
S
S
BnO
ZnI
F
F
F
4h 35
4i 52
BnO
BnO
S
OEt
S
OEt
N
EtO
S
S
S
F
N
N
N
S
S
S
S
S
S
S
S
S
S
S
N
N
N
O
4j 43
4k 49
O
S
N
ZnI
F F
EtO
S
S
EtO
S
EtO
EtO P
ZnBr
S
F
F
EtO
EtO P
O
N
S
O
a Isolated yield.

19
Table 3. Light mediated reactions.
i
R1
ZnX
S
Et
N
Et
S
R2
R1
N
S
Et
Et
S
S
F
F
F
F
R1
Et
3c (1.05 equiv)
S
N
ZnX
R2
Et
Eosin Y-Na2 (2 mol %)
blue LED, rt, 4 h
R2
1
4l-n
i: Me3SiCF2Br, AcONa
Reagent
Product
Yield of 4, %a
S
Ph
ZnBr
F
F
4l
51
Ph
Et
S
N
Et
MeO2C
MeO2C
S
4m
4n
54
32
F
F
Et
ZnBr
S
N
Et
ZnI
S
F
F
Et
S
N
Et
a Isolated yield.