Efficient nucleophilic difluoromethylation of aldehydes with (phenylsulfonyl)difluoromethylzinc and (phenylsulfonyl)difluoromethylcadmium reagents

Article abstract of DOI:10.1016/j.jfluchem.2016.12.005

A new strategy for nucleophilic addition to aldehydes with difluoromethyl organometallic reagents has been developed by functionalizing the difluoromethyl moiety with the phenylsulfonyl group (SO₂Ph). This electron-withdrawing group influences

Full text of DOI:10.1016/j.jfluchem.2016.12.005

Accepted Manuscript
Title: Efficient Nucleophilic Difluoromethylation of
Aldehydes with (Phenylsulfonyl)difluoromethylzinc and
(Phenylsulfonyl)d ifluoromethylcadmium Reagents
Author: Fanzhou Jiang Chuanfa Ni Jinbo Hu
PII:
S0022-1139(16)30435-3
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2016.12.005
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3-11-2016
6-12-2016
6-12-2016
Please cite this article as: Fanzhou Jiang, Chuanfa Ni, Jinbo Hu, Efficient Nucleophilic
Difluoromethylation of Aldehydes with (Phenylsulfonyl)difluoromethylzinc and
(Phenylsulfonyl)d ifluoromethylcadmium Reagents, Journal of Fluorine Chemistry
http://dx.doi.org/10.1016/j.jfluchem.2016.12.005
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Efficient Nucleophilic Difluoromethylation of Aldehydes with
(Phenylsulfonyl)difluoromethylzinc
ifluoromethylcadmium Reagents
and
(Phenylsulfonyl)d
Fanzhou Jiang, Chuanfa Ni, and Jinbo Hu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032,
China
* Correspondence author. Tel.: +86 21 54925174; Fax: +86 21 64166128; E-mail:
jinbohu@sioc.ac.cn.
Invited Contribution for “Special Issue: Bremen Fluorine Days 2016”
1

Highlights
1. (Phenylsulfonyl)difluoromethylzinc and –cadmium reagents were prepared for the
first time.
2. The two reagents reacted smoothly with aldehydes under mild conditions.
3. The phenylsulfonyl group increased the thermodynamic stability and
nucleophilicity of the difluoromethanide anion.
2

Abstract
A new strategy for nucleophilic addition to aldehydes with difluoromethyl
organometallic reagents has been developed by functionalizing the difluoromethyl
moiety with the phenylsulfonyl group (SO2Ph). This electron-withdrawing group
influences both the thermodynamic stability and the nucleophilicity of difluoromethyl
organometallic reagents, which plays an important role in the nucleophilic
difluoromethylation of aldehydes.
Keywords: difluoromethylation; sulfone; aldehyde; organozinc reagent;
organocadmium reagent
3

1. Introduction
Fluoroalkylation reactions have undergone extensive development in the field of
organofluorine chemistry over the past decades.[1] Among various fluoroalkyl groups,
the difluoromethyl group (-CF2H) is considered to be isosteric and isopolar to a
carbinol (-CH2OH) or thiol (-SH) unit.[2] It also can behave as a more lipophilic
hydrogen donor through hydrogen bonding.[3] Moreover, selective incorporation of a
difluoromethylene moiety into medicinal molecules not only has the potential to
modify their interaction with neighboring functional groups, but also has an impact on
their receptor bindings and metabolic processes.[4] Therefore, difluoromethylated
analogues of biologically active molecules promise to be good candidates for
pharmaceuticals. Recent years have witnessed the increasing number of methods for
the introduction of difluoromethylated building blocks.[4b] Nucleophilic
difluoromethylation has been known as a convenient and efficient method to prepare
difluoromethylated compounds.[5] TMSCF2H, as
a
potentially useful
difluoromethanide anion (CF2H-) precursor, has been successively applied for the
nucleophilic addition to different substrates, such as aldehydes, ketones and
imines.[5a-5d] In contrast to this organosilicon compound, difluoromethyl
organometallic reagents are still supposed to be incapable of undergoing nucleophilic
difluoromethylation of carbonyl compounds and related electrophiles.[6]
Difluoromethylzinc (HCF2ZnX) and cadmium (HCF2CdX) reagents were prepared
via direct insertion of the corresponding metal into the C-X bond of CF2HX (X = Br
4

and I).[6] These sluggish difluoromethyl reagents demonstrated fairly good thermal
o
stability at even 65~75 C and only exhibited reactivities with allylic halides,
propargyl halides and other high chemically reactive derivatives.
Difluoromethylcopper reagents (HCF2CuX) derived from difluoromethylcadmium
reagent was more reactive with these halides, whereas easily decomposed when the
temperature was elevated to higher than 30 oC.[6] The difluoromethylcopper species
prepared from TMSCF2H was extensively investigated and successfully applied to the
synthesis of difluoromethylated arenes.[7] Shen’s group reported that a structurally
well-defined difluoromethyl silver complex could difluoromethylate aryl bromides
and iodides under mild conditions in the presence of palladium catalyst.[8]
Recently, Mikami and co-workers succeeded in the trifluoromethylation of
carbonyl compounds with the stable bis(trifluoromethyl)zinc reagent
Zn(CF3)2(TMEDA).[9] As analogues of this isolated organozinc species, the
corresponding bis(difluoromethyl)zinc reagent and its analogues were also
synthesized for palladium or copper catalyzed cross-coupling reactions with aryl
halides.[10] However, difluoromethylation of carbonyl compounds with
difluoromethylzinc reagents has not been achieved yet. In general, trifluoromethyl
organometallic reagents exhibit higher thermodynamic stability than the
corresponding difluoromethyl species.[11] For example, trifluoromethylcopper
reagents are stable at ambient temperature, while the difluoromethylcopper species
could be only maintained below 30 oC.[6,12]
5

The (phenylsulfonyl)difluoromethyl group (PhSO2CF2) was regarded as a useful
functionality, which can undergo further transformation into various groups, such as
difluoromethylene (-CF2-), difluoromethyl (CF2H) and difluoromethylidene (=CF2)
moieties.[4a, 13] In addition, the phenylsulfonyl group could enhance the
nucleophilicity of difluoromethyl anion towards different electrophilic substrates.[13]
The corresponding difluoromethylated organometallic reagents are expected to be
obtained by direct insertion of an appropriate metal into the CX (X = Br and I) bond
of iodo- or bromodifluoromethyl phenyl sulfone (PhSO2CF2I/PhSO2CF2Br (2)).
Herein, we disclose an efficient nucleophilic difluoromethylation of aldehydes with
(phenylsulfonyl)difluoromethylzinc and (phenylsulfonyl)difluoromethylcadmium
reagents under mild conditions.[14]
Scheme 1. Preparation of bromodifluoromethyl phenyl sulfone
2. Results and Discussion
Bromodifluoromethyl phenyl sulfone (2) could be readily prepared from
bromodifluoromethyl phenyl sulfide (PhSCF2Br, 1) and NaIO4 in the presence of
RuCl3·xH2O according to the literature procedures (Scheme 1).[15] With this
difluoromethyl equivalent in hand, we initially began to investigate the reaction
conditions for preparing (phenylsulfonyl)difluoromethylzinc reagent. TMSCl was
6

used to in situ activate zinc powder before PhSO2CF2Br was added into the mixture.
The moderately polar solvent THF was not effective for the insertion of zinc metal
into CBr bond of PhSO2CF2Br (2) even at an elevated temperature (50 oC) (Scheme
2a). The Highly polar solvent DMF was found to be much better and the insertion
proceeded smoothly at room temperature within 15 minutes to afford the
corresponding difluoromethylzinc reagent “XZnCF2SO2Ph (X = Br, CF2SO2Ph)” (3)
19
as a mixture of mono- and bisdifluoromethylzinc in 73% F NMR yield (Figure 1).
The mono/bis species were tentatively assigned via their characteristic 19F NMR
spectrum, which exhibited the singlet at –105.6 ppm (25%) and –106.0 ppm (75%),
respectively.[6b,16] However, these organozinc species gradually decomposed to
difluoromethyl phenyl sulfone (PhSO2CF2H) at room temperature. A lower
temperature could keep “XZnCF2SO2Ph” (3) relatively stable (Scheme 2b). Similarly,
the reaction between zinc powder and PhSO2CF2Br (2) conducted in NMP also
o
rapidly produced “XZnCF2SO2Ph” (3), which also maintains stable at 0 C (Scheme
2c).
7

Scheme 2. Optimized reaction conditions for the preparation of
(phenylsulfonyl)difluoromethylzinc reagent
8

-90
-95
-100
-105
-110
-115
-120
-125
-130 PPM
Figure 1. The composition of (phenylsulfonyl)difluoromethylzinc reagent prepared in
DMF at room temperature
Using the optimized reaction conditions for the preparation of
(phenylsulfonyl)difluoromethylzinc reagent, we made a survey on its reaction with
aldehydes, choosing 2-naphthaldehyde as a model substrate. The difluoromethylzinc
species prepared in DMF exhibited a higher nucleophilicity than that in NMP. The
nucleophilic difluoromethylation proceeded smoothly, providing the difluoromethyl
carbinol in excellent yield within 5 hours at ambient temperature (Table 1).
Table 1. Survey of nucleophilic difluoromethylation of 2-naphthaldehyde with
(phenylsulfonyl)difluoromethylzinc reagent
9

entrya
solvent
DMF
DMF
DMF
NMP
time (h)
3 h
temperature (oC) yield (%)b
r.t.
r.t.
0
70
92
42
49
1
2
3
4
5 h
5 h
10 h
r.t.
aThe amount of PhSO2CF2Br and Zn is 2.0 and 3.0 equivalents relative to
that of 2-naphthaldehyde, respectively. bDetermined by 19F NMR analysis
of the crude reaction mixture using PhCF3 as an internal standard.
Encouraged by the above results, we next examined the substrate scope of the
difluoromethylation reaction with (phenylsulfonyl)difluoromethylzinc reagent. As
shown in Scheme 3, this method exhibited a good tolerance to both aromatic and
aliphatic aldehydes. Aldehydes with electron-withdrawing groups could smoothly
undergo the reaction to give the corresponding difluoromethyl carbinols, whereas the
reaction of aldehydes with electron-donating groups required anhydrous LiCl to
promote the nucleophilic addition process due to their relatively low reactivity.
Besides aromatic aldehydes with various substituents, this reaction was also amenable
to heteroaromatic aldehydes (Table 2).
10

Table 2. Nucleophilic difluoromethylation of various aldehydes with
(phenylsulfonyl)difluoromethylzinc reagenta
4a, 88%
4d, 88%
4g, 84%c
4b, 86%
4e, 90%
4h, 95%
4c, 80%b
4f, 88%
4i, 78%
4j, 93%c
aThe amount of PhSO2CF2Br and Zn is 2.0 and 3.0 equivalents relative to that of the
b
aldehyde, respectively. Isolated yield is reported. 2.0 equivalents of LiCl is added to
the mixture. c1.0 equivalent of LiCl is added to the mixture.
11

Having accomplished the nucleophilic difluoromethylation of aldehydes with
(phenylsulfonyl)difluoromethylzinc reagent, we continued our study with
investigations of the preparation and reaction of other organometallic species for
(phenylsulfonyl)difluoromethylation of aldehydes.
The generation of (phenylsulfonyl)difluoromethylcadmium reagent was found to
be feasible via the insertion of cadmium metal into CBr bond of PhSO2CF2Br (2).
This reaction performed in DMF could complete within 15 minutes and the
o
organocadmium species was stable at the temperature of 0 C (Scheme 3). The
cadmium reagent “XCdCF2SO2Ph (X = Br, CF2SO2Ph)” (5) was formed as a mixture
19
of mono- and bisdifluoromethylcadmium in 90% F NMR yield when the reaction
was conducted at room temperature (Figure 2). The mono/bis species were tentatively
assigned via their characteristic 19F NMR spectrum, which showed the expected
singlet at –100.5 ppm (42%) and –100.9 ppm (58%), respectively, for the CF2 group
with the distinctive 111Cd/113Cd satellites.[6b,16-18]
Scheme 3. Optimized reaction conditions for the preparation of
(phenylsulfonyl)difluoromethylcadmium reagent
12

-99.8
-100.0
-100.2
-100.4
-100.6
-100.8
-101.0
-101.2
PPM
-95
-100
-105
-110
-115
-120
-125
PPM
Figure 2. The composition of (phenylsulfonyl)difluoromethylcadmium reagent
prepared in DMF at room temperature
Then we investigated the optimal reaction conditions for difluoromethylation of
the model substrate 2-naphthaldehyde with (phenylsulfonyl)difluoromethylcadmium
reagent. The nucleophilic addition reaction could occur at room temperature in good
19
yield as determined by F NMR spectroscopy analysis. In contrast to the reaction of
organozinc reagent, a certain amount of by-product was detected by GC-MS analysis.
We
proposed
that
it
might
result
from
the
formylation
of
(phenylsulfonyl)difluoromethyl carbinol product by DMF. Further investigation
demonstrated that anhydrous LiCl could not only guarantee the efficiency of the
desired addition reaction, but also inhibit the formation of the formylated by-product.
Compared with the nucleophilic addition to 2-naphthaldehyde with
(phenylsulfonyl)difluoromethylzinc reagent, this reaction proceeded more easily even
13

o
at the temperature of 0 C, suggesting that (phenylsulfonyl)difluoromethylcadmium
reagent had better nucleophilicity toward aldehydes than the
a
(phenylsulfonyl)difluoromethylzinc species (Table 3).
Table 3. Survey of nucleophilic difluoromethylation of 2-naphthaldehyde with
(phenylsulfonyl)difluoromethylcadmium reagent
entrya
additive
time (h)
3 h
temperature (oC) yield (%)b
-
r.t.
r.t.
0
75
92
91
93
82
1
2
3
4
5
-
5 h
-
5 h
LiCl (1.0 eq)
LiCl (2.0 eq)
5 h
r.t.
r.t.
5 h
aThe amount of PhSO2CF2Br and Cd is 2.0 and 3.0 equivalents relative to that
of 2-naphthaldehyde, respectively. bDetermined by 19F NMR analysis of the
c
crude reaction mixture using PhCF3 as an internal standard. The formylation
product is detected by GC-MS analysis.
14

Similar to the reaction of (phenylsulfonyl)difluoromethylzinc species, this method
also proved to be amenable to diverse substrates including both (hetero)aryl and
aliphatic aldehydes (Table 4). However, the further formylation of the
(phenylsulfonyl)difluoromethyl carbinols in the absence of LiCl was found to be
general. Therefore, the addition of anhydrous LiCl is of great importance to inhibit the
undesired formylation process.
Table 4. Nucleophilic difluoromethylation of various aldehydes with
(phenylsulfonyl)difluoromethylcadmium reagenta
4a, 90%
4h, 84%
4l, 68%
4b, 88%
4c, 80%b
4k, 88%
4f, 79%
4i, 72%
4m, 80%
15

4n, 86%
aThe amount of PhSO2CF2Br ,Cd and LiCl is 2.0, 3.0 and 1.0 equivalents relative to
that of the aldehyde, respectively. Isolated yield is reported. b2.0 equivalents of LiCl
are added to the mixture.
3. Conclusions
In summary, we have developed
a
new method for nucleophilic
difluoromethylation of aldehydes by using (phenylsulfonyl)difluoromethylzinc and
(phenylsulfonyl)difluoromethylcadmium reagents. The phenylsulfonyl group plays a
crucial role in increasing the stability of the difluoromethyl anion. Meanwhile, the
introduction of phenylsulfonyl group can also enhance the nucleophilicity of the
difluoromethanide anion towards various aldehydes. By taking advantage of the dual
roles of phenylsulfonyl group, an efficient nucleophilic addition of difluoromethyl
organometallic reagent to aldehydes has been achieved under mild conditions. This
method also promises to be useful for the development of other new
difluoromethylation reactions.
4. Experimental
Unless otherwise mentioned, solvents and reagents were purchased from
commercial sources and used as received. Chlorotrimethylsilane (TMSCl) was
distilled over CaH2. The solvent DMF and NMP were distilled over CaH2. The
16

solvent THF was distilled over Na. Infrared (IR) spectra were recorded on a Shimadzu
1
IR-440 or Bio-Rad FTS-185 spectrometer. H, 13C and 19F NMR spectra were
recorded on a Bruker DPX-400 NMR, Agilent MR-400 NMR or MR-500 NMR
1
spectrometer. H NMR chemical shifts were determined relative to internal (CH3)4Si
13
(TMS) at δ 0.0 or to the signal of a residual protonated solvent: CDCl3 δ 7.26. C
NMR chemical shifts were determined relative to internal TMS at δ 0.0. 19F NMR
chemical shifts were determined relative to CFCl3 at δ 0.0. MS (EI-MS) were
obtained on a Agilent 5975C gas chromatography and HP5989A mass spectrometer.
HRMS (EI) were recorded on a SATURN 2000 mass spectrometer. MS (ESI) were
obtained on an AGILENT1100 mass spectrometer. HRMS (ESI) were recorded on a
FTMS-7 mass spectrometer.
4.1. Preparation of (bromodifluoromethyl)(phenyl)sulfane (1)[17a]
Under an inert atmosphere, NaH (5.760 g, 240 mmol, 60% in w.t.) was added to a
dried round-bottom flask. Anhydrous DMF (250 mL) was added and the mixture was
stirred in an ice-water cold bath. Five minutes later, PhSH (20.5 mL, 200 mmol) was
gradually injected into the flask. After the injection, the mixture continued to be
stirred in the cold bath for another 10 minutes. The cold bath was removed and the
temperature was elevated to room temperature for 20 minutes. The mixture was
stirred in the ice-water cold bath once again. After 5 minutes, CF2Br2 (27.3 mL, 320
mmol) was added into the mixture in three parts, and then the cold bath was removed
10 minutes later. The mixture was allowed to warm to room temperature for another 4
hours. Excess sodium hydride was quenched by dropwise addition of water (150 mL),
and 2 M HCl was used to neutralize the reaction mixture. After extraction with ethyl
acetate for three times, the organic phase was washed with brine, and then dried over
anhydrous Na2SO4. After the solution was filtered and most of the solvent was
evaporated under vacuum, the residue was distilled under vacuum (about 2 mmHg)
o
and the fraction from 63 to 66 C was collected. The collection was distilled again to
give (bromodifluoromethyl)(phenyl)sulfane (1) as a colorless liquid (20.239 g, 42%).
(Bromodifluoromethyl)(phenyl)sulfane (1)
17

Colorless liquid. 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 7.6 Hz, 2H), 7.52 (t, J
= 7.4 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -22.12 (s). MS
(EI, m/z): 238 (M+, 14.29), 159 (100.00), 77 (25.29), 109 (16.17), 240 (14.90), 238
(14.29), 160 (9.76), 65 (7.84), 161 (5.72).
4.2. Preparation of (bromodifluoromethyl)(phenyl)sulfone (2)[17a]
(Bromodifluoromethyl)(phenyl)sulfane (1) (20.239 g, 84.7 mmol) was added to a
dried round-bottom flask. Acetonitrile (60 mL), water (150 mL) and CCl4 (60 mL)
were added and the mixture was stirred at room temperature. NaIO4 (36.233 g, 169.4
mmol) and RuCl3·xH2O (15 mg) were added into the mixture. After 30 minutes,
another portion of NaIO4 (36.233 g, 169.4 mmol) was added. The mixture continued
to be stirred until the completion of the reaction as monitored by thin layer
chromatography (TLC). The crude mixture was filtered by the diatomaceous earth and
the precipitate was washed with CH2Cl2. After most of the solvent was evaporated
under vacuum, the water phase was extracted with ethyl acetate for three times. The
organic layer was dried over anhydrous Na2SO4. After the solution was filtered and
evaporated under vacuum, the residue was subjected to silica gel column
chromatography (eluting with petroleum ether/ethyl acetate) to give
bromodifluoromethyl phenyl sulfone (2) as a white solid (17.932 g, 78%).
((Bromodifluoromethyl)sulfonyl)benzene (2)
1
White solid. H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.9 Hz, 2H), 7.83 (t, J =
19
7.5 Hz, 1H), 7.66 (t, J = 7.8 Hz, 2H). F NMR (376 MHz, CDCl3) δ -57.62 (s). MS
(EI, m/z): 270 (M+, 5.55), 141 (100.00), 77 (78.67), 51 (14.69), 125 (8.63), 142 (8.11),
50 (6.29), 272 (6.14), 143 (5.8).
18

4.3. Nucleophilic difluoromethylation of aldehydes with organozinc and
organocadmium reagents
4.3.1. Typical procedures for nucleophilic difluoromethylation of aldehydes with
(phenylsulfonyl)difluoromethylzinc reagent (Method A)
In the glove box, zinc powder (206.0 mg, 3.15 mmol) was added into a Schlenk
tube. Anhydrous DMF (10.5 mL) was added and the mixture was stirred at room
temperature. Chlorotrimethylsilane (66.5 μL, 0.52 mmol) was then added into the
mixture to activate zinc powder. Five minutes later, PhSO2CF2Br (2) (2.1 mmol) was
added into the suspension. The reaction proceeded smoothly in 15 minutes to give
(phenylsulfonyl)difluoromethylzinc reagent (“XZnCF2SO2Ph”, 3). The mixture was
kept at room temperature to precipitate the remaining zinc powder, and the solution
was directly used for next step.
In the glove box, 2-naphthaldehyde (156.2 mg, 1.0 mmol) was added into another
Schlenk tube. Anhydrous DMF (5 mL) was added and the mixture was stirred at room
temperature. The DMF solution of “XZnCF2SO2Ph” (3) (10 mL, corresponding to the
reaction of ca. 2.0 mmol of PhSO2CF2Br and ca. 3.0 mmol of zinc powder) was added
to the solution of 2-naphthaldehyde dropwise. The mixture was stirred at room
temperature for 5 hours, and aqueous HCl (2 M, 10 mL) was added to quench the
reaction. After extraction with ethyl acetate for three times, the organic phase was
washed with brine, and then dried over anhydrous Na2SO4. After the solution was
filtered and evaporated under vacuum, the residue was subjected to silica gel column
chromatography (eluting with petroleum ether/ethyl acetate) to give the corresponding
difluoromethylated carbinol 4a as a white solid (307.5 mg, 88%).
4.3.2. Typical procedures for nucleophilic difluoromethylation of aldehydes with
(phenylsulfonyl)difluoromethylcadmium reagent (Method B)
In the glove box, cadmium powder (354.1 mg, 3.15 mmol) was added into a
Schlenk tube. Anhydrous DMF (10.5 mL) was added and the mixture was stirred at
room temperature. Chlorotrimethylsilane (66.5 μL, 0.52 mmol) was then added into
the mixture to activate cadmium powder. Two and a half minutes later, PhSO2CF2Br
19

(2) (569.3 mg, 2.1 mmol) was added into the suspension. The reaction proceeded
smoothly in 15 minutes to give (phenylsulfonyl)difluoromethylcadmium reagent
(“XCdCF2SO2Ph”, 5). The mixture was kept at room temperature to precipitate the
remaining zinc powder, and the solution was directly used for next step.
In the glove box, 2-naphthaldehyde (156.2 mg, 1.0 mmol) and anhydrous LiCl
(42.4 mg, 1.0 mmol) was added into another Schlenk tube. Anhydrous DMF (5 mL)
was added and the mixture was stirred at room temperature. The DMF solution of
“XCdCF2SO2Ph” (5) (10 mL, corresponding to the reaction of ca. 2.0 mmol of
PhSO2CF2Br and ca. 3.0 mmol of zinc powder) was added to the solution of
2-naphthaldehyde dropwise. The mixture was stirred at room temperature for 5 hours,
and aqueous HCl (2 M, 10 mL) was added to quench the reaction. After extraction
with ethyl acetate for three times, the organic phase was washed with brine, and then
dried over anhydrous Na2SO4. After the solution was filtered and evaporated under
vacuum, the residue was subjected to silica gel column chromatography (eluting with
petroleum ether/ethyl acetate) to give the corresponding difluoromethylated carbinol
4a as a white solid (314.7 mg, 90%).
4.3.3. Characterization data for the isolated carbinol compounds 4
2,2-Difluoro-1-(naphthalen-2-yl)-2-(phenylsulfonyl)ethan-1-ol (4a) [17c]
1
88% yield (Method A); 90% yield (Method B). White solid. H NMR (400 MHz,
CDCl3) δ 8.02 (d, J = 7.4 Hz, 2H), 7.97 (s, 1H), 7.89 – 7.80 (m, 3H), 7.75 (t, J = 7.5
Hz, 1H), 7.64 – 7.55 (m, 3H), 7.54 – 7.47 (m, 2H), 5.76 (d, J = 20.8 Hz, 1H), 3.43 (s,
1H). 19F NMR (376 MHz, CDCl3) δ -103.68 (d, J = 237.9 Hz), -118.98 (dd, J = 238.0,
21.3 Hz). 13C NMR (125 MHz, CDCl3) δ 135.6 , 133.9 , 133.0 , 132.8 , 131.1 , 130.7 ,
129.4 , 128.4 , 128.4 , 128.2 , 127.8 , 126.9 , 126.5 , 125.0 , 120.5 (dd, J = 298.8,
289.1 Hz), 71.5 (dd, J = 26.4, 19.8 Hz). MS (EI, m/z): 348 (M+, 11.24), 157 (100.00),
129 (46.89), 128 (27.56), 127 (14.75), 159 (11.93), 77 (11.71), 158 (11.47).
20

1-([1,1'-Biphenyl]-4-yl)-2,2-difluoro-2-(phenylsulfonyl)ethan-1-ol (4b)
o
86% yield (Method A); 88% yield (Method B). White solid. m.p.: 141-143 C. IR
(KBr): 3559.7, 3092.9, 3062.2, 3030.3, 1599.8, 1581.9, 1567.1, 1519.4, 1487.5,
1448.3, 1408.1, 1387.4, 1331.6, 1312.9, 1253.3, 1200.5, 1186.6, 1154.0, 1109.2,
1089.4, 1081.3, 1023.8, 1001.3, 856.4, 833.5, 794.3, 753.2, 753.2, 720.6, 669.8, 684.5,
1
629.4, 617.2, 589.0, 555.8, 530.3, 431.9. H NMR (400 MHz, CDCl3) δ 8.02 (d, J =
7.4 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H), 7.66 – 7.52 (m, 8H), 7.44 (t, J = 7.6 Hz, 2H),
7.36 (t, J = 7.3 Hz, 1H), 5.63 (d, J = 20.5 Hz, 1H), 3.34 (s, 1H). 19F NMR (376 MHz,
CDCl3) δ -103.82 (d, J = 237.8 Hz), -119.17 (dd, J = 237.8, 21.2 Hz). 13C NMR (125
MHz, CDCl3) δ 142.5 , 140.5 , 135.7 , 132.8 , 132.6 , 130.8 , 129.5 , 128.9 , 128.6 ,
127.7 , 127.3 , 127.3 , 120.3 (dd, J = 298.7, 288.9 Hz), 71.2 (dd, J = 26.5, 19.9 Hz).
MS (EI, m/z): 374 (M+, 5.72), 183 (100.00), 155 (22), 184 (14.91), 77 (13.9), 152
(10.59), 153 (8.03), 154 (7.84), 165(7.45). HRMS (EI): m/z calcd. For C20H16O3F2S
(M+) 374.0788, found 374.0797. Anal. Calcd for C20H16F2O3S: C, 64.16; H, 4.31.
Found: C, 64.10; H, 4.54.
2,2-Difluoro-1-(4-methoxyphenyl)-2-(phenylsulfonyl)ethan-1-ol (4c) [17c]
80% yield (Method A, 2.0 equiv of LiCl was used as an additive); 80% yield
1
(Method B, 2.0 equiv of LiCl was used as an additive). White solid. H NMR (400
MHz, CDCl3) δ 8.00 (d, J = 7.6 Hz, 2H), 7.76 (t, J = 7.5 Hz, 1H), 7.61 (t, J = 7.9 Hz,
2H), 7.40 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 5.52 (dt, J = 21.2, 3.0 Hz, 1H),
3.80 (s, 3H), 3.24 (d, J = 3.4 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -104.05 (d, J =
13
237.2 Hz), -119.30 (dd, J = 237.2, 21.1 Hz). C NMR (125 MHz, CDCl3) δ 160.5 ,
135.5 , 132.8 , 130.6 , 129.4 , 129.3 , 125.7 , 120.3 (dd, J = 298.3, 288.4 Hz), 113.9 ,
21

70.9 (dd, J = 26.5, 19.8 Hz), 55.3 . MS (EI, m/z): 328 (M+, 3.43), 137 (100.00), 77
(11.96), 109 (10.49), 138 (8.29), 139 (6.14), 94 (5.2), 51 (3.3).
4-(2,2-Difluoro-1-hydroxy-2-(phenylsulfonyl)ethyl)benzonitrile (4d)
o
88% yield (Method A). White solid. m.p.: 132-134 C. IR (KBr): 3396.7, 3097.4,
2237.0, 1607.4, 1583.8, 1505.0, 1448.7, 1404.7, 1348.8, 1337.0, 1314.9, 1298.0,
1245.6, 1200.5, 1177.2, 1158.3, 1104.6, 1091.6, 1008.5, 863.4, 829.3, 791.2, 755.2,6,
1
742.0, 700.2, 681.7, 617.9, 590.4, 564.3, 552.8, 481.4, 457.0, 428.7. H NMR (400
MHz, CDCl3) δ 8.00 (d, J = 7.5 Hz, 2H), 7.83 – 7.77 (m, 1H), 7.72 – 7.58 (m, 6H),
5.65 (dt, J = 20.5, 3.0 Hz, 1H), 3.63 (d, J = 3.4 Hz, 1H). 19F NMR (376 MHz, CDCl3)
13
δ -104.31 (d, J = 238.5 Hz), -118.95 (dd, J = 238.4, 20.5 Hz). C NMR (125 MHz,
CDCl3) δ 138.9 , 136.0 , 132.4 , 132.2 , 130.8 , 129.6 , 129.0 , 119.8 (dd, J = 299.1,
289.9 Hz), 118.4 , 113.3 , 70.6 (dd, J = 26.0, 20.1 Hz). MS (EI, m/z): 323 (M+, 0.66),
132 (100.00), 77 (26.65), 134 (14.9), 104 (14.49), 78 (14.31), 143 (14.06), 51 (9.37),
133 (9.01). HRMS (EI): m/z calcd. For C15H11NO3F2S (M+) 323.0428, found
323.0421.
2,2-Difluoro-1-(3-iodophenyl)-2-(phenylsulfonyl)ethan-1-ol (4e)
o
90% yield (Method A). White solid. m.p.: 117-118 C. IR (KBr): 3535.3, 3067.8,
1810.5, 1683.8, 1591.0, 1581.5, 1567.0, 1540.6, 1469.8, 1448.1, 1424.3, 1394.2,
1333.1, 1311.3, 1179.0, 1155.2, 1107.8, 1087.4, 1074.3, 1060.7, 1025.1, 1007.7,
996.6, 914.5, 903.4, 845.9, 814.8, 767.0, 756.6, 717.9, 683.6, 658.2, 637.4, 616.6,
586.2, 541.6, 518.1, 476.3, 455.0, 440.2, 420.6. 1H NMR (400 MHz, CDCl3) δ 8.00 (d,
J = 7.4 Hz, 2H), 7.84 (s, 1H), 7.83 – 7.73 (m, 1H), 7.75 – 7.67 (m, 1H), 7.68 – 7.59
(m, 2H), 7.44 (d, J = 7.8 Hz, 1H), 7.11 (t, J = 7.8 Hz, 1H), 5.52 (d, J = 21.3 Hz, 1H),
3.42 (s, 1H). 19F NMR (376 MHz, CDCl3) δ -103.79 (d, J = 238.3 Hz), -119.38 (dd, J
22

= 238.0, 21.2 Hz). 13C NMR (125 MHz, CDCl3) δ 138.7 , 137.0 , 135.9 , 135.8 ,
132.5 , 130.8 , 130.2 , 129.5 , 127.5 , 119.9 (dd, J = 299.2, 289.5 Hz), 94.2 , 70.5 (dd,
J = 26.4, 20.0 Hz). MS (EI, m/z): 424 (M+, 8.93), 233 (100.00), 78 (35.41), 77 (27.05),
91 (26.03), 203 (19.38), 144 (18.16), 127 (11.78), 51 (10.92). HRMS (EI): m/z calcd.
For C14H11O3F2SI (M+) 423.9442, found 423.9948.
1-(4-Bromothiophen-2-yl)-2,2-difluoro-2-(phenylsulfonyl)ethan-1-ol (4f)
o
88% yield (Method A); 79% yield (Method B). White solid. m.p.: 122-124 C. IR
(KBr): 3853.2, 3648.8, 3447.0, 3117.9, 3088.4, 3064.5, 2905.4, 1583.5, 1525.6,
1478.7, 1450.8, 1427.2, 1389.4, 1355.3, 1324.5, 1314.1, 1288.6, 1203.4, 1182.4,
1153.2, 1122.0, 1081.6, 1024.8, 988.7, 872.2, 856.5, 825.4, 798.5, 771.9, 746.9, 728.3,
683.4, 621.8, 596.6, 582.0, 556.9, 518.0, 453.4, 427.4. 1H NMR (400 MHz, CDCl3) δ
8.00 (d, J = 7.8 Hz, 2H), 7.84 – 7.75 (m, 1H), 7.67 – 7.61 (m, 2H), 7.28 (d, J = 1.5 Hz,
1H), 7.09 (s, 1H), 5.79 (d, J = 19.9 Hz, 1H), 3.51 (s, 1H). 19F NMR (376 MHz, CDCl3)
13
δ -104.53 (dd, J = 237.0, 2.5 Hz), -119.18 (dd, J = 237.0, 20.0 Hz). C NMR (125
MHz, CDCl3) δ 137.3 , 135.9 , 132.5 , 130.8 , 130.3 , 129.6 , 124.7 , 119.3 (dd, J =
299.3, 289.7 Hz), 109.7 , 67.8 (dd, J = 27.3, 20.9 Hz). MS (EI, m/z): 382 (M+, 4.16),
191 (100.00), 193 (97.5), 84 (31.41), 77 (30.37), 51 (14.34), 78 (10.79), 242 (10.76),
240 (10.09). HRMS (EI): m/z calcd. For C12H9O3F2S2Br (M+) 381.9145, found
381.9143.
1-(5-Bromofuran-2-yl)-2,2-difluoro-2-(phenylsulfonyl)ethan-1-ol (4g)
84% yield (Method A, 1.0 equiv of LiCl was used as an additive). White solid.
o
m.p.: 96-97 C. IR (KBr): 3466.7, 3137.6, 3118.2, 3058.8, 1583.4, 1497.9, 1478.0,
1448.7, 1408.3, 1364.2, 1336.8, 1312.4, 1275.5, 1227.7, 1198.3, 1178.5, 1157.9,
1108.8, 1087.2, 1074.9, 1017.5, 1000.0, 943.8, 924.8, 799.9, 768.3, 751.8, 710.3,
1
682.9, 605.3, 582.0, 532.3, 494.6, 438.2. H NMR (400 MHz, CDCl3) δ 7.99 (d, J =
23

7.4 Hz, 2H), 7.78 (t, J = 7.5 Hz, 1H), 7.63 (t, J = 7.8 Hz, 2H), 6.53 (d, J = 3.4 Hz, 1H),
6.32 (d, J = 3.4 Hz, 1H), 5.53 (dt, J = 18.6, 4.7 Hz, 1H), 3.23 (d, J = 4.9 Hz, 1H). 19F
NMR (376 MHz, CDCl3) δ -105.91 (dd, J = 237.8, 4.3 Hz), -116.43 (dd, J = 237.8,
18.5 Hz). 13C NMR (125 MHz, CDCl3) δ 148.9 , 135.8 , 132.7 , 130.8 , 129.5 , 123.7 ,
119.6 (dd, J = 298.2, 291.3 Hz), 113.9 , 112.7 , 66.0 (dd, J = 26.7, 21.4 Hz). MS (EI,
m/z): 366 (M+, 4.41), 175 (100.00), 177 (96.71), 77 (18.64), 51 (10.3), 224 (10.12),
226 (9.89), 178 (5.96), 101 (5.79). HRMS (EI): m/z calcd. For C12H9O4F2SBr (M+)
365.9373, found 365.9385.
Methyl 4-(2,2-difluoro-1-hydroxy-2-(phenylsulfonyl)ethyl)benzoate (4h)
o
95% yield (Method A); 84% yield (Method B). White solid. m.p.: 117-119 C. IR
(KBr): 3503.9, 3066.1, 2955.8, 1731.3, 1717.9, 1610.2, 1477.6, 1449.3, 1437.4,
1416.4, 1335.8, 1313.1, 1281.1, 1192.9, 1178.3, 1157.9, 1108.9, 1087.6, 1017.9,
1003.6, 962.5, 872.8, 842.4, 812.1, 763.3, 750.2, 718.0, 698.1, 684.3, 623.2, 587.2,
1
555.8, 535.3, 491.3, 440.2. H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 8.4 Hz, 2H),
8.00 (d, J = 7.3 Hz, 2H), 7.78 (t, J = 7.5 Hz, 1H), 7.63 (t, J = 7.9 Hz, 2H), 7.56 (d, J =
8.1 Hz, 2H), 5.65 (dt, J = 21.4, 2.9 Hz, 1H), 3.91 (s, 3H), 3.54 (d, J = 3.9 Hz, 1H). 19F
NMR (376 MHz, CDCl3) δ -104.01 (d, J = 238.6 Hz), -119.10 (dd, J = 238.1, 21.0
13
Hz). C NMR (125 MHz, CDCl3) δ 166.8 , 138.6 , 135.8 , 132.7 , 131.2 , 130.8 ,
129.7 , 129.5 , 128.2 , 120.1 (dd, J = 299.2, 289.5 Hz), 71.0 (dd, J = 26.1, 20.1 Hz),
52.4 . MS (EI, m/z): 356 (M+, 0.34), 165 (100.00), 77 (17.22), 166 (10.57), 59 (9.57),
78 (7.98), 105 (6.54), 214 (5.84), 167 (5.38). HRMS (EI): m/z calcd. For C16H14O5F2S
(M+) 356.0530, found 356.0536. Anal. Calcd for C16H14F2O5S: C, 53.93; H, 3.96.
Found: C, 53.75; H, 3.96.
1,1-Difluoro-4-phenyl-1-(phenylsulfonyl)butan-2-ol (4i) [17b]
24

78% yield (Method A); 72% yield (Method B). Light yellow liquid. 1H NMR (400
MHz, CDCl3) δ 7.98 (d, J = 7.7 Hz, 2H), 7.80 – 7.75 (m, 1H), 7.66 – 7.60 (m, 2H),
7.34 – 7.28 (m, 2H), 7.25 – 7.19 (m, 3H), 4.50 – 4.37 (m, 1H), 3.03 – 2.91 (m, 1H),
19
2.83 – 2.75 (m, 1H), 2.73 (d, J = 5.1 Hz, 1H), 2.19 – 1.94 (m, 2H). F NMR (376
MHz, CDCl3) δ -108.26 (dd, J = 236.7, 5.6 Hz), -116.81 (dd, J = 236.5, 18.0 Hz). 13C
NMR (125 MHz, CDCl3) δ 140.7 , 135.6 , 132.9 , 130.7 , 129.5 , 128.7 , 128.6 ,
126.3 , 121.4 (dd, J = 294.8, 291.8 Hz), 68.8 (dd, J = 24.5, 21.1 Hz), 31.1 , 31.0. MS
(EI, m/z): 326 (M+, 1.3), 91 (100.00), 144 (41.77), 104 (41.16), 143 (39.25), 77
(18.79), 147 (18.03), 105 (14.65).
2,2-Difluoro-1-mesityl-2-(phenylsulfonyl)ethan-1-ol (4j)
93% yield (Method A, 1.0 equiv of LiCl was used as an additive). White solid.
o
m.p.: 87-88 C. IR (KBr): 3749.4, 3647.6, 3522.4, 3095.6, 2970.8, 2922.5, 2334.1,
2245.5, 1611.7, 1582.4, 1557.7, 1540.2, 1506.5, 1477.9, 1409.5, 1384.9, 1325.8,
1311.0, 1195.3, 1179.2, 1157.5, 1140.3, 1119.3, 1080.6, 1028.7, 987.4, 959.7, 929.7,
907.2, 849.5, 814.0, 776.7, 756.4, 731.9, 707.8, 682.9, 650.5, 625.7, 596.0, 569.3,
552.2, 540.0, 520.7, 493.9, 444.5. 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 7.7 Hz,
2H), 7.82 – 7.73 (m, 1H), 7.63 (t, J = 7.9 Hz, 2H), 6.85 (s, 2H), 6.14 (dd, J = 26.8, 4.5
Hz, 1H), 3.09 (d, J = 4.4 Hz, 1H), 2.50 (s, br., 3H), 2.33 (s, br., 3H), 2.25 (s, 3H). 19F
NMR (376 MHz, CDCl3) δ -102.65 (d, J = 236.4 Hz), -114.42 (dd, J = 236.5, 26.7
13
Hz). C NMR (125 MHz, CDCl3) δ 139.3 , 138.7 , 137.9 , 135.6 , 132.7 , 131.7 ,
130.8 , 129.5 , 129.2 , 127.0 , 121.8 (dd, J = 302.8, 288.0 Hz), 68.2 (dd, J = 27.5, 19.7
Hz), 20.9 . MS (EI, m/z): 340 (M+, 3.83), 149 (100.00), 84 (41.09), 86 (28.14), 121
(13.16), 150 (12.67), 77 (9.02), 105 (8.16), 147 (6.83). HRMS (EI): m/z calcd. For
C17H18O3F2S (M+) 340.0945, found 340.0941.
1-(4-Chlorophenyl)-2,2-difluoro-2-(phenylsulfonyl)ethan-1-ol (4k) [17b]
25

1
88% yield (Method B). White solid. H NMR (400 MHz, CDCl3) δ 8.00 (d, J =
7.5 Hz, 2H), 7.82 – 7.75 (m, 1H), 7.63 (t, J = 7.9 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H),
7.36 (d, J = 8.6 Hz, 2H), 5.56 (dt, J = 21.0, 3.0 Hz, 1H), 3.41 (d, J = 3.7 Hz, 1H). 19F
NMR (376 MHz, CDCl3) δ -104.17 (dd, J = 238.0, 2.5 Hz), -119.38 (dd, J = 237.9,
20.9 Hz). 13C NMR (125 MHz, CDCl3) δ 135.8 , 135.6 , 132.6 , 132.2 , 130.7 , 129.5 ,
129.5 , 128.8 , 120.0 (dd, J = 298.7, 289.2 Hz), 70.7 (dd, J = 26.2, 20.0 Hz). MS (EI,
m/z): 332 (M+, 2.53), 141 (100.00), 143 (45.53), 77 (34.7), 78 (11.21), 142 (8.98), 51
(8.8), 113 (7.6), 40 (6.23).
1-(4-(tert-Butyl)phenyl)-2,2-difluoro-2-(phenylsulfonyl)ethan-1-ol (4l) [17b]
1
68% yield (Method B). White solid. H NMR (400 MHz, CDCl3) δ 8.00 (d, J =
7.8 Hz, 2H), 7.76 (t, J = 7.7 Hz, 1H), 7.61 (t, J = 7.8 Hz, 2H), 7.40 (s, 4H), 5.55 (dt, J
= 21.5, 3.2 Hz, 1H), 3.20 (d, J = 3.9 Hz, 1H), 1.30 (s, 9H). 19F NMR (376 MHz,
CDCl3) δ -103.65 (dd, J = 237.8, 2.5 Hz), -119.31 (dd, J = 237.7, 21.4 Hz). 13C NMR
(125 MHz, CDCl3) δ 152.6 , 135.5 , 132.9 , 130.6 , 129.3 , 127.8 , 125.4 , 120.3 (dd, J
= 298.6, 288.6 Hz), 71.1 (dd, J = 26.7, 19.6 Hz), 34.7 , 31.2 . MS (EI, m/z): 354 (M+,
1.83), 163 (100.00), 164 (12.26), 57 (11.82), 197 (8.85), 77 (8.75), 91 (5.25), 133
(4.19), 148 (3.67).
(E)-1,1-Difluoro-4-phenyl-1-(phenylsulfonyl)but-3-en-2-ol (4m) [17b]
1
80% yield (Method B). White solid. H NMR (400 MHz, CDCl3) δ 8.01 (d, J =
7.5 Hz, 2H), 7.77 (t, J = 7.5 Hz, 1H), 7.63 (t, J = 7.9 Hz, 2H), 7.44 – 7.39 (m, 2H),
7.39 – 7.25 (m, 3H), 6.89 (d, J = 15.9 Hz, 1H), 6.25 (dd, J = 15.9, 6.6 Hz, 1H), 5.20 –
5.09 (m, 1H), 3.00 (d, J = 5.5 Hz, 1H). 19F NMR (376 MHz, CDCl3) δ -106.58 (dd, J
26

13
= 237.3, 5.1 Hz), -116.22 (dd, J = 237.2, 17.1 Hz). C NMR (125 MHz, CDCl3) δ
136.5 , 135.7 , 133.1 , 130.8 , 129.5 , 128.8 , 128.7 , 127.1 , 120.6 (dd, J = 296.5,
292.3 Hz), 120.6 , 71.0 (dd, J = 25.3, 21.4 Hz). MS (EI, m/z): 324 (M+, 3.56), 133
(100.00), 115 (17.01), 134 (14.37), 77 (12.84), 182 (8.63), 55 (7.33), 103 (4.76), 78
(4.36).
2,2-Difluoro-2-(phenylsulfonyl)-1-(4-(trifluoromethyl)phenyl)ethan-1-ol (4n)
o
86% yield (Method B). White solid. m.p.: 78-80 C. IR (KBr): 3529.8, 3064.3,
2949.6, 1940.7, 1823.0, 1708.4, 1622.1, 1583.1, 1478.1, 1449.3, 1419.8, 1399.4,
1332.7, 1165.3, 1129.5, 1114.0, 1089.6, 1068.7, 1020.1, 1008.8, 861.2, 829.2, 796.1,
1
763.4, 728.6, 710.3, 684.0, 658.3, 635.9, 623.8, 603.7, 584.5, 535.0, 473.9, 442.9. H
NMR (400 MHz, CDCl3) δ 8.00 (d, J = 7.8 Hz, 2H), 7.79 (t, J = 7.5 Hz, 1H), 7.69 –
7.56 (m, 6H), 5.66 (d, J = 20.9 Hz, 1H), 3.51 (d, J = 3.1 Hz, 1H). 19F NMR (376 MHz,
13
CDCl3) δ -62.85 , -104.13 (d, J = 238.4 Hz), -119.23 (dd, J = 238.4, 20.9 Hz). C
NMR (125 MHz, CDCl3) δ 137.6 , 135.9 , 132.5 , 131.7 (q, J = 32.5 Hz), 130.8 ,
129.6 , 128.6 , 125.5 (q, J = 3.8 Hz), 124.0 (d, J = 272.3 Hz), 120.0 (dd, J = 299.1,
289.7 Hz), 70.8 (dd, J = 26.1, 20.1 Hz). MS (EI, m/z): 366 (M+, 0.37), 175 (100.00),
127 (23.49), 77 (18.87), 177 (16.19), 78 (13.51), 143 (12.55), 176 (9.26), 51 (6.41).
HRMS (EI): m/z calcd. For C15H11O3F 5(M+) 366.0349, found 366.0363.
Acknowledgements
Support of our work by the National Basic Research Program of China
(2015CB931900), the National Natural Science Foundation of China (21632009,
21421002 and 21372246), the Chinese Academy of Sciences, Shanghai Academic
27

Research Leader Program (15XD1504400), and the Youth Innovation Promotion
Association CAS (2014231) is gratefully acknowledged.
References References
[1] (a) P. Kirsch, Modern fluoroorganic chemistry : synthesis, reactivity, applications,
2nd, Wiley-VCH: Weinheim, 2013.
(b) W. B. Farnham, Chem. Rev. 96 (1996) 1633.
(c) G. K. S. Prakash, A. K. Yudin, Chem. Rev. 97 (1997) 757.
(d) G. K. S. Prakash, M. Mandal, J. Fluorine Chem. 112 (2001) 123.
(e) R. P. Singh, J. M. Shreeve, Tetrahedron 56 (2000) 7613.
(f) J.-A. Ma, D. Cahard, J. Fluorine Chem. 128 (2007) 975.
(g) M. Medebielle, W. R. Dolbier Jr., J. Fluorine Chem. 129 (2008) 930.
(h) A. Studer, Angew. Chem., Int. Ed. 51 (2012) 8950.
(i) T. Umemoto, Chem. Rev. 96 (1996) 1757.
[2] (a) G. M. Blackburn, D. E. Kent, F. Kolkmann, J. Chem. Soc., Chem. Commun.
(1981) 1188.
(b) G. M. Blackburn, D. E. Kent, F. Kolkmann, J. Chem. Soc., Perkin Trans. 1
(1984) 1119.
(c) Motherwell, W. B.; Tozer, M. J.; Ross, B. C. J. Chem. Soc., Chem. Commun.
1989, 1437.
(d) J.-B. Han, H.-L. Qin, S.-H. Ye, L. Zhu, C.-P. Zhang, J. Org. Chem. 81 (2016)
2506.
[3] (a) J. A. Erickson, J. I. McLoughlin, J. Org. Chem. 60 (1995) 1626.
(b) R. Sasson, A. Hagooly, S. Rozen, Org. Lett. 5 (2003) 769.
(c) Y. Li, J. Hu, Angew. Chem., Int. Ed. 44 (2005) 5882.
28

(d) G. K. S. Prakash, C.Weber, S. Chacko, G. A. Olah, Org. Lett. 9 (2007) 1863.
[4] (a) J. Hu, W. Zhang, F. Wang, Chem. Commun. (2009) 7465.
(b) M.-C. Belhomme, T. Besset, T. Poisson, X. Pannecoucke, Chem. Eur. J. 21
(2015) 12836.
[5] (a) Y. Zhao, W. Huang, J. Zheng, J. Hu, Org. Lett. 13 (2011) 5342.
(b) G.-F. Du,; Y. Wang,; C.-Z. Gu,; B. Dai,; L. He, RSC Adv. 5 (2015) 35421.
(c) O. M. Michurin, D. S. Radchenko, I. V. Komarov, Tetrahedron 72 (2016) 1351.
(d) D. Chen, C. Ni, Y. Zhao, X. Cai, X. Li, P. Xiao, J. Hu, Angew. Chem., Int. Ed.
55 (2016) 12632; and references therein.
(e) C. Ni, L. Zhu, J. Hu, Acta Chim. Sin. 73 (2015) 90.
[6] (a) R. Eujen, B. Hoge, D. J. Brauer, J. Organomet. Chem. 519 (1996) 7.
(b) D. J. Burton, G. A. Hartgraves, J. Fluorine Chem. 128 (2007) 1198.
(c) Other method on fluorinated organozincs derived from difluorocarbene
insertion is as below: V. V. Levin, A. A. Zemtsov, M. I. Struchkova, A. D. Dilman,
Org. Lett. 15 (2013) 917.
[7] (a) G. K. S. Prakash, S. K. Ganesh, J. P. Jones, A. Kulkarni, K. Masood, J. K.
Swabeck, G. A. Olah, Angew. Chem., Int. Ed. 51 (2012) 12090.
(b) P. S. Fier, J. F. Hartwig, J. Am. Chem. Soc. 134 (2012) 5524.
(c) X.-L. Jiang, Z.-H. Chen, X.-H. Xu, F.-L. Qing, Org. Chem. Front. 1 (2014) 774.
(d) C. Matheis, K. Jouvin, L. J. Goossen, Org. Lett. 16 (2014) 5984.
(e) B. Bayarmagnai, C. Matheis, K. Jouvin, L. J. Goossen, Angew. Chem. Int. Ed.
54 (2015) 5753.
(f) K. Jouvin, C. Matheis, L. J. Goossen, Chem. Eur. J. 21 (2015) 14324.
[8] Y. Gu, X. Leng, Q. Shen, Nature Commun. 5 (2014) 5405.
[9] K. Aikawa, W. Toya, Y. Nakamura, K. Mikami, Org. Lett. 17 (2015) 4996.
[10] (a) H. Serizawa, K. Ishii, K. Aikawa, K. Mikami, Org. Lett. 18 (2016) 3686.
(b) K. Aikawa, H. Serizawa, K. Ishii, K. Mikami, Org. Lett. 18 (2016) 3690.
(c) L. Xu, D. A. Vicic, J. Am. Chem. Soc. 138 (2016) 2536.
[11] (a) G. K. S. Prakash, J. Hu, Acc. Chem. Res. 40 (2007) 921.
(b) J. Hu, J. Fluorine Chem. 130 (2009) 1130.
29