Synthesis of Difluoromethyl Ketones from Weinreb Amides, and Tandem Addition/Cyclization of o-Alkynylaryl Weinreb Amides

Article abstract of DOI:10.1002/ejoc.201701322

[Difluoro(phenylsulfanyl)methyl]trimethylsilane (PhSCF₂SiMe₃) underwent a fluoride-induced nucleophilic addition to the carbonyl group of Weinreb amides to provide the corresponding difluoro(phenylsulfanyl)methyl ketones. These were

Full text of DOI:10.1002/ejoc.201701322

A Journal of
Accepted Article
Title: Synthesis of Difluoromethyl Ketones from Weinreb Amides and
Tandem Addition/Cyclization of o-Alkynylaryl Weinreb Amides
Authors: Jongkonporn Phetcharawetch, Nolan M Betterley, Darunee
Soorukram, Manat Pohmakotr, Vichai Reutrakul, and Chutima
Kuhakarn
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701322
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10.1002/ejoc.201701322
European Journal of Organic Chemistry
FULL PAPER
Synthesis of Difluoromethyl Ketones from Weinreb Amides and
Tandem Addition/Cyclization of o-Alkynylaryl Weinreb Amides
Jongkonporn Phetcharawetch,[a] Nolan M. Betterley,[a] Darunee Soorukram,[a] Manat
Pohmakotr,[a] Vichai Reutrakul,[a] and Chutima Kuhakarn*[a]
Abstract:
(Difluoro(phenylsulfanyl)methyl)trimethylsilane
PhSCF2SiMe3 (1) has not been reported. As a part of our
continuing effort to demonstrate the synthetic utility of 1, herein
we report fluoride-induced nucleophilic addition of 1 to Weinreb
amides. It was anticipated that the resulting substitution adduct
could be utilized for the synthesis of difluoromethyl ketones after
reductive cleavage of the phenylsulfanyl group (Scheme 1).
(PhSCF2SiMe3) underwent fluoride-induced nucleophilic addition to
the carbonyl group of Weinreb amides to provide the corresponding
difluoro(phenylsulfanyl)methyl ketones which can be converted into
difluoromethyl ketones through selective reductive cleavage of the
phenylsulfanyl group. The reaction of o-alkynyl Weinreb amides
derived from benzoic acid derivatives resulted in the formation of
cyclized products through 5-exo-dig cyclization.
Introduction
Scheme 1. Synthesis of difluoromethyl ketones.
In recent years, the importance of fluorinated molecules has
been recognized in various fields including agrochemistry,
pharmaceutical chemistry and materials sciences due to the
unique effects that fluorine has on the chemical and physical
properties of the compounds.[1] Therefore, tremendous efforts
are being directed towards the development of efficient
methodology for the introduction of fluorine atom or fluorine-
containing synthon into organic molecules.[2] Among fluoride-
Results and Discussion
Inspired by the recent work described by Leadbeater and co-
workers,[18] we initially employed CsF as a fluoride source and
used 2a as a benchmark substrate to react with PhSCF2SiMe3
(1). The results are summarized in Table 1. Treatment of 2a with
PhSCF2SiMe3 (1, 2 equiv.) in the presence of CsF (20 mol%) in
toluene at 0 oC to room temperature for 20 h followed by
quenching with TBAF resulted in the recovery of 2a (60% yield).
The desired adduct 3a and the double addition adduct 4a were
obtained in only 19% and 10% yields, respectively (Table 1,
Entry 1). Similar results were observed when THF was
employed as the solvent in place of toluene (Table 1, Entry 2).
Gratifyingly, when tetrabutylammonium difluorotriphenylsilicate
(TBAT) was employed as a fluoride source, better conversion
was observed (Table 1, Entry 3). The optimal reaction conditions
were to use TBAT (20 mol%) in toluene at 0 oC to room
temperature for 2 h leading to the desired adduct 3a in 91%
yield without the formation of double addition adduct 4a (Table 1,
Entry 4). In agreement with Leadbeater’s work, we also found
mediated
nucleophilic
fluoroalkylation
reactions
with
(fluoroalkyl)silanes, studies on CF3SiMe3 (Rupert–Prakash
[5]
reagent),[3] PhSO2CF2SiMe3,[4] and PhSCF2SiMe3
documented in the literature.
were well
Unlike well-known trifluoromethylation chemistry, far fewer
methods for the installation of the difluoromethyl group (CF2H)
into organic molecules have been reported. The methods entail
deoxygenative
fluorination
of
carbonyl
compounds,[6]
7]
difluorocarbene substrates,[2h,
TMSCF2H and other related
reactions,[8] and Bu3SnCF2H.[9] In particular, difluoromethyl
ketones were reported to be prepared from a variety of starting
compounds including enamines or imines,[10] arylacetylenes or
arenes,[11] aldehydes or acid chlorides,[12] trifluoromethyl
ketones,[13] 1-trifluoromethyl-1,3-diketones,[14] β-keto acids or β-
that toluene,
a non-polar solvent was important for the
keto
bromodifluoroacetate.[16]
esters,[15]
and
arylboronic
acids
with
stabilization of the initially formed neutral silyl enol ether adduct
5a. Without pre-formation of 5a, if the more electrophilic product
3a is formed first, this leads to undesired double addition leading
to compound 4a. Therefore, when the reaction of 2a with 1 was
quenched with water, the silyl enol ether adduct 5a could be
detected; after chromatographic purification 5a was isolated in
8% yield (Table 1, Entry 5). It is worth noting TBAT proved to be
a better initiator towards PhSCF2SiMe3 and toluene, a non-polar
solvent, was crucial for the stabilization of the initially formed
neutral silyl enol ether adduct which can be readily cleaved upon
treatment with TBAF to yield 3a as the product.
Although fluoride-catalyzed nucleophilic substitution
reactions of CF3SiMe3 to carboxylic acid derivatives, including
esters[17] and Weinreb amides[18] were documented to access
trifluoromethyl
ketones,
the
installation
of
difluoro(phenylsulfanyl)methyl moiety to Weinreb amides with
[a]
Department of Chemistry and Center of Excellence for Innovation in
Chemistry (PERCH-CIC), Faculty of Science, Mahidol University,
Rama VI Road, Bangkok 10400, Thailand
E-mail: chutima.kon@mahidol.ac.th
http://chemistry.sc.mahidol.ac.th/en/
Tel: (+)-66-2-2015395; Fax: (+)-66-2-3547151
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201701322
European Journal of Organic Chemistry
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Table 1. Optimization of reaction conditions.[a]
Table 2. Evaluation of substrate scope and limitation of the reaction.[a]
Entry
1
Substrate; R =
2a; 3,4,5-(MeO)3C6H2
2b; 3,5-(MeO)2C6H3
2c; 3-MeOC6H4
2d; 3-MeC6H4
2e; 4-tBuC6H4
2f; C6H5
Product 3; yield (%)[b]
3a; 91
Yield (%)[b]
Entry
F source
Solvent
Time (h)
3b; 97
2a
60
55
40
3
3a
4a
10
19
6
5a
‒
2
3c; 92
3
1
CsF
toluene
THF
20
20
20
2
19
15
39
91
79
3d; 91
3e; 98 (95)[c]
4
2
CsF
‒
5
3
TBAT
TBAT
TBAT
THF
‒
3f; 93
6
4
5[c]
toluene
toluene
‒
‒
2g; 4-ClC6H4
2h; 4-BrC6H4
2i; 3-ClC6H4
3g; 88
7
2
7
‒
8
3h; 90
8
[a] Typical reaction conditions: 2a (0.5 mmol), F source (20 mol%), PhSCF2SiMe3 (2
equiv.), solvent (0.25 mL), 0 oC to rt.
3i; 93
9
2j; 3-F3CC6H4
2k; 4-O2NC6H4
2l; 2-MeC6H4
2m; 2-ClC6H4
2n; 2-BrC6H4
2o; 2-IC6H4
3j; 94
10
11
12
13
14
15
16
17
18
19
[b] Isolated yield.
3k; 54
[c] Aqueous work-up at room temperature without TBAF.
3l; 61[d]
3m; 86
3n; 75
With the optimal conditions in hand, the scope and
limitations of the reaction were next evaluated by employing a
range of structurally different Weinreb amide substrates and the
results were shown in Table 2. Non-substitued Weinreb amide
and Weinreb amides bearing electron-donating groups on the
aromatic rings readily underwent the reaction and yielded the
corresponding products 3 in excellent yields (9198% yields)
(Table 2, Entries 16). It should be emphasized that the reaction
of 2e can be scaled up (from 1 mmol to 5 mmol) and 3e was
obtained in comparable yield (Table 2, Entry 5). Electron-
deficient substituted aromatic Weinreb amides at the para and
meta positions (p-Cl, p-Br, m-Cl and m-CF3) were compatible
substrates and gave products 3 in high yields (8894% yields)
(Table 2, Entries 710). Low yield (54% yield) was obtained
when 2k was employed as a substrate, possibly due to the
intrinsic insolubility of 2k in toluene. Leadbeater found that
CF3TMS failed to react with Weinreb amides containing ortho
substitution, and was attributed to the steric bulk of the ortho
substituent thereby hindering the formation of a pentavalent
silicon intermediate.[18] To our surprise, Weinreb amides
possessing ortho substituents also gave their corresponding
products 3 in moderate to good yields (6186% yields) (Table 2,
Entries 1215). Compound 2p, a Weinreb amide derived from 2-
naphthoic acid, also readily reacted with 1 to yield 3p in 97%
yield (Table 2, Entry 16). Aliphatic Weinreb amides (2q2s) were
also investigated and they readily underwent the reaction to
provide the corresponding products 3q‒3s in low to moderate
yields (Table 2, Entries 1719). Of note is that aliphatic Weinreb
amides 2q with an α-substitution proved to be a poor substrate
and 3q was obtained in low yield (45% yield). Finally,
heteroaromatic Weinreb amide 2t led to the corresponding
product 3t in 83% yield (Table 2, Entry 20).
3o; 77
2p; β-naphthyl
2q; c-C6H11
3p; 97
3q; 45
3r; 77[d]
2r; n-C7H15
2s;
3s; 80
20
2t; 2-thienyl
3t; 83
[a] Typical reaction conditions: 2 (1 mmol), TBAT (20 mol%), PhSCF2SiMe3 (1,
2 equiv.), Toluene (0.5 mL, 2 M), 0 oC to rt, 2 h; then H2O (1.0 mL), TBAF (1.1
equiv. in 1 mL THF), 55 oC, 2 h.
[b] Isolated yield.
[c] 2e (5 mmol) was employed.
[d] Reaction time = 3 h.
Having demonstrated the synthetic utilities of the present
protocol to
a collection of Weinreb derivatives bearing
electronically different diverse substituents, the reactions of α,β-
unsaturated Weinreb amides 2u and 2v were also evaluated
(Scheme 2). Under standard reaction conditions (Table 1), both
2u and 2v gave a mixture of the desired product 3 and a
competing product derived from the Michael addition of N,O-
dimethylhydroxylamine into the β-positions of the product 3.[18]
Pleasingly, when the crude reaction mixtures were stirred in
silica gel (SiO2) in hexane:EtOAc (1:1 v/v) for 2 days followed by
conventional chromatographic purification, 3u and 3v were
isolated in 79% and 82% yields, respectively.
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[a] Typical reaction conditions: 6 (1 mmol), TBAT (20 mol%), TMSCF2SPh (1,
2 equiv.), Toluene (0.5 mL, 2 M), 0 oC to rt, 2 h; then H2O (1.0 mL), TBAF (1.1
equiv. in 1 mL THF), 55 oC, 2 h.
[b] Isolated yield.
At this stage, reductive cleavage of the phenylsulfanyl
group of 3 was investigated and the reaction proved to be
difficult. A preliminary study on the reaction of 3e under various
reduction conditions including Bu3SnH/AIBN;[21] Et3B/O2;[22]
[24]
Mo(CO)6/THF[23] and Ferrocene/LiAlH4
failed to provide the
desired reductive cleavage in decent yield; either complex
mixtures or recovery of 3e were observed. To our delight, it was
found that upon treatment of 3e with Raney nickel in ethanol
(0.0866 g/mL)/H2 (balloon) at 70 °C for 2 h led to chemoselective
reductive cleavage of the phenylsulfanyl group to yield the
corresponding gem-difluoromethyl ketones 9e in good yield
(85% yield). Thus, a collection of compounds 3 containing
various functional groups on the aromatic ring including methoxy,
methyl, t-butyl, and chloro groups, can tolerate the reaction and
yield the corresponding products 9 in good yields (Table 4,
Entries 17). The phenylsulfanyl group in compounds 3 bearing
naphthyl group, aliphatic chain and a thienyl group can also be
easily removed under standard reaction conditions (Table 4,
Entries 810). Finally, 3u and 3v readily underwent reductive
desulfurization although over reduction at , unsaturation
moiety took place to provide 9u and 9v in moderate yields
(Table 4, Entries 1112). To the best of our knowledge,
desulfurization of a phenylsulfanyl group located at the -
position of a carbonyl group mediated by a combination of
Raney nickel/H2 has never been reported. Additionally, the
reductive cleavage of the phenylsulfanyl group of 7a employing
Bu3SnH (1.75 equiv.) and a catalytic amount of AIBN (15 mol%)
in refluxing toluene (0.1 M) for 13 h readily proceeded without
difficulty to yield the corresponding product 10a in 80% yield
(Scheme 3).
Scheme 2. Reaction of α,β-unsaturated Weinreb amides 2u and 2v with
PhSCF2TMS (1).
To extend the synthetic utility of the present work, we also
investigated the reactions of o-alkynyl aromatic Weinreb amides
6 with PhSCF2TMS (1). The results were summarized in Table 3.
When 6a was treated with 1 under the standard reaction
conditions (Table 1), we were pleased to find that 6a readily
underwent tandem fluoride-induced nucleophilic addition
followed by intramolecular 5-exo-dig cyclization to provide 7a in
89% yield along with a simple substitution product 8a (5% yield)
(Table 3, Entry 1). Weinreb amides 6b‒6g bearing a series of
electronically different groups (p-OMe, p-Br, m-F, m-CF3, and
m,p-methylenedioxy) on the phenyl ring of the arylethynyl moiety
led to the corresponding adducts in moderate to good yields
(50%82% yields) (Table 3, Entries 2‒7). Unfortunately, aliphatic
Weinreb amide 6h failed to produce the desired adduct (Table 3,
Entry 8) likely due to the inability of the aliphatic chain to
stabilize the olefinic carbanion intermediate formed from internal
nucleophilic attach of the hydroxyl group.[19] It is worth
mentioning here that similar trifluoromethylation/cyclization of o-
alkynyl aromatic aldehydes were previously reported and in all
cases
underwent
exclusively
intramolecular
5-exo-dig
cyclization.[20] Therefore, the configuration of the resulting
adducts 7 in this work was assigned on the same experimental
and theoretical basis.
Table 4. Reductive cleavage of the phenylsulfanyl group of 3.[a]
Table 3. Reactions of o-alkynyl aromatic Weinreb amides 6.[a]
Entry
Substrate; R =
Time
(h)
1
Product 9; yield (%)[b]
3a; 3,4,5-(MeO)3C6H2
3b; 3,5-(MeO)2C6H3
3c; 3-MeOC6H4
3d; 3-MeC6H4
3e; 4-tBuC6H4
3f; C6H5
9a; R′ = R, 82
9b; R′ = R, 87
9c; R′ = R, 88
9d; R′ = R, 76
9e; R′ = R, 85
9f; R′ = R, 90
9i; R′ = R, 88
9p; R′ = R, 84
9r; R′ = R, 89
1
3
2
Product; yield (%)[b]
4
3
Entry
Substrate; R =
1.5
2
4
6
7
8
5
1
2
3
4
5
6
6a; C6H5
6a; ‒
6b; 26
6c; 31
6d; 20
6e; 7
6f; 12
6g; 15
7a; 89
7b; 59
7c; 50
7d; 77
7e; 82
7f; 76
8a; 5
8b; 6
8c; ‒
8d; ‒
8e; ‒
8f; ‒
3
6
6b; 4-MeOC6H4
6c; 4-BrC6H4
6d; 3-FC6H4
6e; 3-F3CC6H4
6f; β-naphthyl
6g;
3i; 3-ClC6H4
2
7
3p; β-naphthyl
3r; n-C7H15
3
8
6
9
10
11[c]
12[c]
3t; 2-thienyl
3
4
4
9t; R′ = R, 92
3u; C6H5CH=CH
3v; 4-ClC6H4CH=CH
9u; R′ = C6H5CH2CH2, 67
9v; R′ = 4-ClC6H4CH2CH2, 60
7
8
7g; 65
7h; 0
8g; 7
6h; n-C6H13
6h; 63
8h; 29
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[a] Typical reaction conditions: 3 (0.3 mmol), Raney-Nickel in EtOH (0.0866
g/mL, 7 mL), H2 (balloon), 70 oC.
[b] Isolated yield; importantly no heating during solvent removal.
[c] Reductive removal of the phenylsulfnyl group of 3u and 3v using Bu3SnH,
AIBN in refluxing toluene (13 h) gave 9u and 9v in 66% and 72% yields,
respectively.
10 min. Then, the ice bath was removed and the reaction mixture was
allowed to stir at room temperature for 2 hours. The reaction was
quenched with water (1 mL) followed by TBAF (1.1 eq, 1 M in THF, 1 mL).
The flask was equipped with a reflux condenser, open to air, and heated
to 55 °C for 2 hours. The reaction flask was cooled to room temperature
and the reaction mixture was diluted with CH2Cl2 (15 mL), and
transferred to a separatory funnel. The organic layer was washed with
water (3 X 15 mL), followed by a brine solution (15 mL). The organic
layer was dried with anhydrous MgSO4, filtered and concentrated
(aspirator) to crude mixtures which were purified by column
chromatography to yield pure products 3, 7 and 8.
Scheme 3. Reductive desulfanylation of 7a.
Conclusions
2,2-Difluoro-2-(phenylsulfanyl)-1-(3,4,5-trimethoxyphenyl)ethanone
(3a): Nucleophilic addition of 1 (433 mg, 2 mmol) to 2a (255 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3a (322 mg,
91%) as a yellow solid [m.p. 7778 °C (EtOAc/hexanes)] after purification
by column chromatography (SiO2, 10% EtOAc/hexanes). IR (neat):  =
2943, 2839, 1695, 1581, 1504, 1417, 1335, 1128 cm-1. 1H NMR (400
MHz, CDCl3):  = 7.61 (d, J = 7.1 Hz, 2H, ArH), 7.49-7.45 (m, 1H, ArH),
7.41-7.37 (m, 4H, ArH), 3.96 (s, 3H, OCH3), 3.90 (s, 6H, 2  OCH3) ppm.
13C NMR (100 MHz, CDCl3):  = 184.0 (t, J = 27.8 Hz, CO), 152.8 (2  C),
144.1 (C), 136.8 (2  CH), 130.5 (CH), 129.3 (2  CH), 125.8 (C), 124.9
(C), 124.0 (t, J = 289.2 Hz, CF2), 108.0 (2  CH), 61.0 (OCH3), 56.2 (2 
OCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -76.2 (s, 2F, CF2) ppm.
HRMS (ESI-TOF) calcd. for C17H16F2O4SNa [M + Na]+ 377.0635, found
377.0636.
In conclusion, we have reported the synthesis of
difluoromethyl ketones. The reaction involved fluoride-induced
nucleophilic substitution of PhSCF2SiMe3 (1) to Weinreb amides
followed by Raney nickel/H2 mediated chemoselective reductive
desulfurization. With o-alkynyl aromatic Weinreb amide
substrates, a tandem nucleophilic addition of PhSCF2SiMe3 (1)
followed by 5-exo-dig cyclization readily took place under
standard reaction conditions to provide the corresponding
phthalans in moderate to good yields.
Experimental Section
1-(3,5-Dimethoxyphenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone
(3b): Nucleophilic addition of 1 (433 mg, 2 mmol) to 2b (225 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3b (315
mg, 97%) as a yellowish brown solid [m.p. 7879 °C (EtOAc/hexanes)]
after purification by column chromatography (SiO2, 2% EtOAc/hexanes).
IR (neat):  = 2970, 2940, 2842, 1695, 1591, 1451, 1356, 1302, 1206,
1158, 1064, 1019, 742 cm-1. 1H NMR (400 MHz, CDCl3):  = 7.60 (d, J =
7.2 Hz, 2H, ArH), 7.48-7.45 (m, 1H, ArH), 7.39 (t, J = 7.4 Hz, 2H, ArH),
7.26 (br s, 2H, ArH), 6.73 (t, J = 2.3 Hz, 1H, ArH), 3.84 (s, 6H, 2  OCH3)
ppm. 13C NMR (100 MHz, CDCl3):  = 184.8 (t, J = 27.8 Hz, CO), 160.6
(2  C), 136.7 (2  CH), 132.6 (C), 130.4 (CH), 129.2 (2  CH), 124.7 (C),
123.6 (t, J = 289.2 Hz, CF2), 108.0 (2  CH), 107.2 (CH), 55.5 (2  OCH3)
ppm. 19F NMR (376 MHz, CDCl3):  = -77.4 (s, 2F, CF2) ppm. HRMS
General: Tetrahydrofuran (THF) was freshly distilled from sodium
benzophenone ketyl under argon. Dichloromethane (CH2Cl2) was freshly
distilled from calcium hydride under argon. N,N-Dimethylformamide
(DMF) was distilled from calcium oxide and stored over activated
molecular sieves (4 Å). Toluene was distilled from calcium hydride and
stored over activated molecular sieves (4 Å). Common solvents for
purification (hexanes, dichloromethane, acetone and ethyl acetate) were
distilled before used. 1H NMR (400 MHz), 13C (100 MHz), and 19F (376
MHz) spectra reported in ppm were recorded on a Bruker AscendTM
spectrometer and chemical shift () were measured with
trichlorofluoromethane ( = 0) as an internal reference. Melting Points
(uncorrected) were recorded in degrees celsius (°C) using digital Sanyo
Gallenkamp. The Infrared spectra were recorded with a Bruker ALPHA
FT-IR spectrometer. The high-resolution mass spectra (HRMS) were
recorded with a Micromass model VQTOF2 mass spectrometer in ESI
mode. All reactions were performed under an argon atmosphere using
dried glassware. Column chromatography was performed with silica gel
(SiO2) 60 (Merck, 63-200 μm). Reagent PhSCF2SiMe3 (1) was
synthesized according to known literature procedures.[4a] Weinreb
Amides were synthesized by known procedures (see Supplementary
information).
(ESI-TOF) calcd. for C16H14F2O3SNa [M
347.0525.
+
Na]+ 347.0529, found
2,2-Difluoro-1-(3-methoxyphenyl)-2-(phenylsulfanyl)ethanone (3c):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2c (195 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3c (271
mg, 92%) as
a pale yellow oil after purification by column
chromatography (SiO2, 5% EtOAc/hexanes). IR (neat):  = 3007, 2941,
2837, 1701, 1580, 1274, 1227, 1125, 1037, 994, 747,726, 689 cm-1. 1H
NMR (400 MHz, CDCl3):  = 7.76 (d, J = 7.2 Hz, 1H, ArH), 7.62-7.60 (m,
3H, ArH), 7.48-7.37 (m, 4H, ArH), 7.20 (dd, J = 8.2, 1.9 Hz, 1H, ArH),
3.85 (s, 3H, OCH3) ppm. 13C NMR (100 MHz, CDCl3):  = 185.1 (t, J =
28.0 Hz, CO), 159.6 (C), 136.7 (2  CH), 132.3 (C), 130.4 (CH), 129.6
(CH), 129.2 (2  CH), 124.8 (C), 123.7 (t, J = 289.2 Hz, CF2), 123.1 (CH),
121.3 (CH), 114.4 (CH), 55.4 (OCH3) ppm. 19F NMR (376 MHz, CDCl3): 
= -77.5 (s, 2F, CF2) ppm. HRMS (ESI-TOF) calcd. for C15H12F2O2SNa
[M + Na]+ 317.0424, found 317.0423.
General
procedure
A
for
the
synthesis
of
difluoro
(phenylsulfanyl)methyl ketones 3, 7 & 8: To an oven dried round
bottom flask equipped with a magnetic bar was added TBAT (20 mol%)
and Weinreb amide (1.0 mmol). Dry toluene (0.5 mL) was added to the
reaction flask at room temperature. Then, the flask was cooled to 0 °C for
10 minutes. TMSCF2SPh (1, 2.0 mmol) was added to reaction mixture
under an argon atmosphere. The reaction was allowed to stir at 0 °C for
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1
2,2-Difluoro-2-(phenylsulfanyl)-1-(m-tolyl)ethanone (3d): Nucleophilic
addition of 1 (433 mg, 2 mmol) to 2d (179 mg, 1 mmol) using TBAT (108
mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3d (253 mg, 91%) as a pale
yellow oil after purification by column chromatography (SiO2, 2%
EtOAc/hexanes). IR (neat):  = 3063, 2924, 1700, 1603, 1584, 1475,
1440, 1275, 1124, 1064, 1024, 748, 722, 688 cm-1. 1H NMR (400 MHz,
CDCl3):  = 7.94 (d, J = 7.7 Hz, 1H, ArH), 7.91 (s, 1H, ArH), 7.61 (d, J =
7.4 Hz, 2H, ArH), 7.47-7.46 (m, 2H, ArH), 7.41-7.37 (m, 3H, ArH), 2.42
(s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3):  = 185.4 (t, J = 27.9 Hz,
CO), 138.6 (C), 136.8 (2  CH), 135.5 (CH), 131.1 (C), 130.8 (CH), 130.4
(CH), 129.2 (2  CH), 128.5 (CH), 127.7 (CH), 124.9 (C), 123.8 (t, J =
289.3 Hz, CF2), 21.3 (CH3) ppm. 19F NMR (376 MHz, CDCl3):  = -77.4
(s, 2F, CF2) ppm. HRMS (ESI-TOF) calcd. for C15H12F2OSNa [M + Na]+
301.0475, found 301.0474.
(neat):  = 3063, 1703, 1583, 1266, 1131, 1072, 825 cm-1. H NMR (400
MHz, CDCl3):  = 7.98 (d, J = 8.5 Hz, 2H, ArH), 7.65 (d, J = 8.7 Hz, 2H,
ArH), 7.58 (d, J = 7.3 Hz, 2H, ArH), 7.49-7.45 (m, 1H, ArH), 7.41-7.37 (m,
2H, ArH) ppm. 13C NMR (100 MHz, CDCl3):  = 184.4 (t, J = 28.5 Hz,
CO), 136.7 (2  CH), 132.1 (2  CH), 131.8 (2  CH), 130.6 (CH), 130.3
(C), 129.8 (C), 129.3 (2  CH), 124.5 (C), 123.5 (t, J = 288.8 Hz, CF2)
ppm. 19F NMR (376 MHz, CDCl3):  = -78.1 (s, 2F, CF2) ppm. HRMS
(ESI-TOF) calcd. for C14H9BrF2OSNa [M
364.9421 and 366.9397.
+
Na]+ 364.9423 found
1-(3-Chlorophenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone
(3i):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2i (200 mg, 1 mmol) using
TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3i (278 mg, 93%)
as a pale yellow oil after purification by column chromatography (SiO2,
1% EtOAc/hexanes). IR (neat):  = 3068, 1704, 1568, 1474, 1256, 1134,
995, 904, 744, 713, 688 cm-1. 1H NMR (400 MHz, CDCl3):  = 8.06 (s,
1H, ArH), 8.02 (d, J = 7.9 Hz, 1H, ArH), 7.63-7.58 (m, 3H, ArH), 7.49-
7.44 (m, 2H, ArH), 7.42-7.37 (m, 2H, ArH) ppm. 13C NMR (100 MHz,
CDCl3):  = 184.1 (t, J = 28.7 Hz, CO), 136.7 (2  CH), 135.0 (C), 134.5
(CH), 132.6 (C), 130.6 (CH), 130.2 (CH), 130.0 (CH), 129.3 (2  CH),
128.5 (CH), 124.4 (C), 123.4 (t, J = 288.9 Hz, CF2) ppm. 19F NMR (376
MHz, CDCl3):  = -78.3 (s, 2F, CF2) ppm. HRMS (ESI-TOF) calcd. for
C14H9ClF2OSNa [M + Na]+ 320.9928, found 320.9929 and 322.9898.
1-(4-(tert-Butyl)phenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone (3e):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2e (221 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3e (314
mg, 98%) as
a pale yellow oil after purification by column
chromatography (SiO2, 2% EtOAc/hexanes). IR (neat):  = 2964, 2906,
2870, 1698, 1603, 1474, 1271, 1106 cm-1.1H NMR (400 MHz, CDCl3): 
= 8.08 (d, J = 8.4 Hz, 2H, ArH), 7.62 (d, J = 7.3 Hz, 2H, ArH), 7.52 (d, J =
8.6 Hz, 2H, ArH), 7.48-7.45 (m, 1H, ArH), 7.41-7.37 (m, 2H, ArH), 1.36
(s, 9H, 3  CH3) ppm. 13C NMR (100 MHz, CDCl3):  = 184.6 (t, J = 27.7
Hz, CO), 158.6 (C), 136.6 (2  CH), 130.4 (t, J = 2.2 Hz, 2  CH), 130.3
(CH), 129.1 (2  CH), 128.3 (C), 125.6 (2  CH), 124.8 (C), 123.8 (t, J =
289.2 Hz, CF2), 35.1 (C), 30.7 (3  CH3) ppm. 19F NMR (376 MHz,
CDCl3):  = -77.5 (s, 2F, CF2) ppm. HRMS (ESI-TOF) calcd. for
C18H18F2OSNa [M + Na]+ 343.0944, found 343.0941.
2,2-Difluoro-2-(phenylsulfanyl)-1-(3-(trifluoromethyl)phenyl)
ethanone (3j): Nucleophilic addition of 1 (433 mg, 2 mmol) to 2j (233
mg, 1 mmol) using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL)
gave 3j (312 mg, 94%) as a colorless oil after purification by column
chromatography (SiO2, 2% EtOAc/hexanes). IR (neat):  = 3068, 1711,
1613, 1441, 1333, 1251, 1130, 1075, 750, 690 cm-1. 1H NMR (400 MHz,
CDCl3):  = 8.35 (br s, 1H, ArH), 8.31 (d, J = 8.0 Hz, 1H, ArH), 7.91 (d, J
= 7.8 Hz, 1H, ArH), 7.66 (t, J = 7.8 Hz, 1H, ArH), 7.59 (d, J = 7.3 Hz, 2H,
2,2-Difluoro-1-phenyl-2-(phenylsulfanyl)ethanone (3f): Nucleophilic
addition of 1 (433 mg, 2 mmol) to 2f (165 mg, 1 mmol) using TBAT (108
mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3f (246 mg, 93%) as a pale
yellow oil after purification by column chromatography (SiO2, 1%
EtOAc/hexanes). Data is in agreement with previously reported
literature.[25] IR (neat):  = 3062, 1700, 1560, 1449, 1442, 1268, 1129,
1002, 823, 747, 684 cm-1. 1H NMR (400 MHz, CDCl3):  = 8.13 (d, J = 7.8
Hz, 2H, ArH), 7.68-7.64 (m, 1H, ArH), 7.60 (d, J = 7.4 Hz, 2H, ArH), 7.52-
7.45 (m, 3H, ArH), 7.41-7.37 (m, 2H, ArH) ppm. 13C NMR (100 MHz,
CDCl3):  = 185.2 (t, J = 28.0 Hz, CO), 136.7 (2  CH), 134.6 (CH), 131.1
(C), 130.5 (3  CH), 129.3 (2  CH), 128.7 (2  CH), 124.7 (C), 123.7 (t, J
= 289.1 Hz, CF2) ppm. 19F NMR (376 MHz, CDCl3):  = -77.7 (s, 2F,
CF2) ppm. HRMS (ESI-TOF) calcd. for C14H10F2OSNa [M + Na]+
287.0318, found 287.0316.
ArH), 7.49-7.46 (m, 1H, ArH), 7.41-7.37 (t, J = 7.5 Hz, 2H, ArH) ppm. 13
C
NMR (100 MHz, CDCl3):  = 184.2 (t, J = 29.0 Hz, CO), 136.8 (2  CH),
133.5 (CH), 131.8 (C), 131.4 (q, J = 33.1 Hz, C), 130.9 (appt. d, J = 3.4
Hz, CH), 130.7 (CH), 129.4 (3  CH), 127.2 (appt. d, J = 3.1 Hz, CH),
124.2 (C), 123.4 (t, J = 288.6 Hz, CF2), 123.4 (q, J = 271.0 Hz, CF3) ppm.
19F NMR (376 MHz, CDCl3):  = -63.5 (s, 3F, CF3), -78.4 (s, 2H, CF2)
ppm. HRMS (ESI-TOF) calcd. for C15H9F5OSNa [M + Na]+ 355.0192,
found 355.0190.
2,2-Difluoro-1-(4-nitrophenyl)-2-(phenylsulfanyl)ethanone
(3k):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2k (210 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3k (167
mg, 54%) as a yellow solid [m.p. 4951 °C (CH2Cl2/hexanes)] after
purification by column chromatography (SiO2, 40% CH2Cl2/hexanes). IR
(neat):  = 1711, 1603, 1524, 1348, 1262, 1131, 988, 814, 689 cm-1. 1H
NMR (400 MHz, CDCl3):  = 8.34 (d, J = 9.0 Hz, 2H, ArH), 8.27 (d, J =
8.9 Hz, 2H, ArH), 7.56 (d, J = 7.4 Hz, 2H, ArH), 7.48 (t, J = 7.4 Hz, 1H,
ArH), 7.39 (t, J = 7.5 Hz, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3):  =
183.9 (t, J = 29.3 Hz, CO), 150.9 (C), 136.7 (2  CH), 135.7 (C), 131.4 (2
 CH), 130.8 (CH), 129.5 (2  CH), 123.9 (C), 123.7 (2  CH), 123.1 (t, J
= 288.5 Hz, CF2) ppm. 19F NMR (376 MHz, CDCl3):  = -79.1 (s, 2F, CF2)
ppm. HRMS (ESI-TOF) calcd. for C14H9F2NO3SNa [M + Na]+ 332.0169,
found 332.0168.
1-(4-Chlorophenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone
(3g):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2g (200 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3g (263
mg, 88%) as
a pale yellow oil after purification by column
chromatography (SiO2, 1% EtOAc/hexanes). IR (neat):  = 3064, 1701,
1
1587, 1267, 1092, 1015, 827, 744 cm-1. H NMR (400 MHz, CDCl3):  =
8.06 (d, J = 8.6 Hz, 2H, ArH), 7.58 (d, J = 7.3 Hz, 2H, ArH), 7.49-7.45 (m,
3H, ArH), 7.41-7.37 (m, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3):  =
184.1 (t, J = 28.4 Hz, CO), 141.4 (C), 136.7 (2  CH), 131.8 (2  CH),
130.6 (CH), 129.4 (C), 129.3 (2  CH), 129.1 (2  CH), 124.5 (C), 123.5
(t, J = 288.8 Hz, CF2) ppm. 19F NMR (376 MHz, CDCl3):  = -78.0 (s, 2F,
CF2) ppm. HRMS (ESI-TOF) calcd. for C14H9ClF2OSNa [M + Na]+
320.9928, found 320.9950 and 322.9923.
2,2-Difluoro-2-(phenylsulfanyl)-1-(o-tolyl)ethanone (3l): Nucleophilic
addition of 1 (433 mg, 2 mmol) to 2l (179 mg, 1 mmol) using TBAT (108
mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3l (170 mg, 61%) as a
colorless oil after purification by column chromatography (SiO2, 2%
EtOAc/hexanes). IR (neat):  = 3064, 2971, 2930, 1704, 1254, 1112,
1-(4-Bromophenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone
(3h):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2h (244 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3h (309
mg, 90%) as a colorless solid [m.p. 3839 °C (EtOAc/hexanes)] after
purification by column chromatography (SiO2, 2% EtOAc/hexanes). IR
748, 730 cm-1. H NMR (400 MHz, CDCl3):  = 7.98 (dd, J = 7.8, 1.0 Hz,
1
1H, ArH), 7.61 (d, J = 7.2 Hz, 2H, ArH), 7.49-7.44 (m, 2H, ArH), 7.41-
7.37 (m, 2H, ArH), 7.32-7.27 (m, 2H, ArH), 2.46 (s, 3H, CH3) ppm. 13C
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701322
European Journal of Organic Chemistry
FULL PAPER
NMR (100 MHz, CDCl3):  = 188.1 (t, J = 27.8 Hz, CO), 140.9 (C), 136.7
(2  CH), 132.9 (CH), 132.1 (CH), 131.3 (C), 130.4 (CH), 130.1 (t, J = 4.6
Hz, CH), 129.2 (2  CH), 125.4 (CH), 125.0 (C) 123.6 (t, J = 290.6 Hz,
CF2), 21.3 (CH3) ppm. 19F NMR (376 MHz, CDCl3):  = -77.2 (s, 2F, CF2)
ppm. HRMS (ESI-TOF) calcd. for C15H12F2OSNa [M + Na]+ 301.0475,
found 301.0476.
(CH), 128.3 (C), 127.7 (CH), 127.0 (CH), 124.9 (C), 124.8 (t, J = 1.7 HZ,
CH), 123.9 (t, J = 289.2 Hz, CF2) ppm. 19F NMR (376 MHz, CDCl3):  =
-76.8 (s, 2F, CF2) ppm. HRMS (ESI-TOF) calcd. for C18H12F2OSNa [M +
Na]+ 337.0475, found 337.0475.
1-Cyclohexyl-2,2-difluoro-2-(phenylsulfanyl)ethanone
(3q):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2q (171 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3q (122
mg, 45%) as a colorless oil after purification by column chromatography
(SiO2, 100% hexanes). IR (neat):  = 3063, 2934, 2857, 1736, 1475,
1450, 1443, 1101 cm-1. 1H NMR (400 MHz, CDCl3):  = 7.59-7.57 (m,
2H, ArH), 7.48-7.43 (m, 1H, ArH), 7.41-7.37 (m, 2H, ArH), 2.84 (tt, J =
11.2, 3.2 Hz, 1H, CH), 1.87-1.78 (m, 4H, CH2), 1.70-1.67 (m, 1H, CH),
1.44-1.17 (m, 5H, CH2 & CH) ppm. 13C NMR (100 MHz, CDCl3):  =
199.1 (t, J = 27.4 Hz, CO), 136.6 (2  CH), 130.4 (CH), 129.2 (2  CH),
124.8 (C), 122.9 (t, J = 290.7 Hz, CF2), 44.9 (CH), 28.5 (2  CH2), 25.4
(CH2), 25.3 (2  CH2) ppm. 19F NMR (376 MHz, CDCl3):  = -85.0 (s, 2F,
CF2) ppm. HRMS (ESI-TOF) calcd. for C14H16F2OSNa [M + Na]+
293.0788, found 293.0790.
1-(2-Chlorophenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2m (200 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3m (257
(3m):
mg, 86%) as
a pale yellow oil after purification by column
chromatography (SiO2, 3% EtOAc/hexanes). IR (neat):  = 2973, 2936,
1649, 1435, 1380, 983, 767, 742 cm-1. 1H NMR (400 MHz, CDCl3):  =
7.70 (d, J = 7.9 Hz, 1H, ArH), 7.63 (d, J = 7.4 Hz, 2H, ArH), 7.49-7.44 (m,
3H, ArH), 7.41-7.40 (m, 2H, ArH), 7.35-7.31 (m, 1H, ArH) ppm. 13C NMR
(100 MHz, CDCl3):  = 187.0 (t, J = 30.2 Hz, CO), 136.6 (2  CH), 133.0
(C), 132.9 (CH), 132.6 (C), 130.9 (CH), 130.5 (CH), 129.6 (t, J = 3.0 Hz,
CH), 129.3 (2  CH), 126.4 (CH), 124.4 (C), 122.6 (t, J = 290.6 Hz, CF2)
ppm. 19F NMR (376 MHz, CDCl3):  = -80.1 (s, 2F, CF2) ppm. HRMS
(ESI-TOF) calcd. for C14H9ClF2OSNa [M
+
Na]+ 320.9928, found
320.9929 and 322.9904.
1,1-Difluoro-1-(phenylsulfanyl)nonan-2-one (3r): Nucleophilic addition
of 1 (433 mg, 2 mmol) to 2r (187 mg, 1 mmol) using TBAT (108 mg, 0.2
mmol) in dry toluene (0.5 mL) gave 3r (221 mg, 77%) as a colorless oil
after purification by column chromatography (SiO2, 100% hexanes). IR
(neat):  = 2955, 2927, 2856, 1744, 1442, 1100, 1024, 748, 690 cm-1. 1H
NMR (400 MHz, CDCl3):  = 7.59 (d, J = 7.4 Hz, 2H, ArH), 7.48-7.44 (m,
1H, ArH), 7.41-7.37 (m, 2H, ArH), 2.65 (t, J = 7.2 Hz, 2H, CH2), 1.61-1.58
(m, 2H, CH2), 1.23 (br s, 8H, CH2), 0.90-0.87 (m, 3H, CH3) ppm. 13C
NMR (100 MHz, CDCl3):  = 196.4 (t, J = 28.5 Hz, CO), 136.5 (2  CH),
130.4 (CH), 129.3 (2  CH), 124.7 (C), 122.6 (t, J = 289.4 Hz, CF2), 36.3
(CH2), 31.6 (CH2), 28.9 (CH2), 28.8 (CH2), 22.8 (CH2), 22.5 (CH2), 14.0
(CH3) ppm. 19F NMR (376 MHz, CDCl3):  = -85.5 (s, 2F, CF2) ppm.
HRMS (ESI-TOF) calcd. for C15H20F2OSNa [M + Na]+ 309.1101, found
309.1105.
1-(2-Bromophenyl)-2,2-difluoro-2-(phenylsulfanyl)ethanone
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2n (244 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3n (257
(3n):
mg, 75%) as
a pale yellow oil after purification by column
chromatography (SiO2, 2% EtOAc/hexanes). IR (neat):  = 3063, 1723,
1586, 1474, 1441, 1433, 1283, 1246, 1121, 986, 737 cm-1. 1H NMR (400
MHz, CDCl3):  = 7.69-7.65 (m, 2H, ArH), 7.63-7.61 (m, 2H, ArH), 7.48-
7.44 (m, 1H, ArH), 7.41-7.36 (m, 4H, ArH) ppm. 13C NMR (100 MHz,
CDCl3):  = 187.7 (t, J = 30.3 Hz, CO), 136.6 (2  CH), 134.6 (C), 134.2
(CH), 132.9 (CH), 130.5 (CH), 129.6 (t, J = 3.0 Hz, CH), 129.3 (2  CH),
126.9 (CH), 124.5 (C), 122.4 (t, J = 290.6 Hz, CF2), 120.9 (C) ppm. 19F
NMR (376 MHz, CDCl3):  = -80.0 (s, 2F, CF2) ppm. HRMS (ESI-TOF)
calcd. for C14H9BrF2OSNa [M + Na]+ 364.9423, found 364.9427 and
366.9410.
1,1-Difluoro-1-(phenylsulfanyl)-4-(3,4,5-trimethoxyphenyl)butan-2-
one (3s): Nucleophilic addition of 1 (433 mg, 2 mmol) to 2s (283 mg, 1
mmol) using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3s
2,2-Difluoro-1-(2-iodophenyl)-2-(phenylsulfanyl)ethanone
(3o)
:
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2o (291 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3o (300
(306 mg, 80%) as a colorless oil after purification by column
chromatography (SiO2, 10% EtOAc/hexanes). IR (neat):  = 2939, 2839,
1744, 1590, 1509, 1460, 1239, 1128 cm-1. 1H NMR (400 MHz, CDCl3): 
= 7.47-7.43 (m, 3H, ArH), 7.38-7.34 (m, 2H, ArH), 6.38 (s, 2H, ArH), 3.85
(s, 6H, 2  OCH3), 3.83 (3H, OCH3), 2.99 (t, J = 7.2 Hz, 2H, CH2), 2.86 (t,
J = 7.2 Hz, 2H, CH2) ppm. 13C NMR (100 MHz, CDCl3):  = 195.1 (t, J =
29.0 Hz, CO), 153.1 (2  C), 136.5 (2  CH), 135.6 (2  C), 130.4 (CH),
129.2 (2  CH), 124.2 (C), 122.2 (t, J = 289.3 Hz, CF2), 105.3 (2  CH),
60.7 (OCH3), 55.9 (2  OCH3), 38.0 (CH2), 28.9 (CH2) ppm. 19F NMR
(376 MHz, CDCl3):  = -86.3 (s, 2F, CF2) ppm. HRMS (ESI-TOF) calcd.
for C19H20F2O4SNa [M + Na]+ 405.0948, found 405.0951.
mg, 77%) as
a pale yellow oil after purification by column
chromatography (SiO2, 2% EtOAc/hexanes). IR (neat):  = 3061, 2919,
2849, 1718, 1579, 1440, 1429, 1245, 1115, 732 cm-1. 1H NMR (400 MHz,
CDCl3):  = 8.00 (dd, J = 8.0, 0.7 Hz, 1H, ArH), 7.73 (dd, J = 7.8, 1.2 Hz,
1H, ArH), 7.63 (d, J = 7.3 Hz, 2H, ArH), 7.48-7.37 (m, 4H, ArH), 7.20 (td,
J = 7.7, 1.5 Hz, 1H, ArH) ppm. 13C NMR (100 MHz, CDCl3):  = 188.1 (t,
J = 29.7 Hz, CO), 141.3 (CH), 137.4 (C), 136.7 (2  CH), 133.0 (CH),
130.5 (CH), 129.6 (t, J = 3.5 Hz, CH), 129.3 (2  CH), 127.6 (CH), 124.5
(C), 122.3 (t, J = 290.7 Hz, CF2), 93.5 (C) ppm. 19F NMR (376 MHz,
CDCl3):  = -79.0 (s, 2F, CF2) ppm. HRMS (ESI- TOF) calcd. for
C14H9IF2OSNa [M + Na]+ 412.9285, found 412.9288.
2,2-Difluoro-2-(phenylsulfanyl)-1-(thiophen-2-yl)ethanone
(3t):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2t (171 mg, 1 mmol) using
TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3t (224 mg, 83%)
as a pale yellow oil after purification by column chromatography (SiO2,
2% EtOAc/hexanes). IR (neat):  = 3104, 1672, 1408, 1355, 1127, 1060,
964, 820, 721, 689 cm-1. 1H NMR (400 MHz, CDCl3):  = 7.99-7.98 (m,
1H, ArH), 7.81 (dd, J = 4.9, 0.8 Hz, 1H, ArH), 7.61 (d, J = 7.2 Hz, 2H,
ArH), 7.48-7.44 (m, 1H, ArH), 7.40-7.37 (m, 2H, ArH), 7.18 (dd, J = 4.7,
4.1 Hz, 1H, ArH) ppm. 13C NMR (100 MHz, CDCl3):  = 178.6 (t, J = 29.4
Hz, CO), 137.2 (C), 137.0 (CH), 136.8 (2  CH), 136.4 (t, J = 4.0 Hz,
CH), 130.5 (CH), 129.3 (2  CH), 128.7 (CH), 124.6 (C), 123.2 (t, J =
288.5 Hz, CF2) ppm. 19F NMR (376 MHz, CDCl3):  = -78.9 (s, 2F, CF2)
ppm. HRMS (ESI-TOF) calcd. for C12H8F2OS2Na [M + Na]+ 292.9882,
found 292.9887.
2,2-Difluoro-1-(naphthalen-2-yl)-2-(phenylsulfanyl)ethanone
(3p):
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2p (215 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3p (305
mg, 97%) as a yellow solid [m.p. 5859 °C (EtOAc/hexanes)] after
purification by column chromatography (SiO2, 2% EtOAc/hexanes). IR
(neat):  = 3063, 1685, 1624, 1594, 1471, 1438, 1288, 1110, 1027, 753
cm-1. 1H NMR (400 MHz, CDCl3):  = 8.74 (s, 1H, ArH), 8.13 (dd, J = 8.7,
1.4 Hz, 1 H, ArH), 7.98 (d, J = 8.1 Hz, 1 H, ArH), 7.93-7.88 (m, 2H, ArH),
7.68-7.65 (m, 3H, ArH), 7.61-7.57 (m, 1H, ArH), 7.50-7.46 (m, 1H, ArH),
7.42-7.38 (m, 2H, ArH) ppm. 13C NMR (100 MHz, CDCl3):  = 185.1 (t, J
= 28.0 Hz, CO), 136.7 (2  CH), 136.0 (C), 133.2 (t, J = 3.6 Hz, CH),
132.1 (C), 130.4 (CH), 130.1 (CH), 129.5 (CH), 129.2 (2  CH), 128.5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701322
European Journal of Organic Chemistry
FULL PAPER
(E)-1,1-Difluoro-4-phenyl-1-(phenylsulfanyl)but-3-en-2-one
(3u):
126.5 (C), 124.3 (CH), 119.3 (CH), 113.9 (2  CH), 105.6 (t, J = 25.9 Hz,
C), 98.5 (CH), 60.2 (OCH3), 55.2 (OCH3), 37.1 (NCH3) ppm. 19F NMR
(376 MHz, CDCl3):  = -78.0 (d, J = 209.4 Hz, 1F), -80.0 (d, J = 209.1 Hz,
1F) ppm. HRMS (ESI-TOF) calcd. for C25H23F2NO3SNa [M + Na]+
478.1264, found 478.1266.
Nucleophilic addition of 1 (433 mg, 2 mmol) to 2u (191 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3u (229
mg, 79%) as a pale yellow solid [m.p. 6466 °C (EtOAc/hexanes)] after
purification by column chromatography (SiO2, 5% EtOAc/hexanes). IR
(neat):  = 3062, 3028, 1704, 1607, 1575, 1335, 1047, 748 cm-1. 1H NMR
(400 MHz, CDCl3):  = 7.86 (d, J = 15.9 Hz, 1H, C=CH), 7.63-7.58 (m,
4H, ArH), 7.47-7.37 (m, 6H, ArH), 7.03 (d, J = 15.9 Hz, 1H, C=CH) ppm.
13C NMR (100 MHz, CDCl3):  = 184.3 (t, J = 28.4 Hz, CO), 148.2 (CH),
136.7 (2  CH), 133.8 (C), 131.7 (CH), 130.5 (CH), 129.3 (2  CH), 129.1
(2  CH), 129.0 (2  CH), 124.7 (C), 122.8 (t, J = 288.7 Hz, CF2), 117.6
(CH) ppm. 19F NMR (376 MHz, CDCl3):  = -86.7 (s, 2F, CF2) ppm.
HRMS (ESI-TOF) calcd. for C16H12F2OSNa [M + Na]+ 313.0475, found
313.0477.
(Z)-N-(3-(4-Bromobenzylidene)-1-(difluoro(phenylsulfanyl)methyl)-
1,3-dihydroisobenzofuran-1-yl)-N,O-dimethylhydroxylamine
(7c):
According to the general procedure A, nucleophilic addition of 1 (433 mg,
2 mmol) to 6c (344 mg, 1 mmol) using TBAT (108 mg, 0.2 mmol) in dry
toluene (0.5 mL) gave 7c (252 mg, 50%) as a yellow sticky oil after
purification by column chromatography (SiO2, 2% EtOAc/hexanes). IR
(neat):  = 2932, 2894, 2810, 1662, 1488, 1467, 1055, 1008, 962, 750
1
cm-1. H NMR (400 MHz, Pyr.-d5):  = 7.97-7.92 (m, 3H, ArH), 7.79-7.77
(m, 1H, ArH), 7.73-7.71 (m, 2H ArH), 7.59-7.50 (m, 4H, ArH), 7.39-7.29
(m, 3H, ArH), 6.35 (s, 1H, C=CH), 3.66 (s, 3H, OCH3), 2.71 (s, 3H, NCH3)
ppm. 13C NMR (100 MHz, Pyr.-d5):  = 155.0 (C), 137.6 (2  CH), 136.7
(C), 136.5 (C), 135.8 (C), 132.5 (2  CH), 131.6 (CH), 131.2 (2  CH),
130.9 (CH), 130.1 (CH), 130.0 (2  CH), 129.0 (dd, J = 287.5, 285.6 Hz,
CF2), 127.1 (C), 125.4 (CH), 121.1 (CH), 120.4 (C), 107.4 (dd, J = 27.0,
24.4 Hz, C), 98.7 (CH), 60.7 (OCH3), 37.7 (NCH3) ppm. 19F NMR (376
MHz, Pyr.-d5):  = -76.0 (d, J = 209.1 Hz, 1F), -78.4 (d, J = 208.3 Hz, 1F)
(E)-4-(4-chlorophenyl)-1,1-difluoro-1-(phenylsulfanyl)but-3-en-2-one
(3v): Nucleophilic addition of 1 (433 mg, 2 mmol) to 2v (226 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 3v (266
mg, 82%) as a pale yellow solid [m.p. 5960 °C (EtOAc/hexanes)] after
purification by column chromatography (SiO2, 5% EtOAc/hexanes). IR
(neat):  = 3062, 1705, 1605, 1589, 1490, 1328, 1090, 1041, 944, 814,
748 cm-1. 1H NMR (400 MHz, CDCl3):  = 7.79 (d, J = 15.9 Hz, 1H,
C=CH), 7.61 (d, J = 7.2 Hz, 2H, ArH), 7.52-7.49 (m, 2H, ArH), 7.47-7.43
(m, 1H, ArH), 7.40-7.37 (m, 4H, ArH), 6.98 (d, J = 15.9 Hz, 1H, C=CH)
ppm. 13C NMR (100 MHz, CDCl3):  = 184.0 (t, J = 28.6 Hz, CO), 146.5
(CH), 137.7 (C), 136.6 (2  CH), 132.2 (C), 130.5 (CH), 130.1 (2  CH),
129.3 (4  CH), 124.6 (C), 122.7 (t, J = 288.6 Hz, CF2), 118.0 (CH) ppm.
19F NMR (376 MHz, CDCl3):  = -86.8 (s, 2F, CF2) ppm. HRMS (ESI-
TOF) calcd. for C16H11ClF2OSNa [M + Na]+ 347.0085, found 347.0087,
and 349.0055.
ppm. HRMS (ESI-TOF) calcd. for C24H20BrF2NO2SNa [M
526.0264 found 526.0263 and 528.0246.
+
Na]+
(Z)-N-(1-(Difluoro(phenylsulfanyl)methyl)-3-(3-fluorobenzylidene)-
1,3-dihydroisobenzofuran-1-yl)-N,O-dimethylhydroxylamine
(7d):
According to the general procedure A, nucleophilic addition of 1 (433 mg,
2 mmol) to 6d (283 mg, 1 mmol) using TBAT (108 mg, 0.2 mmol) in dry
toluene (0.5 mL) gave 7d (341 mg, 77%) as a yellow sticky oil after
purification by column chromatography (SiO2, 1% EtOAc/hexanes). IR
1
(Z)-N-(3-Benzylidene-1-(difluoro(phenylsulfanyl)methyl)-1,3-
(neat):  = 2934, 2895, 1611, 1441, 1272, 1057, 751 cm-1. H NMR (400
dihydroisobenzofuran-1-yl)-N,O-dimethylhydroxylamine
(7a):
MHz, CDCl3):  = 7.76 (d, J = 7.5 Hz, 1H, ArH), 7.68-7.30 (m, 12H, ArH),
6.94-6.90 (m, 1H, ArH), 6.03 (s, 1H, C=CH), 3.61 (s, 3H, OCH3), 2.68 (s,
3H, NCH3) ppm. 13C NMR (100 MHz, CDCl3):  = 163.0 (d, J = 242.0 Hz,
CF), 154.0 (C), 137.7 (C), 137.6 (C), 136.7 (2  CH), 135.6 (d, J = 9.2
Hz, C), 130.3 (CH), 129.7 (CH), 129.6 (d, J = 8.6 Hz, CH), 129.0 (CH),
128.8 (2  CH), 127.6 (t, J = 286.1 Hz, CF2), 126.3 (C), 124.3 (CH),
124.3 (d, J = 2.3 Hz, CH), 119.8 (CH), 115.0 (d, J = 22.5 Hz, CH), 112.8
(d, J = 21.4 Hz, CH), 106.2 (t, J = 25.9 Hz, C), 97.8 (d, J = 2.5 Hz, CH),
60.2 (OCH3), 37.2 (NCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -77.9 (d,
J = 208.7 Hz, 1F), -80.0 (d, J = 210.9 Hz, 1F), -114.0 to -114.1 (m, 1F)
ppm. HRMS (ESI-TOF) calcd. for C24H20F3NO2SNa [M + Na]+ 466.1065,
found 466.1053.
According to the general procedure A, nucleophilic addition of 1 (433 mg,
2 mmol) to 6a (265 mg, 1 mmol) using TBAT (108 mg, 0.2 mmol) in dry
toluene (0.5 mL) gave 7a (379 mg, 89%) as a brown oil after purification
by column chromatography (SiO2, 2% EtOAc/hexanes). IR (neat):  =
3062, 2934, 1778, 1703, 1467, 1441, 1270, 1036, 900, 749, 689 cm-1. H
1
NMR (400 MHz, CDCl3):  = 7.83 (d, J = 7.3 Hz, 2H, ArH), 7.71 (d, J =
7.6 Hz, 1H, ArH), 7.59-7.57 (m, 3H, ArH), 7.50-7.46 (m, 1H, ArH), 7.42-
7.35 (m, 4H, ArH), 7.32-7.28 (m, 2H, ArH), 7.22-7.18 (m, 1H, ArH), 6.03
(s, 1H, C=CH), 3.60 (s, 3H, OCH3), 2.62 (s, 3H, NCH3) ppm. 13C NMR
(100 MHz, CDCl3):  = 153.0 (C), 136.7 (2  CH), 136.0 (C), 135.4 (C),
135.2 (C), 130.2 (CH), 129.6 (CH), 129.4 (C), 128.7 (2  CH), 128.6 (2 
CH), 128.4 (2  CH), 127.7 (t, J = 286.3 Hz, CF2), 126.4 (C), 126.0 (CH),
124.3 (CH), 119.6 (CH), 105.8 (t, J = 26.0 Hz, C), 98.8 (CH), 60.2
(OCH3), 37.1 (NCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -78.0 (d, J =
209.4 Hz, 1F), -80.0 (d, J = 209.4 Hz, 1F) ppm. HRMS (ESI-TOF) calcd.
for C24H21F2NO2SNa [M + Na]+ 448.1159, found 448.1158.
(Z)-N-(1-(Difluoro(phenylsulfanyl)methyl)-3-(3-
(trifluoromethyl)benzylidene)-1,3-dihydroisobenzofuran-1-yl)-N,O-
dimethylhydroxylamine (7e): According to the general procedure A,
nucleophilic addition of 1 (433 mg, 2 mmol) to 6e (333 mg, 1 mmol) using
TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 7e (405 mg, 82%)
as a yellow sticky oil after purification by column chromatography (SiO2,
3% EtOAc/hexanes). IR (neat):  = 2935, 2896, 1665, 1468, 1441, 1330,
1121, 1056 cm-1. 1H NMR (400 MHz, CDCl3):  = 8.07 (br s, 1H, ArH),
8.04 (d, J = 7.6 Hz, 1H, ArH), 7.76 (d, J =7.5 Hz, 1H, ArH), 7.60 (d, J =
7.4 Hz, 3H, ArH), 7.52-7.43 (m, 4H, ArH), 7.40-7.30 (m, 3H, ArH), 6.06
(s, 1H, C=CH), 3.57 (s, 3H, OCH3), 2.69 (s, 3H, NCH3) ppm. 13C NMR
(100 MHz, CDCl3):  = 154.4 (C), 136.7 (2  CH), 136.3 (C), 135.7 (C),
135.5 (C), 131.4 (CH), 130.7 (q, J = 31.7 Hz, C), 130.4 (CH), 129.8 (CH),
129.1 (CH), 128.8 (3  CH), 127.6 (t, J = 289.6 Hz, CF2), 127.1 (q, J =
270.9 Hz, CF3), 126.2 (C), 125.2-125.1 (m, CH), 124.3 (CH), 122.4-122.5
(m, CH), 119.9 (CH), 106.3 (t, J = 25.9 Hz, C), 97.4 (CH), 60.3 (OCH3),
37.3 (NCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -63.3 (s, 3F, CF3),
-78.1 (d, J = 210.2 Hz, 1F), -80.1 (d, J = 210.2 Hz, 1F) ppm. HRMS (ESI-
TOF) calcd. for C25H20F5NO2SNa [M + Na]+ 516.1033, found 516.1030.
(Z)-N-(1-(Difluoro(phenylsulfanyl)methyl)-3-(4-methoxybenzylidene)-
1,3-dihydroisobenzofuran-1-yl)-N,O-dimethylhydroxylamine
(7b):
According to the general procedure A, nucleophilic addition of 1 (433 mg,
2 mmol) to 6b (295 mg, 1 mmol) using TBAT (108 mg, 0.2 mmol) in dry
toluene (0.5 mL) gave 7b (269 mg, 59%) as a yellowish brown sticky oil
after purification by column chromatography (SiO2, 2% EtOAc/hexanes).
IR (neat):  = 2933, 2895, 2835, 1603, 1510, 1249, 1176, 1053, 1033,
962 cm-1. 1H NMR (400 MHz, CDCl3):  = 7.83 (d, J = 8.7 Hz, 2H, ArH),
7.73 (d, J = 7.6 Hz, 1H, ArH), 7.63 (d, J = 7.1 Hz, 2H, ArH), 7.56 (d, J =
7.7 Hz, 1H, ArH), 7.47 (t, J = 7.4 Hz, 1H, ArH), 7.41-7.31 (m, 4H, ArH),
6.03 (s, 1H, C=CH), 3.84 (s, 3H, OCH3), 3.65 (s, 3H, OCH3), 2.64 (s, 3H,
NCH3) ppm. 13C NMR (100 MHz, CDCl3):  = 157.9 (C), 151.5 (C), 136.7
(2  CH), 136.2 (C), 134.9 (C), 130.2 (CH), 129.9 (2  CH), 129.6 (CH),
128.7 (2  CH), 128.2 (CH), 128.2 (C), 127.8 (t, J = 286.3 Hz, CF2),
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701322
European Journal of Organic Chemistry
FULL PAPER
1
(Z)-N-(1-(Difluoro(phenylsulfanyl)methyl)-3-(naphthalen-2-
ylmethylene)-1,3-dihydroisobenzofuran-1-yl)-N,O-
1591, 1510, 1248, 1028, 832, 750 cm-1. H NMR (400 MHz, CDCl3):  =
7.92 (d, J = 7.8 Hz, 1H, ArH), 7.67-7.61 (m, 3H, ArH), 7.55-7.49 (m, 3H,
ArH), 7.44-7.33 (m, 4H, ArH), 6.88 (d, J = 8.7 Hz, 2H, ArH), 3.84 (s, 3H,
OCH3) ppm. 13C NMR (100 MHz, CDCl3):  = 186.4 (t, J = 28.8 Hz, CO),
160.0 (C), 136.7 (2  CH), 133.8 (CH), 133.5 (2  CH), 132.3 (CH), 130.4
(CH, C), 129.5 (t, J = 4.1 Hz, CH), 129.2 (2  CH), 127.0 (CH), 124.8 (C),
124.4 (C), 123.3 (t, J = 290.7 Hz, CF2), 114.9 (C), 114.0 (2  CH), 95.2
(C), 86.3 (C), 55.3 (OCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -78.5 (s,
2F, CF2) ppm. HRMS (ESI-TOF) calcd. for C23H16F2O2SNa [M + Na]+
417.0737, found 417.0734.
dimethylhydroxylamine (7f): According to the general procedure A,
nucleophilic addition of 1 (433 mg, 2 mmol) to 6f (315 mg, 1 mmol) using
TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 7f (361 mg, 76%)
as a yellow sticky oil after purification by column chromatography (SiO2,
2% EtOAc/hexanes). IR (neat):  = 2930, 2892, 2810, 1660, 1624, 1596,
1504, 1464, 1439, 1337, 1051, 744 cm-1. 1H NMR (400 MHz, CDCl3):  =
8.29 (s, 1H, ArH), 8.12 (d, J = 8.6 Hz, 1H, ArH), 7.90 (t, J = 7.5 Hz, 2H,
ArH), 7.85 (d, J = 7.6 Hz, 1H, ArH), 7.78 (d, J = 7.6 Hz, 1H, ArH), 7.65 (t,
J = 7.1 Hz, 3H, ArH), 7.54-7.32 (m, 7H, ArH), 6.24 (s, 1H, C=CH), 3.67
(s, 3H, CH3), 2.71 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3):  =
153.5 (C), 136.7 (CH), 136.1 (C), 135.3 (C), 133.7 (C), 133.1 (C), 132.0
(C), 130.3 (CH), 129.7 (CH), 128.8 (CH), 128.7 (CH), 128.1 (CH), 127.9
(CH), 127.8 (t, J = 286.2 Hz, CF2), 127.5 (CH), 127.3 (CH), 127.1 (CH),
126.5 (C), 125.8 (CH), 125.3 (CH), 124.4 (CH), 119.7 (CH), 106.0 (t, J =
26.1 Hz, C), 99.0 (CH), 60.2 (CH3), 37.2 (CH3) ppm. 19F NMR (376 MHz,
CDCl3):  = -78.0 (d, J = 209.4 Hz, 1F), -80.0 (d, J = 209.4 Hz, 1F) ppm.
HRMS (ESI-TOF) calcd. for C28H23F2NO2SNa [M + Na]+ 498.1315, found
498.1313.
1-(2-(Benzo[d][1,3]dioxol-5-ylethynyl)phenyl)-2,2-difluoro-2-
(phenylsulfnayl)ethanone (8g): According to the general procedure A,
nucleophilic addition of 1 (433 mg, 2 mmol) to 6g (309 mg, 1 mmol) using
TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 8g (29 mg, 91%)
as a yellow sticky oil after purification by column chromatography (SiO2,
2% EtOAc/hexanes). IR (neat):  = 2898, 2204, 1708, 1490, 1227, 1035,
747, 689 cm-1. 1H NMR (400 MHz, CDCl3):  = 7.93 (d, J = 7.3 Hz, 1H,
ArH), 7.66-7.60 (m, 3H, ArH), 7.55-7.51 (m, 1H, ArH), 7.45-7.34 (m, 4H,
ArH), 7.10 (dd, J = 8.0, 1.5 Hz, 1H, ArH), 7.00 (d, J = 1.2 Hz, 1H, ArH),
6.80 (d, J = 8.0 Hz, 1H, ArH), 6.00 (s, 2H, CH2) ppm.13C NMR (100 MHz,
CDCl3):  = 186.3 (t, J = 28.4 Hz, CO), 148.3 (C), 147.4 (C), 136.8 (2 
CH), 133.9 (C), 132.4 (CH), 130.4 (CH), 129.6 (t, J = 4.3 Hz, CH), 129.3
(2  CH), 127.2 (CH), 126.9 (CH), 124.8 (C), 124.2 (C), 123.3 (t, J =
290.7 Hz, CF2), 116.1 (C), 111.8 (CH), 108.5 (CH), 101.4 (CH2), 95.0 (C),
86.0 (C) ppm. 19F NMR (376 MHz, CDCl3):  = -78.5 (s, 2 F, CF2) ppm.
HRMS (ESI-TOF) calcd. for C23H14F2O3SNa [M + Na]+ 431.0529, found
431.0529.
(Z)-N-(3-(Benzo[d][1,3]dioxol-5-ylmethylene)-1-
(difluoro(phenylsulfanyl)methyl)-1,3-dihydroisobenzofuran-1-yl)-
N,O-dimethylhydroxylamine (7g): According to the general procedure
A, nucleophilic addition of 1 (433 mg, 2 mmol) to 6g (309 mg, 1 mmol)
using TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 7g (305
mg, 65%) as
a yellow sticky oil after purification by column
chromatography (SiO2, 2% EtOAc/hexanes). IR (neat):  = 2891, 2811,
1664, 1487, 1440, 1255, 1037, 959, 736 cm-1. 1H NMR (400 MHz,
CDCl3):  = 7.73 (d, J = 7.6 Hz, 1H, ArH), 7.63-7.60 (m, 3H, ArH), 7.55-
7.53 (m, 1H, ArH), 7.46 (t, J = 7.4 Hz, 1H, ArH), 7.41-7.37 (m, 2H, ArH),
7.35-7.31 (m, 2H, ArH), 7.19 (dd, J = 8.1, 1.2 Hz, 1H, ArH), 6.85 (d, J =
8.1 Hz, 1H, ArH), 5.99 (s, 1H, C=CH), 5.97 (s, 2H, CH2), 3.62 (s, 3H,
OCH3), 2.65 (s, 3H, NCH3) ppm. 13C NMR (100 MHz, CDCl3):  = 151.7
(C), 147.7 (C), 145.8 (C), 136.7 (2  CH), 136.0 (C), 135.0 (C), 130.2
(CH), 129.8 (C), 129.6 (CH), 128.7 (2  CH), 128.3 (CH), 127.7 (t, J =
286.2 Hz, CF2), 126.4 (C), 124.3 (CH), 122.6 (CH), 119.4 (CH), 108.8
(CH), 108.3 (CH), 105.7 (t, J = 25.9 Hz, C), 100.8 (CH2), 98.7 (CH), 60.1
(OCH3), 37.1 (NCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -78.0 (d, J =
209.4 Hz, 1F), -80.0 (d, J = 209.1 Hz, 1F) ppm. HRMS (ESI-TOF) calcd.
for C25H21F2NO4SNa [M + Na]+ 492.1057, found 492.1075.
2,2-Difluoro-1-(2-(oct-1-yn-1-yl)phenyl)-2-(phenylsulfanyl)ethanone
(8h): According to the general procedure A, nucleophilic addition of 1
(433 mg, 2 mmol) to 6h (273 mg, 1 mmol) using TBAT (108 mg, 0.2
mmol) in dry toluene (0.5 mL) gave 8h (116 mg, 29%) as a yellow sticky
oil after purification by column chromatography (SiO2, 10%
CH2Cl2/hexanes). IR (neat):  = 2930, 2858, 2227, 1713, 1264, 985, 735
cm-1. 1H NMR (400 MHz, CDCl3):  = 7.81 (d, J = 7.1 Hz, 1H, ArH), 7.62
(d, J = 7.2 Hz, 2H, ArH), 7.54-7.53 (m, 1H, ArH), 7.48-7.43 (m, 2H, ArH),
7.40-7.36 (m, 2H, ArH), 7.33-7.29 (m, 2H, ArH), 2.42 (t, J = 7.1 Hz, 2H,
CH2), 1.64-1.57 (m, 2H, CH2), 1.49-1.41 (m, 2H, CH2), 1.35 (m, 4H, 2 
CH2), 0.92-0.88 (m, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3):  =
187.0 (t, J = 28.6 Hz, CO), 136.7 (2  CH), 134.5 (C), 134.1 (2  CH),
132.0 (CH), 130.3 (CH), 129.2 (2  CH), 129.0 (t, J = 3.9 Hz, CH), 126.7
(CH), 124.9 (C), 124.6 (C), 123.2 (t, J = 290.8 Hz, CF2), 96.8 (C), 78.3
(C), 31.3 (CH2), 28.6 (CH2), 28.4 (CH2), 22.5 (CH2), 19.7 (CH2), 14.1
(CH3) ppm. 19F NMR (376 MHz, CDCl3):  = -78.7 (s, 2F, CF2) ppm.
HRMS (ESI-TOF) calcd. for C22H22F2OSNa [M + Na]+ 395.1257, found
395.1250.
2,2-Difluoro-1-(2-(phenylethynyl)phenyl)-2-(phenylsulfanyl)ethanone
(8a): According to the general procedure A, nucleophilic addition of 1
(433 mg, 2 mmol) to 6a (265 mg, 1 mmol) using TBAT (108 mg, 0.2
mmol) in dry toluene (0.5 mL) gave 8a (18 mg, 5%) as a yellow sticky oil
after purification by column chromatography (SiO2, 2% EtOAc/hexanes).
IR (neat):  = 3062, 2216, 1711, 1493, 1442, 1101, 753, 689 cm-1. 1H
NMR (400 MHz, CDCl3):  = 7.94 (dd, J = 7.9, 0.7 Hz, 1H, ArH), 7.70-
7.68 (m, 1H, ArH), 7.62 (d, J = 7.2 Hz, 2H, ArH), 7.59-7.53 (m, 3H, ArH),
7.44-7.33 (m, 7H, ArH) ppm. 13C NMR (100 MHz, CDCl3):  = 186.3 (t, J
= 28.6 Hz, CO), 136.7 (2  CH), 134.1 (CH), 132.3 (CH), 131.9 (2  CH),
130.4 (CH), 129.5 (t, J = 4.1 Hz, CH), 129.3 (2  CH), 128.7 (CH), 128.3
(2  CH), 127.5 (CH), 124.8 (C), 124.0 (C), 123.2 (t, J = 290.6 Hz, CF2),
122.8 (C), 94.8 (C), 87.3 (C) ppm. 19F NMR (376 MHz, CDCl3):  = -78.6
(s, 2F, CF2) ppm. HRMS (ESI-TOF) calcd. for C22H14F2OSNa [M + Na]+
387.0631, found 387.0628.
General procedure B for reductive desulfurization of phenylsulfanyl
group employing Raney nickel/H2: To a 10 mL round bottom flask
equipped with a magnetic bar was added 3 (0.3 mmol). Raney nickel W-
2[26] [Note: The activity of Raney-nickel from each prepared batch is
different and has a lifetime of 2 to 3 weeks for consistent results] in EtOH
(0.0866 g/mL, 7 mL) was added to the flask. The flask was equipped with
a reflux condenser and equipped with a H2 balloon. The flask was heated
to 70 °C. The reaction was monitored by 1H, and 19F NMR spectrometer.
After the completion of the reaction, the reaction was cooled to room
temperature and filtered through celite to remove Raney-nickel. The
organic layer was concentrated (aspirator) to yield a crude reaction
mixture. Products were purification by column chromatography
(CH2Cl2/hexanes) to give compound 9.
2,2-Difluoro-1-(2-((4-methoxyphenyl)ethynyl)phenyl)-2-
(phenylsulfanyl)ethanone (8b): According to the general procedure A,
nucleophilic addition of 1 (433 mg, 2 mmol) to 6b (295 mg, 1 mmol) using
TBAT (108 mg, 0.2 mmol) in dry toluene (0.5 mL) gave 8b (24 mg, 6%)
as a yellow sticky oil after purification by column chromatography (SiO2,
2% EtOAc/hexanes). IR (neat):  = 3062, 2958, 2931, 2838, 2212, 1708,
2,2-Difluoro-1-(3,4,5-trimethoxyphenyl)ethanone (9a): According to
the general procedure B, desulfurization of 3a (106 mg, 0.3 mmol) with
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701322
European Journal of Organic Chemistry
FULL PAPER
Raney nickel in EtOH (7 mL) gave 9a (202 mg, 82%) as a white solid
[m.p. 6970 °C (EtOAc/hexanes)] after purification by column
chromatography (SiO2, 50% CH2Cl2/hexanes). Data is in agreement with
previously reported literature.[27] IR (neat):  = 2945, 2844, 1703, 1584,
1505, 1419, 1325, 1128 cm-1. 1H NMR (400 MHz, CDCl3):  = 7.32 (s,
2H, ArH), 6.26 (t, J = 53.6 Hz, 1H, CHF2), 3.95 (s, 3H, OCH3), 3.91 (s,
6H, 2  OCH3) ppm. 13C NMR (100 MHz, CDCl3):  = 186.3 (t, J = 25.1
Hz, CO), 153.2 (2  C), 144.3 (C), 126.2 (C), 111.4 (t, J = 252.6 Hz,
CHF2), 107.4 (2  CH), 61.0 (OCH3), 56.3 (2  OCH3) ppm. 19F NMR
(376 MHz, CDCl3):  = -121.2 (d, J = 53.4 Hz, 2F, CF2) ppm. HRMS (ESI-
TOF): calcd. for C11H13F2O4 [M + H]+ 247.0782, found 247.0789.
(2  CH), 128.9 (C), 126.0 (2  CH), 111.2 (t, J = 252.1 Hz, CHF2), 35.4
(C), 30.9 (3  CH3) ppm. 19F NMR (376 MHz, CDCl3):  = -122.4 (d, J =
53.4 Hz, 2F, CF2) ppm. HRMS (ESI-TOF): calcd. for C12H14F2ONa [M +
Na]+ 235.0910, found 235.0909.
2,2-Difluoro-1-phenylethanone (9f): According to the general
procedure B, desulfurization of 3e (79 mg, 0.3 mmol) with Raney nickel in
EtOH (7 mL) gave 9e (141 mg, 90%) as a colorless oil after purification
by column chromatography (SiO2, 20% CH2Cl2/hexanes). Data is in
agreement with previously reported literature.[14a] IR (neat):  = 2956,
2924, 2853, 1710, 1598, 1452, 1062, 703 cm-1. 1H NMR (400 MHz,
CDCl3):  = 8.08 (d, J = 7.6 Hz, 2H, ArH), 7.68 (t, J = 7.4 Hz, 1H, ArH),
7.54 (t, J = 7.8 Hz, 2H, ArH), 6.30 (t, J = 53.5 Hz, 1H, CF2H) ppm. 13C
NMR (100 MHz, CDCl3):  = 187.6 (t, J = 25.1 Hz, CO), 134.9 (CH),
131.5 (C), 129.6 (2  CH), 129.0 (2  CH), 111.2 (t, J = 252.2 Hz, CHF2)
ppm. 19F NMR (376 MHz, CDCl3):  = -122.4 (d, J = 53.4 Hz, 2F, CF2)
ppm. HRMS (ESI-TOF): calcd. for C8H6F2ONa [M + Na]+ 179.0284, found
179.0283.
1-(3,5-Dimethoxyphenyl)-2,2-difluoroethanone (9b): According to the
general procedure B, desulfurization of 3b (97 mg, 0.3 mmol) with Raney
nickel in EtOH (7 mL) gave 9b (188 mg, 87%) as a colorless oil after
purification by column chromatography (SiO2, 30% CH2Cl2/hexanes).
Data is in agreement with previously reported literature.[27] IR (neat):  =
3008, 2944, 2843, 1709, 1591, 1427, 1300, 1205, 1157, 1052, 787 cm-1.
1H NMR (400 MHz, CDCl3):  = 7.17-7.16 (m, 2H, ArH), 6.73 (t, J = 2.3
Hz, 1H, ArH), 6.28 (t, J = 53.5 Hz, 1H, CF2H), 3.83 (s, 6H, 2  OCH 3)
ppm. 13C NMR (100 MHz, CDCl3):  = 187.1 (t, J = 24.9 Hz, CO), 161.0
(2  C), 133.1 (C), 110.8 (t, J = 251.8 Hz, CHF2), 107.4 (CH), 107.1 (2 
CH), 55.6 (2  OCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -122.5 (d, J
= 53.4 Hz, 2F, CF2) ppm. HRMS (ESI-TOF): calcd. for C10H10F2O3Na
[M + Na]+ 239.0496, found 239.0500.
1-(3-Chlorophenyl)-2,2-difluoroethanone (9i): According to the general
procedure B, desulfurization of 3i (90 mg, 0.3 mmol) with Raney nickel in
EtOH (7 mL) gave 9i (168 mg, 88%) as a pale yellow oil after purification
by column chromatography (SiO2, 25% CH2Cl2/hexanes). Data is in
agreement with previously reported literature.[14a] IR (neat):  = 2926,
2855, 1712, 1571, 1238, 1142, 1064, 747 cm-1. 1H NMR (400 MHz,
CDCl3):  = 8.04 (br s, 1H, ArH), 7.97 (d, J = 7.9 Hz, 1H, ArH), 7.65 (ddd,
J = 8.0, 2.0, 0.9 Hz, 1H, ArH), 7.48 (t, J = 7.9 Hz, 1H, ArH), 6.25 (t, J =
53.4 Hz, 1H, CF2H) ppm. 13C NMR (100 MHz, CDCl3):  = 186.5 (t, J =
25.9 Hz, CO), 135.3 (C), 134.8 (CH), 132.8 (C), 130.3 (CH), 129.5 (CH),
127.7 (CH), 111.1 (t, J = 252.6 Hz, CHF2) ppm. 19F NMR (376 MHz,
CDCl3):  = -122.3 (d, J = 53.4 Hz, 2F, CF2) ppm. HRMS (ESI-TOF):
2,2-Difluoro-1-(3-methoxyphenyl)ethanone (9c): According to the
general procedure B, desulfurization of 3c (88 mg, 0.3 mmol) with Raney
nickel in EtOH (7 mL) gave 9c (164 mg, 88%) as a colorless oil after
purification by column chromatography (SiO2, 30% CH2Cl2/hexanes).
Data is in agreement with previously reported literature.[27] IR (neat):  =
2946, 2841, 1707, 1598, 1582, 1268, 1127, 1050 cm-1. 1H NMR (400
MHz, CDCl3):  = 7.67 (d, J = 7.7 Hz, 1H, ArH), 7.57 (br s, 1H, ArH), 7.44
(t, J = 8.0 Hz, 1H, ArH), 7.22 (ddd, J = 8.3, 2.6, 0.8 Hz, 1H, ArH), 6.30 (t,
J = 53.5 Hz, 1H, CF2H), 3.88 (s, 3H, OCH3) ppm. 13C NMR (100 MHz,
CDCl3):  = 187.3 (t, J = 25.1 Hz, CO), 159.9 (C), 132.6 (C), 129.9 (CH),
122.2 (CH), 121.7 (CH), 113.4 (CH), 110.9 (t, J = 251.8 Hz, CHF2), 55.5
(OCH3) ppm. 19F NMR (376 MHz, CDCl3):  = -122.4 (d, J = 53.4 Hz, 2F,
CF2) ppm. HRMS (ESI-TOF): calcd. for C9H8F2O2Na [M + Na]+ 209.0390,
found 209.0411.
calcd for C8H5ClF2ONa [M
214.9869.
+
Na]+ 212.9895 found 212.9900 and
2,2-Difluoro-1-(naphthalen-2-yl)ethanone (9p): According to the
general procedure B, desulfurization of 3p (94 mg, 0.3 mmol) with Raney
nickel in EtOH (7 mL) gave 9p (173 mg, 84%) as a pale yellow solid [m.p.
6062 °C (EtOAc/hexanes)] after purification by column chromatography
(SiO2, 30% CH2Cl2/hexanes). Data is in agreement with previously
reported literature.[14a] IR (neat):  = 2994, 2926, 1703, 1620, 1468, 1356,
1116, 1051, 1009, 801, 750 cm-1. 1H NMR (400 MHz, CDCl3):  = 8.64 (s,
1H, ArH), 8.08-7.88 (m, 4H, ArH), 7.68-7.57 (m, 2H, ArH), 6.42 (t, J =
53.5 Hz, 1H, CF2H) ppm. 13C NMR (100 MHz, CDCl3):  = 187.5 (t, J =
25.0 Hz, CO), 136.2 (C), 132.4 (t, J = 2.9 Hz, CH), 132.2 (C), 130.0 (CH),
129.6 (CH), 128.9 (CH), 128.7 (C), 127.8 (CH), 127.2 (CH), 124.0 (CH),
111.3 (t, J = 252.2 Hz, CHF2) ppm. 19F NMR (376 MHz, CDCl3):  =
-121.8 (d, J = 53.8 Hz, 2F, CF2) ppm. HRMS (ESI-TOF): calcd. for
C12H8F2ONa [M + Na]+ 229.0441, found 229.0440.
2,2-Difluoro-1-(m-tolyl)ethanone (9d): According to the general
procedure B, desulfurization of 3d (83 mg, 0.3 mmol) with Raney nickel
in EtOH (7 mL) gave 9d (129 mg, 76%) as a colorless oil after purification
by column chromatography (SiO2, 25% CH2Cl2/hexanes). Data is in
agreement with previously reported literature.[14a] IR (neat):  = 2956,
1
2925, 2853, 1711, 1264, 1133, 1060 cm-1. H NMR (400 MHz, CDCl3): 
= 7.88 (br s, 2H, ArH), 7.49 (d, J = 7.6 Hz, 1H, ArH), 7.41 (t, J = 7.9 Hz,
1H, ArH), 6.30 (t, J = 53.5 Hz, 1H, CHF2), 2.43 (s, 3H, CH3) ppm.
13C NMR (100 MHz, CDCl3):  = 187.7 (t, J = 25.0 Hz, CO), 138.9 (C),
135.7 (CH), 131.5 (C), 130.0 (CH), 128.8 (CH), 126.8 (CH), 111.0 (t, J =
252.0 Hz, CHF2), 21.3 (CH3) ppm. 19F NMR (376 MHz, CDCl3): = -122.6
(d, J = 53.4 Hz, 2F, CF2) ppm. HRMS (ESI-TOF): calcd. for C9H8F2ONa
[M + Na]+ 193.0441, found 193.0453.
1,1-Difluorononan-2-one (9r): According to the general procedure B,
desulfurization of 3r (86 mg, 0.3 mmol) with Raney nickel in EtOH (7 mL)
gave 9r (159 mg, 89%) as a colorless oil after purification by column
chromatography (SiO2, 100% CH2Cl2). IR (neat):  = 2956, 2921, 2851,
1722, 1463, 1378, 1261 cm-1. 1H NMR (400 MHz, CDCl3):  = 5.61 (t, J =
54.1 Hz, 1H, CHF2), 2.59 (t, J = 7.3 Hz, 2H, CH2), 1.59-1.55 (m, 2H,
CH2), 1.24-1.21 (m, 8H, 4  CH2), 0.83-0.80 (m, 3H, CH3) ppm. 13C NMR
(100 MHz, CDCl3):  = 200.0 (t, J = 25.9 Hz, CO), 109.9 (t, J = 251.3 Hz,
CHF2), 36.0 (CH2), 31.6 (CH2), 28.9 (2  CH2), 22.6 (CH2), 22.3 (CH2),
14.0 (CH3) ppm. 19F NMR (376 MHz, CDCl3):  = -127.5 (d, J = 54.1 Hz,
2F, CF2) ppm. HRMS (ESI-TOF): calcd. for C9H15F2O [M - H]- 177.1091,
found 177.1080.
1-(4-(tert-Butyl)phenyl)-2,2-difluoroethanone (9e): According to the
general procedure B, desulfurization of 3e (96 mg, 0.3 mmol) with Raney
nickel in EtOH (7 mL) gave 9e (180 mg, 85%) as a colorless oil after
purification by column chromatography (SiO2, 10% CH2Cl2/hexanes).
Data is in agreement with previously reported literature.[15a] IR (neat):  =
2965, 2871, 1698, 1605, 1298, 1141, 1109, 1061 cm-1. 1H NMR (400
MHz, CDCl3):  = 8.02 (d, J = 8.3 Hz, 2H, ArH), 7.55 (d, J = 8.5 Hz, 2H,
ArH), 6.29 (t, J = 53.6 Hz, 1H, CF2H), 1.35 (s, 9H, 3  CH3) ppm. 13C
NMR (100 MHz, CDCl3):  = 187.2 (t, J = 24.9 Hz, CO), 159.0 (C), 129.6
2,2-Difluoro-1-(thiophen-2-yl)ethanone (9t): According to the general
procedure B, desulfurization of 3t (81 mg, 0.3 mmol) with Raney nickel in
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701322
European Journal of Organic Chemistry
FULL PAPER
EtOH (7 mL) gave 9t (149 mg, 92%) as a pale yellow oil after purification
by column chromatography (SiO2, 20% CH2Cl2/hexanes). Data is in
agreement with previously reported literature.[27] IR (neat):  = 3107,
2924, 2852, 1676, 1412, 1056, 725 cm-1. 1H NMR (400 MHz, CDCl3):  =
8.02-8.01 (m, 1H, ArH), 7.85 (dd, J = 4.9, 0.9 Hz, 1H, ArH), 7.24 (dd, J =
4.8, 4.1 Hz, 1H, ArH), 6.18 (t, J = 53.7 Hz, 1H, CF2H) ppm. 13C NMR
(100 MHz, CDCl3):  = 181.1 (t, J = 26.5 Hz, CO), 137.7 (C), 136.7 (CH),
135.5 (CH), 128.9 (CH), 110.8 (t, J = 252.4 Hz, CHF2) ppm. 19F NMR
(376 MHz, CDCl3):  = -122.1 (d, J = 53.8 Hz, 2F, CF2) ppm. HRMS (ESI-
TOF) calcd. for C6H4F2OSNa [M + Na]+ 184.9849, found 184.9860.
(CH), 60.5 (OCH3), 35.6 (NCH3) ppm. 19F NMR (376 MHz, CDCl3):  =
129.6 (dd, J = 287.3, 54.9 Hz, 1F), 135.5 (dd, J = 285.4, 56.8 Hz, 1F)
ppm. HRMS (ESI-TOF) calcd. for C18H17F2NO2Na [M  Na] 340.1125,
found 340.1127.
1,1-Difluoro-4-phenylbutan-2-one (9u): According to the general
procedure C, reductive desulfurization of 3u (174 mg, 0.6 mmol) using
AIBN (15 mg, 0.09 mmol), and Bu3SnH (306 mg, 1.05 mmol) in dry
toluene (6 mL) gave 9u (73 mg, 66%) as colorless oil after purification by
column chromatography (SiO2, 40% CH2Cl2/hexanes).
1,1-Difluoro-4-phenylbutan-2-one (9u): According to the general
procedure B, desulfurization of 3u (87 mg, 0.3 mmol) with Raney nickel
in EtOH (7 mL) gave 9u (37 mg, 67%) as a colorless oil after purification
by column chromatography (SiO2, 40% CH2Cl2/hexanes). Data is in
agreement with previously reported literature.[28] 1H NMR (400 MHz,
CDCl3):  = 7.32-7.29 (m, 2H, ArH), 7.24-7.19 (m, 3H, ArH), 5.68 (t, J =
54.0 Hz, 1H, CF2H), 3.04-2.94 (m, 4H, 2  CH2) ppm. 13C NMR (100
MHz, CDCl3):  = 198.9 (t, J = 26.5 Hz, CO), 139.9 (C), 128.6 (2  CH),
128.3 (2  CH), 126.5 (CH), 109.8 (t, J = 251.3 Hz, CHF2), 37.7 (CH2),
28.3 (CH2) ppm. 19F NMR (376 MHz, CDCl3):  = -127.5 (d, J = 53.8 Hz,
2F, CF2) ppm. HRMS (ESI-TOF): calcd. for C10H9F2O [M - H]- 183.0621,
found 183.0626.
4-(4-Chlorophenyl)-1,1-difluorobutan-2-one (9v): According to the
general procedure C, reductive desulfurization of 3v (195 mg, 0.6 mmol)
using AIBN (15 mg, 0.09 mmol), and Bu3SnH (306 mg, 1.05 mmol) in dry
toluene (6 mL) gave 9v (94 mg, 72%) as colorless oil after purification by
column chromatography (SiO2, 40% CH2Cl2/hexanes).
Acknowledgements
We thank the Thailand Research Fund (BRG5850012 and
IRN58W0005), the Center of Excellence for Innovation in
Chemistry (PERCH-CIC), Postgraduate Education Research
Development Office, the Office of the Higher Education
Commission, Mahidol University under the National Research
Universities Initiative, and PICS6663 ISMA (France/Thailand) for
financial supports. The Institute for the Promotion of Teaching
Science and Technology and Science Achievement Scholarship
of Thailand (SAST) for financial support through student
scholarship to J.P. are also gratefully acknowledged.
4-(4-Chlorophenyl)-1,1-difluorobutan-2-one (9v): According to the
general procedure B, desulfurization of 3v (97 mg, 0.3 mmol) with Raney
nickel in EtOH (7 mL) gave 9v (40 mg, 60%) as a colorless oil after
purification by column chromatography (SiO2, 40% CH2Cl2/hexanes). IR
(neat):  = 2933, 1747, 1493, 1408, 1343, 1093, 1060, 818 cm-1. 1H NMR
(400 MHz, CDCl3):  = 7.27 (d, J = 8.4 Hz, 2H, ArH), 7.13 (d, J = 8.4 Hz,
2H, ArH), 5.68 (t, J = 53.9 Hz, 1H, CF2H), 3.01-2.97 (m, 2H, CH2), 2.95-
2.91 (m, 2H, CH2) ppm. 13C NMR (100 MHz, CDCl3):  = 198.6 (t, J =
26.4 Hz, CO), 138.3 (C), 132.2 (C), 129.7 (2  CH), 128.7 (2  CH),
109.7 (t, J = 251.4 Hz, CHF2), 37.4 (CH2), 27.6 (CH2) ppm. 19F NMR (376
MHz, CDCl3):  = -127.4 (d, J = 53.8 Hz, 2F, CF2) ppm. HRMS (ESI-
TOF): calcd. for C10H8ClF2O [M - H]- 217.0232, found 217.0229.
Keywords: difluoromethyl ketones
•
Weinreb amides
•
nucleophilic substitution • phthalans • tandem reaction
General procedure C for reductive desulfurization of phenylsulfanyl
group employing Bu3SnH/AIBN: To an oven dried 10 mL round bottom
flask equipped with a magnetic bar was added 7a (255 mg, 0.6 mmol)
and sealed with a septum. Toluene (3.0 mL) was added to the flask
under argon atmosphere. Argon gas was bubbled through a solution of
7a for 15 min. Then, the solution was heated to reflux while a degassed
solution of Bu3SnH (306 mg, 1.05 mmol), and AIBN (15 mg, 0.09 mmol)
in dry toluene (3.0 mL) was added drop wise. After 13 h, the reaction was
cooled to room temperature and purified by column chromatography
(SiO2, 100% hexanes) to remove tin by-product. Then, 20%
EtOAc/hexanes was used as an eluent. Final purification by column
chromatography (SiO2, 2% EtOAc in hexanes) gave 10a (152 mg, 80%)
as a white solid [m.p. 153154 °C (EtOAc/hexanes)].
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(Z)-N-(3-Benzylidene-1-(difluoromethyl)-1,3-dihydroisobenzofuran-1-
yl)-N,O-dimethylhydroxylamine (10a): According to the general
procedure C, reductive desulfurization of 7a (255 mg, 0.6 mmol) using
AIBN (15 mg, 0.09 mmol), and Bu3SnH (306 mg, 1.05 mmol) in dry
toluene (6 mL) gave 10a (152 mg, 80%) as a white solid [m.p. 153154
°C (EtOAc/hexanes)]. IR (neat):  = 1372, 1083, 962, 760 cm1. 1H NMR
(400 MHz, CDCl3):  = 7.77 (d, J = 7.5 Hz, 2H, ArH), 7.58 (d, J = 7.7 Hz,
1 H, ArH), 7.52-7.47 (m, 2H, ArH), 7.41-7.36 (m, 3H, ArH), 7.20 (t, J = 7.4
Hz, 1H, ArH), 6.42 (dd, J = 57.3, 55.6 Hz, 1H, CF2H), 6.01 (s, 1H,
C=CH), 3.69 (s, 3H, OCH3), 2.39 (s, 3H, NCH3) ppm. 13C NMR (100
MHz, CDCl3):  = 153.2 (C), 136.5 (C), 135.5 (C), 133.6 (C), 130.5 (CH),
129.0 (CH), 128.5 (4  CH), 126.0 (CH), 124.3 (CH), 119.7 (CH), 112.4
(dd, J = 247.6, 241.8 Hz, CF2H), 104.3 (dd, J = 28.3, 24.0 Hz, C), 98.5
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701322
European Journal of Organic Chemistry
FULL PAPER
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Entry for the Table of Contents
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Synthesis of organofluorines *
Jongkonporn Phetcharawetch, Nolan M.
Betterley, Darunee Soorukram, Manat
Pohmakotr, Vichai Reutrakul, and
Chutima Kuhakarn*
Page No. – Page No.
Text for Table of Contents
Synthesis of Difluoromethyl Ketones
from Weinreb Amides and Tandem
Addition/Cyclization of o-Alkynylaryl
Weinreb Amides
The synthesis of difluoromethyl ketones was accomplished employing fluoride-
induced nucleophilic substitution of PhSCF2SiMe3 to Weinreb amides followed by
Raney nickel/H2 mediated chemoselective reductive desulfurization.
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