Vinylation of Iododifluoromethylated Alcohols via a Light-Promoted Intramolecular Atom-Transfer Reaction

Article abstract of DOI:10.1055/s-0036-1590855

A method for the synthesis of gem -difluorohomoallylic alcohols by the substitution of iodine in the iododifluoromethyl group by a vinyl fragment is described. The reaction proceeds via an intramolecular iodine atom transfer followed by β-elimination. The reaction is performed in the presence of an iridium photocatalyst, fac -Ir(ppy) ₃, and triphenylphosphine under irradiation with light-emitting diodes.

Full text of DOI:10.1055/s-0036-1590855

SYNTHESIS
0
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1
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X
© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–I
feature
A
en
L. I. Panferova et al.
Feature
Synthesis
Vinylation of Iododifluoromethylated Alcohols via a Light-Promoted
Intramolecular Atom-Transfer Reaction
Liubov I. Panferova
Marina I. Struchkova
Alexander D. Dilman*
Me Me
Si
, Et3N
Cl
OH
OH
then
0
0
0
0
0-
0
0
1
8-
0
4
8
7-
2
2
3
I
R
R
fac-Ir(ppy)3, Ph3P
F
F
F
F
N. D. Zelinsky Institute of Organic Chemistry,
Leninsky prosp. 47, 119991 Moscow, Russian
Federation
NaOAc, 400 nm LED
17 examples
60–91% yield
adil25@mail.ru
Received: 16.05.2017
Accepted after revision: 06.07.2017
Published online: 07.08.2017
demonstrated that the primary addition products of these
reactions can serve as sources of radicals under photoredox
conditions16 (Scheme 1). Herein, we apply this concept for
reactions of compounds 2 containing a double bond as a
part of the silyl fragment. The silicon tether makes the radi-
cal attack intramolecular, thereby alleviating the regioselec-
tivity problem.17 At the same time, facile C–Si bond cleavage
reinstates the double bond affording alcohols 3, with the
overall sequence corresponding to the substitution of
iodine in substrates 118 by the vinyl group.19
DOI: 10.1055/s-0036-1590855; Art ID: ss-2017-z0331-fa
Abstract A method for the synthesis of gem-difluorohomoallylic alco-
hols by the substitution of iodine in the iododifluoromethyl group by a
vinyl fragment is described. The reaction proceeds via an intramolecular
iodine atom transfer followed by β-elimination. The reaction is per-
formed in the presence of an iridium photocatalyst, fac-Ir(ppy)3, and
triphenylphosphine under irradiation with light-emitting diodes.
Key words organofluorine compounds, photocatalysis, silicon
reagents, radical reaction, atom transfer
Previous work
OSiMe3
X
OSiMe3
O
The synthesis of organofluorine compounds has
become an intensively investigated area in recent years,1
apparently, owing to the importance of such compounds in
medicinal chemistry2 and materials science.3 Though di-
verse approaches for the preparation of fluorinated mole-
cules can be envisaged,1 classical ionic reactions4 and tran-
sition-metal-catalyzed cross-couplings5 have dominated
the field for a long time. In contrast, reactions involving flu-
orinated radicals have come to the fore within the last de-
cade.6 The advent of photoredox catalysis with visible light7
has further advanced the scope of methods for the genera-
tion of fluorinated radicals.8
R
R
R
F
F
F
F
X = I, +PPh3
This work
Me Me
Me Me
OH
R
Si
O
OH
F
Si
O
I
R
I
R
R
F
F
1
3
F
F
F
F
F
2
Scheme 1 Applications of difluorinated radicals
Silyl ether 2a, obtained from iododifluoromethyl-substi-
tuted alcohol 1a (R = 4-ClC6H4) and chloro(dimethyl)vinyl-
silane, was evaluated under various conditions upon irradi-
ation with a strip of either blue or 400 nm light-emitting
diodes for 2 hours (Table 1). There was virtually no reaction
until a combination of sodium acetate with a substoichio-
metric amount (0.2 equiv) of triphenylphosphine was used
(entry 6). The application of 400 nm light was also import-
ant, allowing for about 90% conversion of substrate 2a after
2 hours, as there was no reaction with blue light without a
photocatalyst (entry 7). Further addition of 0.25 mol%
fac-Ir(ppy)3 provided a significant rate acceleration, and
complete conversion was observed within 15 minutes!
However, for generality, the reactions were typically performed
Because of
a strong electron-withdrawing effect,
fluorine atoms facilitate the reductive generation of radical
species from perfluorinated substrates.9 In this regard, elec-
tron-deficient sulfonium salts (e.g., Umemoto’s reagents)10
or Togni’s iodanes11 are the most easily reducible reagents,
which are typically used as sources of the trifluoromethyl
radical.12 At the same time, radical processes involving par-
tially fluorinated substrates have been less elaborated,13
which may be associated with difficult access to the corre-
sponding precursors (e.g., partially fluorinated iodides).
Recently, we reported the fluoroalkylation of carbonyl
compounds and iminium ions with iododifluoromethyl14
and phosphinyldifluoromethyl15 nucleophilic reagents, and
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

B
L. I. Panferova et al.
Feature
Synthesis
1
for 2 hours (entry 10). Based on H and 19F NMR analysis,
the product is formed as a mixture of several compounds of
general structure 4 differing in the silicon substituent Y,
presumably acetate or siloxane.
tained from an enolizable aliphatic aldehyde also provided
product 3q, although in a decreased yield of 60%. However,
the iododifluoromethylated alcohol derived from acetophe-
none gave a complex mixture of products.
To obviate the prior isolation of silyl ethers 2, the whole
sequence involving silylation/radical vinylation/desilylation
was performed in a one-pot manner. Thus, alcohols 1 were
treated with chloro(dimethyl)vinylsilane and triethylamine,
followed by addition to the same flask of sodium acetate,
triphenylphosphine, and the photocatalyst under irradia-
tion (400 nm). Then, the mixture was treated with ammo-
nium fluoride, and worked up. A series of alcohols was sub-
jected to this radical vinylation of the iododifluoromethyl
group (Table 2). Various aromatic and heteroaromatic sub-
strates provided good yields of products. The reaction toler-
ates ester and nitrile groups, and works well with electron-
donating and electron-withdrawing substituents, as well as
substituents at the ortho-position. The substrate 1q ob-
Concerning the mechanism, we believe that the reaction
proceeds via an atom transfer/radical addition (ATRA) pro-
cess.20,21 The reaction presumably starts with the formation
of a halogen-bonded complex22 between the iododifluoro-
methyl group and the phosphine23 (Scheme 2). This com-
plex can lead to radical 5 either with assistance of light or
by reduction with the photoexcited iridium(III) complex.
Subsequent exo-dig cyclization with the formation of a five-
membered ring proceeds rapidly, leading to radical 6.
Though oxidation of the primary radical with iridium(IV) is,
in principle, possible, a chain process seems more likely.
Thus, transfer of the iodine atom from the starting iodide 2
can regenerate radical 5 along with formation of iodide 7.
The latter species undergoes rapid fragmentation with con-
Biographical Sketches
Liubov Panferova studied at
the Higher Chemical College of
the Russian Academy of Scienc-
es, and performed undergradu-
ate work in the group of Prof.
Vladimir Grushin at the Institute
of Chemical Research of Catalo-
nia, Spain. In 2015 she joined
the group of A. D. Dilman as a
graduate student at the Zelinsky
Institute of Organic Chemistry.
She is interested in organoele-
ment and organofluorine com-
pounds.
Marina Struchkova graduat-
ed from Moscow State Universi-
ty in 1968, and obtained her
Ph.D. in 1977 from the Moscow
University of Chemical Technol-
ogy. Then, she joined the NMR
laboratory of the Zelinsky Insti-
tute of Organic Chemistry. Her
major interests involve NMR
spectroscopy.
Alexander Dilman received
his Ph.D. from the Zelinsky Insti-
tute of Organic Chemistry in
2001 (with Prof. S. L. Ioffe).
Then, he spent one year as a
postdoc in the group of Prof. H.
B. Kagan at the Université Paris-
Sud, France. In 2003 he re-
turned to the Zelinsky Institute
and started independent work.
In 2008 he completed his habili-
tation studies (Dr. Sci. in Russia),
and in 2011 he became a Head
of Laboratory. His current inter-
ests include the chemistry of or-
ganofluorine compounds.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

C
L. I. Panferova et al.
Feature
Synthesis
certed breaking of carbon–iodine and carbon–silicon
bonds.24 This β-elimination may be facilitated by acetate
anion, which can coordinate to the silicon atom.
Table 2 Synthesis of Alcohols 3
Me Me
Si
, Et3N (1.2 equiv)
OH
F
OH
Cl
1.
In summary, a convenient method for the formal substi-
tution of iodine in iododifluoromethylated alcohols by the
vinyl group is described. The reaction process involves a se-
quence of transformations, such as silylation, light-mediat-
ed atom transfer, and desilylation, which are performed in a
one-pot manner by consecutive addition of the required re-
agents. A combination of sodium acetate, triphenylphos-
phine, and 400 nm light irradiation is a key feature respon-
sible for the reaction efficiency.
(1.1 equiv)
MeCN, rt, 1–3 h
I
R
R
2. Ir(ppy)3 (0.25 mol%), NaOAc (2 equiv)
Ph3P (0.2 equiv), 400 nm LED, 2 h
F
F
F
1
3
3. NH4F
Substrate
Product
Yield
(%) of 3a
OH
F
OH
I
3a
3b
79
91
F
F
F
Cl
Cl
OH
OH
I
F
F
F
F
F
Table 1 Optimization Studies
MeO2C
MeO2C
Me Me
Me Me
reagents
OH
F
OH
F
Si
OH
F
I
Si
O
LED
NH4F
3c
3d
3e
73
79
91
O
Y
I
R
F
MeCN, rt, 2 h
R
NC
NC
R
F
F
F
F
F
2a, R = 4-ClC6H4
4
3a
OH
F
OH
F
I
Entry Reagents (equiv)
LED
Yield (%)
F
F
of 4a
OH
F
OH
F
1
2
–
400 nm
400 nm
blue
0
0
I
NaOAc (2)
F
F
3
NaOAc (2), Eosin Y-Na2 (0.02)
0
Ph
Ph
4
NaOAc (2), Ru(bipy)3(BF4)2 (0.005)
NaOAc (2), Ir(ppy)3 (0.005)
NaOAca (2), Ph3P (0.2)
NaOAc (2), Ph3P (0.2)
Ph3P (0.2)
blue
0
OH
OH
I
I
5
400 nm
400 nm
blue
0
3f
79
87
80
85b
0
F
F
F
F
F
F
6
MeO
MeO
7
OH
OH
8
400 nm
<3
52
MeO
MeO
MeO
MeO
9
NaOAc (2), Ph3P (0.2), Ru(bipy)3(BF4)2 (0.005) blue
NaOAc (2), Ph3P (0.2), Ir(ppy)3 (0.0025) 400 nm
3g
3h
F
F
10
91 (91)c
OMe
OMe
a Determined by NMR analysis of the reaction mixture.
b Incomplete conversion; 5% of starting 2a.
c Isolated yield of 3a.
OMe OH
OMe OH
I
F
OMe
F
F
OMe
F
Cl
OH
F
Cl
OH
F
I
3i
85
85
81
Me Me
Me Me
F
F
Me Me
Si
Cl
Cl
Br
Si
O
Si
O
PPh3
Ir(ppy)3
O
Br
OH
F
OH
F
I
I
hν
R
R
R
PPh3
I
3j
F
F
2
5
F
F
F
F
F
F
Me Me
Si
Me
Me
Si
Me
2
5
Me
OH
OH
O
F
O
Si
O
OAc
AcO
I
3k
R
R
R
F
F
F
F
I
F
F
F
F
F
6
7
8
Scheme 2 Proposed mechanism
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

D
L. I. Panferova et al.
Feature
Synthesis
Table 2 (continued)
Substrate
then cooled to room temperature. For the workup, for compounds
1e,g–i,l,m, concentrated hydrochloric acid (500 μL) was added [for 1o,
trifluoroacetic acid (0.36 mL, 4.8 mmol) and KHF2 (187 mg, 2.4 mmol)
were added], and the mixture was stirred for 2 h. Then, EtOAc (5.0
mL), saturated aqueous Na2CO3 (2.0 mL), and sodium thiosulfate pen-
tahydrate (333 mg, 1.33 mmol) were added, and stirring was contin-
ued for 5 min. The organic layer was separated, and the aqueous layer
was extracted with EtOAc (2 × 3 mL). The combined organic layers
were filtered through Na2SO4 and concentrated, and the residue was
purified by column chromatography.
Product
Yield
(%) of 3a
OH
I
OH
3l
83
80
F
F
F
F
F
OH
OH
I
3mb
F
F
F
1-(1,1′-Biphenyl-4-yl)-2,2-difluoro-2-iodoethanol (1e)
Reaction time: 2 h.
Yield: 691 mg (96%); white crystals; mp 106–107 °C.
Rf = 0.33 (hexanes/EtOAc, 6:1).
OH
OH
I
3n
3o
89
79
IR (KBr): 3344, 1486, 1168, 1102, 941, 753, 699 cm–1
.
F
F
F
F
F
F
O
S
O
S
1H NMR (300 MHz, CDCl3): δ = 7.73–7.34 (m, 9 H), 4.84–4.70 (m, 1 H),
2.78 (d, J = 4.0 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 142.5, 140.5, 133.6 (d, J = 2.9 Hz),
129.0, 128.5, 127.8, 127.3, 127.2, 107.9 (dd, J = 318.9, 316.7 Hz), 80.1
(t, J = 23.5 Hz).
19F NMR (282 MHz, CDCl3): δ = –48.7 (dd, J = 181.2, 7.5 Hz, 1 F), –53.8
(dd, J = 180.9, 11.0 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C14H11F2IONa: 382.9715; found:
OH
OH
I
F
F
OH
OH
I
3pb
64
60
F
F
F
F
N
N
Ts
Ts
382.9697.
OH
OH
F
I
2,2-Difluoro-2-iodo-1-(3,4,5-trimethoxyphenyl)ethanol (1g)
Reaction time: 7 h.
3qb
F
F
F
Yield: 598 mg (80%); white crystals; mp 174–175 °C.
Rf = 0.36 (hexanes/EtOAc, 1:1).
a Isolated yield.
b Irradiation reaction time: for 3m, 6 h; for 3p, 5 h; for 3q, 15 h.
IR (KBr): 3419, 1597, 1514, 1460, 1420, 1334, 1235, 1131, 966, 644
cm–1
.
1H NMR (300 MHz, CDCl3): δ = 6.70 (s, 2 H), 4.63 (ddd, J = 11.2, 7.2, 4.2
Hz, 1 H), 3.88 (s, 6 H), 3.87 (s, 3 H), 2.91 (d, J = 4.2 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 153.3, 139.0, 130.0, 107.7 (dd, J =
320.1, 317.2 Hz), 105.4, 80.2 (t, J = 22.9 Hz), 61.0, 56.4.
19F NMR (282 MHz, CDCl3): δ = –48.4 (dd, J = 181.1, 7.2 Hz, 1 F), –53.5
(dd, J = 181.0, 11.2 Hz, 1 F).
HRMS (ESI): m/z [M + H]+ calcd for C11H14F2IO: 374.9909; found:
374.9899; m/z [M + Na]+ calcd for C11H13F2IONa: 396.9724; found:
396.9719.
All reactions were performed under an argon atmosphere. Acetoni-
trile was distilled twice, from P2O5 and CaH2 successively, and stored
over 3 Å molecular sieves. 1,2-Dimethoxyethane was distilled from
LiAlH4. Column chromatography was carried out employing silica gel
(230–400 mesh). Precoated silica gel plates F-254 were used for ana-
lytical TLC; visualization was with UV light and/or acidic aqueous
KMnO4 solution. NMR spectra were recorded in CDCl3 using residual
solvent signal as internal standard on a Bruker AM 300 MHz spec-
trometer. IR spectra were recorded on a Bruker alpha-T spectropho-
tometer. High-resolution mass spectra were measured on a Bruker
micrOTOF II spectrometer using electrospray ionization (ESI) and a
time-of-flight mass analyzer. The measurements were done in a posi-
tive ion mode (interface capillary voltage: 4500 V) or in a negative ion
mode (3200 V), with a mass range from m/z 50 to m/z 3000. For 400
nm light irradiation, a strip of diodes 2x smd 3528 (Arlight RT 2-5000
12V UV400 2X) was used. Starting compounds 1a–d, f, j, k, n, p14c and
1q18a have been described previously.
1-(2,6-Dimethoxyphenyl)-2,2-difluoro-2-iodoethanol (1h)
Reaction time: 3 h.
Yield: 612 mg (89%); white crystals; mp 58–59 °C.
Rf = 0.21 (hexanes/EtOAc, 6:1).
IR (KBr): 3411, 1505, 1463, 1216, 1100, 1039, 985, 708, 545 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.01 (d, J = 2.9 Hz, 1 H), 6.90 (dd, J = 9.0,
2.9 Hz, 1 H), 6.85 (d, J = 9.0 Hz, 1 H), 5.17–5.00 (m, 1 H), 4.16 (d, J = 7.3
Hz, 1 H), 3.81 (s, 3 H), 3.78 (s, 3 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 153.6, 151.8, 123.4, 115.5, 115.4,
112.6, 106.5 (dd, J = 322.0, 318.9 Hz), 76.9 (dd, J = 24.5, 23.0 Hz), 56.4,
55.9.
Starting Iododifluoromethylated Alcohols 1e, g–i, l, m, o; General
Procedure
A mixture of NaI (750 mg, 5 mmol) and LiBr (57 mg, 0.66 mmol) was
dried for 3 min under reduced pressure (0.5 mmHg) using a heat gun.
After the mixture was cooled to room temperature, 1,2-dime-
thoxyethane (2 mL), Me3SiCF2Br25 (609 mg, 3 mmol), and aldehyde (2
mmol) were added, and the mixture was stirred at 80 °C for 2–7 h and
19F NMR (282 MHz, CDCl3): δ = –48.8 (dd, J = 177.0, 7.4 Hz, 1 F), –52.8
(dd, J = 177.0, 13.3 Hz, 1 F).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

E
L. I. Panferova et al.
Feature
Synthesis
HRMS (ESI): m/z [M + Na]+ calcd for C10H11F2IO3Na: 366.9613; found:
Yield: 348 mg (60%); yellow oil.
366.9614.
Rf = 0.20 (hexanes/EtOAc, 6:1).
IR (film): 3423, 1419, 1161, 1097, 983, 924, 708, 600 cm–1
.
1-(2,4-Dichlorophenyl)-2,2-difluoro-2-iodoethanol (1i)
Reaction time: 2 h.
1H NMR (300 MHz, CDCl3): δ = 7.41 (d, J = 5.5 Hz, 1 H), 7.22 (d, J = 3.5
Hz, 1 H), 7.07 (dd, J = 5.1, 3.4 Hz, 1 H), 4.92 (td, J = 8.6, 5.1 Hz, 1 H),
3.10 (d, J = 5.3 Hz, 1 H).
Yield: 600 mg (85%); colorless oil.
13C{1H} NMR (75 MHz, CDCl3): δ = 137.2 (d, J = 3.4 Hz), 127.8, 127.1,
106.2 (t, J = 318.9 Hz), 77.2 (t, J = 25.2 Hz).
19F NMR (282 MHz, CDCl3): δ = –50.3 (dd, J = 182.1, 8.3 Hz, 1 F), –53.9
(dd, J = 182.2, 9.4 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C6H5F2IOSNa: 312.8960; found:
312.8966.
Rf = 0.34 (hexanes/EtOAc, 7:1).
IR (film): 3426, 1591, 1476, 1382, 1165, 1105, 1083, 937, 856, 795,
595 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.62 (d, J = 8.5 Hz, 1 H), 7.42 (d, J = 2.2
Hz, 1 H), 7.31 (dd, J = 8.5, 2.2 Hz, 1 H), 5.32 (ddd, J = 10.6, 7.6, 4.9 Hz, 1
H), 3.66 (d, J = 4.9 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 136.2, 134.9, 131.0 (d, J = 2.1 Hz),
130.8, 129.6, 127.6, 105.9 (dd, J = 322.0, 319.4 Hz), 75.9 (dd, J = 25.0,
22.9 Hz).
[1-(4-Chlorophenyl)-2,2-difluoro-2-iodoethoxy](dimethyl)vinyl-
silane (2a)
19F NMR (282 MHz, CDCl3): δ = –50.4 (br d, J = 182.3 Hz, 1 F), –53.5
(dd, J = 182.3, 10.6 Hz, 1 F).
Chloro(dimethyl)vinylsilane (342 μL, 2.2 mmol) and triethylamine
(344 μL, 2.4 mmol) were added to a solution of alcohol 1a (R = 4-
ClC6H4; 636 mg, 2 mmol) in dichloromethane (2 mL) at room tem-
perature. The mixture was stirred for 1 h. Then, water (5 mL) was
added, and the mixture was extracted with hexane (3 × 10 mL). The
combined extracts were filtered through Na2SO4 and concentrated
under reduced pressure, and the residue was purified by column
chromatography (hexane/EtOAc, 20:1).
Anal. Calcd for C8H5Cl2F2IO: C, 27.22; H, 1.43. Found: C, 27.25; H, 1.27.
2,2-Difluoro-2-iodo-1-(naphthalen-1-yl)ethanol (1l)
Reaction time: 4 h.
Yield: 581 mg (87%); yellow oil.
Rf = 0.21 (hexanes/EtOAc, 20:1).
Yield: 707 mg (88%); colorless oil.
IR (film): 3436, 1167, 1091, 1010, 931, 781 cm–1
.
Rf = 0.60 (hexanes/EtOAc, 20:1).
1H NMR (300 MHz, CDCl3): δ = 8.04 (d, J = 8.2 Hz, 1 H), 8.00–7.87 (m, 3
H), 7.68–7.49 (m, 3 H), 5.61 (ddd, J = 11.2, 6.7, 4.5 Hz, 1 H), 2.93 (d, J =
4.5 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 133.8, 131.4, 130.5 (d, J = 2.3 Hz),
130.3, 129.1, 126.8, 126.7, 126.0, 125.2, 123.2, 108.1 (t, J = 321.0 Hz),
76.3 (t, J = 23.8 Hz).
19F NMR (282 MHz, CDCl3): δ = –46.5 (dd, J = 180.0, 6.7 Hz, 1 F), –51.2
(dd, J = 180.0, 11.2 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C12H9F2IONa: 356.9558; found:
IR (film): 1491, 1408, 1256, 1155, 1129, 1093, 1003, 860, 841, 791
cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.44 (d, J = 8.5 Hz, 2 H), 7.38 (d, J = 8.5
Hz, 2 H), 6.20–6.03 (m, 2 H), 5.90–5.76 (m, 1 H), 4.57 (dd, J = 9.9, 7.4
Hz, 1 H), 0.31 (s, 3 H), 0.24 (s, 3 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 136.1, 135.2, 134.8 (d, J = 3.6 Hz),
134.8, 129.7, 128.5, 108.0 (t, J = 318.1 Hz), 79.9 (t, J = 24.3 Hz), –1.5.
19F NMR (282 MHz, CDCl3): δ = –48.2 (dd, J = 179.7, 7.4 Hz, 1 F), –53.9
(dd, J = 179.7, 9.9 Hz, 1 F).
356.9569.
Anal. Calcd for C12H14ClF2IOSi: C, 35.79; H, 3.50. Found: C, 35.74; H,
3.43.
1-(Anthracen-9-yl)-2,2-difluoro-2-iodoethanol (1m)
Reaction time: 4 h.
Vinylation Reaction; General Procedure
Yield: 691 mg (90%); yellow crystals; mp 119–121 °C.
Rf = 0.28 (hexanes/EtOAc, 6:1).
IR (KBr): 3523, 1167, 1078, 912, 860, 730, 692, 580 cm–1
1H NMR (300 MHz, CDCl3): δ = 8.91 (br, 1 H), 8.56 (s, 1 H), 8.14 (br, 1
H), 8.04 (d, J = 8.3 Hz, 2 H), 7.70–7.42 (m, 4 H), 6.69 (ddd, J = 18.3, 9.0,
4.5 Hz, 1 H), 3.21 (d, J = 4.5 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 142.0 (d, J = 2.4 Hz), 132.3 (d, J = 1.8
Hz), 132.2 (d, J = 1.9 Hz), 131.3, 130.7, 128.6, 127.6, 122.9 (dd, J =
249.9, 246.5 Hz), 118.7, 112.4, 73.7 (dd, J = 31.0, 27.6 Hz).
Chloro(dimethyl)vinylsilane (171 μL, 1.1 mmol) and triethylamine
(172 μL, 1.2 mmol) were added to a solution of an alcohol 1 (1 mmol)
in acetonitrile (1.5 mL) at room temperature, and the mixture was
stirred for 2 h. Then, AcONa (164 mg, 2 mmol), triphenylphosphine
(52.4 mg, 0.2 mmol), and fac-Ir(ppy)3 (1.6 mg, 0.0025 mmol) were
added. The reaction vessel was irradiated with 400 nm LEDs (for 3a–
l,n,o, 2 h; for 3m, 6 h; for 3p, 5 h; for 3q, 15 h); during irradiation the
mixture was cooled with room temperature water. Ammonium fluo-
ride (370 mg, 10 mmol) was added, and the mixture was stirred at
room temperature (for 3a–d, 2 h; for 3e–j,l,m,p,q, 6 h; for 3k,n,o, 15
h). For the workup, the mixture was diluted with water (5 mL) and
extracted with hexane/EtOAc (2:1, 3 × 10 mL). The combined extracts
were filtered through Na2SO4 and concentrated under reduced pres-
sure, and the residue was purified by column chromatography.
.
19F NMR (282 MHz, CDCl3): δ = –46.4 (dd, J = 176.0, 9.0 Hz, 1 F), –47.1
(dd, J = 176.0, 18.3 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C16H11F2IONa: 406.9715; found:
406.9719.
1-(4-Chlorophenyl)-2,2-difluorobut-3-en-1-ol (3a)26
Yield: 173 mg (79%); light-yellow oil.
Rf = 0.36 (hexanes/EtOAc, 2:1).
2,2-Difluoro-2-iodo-1-(thien-2-yl)ethanol (1o)
Reaction time: 4 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–I

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L. I. Panferova et al.
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1H NMR (300 MHz, CDCl3): δ = 7.40–7.29 (m, 4 H), 5.93–5.75 (m, 1 H),
5.58 (d, J = 17.1 Hz, 1 H), 5.48 (d, J = 10.9 Hz, 1 H), 4.88 (dt, J = 10.5, 3.7
Hz, 1 H), 2.69 (d, J = 3.7 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 134.7, 134.2, 129.2 (t, J = 26.3 Hz),
129.1, 128.5, 122.1 (t, J = 9.4 Hz), 119.5 (t, J = 244.2 Hz), 75.4 (t, J =
30.5 Hz).
19F NMR (282 MHz, CDCl3): δ = –108.2 (dt, J = 247.0, 9.6 Hz, 1 F),
–110.0 (dt, J = 247.0, 9.6 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C16H14F2ONa: 283.0913; found:
283.0905; m/z [M + K]+ calcd for C16H14F2OK: 299.0652; found:
299.0644.
2,2-Difluoro-1-(4-methoxyphenyl)but-3-en-1-ol (3f)29
Yield: 169 mg (79%); colorless oil.
19F NMR (282 MHz, CDCl3): δ = –108.3 (dt, J = 246.6, 10.5 Hz, 1 F),
–110.4 (dt, J = 246.6, 10.5 Hz, 1 F).
Rf = 0.31 (hexanes/EtOAc, 4:1).
Methyl 4-(2,2-Difluoro-1-hydroxybut-3-en-1-yl)benzoate (3b)27
Yield: 220 mg (91%); white crystals; mp 53–54 °C.
Rf = 0.23 (hexanes/EtOAc, 4:1).
1H NMR (300 MHz, CDCl3): δ = 7.94 (d, J = 8.2 Hz, 2 H), 7.46 (d, J = 6
Hz, 2 H), 5.94–5.75 (m, 1 H), 5.52 (d, J = 17.4 Hz, 1 H), 5.42 (d, J = 11.0
Hz, 1 H), 4.97–4.90 (m, 1 H), 3.94 (d, J = 4.3 Hz, 1 H), 3.85 (s, 3 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 167.2, 141.7 (d, J = 3.4 Hz), 130.0,
129.2 (t, J = 25.3 Hz), 129.2, 127.8, 121.8 (t, J = 9.2 Hz), 119.4 (t, J =
245.5 Hz), 75.3 (t, J = 29.8 Hz), 52.2.
1H NMR (300 MHz, CDCl3): δ = 7.35 (d, J = 8.6 Hz, 2 H), 6.90 (d, J = 8.6
Hz, 2 H), 5.96–5.78 (m, 1 H), 5.61 (d, J = 16.9 Hz, 1 H), 5.47 (d, J = 11.0
Hz, 1 H), 4.86 (td, J = 9.6, 3.2 Hz, 1 H), 3.82 (s, 3 H), 2.48 (d, J = 3.7 Hz, 1
H).
13C{1H} NMR (75 MHz, CDCl3): δ = 159.8, 129.7 (t, J = 25.8 Hz), 128.9,
128.5, 121.3 (t, J = 9.2 Hz), 119.7 (t, J = 244.2 Hz), 113.6, 75.5 (t, J =
28.7 Hz), 55.2.
19F NMR (188 MHz, CDCl3): δ = –106.7 (dt, J = 245.8, 9.6 Hz, 1 F),
–108.7 (dt, J = 245.8, 9.6 Hz, 1 F).
19F NMR (282 MHz, CDCl3): δ = –107.2 (dt, J = 247.8, 10.5 Hz, 1 F),
–110.3 (dt, J = 247.8, 10.5 Hz, 1 F).
2,2-Difluoro-1-(3,4,5-trimethoxyphenyl)but-3-en-1-ol (3g)
Yield: 238 mg (87%); white crystals; mp 56–57 °C.
Rf = 0.40 (hexanes/EtOAc, 1:1).
4-(2,2-Difluoro-1-hydroxybut-3-en-1-yl)benzonitrile (3c)28
Yield: 153 mg (73%); white crystals; mp 66–67 °C.
Rf = 0.28 (hexanes/EtOAc, 3:1).
1H NMR (300 MHz, CDCl3): δ = 7.67 (d, J = 8.3 Hz, 2 H), 7.56 (d, J = 8.3
Hz, 2 H), 5.93–5.76 (m, 1 H), 5.61–5.55 (m, 1 H), 5.51 (d, J = 11.0 Hz, 1
H), 5.00 (dt, J = 8.8, 3.7 Hz, 1 H), 2.69 (d, J = 3.7 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 141.3 (d, J = 4.2 Hz), 132.0, 128.8 (t,
J = 26.4 Hz), 128.5, 122.5 (t, J = 9.2 Hz), 119.3 (t, J = 246.5 Hz), 118.6,
112.6, 75.2 (t, J = 29.3 Hz).
19F NMR (282 MHz, CDCl3): δ = –107.1 (dt, J = 249.3, 8.8 Hz, 1 F),
–110.6 (dt, J = 249.3, 8.8 Hz, 1 F).
IR (KBr): 3463, 2937, 1594, 1422, 1327, 1234, 1129, 1070, 997 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 6.58 (s, 2 H), 5.94–5.77 (m, 1 H), 5.59
(d, J = 17.4 Hz, 1 H), 5.43 (d, J = 11.0 Hz, 1 H), 4.76 (td, J = 9.7, 3.6 Hz, 1
H), 3.79 (s, 6 H), 3.78 (s, 3 H), 3.28 (d, J = 3.8 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 152.8, 138.0, 132.1, 129.7 (t, J =
25.7 Hz), 121.3 (t, J = 9.3 Hz), 119.6 (t, J = 244.4 Hz), 104.9, 75.8 (t, J =
30.0 Hz), 60.8, 56.1.
19F NMR (282 MHz, CDCl3): δ = –107.9 (dt, J = 247.0, 9.7 Hz, 1 F),
–110.2 (dt, J = 247.0, 9.7 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C13H16F2O4Na: 297.0904; found:
297.0909; m/z [M + K]+ calcd for C13H16F2O4K: 313.0648; found:
313.0648.
2,2-Difluoro-1-phenylbut-3-en-1-ol (3d)26
Yield: 145 mg (79%); colorless oil.
Rf = 0.33 (hexanes/EtOAc, 3:1).
1H NMR (300 MHz, CDCl3): δ = 7.54–7.30 (m, 5 H), 5.97–5.80 (m, 1 H),
5.62 (dt, J = 17.3, 2.4 Hz, 1 H), 5.48 (d, J = 11.5 Hz, 1 H), 4.88 (td, J =
10.1, 3.8 Hz, 1 H), 3.00 (d, J = 3.8 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 136.2, 129.5 (t, J = 25.4 Hz), 128.7,
128.2, 127.7, 121.6 (t, J = 9.2 Hz), 119.7 (t, J = 244.4 Hz), 75.9 (t, J =
28.7 Hz).
19F NMR (282 MHz, CDCl3): δ = –108.4 (dt, J = 246.7, 10.1 Hz, 1 F),
–110.1 (dt, J = 246.7, 10.1 Hz, 1 F).
1-(2,6-Dimethoxyphenyl)-2,2-difluorobut-3-en-1-ol (3h)
Yield: 195 mg (80%); colorless oil.
Rf = 0.23 (hexanes/EtOAc, 5:1).
IR (film): 3449, 2947, 1503, 1421, 1221, 1047, 994, 820, 717 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 6.98 (br, 1 H), 6.86 (d, J = 1.5 Hz, 2 H),
5.97 (dq, J = 17.4, 11.2 Hz, 1 H), 5.63 (d, J = 17.4 Hz, 1 H), 5.46 (d, J =
11.2 Hz, 1 H), 5.18 (td, J = 11.0, 6.7 Hz, 1 H), 3.81 (s, 3 H), 3.78 (s, 3 H),
3.62 (d, J = 6.7 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 153.6, 151.7, 130.4 (t, J = 25.4 Hz),
125.4, 120.7 (t, J = 10.0 Hz), 119.8 (t, J = 245.5 Hz), 115.1, 114.7, 112.4,
71.8 (t, J = 29.9 Hz), 56.3, 55.8.
1-(1,1′-Biphenyl-4-yl)-2,2-difluorobut-3-en-1-ol (3e)
Yield: 236 mg (91%); white crystals; mp 78–79 °C.
Rf = 0.35 (hexanes/EtOAc, 5:1).
19F NMR (282 MHz, CDCl3): δ = –110.3 (m, 2 F).
HRMS (ESI): m/z [M + NH4]+ calcd for C12H18F2O3N: 262.1251; found:
262.1249; m/z [M + Na]+ calcd for C12H14F2O3Na: 267.0802; found:
267.0803; m/z [M + K]+ calcd for C12H14F2O3K: 283.0537; found:
283.0543.
IR (KBr): 3375, 1213, 1194, 1155, 1074, 996, 957, 804, 761, 695 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.66–7.57 (m, 4 H), 7.55–7.32 (m, 5 H),
5.90 (dq, J = 17.4, 11.0 Hz, 1 H), 5.65 (d, J = 17.4 Hz, 1 H), 5.52 (d, J =
11.0 Hz, 1 H), 4.98 (td, J = 9.6, 4.0 Hz, 1 H), 2.50 (d, J = 4.0 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 141.8, 140.8, 135.2, 129.6 (t, J =
25.8 Hz), 128.8, 128.2, 127.7, 127.3, 127.1, 121.7 (t, J = 9.2 Hz), 119.8
(t, J = 244.2 Hz), 75.9 (t, J = 30.0 Hz).
1-(2,4-Dichlorophenyl)-2,2-difluorobut-3-en-1-ol (3i)
Yield: 215 mg (85%); colorless oil.
Rf = 0.27 (hexanes/EtOAc, 5:1).
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IR (film): 3402, 1592, 1476, 1420, 1384, 1192, 1144, 1106, 1075,
1044, 995, 859, 805 cm–1
1-(Anthracen-9-yl)-2,2-difluorobut-3-en-1-ol (3m)
Yield: 227 mg (80%); yellow oil.
.
1H NMR (300 MHz, CDCl3): δ = 7.58 (d, J = 8.5 Hz, 1 H), 7.41 (d, J = 2.1
Hz, 1 H), 7.31 (dd, J = 8.5, 2.1 Hz, 1 H), 5.95 (dq, J = 17.5, 11.4 Hz, 1 H),
5.63 (d, J = 17.5 Hz, 1 H), 5.53 (d, J = 11.1 Hz, 1 H), 5.44 (td, J = 10.0, 4.1
Hz, 1 H), 2.76 (d, J = 4.1 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 135.2, 134.4, 132.7, 130.5 (d, J = 2.2
Hz), 129.4 (t, J = 25.2 Hz), 129.2, 122.1 (t, J = 9.3 Hz), 119.5 (t, J = 246.9
Hz), 71.2 (t, J = 29.8 Hz).
Rf = 0.23 (hexanes/EtOAc, 5:1).
IR (film): 3430, 1420, 1159, 1073, 991, 853, 732 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 9.06 (br, 1 H), 8.49 (s, 1 H), 8.18 (br, 1
H), 8.02 (d, J = 7.3 Hz, 2 H), 7.73–7.40 (m, 4 H), 6.49 (dt, J = 12.6, 3.7
Hz, 1 H), 6.04–5.87 (m, 1 H), 5.75 (d, J = 17.4 Hz, 1 H), 5.43 (d, J = 10.8
Hz, 1 H), 2.87 (d, J = 3.7 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 134.0, 130.93, 130.88 (t, J = 25.7
Hz), 130.1, 129.3 (br), 128.2 (br), 126.4 (br), 125.7 (br), 124.9 (br),
121.0 (t, J = 9.5 Hz), 120.8 (t, J = 246.7 Hz), 73.4 (t, J = 30.5 Hz).
19F NMR (282 MHz, CDCl3): δ = –104.9 (dt, J = 243.5, 12.6 Hz, 1 F),
–106.1 (dt, J = 243.5, 12.6 Hz, 1 F).
HRMS (ESI): m/z [M + H]+ calcd for C18H15F2O: 285.1094; found:
285.1085; m/z [M + NH4]+ calcd for C18H18F2NO: 302.1355; found:
302.1351; m/z [M + Na]+ calcd for C18H14F2ONa: 307.0912; found:
307.0905; m/z [M + K]+ calcd for C18H14F2OK: 323.0651; found:
323.0644.
19F NMR (282 MHz, CDCl3): δ = –110.5 (m, 2 F).
HRMS (ESI): m/z [M + Na]+ calcd for C10H8Cl2F2ONa: 274.9809; found:
274.9812.
1-(2-Bromophenyl)-2,2-difluorobut-3-en-1-ol (3j)29
Yield: 224 mg (85%); colorless oil.
Rf = 0.27 (hexanes/EtOAc, 6:1).
1H NMR (300 MHz, CDCl3): δ = 7.62 (d, J = 7.7 Hz, 1 H), 7.57 (dd, J = 7.7,
1.5 Hz, 1 H), 7.36 (td, J = 7.7, 1.5 Hz, 1 H), 7.21 (td, J = 7.7, 1.5 Hz, 1 H),
5.96 (ddd, J = 22.9, 17.4, 11.5 Hz, 1 H), 5.65–5.58 (m, 1 H), 5.55–5.36
(m, 2 H), 2.80 (d, J = 4.5 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 135.7, 132.8, 130.3, 129.8, 129.7 (t,
J = 25.2 Hz), 127.6, 124.2, 121.9 (t, J = 9.2 Hz), 119.7 (t, J = 245.5 Hz),
74.0 (t, J = 29.8 Hz).
2,2-Difluoro-1-(furan-2-yl)but-3-en-1-ol (3n)30
Yield: 155 mg (89%); yellow oil.
Rf = 0.25 (hexanes/EtOAc, 6:1).
1H NMR (300 MHz, CDCl3): δ = 7.44 (s, 1 H), 6.42 (d, J = 9.6 Hz, 2 H),
6.07–5.90 (m, 1 H), 5.75–5.69 (m, 1 H), 5.54 (d, J = 11.3 Hz, 1 H), 5.06–
4.80 (m, 1 H), 2.97 (d, J = 5.8 Hz, 1 H).
19F NMR (282 MHz, CDCl3): δ = –110.4 (m, 2 F).
2,2-Difluoro-1-mesitylbut-3-en-1-ol (3k)
Yield: 183 mg (81%); light-yellow oil.
Rf = 0.38 (hexanes/EtOAc, 5:1).
13C{1H} NMR (75 MHz, CDCl3): δ = 149.6, 143.0, 129.6 (t, J = 25.0 Hz),
121.8 (t, J = 9.4 Hz), 118.6 (t, J = 244.3 Hz), 110.7, 109.6, 70.3 (t, J =
31.0 Hz).
19F NMR (282 MHz, CDCl3): δ = –109.6 (m, 2 F).
IR (film): 3437, 1167, 1142, 1091, 1010, 980, 931, 781, 590 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 6.87 (s, 2 H), 6.10–5.92 (m, 1 H), 5.72
(d, J = 16.8 Hz, 1 H), 5.49 (d, J = 11.0 Hz, 1 H), 5.36 (td, J = 13.9, 4.4 Hz,
1 H), 2.42 (br, 6 H), 2.31 (s, 3 H).
2,2-Difluoro-1-(thien-2-yl)but-3-en-1-ol (3o)27
Yield: 150 mg (79%); yellow oil.
13C{1H} NMR (75 MHz, CDCl3): δ = 137.8, 131.0 (t, J = 26.1 Hz), 130.3
(br), 129.0 (d, J = 2.4 Hz), 120.8 (dd, J = 244.3, 246.9 Hz), 120.6 (t, J =
10.3 Hz), 73.6 (t, J = 29.8 Hz), 21.4 (br), 20.8.
19F NMR (282 MHz, CDCl3): δ = –105.5 (dt, J = 243.9, 13.9 Hz, 1 F),
–109.3 (dt, J = 243.9, 13.9 Hz, 1 F).
Rf = 0.33 (hexanes/EtOAc, 5:1).
1H NMR (300 MHz, CDCl3): δ = 7.53 (d, J = 8.5 Hz, 1 H), 7.39 (d, J = 2.1
Hz, 1 H), 7.27 (dd, J = 8.5, 2.1 Hz, 1 H), 5.92 (dq, J = 17.3, 11.3 Hz, 1 H),
5.60 (dt, J = 17.3, 2.5 Hz, 1 H), 5.49 (d, J = 11.3 Hz, 1 H), 5.40 (td, J =
10.0, 4.4 Hz, 1 H), 3.20 (d, J = 4.4 Hz, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 138.8, 129.3 (t, J = 25.3 Hz), 127.0,
126.9, 126.4, 122.2 (t, J = 9.2 Hz), 119.1 (t, J = 244.5 Hz), 72.6 (t, J =
32.1 Hz).
HRMS (ESI): m/z [M + Na]+ calcd for C13H16F2ONa: 249.1072; found:
249.1061; calcd for C13H16F2OK: 265.0812; found: 265.0801.
2,2-Difluoro-1-(naphthalen-1-yl)but-3-en-1-ol (3l)
Yield: 194 mg (83%); yellow oil.
19F NMR (282 MHz, CDCl3): δ = –108.8 (dt, J = 247.6, 10.0 Hz, 1 F),
–110.4 (dt, J = 247.6, 10.0 Hz, 1 F).
Rf = 0.25 (hexanes/EtOAc, 5:1).
IR (film): 3419, 1421, 1209, 1168, 1073, 988, 954, 787 cm–1
2,2-Difluoro-1-(1-tosyl-1H-indol-3-yl)but-3-en-1-ol (3p)
Yield: 241 mg (64%); colorless oil.
.
1H NMR (300 MHz, CDCl3): δ = 8.10 (d, J = 8.0 Hz, 1 H), 7.89 (m, 2 H),
7.77 (d, J = 7.3 Hz, 1 H), 7.54 (m, 3 H), 6.04–5.87 (m, 1 H), 5.80 (br t, J =
9.2 Hz, 1 H), 5.68–5.60 (m, 1 H), 5.47 (d, J = 11.0 Hz, 1 H), 2.76 (s, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 133.7, 132.4 (d, J = 4.6 Hz), 131.6,
129.7 (t, J = 25.2 Hz), 129.5, 129.0, 126.5, 126.1, 125.8, 125.2, 123.6,
121.6 (t, J = 9.2 Hz), 120.3 (t, J = 245.5 Hz), 71.7 (t, J = 31.0 Hz).
19F NMR (282 MHz, CDCl3): δ = –106.1 (dt, J = 245.9, 9.2 Hz, 1 F),
–108.8 (dt, J = 245.9, 9.2 Hz, 1 F).
HRMS (ESI): m/z [M + Na]+ calcd for C14H12F2ONa: 257.0754; found:
Rf = 0.17 (hexanes/EtOAc, 4:1).
IR (film): 3525, 1448, 1370, 1175, 1123, 1086, 972, 749, 679, 577, 538
cm–1
.
1H NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 8.0 Hz, 1 H), 7.78 (d, J = 8.2
Hz, 2 H), 7.72–7.64 (m, 2 H), 7.35 (td, J = 9.9, 1.1 Hz, 1 H), 7.30–7.22
(m, 3 H), 6.02–5.85 (m, 1 H), 5.63 (d, J = 17.4 Hz, 1 H), 5.49 (d, J = 11
Hz, 1 H), 5.18 (td, J = 9.2, 4.6 Hz, 1 H), 2.52 (d, J = 4.6 Hz, 1 H), 2.37 (s, 3
H).
13C{1H} NMR (75 MHz, CDCl3): δ = 145.3, 135.2 (d, J = 4.4 Hz), 130.1,
129.5 (t, J = 25.2 Hz), 129.2, 127.0, 125.7, 125.1, 123.6, 122.0 (t, J = 9.2
Hz), 121.0, 118.2 (d, J = 122.8 Hz), 113.7, 70.4 (t, J = 31.9 Hz), 21.7.
257.0748.
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19F NMR (282 MHz, CDCl3): δ = –108.1 (dt, J = 247.9, 9.2 Hz, 1 F),
–109.8 (dt, J = 247.9, 9.2 Hz, 1 F).
HRMS (ESI): m/z [M + H]+ calcd for C19H18F2NO3S: 378.0965; found:
378.0970; m/z [M + NH4]+ calcd for C19H21F2N2O3S: 395.1232; found:
395.1235; m/z [M + Na]+ calcd for C19H17F2NO3SNa: 400.0786; found:
400.0789; m/z [M + K]+ calcd for C19H17F2NO3SK: 416.0529; found:
416.0529.
(3) (a) Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH:
Weinheim, 2004. (b) Babudri, F.; Farinola, G. M.; Naso, F.; Ragni,
R. Chem. Commun. 2007, 1003. (c) Hird, M. Chem. Soc. Rev. 2007,
36, 2070.
(4) (a) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757.
(b) Ma, J.-A.; Cahard, D. J. Fluorine Chem. 2007, 128, 975.
(c) Shimizu, M.; Hiyama, T. Angew. Chem. Int. Ed. 2005, 44, 214.
(d) Dilman, A. D.; Levin, V. V. Mendeleev Commun. 2015, 25, 239.
(e) Uneyama, K. Organofluorine Chemistry; Blackwell: Oxford,
2006. (f) Chemistry of Organic Fluorine Compounds II: A Critical
Review, ACS Monograph Series 187; Hudlicky, M.; Pavlath, A. E.,
Eds.; American Chemical Society: Washington D.C., 1995.
(5) (a) Liu, T.; Shen, Q. Eur. J. Org. Chem. 2012, 6679. (b) Wang, H.;
Vicic, D. A. Synlett 2013, 24, 1887. (c) Chu, L.; Qing, F.-L. Acc.
Chem. Res. 2014, 47, 1513. (d) Tomashenko, O. A.; Grushin, V. V.
Chem. Rev. 2011, 111, 4475.
4,4-Difluoro-1-phenylhex-5-en-3-ol (3q)26
Yield: 127 mg (60%); colorless oil.
Rf = 0.32 (hexanes/EtOAc, 4:1).
1H NMR (300 MHz, CDCl3): δ = 7.46–7.34 (m, 2 H), 7.35–7.23 (m, 3 H),
6.17–5.94 (m, 1 H), 5.85–5.73 (m, 1 H), 5.61 (d, J = 11.3 Hz, 1 H), 3.96–
3.76 (m, 1 H), 3.09–2.94 (m, 1 H), 2.86–2.72 (m, 1 H), 2.43 (br, 1 H),
2.10–1.95 (m, 1 H), 1.95–1.78 (m, 1 H).
13C{1H} NMR (75 MHz, CDCl3): δ = 141.3, 129.8 (t, J = 26.0 Hz), 128.6,
126.2, 121.4 (t, J = 9.4 Hz), 120.4 (t, J = 242.8 Hz), 72.7 (dd, J = 30.2,
28.4 Hz), 31.8 (t, J = 2.5 Hz), 31.6.
19F NMR (282 MHz, CDCl3): δ = –109.2 (dt, J = 249.0, 10.6 Hz, 1 F),
–112.8 (dt, J = 249.0, 10.6 Hz, 1 F).
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Funding Information
(9) Andrieux, C. P.; Gelis, L.; Medebielle, M.; Pinson, J.; Saveant, J. M.
J. Am. Chem. Soc. 1990, 112, 3509.
This work was supported by the Russian Science Foundation (project
17-13-01041).
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Acknowledgment
We are grateful to Mr. R. Larkovich for experimental assistance.
Supporting Information
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Shabat, D.; Baran, P. S. Angew. Chem. Int. Ed. 2013, 52, 3949.
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Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590855.
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