2,2-Difluorovinyl Pinacolborane – A New Versatile Reagent for the Suzuki–Miyaura Reaction

Article abstract of DOI:10.1002/ejoc.201901118

A novel fluorinated reagent for the synthesis of gem-difluorostyrenes and their heterocyclic analogues – 2,2-difluorovinyl pinacolborane (CF₂=CHBPin) was developed. In particular, borylation of 1,1-difluoroethylene with isopropoxy pinacolborane

Full text of DOI:10.1002/ejoc.201901118

DOI: 10.1002/ejoc.201901118
Communication
Fluorinated Boronates
2,2-Difluorovinyl Pinacolborane – A New Versatile Reagent for
the Suzuki–Miyaura Reaction
Oleksandr P. Blahun,[a,b] Mykhailo O. Redka,[a,b] Zoia V. Voitenko,[b] Andrii I. Kysil,[b]
Alexey V. Dobrydnev,[a,b] and Oleksandr O. Grygorenko*[a,b]
Abstract: A novel fluorinated reagent for the synthesis of +4 °C for months. The Pd(dppf)Cl2-catalyzed cross-coupling of
gem-difluorostyrenes and their heterocyclic analogues – 2,2-di- this reagent with (het)aryl and vinyl bromides works well with
fluorovinyl pinacolborane (CF2=CHBPin) was developed. In broad spectrum of substrates and is characterized by good
particular, borylation of 1,1-difluoroethylene with isopropoxy yields, functional group tolerance, sufficient reproducibility, as
pinacolborane afforded the title compound on a multigram well as scalability.
scale as stable, easy-to-handle liquid which can be stored at
Introduction
yldifluoroacetate,[16] respectively, can be also considered as
powerful methods to access gem-difluorostyrenes.
Introducing the fluorine-containing functionalities into organic
molecules typically endows the organic molecules with unique
chemical, physical, as well as biological properties.[1] In particu-
lar, 1,1-difluoroalkenes were used as building blocks in drug
discovery since they have been considered as lipophilic bio-
isosteres for carbonyl compounds[2] and possessed cytotoxic[3]
and enzyme inhibitory activities.[4] Apart from that, gem-difluor-
inated alkenes (in particular, gem-difluorostyrenes) are of great
value for organic synthesis since they can be straightforward
precursors of other fluorinated compounds (e.g. monofluorin-
ated alkenes,[5] di- and trifluoromethyl-substituted com-
pounds,[6] fluorinated heterocycles,[7] fluorinated vinylsilanes,[8]
as well as polymers).[9] Hence efficient methods for the prepara-
tion of gem-difluorostyrenes are of high request.
At the same time, the cross-coupling reactions are attracting
increasing interest as the methods for synthesis of gem-di-
fluorostyrenes. Two alternative retrosynthetic disconnections
can be proposed for that purpose, leading to a nucleophilic
There are several approaches for introduction of the 2,2-di-
fluorovinyl moiety into an aromatic core. The most common
methods rely on the use of aldehydes as starting substrates.
Among such methods are Wittig-type reactions with either di-
fluoromethyltriphenylphosphonium bromide[10] or (triphenyl-
phosphonio)difluoroacetate.[11] The alternative techniques are
based on Ph3P-mediated reactions with methyl 2,2-difluoro-2-
(fluorosulfonyl)acetate (MDFA),[12] sodium chlorodifluoroacet-
ate,[13] or (chlorodifluoromethyl)trimethylsilane.[14] The modi-
fied Julia and Julia–Kocienski olefinations with the use of
bromodifluoromethylphenyl sulfone[15] and 2-pyridinyl sulfon-
[a] Enamine Ltd.,
Chervonotkatska Street 78, Kyiv 02094, Ukraine
https://www.enamine.net
[b] Taras Shevchenko National University of Kyiv,
Volodymyrska Street 60, Kyiv 01601, Ukraine
E-mail: gregor@univ.kiev.ua
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201901118.
Figure 1. gem-Difluorovinylation of (hetero)aromatic substrates via palladium-
catalyzed cross-couplings.
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gem-difluorovinylating reagent and an electrophilic (hetero)aro-
matic substrate (Figure 1a[17] and Figure 1b[18]) and vice versa
(Figure 1c).[19] Although the former approach is characterized
by wide variety of accessible (het)aryl halides, it suffers either
from modest functional group tolerance (in the case of the
organozinc reagent) or toxicity of organotin derivatives; more-
over, notorious separation of the corresponding by-products
might be an issue. On the contrary, the use of the electrophilic
agents such as difluorovinyl tosylate is experimentally more
convenient but limited by availability of the appropriate bor-
onic derivatives.
These limitations prompted our current work on develop-
ment of a novel gem-difluorovinylating reagent for the Suzuki–
Miyaura reaction. Considering the huge number of commer-
cially and synthetically available aryl- and hetaryl bromides as
electrophilic substrates for the cross-coupling reactions, we en-
visioned an organoboron reagent bearing appropriately func-
tionalized olefinic moiety for that purpose. In this view, we have
aimed at the preparation of a simple fluorinated organoboronic
derivative 1, as well as its study in the palladium-catalyzed
cross-couplings.
Table 1. Optimization of the Suzuki–Miyaura reaction conditions.[a]
Entry
Catalyst
Base
Solvent
T, °C
Yield,%[b]
1
2
3
4
5
6
7
8
9
10
Pd(OAc)2
Pd(OAc)2+XantPhos K2CO3
Pd(PPh3)4 K2CO3
Pd(dppf)Cl2·CH2Cl2 K2CO3
Pd(dppf)Cl2·CH2Cl2 K2CO3
Pd(dppf)Cl2·CH2Cl2 K3PO4
Pd(dppf)Cl2·CH2Cl2 Cs2CO3
Pd(dppf)Cl2·CH2Cl2 Na2CO3
Pd(dppf)Cl2·CH2Cl2 K2CO3
Pd(dppf)Cl2·CH2Cl2 K2CO3
K2CO3
THF/H2O (2:1)
THF/H2O (2:1)
THF/H2O (2:1)
THF/H2O (2:1)
50
50
50
50
0
21
42
52
20
58
75
73
95
100
PhMe/H2O (1:1) 60
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
60
60
60
90
60
[a] Reaction conditions: 4a (1 equiv.), CF2=CHBPin (1.1 equiv.), catalyst
(2.5 mol-%), base (3 equiv.), 14 h. [b] Yield of 5a by 1H NMR.
1,4-dioxane turned out to be an optimal solvent (Table 1, en-
tries 6–10). The use of other bases (K3PO4, Cs2CO3, and Na2CO3
instead of K2CO3) did not improve the yield of the product
(Table 1, entries 6–8, respectively).
Optimization of the reaction temperature showed that slight
heating was necessary, and 60 °C turned to give the best results
(Table 1, entries 5–8 and 10). If the temperature was increased
to 90 °C, the target reaction was accompanied with reductive
debromination (Table 1, entry 9).
Based on the optimized reaction conditions found, we have
studied the substrate scope (Scheme 2). It was found that both
aromatic and heteroaromatic aryl bromides were successfully
gem-difluorovinylated with CF2=CHBPin. Moreover, the reaction
tolerated many common functional groups, such as aldehyde
(5b), ether (5d,f), ester (5e,j,k), as well as amino (5g) and gave
the corresponding gem-difluorostyrenes in moderate to excel-
lent yields. Besides, the method did not work with aryl chlorides
(no coupling product was observed with methyl 4-chlorobenzo-
ate). As it might be expected, the best results were obtained
with electron-poor substrates, whereas with electron-rich p-
methoxy and p-amino derivatives, the yields were moderate.
Moreover, the reaction was not particularly sensitive to steric
hindrance and tolerated methoxycarbonyl group (5e) or fused
[d]thiazole ring (5i) in the ortho position to the halogen. As
it was mentioned above, the reaction was also applicable to
heteroaryl bromides, so that the corresponding pyridine (5f)
and pyrimidine (5h) derivatives bearing the gem-difluorovinyl
substituent were isolated in good yields.
Results and Discussion
The target compound 1 was synthesized in a straightforward
manner using an one-step procedure. Namely, 1,1-difluoroeth-
ylene (2) was treated with sBuLi at –100 °C and then – with
isopropoxy pinacolborane (3). After the standard work-up pro-
cedure and distillation of the crude product, 2,2-difluorovinyl
pinacolborane (1) was isolated in 42 % yield (Scheme 1). Nota-
bly, the reaction could be performed on up to 63 g scale of the
product without significant changes in its outcome.
Scheme 1. Synthesis of 2-(2,2-difluorovinyl)-4,4,5,5-tetramethyl-1,3,2-dioxa-
borolane (1).
With boronic ester 1 in hands, we then attempted to find
the most favorable reaction conditions for the gem-difluoro-
olefination of (het)aryl bromides. We started our investigation
with screening of palladium catalysts under model reaction
conditions: 4-bromo-1,1′-biphenyl (4a) as a substrate and K2CO3
as a base, THF/H2O (2:1) as a solvent, gentle heating (50 °C),
14 h (Table 1, entries 1–4). The best results were obtained when
Pd(dppf)Cl2·CH2Cl2 was used as the catalyst (52 % yield, Table 1,
entry 4); it was used for further optimization.
It should be noted that no cross-coupling of the target gem-
difluorostyrenes 5 with the organoboron reagent (mentioned
in the previous publication[5b]) was observed.
Next, the effect of the solvent and the base was studied.
Finally, the optimized reaction conditions were applied to
With the use of a two-phase solvent system (toluene/H2O), the vinyl bromide 4l, and the corresponding gem-difluorodiene 5l
conversion decreased dramatically and the output of the de- was isolated. However, it turned out to have limited stability
sired styrene was less than 20 % (Table 1, entry 5). Meanwhile, and decomposed at r.t. within a day.
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and 376.5 MHz, respectively). 13C and 11B NMR spectra were re-
corded on a Bruker 170 Avance 500 spectrometer (at 125.9 MHz
and 160.4 MHz, respectively). Chemical shifts are reported in ppm
downfield from TMS as an internal standard. Elemental analyses
were performed at the Laboratory of Organic Analysis, Department
of Chemistry, Taras Shevchenko National University of Kyiv. Mass
spectra were recorded on an Agilent 1100 LCMSD SL instrument
(chemical ionization (APCI)) and Agilent 5890 Series II 5972 GC–MS
instrument (electron impact ionization (EI)).
2-(2,2-Difluorovinyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(1): A solution of CH2=CF2 (32.0 g, 0.500 mol) in a mixture of THF
(800 mL) and Et2O (200 mL) was cooled to –100 °C. Then sBuLi
(1.2 L, 1.4
M in cyclohexane, 0.900 mol) was added upon stirring
over 20 min while maintaining a temperature of –100 °C. The reac-
tion mixture was warmed to –90 °C and stirred at this temperature
for another 20 min. Then a solution of (iPrO)BPin (149 g, 0.800 mol)
in Et2O (320 mL) was added upon stirring at –100 °C over 20 min.
The reaction mixture was warmed to –90 °C and left at this temper-
ature for 30 min. Then it was warmed to –40 °C and quenched with
a solution of NH4Cl (64.2 g, 1.20 mol) in H2O (200 mL). The organic
layer was separated, washed with brine (2 × 200 mL), dried (Na2SO4)
and the solvents evaporated in vacuo at 30 °C. The residue was
distilled in vacuo giving the title compound 1 as colorless liquid.
Yield (63.8 g, 42 %); b.p. 79 °C (100 mBar); 1H NMR (400 MHz, CDCl3):
δ = 3.96 (dd, J = 35.6, 6.3 Hz, 1H), 1.29 (s, 12H) ppm; 13C NMR
(126 MHz, CDCl3): δ = 163.1 (dd, J = 303.2, 300.9 Hz), 83.6, 63.9,
24.7 ppm; 19F{1H} NMR (376 MHz, CDCl3): δ = –61.2 (s, 1F), –66.0 (s,
1F) ppm; 11B NMR (160 MHz, CDCl3): δ = 29.72 ppm; MS (EI): m/z =
190 [M]+; elemental analysis calcd. (%) for C8H13BF2O2: C 50.57,
H 6.90; found C 50.89, H 6.59.
General Procedure for the Preparation of ꢀ,ꢀ-difluorostyrenes
5a–k and ꢀ,ꢀ-difluorodiene 5l: The corresponding bromide 4e–l
(2.5 mmol) was dissolved in 1,4-dioxane (15 mL) under argon at-
mosphere. Then CF2=CHBPin (0.520 g, 2.75 mmol), K2CO3 (1.04 g,
7.5 mmol), and Pd(dppf)Cl2·CH2Cl2 (51 mg, 62.5 μmol) were added
sequentially. The reaction mixture was stirred at 60 °C for 14 h, then
cooled to r.t., evaporated in vacuo, and the residue was subjected
to HPLC (5a–k) or purified by column chromatography (hexane/
EtOAc (10:1) as eluent, 5l).
Scheme 2. Substrate scope for the Suzuki–Miyaura reaction with 1.
Conclusions
A new reagent for the Suzuki–Miyaura reaction, namely, 2,2-
difluorovinyl pinacolborane, was developed via one-step multi-
gram lithiation–borylation of 1,1-difluoroethylene. The title
compound is easy-to-handle high-boiling liquid with sufficient
stability (no degradation was observed upon storage at +4 °C
for several months). The Pd(dppf)Cl2-catalyzed reaction of this
reagent with (het)aryl and vinyl bromides proved to be a versa-
tile synthetic method providing a wide range of gem-difluoro-
styrenes, their heterocyclic analogues, as well as gem-difluorodi-
ene. The utility of this method was confirmed by broad sub-
strate compatibility, functional group tolerance, and good re-
producibility.
4-(2,2-Difluorovinyl)-1,1′-biphenyl (5a): from 4a (2.00 g,
8.58 mmol), white solid (1.75 g, 95 %), m.p. 85–86 °C; 1H NMR
(400 MHz, CDCl3): δ = 7.65–7.56 (m, 4H), 7.50–7.40 (m, 4H), 7.40–
7.33 (m, 1H), 5.34 (dd, J = 26.3, 3.7 Hz, 1H) ppm; 13C NMR (126 MHz,
CDCl3): δ = 156.5 (dd, J = 298.4, 288.5 Hz), 140.6, 140.0, 129.5 (t, J =
6.4 Hz), 129.0, 128.1 (dd, J = 6.4, 3.5 Hz), 127.6, 127.5, 127.1, 82.1
(dd, J = 29.2, 13.6 Hz) ppm; 19F NMR (376 MHz, CDCl3): δ = –82.4
(d, J = 30.8 Hz, 1F), –84.3 (d, J = 30.8 Hz, 1F) ppm; MS (EI): m/z =
216 [M]+; elemental analysis calcd. (%) for C14H10F2: C 77.77, H 4.66;
found C 78.15, H 4.87.
4-(2,2-Difluorovinyl)benzaldehyde (5b): from 4b (0.500 g,
2.70 mmol), yellowish liquid (408 mg, 90 %); 1H NMR (400 MHz,
CDCl3): δ = 9.98 (s, 1H), 7.84 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.1 Hz,
2H), 5.36 (dd, J = 25.8, 3.5 Hz, 1H) ppm; 13C NMR (126 MHz, CDCl3):
δ = 191.6, 157.1 (dd, J = 301.4, 291.9 Hz), 137.0 (t, J = 6.8 Hz), 135.0,
130.2, 128.2 (dd, J = 6.8, 3.7 Hz), 82.3 (dd, J = 30.2, 12.9 Hz) ppm;
19F NMR (376 MHz, CDCl3): δ = –78.6 (d, J = 21.0 Hz, 1F), –80.4 (d,
J = 21.0 Hz, 1F) ppm; MS (APCI): m/z = 169 [M+H]+; elemental analy-
sis calcd. (%) for C9H6F2O: C 64.29, H 3.60; found C 64.32, H 3.83.
Experimental Section
The solvents were purified according to the standard procedures.[20]
All the starting materials were obtained from Enamine Ltd. and
UORSY. Melting points were measured on MPA100 OptiMelt auto-
mated melting point system. Analytical TLC was performed using
Polychrom SI F254 plates. HPLC chromatography was performed on
an Agilent 1200 instrument with a C18-modified silica gel column
1-(2,2-Difluorovinyl)-4-nitrobenzene (5c): from 4c (0.500 g,
2.48 mmol), crystalline brownish solid (408 mg, 89 %), m.p. 34–
36 °C; 1H NMR (400 MHz, [D6]DMSO): δ = 8.24 (d, J = 8.8 Hz, 2H),
1
and gradient MeOH – H2O as eluent. H and 19F NMR spectra were
recorded on a Varian Unity Plus 400 spectrometer (at 400.4 MHz
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7.63 (d, J = 8.8 Hz, 2H), 6.06 (dd, J = 27.6, 3.9 Hz, 1H) ppm; 13C NMR
(126 MHz, [D6]DMSO): δ = 156.2 (dd, J = 301.1, 289.8 Hz), 146.0,
137.3 (dd, J = 8.1, 6.7 Hz), 128.6 (dd, J = 6.7, 3.6 Hz), 124.0, 81.7 (dd,
J = 30.9, 10.2 Hz) ppm; 19F NMR (376 MHz, [D6]DMSO): δ = –78.7 (d,
J = 21.7 Hz, 1F), –80.4 (d, J = 21.7 Hz, 1F) ppm; MS (EI): m/z = 185
[M]+; elemental analysis calcd. (%) for C8H5F2NO2: C 51.90, H 2.72,
N 7.57; found C 51.92, H 3.02, N 7.20.
151.1 (d, J = 5.0 Hz), 134.1, 126.0 (t, J = 7.0 Hz), 125.9, 124.3 (dd,
J = 11.0, 2.0 Hz), 120.5, 78.5 (dd, J = 31.8, 12.3 Hz) ppm; 19F NMR
(376 MHz, CDCl3): δ = –81.0 (d, J = 25.1 Hz, 1F), –81.6 (d, J = 24.9 Hz,
1F) ppm; MS (APCI): m/z = 198 [M+H]+; elemental analysis calcd.
(%) for C9H5F2NS: C 54.82, H 2.56, N 7.10, S 16.26; found C 54.94,
H 2.32, N 7.03, S 16.44.
Methyl 3-(2,2-difluorovinyl)benzoate (5j): from 4j (0.500 g,
2.33 mmol), yellowish liquid (248 mg, 54 %); 1H NMR (400 MHz,
CDCl3): δ = 7.98 (s, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 7.8 Hz,
1H), 7.41 (t, J = 7.8 Hz, 1H), 5.32 (dd, J = 25.9, 3.6 Hz, 1H), 3.92 (s,
3H) ppm; 13C NMR (126 MHz, CDCl3): δ = 166.9, 156.7 (dd, J = 299.0,
289.3 Hz), 131.9 (dd, J = 6.6, 3.3 Hz), 130.9 (t, J = 6.6 Hz), 130.8,
128.91, 128.87 (t, J = 3.9 Hz), 128.2, 81.8 (dd, J = 29.9, 13.5 Hz),
52.3 ppm; 19F NMR (376 MHz, CDCl3): δ = –81.6 (d, J = 28.7 Hz, 1F),
–83.4 (d, J = 28.7 Hz, 1F) ppm; MS (EI): m/z = 198 [M]+; elemental
analysis calcd. (%) for C10H8F2O2: C 60.61, H 4.07; found C 60.96, H
4.28.
1-(2,2-Difluorovinyl)-4-methoxybenzene (5d): from 4d (0.500 g,
2.67 mmol), brownish liquid (227 mg, 50 %); 1H NMR (400 MHz,
[D6]DMSO): δ = 7.30 (d, J = 8.5 Hz, 2H), 6.95 (d, J = 8.5 Hz, 2H), 5.70
(dd, J = 28.3, 4.3 Hz, 1H), 3.75 (s, 3H) ppm; 13C NMR (126 MHz,
[D6]DMSO): δ = 158.3, 154.8 (dd, J = 295.6, 284.6 Hz), 128.8 (dd, J =
6.1, 3.5 Hz), 121.8 (t, J = 6.1 Hz), 114.2, 81.6 (dd, J = 28.7, 12.0 Hz),
55.0 ppm; 19F NMR (376 MHz, [D6]DMSO): δ = –85.9 (d, J = 39.7 Hz,
1F), –87.7 (d, J = 39.8 Hz, 1F) ppm; MS (EI): m/z = 170 [M]+; elemen-
tal analysis calcd. (%) for C9H8F2O: C 63.53, H 4.74; found C 63.14,
H 4,93.
Ethyl 4-(2,2-difluorovinyl)benzoate (5k): from 4k (0.500 g,
2.18 mmol), brownish liquid (347 mg, 75 %); 1H NMR (400 MHz,
CDCl3): δ = 8.00 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 5.33 (dd,
J = 25.9, 3.6 Hz, 1H), 4.37 (q, J = 7.1 Hz, 2H), 1.39 (t, J = 7.1 Hz, 3H)
ppm; 13C NMR (126 MHz, CDCl3): δ = 166.3, 156.9 (dd, J = 300.5,
290.6 Hz), 135.2 (t, J = 6.8 Hz), 130.0, 129.1 (d, J = 2.2 Hz), 127.5
Methyl 2-(2,2-difluorovinyl)benzoate (5e): from 4e (0.500 g,
2.33 mmol), yellowish liquid (364 mg, 79 %); 1H NMR (400 MHz,
CDCl3): δ = 7.96 (d, J = 7.9 Hz, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.50 (t,
J = 7.7 Hz, 1H), 7.31 (t, J = 7.7 Hz, 1H), 6.28 (dd, J = 25.9, 4.2 Hz,
1H), 3.90 (s, 3H) ppm; 13C NMR (126 MHz, CDCl3): δ = 167.5, 156.6
(dd, J = 298.1, 287.4 Hz), 132.3, 131.6 (dd, J = 8.6, 5.1 Hz), 131.0,
129.6 (d, J = 8.6 Hz), 128.7 (d, J = 5.1 Hz), 127.1, 80.4 (dd, J = 32.8,
10.9 Hz), 52.3 ppm; 19F NMR (376 MHz, CDCl3): δ = –83.0 (d, J =
28.6 Hz, 1F), –84.8 (d, J = 28.6 Hz, 1F) ppm; MS (EI): m/z = 198 [M]+;
elemental analysis calcd. (%) for C10H8F2O2: C 60.61, H 4.07; found
C 60.77, H 3.97.
(dd, J = 6.8, 3.5 Hz), 82.2 (dd, J = 29.8, 13.1 Hz), 61.1, 14.5 ppm; 19
F
NMR (376 MHz, CDCl3): δ = –79.8 (d, J = 24.3 Hz, 1F), –81.8 (d, J =
24.3 Hz, 1F) ppm; MS (EI): m/z = 212 [M]+; elemental analysis calcd.
(%) for C11H10F2O2: C 62.26, H 4.75; found C 62.32, H 4.77.
(E)-tert-Butyl 4-(4,4-difluorobuta-1,3-dien-1-yl)piperidine-1-
carboxylate (5l): from 4l (0.500 g, 1.70 mmol), brownish liquid
2-(2,2-Difluorovinyl)-6-methoxypyridine (5f): from 4f (0.500 g,
2.66 mmol), yellowish liquid (368 mg, 81 %); 1H NMR (400 MHz,
CDCl3): δ = 7.52 (t, J = 7.6 Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H), 6.58 (d,
J = 8.3 Hz, 1H), 5.40 (dd, J = 25.2, 3.9 Hz, 1H), 3.92 (s, 3H) ppm; 13C
NMR (126 MHz, CDCl3): δ = 163.7, 157.7 (dd, J = 302.6, 289.8 Hz),
148.4 (dd, J = 10.5, 7.6 Hz), 138.9, 115.3 (dd, J = 8.3, 4.1 Hz), 108.8,
83.8 (dd, J = 29.1, 10.9 Hz), 53.4 ppm; 19F NMR (376 MHz, CDCl3):
δ = –77.7 (d, J = 18.5 Hz, 1F), –81.5 (d, J = 18.5 Hz, 1F) ppm; MS
(EI): m/z = 171 [M]+; elemental analysis calcd. (%) for C8H7F2NO:
C 56.14, H 4.12, N 8.18; found C 55.9, H 3.96, N 8.18.
1
(210 mg, 45 %); H NMR (400 MHz, CDCl3): δ = 5.86 (t, J = 10.8 Hz,
1H), 5.28 (t, J = 10.8 Hz, 1H), 5.16 (ddt, J = 23.6, 11.5, 1.6 Hz, 1H),
4.09 (d, J = 13.2 Hz, 2H), 2.77 (td, J = 13.2, 2.8 Hz, 2H), 2.37 (q, J =
10.6 Hz, 1H), 1.63–1.52 (m, 2H), 1.47 (s, 9H), 1.34–1.27 (m, 2H) ppm;
13C NMR (126 MHz, CDCl3): δ = 157.0 (dd, J = 297.4, 291.1 Hz), 154.9,
135.1 (dd, J = 11.2, 3.3 Hz), 116.4 (d, J = 4.0 Hz), 79.7, 78.0 (dd, J =
26.7, 16.6 Hz), 43.6 (2C), 35.1, 31.7, 28.4 ppm; 19F NMR (376 MHz,
CDCl3): δ = –85.81 (t, J = 25.3 Hz, 1F), –86.76 (d, J = 26.9 Hz, 1F)
ppm; MS (APCI): m/z = 218 [M – C4H8+H]+. The compound had
limited storage stability, so that no satisfactory elemental analysis
could be obtained.
4-(2,2-Difluorovinyl)aniline (5g): from 4g (0.500 g, 2.91 mmol),
yellowish oil (162 mg, 36 %); 1H NMR (400 MHz, [D6]DMSO): δ =
7.02 (d, J = 8.3 Hz, 2H), 6.55 (d, J = 8.3 Hz, 2H), 5.50 (dd, J = 28.7,
4.5 Hz, 1H), 5.23 (s, 2H) ppm; 13C NMR (126 MHz, CDCl3): δ = 155.7
(dd, J = 295.9, 285.6 Hz), 145.5, 128.8 (dd, J = 6.2, 3.5 Hz), 120.5 (t,
J = 6.2 Hz), 115.4, 81.9 (dd, J = 28.9, 14.2 Hz) ppm; 19F NMR
(376 MHz, CDCl3): δ = –85.8 (d, J = 39.4 Hz, 1F), –88.1 (d, J = 39.4 Hz,
1F) ppm; MS (EI): m/z = 155 [M]+; elemental analysis calcd. (%) for
C8H7F2N: C 61.93, H 4.55, N 9.03; found C 62.27, H 4.80, N 9.28.
Acknowledgments
The work was funded by Enamine Ldt. Additional funding from
Ministry of Education and Science of Ukraine, Grants No.
19BF037–03 (A. V. D. and O. O. G.) and 19BF037–06 (Z. V. V. and
A. I. K.) is also acknowledged. The authors thank Prof. Andrey A.
Tolmachev for his encouragement and support, and Ms. Yuliya
Kuchkovska for her help with manuscript preparation.
5-(2,2-Difluorovinyl)-2-methylpyrimidine (5h): from 4h (0.500 g,
2.89 mmol), yellowish liquid (315 mg, 70 %); 1H NMR (400 MHz,
CDCl3): δ = 8.58 (s, 2H), 5.20 (dd, J = 26.6, 2.4 Hz, 1H), 2.70 (s, 3H)
ppm; 13C NMR (126 MHz, CDCl3): δ = 166.5 (t, J = 2.4 Hz), 157.0 (dd,
J = 299.1, 292.1 Hz), 155.2 (dd, J = 6.8, 3.5 Hz), 122.0 (t, J = 6.8 Hz),
76.6 (dd, J = 31.8, 15.7 Hz), 25.8 ppm; 19F NMR (376 MHz, CDCl3):
δ = –78.9 (d, J = 23.8 Hz, 1F), –80.4 (d, J = 23.8 Hz, 1F) ppm; MS
(EI): m/z = 156 [M]+; elemental analysis calcd. (%) for C7H6F2N2:
C 53.85, H 3.87, N 17.94; found C 53.53, H 4.03, N 18.07.
Keywords: Organofluorine compounds · Organoboron
compounds · C–C coupling · Homogeneous catalysis
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Received: July 31, 2019
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