Hafiza Tayyaba Shahzadi1, Saman Fatima1, Naseem Akhter1,2, Meshari Alazmi3, Alshammari Nawaf4, Kamaleldin B Said5, Amer AlGhadhban6, Abdel Moneim E Sulieman4, Rahman Shah Zaib Saleem1, Ghayoor Abbas Chotana1. 1. Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore 54792, Pakistan. 2. Department of Chemistry, Government Sadiq College Women University, Bahawalpur 63100, Pakistan. 3. College of Computer Science and Engineering, University of Ha'il, P.O. Box 2440, Ha'il 81451, Saudi Arabia. 4. College of Science, University of Ha'il, P.O. Box 2440, Ha'il 81451, Saudi Arabia. 5. College of Medicine, University of Ha'il, Ha'il 81451, Saudi Arabia. 6. College of Engineering, University of Ha'il, Ha'il 81451, Saudi Arabia.
Abstract
Iridium-catalyzed C-H borylation of CF3-substituted pyridines is described in this paper. The boronic ester group can be installed on the α, β, or γ position of pyridine by an appropriate substitution pattern. Sterically governed regioselectivity provides convenient access to a variety of CF3-substituted pyridylboronic esters. These catalytic C-H borylation reactions were carried out neatly without the use of any solvent. Several functional groups, such as halo, ester, alkoxy, amino, etc., are compatible with this methodology. These pyridylboronic esters are amenable to column chromatography and the products were isolated in good to excellent yields. α-Borylated pyridines, although isolated in good yields, do not have a long shelf life. The boronic ester derivatives of these CF3-substituted pyridines can serve as useful precursors in the synthesis regime.
Iridium-catalyzed C-H borylation of CF3-substituted pyridines is described in this paper. The boronic ester group can be installed on the α, β, or γ position of pyridine by an appropriate substitution pattern. Sterically governed regioselectivity provides convenient access to a variety of CF3-substituted pyridylboronic esters. These catalytic C-H borylation reactions were carried out neatly without the use of any solvent. Several functional groups, such as halo, ester, alkoxy, amino, etc., are compatible with this methodology. These pyridylboronic esters are amenable to column chromatography and the products were isolated in good to excellent yields. α-Borylated pyridines, although isolated in good yields, do not have a long shelf life. The boronic ester derivatives of these CF3-substituted pyridines can serve as useful precursors in the synthesis regime.
Pyridine and its derivatives
are among the most prevalent heteroaromatics
in organic chemistry. In addition to the dominant structural unit
in pharmaceuticals and agrochemicals, they are also used as biological
probes, drug candidates, clinically used drugs, functionalized materials,
and ligands (Figure ).[1−4]
Figure 1
Representation
of biologically active pyridines.
Representation
of biologically active pyridines.Installation of various functional groups on the pyridine core
can have a huge impact on its properties. Introduction of fluorinated
groups is highly desirable, as it enhances the stability and functional
group compatibility.[5,6] Among other fluorine-containing
groups, the trifluoromethyl (CF3) group exhibits enhanced
binding selectivity, lipophilicity, and chemical and metabolic stability.[7,8] Hence, development of new methodologies for the incorporation of
trifluoromethyl and its related groups on the pyridine is of great
synthesis value. Several protocols are available for the trifluoromethylation
of pyridine.[9,10] In addition, preparation of boronic
ester derivatives of trifluoromethylpyridines can be very useful since
the arylboronate esters are highly versatile intermediates that can
be readily converted into a wide range of other functional groups.[11−13]Pyridylboronic esters are generally synthesized by metal-halogen
exchange or by Miyaura borylation.[14] Iridium-catalyzed
aromatic C–H borylation was introduced by the groups of Smith–Maleczka,
and the method proposed by Hartwig–Miyaura is a highly atom-economical
green chemistry approach to prepare (hetero)arylboronic esters.[15] Marder has investigated the application of this
iridium-catalyzed borylation protocol to various substituted pyridines
and quinolines.[16] Recently, Steel and coworkers
utilized iridium-catalyzed borylation methodology to derivatize 2-halopyridines.[17]Our group is interested in the applications
of iridium-catalyzed
borylation and Suzuki coupling in organic synthesis.[13,18−25] In 2016, we described the application of this methodology to functionalize
2,6-bis(trifluoromethyl)pyridine.[26] Herein,
we describe the application of iridium-catalyzed borylation to various
trifluoromethyl-substituted pyridines.
Results and Discussion
Most of the trifluoromethylpyridines used in this study are liquids
at room temperature or have low melting points. Together with the
liquid borylating agent, pinacolborane, they both assist in the dissolution
of the precatalyst/ligand, and hence there is no need to use any additional
solvent. The iridium precatalyst and ligand were weighed in air and
were transferred to the Schlenk flask under positive nitrogen pressure,
followed by pinacolborane and the trifluoromethylpyridine substrate.
The flask was then heated in an oil bath at 80 °C, and the progress
of the reaction was monitored by GC–MS.We started with
the borylation of 2,3-bis-trifluoromethyl-substituted
pyridine (Scheme ).
A steric bulk of the trifluoromethyl group at 3-position directed
the catalytic borylation specifically at the 5-position, and the resulting
pyridylboronic ester was isolated in 82% yield (entry 1a). The 3-methyl and 3-bromo-substituted 2-trifluoromethylpyridines
were also selectively borylated at the 5-position (entries 1b and 1c). A similar selectivity was again obtained by
changing the 2-substituent on pyridine but retaining the trifluoromethyl
group at the 3-position (entries 1d–1g). While the 2-methoxy (1g) and 2-fluoro (1d) derivatives gave a good yield, the presence of a chloro or bromo
substituent at the 2-position (1e and 1f) resulted in incomplete conversion and hence reduced isolated yields.
In the case of 2-fluoro and 2-chloro (entries 1d and 1e) formation, a significant amount (∼7%) of isomeric
monoborylated product was also observed in the crude GC–MS,
which is consistent with the literature.[16,27] For 2-bromo-3-trifluoromethylpyridine (entry 1f), the
reaction stopped at 31% conversion. Addition of the catalyst and pinacolborane
at this stage was not helpful in in enhancing the conversion.
Scheme 1
Iridium-Catalyzed Borylation of 2,3-Disubstituted Trifluoromethylpyridines
Yields are reported for the isolated
compounds.
Iridium-Catalyzed Borylation of 2,3-Disubstituted Trifluoromethylpyridines
Yields are reported for the isolated
compounds.Next, we examined 2,4-disubstituted
pyridines (Scheme ). When the 4-substituent was
bulky CF3, the borylation selectively took place at the
6-position (entries 2a–2c) and the
products were isolated in good to excellent yields. For 2b, the reaction was usually complete in 1–2 h, and prolonged
heating for 16 h resulted in the formation of trace amounts (∼1.7%)
of the side product with mass = 328 (see Figure S58). A GC–MS library search matched this mass with
a compound of formula C12H4N2F8, which could potentially arise from the homo-coupling of 2b. In contrast, catalytic borylation of 2c never
proceeded to full conversion, resulting in a lower isolated yield.
For 2c, 56 mg (31%) starting pyridine was also recovered.
When the 4-substituent was of small size, such as Cl, a mixture of
5- and 6-borylated products was obtained in 1:3 ratio, respectively
(entry 2g). These α- or 6-borylated pyridines (2a, 2b, 2c, and major isomer of 2g) are not shelf stable and are found to be decomposed upon
standing at ambient temperatures in closed vials for 6 months. The
instability of α-borylated pyridine derivatives is well known
in literature.[28] Access to these 6-borylated
(or α-borylated) pyridines by Miyaura borylation has been reported
to be problematic due to in situ Suzuki coupling.[14] Very recently, Leonori has reported an alternate radical-based
approach to prepare α-borylated pyridines using BH3–NMe3.[29]
Scheme 2
Iridium-Catalyzed
Borylation of 2,4-Disubstituted Trifluoromethylpyridines,,
3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin.
Mixture of 5- and 6-borylated isomers in 1:3 ratio.
Yields are reported for isolated
compounds.
Iridium-Catalyzed
Borylation of 2,4-Disubstituted Trifluoromethylpyridines,,
3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin.Mixture of 5- and 6-borylated isomers in 1:3 ratio.Yields are reported for isolated
compounds.When the 4-substitent was amino,
the traceless borylation protocol
developed by Smith III and Maleczka Jr.[30] yielded a 5-borylated product as a single isomer (entry 2f). No catalytic borylation was observed with 2-bromo- and 2-amino-substituted
4-trifluoromethylpyridines (entries 2d and 2e). The C–Br bond in the case of 2d is probably
highly activated, which might be leading to catalyst deactivation.
For the borylation of 2-amino pyridines, such as 2e,
the presence of an additional substituent at the pyridine 6-position
is critical as per literature.[30] In contrast
to 2e, the isomeric substrate, 2-trifluoromethyl-4-aminopyridine,
easily underwent traceless borylation, and the product 2f was isolated in 83% yield. The presence of any substituent (other
than amino or bromo) at the 2-position is essential for borylation
at 6-position, as in the case of 4-trifluoromethylpyridine (2i) and 3,4-bis(trifluoromethyl)pyridine (2h)
formation of a borylated product was not detected by the GC–MS
analysis of the crude reaction mixture. Interestingly, 4-trifluoromethylpyridine
has been used as a ligand for iridium-catalyzed ortho-selective borylation of benzoate esters.[31]Catalytic borylation of 5-substituted 2-trifluromethylpyridines
was also examined (Scheme ). In this case, borylation selectively took place ortho to the smaller 5-substituent, and the resulting 4-borylated
pyridines were isolated in excellent yields, except for the 5-bromo
case (entry 3c), where the reaction did not go beyond
49% conversion.
Scheme 3
Iridium-Catalyzed Borylation of 5-Substituted 2-Trifluoromethylpyridines,
3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin.
Yields are reported for isolated compounds.
Iridium-Catalyzed Borylation of 5-Substituted 2-Trifluoromethylpyridines,
3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin.Yields are reported for isolated compounds.In the case of 2-substituted 5-trifluoromethylpyridines,
borylation
took place selectively ortho to the smaller 2-substituent
at the 3-position (Scheme ). Catalytic borylation in the case of 4d was
accompanied by the ∼9% unidentified side product. In contrast
to successful borylation for 3b and 3c,
attempted borylation in case of 4b and 4c was not successful. A similar behavior has been reported for the
cyanopyridines, where 2-cyano-5-bromopyridine was easily borylated
but no borylation was observed for its isomer, i.e., 2-bromo-5-cyanopyridine.[32] Although 4b was isolated in only
6% yield, 438 mg of the starting material was also recovered, making
the isolated yield almost quantitative. The C–X bond in 2-halopyridines
is highly activated and may result in catalyst deactivation. Attempted
traceless borylation in case of 4e was also not successful.
In their original paper on aminopyridine borylation, Smith III and
coworkers have indicated that the presence of any substituent at the
α position of the pyridine is critical for the success of these
reactions.[30]
Scheme 4
Iridium-Catalyzed
Borylation of 2-Substituted 5-Trifluoromethylpyridines,,,
Isolated yield is 99%
based on
the recovered starting material.
Isolated product contains ∼9% of the unidentified side product.
3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin.
Yields are reported for isolated compounds.
Iridium-Catalyzed
Borylation of 2-Substituted 5-Trifluoromethylpyridines,,,
Isolated yield is 99%
based on
the recovered starting material.Isolated product contains ∼9% of the unidentified side product.3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin.Yields are reported for isolated compounds.For 2-substituted-6-trifluoromethylpyridines, borylation
took place
selectively at the 4-position (Scheme ). Besides the 2-chloro and 2-bromo substituents (entries 5a and 5b), the 2-iodo group was also tolerable
(entry 5c) although the product was isolated in a low
25% yield (along with 52% recovered starting iodopyridine). For the
2-amino case (entry 5f), formation of ∼4% of a
minor borylated isomer was also observed along with the major 4-borylated
product. This traceless borylation was carried out neatly in the absence
of any solvent, which resulted in slight deviation from the 99% selectivity
as reported in the literature.[30]
Scheme 5
Iridium-Catalyzed
Borylation of 6-Substituted 2-Trifluoromethylpyridines,
Mixture of 4- and 3-borylated
isomers in 24:1 ratio.
3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin. Yields are reported
for isolated compounds.
Iridium-Catalyzed
Borylation of 6-Substituted 2-Trifluoromethylpyridines,
Mixture of 4- and 3-borylated
isomers in 24:1 ratio.3,4,7,8-Tetramethyl-1,10-phenanthroline
ligand was used along with 3.0 equiv of HBPin. Yields are reported
for isolated compounds.The synthetic utility
of the synthesized boronic esters was demonstrated
by employing oxidation and Suzuki coupling reactions (Schemes and ).
Scheme 6
Oxidation of 5-(4,4,5,5-Tetramethyl-1,3,2-Dioxaborolan-2-yl)-2,3-Bis(Trifluoromethyl)-Pyridine
Scheme 7
Suzuki Coupling of 5-(4,4,5,5-Tetramethyl-1,3,2-Dioxaborolan-2-yl)-2,3-Bis(Trifluoromethyl)Pyridine
In conclusion, iridium-catalyzed C–H
borylation of trifluoromethyl-substituted
pyridines has been successfully carried out. Various substitution
patterns were evaluated and excellent regioselectivities based on
sterics were obtained. These trifluoromethyl-substituted pyridylboronic
esters are amenable to column chromatography, and most of the synthesized
compounds have been isolated in pure form for the first time. However,
the α-(2-position) borylated pyridylboronic acid pinacol esters
do not have a long shelf life and were decomposed in closed vials
at ambient temperatures within 6 months. These trifluoromethyl-substituted
pyridylboronic esters can potentially be very useful synthesis intermediates.
Experimental
Details
Commercially available reagents, substrates, and
other chemicals
were used without any purification. Solvents for column chromatography
were distilled before use. All reactions were carried out in air-free
25-mL Schlenk flasks that were closed under nitrogen. Catalytic borylation
reactions were done neatly without the use of any solvent. Thin-layer
chromatography (TLC) was carried out using 250-μm-thick TLC
plates, and visualization was achieved under a 254 nm UV lamp. Purification
by column chromatography was carried out using silica gel (particle
size: 40–63 μm, 230–400 mesh). The yields are
reported for the isolated materials. Each borylation reaction was
run at least twice, and the approximate reaction times have been indicated.IR spectra were recorded neatly by employing a compact ATR FT-IR
spectrometer. All reported melting points are uncorrected. The reactions
were monitored by a single-quadrupole GC–MS system operating
in EI mode. 1H NMR and 13C NMR spectra were
recorded at 600.19 and 150.93 MHz, respectively. The chemical shifts
in the 1H NMR spectra are referenced with the residual
proton resonances of the corresponding deuterated solvent (CDCl3: δ = 7.26). The chemical shifts in the 13C NMR spectra are reported relative to the central peak of CDCl3 (δ = 77.0).The carbon atom attached to the boron atom
in boronic esters is typically not observed in the 13C
NMR spectra due to broadening from and coupling with boron. Regiochemical
assignments of the pyridylboronic esters are based on NMR spectroscopy
(1H and 13C NMR). The abbreviations used are
as follows: HBPin for 4,4,5,5-tetramethyl-1,3,2-dioxaborolane; dtbbpy
for 4,4′-di-tert-butyl-2,2′-bipyridyl; and tmphen for
3,4,7,8-tetramethyl-1,10-phenanthroline.
Procedures
General Procedure
for Borylation of Trifluoromethyl-Substituted
Pyridines
The [Ir(OMe)(COD)]2 precatalyst and
dtbbpy ligand were weighed in air. In a fume hood, a Schlenk flask,
equipped with a magnetic stirring bar, was filled with nitrogen and
evacuated (at least three cycles). Under positive nitrogen pressure,
the [Ir(OMe)(COD)]2 precatalyst (1 mol %, 0.01 mmol, 6.6
mg) and 4,4-di-tert-butyl bipyridine ligand (2 mol
%, 0.02 mmol, 5.4 mg) were added to the Schlenk flask. Pinacolborane
(HBPin) (1.5 equiv, 1.5 mmol, 192 mg, 218 μL) and trifluoromethylpyridine
substrate (1 equiv, 1 mmol) were added using a micropipette. The Schlenk
flask was closed and the reaction mixture was heated at 80 °C
using an oil bath. The progress of the catalytic reactions was monitored
by TLC and/or GC–MS. Once the reaction was judged to be complete
by GC–MS (or when no further conversion was observed), the
reaction flask was brought out of the oil bath, cooled to room temperature,
and opened to air. The crude reaction mixture was taken out of the
flask by dissolving in the solvent (dichloromethane), and the volatiles
were removed under vacuum using a rotary evaporator. The crude product
thus obtained was purified by column chromatography using silica gel
as the stationary phase.
General Procedure for Traceless Borylation
of Amino-Substituted
Pyridines
The [Ir(OMe)(COD)]2 precatalyst and
tmphen ligand were weighed in air. In a fume hood, a Schlenk flask,
equipped with a magnetic stirring bar, was filled with nitrogen and
evacuated (at least three cycles). Under positive nitrogen pressure,
pinacolborane (HBPin) (1.5 equiv, 1.5 mmol, 192 mg, 218 μL)
and trifluoromethylpyridine substrate (1 equiv, 1 mmol) were added
using a micropipette and the mixture was stirred at room temperature
for 1 h in a closed Schlenk flask. Under nitrogen flow, the [Ir(OMe)(COD)]2 precatalyst (1 mol %, 0.01 mmol, 6.6 mg), 3,4,7,8-tetramethyl-1,10-phenanthroline
ligand (2 mol %, 0.02 mmol, 4.7 mg), and additional pinacolborane
(HBPin) (1.5 equiv, 1.5 mmol, 192 mg, 218 μL) were added to
the Schlenk flask. The Schlenk flask was closed again and the reaction
mixture was heated at 80 °C in an oil bath. The progress of the
traceless borylation reaction was monitored by TLC and/or GC–MS.
Once the reaction was judged to be complete by GC–MS, the reaction
flask was brought out of the oil bath, cooled to room temperature,
and opened to air. The crude reaction mixture was taken out of the
flask by dissolving in the solvent (dichloromethane), and the volatiles
were removed under vacuum using a rotary evaporator. The crude product
thus obtained was purified by column chromatography using silica gel
as the stationary phase.
Mix of 4-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-6-(trifluoromethyl)pyridine
and 4-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyridine
(2g + 2g′)
The general borylation procedure was applied to 4-chloro-2-(trifluoromethyl)pyridine
(181 mg, 1 mmol, 1 equiv) for 3 h. Column chromatography (DCM, Rf = 0.3) furnished the product as a very light
yellow sticky solid (227 mg, 84%), which was a mixture of two monoborylated
isomers in 3:1 ratio by 1H NMR. The major isomer A is highly
susceptible to deborylation upon standing. Regioisomeric assignment
is based on NMR spectroscopy.FT-IR (ATR): 3068, 2981, 2934,
1368, 1300, 1285, 1133, 1098, 963, 878, 846, 731, 697 cm–1.1H NMR (600 MHz, CDCl3) Isomer A δ:
7.99 (d, J = 1.8 Hz, 1H), 7.69 (d, J = 1.8 Hz, 1H), 1.38 (s, 12H, 4CH3 of BPin); Isomer B
δ: 8.90 (s, 1H), 7.65 (s, H), 1.38 (s, 12H, 4CH3 of
BPin).13C NMR (151 MHz, CDCl3) Isomer
A δ:
150.1 (q, 2JC–F = 35.0
Hz, C), 144.9 (C), 133.2 (CH), 122.1 (q, 3JC–F = 3.0 Hz, CH), 121.0 (q, 1JC–F = 274.8 Hz, C), 85.35 (2C), 24.85
(4CH3 of BPin); 13C NMR (151 MHz, CDCl3) Isomer B δ: 156.9 (CH), 151.3 (C), 150.5 (q, 2JC–F = 35.0 Hz, C), 121.5 (q, 3JC–F = 2.4 Hz, C), 120.9
(q, 1JC–F = 274.8 Hz,
C), 85.0 (2C), 24.8 (4CH3 of BPin).GC–MS
(EI) major isomer: m/z (%) = 307
(26) (M)+, 292 (21), 288 (15), 274 (15), 264 (17), 251
(100), 208 (72), 188 (42), 181 (14), 85 (29), 82 (53), 67 (25). GC–MS
retention time 9.11 min.GC–MS (EI) minor isomer: m/z (%) = 307 (10) (M)+, 292
(100), 272 (87), 264 (14), 250
(47), 230 (92), 223 (21), 208 (42), 85 (12).
The general traceless borylation procedure was applied
to 6-(trifluoromethyl)pyridin-2-amine
(162 mg, 1 mmol, 1 equiv) using 3,4,7,8-tetramethyl-1,10-phenanthroline
ligand (4.7 mg, 0.02 mmol, 2 mol %) and 3 equiv of pinacolborane for
1 h. The ratio of the major to minor monoborylated isomer was 96:4
by GC–MS.Pale yellowish liquid; yield: 257 mg (89%); Rf = 0.25 (CH2Cl2).FT-IR (ATR): 3322, 3206, 2981, 1640, 1553, 1436, 1317, 1277, 1191,
1129, 966, 862, 845 cm–1.1H NMR
(600 MHz, CDCl3): major isomer δ
= 7.31 (s, 1H), 7.02 (s, 1H), 4.86 (s, 2H, NH2), 1.33 (br
s, 12H, 4CH3 of BPin).1H NMR (600 MHz,
CDCl3): minor isomer δ
= 7.97 (d, J = 7.4 Hz, 1H), 6.89 (d, J = 7.4 Hz, 1H), 4.86 (s, 2H, NH2), 1.33 (br s, 12H, 4CH3 of BPin).13C NMR {1H} (151 MHz,
CDCl3):
major isomer δ = 158.1 (C), 145.7 (q, 2JC–F = 33.8 Hz, C), 121.7 (q, 1JC–F = 273.9 Hz, C), 117.9 (CH), 114.4
(distorted q, CH), 84.7 (2C), 24.8 (4CH3 of BPin).19F {1H} NMR (376 MHz, CDCl3):
major isomer δ = −68.4 (s, CF3).19F {1H} NMR (376 MHz, CDCl3):
minor isomer δ = −69.1 (s, CF3).11B NMR (192 MHz, CDCl3): δ = 29.9.GC–MS (EI): m/z (%) =
288 (33) (M)+, 287 (12), 231 (100), 230 (32), 215 (19),
211 (10), 189 (12), 188 (12), 187 (5), 169 (9), 168 (4).
5,6-Bis(trifluoromethyl)pyridin-3-ol
(6)
In an oven-dried round-bottom flask,
5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-bis(trifluoromethyl)pyridine
(341 mg, 1 mmol) and acetone (3 mL) were added. Stirring produced
a homogeneous solution. An aqueous solution of oxone (615 mg, 1 mmol,
1 equiv in 3 mL of water) was added dropwise over 2–4 min.
After complete addition, the reaction mixture was vigorously stirred
for 30 min. After the completion of the reaction, an aqueous solution
of NaHSO3 (1 mL) was added. The reaction mixture was extracted
with DCM (15 mL × 3). The combined organics were washed with
brine. The organic layer was separated and dried using anhydrous sodium
sulfate (2 g) and filtered. Volatiles were removed under reduced pressure
using a rotary evaporator. The product was isolated by column chromatography.White solid; yield: 211 mg (91%); mp 64–66 °C; Rf = 0.4 (ethyl acetate/hexanes 1:1).FT-IR
(ATR): 3300 (br), 2997, 1604, 1579, 1462, 1248, 1099, 1038,
901, 750 cm–1.1H NMR (600 MHz,
CDCl3): δ = 8.44 (d, J = 2.4 Hz,
1H), 7.63 (d, J = 2.4 Hz, 1H),
2.43 (br s, 1H, OH).13C NMR {1H} (151
MHz, CDCl3):
δ = 154.7 (C), 139.4 (CH), 136.9 (distorted q, C), 126.6 (distorted
q, C), 122.6 (distorted q, CH), 120.8 (distorted q, 2 CF3).19F NMR (376 MHz, CDCl3): δ
= −60.2
(m, CF3), −63.2 (m, CF3).GC–MS
(EI): m/z (%) =
231 (100) (M)+, 230 (7), 229 (3), 213 (4), 212 (30), 183
(2), 182 (5), 181 (45), 163 (4), 162 (60), 160 (2), 114 (11), 106
(3), 69 (3).
Authors: Scott A Sadler; Hazmi Tajuddin; Ibraheem A I Mkhalid; Andrei S Batsanov; David Albesa-Jove; Man Sing Cheung; Aoife C Maxwell; Lena Shukla; Bryan Roberts; David C Blakemore; Zhenyang Lin; Todd B Marder; Patrick G Steel Journal: Org Biomol Chem Date: 2014-10-07 Impact factor: 3.876
Authors: Jiang Wang; María Sánchez-Roselló; José Luis Aceña; Carlos del Pozo; Alexander E Sorochinsky; Santos Fustero; Vadim A Soloshonok; Hong Liu Journal: Chem Rev Date: 2013-12-03 Impact factor: 60.622
Authors: Ghayoor A Chotana; Jose R Montero Bastidas; Susanne L Miller; Milton R Smith; Robert E Maleczka Journal: Molecules Date: 2020-04-10 Impact factor: 4.411
Figure 1
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Scheme 5
Scheme 6
Scheme 7