Facile Synthesis of Halogen Decorated para -/ meta -Hydroxybenzoates by Iridium-Catalyzed Borylation and Oxidation

Article abstract of DOI:10.1055/s-0037-1610538

Hydroxybenzoates are an important class of phenols that are widely used as preservatives and antiseptics in the food and pharmaceutical industries. In this report, a facile preparation of 2,6- and 2,3-disubstituted 4/5-hydroxybenzoates by iridium-catalyze

Full text of DOI:10.1055/s-0037-1610538

SYNTHESIS
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–G
paper
A
en
T. Shahzadi et al.
Paper
Synthesis
Facile Synthesis of Halogen Decorated para-/meta-Hydroxy-
benzoates by Iridium-Catalyzed Borylation and Oxidation
Tayyaba Shahzadi
HBPin
[Ir], dtbbpy
Oxone®
X
Y
X
X
Y
Rahman S. Z. Saleem
Ghayoor A. Chotana*
RO2C
RO2C
RO2C
80 °C
16–24 h
BPin
OH
Y
r.t., 0.5 h
12 examples of
sterically governed
borylation
12 examples of
para-/meta-
hydroxybenzoates
Department of Chemistry & Chemical Engineering,
Syed Babar Ali School of Science & Engineering, Lahore
University of Management Sciences, Lahore 54792,
Pakistan
X, Y = F, Cl, Br, CF3, Me, OMe
71–98% yield
75–97% yield
ghayoor.abbas@lums.edu.pk
Received: 10.05.2018
Accepted after revision: 04.07.2018
Published online: 09.08.2018
R
O
O
Vanillic acid
Flavoring
O
OH
OH
O
O
agent
H
DOI: 10.1055/s-0037-1610538; Art ID: ss-2018-z0330-op
HO
Ferutinin
O
Abstract Hydroxybenzoates are an important class of phenols that are
widely used as preservatives and antiseptics in the food and pharma-
ceutical industries. In this report, a facile preparation of 2,6- and 2,3-
disubstituted 4/5-hydroxybenzoates by iridium-catalyzed borylation of
respective disubstituted benzoate esters followed by oxidation is de-
scribed. This synthetic route allows for the incorporation of halogens in
the final hydroxybenzoates with substitution patterns not readily acces-
sible by the traditional routes of aromatic functionalization.
HO
Phytoestrogen
OH
Parabens
O
Cl
Food preservative
N
Trimebutine
Antimuscarinic agent
O
O
Chloroprocaine
Local Anesthetic
O
O
NH2
N
O
O
Dazoxiben
Thromboxane
synthase
inhibitor
O
HO
Key words iridium-catalyzed C–H borylation, oxidation, Oxone®,
hydroxybenzoates, parabens, preservatives, halogen, trifluoromethyl
O
N
Pirodavir
N
O
O
Antipicornavirus
Hydroxybenzoates are important synthetic precursors
to many drugs, polymers, herbicides, and antioxidants.1–4
4-Hydroxybenzoates, also known as parabens, are widely
used as antimicrobial preservatives in food, pharmaceuti-
cals, and cosmetics.5–7 Approximately 8000 tons of para-
bens are consumed annually around the globe.8 This scaf-
fold is also found in many natural products and molecules
of biological relevance (Figure 1). Recently, 3,5-dihalogen-
substituted 4-hydroxybenzoates have been reported to
possess enhanced antimicrobial properties along with re-
duced risk of breast cancer as compared to the parent para-
ben.9 3-Hydroxybenzoates have shown excellent antifungal
properties10 and 2-hydroxybenzoates such as methyl salic-
ylate are active ingredient of many analgesics.
Classical approaches to access hydroxybenzoates in-
clude esterification of hydroxybenzoic acids using sulfuric
acid, p-toluenesulfonic acid, or cation-exchange resins as
catalyst.11 The starting hydroxybenzoic acids used for ester-
ification are in turn synthesized either using Kolbe–Schmitt
process by heating potassium phenoxide in a stream of car-
bon dioxide, or by heating p-cresol with various metallic
N
N
N
O
Figure 1 Hydroxybenzoic acid derivatives of commercial significance
oxides.12 The harsh reaction conditions used in these tradi-
tional approaches result in limited functional group toler-
ance. These classical routes also rely on early incorporation
of the hydroxyl functional group, which limits the subse-
quent derivatizations ortho to the hydroxyl group.
Keeping in view of their immense utility in pharmaceu-
tical, cosmetic, and food industries, there is need to develop
new green synthetic methodologies to access novel hy-
droxybenzoates with additional useful functional groups to
find next generation compounds with better activities and
reduced side effects.9,13–16 In this direction, development of
methodologies that allow introduction of a hydroxyl group
later in the synthetic route is an ideal approach for obtain-
ing new and unique substitution patterns not accessible
through the traditional routes.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

B
T. Shahzadi et al.
Paper
Synthesis
During the last two decades, several new methodologies
have been developed to synthesize substituted phenols un-
der mild reaction conditions and with improved functional
group compatibilities. Among these, the most convenient
route is through the oxidation of arylboronic acids and es-
ters.17 Various oxidizing agents utilized for this purpose in-
clude Oxone®,18 hydrogen peroxide,19 hydrazine deriva-
tives,20–22 sodium ascorbate,23 photocatalysts,24,25 and elec-
trocatalysts,26 etc. In addition, alternative synthetic routes
recently reported for the preparation of phenols include
nucleophilic aromatic substitutions,27,28 transition-metal-
catalyzed hydroxylation of aryl halides,29,30 and hydroxyl-
ation of arylsilanes.31–33 However, all these methods need
pre-functionalization of the aromatic ring in the form of
halogen or nitro groups, which are ultimately converted to
the hydroxyl group. Since incorporation of halogens often
results in improved bioactivities,9 it is desirable to develop
methods for the preparation of halogenated hydroxybenzo-
ates with new substitution patterns not readily accessible
through the traditional aromatic functionalization routes.
The group of Smith and Maleczka has reported iridium-
catalyzed aromatic C–H borylation/oxidation route for the
synthesis of meta-substituted phenols directly from the hy-
drocarbon feedstock.34–37 This transition-metal-catalyzed
reaction is highly selective for aromatic C–H activation in
the presence of other functional groups and thus allows for
the incorporation of various substituents including halo-
gens into the final phenol products. Moreover, sterically
governed regioselectivity observed in this C–H functional-
ization reaction is complementary to that obtained through
the traditional electrophilic aromatic substitution and di-
rected ortho-metalation approaches. Building on the foun-
dations of Smith and Maleczka methodology for the prepa-
ration of halogenated phenols, we explored the application
of this route to the borylation/oxidation of 2,6- and 2,3-
substituted benzoic esters to prepare the corresponding 4-
and 5-hydroxybenzoate esters.
Y
X
Y
X
HBPin (1.5 equiv)
[Ir(OMe)COD]2 (1 mol%)
RO2C
Me
RO2C
BPin
dtbbpy (2 mol%)
80 °C, 16–24 h
1a–f
Cl
MeO
MeO2C
BPin
MeO2C
BPin
BPin
MeO2C
BPin
1a
72%
1b
82%
1c
98%
Cl
Br
Cl
Br
Br
Me
F
MeO2C
BPin
MeO2C
MeO2C
BPin
1d
1e
71%
1f
88%
77%
Me
Cl
Scheme 1 Iridium-catalyzed C–H borylation of 2,6- and 2,5-disubsti-
tuted benzoates
Catalytic borylation of 2,3-disubstituted benzoate esters
also took place on the least sterically hindered 5-position
(Scheme 2). Halogenated and trifluoromethyl-substituted
benzoic esters were examined. Since it has been known that
the antimicrobial activity of the parabens increases with in-
creasing the alkyl chain length of benzoic ester, the ethyl
and n-propyl esters were also included in this study
(Scheme 2, entries 2c, 2e, and 2f).
RO2C
RO2C
HBPin (1.5 equiv)
[Ir(OMe)COD]2 (1 mol%)
Y
Y
BPin
2a–f
dtbbpy (2 mol%)
80 °C, 16–24 h
X
X
EtO2C
Cl
MeO2C
Br
MeO2C
BPin
Cl
BPin
BPin
2a
71%
2b
2c
73%
82%
Me
Cl
Cl
MeO2C
EtO2C
PrO2C
Cl
BPin
Cl
BPin
Cl
BPin
2d
2e
2f
81%
73%
83%
F3C
F3C
F3C
We started with the iridium-catalyzed borylation of
2,6-disubstituted benzoate esters. Using the standard bory-
lation protocol, precatalyst [Ir(OMe)(COD)]2 and dtbbpy li-
gand were weighed in air and transferred to a Schlenk flask
under nitrogen atmosphere. Pinacolborane (HBpin) and
benzoate ester substrate were subsequently added to the
flask and the mixture was heated at 80 °C using an oil bath.
The progress of reaction was monitored by GC-MS. Since re-
gioselectivity in iridium-catalyzed C–H borylation is gov-
erned by sterics, catalytic borylation selectively took place
at the least hindered site, that is, the 4-position (Scheme 1,
entries 1a–e). In the case of 2-bromo-5-fluoro-substituted
benzoate ester, the small size of fluorine allowed borylation
ortho to itself (Scheme 1, entry 1f).38 The resulting aryl-
boronate esters were isolated in good to excellent yields.
Scheme 2 Iridium-catalyzed C–H borylation of 2,3-disubstituted ben-
zoates
The synthesized boronic esters were then subjected to
oxidation using Oxone® (Scheme 3).34 The desired hydroxyl
benzoates were isolated in good to excellent yields. In the
case of 3b and 3f, small amounts (<1%) of protodeboryla-
tion was detected by GC-MS. This synthetic route allowed
the ready preparation of 2,6- and 2,5-halo-substituted 4-
hydroxybenzoates. It is interesting to note that the closely
related isomeric 3,5-disubstituted 4-hydroxylbenzoate es-
ters have recently been reported to exhibit improved anti-
microbial activities together with diminished side effects
commonly associated with unsubstituted parabens.9
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

C
T. Shahzadi et al.
Paper
Synthesis
were carried out in air-free 25 mL Schlenk flask (0–4 mm valve, 175
mm OAH). Analytical TLC was carried out using 250 μm thick Sil-
iaPlate™ TLC Plates. Visualization was achieved under a UV lamp (254
nm and 365 nm). Column chromatography was carried out using Sil-
iaFlash® (particle size: 40–63 μm, 230–400 mesh). All reported yields
are for isolated materials. Reaction times and yields are not opti-
mized. HBPin: pinacolborane; dtbbpy: 4,4′-di-tert-butyl-2,2′-bipyr-
idyl.
Y
Y
Oxone® (1 equiv)
acetone–H2O (1:1)
RO2C
BPin
RO2C
OH
3a–f
r.t., 20–30 min
Cl
X
X
Me
MeO
MeO2C
OH
MeO2C
OH
MeO2C
OH
3a
93%
3b 97%
3c
96%
IR spectra were recorded as neat using a Bruker Alpha-P IR instru-
ment in the ATR geometry with a diamond ATR unit. Melting points
were taken on Electrothermal IA9100 melting point apparatus. Reac-
tions were monitored by a GC-MS operating in EI mode. 1H NMR
spectra were recorded at 500 MHz, and 13C NMR spectra were record-
ed at 125 MHz at ambient temperature. The chemical shifts in 1H
NMR spectra are reported using TMS as internal standard and were
referenced with the residual proton resonances of the corresponding
Cl
Br
Cl
Br
Me
F
MeO2C
Me
OH
MeO2C
OH
MeO2C
OH
3d
97%
3e
3f
96%
75%
Cl
Br
Scheme 3 Synthesis of 2,6- and 2,5-disubstituted 4-hydroxybenzoates
deuterated solvent (DMSO-d6: δ = 2.50). The chemical shifts in the 13
C
Similarly, 2,3-disubstituted 5-borylated benzoate esters
were oxidized to the corresponding 5-hydroxy benzoates
(Scheme 4). Although ortho-substituted phenols are readily
available by traditional electrophilic aromatic substitution,
however, access to meta-substituted phenols is more chal-
lenging and requires long synthetic routes.39 The current
synthetic route provides ready access to these difficult to
prepare meta-halogenated phenols.
NMR spectra are reported relative to TMS (δ = 0) or the central peak
of DMSO-d6 (δ = 39.5) for calibration.
Standard abbreviations were used for denoting the multiplicities. All
coupling constants are apparent J values measured at the indicated
field strengths. In 13C NMR spectra of arylboronic esters, the carbon
atom attached to the boron atom of BPin group is typically not ob-
served due to broadening from and coupling with boron. Regiochem-
istry of the borylated products was assigned by NMR spectroscopy
(1H and 13C NMR).
RO2C
RO2C
Oxone® (1 equiv)
acetone–H2O (1:1)
Borylation of Arenes; General Procedure
Y
BPin
Y
OH
4a–f
In a fume hood, an oven dried Schlenk flask equipped with a magnet-
ic stirring bar was filled with N2 and evacuated (three cycles). Under
N2 atmosphere [Ir(OMe)(COD)]2 (13.3 mg, 0.01 mmol, 1 mol%), 4,4-di-
tert-butyl-2,2′-bipyridyl (10.7 mg, 0.02 mmol, 2 mol%), and pinacol-
borane (HBPin) (436 μL, 384 mg, 3 mmol, 1.5 equiv) were added. The
appropriate arene substrate (2 mmol, 1 equiv) was added via micropi-
pette under N2 atmosphere. The Schlenk flask was closed and the re-
action mixture was heated at 80 °C in an oil bath. The progress of re-
action was monitored by GC-MS and TLC. Upon completion of reac-
tion, Schlenk flask was cooled to r.t. and exposed to air. The contents
of the flask were dissolved in CH2Cl2 (3–5 mL) and taken out in a
round-bottomed flask. The volatile organics were removed under re-
duced pressure using a rotary evaporator. The crude product was pu-
rified by column chromatography (silica gel, hexanes–CH2Cl2 1:1).
r.t., 20–30 min
MeO2C
X
X
EtO2C
Cl
MeO2C
Br
OH
Cl
OH
OH
4a
97%
4b
92%
4c
92%
Me
Cl
Cl
MeO2C
EtO2C
PrO2C
Cl
OH
Cl
OH
Cl
OH
4d
94%
4e
4f
82%
87%
F3C
F3C
F3C
Scheme 4 Synthesis of 2,3-disubstituted 5-hydroxybenzoates
Methyl 2-Chloro-6-methyl-4-(4,4,5,5-tetramethyl-1,3,2-diox-
aborolan-2-yl)benzoate (1a)
In summary, iridium-catalyzed borylation and subse-
quent oxidation of benzoates esters is an efficient protocol
for synthesis of various substituted hydroxybenzoates. This
method is particularly attractive for the preparation of ha-
logenated hydroxybenzoates where the halogen substitu-
ent is present meta to the ortho/para directing hydroxyl
group.
General borylation procedure was applied to methyl 2-methyl-6-
chlorobenzoate (368 mg, 2 mmol, 1 equiv) for 24 h; colorless solid;
yield: 447 mg (72%); mp 73–74 °C; Rf = 0.3 (hexanes–CH2Cl2 1:1).
FT-IR (ATR): 2977, 1732, 1550, 1442, 1354, 1269, 1124, 1080, 958,
886, 848, 860, 813, 686 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 7.54 (s, 1 H), 7.51 (s, 1 H), 3.89 (s, 3
H, CH3), 2.27 (s, 3 H, CH3), 1.30 (s, 12 H, 4 × CH3 of BPin).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 166.8 (C=O), 136.3 (C), 135.7
(C), 134.5 (CH), 131.7 (CH), 129.0 (C), 84.3 (2 C), 52.7 (CH3), 24.6 (4 ×
CH3 of BPin), 18.7 (CH3).
GC-MS (EI): m/z (%) = 310 [20, (M)+], 295 (16), 279 (26), 275 (17), 243
(100), 233 (89), 211 (54), 201 (26), 179 (21), 175 (18).
All reactions were carried out under N2 atmosphere. All commercially
available chemicals and reagents were used without further purifica-
tion unless otherwise noted. EtOAc, hexanes, and CH2Cl2 were dis-
tilled before use. Carboxylate esters, if not readily commercially avail-
able, were prepared by acid-catalyzed esterification of the corre-
sponding carboxylic acid. Iridium-catalyzed borylation reactions
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

D
T. Shahzadi et al.
Paper
Synthesis
Methyl 2-Bromo-6-chloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)benzoate (1b)
GC-MS (EI): m/z (%) = 332 [10, (M + 2)+], 330 [17, (M)+], 315 (28), 299
(21), 244 (100), 231 (25), 213 (17), 199 (24).
General borylation procedure was applied to 2-bromo-6-chloroben-
zoate (500 mg, 2 mmol, 1 equiv) for 18 h; colorless solid; yield: 614
mg (82%); mp 83–84 °C; Rf = 0.3 (hexanes–CH2Cl2 1:1).
Methyl 2-Bromo-5-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)benzoate (1f)
General borylation procedure was applied to methyl 2-bromo-5-fluo-
robenzoate (464 mg, 2 mmol, 1 equiv) for 24 h; colorless solid; yield:
634 mg (88%); mp 95 °C; Rf = 0.3 (hexanes–CH2Cl2 1:1).
FT-IR (ATR): 2975, 1736, 1531, 1469, 1370, 1349, 1331, 1278, 1193,
1138, 1116, 1056 956, 880, 847, 815, 783, 756, 705 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 7.80 (d, J = 1.0 Hz, 1 H), 7.70 (d, J =
FT-IR (ATR): 2978, 2930, 1724, 1593, 1482, 1447, 1371, 1253, 1195,
0.5 Hz, 1 H), 3.92 (s, 3 H, CH3), 1.30 (s, 12 H, 4 × CH3 of BPin).
1127, 1025, 965, 849, 777, 712, 670 cm–1
.
13C NMR {1H} (125 MHz, DMSO-d6): δ = 165.1 (C=O), 137.1 (C), 136.2
(CH), 133.5 (CH), 130.3 (C), 119.10 (C), 84.8 (2 C), 53.3 (CH3), 24.6 (4 ×
CH3 of BPin).
1H NMR (500 MHz, DMSO-d6): δ = 7.84 (d, 4JH,F = 5.0 Hz, 1 H), 7.60 (d,
3JH,F = 9.0 Hz, 1 H), 3.87 (s, 3 H, CH3), 1.31 (s, 12 H, 4 × CH3 of BPin).
4
13C NMR {1H} (125 MHz, DMSO-d6): δ = 165.3 (d, JC,F = 1.6 Hz, C=O),
GC-MS (EI): m/z (%) = 376 [19, (M + 2)+], 374 [15, (M)+], 359 (22), 343
(10), 290 (100), 275 (19), 257 (13), 244 (11), 217 (10).
1
3
164.3 (d, JC,F = 250.5 Hz, C=O), 140.9 (d, JC,F = 8.2 Hz, CH), 136.7 (d,
3JC,F = 8.1 Hz, C), 117.9 (d, 2JC,F = 27.5 Hz, CH), 114.3 (d, 4JC,F = 3.5 Hz, C),
84.5 (2 C), 52.9 (CH3), 24.5 (4 × CH3 of BPin).
GC-MS (EI): m/z (%) = 358 [40, (M)+], 343 (36), 316 (80), 300 (27), 298
Methyl 2-Bromo-6-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-diox-
aborolan-2-yl)benzoate (1c)
(95), 259 (58), 254 (100), 227 (85).
General borylation procedure was applied to methyl 2-bromo-6-me-
thoxybenzoate (488 mg, 2 mmol, 1 equiv) for 40 h; colorless solid;
yield: 730 mg (98%); mp 116–118 °C; Rf = 0.5 (hexanes–CH2Cl2 1:1).
Methyl 2-Bromo-3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-diox-
aborolan-2-yl)benzoate (2a)
FT-IR (ATR): 2979, 1739, 1387, 1350, 1264, 1249, 1122, 1078, 1036,
964, 909, 851 767, 712 cm−1
.
General borylation procedure was applied to methyl 2-bromo-3-
methylbenzoate (456 mg, 2 mmol, 1 equiv) for 24 h; colorless solid;
yield: 502 mg (71%); mp 75–76 °C; Rf = 0.4 (hexanes–CH2Cl2 1:1).
1H NMR (500 MHz, DMSO-d6): δ = 7.42 (s, 1 H), 7.25 (s, 1 H), 3.84 (s, 6
H, 2 × CH3), 1.31 (s, 12 H, 4 × CH3 of BPin).
FT-IR (ATR): 2978, 2965, 1724, 1593, 1275, 1252, 1194, 1128, 1025,
13C NMR {1H} (125 MHz, DMSO-d6): δ = 165.7 (C=O), 156.3 (C), 129.4
(CH), 127.8 (C), 118.5 (C), 115.3 (CH), 84.5 (2 C), 56.3 (CH3), 52.7
(CH3), 24.6 (4 × CH3 of BPin).
965, 849, 777, 712, 670 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 7.75–7.74 (m, 1 H), 7.71–7.70 (m, 1
H), 3.85 (s, 3 H, CH3), 2.42 (s, 3 H, CH3), 1.30 (s, 12 H, 4 × CH3 of BPin).
GC-MS (EI): m/z (%) = 372 [58, (M + 2)+], 370 [62, (M)+], 339 (68), 284
(42), 270 (34), 253 (59), 239 (100), 196 (23).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 166.7 (C=O), 138.9 (C), 138.7
(CH), 133.7 (C), 133.1 (CH), 125.5 (C), 84.2 (2 C), 52.6 (CH3), 24.6 (4 ×
CH3 of BPin), 22.9 (CH3)
Methyl 2,6-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)benzoate (1d)
GC-MS (EI): m/z (%) = 354 [38, (M)+], 339 (18), 311 (100), 279 (19),
255 (29), 223 (30), 143 (41).
General borylation procedure was applied to methyl 2,6-dimethyl-
benzoate (164 mg, 1 mmol, 1 equiv) for 36 h; colorless solid; yield:
223 mg (77%); mp 77–78 °C; Rf = 0.5 (hexanes–CH2Cl2 1:1).
Methyl 2,3-Dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)benzoate (2b)
FT-IR (ATR): 2980, 1732, 1610, 1365, 1321, 1260, 1126, 1077, 965,
909, 887, 850, 810, 739, 686 cm–1
.
General borylation procedure was applied to methyl 2,3-dichloroben-
zoate (408 mg, 2 mmol, 1 equiv) for 24 h; colorless solid; yield: 541
mg (82%); mp 89–91 °C; Rf = 0.4 (hexanes–CH2Cl2 1:1).
1H NMR (500 MHz, DMSO-d6): δ = 7.39 (s, 2 H), 3.85 (s, CH3), 2.22 (s, 6
H, 2 × CH3), 1.29 (s, 12 H, 4 × CH3 of BPin).
FT-IR (ATR): 2977, 1727, 1592, 1439, 1351, 1268, 1242, 1205, 1129,
13C NMR {1H} (125 MHz, DMSO-d6): δ = 169.4 (C=O), 136.4 (C), 133.5
(2 C), 133.4 (2 × CH), 83.8 (2 C), 52.0 (CH3), 24.6 (4 × CH3 of BPin), 18.9
(2 CH3).
1047, 984, 963, 904, 851 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 7.94 (d, J = 1.5 Hz, 1 H), 7.92 (d, J =
1.5 Hz, 1 H), 3.88 (s, 3 H, CH3), 1.31 (s, 12 H, 4 × CH3 of BPin).
GC-MS (EI): m/z (%) = 290 [52, (M)+], 275 (42), 258 (46), 204 (100),
191 (90), 172 (26), 158 (72), 131 (32), 105 (23).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.7 (C=O), 138.1 (CH), 134.5
(CH), 133.2 (C), 132.8 (C), 132.4 (C), 84.7 (2 C), 52.9 (CH3), 24.6 (4 ×
CH3 of BPin).
Methyl 2,6-Dichloro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)benzoate (1e)
GC-MS (EI): m/z (%) = 332 [12, (M + 2)+], 330 [17, (M+)], 315 (17), 299
(23), 287 100), 255 (38), 231 (52), 199 (43).
General borylation procedure was applied to methyl 2,6-dichloroben-
zoate (412 mg, 2 mmol, 1 equiv) for 20 h; colorless solid; yield: 472
mg (71%); mp 75–76 °C; Rf = 0.5 (hexanes–CH2Cl2 1:1).
Ethyl 2,3-Dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)benzoate (2c)
FT-IR (ATR): 2983, 2951, 1745, 1609, 1359, 1341, 1271, 1160, 1100,
797 cm–1
.
General borylation procedure was applied to ethyl 2,3-dichloroben-
zoate (436 mg, 2 mmol, 1 equiv) for 18 h,; colorless solid; yield: 502
mg (73%); mp 66–67 °C; Rf = 0.4 (hexanes–CH2Cl2 1:1).
1H NMR (500 MHz, DMSO-d6): δ = 7.67 (s, 2 H), 3.93 (s, 3 H, CH3), 1.31
(s, 12 H, 4 × CH3 of BPin).
FT-IR (ATR): 2979, 1730, 1590, 1470, 1353, 1239, 1127, 1030, 968,
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.3 (C=O), 135.0 (C), 133.1
(2 × CH), 130.5 (2 C), 84.8 (2 C), 53.3 (CH3), 24.6 (4 × CH3 of BPin).
904, 847, 777, 748, 704 cm–1
.
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1H NMR (500 MHz, DMSO-d6): δ = 7.91 (d, J = 1.5 Hz, 1 H), 7.89 (d, J =
1.5 Hz, 1 H), 4.35 (q, J = 7.0 Hz, 2 H, CH2), 1.34 (s, 12 H, 4 × CH3 of
BPin), 1.32 (t, J = 7.0 Hz, 3 H, CH3).
GC-MS (EI): m/z (%) = 392 [5, (M+)], 377 (20), 333 (23), 307 (100), 289
(21), 251 (36), 233 (43), 205 (37).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.4 (C=O), 137.9 (CH), 134.1
(CH), 133.1 (C), 132.9 (C), 132.6 (C), 84.7 (2 C), 61.9 (CH2), 24.9 (4 ×
CH3 of BPin), 13.9 (CH3).
GC-MS (EI): m/z (%) = 346 [11, (M + 2)+], 344 [17, (M)+], 301 (95), 273
(100), 255 (36), 245 (31), 217 (40), 199 (47).
Oxidation Boronic Estes 1 and 2; General Procedure
An oven-dried round-bottomed flask equipped with a magnetic stir-
ring bar was charged with the respective boronic ester substrate 1 or
2 (1 mmol, 1 equiv) and acetone (3 mL). The mixture was stirred to
generate a homogeneous solution. An aqueous solution of Oxone® (1
equiv in 3 mL/mmol H2O) was added dropwise over 2–4 min. The re-
action mixture was vigorously stirred for 20–30 min. After the com-
pletion of reaction, an aq solution of NaHSO3 (1 mL) was added to
quench the reaction. The mixture was extracted with CH2Cl2 (3 × 15
mL) and the combined organics were washed with brine. The organic
layer was separated, dried (anhyd Na2SO4, 2 g), and filtered. Volatile
organics were removed using rotary evaporator. The crude product
was purified by column chromatography (silica gel, hexanes–EtOAc
1:1).
Methyl 2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
3-(trifluoromethyl)benzoate (2d)
General borylation procedure was applied to methyl 2-chloro-3-(tri-
fluoromethyl)benzoate (476 mg, 2 mmol, 1 equiv) for 24 h; colorless
solid; yield: 531 mg (73%); mp 125–126 °C; Rf = 0.4 (hexanes–CH2Cl2
1:1).
FT-IR (ATR): 2980, 1723, 1601, 1299, 1271, 1138, 980, 847, 685 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 8.22 (d, J = 1.5 Hz, 1 H), 8.08 (d, J =
1.5 Hz, 1 H), 3.90 (s, 3 H, CH3), 1.32 (s, 12 H, 4 × CH3 of BPin).
Methyl 2-Chloro-4-hydroxy-6-methylbenzoate (3a)
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.7 (C=O), 139.6 (CH), 134.8
General oxidation procedure was applied to methyl 2-chloro-6-meth-
yl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1a; 310
mg, 1 mmol, 1 equiv) for 0.5 h; pale yellow solid; yield: 186 mg (93%);
mp 88–89 °C; Rf = 0.7 (hexanes–EtOAc 1:1).
3
2
(q, JC,F = 4.8 Hz, CH), 133.3 (C), 132.4 (C), 127.8 (q, JC,F = 30.5 Hz, C),
1
122.5 (q, JC,F = 271.7 Hz, CF3), 84.8 (2 C), 53.1 (CH3), 24.6 (4 × CH3 of
BPin).
FT-IR (ATR): 3409, 2979, 1712, 1604, 1450, 1270, 1138, 950, 851 cm–1
.
GC-MS (EI): m/z (%) = 364 [6, (M)+], 349 (21), 333 (19), 321 (100), 303
1H NMR (500 MHz, DMSO-d6): δ = 10.23 (br s, 1 H, OH), 6.70 (dd, J =
2.0, 0.5 Hz, 1 H), 6.64 (dd, J = 2.5, 1.0 Hz, 1 H), 3.81 (s, 3 H, CH3), 2.18
(s, 3 H, CH3).
(7), 289 (36), 265 (36), 233 (49), 205 (37).
Ethyl 2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-
(trifluoromethyl)benzoate (2e)
13C NMR {1H} (125 MHz, DMSO-d6): δ = 167.2 (C=O), 158.7 (C), 138.3
General borylation procedure was applied to ethyl 2-chloro-3-(triflu-
oromethyl)benzoate (504 mg, 2 mmol, 1 equiv) for 24 h; colorless sol-
id; yield: 629 mg (83%); mp 65–68 °C; Rf = 0.4 (hexanes–CH2Cl2 1:1).
(C), 130.4 (C), 124.1 (C), 115.8 (CH), 113.4 (CH), 52.2 (CH3), 19.4 (CH3).
GC-MS (EI): m/z (%) = 200 [52, (M)+], 169 (100), 141 (24), 77 (36).
FT-IR (ATR): 2981, 2934, 1735, 1601, 1297, 1135, 1016, 964, 917 848
Methyl 2-Bromo-6-chloro-4-hydroxybenzoate (3b)
cm–1
.
General oxidation procedure was applied to methyl 2-chloro-6-bro-
mo-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
188 mg, 0.5 mmol, 1 equiv) for 0.5 h; colorless solid; yield: 129 mg
(97%); mp 115–118 °C; Rf = 0.3 (CH2Cl2).
1H NMR (500 MHz, DMSO-d6): δ = 8.17 (d, J = 1.5 Hz, 1 H), 8.07 (d, J =
1.5 Hz, 1 H), 4.37 (q, J = 7.0 Hz, 2 H, CH2), 1.33 (s, 12 H, 4 × CH3 of
BPin), 1.31 (t, J = 7.0 Hz, 3 H, CH3).
(1b;
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.4 (C=O), 139.2 (CH), 134.7
FT-IR (ATR): 3202, 2953, 1686, 1599, 1562, 1424, 1275, 1241, 1134,
3
2
933, 848, 770 cm–1
.
(q, JC,F = 5.1 Hz, CH), 133.8 (C), 132.2 (C), 127.7 (q, JC,F = 30.3 Hz, C),
122.5 (q, 1JC,F = 271.6 Hz, C), 84.8 (C), 62.1 (CH2), 24.6 (4 × CH3 of BPin),
13.9 (CH3).
1H NMR (500 MHz, DMSO-d6): δ = 10.81 (br s, 1 H, OH), 7.05 (d, J = 2.2
Hz, 1 H), 6.94 (d, J = 2.5 Hz, 1 H), 3.85 (s, 3 H, CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 165.6 (C=O), 159.5 (C), 131.1
GC-MS (EI): m/z (%) = 378 [7, (M)+], 335 (92), 307 (100), 289 (36), 251
(42), 233 (44), 205 (27).
(C), 125.7 (C), 119.6 (C), 118.2 (CH), 115.5 (CH), 52.9 (CH3).
GC-MS (EI): m/z (%) = 266 [22, (M + 2)+], 264 [18, (M)+], 235 (100), 233
(79), 177 (8).
Propyl 2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-
3-(trifluoromethyl)benzoate (2f)
General borylation procedure was applied to propyl 2-chloro-3-(tri-
fluoromethyl)benzoate (532 mg, 2 mmol, 1 equiv) for 24 h; colorless
oil; yield: 635 mg (81%); Rf = 0.4 (hexanes–CH2Cl2 1:1).
Methyl 2-Bromo-6-methoxy-4-hydroxybenzoate (3c)
General oxidation procedure was applied to methyl 2-bromo-6-me-
thoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) (1c; 370 mg, 1
mmol, 1 equiv) for 20 min; colorless solid; yield: 251 mg (96%); mp
107–109 °C; Rf = 0.3 (CH2Cl2).
FT-IR (ATR): 2978, 1736, 1601, 1374, 1297, 1279, 1193, 1136, 1050,
965, 848, 689 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 8.16 (d, J = 1.5 Hz, 1 H), 8.07 (d, J =
1.5 Hz, 1 H), 4.29 (t, J = 6.5 Hz, 2 H, CH2), 1.73 (m, 2 H, CH2), 1.31 (s, 12
H, 4 × CH3 of BPin), 0.95 (t, J = 7.0 Hz, 3 H, CH3).
FT-IR (ATR): 3235, 2980, 1692, 1598, 1452, 1426, 1293, 1236, 1155,
1106, 1035, 946, 820 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 10.32 (br s, 1 H, OH), 6.60 (d, J = 2.0
Hz, 1 H), 6.48 (d, J = 2.0 Hz, 1 H), 3.76 (s, 3 H, CH3), 3.73 (s, 3 H, CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 166.2 (C=O), 160.1 (C), 158.1
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.5 (C=O), 139. 2 (CH),
3
2
134.7 (q, JC,F = 4.9 Hz, C), 133.8 (CH), 132.1 (C), 127.7 (q, JC,F = 30.1
1
Hz, C), 122.5 (q, JC,F = 272.1 Hz, CF3), 84.8 (2 C), 67.5 (CH2), 24.6 (4 ×
(C), 119.1 (C), 116.5 (C), 110.6 (CH), 98.7 (CH), 55.9 (CH3), 52.3 (CH3).
CH3 of BPin), 21.4 (CH2), 10.3 (CH3).
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F
T. Shahzadi et al.
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GC-MS (EI): m/z (%) = 262 [18, (M + 2)+], 260 [22, (M)+], 231 (95), 229
GC-MS (EI): m/z (%) = 246 [57, (M + 2)+], 244 [60, (M)+], 213 (100), 185
(100), 214 (6), 186 (11), 158 (4), 150 (5).
(25), 106 (7).
Methyl 2,6-Dimethyl-4-hydroxybenzoate (3d)
Methyl 2,3-Dichloro-5-hydroxybenzoate (4b)
General oxidation procedure was applied to methyl 2,6-dimethyl-4-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1d; 145 mg,
0.5 mmol, 1 equiv) for 0.5 h; colorless solid; yield: 87 mg (97%); mp
111–113 °C; Rf = 0.5 (hexanes–EtOAc 1:1).
General oxidation procedure was applied to methyl 2,3-dichloro-5-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (2b; 331 mg,
1 mmol, 1 equiv) for 0.5 h; colorless solid; yield: 202 mg (92%); mp
145–147 °C; Rf = 0.7 (hexanes–EtOAc 1:1).
FT-IR (ATR): 3188, 2965, 1689, 1605, 1299, 1125, 930, 692 cm–1
1H NMR (500 MHz, DMSO-d6): δ = 9.64 (br s, 1 H, OH), 6.46 (s, 2 H, 2 ×
CH), 3.77 (s, 3 H, CH3), 2.16 (s, 6 H, 2 × CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 169.5 (C=O), 158.0 (C), 136.9
.
FT-IR (ATR): 3304, 2953, 1704, 1589, 1456, 1413, 1311, 1241, 996,
949, 854, 778, 742, 630 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 10.55 (br s, 1 H, OH), 7.18 (d, J = 3.0
Hz, CH), 7.10 (d, J = 3.0 Hz, CH), 3.85 (s, 3 H, CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 165.1 (C=O), 156.6 (C), 133.24
(2 C), 124.3 (C), 114.4 (2 CH), 51.5 (CH3), 19.8 (2 × CH3).
(C), 133.17 (C), 119.8 (CH), 118.7 (C), 116.2 (CH), 52.8 (CH3).
GC-MS (EI): m/z (%) = 222 [40, (M + 2)+], 220 [64, (M)+], 189 (100), 161
GC-MS (EI): m/z (%) = 180 [54, (M)+], 149 (100), 121 (25), 103 (3), 91
(16).
(16), 133 (10).
Methyl 2,6-Dichloro-4-hydroxybenzoate (3e)
Ethyl 2,3-Dichloro-5-hydroxybenzoate (4c)
General oxidation procedure was applied to methyl 2,6-dichloro-4-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1e; 161 mg,
0.5 mmol, 1 equiv) for 0.5 h; colorless solid; yield: 166 mg (75%); mp
106–107 °C; Rf = 0.5 (hexanes–EtOAc 1:1).
General oxidation procedure was applied to ethyl 2,3-dichloro-5-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (2c; 345 mg, 1
mmol, 1 equiv) for 20 min; colorless solid; yield: 215 mg (92%); mp
109–111 °C; Rf = 0.7 (hexanes–EtOAc 1:1).
FT-IR (ATR): 3385, 2980, 1696, 1434, 1352, 1136 cm–1
.
FT-IR (ATR): 3388, 2992, 1702, 1606, 1568, 1434, 1398, 1368, 1284,
1H NMR (500 MHz, DMSO-d6): δ = 10.85 (br s, 1 H, OH), 6.91 (s, 2 H, 2
× CH), 3.85 (s, 3 H, CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.9 (C=O), 159.5 (C), 131.3
(2 C), 123.6 (C), 115.2 (2 CH), 52.9 (CH3).
GC-MS (EI): m/z (%) = 222 [22, (M + 2)+], 220 [37, (M)+], 189 (100), 161
(5), 133 (17), 97 (3).
1220, 1022, 868, 780, 610 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 10.54 (br s, 1 H, OH), 7.18 (d, J = 3.0
Hz, CH), 7.09 (d, J = 3.0 Hz, CH), 4.31 (q, J = 7.0 Hz, 2 H, CH2), 1.30 (t, J =
70 Hz, 3 H, CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.7 (C=O), 156.6 (C), 133.5
(C), 133.2 (C), 119.7 (CH), 118.6 (C), 116.1 (CH), 61.7 (CH2), 13.1 (CH3).
GC-MS (EI): m/z (%) = 236 [34, (M + 2)+], 234 [56, (M)+], 219 (8), 208
(35), 191 (11), 189 (100), 161 (17).
Methyl 2-Bromo-5-fluoro-4-hydroxybenzoate (3f)
General oxidation procedure was applied to methyl 2-bromo-5-fluo-
ro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (1f; 358
mg, 1 mmol, 1 equiv) for 0.5 h; colorless solid; yield: 238 mg (96%);
mp 148–151 °C; Rf = 0.6 (hexanes–EtOAc 1:1).
Methyl 2-Chloro-3-(trifluoromethyl)-5-hydroxybenzoate (4d)
General oxidation procedure was applied to methyl 2-chloro-5-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluorometh-
yl)benzoate (2d; 365 mg, 1 mmol, 1 equiv) for 20 min; colorless semi-
solid; yield: 240 mg (94%); Rf = 0.6 (hexanes–EtOAc 1:1).
FT-IR (ATR): 3360, 3086, 2979, 1747, 1704, 1445, 1261, 1159, 892 cm–
1
.
1H NMR (500 MHz, DMSO-d6): δ = 11.25 (br s, 1 H, OH), 7.68 (d, J =
11.5 Hz, 1 H), 7.26 (s, J = 8.0 Hz, 1 H), 3.80 (s, 1 H, CH3).
FT-IR (ATR): 3385, 2980, 1729, 1434, 1352, 1136 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 10.78 (br s, 1 H, OH), 7.34 (s, 2 H, 2
× CH), 3.87 (s, 3 H, CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 165.0 (C=O), 153.4 (C), 134.8
(CH), 128.8 (q, 2JC,F = 30.5 Hz, C), 122.4 (q, 1JC,F = 271.6 Hz, CF3), 120.2
(CH), 117.5 (C), 117.1 (q, 3JC,F = 5.4 Hz, C), 52.9 (CH3).
4
13C NMR {1H} (125 MHz, DMSO-d6): δ = 164.3 (d, JC,F = 1.5 Hz, C),
149.5 (d, 1JC,F = 242.2 Hz, C), 149.2 (d, 2JC,F = 12.7 Hz, C), 122.7 (d, 3JC,F
=
3
2
3.1 Hz, CH), 121.3 (d, JC,F = 5.7 Hz, C), 119.2 (d, JC,F = 21.1 Hz, CH),
116.3 (d, 4JC,F = 3.1 Hz, C), 52.3 (s, CH3).
GC-MS (EI): m/z (%) = 250 [25, (M + 2)+], 248 [26, (M)+], 219 (100), 217
(95), 189 (11), 161 (6).
GC-MS (EI): m/z (%) = 256 [11, (M + 2)+], 254 (22, (M)+], 225 (32), 223
(100), 195 (35), 132 (13).
Methyl 2-Bromo-5-hydroxy-3-methylbenzoate (4a)
Ethyl 2-Chloro-3-(trifluoromethyl)-5-hydroxybenzoate (4e)
General oxidation procedure was applied to methyl 2-bromo-3-
methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (2a;
177 mg, 0.5 mmol, 1 equiv) for 0.5 h; colorless semi-solid; yield: 118
mg (97%); Rf = 0.7 (hexanes–EtOAc 1:1).
General oxidation procedure was applied to ethyl 2-chloro-5-(4,4,5,5-
tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)benzoate
(2e; 378 mg, 1 mmol, 1 equiv) for 0.5 h; colorless solid; yield: 233 mg
(87%); mp 113–115 °C; Rf = 0.6 (hexanes–EtOAc 1:1).
FT-IR (ATR): 3359, 2979, 1712, 1587, 1436, 1327, 1141, 980, 850, 672
cm–1
.
FT-IR (ATR): 3389, 2986, 1700, 1589, 1438, 1376, 1316, 1257, 1136,
1021, 980, 888, 785, 696 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 9.97 (br s, 1 H, OH), 6.91 (dd, J = 3.0,
0.5 Hz, 1 H), 6.85 (dd, J = 2.5, 0.5 Hz, 1 H), 3.82 (s, 3 H, CH3), 2.31 (s, 3
H, CH3).
1H NMR (500 MHz, DMSO-d6): δ = 10.78 (br s, 1 H, OH), 7.34 (d, J = 3.0
Hz, CH), 7.33 (d, J = 3.0 Hz, CH), 4.34 (q, J = 7.5 Hz, CH2), 1.31 (t, J = 7.5
Hz, CH3).
13C NMR {1H} (125 MHz, DMSO-d6): δ = 167.1 (C=O), 156.3 (C), 140.0
(C), 134.7 (C), 120.2 (CH), 114.3 (CH), 110.0 (C), 52.5 CH3), 23.2 (CH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G

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T. Shahzadi et al.
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13C NMR {1H} (151 MHz, CDCl3): δ = 166.1 (C=O), 154.2 (C), 134.6 (C),
(8) Ramaswamy, B. R.; Kim, J.-W.; Isobe, T.; Chang, K.-H.; Amano,
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2
1
130.9 (q, JC,F = 31.6 Hz, C), 122.2 (q, JC,F = 274.1 Hz, C), 121.9 (C),
120.3 (CH), 117.8 (q, 3JC,F = 5.4 Hz, CH), 62.7 (CH2), 14.1 (CH3).
(9) Bergquist, B. L.; Jefferson, K. G.; Kintz, H. N.; Barber, A. E.;
Yeagley, A. A. ACS Med. Chem. Lett. 2018, 9, 51.
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GC-MS (EI): m/z (%) = 270 [8, (M + 2)+], 268 [24, (M)+], 240 (37), 223
(100), 195 (23).
Propyl 2-Chloro-3-(trifluoromethyl)-5-hydroxybenzoate (4f)
General oxidation procedure was applied to propyl 2-chloro-5-
(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluorometh-
yl)benzoate (2f; 392 mg, 1 mmol, 1 equiv) for 20 min; colorless solid;
yield: 231 mg (82%); mp 102–104 °C; Rf = 0.6 (hexanes–EtOAc 1:1).
FT-IR (ATR): 3383, 2979, 1702, 1614, 1590, 1439, 1317, 1258, 1231,
1190, 1144, 996, 956, 886, 783, 696, 671 cm–1
.
1H NMR (500 MHz, DMSO-d6): δ = 10.79 (br s, 1 H, OH), 7.339 (s, 1 H,
CH), 7.338 (s, 1 H, CH), 4.26 (t, J = 6.5 Hz, CH2), 1.71 (m, CH2), 0.96 (t,
J = 7.0 Hz, CH3).
13C NMR {1H}(151 MHz, CDCl3): δ = 166.0 (C=O), 154.2 (C), 134.7 (C),
2
1
130.9 (q, JC,F = 31.4 Hz, C), 122.2 (q, JC,F = 273.9 Hz, C), 121.9 (C),
3
120.3 (CH), 117.8 (q, JC,F = 5.6 Hz, CH), 68.2 (CH2), 21.9 (CH2), 10.5
(CH3).
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48, 2713.
GC-MS (EI): m/z (%) = 282 [18, (M)+], 242 (25), 240 (58), 225 (31), 223
(100), 195 (44), 132 (36).
(21) Zhong, Y.; Yuan, L.; Huang, Z.; Gu, W.; Shao, Y.; Han, W. RSC Adv.
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H.; Wen, X.; Xu, Q.-L. J. Org. Chem. 2017, 82, 5236.
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K. A.; Xiao, W. J. Angew. Chem. Int. Ed. 2012, 51, 784.
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Funding Information
We thank Lahore University of Management Sciences for providing
generous financial support for this research through start-up grant
and faculty initiative fund to G.A.C. We also thank Higher Education
Commission (HEC) of Pakistan for financial support through grant
number NRPU-4426. T.S. is thankful to Lahore University of Manage-
ment Sciences for a Ph.D. fellowship.Hgiher
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Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610538.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–G