Bench-Stable Sulfoxide-Based Boronates: Preparation and Application in a Tandem Suzuki Reaction

Article abstract of DOI:10.1002/adsc.201801000

A set of novel aromatic and heteroaromatic bench-stable sulfoxide-based boronates was prepared. The structure of the boronates was established by means of X-ray crystallography, and the prepared boronates were successively used in Suzuki cross-coupling reactions under different conditions. We also developed a tandem Suzuki reaction so that a base is generated during the nucleophilic addition of Grignard reagents to 4-bromobenzaldehyde. The formed intermediates were smoothly coupled with the prepared boronates and the boronic acids under external base-free conditions. (Figure presented.).

Full text of DOI:10.1002/adsc.201801000

Title: Bench-Stable Sulfoxide-Based Boronates: Preparation and
Application in a Tandem Suzuki Reaction
Authors: Marek Čubiňák, vaclav eigner, and Tomas Tobrman
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801000
Link to VoR: http://dx.doi.org/10.1002/adsc.201801000

10.1002/adsc.201801000
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Bench-Stable Sulfoxide-Based Boronates: Preparation and
Application in a Tandem Suzuki Reaction
Marek Čubiňák,a Václav Eigner,b Tomáš Tobrmana*
a
Department of Organic Chemistry, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague 6,
Czech Republic
E-mail: tomas.tobrman@vscht.cz
Institute of Physics AS CR, v.v.i., Na Slovance 2, 182 21 Prague 8, Czech Republic
b
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201
Abstract. A set of novel aromatic and heteroaromatic bench-
stable sulfoxide-based boronates was prepared. The structure
of the boronates was established by means of X-ray
crystallography, and the prepared boronates were
successively used in Suzuki cross-coupling reactions under
different conditions. We also developed a tandem Suzuki
reaction so that a base is generated during the nucleophilic
addition of Grignard reagents to 4-bromobenzaldehyde. The
formed intermediates were smoothly coupled with the
prepared boronates and the boronic acids under external base-
free conditions.
Keywords: palladium; biaryls; Suzuki-Miyaura reaction;
cross-coupling; boron
nuclear magnetic resonance (NMR) spectroscopy, and
he explained their unusually high stability to be the
result of the reduced flexibility of the formed cyclic
systems and the efficiently polarized -framework.[7]
Later on, the various applications of the MIDA
boronates were highlighted by M.D. Burke’s group,[9]
while currently, the chemistry of the MIDA boronates
is being intensively studied.[10] With respect to recent
achievements regarding the preparation of stable
boronates, it is rather surprising that the practical
applications of boronates bearing sulfur-bridged atoms
remain unknown. The only known examples of sulfur-
based boronates involve phenylboronates derived
from thiotetrafuranose[11] and thiodiglycol.[12] The
known boronates with a sulfinyl bridge are even more
rare, with the only example being the boronate derived
from ethylboronic acid and sulfinylcalix[4]arenes.[13]
The significant lack of research in the field of thio- and
sulfinyl-bridged boronates, as well as our previous
experiences with the application of boronic acids in the
Suzuki reaction,[14] led us to explore the stability and
reactivity of thio- and sulfinyl-bridged boronates in the
present study.
Introduction
Organic synthesis has witnessed significant
progress with regard to the construction of
carboncarbon bonds over the last few decades. While
the desired transformation can be realized using many
different approaches, the cross-coupling reactions that
occur between nucleophilic and electrophilic
templates remain the most frequently used methods for
organic synthesis. The Suzuki reaction[1] has become
the favored approach for the synthesis of CC bonds
within a framework of complex molecules, mainly due
to the good stability and low toxicity of boronic acids.
Yet, despite the good stability of boronic acids, their
derivatives have been extensively studied as reagents
in organic synthesis and material chemistry.[2] The
most significant achievements in this regard have been
obtained in the field of boronic acid esters, that are
called boronates. In addition to the pinacol boronates[3]
and trifluoroborates,[4,5] the N-methyliminodiacetic
acid (MIDA) boronates[6] are commonly used for
synthetic purposes. The MIDA boronates are mixed
anhydrides formed by boronic acid and N-
methyliminodiacetic acid, and their synthesis was
reported in 1986[7] and 1988[8] by B. Wrackmeyer and
H.C. Brown, respectively. Wrackmeyer also studied
the structure of the MIDA boronates by means of
1
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10.1002/adsc.201801000
Advanced Synthesis & Catalysis
Results and Discussion
Additional information concerning the noncovalent
interactions is provided in the supporting material.
Figure 1. The structures of the tested sulfur-based substrates.
Thus, we devised a set of diols containing the sulfur
heteroatom that were tested in order to explore their
behavior with boronic acids (Figure 1). The 2,2’-
thiodiethanol (1a), 2,2’-thiodiacetic acid, and their
sulfoxides/sulfones did not react with the
phenylboronic acid in the presence of MgSO4 with
complete conversion, and the formed boronates were
hydrolytically unstable. The boronate derived from the
chloral hydrate derivative 1c was formed in a
quantitative yield, although the boronate was
hydrolytically unstable. Fortunately, we succeeded
with the boronate containing 2,2'-sulfinylbis(4-
methylphenol) (1d), which was quantitatively
introduced by means of the reaction of phenylboronic
acid with 2,2'-sulfinylbis(4-methylphenol) in the
presence of magnesium sulfate (Scheme 1). Of the
other tested aromatic boronic acids bearing electron-
withdrawing groups (EWG), the electron-donating
groups (EDG) also reacted smoothly with the
sulfoxide 1d, thereby affording the corresponding
boronates 2be in high yields. The 2-
Scheme 1. The preparation of stable sulfoxide-based
boronates.
2a
thienylboronate 2f was also obtained in
2b
high yield. Attempts to prepare a
boronate derived from 2-pyridylboronic
acid were not successful. The prepared
boronates 2af were isolated using
solvent evaporation, and analytically
pure samples were obtained following
recrystallization from tetrahydrofuran
(THF). Moreover, all the prepared
boronates 2ef are shelf-stable, and no
signs of decomposition were observed over a period of
several months. The boronate 2a was also found to be
stable in a deuterated chloroform for a couple of weeks.
The structures of the boronates 2ef were confirmed
by means of 1H, 13C NMR, and elemental analysis.
In the case of the boronate 2a, we were able to
confirm its structure using X-ray crystallography
(Figure 2). Due to the absence of suitable hydrogen
bond donors, the structure packing is governed by
weak non-covalent interactions. The molecules form
weakly bound dimers by means of off-set π···π
interactions assisted by C–H···π and C–H···O
interactions. The dimers are connected to chains in the
direction [010] by the C–H···O bond (Figure 2b). The
chains are then further connected by C–H···π
interactions in the directions [101] and [10-1].
Figure 2. a) The boronate 2a with an atom numbering
scheme. The thermal ellipsoids are drawn at the 50%
probability level. The H atoms are shown as spheres with an
arbitrary radius. b) The chain of noncovalent interactions in
the structure of the boronate 2a. The hydrogen atoms not
involved in the non-covalent interactions were omitted for
the sake of clarity. The off-set π···π interactions are depicted
in blue, while the C–H···π and C–H···O interactions are
depicted in black.
We have chosen to test the behavior of the
phenylboronate 2a in the Suzuki cross-coupling
reaction (Table 1). Based on our previous experiences
2
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10.1002/adsc.201801000
Advanced Synthesis & Catalysis
with the Suzuki reaction,[14ac] we used a 1 M solution
of potassium phosphate as a base (It was proved by 11B
NMR, that boronate 2a hydrolyzes stirring with K3PO4
at 60 °C), in conjunction with toluene as a solvent, and
the effect of the phosphine ligand was evaluated.
Tetrakis(triphenylphosphine)palladium(0) gave the
incomplete conversion of 4-bromobenzaldehyde to the
biphenyl 3aa (Table 1, entry 1). The same reaction,
albeit without a base, failed to give significant
conversion of the aldehyde (Table 1, entry 2). Neither
ligand-free conditions nor the bidentate 1,2-
PdCl2(MeCN)2
DTBPF
PdCl2(MeCN)2
tBuPh2P
100
(96c,d)
100
11
THF
THF
60
12
13
14
60
60
60
(95c)
<5
PdCl2(XPhos)2
MeCN
1,4-
dioxane
PdCl2(XPhos)2
<5
[a]Conversion of 2a to 3aa was determined using 1H NMR.
[b]The reaction was carried out without a base. [c]Isolated
[d]
yield.
In the case of PhB(OH)2 (92%), 2a (95%),
PhBMIDA (90%), PhBPin (88%) quantitative conversion
was achieved with 1 mol % of the catalyst. The isolated
yields are shown in parenthesis.
Bis(diphenylphosphino)ethane
(DPPE)
ligand
improved the conversion to the product 3aa (Table 1,
entries 3 and 4). The electron-rich phosphine ligands
increased the conversion to the product 3aa by up to
98% (Table 1, entries 57). The use of THF decreased
the reaction temperature while maintaining the
quantitative conversion and high isolated yield of the
product 3aa (Table 1, compare entries 7, 8, and 9). The
same results were also obtained using the 1,1'-
bis(diphenylphosphino)ferrocene (DPPF), DTBPF,
and tBuPh2P ligands (Table 1, entries 10, 11, and 12).
The use of other solvents proved ineffective (Table 1,
entries 13 and 14). In the case of DTBPF ligand
PhB(OH)2, 2a, PhBMIDA, PhBPin smoothly coupled
with 4-bromobenzaldehyde in the presence of 1 mol %
of the catalyst affording the product 3aa in quantitative
yields (Table 1, entry 11, note d) while PhBDAN[14dg]
did not react under these conditions. We also tried to
isolate sulfoxide 1d from the crude reaction mixture
with an acid-base reaction/extraction sequence. Thus,
the boronate 2a was coupled with 4-
bromobenzaldehyde in the presence of PdCl2(MeCN)2
and DTBPF ligand, the crude reaction mixture was
treated with aqueous NaOH, water layer was extracted
with ether. Then the water layer was acidified to pH 1
with conc. HCl and extracted with ethyl acetate. The
solvent evaporation afforded 82% of crude sulfoxide
1d, which was purified by crystallization giving 69%
yield of pure sulfoxide 1d.
Optimized reaction conditions (Table 1) were used
to explore the scope of the optimized reaction
conditions. When the phenylboronate 2a was coupled
with electron-rich and electron-poor aryl halides,
access to 4,4’-disubstituted biphenyls was established
(Scheme 2). It is important to note that PdCl2(XPhos)2
is only efficient with the EWG-bearing aryl halides
3ab, ac, and 3ae. The electron-poor boronate 2e also
smoothly coupled under PdCl2(XPhos)2 catalysis,
affording the product 3ed in a 93% yield. The electron-
rich aryl halides 3afah were coupled with the
tBuPh2P or DTBPF ligands. The developed reaction
conditions were also used for the synthesis of the 2-
substituted biphenyls 3ai and 3aj and the
heteroaromatic compounds 3ak,al. The use of the
boronate 2f derived from less stable 2-thienylboronic
acid proved fruitful, affording the substituted
thiophenes 3fm and 3fn. It is worth noting that 5
mol % of the catalysts was used because 1 mol % setup
failed to give quantitative conversion in some cases.
Table 1. Optimization of the reaction conditions.
Temp Conv[a]
Entry
Catalyst
Solvent
(°C)
90
90
90
90
90
90
60
40
(%)
1
2
3
4
5
6
7
8
Pd(PPh3)4
Pd(PPh3)4
Pd(DBA)2
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
84
<5b
11
PdCl2DPPE
40
96
98
97
Pd(PtBu3)2
PdCl2(XPhos)2
PdCl2(XPhos)2
PdCl2(XPhos)2
65
Scheme 2. The scope of the Suzuki reactions of the
boronates 2a and 2f.
100
(94c)
100
(95c)
9
PdCl2(XPhos)2
THF
THF
60
60
PdCl2(MeCN)2
DPPF
10
3
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10.1002/adsc.201801000
Advanced Synthesis & Catalysis
The Suzuki reaction is frequently used to synthesize
the notion that the presence of halide anions can inhibit
the Suzuki reaction.[19]
biphenyl scaffolds that have numerous applications as
chiral ligands in asymmetric synthesis. The substituted
biphenyls are also known as biologically active
compounds. Diflunisal and telmisartan are well-
known examples of these compounds. Another
biologically active type of biphenyl contains a
hydroxylalkyl sidechain. These compounds exhibit the
ability to inhibit activity against the protein tyrosine
phosphatase 1B.[15] The synthesis of such biphenyls is
usually accomplished via the addition of Grignard
reagents to biphenyl carboxaldehydes,[16] or by the
Suzuki reaction of the corresponding substituted
benzenes in the presence of an external base.[17]
However, in our case, we envisioned a novel approach
to a tandem Suzuki reaction in which a base is
generated within the reaction of 4-bromobenzaldehyde
with phenylmagnesium halides and the following
aqueous workup (Table 2). We expected that the
formed Mg2+ base could be used for the subsequent
Suzuki reaction. Recently published protocols in
which magnesium hydroxide promoted the Suzuki
reaction[18] suggested that the designed tandem
reaction is feasible. Thus, we started to test our
hypothesis. 4-Bromobenzaldehyde was mixed with
commercially available phenylmagnesium chloride,
before the reaction mixture was quenched with water,
and the palladium catalyst, ligand, and boronate 2a
were added to finish the tandem reaction. At the
beginning, it became clear that increasing the amount
of phenylmagnesium chloride does not influence the
conversion of 4 to 5aa (Table 2, entries 1–3). When
the reaction mixture was quenched with potassium
phosphate, the quantitative conversion of 4 to 5aa was
achieved (Table 2, entry 4). On the contrary, methanol
inhibited the Suzuki reaction (Table 2, entry 5). The
application of the DTBPF ligand along with 1.5 equiv
of commercially available phenylmagnesium chloride
and bromide led to the quantitative conversion of the
intermediate 4 into the biphenyl 5aa, which were
isolated in yields of 92% and 95%, respectively (Table
2, entries 6 and 7). However, when phenylmagnesium
bromide was prepared with iodine-activated
magnesium, the incomplete conversion of 4 to the
biphenyl 5aa was observed (Table 2, entry 8). This
result indicates that the presence of the iodide anion
inhibits the Suzuki reaction. Indeed, when
phenylmagnesium iodide was used as a reagent, no
product of the Suzuki reaction was formed (Table 2,
entry 9). When the phenylmagnesium bromide was
prepared using non-activated magnesium, the prepared
Grignard reagent smoothly reacted with 4-
bromobenzaldehyde, and the subsequent Suzuki
reaction gave 5aa in an 89% isolated yield (Table 2,
entry 10). Next, we explored the influence of some
commonly used additives on the course of a tandem
Suzuki reaction. Lithium chloride did not affect the
reaction outcome, and the biphenyl 5aa was isolated
in a quantitative yield (Table 2, entry 11). However,
sodium iodide and isopropyl iodide caused the Suzuki
reaction to cease (Table 2, entries 12 and 13). The
observed reactivity pattern is in good agreement with
Optimized reaction conditions were also applied to
other Grignard reagents in order to ascertain the scope
of the developed methodology. It soon became clear
that the aliphatic Grignard reagents 3ah and 5ab are
compatible, while both linear and branched alkyl
chains can be smoothly introduced (Scheme 3). In the
series of 4-substituted Grignard reagents, all the tested
substrates, namely 5ac, ad, and 5ae, successively
reacted during the Suzuki reaction. Additionally, the
3-substituted phenylmagnesium halides 5af and 5ag
underwent the reaction, as well as the 2-
tolylmagnesium chloride 5ah and the 2-
mesitylmagnesium bromide 5ai. 2-Thienylmagnesium
chloride was prepared from 2-iodothiophene using the
IMgCl exchange reaction with iPrMgCl. The
prepared Grignard reagent reacted with the 4-
bromobenzaldehyde, and the solvents were removed
under reduced pressure. The crude intermediate was
co-distilled with toluene to remove the iPrI. The
following Suzuki reaction proceeded with complete
conversion, affording the biphenyl 5aj in a 94%
isolated yield. The tandem Suzuki reaction is not
limited to only phenylboronate 2a, but also applies to
the TBSO group containing boronate 2c, which
smoothly coupled giving biphenyl 5ck in a 95%
isolated yield. The use of acetophenon resulted in
formation of alcohol 5al. Moreover, similar reactivity
was observed in the case of the selected boronic acids
5m–p.
Table 2. Novel tandem Suzuki reaction of 4-
bromobenzaldehyde, phenylmagnesium halides, and the
boronate 2a.
Entry
X
Ligand
DPPF
DPPF
DPPF
DPPF
Additive equiv 4/5aaa
1
2
3
4
Cl
Cl
Cl
Cl
1.5
2.0
3.0
1.5
6/94
10/90
8/92



K3PO4
0/100
(95b)
100/0
0/100
(95b)
0/100
(92b)
4/96
100/0
0/100
(89b)
0/100
(96b)
100/0
90/10
5
6
Cl
Cl
DPPF
DTBPF
MeOHc
2.0
1.5

7
Br
DTBPF
1.5

8
9
10
Brd DTBPF
I2
I2

1.5
1.5
1.5
Ie
DTBPF
DTBPF
Brf
11
Cl
DTBPF
LiCl
1.5
12
13
Cl
Cl
DTBPF
DTBPF
NaI
iPrI
1.5
1.5
[a]
1
[b]
The ratio of 4/5aa was determined using H NMR.
Isolated yield (%). The reaction mixture was quenched
[c]
4
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10.1002/adsc.201801000
Advanced Synthesis & Catalysis
with methanol. [d] Phenylmagnesium bromide was prepared
from bromobenzene and magnesium, which was activated
with iodine. [e] Phenylmagnesium iodide was prepared from
iodobenzene and magnesium, which was activated with
[f]
iodine.
Phenylmagnesium bromide was prepared from
bromobenzene and magnesium without chemical activation.
With the developed tandem Suzuki reaction now
available, we tried to apply the observed reactivity
pattern to the synthesis of bioactive compound 7[15]
using the minimum amount of separation steps. Thus,
easily available aldehyde 6 was treated with 4-
bromophenylmagnesium bromide, which was
prepared using non-activated magnesium. The
subsequent Suzuki reaction with the TBS-protected 4-
hydroxyphenylboronic acid boronate 2c gave the
crude product, which was treated with TBAF, and
careful column chromatography led to the desired
compound 7 in a 79% isolated yield (Scheme 4).
Scheme 4. The preparation of bioactive compound 7 using
the novel tandem Suzuki reaction.
Conclusion
In conclusion, we have developed a simple and
efficient method for the synthesis of stable sulfoxide-
based boronates. The structure of the prepared
boronates was confirmed by means of X-ray
crystallography. The prepared boronates were use in
Suzuki reactions under different catalytic conditions,
including the XPhos, tBuPh2P, DPPF, and DTBPF
ligands. We also discovered that sulfoxide ligand can
be easily recovered from the crude reaction mixture by
an acidbase reaction/extraction sequence. In addition
to the above-mentioned results, we have also
developed a novel external base-free tandem Suzuki
reaction wherein the base is generated within the frame
of the addition of Grignard reagents to the carbonyl
group. The tandem reaction proved to be a highly
sensitive to the presence of the iodide anion and
isopropyl iodide. The developed methodology was
used for the synthesis of bioactive compound 7 in just
two steps.
Experimental Section
All reactions were performed under an argon atmosphere.
NMR spectra were measured on a Varian Gemini 300 (1H,
300.07 MHz; 13C, 75.46 MHz), or a Bruker DRX 500
Avance (1H, 500.13 MHz, 13C, 125.78 MHz) spectrometer
at 298 K. Mass spectra were measured on ZAB-SEQ (VG
Analytical). The dry and degassed solvents were prepared
by PureSolv MD7; silica gel (Merck, Silica Gel 60, 4063
m) was used for column chromatography. Concentration
of Grignard reagents was determined by titration using
iodine. CCDC-1845171 contains the supplementary
crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif
General procedure for the preparation of boronates
2af: Dry THF (7 mL/mmol) was added to a mixture of
boronic acid (1 equiv), 2,2'-sulfinyl bis(4-methyl phenol)
(1d), and MgSO4 (7 equiv). The resultant mixture was
stirred for 20 h at ambient temperature, MgSO4 was
removed by filtration, solvents were evaporated under
reduce pressure affording pure boronates.
Scheme 3. The scope of a tandem Suzuki reaction.
2,2'-sulfinyl bis(4-methyl phenol) phenylboronic ester
(2a): Prepared from phenylboronic acid (0.854 g, 7.0 mmol),
2,2'-sulfinyl bis(4-methylphenol) (1.835 g, 7.0 mmol),
MgSO4 (8.43 g, 70.0 mmol), and dry THF (50 mL), white
1
solid (2.439 g, 100%); mp 222.1–223.5 °C; H NMR (300
MHz, CDCl3)  7.77 (dd, J = 1.8, 7.8 Hz, 2H), 7.40–7.25 (m,
5H), 7.11–7.05 (m, 4H), 2.30 (s, 6H); 13C NMR (75 MHz,
5
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10.1002/adsc.201801000
Advanced Synthesis & Catalysis
CDCl3)  152.9, 136.5, 131.8, 128.8, 127.7, 127.4, 125.2,
121.5, 114.9, 20.2; 11B NMR (160 MHz, CDCl3)  1.67;
HRMS (APCI) m/z calcd for C20H17BO3S [M+H]+:
349.1064, found 349.1068; Anal calcd for C20H17BO3S: C,
68.98; H, 4.92; S, 9.21, found C, 69.06; H, 4.94; S, 9.32.
calcd for C18H15BO3S2: C, 61.03; H, 4.27; S, 18.10, found
C, 61.10; H, 4.23; S, 18.66.
General procedure for the Suzuki reaction of boronates
2af: THF (5.0 mL/mmol) was added to a mixture of aryl
halide (1.0 equiv), boronate X (1.1 equiv), a palladium
catalyst (5 mol %). Then a solution of K3PO4 (3.0 mL/mmol,
1M solution in water) was added, and the resultant mixture
was stirred for 20 h at 60 °C. The crude reaction mixture
was diluted with ether (60 mL), washed with brine (20 mL),
solvents were evaporated under reduce pressure and column
chromatography (silicagel) afforded the title compound.
2,2'-Sulfinylbis(4-methylfenol)−4-bromophenylboronic
ester (2b): Prepared from 4-bromophenylboronic acid
(0.0231 g, 0.115 mmol), 2,2'-sulfinyl bis(4-methylphenol)
(0.0311g, 0.119 mmol), MgSO4 (0.1035 g, 0.86 mmol), and
dry THF (1 mL), white solid (0.0491 g, 100%); mp 226.9–
229.6 °C; 1H NMR (400 MHz, CDCl3)  7.66–7.61 (m, 2H),
7.50–7.45 (m, 2H), 7.27 (dd, J = 1.7 Hz, 8.5 Hz, 2H), 7.08
(d, J = 1.7 Hz, 2H), 7.05 (d, J = 8.5 Hz, 2H), 2.30 (s, 6H);
13C NMR (100 MHz, CDCl3):  152.7, 136.6, 133.7, 130.4,
129.0, 125.2, 122.2, 121.5, 114.9, 20.3; 11B NMR (160 MHz,
CDCl3)  1.71; HRMS (APCI) m/z calcd for C20H16BBrO3S
[M+H]+: 427.0169, found 427.0178; Anal calcd for
C20H16BBrO3S: C, 56.24; H, 3.78; S, 7.51, found C, 56.36;
H, 3.72; S, 7.56.
4-Phenylbenzaldehyde (3aa): Prepared from 4-
bromobenzaldehyde (0.0927 g, 0.50 mmol), boronate 2a
(0.1943 g, 0.56 mmol), PdCl2(XPhos)2 (0.0294 g, 0.026
mmol); hexane/EtOAc/THF (76/4/1); white solid (0.086 g,
1
94%); mp 55.5–56.7 °C; H NMR (300 MHz, CDCl3) 
10.07 (s, 1H), 7.98–7.94 (m, 2H), 7.79–7.74 (m, 2H), 7.67–
7.62 (m, 2H), 7.537.38 (m, 3H), in accordance with
reference.[20]
2,2'-Sulfinylbis(4-methylfenol)−4-(tert-
butyldimethylsilyloxy)phenylboronic
ester
(2c):
4-Acetylbiphenyl
(3ab):
Prepared
from
4’-
Prepared from 4-(tert-butyldimethylsilyloxy)phenylboronic
(1.768 g, 7.01 mmol), 2,2'-sulfinyl bis(4-methylphenol)
(1.839 g, 7.01 mmol), MgSO4 (5.90 g, 49.0 mmol), and dry
THF (50 mL), white solid (2.5185 g, 75%); mp 215.0–
220.0 °C; 1H NMR (400 MHz, CDCl3)  7.61 (d, J = 8.4 Hz,
2H), 7.27 (dd, J = 2.0 Hz, 8.4 Hz, 2H), 7.09–7.05 (m, 4H),
6.82 (d, J = 8.4 Hz, 2H), 2.30 (s, 6H), 0.98 (s, 9H), 0.18 (s,
6H); 13C NMR (100 MHz, CDCl3)  155.5, 153.2, 136.4,
133.1, 128.7, 125.2, 121.6, 119.3, 115.0, 25.8, 20.3, 18.2, -
4.4; 11B NMR (160 MHz, CDCl3)  1.82; HRMS (APCI)
m/z calcd for C26H31BO4SSi [M+H]+: 479.1878, found
479.1881; Anal calcd for C26H31BO4SSi: C, 65.27; H, 6.53;
S, 6.70, found C, 65.38; H, 6.51; S, 6.77.
bromoacetophenone (0.0998 g, 0.50 mmol), boronate 2a
(0.1922 g, 0.55 mmol), PdCl2(XPhos)2 (0.0294 g, 0.026
mmol); hexane/EtOAc (20/1); white solid (0.0931 g, 95%);
1
mp 119.0–121.5 °C; H NMR (300 MHz, CDCl3)  8.06–
8.02 (m, 2H), 7.71–7.62 (m, 4H), 7.54–7.39 (m, 3H), 2.64
(s, 3H), in accordance with reference.[20]
4-Fluorobiphenyl (3ac): Prepared from 1-bromo-4-
fluorobenzene (0.0879 g, 0.50 mmol), boronate 2a (0.1942
g, 0.56 mmol), PdCl2(XPhos)2 (0.0294 g, 0.026 mmol);
hexane/EtOAc (20/1); white solid (0.0680 g, 79%); mp
71.6–72.8 °C; 1H NMR (300 MHz, CDCl3)  7.58–7.51 (m,
4H), 7.47–7.40 (m, 2H), 7.38–7.32 (m, 1H), 7.16–7.09 (m,
2H), in accordance with reference.[21]
2,2'-Sulfinylbis(4-methylfenol)−4-fluorophenylboronic
ester (2d): Prepared from 4-fluorophenylboronic acid
(0.3022 g, 2.160 mmol), 2,2'-sulfinyl bis(4-methylphenol)
(0.5693 g, 2.170 mmol), MgSO4 (1.690 g, 14.0 mmol), and
dry THF (14 mL), white solid (0.7853 g, 99%); mp 241.4–
244.9 °C; 1H NMR (400 MHz, THF-d8)  7.61 (dd, J = 6.0
Hz, 8.4 Hz, 2H), 7.34–7.32 (m, 2H), 7.29 (dd, J = 2 Hz, 8.4
Hz, 2H), 6.97 (d, J = 8.4 Hz, 2H), 6.95–6.89 (m, 2H), 2.27
(s, 6H); 13C NMR (100 MHz, THF-d8)  163.8 (d, J = 242
Hz), 154.0, 137.0, 134.6 (d, J = 7.0 Hz), 129.5, 126.6, 121.9,
116.8, 114. 1 (d, J = 19 Hz), 20.3; 19F NMR (282 MHz,
THF-d8)  -116.1; 11B NMR (160 MHz, THF-d8)  1.35;
HRMS (APCI) m/z calcd for C20H16BFO3S [M+H]+:
367.0970, found 367.0979.
4-(4-cyanophenyl)benzaldehyde (3ed): Prepared from 4-
bromobenzaldehyde (0.0911 g, 0.49 mmol), boronate 2e
(0.2052 g, 0.55 mmol), PdCl2(XPhos)2 (0.0308 g, 0.027
mmol); hexane/EtOAc (4/1); yellow solid (0.0949 g, 93%);
mp 142.6–144.6 °C; 1H NMR (300 MHz, CDCl3)  10.09 (s,
1H), 8.03–7.98 (m, 2H), 7.81–7.71 (m, 6H), in accordance
with reference.[22]
4-Methylbiphenyl (3ae): Prepared from 4-bromobenzene
(0.0975 g, 0.57 mmol), boronate 2a (0.2666 g, 0.77 mmol),
PdCl2(MeCN)2 (0.0080 g, 0.031 mmol), DPPF (0.0171 g,
0.031 mmol); hexane; white solid (0.0650 g, 85%); mp
42.6–43.7 °C; 1H NMR (300 MHz, CDCl3)  7.60–7.56 (m,
2H), 7.52–7.47 (m, 2H), 7.46–7.40 (m, 2H), 7.35–7.30 (m,
1H), 7.28–7.22 (m, 2H), 2.40 (s, 3H), in accordance with
reference.[21]
2,2'-Sulfinylbis(4-methylfenol)−4-cyanophenylboronic
ester (2e): Prepared from 4-cyanophenylboronic acid
(0.4413 g, 3.0 mmol), 2,2'-sulfinyl bis(4-methylphenol)
(0.7887 g, 3.01 mmol), MgSO4 (4.22 g, 35.06 mmol), and
dry THF (20 mL), white solid (1.092 g, 98%); mp 233.0–
236.9 °C; 1H NMR (400 MHz, CDCl3)  7.84 (d, J = 8.0 Hz,
2H), 7.61 (d, J = 8.0 Hz, 2H), 7.29 (dd, J = 1.6 Hz, 8.4 Hz,
2H), 7.11–7.13 (m, 2H), 7.06 (d, J = 8.4 Hz, 2H), 2.31 (s,
6H); 13C NMR (100 MHz, CDCl3)  152.4, 148.0 (brs),
4-Methoxybiphenyl (3af): Prepared from 4-bromoanisole
(0.0928 g, 0.50 mmol), boronate 2a (0.1942 g, 0.56 mmol),
PdCl2(MeCN)2 (0.0076 g, 0.029 mmol), tert-
butyldifenylphosphine (0.0157 g, 0.065 mmol);
hexane/EtOAc (20/1); white solid (0.0820 g, 89%); mp
136.8, 132.4, 130.9, 129.3, 125.3, 121.4, 119.8, 114.8, 111.0, 85.7–86.5 °C; 1H NMR (300 MHz, CDCl3)  7.58–7.50 (m,
20.3; 11B NMR (160 MHz, CDCl3)  1.19; HRMS (APCI)
m/z calcd for C21H16BNO3S [M+H]+: 374.1017, found
374.1022; Anal calcd for C21H16BNO3S: C, 67.58; H, 4.32;
S, 8.59, found C, 67.24; H, 4.35; S, 8.33.
4H), 7.45–7.37 (m, 2H), 7.33–7.26 (m, 1H), 7.00–6.97 (m,
2H), 3.86 (s, 3H), in accordance with reference.[21]
4-(N,N-dimethylamino)biphenyl (3ag): Prepared from 4-
bromo-N,N-dimethylaniline (0.1027 g, 0.51 mmol),
boronate 2a (0.2065 g, 0.59 mmol), PdCl2(MeCN)2 (0.0084
g, 0.029 mmol), DTBPF (0.0152 g, 0.032 mmol);
2,2'-Sulfinylbis(4-methylfenol)−2-thienylboronic ester
(2f): Prepared from 2-thienylboronic acid (0.692 g, 5.41
mmol), 2,2'-sulfinyl bis(4-methylphenol) (1.418 g, 5.41
mmol), MgSO4 (6.51 g, 54.1 mmol), and dry THF (35 mL);
white solid (1.916 g, 100%); mp 231.8–233.6 °C; 1H NMR
(400 MHz, CDCl3)  7.42 (d, J = 4.0 Hz, 2H), 7.27 (dd, J =
2.4 Hz, 8.4 Hz, 2H), 7.15–7.12 (m, 1H), 7.10–7.06 (m, 4H),
2.30 (s, 6H); 13C NMR (100 MHz, CDCl3)  152.7, 136.6,
130.8, 129.1, 127.3, 125.6, 125.2, 121.6, 114.9, 20.3; 11B
NMR (160 MHz, CDCl3)  1.09; HRMS (APCI) m/z calcd
for C18H15BO3S2 [M+H]+: 355.0628, found 355.0627; Anal
1
hexane/EtOAc (20/1); white solid (0.0969 g, 96%); H
1
NMR (300 MHz, CDCl3)  H NMR (300 MHz, CDCl3) 
7.577.49 (m, 5H), 7.39 (m, 2H), 6.81 (d, J = 8.7Hz, 2H),
3.00 (s, 6H), in accordance with reference.[23]
1-(Biphenyl-4-yl)ethanol (3ah): Prepared from 1-(4-
bromophenyl)ethanol (0.0972 g, 0.48 mmol), boronate 2a
(0.1940 g, 0.56 mmol), PdCl2(MeCN)2 (0.0067 g, 0.026
mmol), tert-butyldiphenylphosphine (0.0135 g, 0.056
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801000
Advanced Synthesis & Catalysis
mmol); hexane/EtOAc (15/1); white solid (0.0890 g, 94%);
mp 85.7–86.5 °C; 1H NMR (300 MHz, CDCl3)  7.60–7.58
(m, 4H), 7.49–7.42 (m, 4H), 7.39–7.31 (m, 1H), 4.96 (q, J =
6.3 Hz, 1H), 1.55 (d, J = 6.3 Hz, 3H), in accordance with
reference.[24]
1-(4-Biphenyl)-1-phenylmethanol (5aa): Prepared from 4-
bromobenzaldehyde
(0.0960
g,
0.52
mmol),
phenylmagnesium chloride (0.43 mL, 0.77 mmol),
PdCl2(MeCN)2 (0.0063 g, 0.024 mmol), DTBPF (0.0116 g,
0.024 mmol), boronate 2a (0.1977 g, 0.57 mmol);
hexane/EtOAc (9/1); white solid (0.1291 g, 95%); mp 93.5–
95.0 °C; 1H NMR (300 MHz, CDCl3)  7.61–7.55 (m, 4H),
7.49–7.41 (m, 6H), 7.40–7.26 (m, 4H), 5.91 (d, J = 3.3 Hz,
1H), in accordance with reference.[30]
2-Phenylbenzaldehyde (3ai): Prepared from 2-
bromobenzaldehyde (0.0917 g, 0.50 mmol), boronate 2a
(0.1972 g, 0.57 mmol), PdCl2(MeCN)2 (0.0073 g, 0.028
mmol), tert-butyldiphenylphosphine (0.0244 g, 0.10 mmol);
hexane/EtOAc (20/1); yellow oil (0.0890 g, 98%); 1H NMR
(300 MHz, CDCl3)  9.99 (d, J = 0.9 Hz, 1H), 8.03 (dd, J =
1.5 Hz, 7.8 Hz, 1H), 7.65 (td, J = 1.5 Hz, 7.8 Hz, 1H), 7.53-
7.44 (m, 5H), 7.41–7.37 (m, 2H), in accordance with
reference.[25]
1-(4-Biphenyl)-2-(trimethylsilyl)ethanol (5ab): Prepared
from 4-bromobenzaldehyde (0.0985 g, 0.53 mmol),
(trimethylsilyl)methylmangesium chloride (0.8 mL, 0.80
mmol), PdCl2(MeCN)2 (0.0076 g, 0.029 mmol), DTBPF
(0.0143 g, 0.030 mmol), boronate 2a (0.2186 g, 0.63 mmol);
hexane/EtOAc (9/1); white solid (0.1264 g, 88%); mp 85.8–
87.5 °C; 1H NMR (400 MHz, CDCl3)  7.64–7.56 (m, 4H),
7.48–7.40 (m, 4H), 7.38–7.30 (m, 1H), 4.91 (t, J = 7.6 Hz,
1H), 1.87 (s, 1H), 1.27 (dq, J = 7.6 Hz, 15.2 Hz, 2H), -0.02
(s, 9H), the product slowly decomposed in deuterated
chloroform; 13C NMR (100 MHz, CDCl3)  145.5, 140.8,
140.4, 128.7, 127.2, 127.2, 127.0, 126.2, 72.6, 28.4, -1.1;
HRMS (ESI) m/z calcd for C17H22OSi [M+Na]+: 293.1332,
found 293.1333.
2-(2-thienyl)benzaldehyde (3aj): Prepared from 2-
bromobenzaldehyde (0.0903 g, 0.49 mmol), boronate 2a
(0.1986 g, 0.56 mmol), PdCl2(MeCN)2 (0.0072 g, 0.028
mmol), DPPF (0.0160 g, 0.029 mmol); hexane/EtOAc
1
(20/1); yellow oil (0.0890 g, 96%); H NMR (300 MHz,
CDCl3)  10.18 (s,1H), 8.03–7.98 (m, 1H), 7.65–7.43 (m,
4H), 7.17–7.11 (m, 1H), 7.09–7.05 (m, 1H), in accordance
with reference.[26]
1-(4-Biphenyl)-1-(4-chlorophenyl)methanol
(5ac):
2-Phenylthiophene
(3ak):
Prepared
from
2-
Prepared from 4-bromobenzaldehyde (0.0873 g, 0.47
mmol), 4-chlorophenylmangesium bromide (0.71 mL, 0.71
mmol), PdCl2(MeCN)2 (0.0060 g, 0.023 mmol), DTBPF
(0.0114 g, 0.024 mmol), boronate 2a (0.1954 g, 0.56 mmol);
hexane/EtOAc (20/1);white solid (0.1065 g, 77%); mp
bromothiophene (0.0782 g, 0.48 mmol), boronate 2a
(0.1994 g, 0.57 mmol), PdCl2(MeCN)2 (0.0070 g, 0.027
mmol), tert-butyldiphenylphosphine (0.0175 g, 0.072
mmol); hexane; white solid (0.0690 g, 90%); mp 32.6–
33.5 °C; 1H NMR (300 MHz, CDCl3)  7.65–7.60 (m, 2H),
7.417.35 (m, 2H), 7.337.27 (m, 3H), 7.107.07 (m, 1H),
in accordance with reference.[27]
1
102.2–103.0 °C; H NMR (400 MHz, CDCl3)  7.59–7.55
(m, 4H), 7.46–7.40 (m, 4H), 7.39–7.30 (m, 5H), 5.87 (s, 1H),
2.22 (brs, 1H); 13C NMR (100 MHz, CDCl3):  142.4, 142.1,
140.8, 140.6, 133.3, 128.8, 128.6, 127.9, 127.4, 127.1, 126.9,
75.4; HRMS (APCI) m/z calcd for C19H15ClO [M+H]+:
293.0739, found 293.0739.
3-Phenylpyridine (3al): Prepared from 3-bromopyridine
(0.0780 g, 0.49 mmol), boronate 2a (0.1987 g, 0.57 mmol),
PdCl2(MeCN)2 (0.0066 g, 0.025 mmol), tert-
butyldiphenylphosphine (0.0141 g, 0.058 mmol); the
reaction mixture was stirred for 20 h at 80 °C;
hexane/EtOAc (15/1); yellow oil (0.0650 g, 85%); 1H NMR
(300 MHz, CDCl3)  8.87–8.85 (m, 1H), 8.60 (dd, J = 1.5
Hz, 4.8 Hz, 1H), 7.90–7.86 (m, 1H), 7.60–7.57 (m, 2H),
7.51–7.45 (m, 2H), 7.44–7.34 (m, 2H), in accordance with
reference.[21]
1-(4-Biphenyl)-1-(4-fluorophenyl)methanol
(5ad):
Prepared from 4-bromobenzaldehyde (0.0977 g, 0.53
mmol), 4-fluorophenylmangesium bromide (0.91 mL, 0.79
mmol), PdCl2(MeCN)2 (0.0066 g, 0.025 mmol), DTBPF
(0.0123 g, 0.026 mmol), boronate 2a (0.2096 g, 0.60 mmol);
hexane/EtOAc (9/1); white solid (0.1195 g, 81%); mp 76.6–
78.9 °C; 1H NMR (400 MHz, CDCl3)  7.58 (d, J = 8.0 Hz,
4H), 7.47–7.33 (m, 7H), 7.05 (t, J = 8.8 Hz, 2H), 5.88 (s,
1H), 2.35 (s, 1H); 13C NMR (100 MHz, CDCl3):  162.2 (d,
J = 245 Hz), 142.6, 140.6, 139.5, 139.5, 128.8, 128.2 (d, J
= 8 Hz), 127.4, 127.3, 127.1, 126.9, 115.3 (d, J = 21 Hz),
75.4; HRMS (APCI) m/z calcd for C19H15FO [M-H]-:
277.1034, found 277.1034.
3-(2-Thienyl)pyridine (3fm): Prepared from 3-
bromopyridine (0.0782 g, 0.49 mmol), boronate 2f (0.1980
g, 0.56 mmol), PdCl2(MeCN)2 (0.0072 g, 0.028 mmol), tert-
butyldiphenylphosphine (0.0144 g, 0.059 mmol); the
reaction mixture was stirred for 20 h at 80 °C;
1
hexane/EtOAc (9/1); yellow oil (0.0765 g, 96%); H NMR
(300 MHz, CDCl3)  8.89 (s, 1H), 8.52 (s, 1H), 7.87 (d, J =
7.6 Hz, 1H), 7.38–7.35 (m, 2H), 7.34–7.27 (m, 1H), 7.14–
7.11 (m, 1H), in accordance with reference.[28]
1-(4-Biphenyl)-1-(4-(trifluoromethyl)phenyl)methanol
(5ae): Prepared from 4-bromobenzaldehyde (0.0926 g, 0.50
mmol), 4-(trifluoromethyl)phenylmangesium chloride (1.1
mL, 0.75 mmol), PdCl2(MeCN)2 (0.0071 g, 0.027 mmol),
DTBPF (0.0129 g, 0.027 mmol), boronate 2a (0.2044 g,
0.59 mmol); hexane/EtOAc (9/1);white solid (0.1640 g,
2,2’-Bithiophene (3fn): Prepared from 2-bromothiophene
(0.0820 g, 0.50 mmol), boronate 2f (0.1974 g, 0.56 mmol),
PdCl2(XPhos)2 (0.0366 g, 0.032 mmol); hexane; blue solid
1
100%); mp 95–97 °C; H NMR (400 MHz, CDCl3) 
1
(0.0399 g, 48%); mp 28.0–30.0 °C; H NMR (300 MHz,
7.647.59 (m, 3H), 7.59–7.54 (m, 5H), 7.47–7.41 (m, 4H),
7.35 (t, J = 7.2 Hz, 1H), 5.94 (s, 1H), 2.30 (brs, 1H); 13C
NMR (100 MHz, CDCl3):  147.4 (q, J = 1 Hz), 142.1, 141.0,
140.5, 129.7 (q, J = 32 Hz), 128.8, 127.5, 127.1, 126.6,
125.4 (q, J = 3 Hz), 124.1 (q, J = 270 Hz), 75.5; HRMS
(ESI) m/z calcd for C20H15F3O [M-H]-: 327.1002, found
327.1002.
CDCl3)  7.22–7.17 (m, 4H), 7.03–7.01 (m, 2H), in
accordance with reference.[29]
General procedure for a tandem Suzuki reaction:
A solution of Grignard reagent (1.5 equiv) was added to a
solution of 4-bromobenzaldehyde (1.0 equiv) in dry THF (4
mL) mmol cooled to -78 °C. The resultant mixture was
stirred for 1 h at ambient temperature and the reaction was
quenched with water (1.5 mL/mmol). The resultant mixture
was stirred for 10 min at ambient temperature, and
PdCl2(MeCN)2, DTBPF (5 mol %) boronate 2af (1.1
equiv) or boronic acid (1.2 equiv) was added. The resultant
mixture was stirred for 20 h at 60 °C. Then the mixture was
diluted with ether (40 mL), organic layer was washed with
NH4Cl, and brine. The organic layer was dry over MgSO4,
the solvents were removed under reduce pressure, and
column chromatography (silica gel) afforded the final
product.
1-(4-Biphenyl)-1-(3-thioanisolyl)methanol
(5af):
Prepared from 4-bromobenzaldehyde (0.0920 g, 0.50
mmol), 3-thioanysolylmangesium bromide (1.8 mL, 0.76
mmol), PdCl2(MeCN)2 (0.0065 g, 0.025 mmol), DTBPF
(0.0128 g, 0.027 mmol), boronate 2a (0.1987 g, 0.57 mmol);
hexane/EtOAc (9/1); white solid (0.1341 g, 88%); mp 99.8–
101.5 °C; 1H NMR (400 MHz, CDCl3)  7.60–7.55 (m, 4H),
7.67–7.41 (m, 4H), 7.38–7.32 (m, 2H), 7.29 (d, J = 7.6 Hz,
1H), 7.19–7.15 (m, 2H), 5.85 (s, 1H), 2.48 (s, 3H), 2.31 (brs,
1H); 13C NMR (100 MHz, CDCl3):  144.4, 142.5, 140.7,
140.6, 138.8, 129.0, 128.7, 127.3, 127.1, 127.0, 125.6, 124.5,
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801000
Advanced Synthesis & Catalysis
123.3, 75.9, 15.7; HRMS (APCI) m/z calcd for C20H18OS
[M-H]-: 305.1006, found 305.1005.
1-(4-Biphenyl)-1-phenylethan-1-ol (5al): Prepared from
4-bromoacetophenone
(0.0992
g,
0.50
mmol),
fenylmagnesium bromide (0.40 mL, 0.75 mmol),
PdCl2(MeCN)2 (0.0061 g, 0.024 mmol), DTBPF (0.0122 g,
0.026 mmol), boronate 2a (0.2031 g, 0.583 mmol);
hexane/EtOAc (6/1); white solid (0.112 g, 82%); mp 105.3–
107.0 °C; 1H NMR (400 MHz, CDCl3)  7.607.54 (m, 4H),
7.517.42 (m, 6H), 7.377.33 (m, 3H), 7.297.26 (m, 1H),
2.01 (s, CH3), in accordance with reference.[31]
1-(4-Biphenyl)-1-(3-methoxyphenyl)methanol
(5ag):
Prepared from 4-bromobenzaldehyde (0.0937 g, 0.51
mmol), 3-methoxyphenylmagnesium chloride (0.76 mL,
0.76 mmol), PdCl2(MeCN)2 (0.0062 g, 0.024 mmol),
DTBPF (0.0123 g, 0.026 mmol), boronate 2a (0.1974 g,
0.57 mmol); hexane/EtOAc (9/1); white solid (0.1308 g,
1
88%); mp 85.8–87.5 °C; H NMR (400 MHz, CDCl3) 
7.59–7.55 (m, 4H), 7.48–7.40 (m, 4H), 7.34 (tt, J = 1.2 Hz,
7.2 Hz, 1H), 7.30–7.25 (m, 1H), 7.02–6.98 (m, 2H), 6.85–
6.81 (m, 1H), 5.87 (s, 1H), 3.81 (s, 3H), 2.23 (brs, 1H); 13C
NMR (100 MHz, CDCl3)  159.8, 145.4, 142.7, 140.8,
140.5, 128.7, 127.27, 127.25, 127.1, 126.9, 118.9, 113.0,
112.1, 76.0, 55.2; HRMS (APCI) m/z calcd for C20H18O2
[M-H]-: 289.1234, found 289.1234.
1-(4’-Methoxybiphenyl-4-yl)-1-phenylmethanol (5m):
Prepared from 4-bromobenzaldehyde (0.1006 g, 0.54
mmol), phenylmangesium chloride (0.44 mL, 0.81 mmol),
PdCl2(MeCN)2 (0.0065 g, 0.025 mmol), DTBPF (0.0128 g,
0.027 mmol), 4-methoxyphenylboronic acid (0.0997 g, 0.66
mmol); hexane/EtOAc (9/1);white solid (0.1464 g, 93%);
1
mp 116–117 °C; H NMR (400 MHz, CDCl3)  7.55–7.49
(m, 4H), 7.43 (d, J = 8.0 Hz, 4H), 7.37 (t, J = 7.2 Hz, 2H),
7.29 (tt, J = 1.2, 7.6 Hz, 1H), 6.97 (d, J = 8.8 Hz, 2H), 5.88
(s, 1H), 3.85 (s, 3H), 2.29 (brs, 1H); 13C NMR (100 MHz,
CDCl3):  159.1, 143.8, 140.1, 133.3, 128.5, 128.0, 127.6,
126.9, 126.8, 126.5, 114.2, 76.0, 55.3; HRMS (APCI) m/z
calcd for C20H18O2 [M-H]-: 289.1234, found 289.1236.
1-(4-Biphenyl)-1-(2-methylphenyl)methanol
(5ah):
Prepared from 4-bromobenzaldehyde (0.0906 g, 0.49
mmol), 2-tolylmagnesium chloride (0.99 mL, 0.73 mmol),
PdCl2(MeCN)2 (0.0066 g, 0.025 mmol), DTBPF (0.0127 g,
0.027 mmol), boronate 2a (0.1974 g, 0.57 mmol);
hexane/EtOAc (9/1); colorless oil (0.1302 g, 97%); 1H
NMR (400 MHz, CDCl3)  7.65–7.58 (m, 5H), 7.51–7.37
1-(4’-Acetylbiphenyl-4-yl)-1-phenylmethanol
(5n):
(m, 5H), 7.34–7.23 (m, 2H), 7.23–7.19 (m, 1H), 6.04 (s, 1H), Prepared from 4-bromobenzaldehyde (0.0954 g, 0.52
2.50 (s, 1H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): 
mmol), phenylmangesium chloride (0.42 mL, 0.78 mmol),
141.8, 141.3, 140.7, 140.3, 136.3, 130.5, 128.7, 127.5, 127.2, PdCl2(MeCN)2 (0.0068 g, 0.026 mmol), DTBPF (0.0139 g,
127.1, 127.0, 126.2, 126.1, 73.0, 16.4; HRMS (APCI) m/z
0.029 mmol), 4-acetylphenylboronic acid (0.1040 g, 0.63
mmol); hexane/EtOAc (9/1);white solid (0.1488 g, 95%);
mp 131.0–133.5 °C; 1H NMR (400 MHz, CDCl3)  8.00 (d,
J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 8.4
Hz, 2H), 7.49 (d, J = 8.0 Hz, 2H), 7.44–7.40 (m, 2H), 7.36
(t, J = 7.2 Hz, 2H), 7.31–7.27 (m, 1H), 5.89 (s, 1H), 2.62 (s,
3H), 2.59 (s, 1H); 13C NMR (100 MHz, CDCl3):  197.8,
145.3, 143.9, 143.6, 138.9, 135.7, 128.9, 128.5, 127.7, 127.3,
127.0, 126.5, 75.9, 26.6; HRMS (ESI) m/z calcd for
C21H18O2 [M+Na]+: 325.1199, found 325.1201.
calcd for C20H18O [M-H]-: 273.1285, found 273.1286.
1-(4-Biphenyl)-1-(mesityl)methanol (5ai): Prepared from
4-bromobenzaldehyde
(0.0896
g,
0.48
mmol),
mesitylmangesium bromide (0.97 mL, 0.73 mmol),
PdCl2(MeCN)2 (0.0066 g, 0.025 mmol), DTBPF (0.0115 g,
0.024 mmol), boronate 2a (0.1952 g, 0.56 mmol);
hexane/EtOAc (20/1);white solid (0.1141 g, 79%); mp
76.6–78.9 °C; 1H NMR (400 MHz, CDCl3)  7.61–7.57 (m,
2H), 7.56–7.52 (m, 2H), 7.46–7.40 (m, 2H), 7.37–7.30 (m,
3H), 6.89 (s, 2H), 6.38 (s, 1H), 2.30 (s, 3H), 2.28 (s, 6H);
13C NMR (100 MHz, CDCl3):  142.2, 140.9, 139.4, 137.4,
137.0, 136.4, 130.1, 128.7, 127.1, 127.0, 126.9, 125.9, 70.9,
20.9, 20.6; HRMS (APCI) m/z calcd for C22H22O [M-H]-:
301.1598, found 301.1597.
1-[4’-(2-cyanoprop-2-yl)biphenyl-4-yl]-1-
phenylmethanol
(5o):
(0.0908
Prepared
g,
from
0.49
4-
mmol),
bromobenzaldehyde
phenylmangesium chloride (0.40 mL, 0.74 mmol),
PdCl2(MeCN)2 (0.0063 g, 0.024 mmol), DTBPF (0.0150 g,
0.032 mmol), 4-(2-cyanoprop-2-yl)phenylboronic acid
(0.1121 g, 0.59 mmol); hexane/EtOAc (9/1);white solid
1-(4-Biphenyl)-1-(2-thienyl)methanol (5aj): Prepared
from 4-bromobenzaldehyde (0.0916 g, 0.50 mmol), and 2-
thienylmagnesium chloride (3.4 mL, 0.75 mmol). After 1 h
at room temperature the solvents were removed under
reduce pressure, the crude reaction mixture was co-distilled
with toluene (2x3.5 mL), and dried in vacuo. Then
PdCl2(MeCN)2 (0.0069 g, 0.027 mmol), DTBPF (0.0128 g,
0.027 mmol), boronate 2a (0.2100 g, 0.60 mmol) and the
reaction was finished following the general procedure;
hexane/EtOAc (9/1); white solid (0.1255 g, 94%); mp 105–
109 °C; 1H NMR (400 MHz, CDCl3)  7.63–7.58 (m, 4H),
7.55–7.51 (m, 2H), 7.48–7.42 (m, 2H), 7.36 (tt, J = 1.2, 7.2
Hz, 1H), 7.29 (dd, J = 1.2, 4.8 Hz, 1H), 6.99–6.94 (m, 2H),
6.11 (d, J = 2.4 Hz, 1H), 2.47 (d, J = 2.4 Hz, 1H); 13C NMR
(100 MHz, CDCl3):  148.0, 142.1, 140.9, 140.7, 128.8,
127.34, 127.25, 127.1, 126.71, 126.68, 125.5, 124.9, 72.2;
HRMS (APCI) m/z calcd for C17H14OS [M-H]-: 265.0693,
found 265.0693.
1
(0.1586 g, 99%); mp 92.0–94.0 °C; H NMR (400 MHz,
CDCl3)  7.657.53 (m, 6H), 7.51–7.42 (m, 4H), 7.38 (t, J
= 7.2 Hz, 2H), 7.34–7.28 (m, 1H), 5.85 (s, 1H), 3.20 (s, 1H),
1.76 (s, 6H); 13C NMR (100 MHz, CDCl3):  143.7, 143.2,
140.1, 140.1, 139.0, 128.3, 127.3, 127.2, 126.9, 126.8, 126.4,
125.3, 124.3, 75.5, 36.7, 28.8; HRMS (APCI) m/z calcd for
C23H21NO [M-H]-: 326.1550, found 326.1551.
1-(4’-Methoxybiphenyl-4-yl)-1-phenylmethanol
(5p):
Prepared from 4-bromobenzaldehyde (0.0976 g, 0.53
mmol), 4-fluorophenylmangesium bromide (0.91 mL, 0.80
mmol), PdCl2(MeCN)2 (0.0078 g, 0.030 mmol), DTBPF
(0.0123 g, 0.026 mmol), 4-methoxyphenylboronic acid
(0.096 g, 0.63 mmol); hexane/EtOAc (4/1); white foam
1
(0.1546 g, 95%); H NMR (400 MHz, CDCl3)  7.557.49
(m, 4H), 7.417.37 (m, 4H), 7.067.02 (m, 2H), 6.996.96
(m, 2H), 5.87 (s, 1H), 3.85 (s, 3H); 13C NMR (100 MHz,
CDCl3):  162.1 (d, J = 245.2 Hz), 159.2, 142.0, 140.3,
139.5 (d, J = 2.3 Hz), 133.2, 128.3, 128.15, 128.06, 126.9,
115.3 (d, J = 21.9 Hz), 114.2, 75.4, 55.3. HRMS (APCI) m/z
calcd for C20H17FO2 [M-H]-: 307.1140, found 307.1140.
1[4'-(Tert-butyldimethylsilyloxy)biphenyl-4-yl]-1-
fenylmethanol (5ck): Prepared from 4-bromobenzaldehyde
(0.0924 g, 0.50 mmol), fenylmagnesium bromide (0.75 mL,
0.75 mmol), PdCl2(MeCN)2 (0.0070 g, 0.027 mmol),
DTBPF (0.0131 g, 0.028 mmol), boronate 2c (0.2765 g,
0.58 mmol); hexane/EtOAc (9/1); white solid (0.1862 g,
95%); mp 62.3–64.0°C; 1H NMR (400 MHz, CDCl3)  7.54
(d, J = 8.0 Hz, 2H), 7.50–7.40 (m, 6H), 7.37 (t, J = 7.2 Hz,
2H), 7.33–7.27 (m, 1H), 6.93 (d, J = 8.4 Hz, 2H), 5.87 (s,
1H), 2.41 (s, 1H), 1.04 (s, 9H), 0.27 (s, 6H); 13C NMR (100
MHz, CDCl3):  155.3, 143.7, 142.1, 140.1, 133.8, 128.5,
128.0, 127.5, 126.9, 126.8, 126.5, 120.3, 76.0, 18.2, -4.4;
HRMS (APCI) m/z calcd for C25H30O2Si [M-H]-: 389.1942,
found 389.1942.
4'-[(2-Butylbenzofuran-3-yl)(hydroxy)methyl]-[1,1'-
biphenyl]-4-ol: Prepared from aldehyde 6 (0.0898 g, 0.44
mmol), 4-bromophenylmagnesium bromide (0.75 mL, 0.67
mmol), boronate 2c (0.3601 g, 0.75 mmol), PdCl2(MeCN)2
(0.0058 g, 0.0022 mmol), DTBPF (0.0105 g, 0.022 mmol).
The crude product was treated with TBAF (0.54 mL, 0.54
mmol) in THF (2 mL) for 2 h at ambient temperature;
1
hexan/EtOAc (4/1); white foam (0.1295 g, 79%); H NMR
(300 MHz, CDCl3)  7.51 (s, 4H), 7.46 (d, J = 8.1 Hz, 4H),
7.227.17 (m, 1H), 7.127.07 (m, 1H), 6.88 (d, J = 8.1 Hz,
8
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10.1002/adsc.201801000
Advanced Synthesis & Catalysis
2H), 6.13 (s, 1H), 2.85 (t, J = 7.6 Hz, 2H), 2.13 (br s, 1H),
1.74 (pent, J = 7.6 Hz, 2H), 1.471.34 (m, 2H), 0.96 (t, J =
7.5 Hz, 3H); 13C NMR (126 MHz, CDCl3):  156.4, 155.4,
154.2, 140.8, 139.9, 133.3, 128.3, 127.2, 126.7, 126.5, 123.5,
122.4, 120.5, 116.5, 115.7, 110.8, 68.6, 30.6, 26.5, 22.5,
13.9; HRMS (APCI) m/z calcd for C25H24O3 [M-H]-:
371.1652, found 371.1653.
b) J. A. Gonzalez, O. M. Ogba, G. F. Morehouse, N.
Rosson, K. N. Houk, A. G. Leach, P. H. Y. Cheong, M.
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10671075; c) D. M. Knapp, E. P. Gillis, M. D. Burke,
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[10] Selected recent examples: a) N. A. Isley, Y. Wang, F.
Gallou, S. Handa, D. H. Aue, B. H. Lipshutz, ACS Catal.
2017, 7, 83318337; b) M. L. Lepage, S. Lai, N.
Peressin, R. Hadjerci, B. O. Patrick, D. M. Perring
Angew. Chem. Int. Ed. 2017, 56, 1525715261; c) Y. S.
Lee, C. H. Cheon, Adv. Synth. Catal. 2015, 357,
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D.-H. Tan, L. Yang, H. Wang, Angew. Chem. Int. Ed.
2016, 55, 1006910073.
Acknowledgements
Finacial support from the Grant Agency of the Czech Republic
(Grant No 18-12150S) is gratefully acknowledged.
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Advanced Synthesis & Catalysis
FULL PAPER
Bench-Stable Sulfoxide-Based Boronates:
Preparation and Application in a Tandem Suzuki
Reaction
Adv. Synth. Catal. Year, Volume, Page – Page
Marek Čubiňák, Václav Eigner, Tomáš Tobrman*
11
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