Palladium-catalyzed C-H arylation using aryltrifluoroborates in conjunction with a MnIII oxidant under mild conditions

Article abstract of DOI:10.1016/j.tet.2013.04.114

This paper describes the development of a mild Pd-catalyzed C-H arylation reaction using potassium aryltrifluoroborates in conjunction with Mn(OAc) ₃ as the oxidant. The scope of this transformation is explored with a variety of different aryltrifluoroborates and arylpyridine substrates. Preliminary mechanistic studies suggest that the reaction proceeds via a high-valent Pd mechanism with C-H activation occurring at or before the rate determining step.

Full text of DOI:10.1016/j.tet.2013.04.114

Tetrahedron 69 (2013) 5580e5587
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed CeH arylation using aryltrifluoroborates
in conjunction with a MnIII oxidant under mild conditions
*
Cydney K. Seigerman, Tiffiny M. Micyus, Sharon R. Neufeldt, Melanie S. Sanford
University of Michigan, Department of Chemistry, 930 N. University Ave., Ann Arbor, MI 48109, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
This paper describes the development of a mild Pd-catalyzed CeH arylation reaction using potassium
aryltrifluoroborates in conjunction with Mn(OAc)3 as the oxidant. The scope of this transformation is
explored with a variety of different aryltrifluoroborates and arylpyridine substrates. Preliminary mech-
anistic studies suggest that the reaction proceeds via a high-valent Pd mechanism with CeH activation
occurring at or before the rate determining step.
Received 22 April 2013
Accepted 24 April 2013
Available online 30 April 2013
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
additives are present, stir rate can be a major factor that impacts
reaction yield and scalability.13 Finally, the identification of oxidants
Palladium-catalyzed CeC bond-forming reactions serve as valu-
able synthetic methods for the formation of arylearyl linkages in
a wide variety of synthetic contexts.1 Traditional Pd-catalyzed cross-
coupling sequences suffer from the disadvantage that they require
two pre-functionalized starting materials. This necessitates the in-
dependent preparation of the two coupling partners, which can in-
crease the cost and the numberof steps required for the overall target
synthesis. In contrast, Pd-catalyzed CeH arylation reactions elimi-
nate the need for at least one prefunctionalization step, and thus can
serve as a more expedient strategy for arylearyl bond construction.2
Over the past 10 years, numerous Pd-catalyzed CeH arylation
reactions have been developed.3 Many different aryl coupling
partners have been utilized in these transformations, including
diaryliodonium salts,4 aryl halides,5 aryl CeH bonds,6 and organ-
ometallic reagents.7 Among these, arylboron compounds are par-
ticularly attractive for reasons that include their low toxicity, low
cost, and high stability.8 As such, a number of reports have explored
the use of arylboronic acids,9 arylboronate esters,10 and aryltri-
fluoroborates11 as coupling partners for the CeH arylation of sub-
strates bearing directing groups such as pyridines, anilides, benzoic
acids, and oximes. However, the vast majority of these reactions are
limited by the requirement for relatively high temperatures (usu-
ally ꢀ90 ꢁC).12 Furthermore, additives and promoters such as stoi-
chiometric bases, silver salts, and/or benzoquinone (BQ) are
generally required in all of these transformations. These features
can limit functional group tolerance and also render the reactions
operationally complex. For example, in reactions where insoluble
that are competent and compatible with these transformations can
also be a challenge. To date, the vast majority of reported examples
of Pd-catalyzed CeH arylation with arylboron reagents involve CuII-
or AgI-based oxidants and proceed via PdII/0 catalytic manifolds.
In response to these challenges, we sought to develop an op-
erationally simple and mild method for CeH arylation using readily
available arylboron reagents. Our efforts in this area were inspired
by our recent development of a related room temperature Pd-
catalyzed CeH alkylation reaction using alkyltrifluoroborate salts.
This transformation utilizes MnF3 as a stoichiometric oxidant
and proceeds at unprecedentedly low reaction temperatures
(Scheme 1).14 Unlike rare prior examples of Pd-catalyzed CeH al-
kylation with alkylboron reagents, the MnF3-mediated trans-
formation is believed to involve CeC bond-forming reductive
elimination from a high-valent Pd center. Notably, this alkylation
does not require the use of additives like benzoquinone, and it
proceeds readily at low temperatures (3e6 h at 25e40 ꢁC) under
only mildly acidic conditions. The current paper describes the de-
velopment, optimization, and scope of a related Pd-catalyzed CeH
arylation reaction involving aryltrifluoroborate salts in conjunction
* Corresponding author. Tel.: þ1 734 615 0451; e-mail address: mssanfor@
Scheme 1. Pd-catalyzed CeH alkylation with alkyltrifluoroborates in conjunction with
umich.edu (M.S. Sanford).
MnF3.14
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.04.114

C.K. Seigerman et al. / Tetrahedron 69 (2013) 5580e5587
5581
with a MnIII oxidant. Preliminary investigations of the mechanism
of this transformation are also presented.
with the reaction conditions (1j, 1k, and 1m). Interestingly ortho-
substituted 2-methoxyphenyltrifluoroborate provided the CeH
arylation product 1e in 71% yield, compared to a more modest
52% yield using the electronically similar para-substituted ana-
logue (1f).
2. Results and discussion
2.1. Reaction optimization
A range of substituted 2-arylpyridine derivatives could also be
arylated using this methodology. As shown in Table 3, good to ex-
cellent yields were obtained for arylpyridine substrates bearing
electron-donating substituents at the 20- or 40-position (2ae4a,
10a). More modest conversions and yields were attained with
substrates bearing electron-withdrawing groups on either the
arene or the pyridine ring. In some cases where significant starting
material remained at the end of the reaction, difficulty in separating
phenylated product from starting material led to low isolated yields
relative to the calibrated GC yields of the crude reaction mixture
(6a, 7a, and 13a). However, the low isolated yields of 11a and 12a
are comparable to the GC yields observed for the crude reaction
mixtures, and reflect inherently low reactivity/conversion of these
substrates under the standard conditions.
We first tested the Pd(OAc)2-catalyzed CeH arylation of 3-
methyl-2-phenylpyridine (1) with PhBF3K under the conditions
that had proven optimal for CeH alkylation with CH3BF3K
[0.10 equiv Pd(OAc)2, 4 equiv MnF3, 2 equiv RBF3K, 8:1:1 TFE/AcOH/
H2O (TFE¼2,2,2-trifluoroethanol), 40 ꢁC, 6 h]. As shown in Eq. 1, this
reaction provided the ortho-phenylated product 1a in moderate
yield (46%), along with a substantial quantity (14%) of the ortho-
acetoxylated product 1-OAc. Interestingly, however, the use of
a different MnIII oxidant [Mn(OAc)3] in place of MnF3 provided
a comparable yield of 1a (34%) without formation of the undesired
acetoxylated product 1-OAc. Consequently, all subsequent optimi-
zation studies were conducted with Mn(OAc)3 as the oxidant.
Increasing the reaction time to 18 h and the reaction tempera-
ture to 50 ꢁC using 2.5 equiv Mn(OAc)3 and 4 equiv PhBF3K pro-
vided a modest improvement in reaction yield (Table 1, entry 2 vs
entry 1). Evaluation of a number of solvent systems under these
conditions (entries 3e7) showed that a 1:1 mixture of TFE and
AcOH provided the highest yield of 1a at 50 ꢁC (77%, entry 7).
Lowering the temperature to 40 or 25 ꢁC resulted in a decrease in
yield and conversion (entries 8 and 9). The addition of 1 equiv of
NaOAc, an additive that is sometimes used to modulate alkene
oxidation reactions using Mn(OAc)3,15 had a negligible impact on
the yield and conversion with substrate 1 (compare entry 7 with
entry 10). Nevertheless, this additive was subsequently found to
provide an improvement in yield with some other substrates and
aryltrifluoroborates; consequently it was routinely added to the
scale-up reactions shown in Tables 2 and 3. The addition of 1 equiv
of benzoquinone, which is known to promote the reductive elimi-
nation step of PdII/0-catalyzed CeH arylation reactions, resulted in
a significant reduction in both yield and conversion (compare entry
7 with entry 11). Under the optimized reaction conditions, phe-
nylboronic acid, phenylboronic acid pinacol ester, and triphe-
nylboroxine were less effective arylating reagents than PhBF3K
(compare entry 7 with entries 12e14). Finally, as expected, no
product was formed in the absence of Pd (entry 15), and only trace
quantities of 1a could be detected when MnIII was excluded from
the reaction mixture (entry 16).
Table 1
Optimization of the Pd(OAc)2-catalyzed CeH phenylation of 1a
Entry
1c
2
3
4
5
6
7
Solvent
Temp (ꢁC)
Convb (%)
Yieldb (%)
TFE/AcOH/H2O (8:1:1)
TFE/AcOH/H2O (8:1:1)
TFE
40
50
50
50
50
50
50
40
25
50
50
50
50
50
50
50
73
68
34
76
81
77
84
73
35
86
56
60
82
51
6
34
56d
26
50d
55d
58d
77
70
30
77
34
50
60
38
0
AcOH
AcOH/H2O (9:1)
TFE/AcOH (9:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
TFE/AcOH (1:1)
8
9
10e
11f
12g
13h
14i
15e,j
16k
ꢂ 2
2
a
General conditions:
1 (1 equiv), Pd(OAc)2 (0.10 equiv), PhBF3K (4 equiv),
Mn(OAc)3 (2.5 equiv), solvent (0.067 M in 1), 18 h.
b
Determined by gas chromatographic analysis of the crude reaction mixture
2.2. Substrate scope
using neopentylbenzene as a standard.
c
Reaction run for 6 h using 4 equiv Mn(OAc)3 and 2 equiv PhBF3K.
CeH acetoxylation product (w3%) formed.
NaOAc (1 equiv) added.
Benzoquinone (1 equiv) added.
PhB(OH)2 (4 equiv) was used instead of PhBF3K.
Phenylboronic acid pinacol ester (4 equiv) was used instead of PhBF3K.
1,3,5-Triphenylboroxine (4 equiv) was used instead of PhBF3K.
CeH arylation of 1 proceeded smoothly using diverse aryltri-
fluoroborates (Table 2). Both electron-withdrawing and electron-
donating substituents on the ArBF3K reagent were well tolerated
in this transformation. In general, electron-neutral and electron-
rich aryltrifluoroborates provided the highest yields (between
52 and 80% for mono-arylation products 1ae1f and 1n). Poten-
tially sensitive iodide and aldehyde substituents were compatible
d
e
f
g
h
i
j
Control reaction without Pd.
k
Control reaction without MnIII
.

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C.K. Seigerman et al. / Tetrahedron 69 (2013) 5580e5587
Table 2
Palladium-catalyzed CeH arylation of 1 with diverse aryltrifluoroborate saltsa
a
Isolated yields.
2.3. Mechanistic studies
conversion, 7% yield). Notably, this reagent may effect CeC bond
formation, albeit in low yields, by promoting reductive elimination
from PdII (rather than serving to oxidize PdII).
A key mechanistic question in this arylation system concerns
the role of Mn(OAc)3. MnIII reagents have been previously utilized
as oxidants for CeH bond functionalization reactions proposed to
involve high-valent Pd-catalysis.14,16 Furthermore, our group has
recently reported a Pd-catalyzed CeH alkylation reaction employ-
ing alkyltrifluoroborates and MnF3 as a stoichiometric oxidant (Eq.
1, vide supra).14 Preliminary mechanistic evidence in that system
suggests that MnF3 serves as an oxidant for PdII. Based on this
precedent, we hypothesize that Mn(OAc)3 likely serves an analo-
gous role in the current arylation system.
To preliminarily probe this possibility, we examined the effect of
substituting Mn(OAc)3 with other oxidants under the optimized
reaction conditions. A number of oxidants commonly used to
promote PdII/0-catalyzed CeH arylation with organoboron com-
pounds were tested. As shown in Table 4, CuII and AgI-based oxi-
dants provided <10% conversion of 1 and <2% yield of the arylation
product 1a (entries 3e5). Low conversion was similarly observed
when benzoquinone was used in place of Mn(OAc)3 (entry 6, 17%
In marked contrast, a number of oxidants that are known to be
competent for the oxidation of PdII to PdIV were capable of pro-
moting this transformation.17 In particular, the hypervalent iodine
reagents PhI(OAc)2 and PhI(TFA)2 were highly effective oxidants,
providing near quantitative conversion and >80% yield of 1a (Table
4, entries 11 and 12). These results are consistent with a reaction
mechanism involving oxidation of a PdII intermediate by the
bystanding stoichiometric oxidant. Arylation using other known
oxidants for PdII, including N-chlorosuccinimide (NCS),18 N-fluoro-
2,4,6-trimethylpyridinium triflate (NFTPT),19 K2S2O8,20 and t-
BuOOH20 could also be achieved, albeit in modest yield (2e11%).
Notably, the use of these oxidants resulted in extensive side re-
actions of the starting material (32e100% conversion) to form an
ortho-chlorinated product (using NCS, entry 9, w22% yield) and/or
mixtures of other unidentified side products.
We also conducted experiments to determine the kinetic iso-
tope effect associated with this transformation. The intermolecular

C.K. Seigerman et al. / Tetrahedron 69 (2013) 5580e5587
5583
Table 3
Palladium-catalyzed CeH phenylation of diverse arylpyridine substratesa
a Isolated yields.
bGC yield (from crude reaction mixture) was 24%.
cGC yield (from crude reaction mixture) was 38%.
dGC yield (from crude reaction mixture) was 32%.
eGC yield (from crude reaction mixture) was 20%.
fGC yield (from crude reaction mixture) was 56%.
Table 4
conditions were employed, although the reactions were run at
a lower temperature (36 ꢁC) in order to more conveniently monitor
reaction progress. As shown in Fig. 1, the initial reaction rates were
significantly different for 1 versus 1-d5, with kH/kD¼8.3. This large
KIE is markedly different than that observed for a related Pd-
catalyzed CeH arylation of arylpyridines using diaryliodonium re-
agents (kH/kD¼1).21 In the latter system, the rate-limiting step was
shown to be oxidation of PdII to PdIV by Ph2Iþ, with CeH activation
taking place after the turnover-limiting step (i.e., the resting state of
the catalyst is a palladacycle). In contrast, the large KIE observed for
CeH arylation using ArBF3K and Mn(OAc)3 indicates that the
Evaluation of different oxidants for Pd-Catalyzed CeH phenylation of 1a
Entry
Oxidant
Convb (%)
Yieldb (%)
1
2
3
4
5
6
Mn(OAc)3
MnF3
AgCO3
Ag2O
Cu(OAc)2
BQ
84
95
ꢂ2
ꢂ2
16
77
57
ꢂ2
nd
nd
7
17
7
8
9
10
11
12
K2S2O8
t-BuOOH
NCS
NFTPT
PhI(OAc)2
PhI(OTFA)2
100
32
64
100
98
99
2
6
6c
11
83
91
a
Conditions: 1 (1 equiv), Pd(OAc)2 (0.10 equiv), PhBF3K (4 equiv), oxidant
(2.5 equiv), AcOH/TFE (1:1, 0.067 M in 1), 50 ꢁC, 18 h.
b
Determined by gas chromatographic analysis of the crude reaction mixture
using neopentylbenzene or hexadecane as an internal standard.
c
CeH chlorination product (w22%) formed.
kinetic isotope effect was established by comparing the initial
rates of phenylation of 3-methyl-2-phenylpyridine (1) and 3-
methyl-2-phenylpyridine-d5 (1-d5) (Eq. 2). The optimized reaction
Fig. 1. Initial rates of CeH arylation with 1 versus 1-d5.

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C.K. Seigerman et al. / Tetrahedron 69 (2013) 5580e5587
catalyst resting state under these conditions is not cyclometalated
and that CeH bond cleavage occurs before or during the turnover-
limiting step.
4.3. Instrumentation
NMR spectra were obtained on a Varian vnmrs 700 (699.76 MHz
for 1H; 175.95 MHz for 13C) and a Varian MR400 (376.87 MHz for
19F). 1H and 13C chemical shifts are reported in parts per million
(ppm) relative to TMS, with the residual solvent peak used as an
internal reference. Multiplicities are reported as follows: singlet (s),
doublet (d), doublet of doublets (dd), doublet of doublet of doublets
(ddd), triplet (t), quartet (q), and multiplet (m). IR spectra were
obtained on a PerkineElmer Spectrum BX FT-IR spectrometer.
Melting points were determined with a Mel-Temp 3.0, a Laboratory
Devices Inc, USA instrument, and are uncorrected. HRMS data were
obtained on a Micromass AutoSpec Ultima Magnetic Sector mass
spectrometer. Gas chromatography was performed on a Shimadzu
GC-17A equipped with a Restek RtxÓ-5 column (15 m, 0.25 mm ID,
ð2Þ
0.25 mm df) and an FID detector. GC yields are reported relative to
neopentylbenzene or hexadecane as an internal standard.
4.4. General procedures
4.4.1. General procedure A for isolated products. Substrate, solvent,
NaOAc, Pd(OAc)2, and Mn(OAc)3$2H2O were combined in a 20 mL
scintillation vial. The vial was sealed with a Teflon-lined cap and
heated at 50 ꢁC for 18 h with vigorous stirring. After cooling to room
temperature, the reaction mixture was diluted with EtOAc (50 mL)
and washed with 10 wt % aqueous Na2SO3 (1ꢃ15 mL), saturated
aqueous NaHCO3 (2ꢃ25 mL), and brine (1ꢃ10 mL). The combined
aqueous layers were extracted with EtOAc (2ꢃ25 mL). The organic
layers were then combined, dried over MgSO4, filtered, and con-
centrated to afford the crude product, which was purified by col-
umn chromatography on silica gel. The characterization data (1H
and 13C NMR spectra, IR, and melting points, where appropriate) for
previously reported products matched that reported in the
literature.
3. Conclusion
In summary, this paper describes the development of a mild Pd-
catalyzed CeH arylation reaction using aryltrifluoroborates in
conjunction with Mn(OAc)3. This transformation proceeds in good
yield for arylpyridine substrates bearing electron-donating sub-
stituents at the 20- and 40-positions, and moderate yields for sub-
strates bearing electron-withdrawing substituents. A variety of
substituted aryl groups can be installed using the corresponding
ArBF3K reagents. Preliminary mechanistic studies suggest that the
reaction likely involves high-valent Pd-catalysis and that CeH ac-
tivation occurs at or before the rate-determining step. Ongoing
work aims to elucidate the mechanistic details of this CeH aryla-
tion, as well as of the analogous CeH alkylation reactions.
4.4.2. General procedure B for kinetic experiments. Kinetics experi-
ments were run in 4 mL scintillation vials sealed with Teflon-lined
caps. Each data point within a kinetics run represents a reaction in
an individual vial, with each vial containing a constant concentration
of oxidant, catalyst, and substrate. The reported value of initial rate at
each time point is the average of three trials, and error is reported as
standard deviation. To Pd(OAc)2 (1.1 mg, 0.0050 mmol, 0.1 equiv) and
PhBF3K (36.8 mg, 0.20 mmol, 4 equiv) in a 4 mL vial was added
0.75 mL of a 0.067 M stock solution of substrate (0.050 mmol,
1 equiv) in AcOH/TFE (1:1), followed by Mn(OAc)3$H2O (33.5 mg,
0.125 mmol, 2.5 equiv). The reaction mixtures were heated to 36 ꢁC
under vigorous stirring on an aluminum heating-block. The
reaction mixtures were quenched after the indicated time by adding
0.5 mL of 10 wt % aqueous Na2SO3 and shaking vigorously. The crude
reaction mixtures were then diluted with EtOAc (3 mL), and neo-
pentylbenzene was added as an internal standard. The reactions
were analyzed by gas chromatography, and the calibrated GC yields
of products were determined relative to neopentylbenzene.
4. Experimental section
4.1. General
All reactions were performed with magnetic stirring in scintil-
lation vials. Flash chromatography was performed on EM Science
silica gel 60 (0.040e0.063 mm particle size, 230e400 mesh) and
thin layer chromatography was performed on Merck TLC plates
pre-coated with silica gel 60 F254
.
4.2. Materials
Pyridine substrates 7 and 8 were prepared according to litera-
ture procedures.22,23 Substrates 1e6 and 9 were synthesized via
Suzuki coupling of 2-bromo-3-methylpyridine with the corre-
sponding arylboronic acids.24 Pyridine substrates 11e13 were also
prepared Suzuki couplings of 2-bromopyridine derivatives with o-
tolylphenylboronic acid.24 Substrate 10 was prepared by Suzuki
coupling of 2-methoxyphenylboronic acid with 2-chloropyridine.25
Potassium 2,6-dimethylphenyltrifluoroborate and potassium 3-
acetylphenyltrifluoroborate were synthesized from the corre-
sponding boronic acids and KHF2.26 The rest of the aryltri-
fluoroborates were obtained from commercial sources (Alfa
Aesar, Aldrich, and Frontier Scientific). Pd(OAc)2, MnF3, and
Mn(OAc)3$2H2O were obtained from Pressure Chemical, Alfa Aesar,
and Strem, respectively. 2,2,2-Trifluoroethanol was obtained from
TCI America, and all other solvents were obtained from Fisher
Chemical. All commercial substrates, reagents, and solvents were
used as received and without further purification.
4.5. Characterization data for new compounds
4.5.1. 2-(30,50-Dimethyl-[1,10-biphenyl]-2-yl)-3-methylpyridine
(1b). General procedure A was followed using substrate 1 (85 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium 3,5-dimethyl
phenyltrifluoroborate (424 mg, 2.0 mmol, 4.0 equiv), and
Mn(OAc)3$2H2O (335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1;
7.5 mL total) at 50 ꢁC for 18 h. Product 1b was obtained as a clear
viscous liquid (110.0 mg, 81% yield, Rf¼0.12 in 80% hexanes/20%
Et2O). 1H NMR (700 MHz, C6D6):
J¼7.2, 1.5 Hz, 1H), 7.43 (dd, J¼7.4, 1.5 Hz, 1H), 7.27e7.21 (multiple
d
8.53 (d, J¼4.7 Hz, 1H), 7.52 (dd,

C.K. Seigerman et al. / Tetrahedron 69 (2013) 5580e5587
5585
peaks, 2H), 6.93 (s, 2H), 6.78 (d, J¼7.7 Hz, 1H), 6.65 (dd, J¼7.7, 4.7 Hz,
J¼7.9 Hz, 2H), 7.13 (dd, J¼7.6, 4.7 Hz, 1H), 1.80 (s, 3H). 13C{1H} NMR
1H), 6.62 (s, 1H), 2.02 (s, 6H), 1.67 (s, 3H). 13C{1H} NMR (176 MHz,
(176 MHz, CDCl3): d 232.3, 158.7, 147.0, 146.1, 139.6, 139.0, 138.0, 131.8,
CDCl3):
d
159.9, 146.5, 141.0, 140.9, 139.6, 137.5, 137.2, 131.8, 129.9,
131.6, 130.3, 130.0, 129.7, 128.8, 122.7, 119.0, 110.6, 19.0. IR (thin film):
2226.5 cmꢄ1. HRMS EI (m/z): [MþH]þ calcd for C19H15N2: 271.1235;
found: 271.1234.
129.8, 129.7, 128.4, 127.3, 122.0, 121.3, 21.3, 19.0. HRMS EI (m/z):
[MþH]þ calcd for C20H20N: 274.1590; found: 274.1593.
4.5.2. 2-(40-(tert-Butyl)-[1,10-biphenyl]-2-yl)-3-methylpyridine
(1c). General procedure A was followed using substrate 1 (85 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium 4-tert-butylphenyl-
trifluoroborate (480 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at
50 ꢁC for 18 h. Product 1c was obtained as a clear oil (115.8 mg, 77%
yield, Rf¼0.16 in 80% hexanes/20% Et2O). 1H NMR (700 MHz, acetone-
4.5.6. 20-(3-Methylpyridin-2-yl)-[1,10-biphenyl]-4-carbaldehyde
(1j). General procedure A was followed using substrate 1 (42 mg,
0.25 mmol, 1.0 equiv), Pd(OAc)2 (5.6 mg, 0.025 mmol, 0.10 equiv),
NaOAc (21 mg, 0.25 mmol, 1.0 equiv), potassium 4-formylphenyl
trifluoroborate (212 mg, 1.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(168 mg, 0.625 mmol, 2.5 equiv) in TFE/AcOH (1:1; 3.8 mL total) at
50 ꢁC for 18 h. Product 1j was obtained as a white solid (25.6 mg, 37%
yield, Rf¼0.07 in 60% hexanes/40% Et2O, mp¼126.1e127.8 ꢁC). 1H
d6):
d
8.43 (dd, J¼4.8, 1.1 Hz, 1H), 7.57e7.44 (multiple peaks, 2H), 7.43
NMR (700 MHz, CDCl3):
d
9.94 (s, 1H), 8.49 (d, J¼4.8 Hz, 1H), 7.68 (d,
(td, J¼7.5, 1.8 Hz, 1H), 7.38 (dd, J¼7.6, 1.1 Hz, 1H), 7.32 (dd, J¼7.6, 1.1 Hz,
1H), 7.22 (d, J¼8.6 Hz, 2H), 7.15 (dd, J¼7.7, 4.8 Hz, 1H), 7.06 (d,
J¼8.6 Hz, 2H), 1.74 (s, 3H), 1.24 (s, 9H). 13C{1H} NMR (176 MHz, CDCl3):
J¼8.4 Hz, 2H), 7.53e7.47 (multiple peaks, 3H), 7.44 (m, 1H), 7.33 (d,
J¼7.6 Hz, 1H), 7.29 (d, J¼8.2 Hz, 2H), 7.12 (dd, J¼7.6, 4.8 Hz, 1H), 1.80 (s,
3H). 13C{1H} NMR (176 MHz, CDCl3):
d 192.2, 158.9, 147.7, 146.9, 139.7,
d
159.8, 149.6, 146.7, 140.6, 139.5, 138.2, 137.5, 131.8, 130.1, 129.8, 128.9,
139.5, 137.9, 134.7, 131.7, 130.3, 130.0, 129.8, 129.4, 128.7, 128.6, 122.6,
19.0. IR (thin film): 1701.6,1604.9 cmꢄ1. HRMS EI (m/z): [MþH]þ calcd
for C19H16NO: 274.1226; found: 274.1225.
128.4, 127.3, 124.8, 122.2, 34.5, 31.4, 18.9. HRMS EI (m/z): [MþH]þ
calcd for C22H24N: 302.1903; found: 302.1907.
4.5.3. 2-(20-Methoxy-[1,10-biphenyl]-2-yl)-3-methylpyridine (1e).
General procedure A was followed using substrate 1 (85 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium 2-methoxy
phenyltrifluoroborate (428 mg, 2.0 mmol, 4.0 equiv), and
Mn(OAc)3$2H2O (335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1;
7.5 mL total) at 50 ꢁC for 18 h. Product 1e was obtained as a pale
yellow liquid (98.2 mg, 71% yield, Rf¼0.17 in 60% hexanes/40%
4.5.7. 2-(30-Fluoro-[1,10-biphenyl]-2-yl)-3-methylpyridine (1l). General
procedure A was followed using substrate 1 (94 mg, 0.50 mmol,
1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv), NaOAc (41 mg,
0.50 mmol, 1.0 equiv), potassium 3-fluorophenyltrifluoroborate
(404 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O (335 mg,
1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at 50 ꢁC for 18 h.
Product 1l was obtained as a greasy yellow solid (75.3 mg, 57% yield,
Rf¼0.13 in 80% hexanes/20% Et2O). 1H NMR (700 MHz, CDCl3):
d 8.49
Et2O). 1H NMR (700 MHz, C6D6):
d
8.40 (dd, J¼4.8, 1.1 Hz, 1H), 7.53
(d, J¼4.6 Hz,1H), 7.50e7.43 (multiple peaks, 3H), 7.40 (d, J¼7.0 Hz, 1H),
7.34 (d, J¼7.7 Hz, 1H), 7.41e7.09 (multiple peaks, 2H), 6.90e6.82
(multiple peaks, 3H), 1.80 (s, 3H). 13C{1H} NMR (176 MHz, CDCl3):
(dd, J¼7.7, 1.1 Hz, 1H), 7.50 (dd, J¼7.5, 1.1 Hz, 1H), 7.27e7.20 (mul-
tiple peaks, 3H), 6.95 (td, J¼8.0, 1.8 Hz, 1H), 6.83 (dd, J¼7.7, 1.1 Hz,
1H), 6.67 (t, J¼7.5 Hz, 1H), 6.57 (dd, J¼7.8, 4.8 Hz, 1H), 6.43 (d,
J¼8.0 Hz, 1H), 3.12 (s, 3H), 1.87 (s, 3H). 13C{1H} NMR (176 MHz,
d
162.4 (d, 1JCeF¼245.3 Hz), 159.2, 146.8, 143.5 (d, 3JCeF¼7.5 Hz), 139.6,
139.5 (d, 4JCeF¼2.0 Hz), 137.7, 131.7, 130.1, 129.7, 129.3 (d, 3JCeF¼8.6 Hz),
4
2
CDCl3):
d
159.6, 156.1, 146.1, 140.4, 137.6, 137.2, 132.2, 131.6, 131.1,
128.6, 128.1, 125.2 (d, JCeF¼2.9 Hz), 122.4, 116.2 (d, JCeF¼21.4 Hz),
130.0, 129.7, 128.4, 127.7, 127.3, 121.7, 120.1, 110.4, 55.0, 18.9. HRMS
113.7 (d, 2JCeF¼21.0 Hz), 19.0 19F{1H} NMR (377 MHz, CDCl3):
ꢄ113.7
d
EI (m/z): [MþH]þ calcd for C19H18NO: 276.1383; found: 276.1384.
(m, 1F). HRMS EI (m/z): [MþH]þ calcd for C18H15FN: 264.1183; found:
264.1186.
4.5.4. 2-(30-Nitro-[1,10-biphenyl]-2-yl)-3-methylpyridine (1g). General
procedure A was followed using substrate 1 (85 mg, 0.50 mmol,
1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv), NaOAc (41 mg,
0.50 mmol, 1.0 equiv), potassium 3-nitrophenyltrifluoroborate
(458 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O (335 mg,
1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at 50 ꢁC for 18 h.
Product 1g was obtained as a pale yellow solid (79.3 mg, 55% yield,
Rf¼0.13 in 60% hexanes/40% Et2O, mp¼75.7e76.5 ꢁC). 1H NMR
4.5.8. 2-(40-Iodo-[1,10-biphenyl]-2-yl)-3-methylpyridine(1m). General
procedure A was followed using substrate 1 (85 mg, 0.50 mmol,
1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv), NaOAc (41 mg,
0.50 mmol, 1.0 equiv), potassium 4-iodophenyltrifluoroborate
(608 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O (335 mg,
1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at 50 ꢁC for 18 h.
Product 1m was obtained as a white solid (87.5 mg, 41% yield, Rf¼0.11
in 80% hexanes/20% Et2O, mp¼108.6e113.9 ꢁC). 1H NMR (700 MHz,
(700 MHz, acetone-d6):
d
8.43 (dd, J¼4.8, 1.1 Hz, 1H), 8.06 (ddd, J¼8.2,
2.4, 1.0 Hz, 1H), 7.97 (t, J¼2.0 Hz, 1H), 7.62e7.55 (multiple peaks, 4H),
7.51 (t, J¼8.0 Hz, 1H), 7.47 (d, J¼7.7 Hz, 1H), 7.44 (d, J¼7.4 Hz, 1H), 7.18
(dd, J¼7.7, 4.8 Hz, 1H), 1.85 (s, 3H). 13C{1H} NMR (176 MHz, CDCl3):
C6D6):
d
8.55 (d, J¼4.6 Hz, 1H), 7.52 (m, 1H), 7.36 (d, J¼8.4 Hz, 2H),
7.30e7.27 (multiple peaks, 3H), 6.87 (d, J¼8.4 Hz, 2H), 6.82 (d,
J¼7.8 Hz, 1H), 6.71 (dd, J¼7.7, 4.6 Hz, 1H), 1.65 (s, 3H). 13C{1H} NMR
d
158.6, 148.0, 147.0, 142.8, 139.7, 138.3, 138.0, 135.4, 131.6, 130.2, 129.7,
(176 MHz, CDCl3): d 159.2, 146.8, 140.8, 139.6, 139.5, 137.8, 137.1, 131.7,
128.9, 128.8, 128.7, 124.1, 122.7, 121.7, 19.0. IR (thin film): 1527.2,
1349.5 cmꢄ1. HRMS EI (m/z): [MþH]þ calcd for C18H15N2O2: 291.1128;
found: 291.1133.
131.3, 130.1, 129.6, 128.6, 128.0, 122.4, 92.8, 19.0. HRMS EI (m/z):
[MþH]þ calcd for C18H15IN: 372.0244; found: 372.0245.
4.5.9. 2-(30-Methoxy-[1,10-biphenyl]-2-yl)-3-methylpyridine
(1n). General procedure A was followed using substrate 1 (85 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium 3-methoxyphenyl
trifluoroborate (428 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at 50 ꢁC
for 18 h. Product 1n was obtained as a pale yellow liquid (102.0 mg, 74%
4.5.5. 2-(40-Cyano-[1,10-biphenyl]-2-yl)-3-methylpyridine (1h). General
procedure A was followed using substrate 1 (85 mg, 0.50 mmol,
1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv), NaOAc (41 mg,
0.50 mmol, 1.0 equiv), potassium 4-cyanophenyltrifluoroborate
(418 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O (335 mg,
1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at 50 ꢁC for 18 h.
Product 1h was obtained as a pale yellow solid (65.2 mg, 48% yield,
Rf¼0.10 in 60% hexanes/40% Et2O, mp¼153.6e157.4 ꢁC). 1H NMR
1
yield, Rf¼0.18 in 60% hexanes/40% Et2O). H NMR (700 MHz, C6D6):
d
8.51 (d, J¼4.7 Hz, 1H), 7.59e7.43 (multiple peaks, 3H), 7.40 (d,
(700 MHz, CDCl3):
2H), 7.47e7.41 (multiple peaks, 4H), 7.36 (d, J¼7.7 Hz, 1H), 7.22 (d,
d
8.46 (d, J¼4.7 Hz, 1H), 7.53e7.49 (multiple peaks,
J¼7.4 Hz, 1H), 7.31 (d, J¼7.8 Hz, 1H), 7.13e7.09 (multiple peaks, 2H),
6.80 (d, J¼7.6 Hz, 1H), 6.72 (dd, J¼8.2, 2.5 Hz, 1H), 6.59 (s, 1H), 3.55 (s,

5586
C.K. Seigerman et al. / Tetrahedron 69 (2013) 5580e5587
3H), 1.77 (s, 3H). 13C{1H} NMR (176 MHz, CDCl3):
142.6, 140.6, 139.6, 137.6, 132.0, 130.0, 129.7, 129.0, 128.5, 127.7, 122.3,
121.7, 114.4, 113.4, 55.1, 19.0. HRMS EI (m/z): [MþH]þ calcd for
C19H18NO: 276.1388; found: 276.1389.
d
159.8, 159.0, 146.6,
7.99 (s, 1H), 7.96 (d, J¼7.8 Hz, 1H), 7.59 (d, J¼7.8 Hz, 1H), 7.33 (d,
J¼7.8 Hz, 1H), 7.23e7.17 (multiple peaks, 3H), 7.16e7.12 (multiple
peaks, 3H), 1.76 (s, 3H). 13C{1H} NMR (176 MHz, CDCl3):
d 192.2,
158.3, 146.9, 145.5, 141.9, 139.8, 137.9, 136.4, 131.6, 131.4, 131.1, 129.3,
128.6, 128.2, 127.5, 122.8, 18.8. IR (thin film): 1697.8 cmꢄ1. HRMS EI
(m/z): [MþH]þ calcd for C19H16NO: 274.1226; found: 274.1232.
4.5.10. 2-(5-(tert-Butyl)-[1,10-biphenyl]-2-yl)-3-methylpyridine
(2a). General procedure A was followed using substrate 2 (113 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phenyl-
trifluoroborate (368 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at
50 ꢁC for 18 h. Product 2a was obtained as a pale yellow solid
(130.0 mg, 86% yield, Rf¼0.15 in 80% hexanes/20% Et2O,
4.5.14. 2-(5-Chloro-[1,10-biphenyl]-2-yl)-3-methylpyridine
(7a). General procedure A was followed using substrate 7 (102 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phenyl-
trifluoroborate (368 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at
50 ꢁC for 18 h. Product 7a was obtained as a clear viscous oil (19.5 mg,
14% yield, Rf¼0.08 in 88% hexanes/12% Et2O). 1H NMR (700 MHz,
mp¼129.6e133.0 ꢁC). 1H NMR (700 MHz, C6D6):
8.53 (d, J¼4.8 Hz,
d
1H), 7.59 (d, J¼2.0 Hz, 1H), 7.53 (d, J¼8.0 Hz, 1H), 7.37e7.32 (mul-
tiple peaks, 3H), 7.03e6.99 (multiple peaks, 2H), 6.95 (dd, J¼7.1,
1.0 Hz, 1H), 6.78 (dd, J¼7.7, 1.0 Hz, 1H), 6.64 (dd, J¼7.7, 4.8 Hz, 1H),
CDCl3):
d
8.49 (d, J¼4.5, 1H), 7.46 (d, J¼2.1 Hz, 1H), 7.42 (dd, J¼8.2,
2.1 Hz, 1 H), 7.35 (d, J¼8.1 Hz, 1H), 7.30 (d, J¼7.3, 1H), 7.20e7.14
1.67 (s, 3H), 1.26 (s, 9H). 13C{1H} NMR (176 MHz, CDCl3):
d 159.7,
(multiple peaks, 3H), 7.13e7.07 (multiple peaks, 3H), 1.74 (s, 3H). 13C
151.3, 146.7, 141.9, 140.3, 137.5, 136.7, 131.8, 129.7, 129.4, 127.9, 126.8,
126.5, 124.6, 122.0, 34.8, 31.5, 19.1. HRMS EI (m/z): [MþH]þ calcd for
C22H24N: 302.1909; found: 302.1903.
{1H} NMR (176 MHz, CDCl3):
d 158.5, 146.9, 142.5, 139.9, 138.1, 137.7,
134.2,131.8,131.5,129.7, 129.2,128.1,127.6,127.3,122.5, 18.9. HRMS EI
(m/z): [MþH]þ calcd for C18H15ClN: 280.0888; found: 280.0893.
4.5.11. 2-(5-Methoxy-[1,10-biphenyl]-2-yl)-3-methylpyridine
(4a). General procedure A was followed using substrate 4 (100 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phenyl-
trifluoroborate (368 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at
50 ꢁC for 18 h. Product 4a was obtained as a clear oil (102.1 mg, 71%
yield, Rf¼0.14 in 60% hexanes/40% Et2O). 1H NMR (700 MHz, C6D6):
4.5.15. 2-(4-Bromo-[1,10-biphenyl]-2-yl)-3-methylpyridine
(8a). General procedure A was followed using substrate 8 (124 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phenyltrifluoroborate
(368 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O (335 mg,
1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at 50 ꢁC for 18 h.
Product 8a was obtained as a white solid (74.3 mg, 46% yield, Rf¼0.29
in 80% hexanes/20% Et2O, mp¼84.7e88.2 ꢁC). 1H NMR (700 MHz,
d
8.53 (d, J¼4.7 Hz, 1H), 7.44 (d, J¼8.4 Hz, 1H), 7.28 (multiple peaks,
C6D6):
d
8.42 (d, J¼4.6 Hz, 1H), 7.65 (d, J¼2.0 Hz, 1H), 7.32 (dd, J¼8.3,
2H), 7.06 (d, J¼2.7, 1H), 6.99e6.90 (multiple peaks, 3H), 6.84 (dd,
J¼8.3, 2.7 Hz, 1H), 6.78 (d, J¼7.5 Hz, 1H), 6.64 (dd, J¼7.5, 4.8 Hz, 1H),
2.0 Hz, 1H), 7.10 (d, J¼7.1 Hz, 2H), 6.97e6.88 (multiple peaks, 4H), 6.69
(d, J¼7.6, 1H), 6.60 (dd, J¼7.8, 4.7 Hz, 1H), 1.49 (s, 3H). 13C{1H} NMR
3.34 (s, 3H), 1.68 (s, 3H). 13C{1H} NMR (176 MHz, CDCl3):
d
159.6,
(176 MHz, CDCl3): d 157.9, 146.7, 141.2, 139.9, 139.6, 137.7, 132.8, 131.6,
159.4, 146.7, 142.1, 141.2, 137.5, 132.3, 132.0, 131.3, 129.3, 127.9, 126.9,
122.0, 115.1, 113.1, 55.5, 19.0. HRMS EI (m/z): [MþH]þ calcd for
C19H18NO: 276.1383; found: 276.1385.
131.4, 131.2, 129.0, 127.9, 127.0, 122.5, 121.4, 18.7. HRMS EI (m/z):
[MþH]þ calcd for C18H15BrN: 324.0388; found: 324.0384.
4.5.16. 2-(4-Methoxy-[1,10-biphenyl]-2-yl)-3-methylpyridine
(9a). General procedure A was followed using substrate 9 (100 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phenyl-
trifluoroborate (368 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at
50 ꢁC for 18 h. Product 9a was obtained as a pale yellow oil (51.9 mg,
38% yield, Rf¼0.18 in 60% hexanes/40% Et2O). 1H NMR (700 MHz,
4.5.12. 2-(5-Fluoro-[1,10-biphenyl]-2-yl)-3-methylpyridine (5a).
General procedure A was followed using substrate 5 (94 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phenyl-
trifluoroborate (368 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at
50 ꢁC for 18 h. Product 5a was obtained as a white powder (60.5 mg,
46% yield, Rf¼0.13 in 80% hexanes/20% Et2O, mp¼97.2e99.4 ꢁC). 1H
CDCl3):
d
8.51 (d, J¼4.9 Hz, 1H), 7.38 (d, J¼8.6 Hz, 1H), 7.29 (d,
NMR (700 MHz, C6D6):
d
8.47 (d, J¼4.8 Hz, 1H), 7.25 (dd, J¼8.2,
J¼7.7 Hz, 1H), 7.15e7.12 (multiple peaks, 3H), 7.10 (dd, J¼7.7, 4.9 Hz,
1H), 7.09e7.06 (multiple peaks, 2H), 7.03 (dd, J¼8.6, 2.7 Hz, 1H),
6.94 (d, J¼2.7 Hz, 1H), 3.37 (s, 3H), 1.75 (s, 3H). 13C{1H} NMR
6.0 Hz, 1H), 7.08 (d, J¼7.5 Hz, 2H), 7.07 (dd, J¼9.9, 2.3 Hz, 1H),
6.94e6.87 (multiple peaks, 3H), 6.85 (td, J¼8.4, 2.6 Hz, 1H), 6.74 (d,
J¼7.6 Hz, 1H), 6.62 (dd, J¼7.6, 4.8 Hz, 1H), 1.54 (s, 3H). 13C{1H} NMR
(176 MHz, CDCl3):
d 159.5, 159.0, 146.7, 140.9, 140.6, 137.7, 133.6,
(176 MHz, CDCl3):
d
162.7 (d, 1JCeF¼246.8 Hz), 158.7, 146.8, 142.9 (d,
131.7, 131.1, 129.3127.9, 126.3, 122.3, 114.8, 114.7, 55.6, 18.9. HRMS EI
3JCeF¼7.5 Hz), 140.1 (d, 4JCeF¼2.1 Hz), 137.7, 135.7 (d, 4JCeF¼3.2 Hz),
(m/z): [MþH]þ calcd for C19H18NO: 276.1383; found: 276.1384.
3
131.9, 131.8 (d, JCeF¼8.5 Hz), 129.2, 128.1, 127.3, 122.4, 116.5 (d,
2JCeF¼21.8 Hz), 114.4 (d, JCeF¼21.5 Hz), 18.9. 19F{1H} NMR
4.5.17. 2-(3-Methyl-[1,10-biphenyl]-2-yl)-5-(trifluoromethyl)pyridine
(13a). General procedure A was followed using substrate 14
(137 mg, 0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol,
0.10 equiv), NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phe-
nyltrifluoroborate (368 mg, 2.0 mmol, 4.0 equiv), and
Mn(OAc)3$2H2O (335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1;
7.5 mL total) at 50 ꢁC for 18 h. Product 13a was obtained as pale
yellow needles (45.5 mg, 29% yield, Rf¼0.29 in 94% hexanes/6%
2
(377 MHz, C6D6):
d
ꢄ114.3 (m, 1F). HRMS EI (m/z): [MþH]þ calcd for
C18H15FN: 264.1183; found: 264.1189.
4.5.13. 6-(3-Methylpyridin-2-yl)-[1,10-biphenyl]-3-carbaldehyde
(6a). General procedure A was followed using substrate 6 (99 mg,
0.50 mmol, 1.0 equiv), Pd(OAc)2 (11 mg, 0.050 mmol, 0.10 equiv),
NaOAc (41 mg, 0.50 mmol, 1.0 equiv), potassium phenyl-
trifluoroborate (368 mg, 2.0 mmol, 4.0 equiv), and Mn(OAc)3$2H2O
(335 mg, 1.25 mmol, 2.5 equiv) in TFE/AcOH (1:1; 7.5 mL total) at
50 ꢁC for 18 h. Product 6a was obtained as a white solid (13.5 mg,
10% yield, Rf¼0.09 in 80% hexanes/20% Et2O, mp¼105.4e106.4 ꢁC).
Et2O, mp¼101.3e104.3 ꢁC). 1H NMR (700 MHz, acetone-d6):
d 8.94
(s, 1H), 7.91 (dd, J¼8.3, 2.2 Hz, 1H), 7.42 (t, J¼7.6 Hz, 1H), 7.35 (d,
J¼7.7 Hz, 1H), 7.28 (d, J¼7.7 Hz, 1H), 7.19e7.12 (multiple peaks, 4H),
7.07e7.03 (multiple peaks, 2H), 2.13 (s, 3H). 13C{1H} NMR (176 MHz,
1H NMR (700 MHz, CDCl3):
d
10.13 (s, 1H), 8.52 (d, J¼4.5 Hz, 1H),
CDCl3):
d
163.6, 145.9 (q, JCeF¼4.2 Hz), 141.4, 141.2, 138.2, 136.7,
3

C.K. Seigerman et al. / Tetrahedron 69 (2013) 5580e5587
5587
132.9 (q, 3JCeF¼3.4 Hz), 129.8, 129.7, 128.8, 128.0, 127.9, 126.8, 125.6,
124.3 (q, 2JCeF¼34 Hz), 123.8 (q, 1JCeF¼272.8 Hz), 20.6. 19F{1H} NMR
272; (m) Salvanna, N.; Reddy, G. C.; Das, B. Tetrahedron 2013, 69, 2220; (n) Gao, D.-
W.; Shi, Y.-C.; Gu, Q.; Zhao, Z.-L.; You, S.-L. J. Am. Chem. Soc. 2013, 135, 86.
10. (a) Giri, R.; Maugel, N.; Li, J.-J.; Wang, D.-H.; Breazzano, S. P.; Saunders, L. B.; Yu,
J.-Q. J. Am. Chem. Soc. 2007, 129, 3510; (b) Romero-Revilla, J. A.; García-Rubia, A.;
(377 MHz, CDCl3):
d
ꢄ62.8. (s, 3F). HRMS EI (m/z): [MþH]þ calcd for
ꢀ
ꢀ
ꢀ
ꢀ~
Arrayas, R.; Fernandez-Ibanez, M. A.; Carretero, J. C. J. Org. Chem. 2011, 76, 9525;
(c) Wasa, M.; Chan, K. S. L.; Yu, J.-Q. Chem. Lett. 2011, 40, 1004.
11. (a) Ge, H.; Niphakis, M. J.; Georg, G. I. J. Am. Chem. Soc. 2008,130, 3708; (b) Zhao, J.;
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Q. J. Am. Chem. Soc. 2008, 130, 17676; (d) Chu, J.-H.; Tsa, S.-L.; Wu, M.-J. Synthesis
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C19H15F3N: 314.1151; found: 314.1153.
Acknowledgements
This work was supported by the NIH NIGMS (GM073836).
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