Pd-Catalyzed Homo Cross-Dehydrogenative Coupling of 2-Arylpyridines by Using I2 as the Sole Oxidant

Article abstract of DOI:10.1055/s-0035-1561399

A palladium-catalyzed homo cross-dehydrogenative coupling (CDC) of 2-arylpyridines via C-H activation is described. This reaction employs I₂ as the sole oxidant without any other additives, which complements the hypervalent iodine chemistry, such as of phenyliodonium diacetate (PIDA) or IOAc, in C-H activation research field. A tentative mechanism involving a Pd(II)-Pd(IV) catalytic cycle is proposed to rationalize this homo CDC reaction.

Full text of DOI:10.1055/s-0035-1561399

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2016, 48, A–F
feature
A
W. Liu et al.
Feature
Synthesis
Pd-Catalyzed Homo Cross-Dehydrogenative Coupling of
2-Arylpyridines by Using I2 as the Sole Oxidant
Wenbo Liu
Youquan Zhu
N
N
Pd(OAc)2 (10 mol%)
Chao-Jun Li*
81%
I2 (1.6 equiv)
air
Department of Chemistry and FQRNT Center for
Green Chemistry and Catalysis, McGill University,
801 Sherbrooke Street West, Montreal, QC, H3A
0B8, Canada
DCE, 110 °C
N
cj.li@mcgill.ca
9 examples
28–81%
2 as the sole oxidant
I
Received: 11.01.2016
Accepted after revision: 12.02.2016
Published online: 10.03.2016
H atoms are removed from the starting materials; and 2.
they avoid the pre-synthesis of both coupling partners,
which would eliminate the waste from the beginning.
DOI: 10.1055/s-0035-1561399; Art ID: ss-2016-z0022-fa
Abstract A palladium-catalyzed homo cross-dehydrogenative cou-
pling (CDC) of 2-arylpyridines via C–H activation is described. This reac-
tion employs I2 as the sole oxidant without any other additives, which
complements the hypervalent iodine chemistry, such as of phenyliodo-
nium diacetate (PIDA) or IOAc, in C–H activation research field. A tenta-
tive mechanism involving a Pd(II)–Pd(IV) catalytic cycle is proposed to
rationalize this homo CDC reaction.
(a) Traditional cross coupling:
Ar2
M (cat.)
Ar2
M
Ar1
Ar1
X
(b) C–H activation involved coupling:
M (cat.)
Ar2
Ar2
Key words palladium, biaryl, iodine, C–H activation, cross-dehydro-
genative coupling
H
Ar1
X
Ar1
(c) Cross-dehydrogenative coupling:
Biaryl structural motifs are ubiquitous in natural prod-
ucts, pharmaceuticals, photo-electronics, and agrochemi-
cals.1 Over the past few decades, many elegant methods
have been developed to synthesize biaryls, in which palladi-
um-catalyzed cross-coupling reactions, such as the Suzuki
and Negishi reactions, are the most efficient and reliable.2
However, these traditional coupling reactions carry some
fundamental limitations, such as entailing pre-synthesis of
both coupling partners, i.e. the electrophiles (R-X) and the
nucleophiles (R-M), which would generate additional waste
and decrease the overall efficiency [Scheme 1 (a)]. A more
economical strategy employ one C–H bond as the precur-
sor, which could be coupled with another reactant.3 This
strategy has an advantage in that it only requires one pre-
functionalized starting material [Scheme 1 (b)]. Clearly, if
both substrates contribute C–H bonds as the coupling pre-
cursors (‘cross-dehydrogenative coupling’ CDC),4 no pre-
synthesized precursors would be mandatory [Scheme 1
(c)]. This type of reaction is superior to the first two types
because: 1. they show higher atom economy since only two
M (cat.)
oxidant
Ar2
Ar2
H
Ar1
Ar1
H
Scheme 1 Evolution of three strategies to synthesize biaryls
I2 is a cheap and versatile oxidant widely utilized in or-
ganic synthesis.5 However, I2 has been rarely used as the
sole oxidant in C–H activation protocols because it usually
requires activation by other additives such as metal salts to
form more reactive iodine species in situ.6 In contrast to I2,
hypervalent iodine compounds, such as PIDA,7 NIS,8 and
IOAc,9 are extensively employed in C–H activation reactions.
However, hypervalent iodine compounds are usually ex-
pensive and difficult to synthesize and store. Therefore, a
C–H activation process, which can be mediated by I2 with-
out other additives to replace hypervalent iodine oxidants,
is desirable and complementary to current hypervalent
chemistry.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

B
W. Liu et al.
Feature
Synthesis
To circumvent the regioselectivity issue, directing
groups, among which pyridine is popular, are necessary to
coordinate with the metal catalyst.10,11 For the dimerization
of 2-arylpyridines (Scheme 2), Sanford and co-workers12 re-
ported a protocol that involved a Pd(II) and Pd(IV) cycle us-
ing oxone as the terminal oxidant. Although oxone13 is rela-
tively cheap and environmentally benign, its solubility is-
sues in regular organic solvents limit its applicability.
Moreover, Yu and co-workers14 have developed another
protocol to achieve the dimerization of 2-arylpyridines us-
ing a stoichiometric amount of a copper salt. Although cop-
per is abundant, the use of a stoichiometric amount of cop-
per salt would, unfortunately, categorize this method as
‘not green’. Our group15 also reported a reaction for the
homo-coupling of 2-arylpyridines using a Ru catalyst and
FeCl3 as the stoichiometric oxidant. Herein, we wish to de-
scribe another method to homo-dimerize 2-arylpyridines
by using a Pd catalyst and I2 as the sole oxidant.
Recently, we initiated a program towards the applica-
tion of UV photochemistry in organic synthesis. As an ex-
tension of previous work,16 we envisioned to combine C–H
activation with photochemistry to achieve the coupling of
2-phenylpyridine with non-activated alkyl halides. Unfor-
tunately, when 2-phenylpyridine was reacted with cyclo-
hexyl iodide under classical Pd(OAc)2 catalyzed C–H activa-
tion conditions in the presence of both UV and heating, we
could not detect any of the desired coupling product. How-
ever, by carefully examining the GC/MS trace, we could
identify the homo-dimerization product at an approximate
5% yield [Scheme 3 (a)]. Inspired by this unexpected result,
we designed a serial of control experiments and rapidly
concluded that the iodine radical from cyclohexyl iodide
Biographical sketches
Wenbo Liu obtained his B.Sc
from University of Science and
Technology of China (Hefei, Chi-
na) in 2010. He studied chemi-
Columbia (Vancouver, Canada),
where he finished the total syn-
thesis of two soluble carbocyclic
Janus-AT phosphoramidites and
obtained the M.Sc degree in
2013. Following that, he moved
to McGill University (Montreal,
Canada) to study green chemis-
try under the tutelage of Profes-
sor Chao-Jun Li. His current
research interest focuses upon
solving challenging synthetic
problems by using organic pho-
tochemistry.
cal
biology
under
the
supervision of Professor David
M. Perrin at University of British
You-Quan Zhu received his
Ph.D. in 2005 with Prof. H.-Z.
Yang and has worked at Nankai
University in Tianjin (China) as
an associate professor since
then. Currently, he is a visiting
scholar in the group of Prof. Dr.
C.-J. Li at McGill University in
Montreal (Canada). His research
interests focus on the develop-
ment of new sustainable cata-
lytic methodologies for selective
constructions of carbon–carbon
bonds and the discovery of nov-
el ecofriendly pesticides.
Chao-Jun Li received his Ph.D.
at McGill University (1992) and
was a NSERC Postdoctoral Fel-
low at Stanford University
(1992–1994). He was on the
faculty at Tulane University (US)
(1994–2003). Since 2003, he
has been
a
Canada Research
Association for the Advance-
ment of Sciences (AAAS), a Fel-
low of the American Chemical
Society, a Fellow of the Royal
Society of Chemistry (UK), and
a Fellow of the Chemical Insti-
tute of Canada.
Chair in Green Chemistry and E.
B. Eddy Chair Professor of
Chemistry at McGill University.
He is a Fellow of the Royal Soci-
ety of Canada (Academy of Sci-
ences), a Fellow of the American
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

C
W. Liu et al.
Feature
Synthesis
this reaction were: 10 mol% Pd(OAc)2, 1.6 equiv I2, DCE as
the solvent, at 110 °C for 24 hours.
Sanford and co-workers:
N
Having obtained the optimized reaction conditions, we
briefly investigated the scope of this reaction (Figure 1). 2-
(4-Methylphenyl)pyridine dimerized to give 2b in a similar
yield (76%) to 2-phenylpyridine, which gave 2a in 81% yield.
Substrates with the electron-withdrawing group (F) and
electron-donating group (OMe) in the para position of phe-
nyl ring gave the respective dimerization products 2c and
2j smoothly. When the Cl was at the para position of the
phenyl ring, the reaction yield dropped dramatically to 28%
(2d). 2-(Biphenyl-4-yl)pyridine and 2-(4-tert-butylphe-
nyl)pyridine also produced the desired products 2e and 2f,
respectively, albeit with slightly lower yields (51% and 40%).
Besides the 2-phenylpyridine derivatives, 2-(2-naphth-
yl)pyridine was also applicable to our reaction conditions
and gave 2g in 68% yield. The methyl substitution of the
pyridine ring in the phenylpyridine did not bring a signifi-
cant change and the reaction proceeded to give 2h in 63%
N
Pd(OAc)2 (5 mol%)
41%
Oxone (2 equiv)
i-PrOH, r.t.
N
Yu and co-workers:
N
N
Cu(OAc)2 (1 equiv)
85%
I2 (1 equiv), air
MeCN, 130 °C
N
Li and co-workers:
N
N
[Ru(p-cymene)Cl2]2 (2.5 mol%)
87%
Table 1 Solvent and Additive Effects of this Reaction
FeCl3 (1 equiv),
chlorobenzene, 110 °C
N
N
N
Pd(OAc)2 (10 mol%)
I2, additive
110 °C
24 h
This work:
N
N
1
N
Pd(OAc)2 (10 mol%)
2
81%
I
2 (1.6 equiv), air
DCE, 110 °C
Entry Pd catalyst
Solvent
Additive (equiv) Yielda (%)
1
2b
3
4
5
6
7
8
9
–
DCE
–
0
0
N
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
DCE
–
p-dioxane
H2O
–
65
0
Scheme 2 Previous work on the homocoupling of 2-arylpyridine and
–
this work
PhCl
–
15
24
4
DCE/H2O (1:4)
DMSO/H2O (1:4)
CHCl3
DMF
–
–
under UV irradiation was essential for dimerization. There-
fore, we speculated whether I2 was able to promote this re-
action if heated. To our delight, when I2 was added to the
reaction, the dimerization product could be obtained in 35%
yield [Scheme 3 (b)]. Encouraged by this result, we exten-
sively investigated the temperature, concentration, reaction
time,17 solvent, and additive effects of this reaction (Table
1). Control experiments confirmed that both Pd(OAc)2 and
I2 are indispensable for this reaction (entries 1 and 2). Vari-
ous solvents were screened (entries 3–10) and 1,2-dichlo-
roethane (DCE, entry 10) gave the highest yield (83%). We
also investigated diverse additives, including common acids
and bases (entries 11–16), but these are not beneficial to
increasing the yields. Finally, the optimized conditions for
–
45
0
–
10
DCE
–
83 (81)c
25
43
67
65
55
0
11
12
13
14
15
16
DCE
Cs2CO3 (0.5)
Na2CO3 (0.5)
NaOAc (0.5)
AcOH (0.5)
TfOH (0.5)
Et3N (0.5)
DCE
DCE
DCE
DCE
DCE
a The yield was determined by using 1H NMR through using mesitylene as
the internal standard.
b Without I2.
c Isolated yield.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

D
W. Liu et al.
Feature
Synthesis
(a) Initial discovery:
N
N
I
N
Pd(OAc)2 (10% mol)
Cu(OAc)2 (2 equiv)
p-dioxane, 80 °C
UV (254 nm), 2 h
N
not observed
5%
(b) Control experiments:
N
N
Pd(OAc)2 (10% mol)
35%
I2
80 °C
5 h
N
Scheme 3 A serendipitous discovery and control experiment
yield. The reaction did not take place using a para-acetyl
substituted substrate probably because the carbonyl group
competed with the N atom to coordinate with the catalyst.
A tentative mechanism was proposed to rationalize this
transformation (Scheme 4). First, palladium(II) acetate
could activate the ortho C–H bond of A through the N-di-
rection to generate the intermediate B,10 which possibly un-
N
D
I
I
N
N
Pd(IV)
Pd(II)
Pd(II)
I
N
C
B
N
N
I2
E
Pd(IV)
N
Pd(II)
A
Pd(II)
B
N
F
N
Scheme 4 Proposed mechanism to rationalize this transformation
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

E
W. Liu et al.
Feature
Synthesis
Solvents and reagents were purchased from Sigma-Aldrich and were
1
used without further purification unless otherwise specified. H and
F
Cl
13C NMR spectra were recorded on Bruker 400 MHz, or 500 MHz
spectrometers and 19F NMR spectra were recorded on a Bruker 400
MHz spectrometer; internal reference of δ = 7.26 or 77.0 CHCl3 as
standard. All NMR spectra were recorded at r.t. (23 °C) unless other-
wise indicated. HRMS was conducted using electro-spraying ioniza-
tion (ESI), and was performed by McGill University on a Thermo-Sci-
entific Exactive Orbitrap. Protonated molecular ions [M + H]+ or sodi-
um adducts [M + Na]+, were used for empirical formula confirmation.
All preparative chromatography was performed through using gradi-
ent elution (hexanes/EtOAc) on a Biotage Isolera™ One automated
chromatography system with SNAP ultra silica gel cartridges and
sample cartridges.
N
N
N
N
N
N
N
N
F
Cl
2b
76% (80%)
2a
2c
2d
81% (86%)
65% (75%)
28% (35%)
N
N
N
Arylpyridines 1 are known compounds, with characterization data
available in the literature: 1a,h,j,15 1b–e,12 1f,18 1g,14 1i.19
2-Arylpyridines 1; General Procedure
N
N
N
2-Bromopyridine (191 μL, 2 mmol), Pd(OAc)2 (10 mg, 0.02 mmol),
and arylboronic acid (4 mmol) were added to a 25-mL round-bottom
flask in air without any precautions. Subsequently, i-Pr2NH (1 mL)
and H2O (4 mL) were added into the flask. Then a condenser was set
on the round-bottom flask and the reaction was heated to reflux for
16 h. The mixture was then transferred to a 100-mL separation funnel
and EtOAc (20 mL) and H2O (20 mL) were added. The organic layer
were collected and the solvent was removed used a rota-vapor. The
crude product was purified by column chromatography.
2f
2g
2e
51% (60%)
40% (47%)
68% (75%)
O
O
N
N
N
2,2′-Di(pyridin-2-yl)biphenyl (2a);15 Typical Procedure for Homo
Cross-Dehydrogenative Coupling
N
N
O
N
To a 5-mL V-shape tube were added Pd(OAc)2 (2.5 mg, 0.01 mmol), I2
(40 mg, 0.16 mmol), 2-phenylpyridine (30 μL, 0.2 mmol), and DCE
(0.5 mL). Then the tube was heated in a pre-heated 110 °C oil bath for
24 h. Subsequently, the volatiles were removed by rota-vapor and the
residue was purified by column chromatography (30% EtOAc in hex-
ane) to give the product as a white solid: yield: 24 mg (81%).
O
2j
2h
2i
70% (75%)
63% (70%)
0% (<5%)
Figure 1 Scope of this reaction. Reagents and conditions: 2-arylpyridine
(0.2 mmol), Pd(OAc)2 (0.01 mmol), I2 (0.16 mmol), DCE (0.5 mL), 110
°C, 24 h. All yields refer to isolated yields and the average of two parallel
runs, the conversion is indicated in parenthesis based on the 1H NMR
analysis of the crude mixture.
1H NMR (400 MHz, CDCl3): δ = 8.33 (d, J = 4.8 Hz, 2 H), 7.53–7.56 (m, 2
H), 7.32–7.44 (m, 8 H), 7.01–7.05 (m, 2 H), 6.78 (d, J = 7.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 157.8, 148.8, 139.7, 139.5, 135.1,
131.2, 129.9, 128.5, 127.6, 124.3, 121.1.
2,2′-(5,5′-Dimethylbiphenyl-2,2′-diyl)dipyridine(2b)12
White solid: yield: 25 mg (76%).
dergoes oxidative addition with I2, producing the interme-
diate C. Subsequently, reductive elimination from C could
result in the intermediate D, which could react with anoth-
er B to generate the intermediate E. Finally, reductive elimi-
nation based on E would afford the desired coupling prod-
uct F and regenerate the catalyst.
1H NMR (400 MHz, CDCl3): δ = 8.26 (dd, J1 = 5.0 Hz, J2 = 0.9, 2 H), 7.41
(d, J = 7.8 Hz, 2 H), 7.28 (m, 4 H), 7.21 (dd, J1 = 7.8 Hz, J2 = 0.9 Hz, 2 H),
6.96 (dd, J1 = 4.8 Hz, J2 = 1.2 Hz, 2 H), 6.66 (dd, J1 = 8.1 Hz, J2 = 0.9 Hz, 2
H), 2.43 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 157.8, 148.7, 139.6, 138.3, 137.0,
135.0, 131.8, 129.8, 128.4, 124.2, 120.8, 21.2.
In summary, we have developed a Pd-catalyzed di-
merization reaction of 2-arylpyridines through C–H activa-
tion. This reaction uses I2 as the sole oxidant to achieve the
catalytic cycle and has a relatively broad substrate scope.
Complementary to the application of hypervalent iodine
compounds in C–H activation, our protocol is expected to
enrich iodine chemistry for C–H functionalization.
2,2′-(5,5′-Difluorobiphenyl-2,2′-diyl)dipyridine (2c)12
White solid: yield: 22 mg (65%).
1H NMR (400 MHz, CDCl3): δ = 8.31 (dd, J1 = 5.0 Hz, J2 = 0.9 Hz, 2 H),
7.48–7.53 (m, 2 H), 7.36 (dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 2 H), 7.01–7.14 (m,
6 H), 6.76 (d, J = 7.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 162.6 (d, JC-F = 989.1 Hz), 156.7, 149.0,
140.8 (d, JC-F = 25.2 Hz), 136.0, 135.4, 132.0 (d, JC-F = 29.7 Hz), 124.1,
121.4, 117.7 (d, JC-F = 86.7 Hz), 115.0 (d, JC-F = 81.9 Hz).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F

F
W. Liu et al.
Feature
Synthesis
19F NMR (376 MHz, CDCl3): δ = –113.37.
Acknowledgment
We are grateful to the Canada Research Chair (Tier I) Foundation (to C.
J. Li), CFI, and NSERC for support of research. W. Liu is grateful for
DDTP program for a scholarship.
2,2′-(5,5′-Dichlorobiphenyl-2,2′-diyl)dipyridine (2d)12
White solid: yield: 11 mg (28%).
1H NMR (400 MHz, CDCl3): δ = 8.28 (dd, J1 = 5.1 Hz, J2 = 0.9 Hz, 2 H),
7.32–7.46 (m, 8 H), 7.03 (dd, J1 = 5.1 Hz, J2 = 0.9 Hz, 2 H), 6.70 (dd, J1 =
7.8 Hz, J2 = 0.9 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 156.4, 149.0, 140.1, 138.2, 135.5,
134.5, 131.5, 130.7, 128.3, 124.1, 121.5.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561399.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
4′,6′′-Di(pyridin-2-yl)-1,1′:3′,1′′:3′′,1′′′-quaterphenyl (2e)12
White solid: yield: 23 mg (51%).
References
1H NMR (400 MHz, CDCl3): δ = 8.38 (dd, J1 = 4.8 Hz, J2 = 0.9 Hz, 2 H),
7.76 (d, J = 0.9 Hz, 2 H), 7.66–7.74 (m, 8 H), 7.47 (t, J = 7.8 Hz, 4 H),
7.38 (m, 4 H), 7.05 (dd, J1 = 4.8 Hz, J2 = 1.2 Hz, 2 H), 6.90 (d, J = 7.8 Hz,
2 H).
13C NMR (100 MHz, CDCl3): δ = 157.5, 149.0, 141.2, 140.0, 138.8,
135.2, 130.6, 129.8, 128.8, 127.5, 127.0, 126.4, 124.4, 121.2.
(1) (a) Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58,
9633. (b) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire,
M. Chem. Rev. 2002, 102, 1359. (c) Tohma, H.; Morioka, H.;
Takizawa, S.; Arisawa, M.; Kita, Y. Tetrahedron 2001, 57, 345.
(2) (a) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
4020. (b) Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 2719.
(c) Milne, J. E.; Buchwald, S. L. J. Am. Chem. Soc. 2004, 126,
13028.
2,2′-(5,5′-Di-tert-butylbiphenyl-2,2′-diyl)dipyridine (2f)
(3) (a) Murai, S.; Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.;
Sonoda, M.; Chatani, N. Nature (London) 1993, 366, 529.
(b) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731.
(c) Dyker, G. Angew. Chem. Int. Ed. 1999, 38, 1699. (d) Alberico,
D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174.
(4) (a) Li, C.-J. Acc. Chem. Res. 2009, 42, 335. (b) Li, Z.; Li, C.-J. J. Am.
Chem. Soc. 2004, 126, 11810. (c) Girard, S. A.; Knauber, T.; Li, C.-J.
Angew. Chem. Int. Ed. 2014, 53, 74.
White solid: yield: 17 mg (40%).
1H NMR (400 MHz, CDCl3): δ = 8.50 (d, J = 4.9 Hz, 2 H), 7.61 (d, J = 8.2
Hz, 2 H), 7.43–7.35 (m, 4 H), 7.14 (d, J = 1.9 Hz, 2 H), 7.08–7.03 (m, 2
H), 7.00 (d, J = 8.0 Hz, 2 H), 1.20 (s, 18 H).
13C NMR (100 MHz, CDCl3): δ = 159.0, 151.0, 149.1, 139.6, 137.2,
135.1, 129.8, 129.2, 124.7, 124.2, 120.9, 34.4, 31.1.
HRMS (ESI): m/z [M + H]+ calcd for C30H33N2: 421.2638; found:
421.2635.
(5) (a) Cai, Z.-J.; Wang, S.-Y.; Ji, S.-J. Org. Lett. 2013, 15, 5226.
(b) Kanth, J. V. B.; Periasamy, M. J. Org. Chem. 1991, 56, 5964.
(6) Wang, X.-C.; Hu, Y.; Bonacorsi, S.; Hong, Y.; Burrell, R.; Yu, J.-Q.
J. Am. Chem. Soc. 2013, 135, 10326.
(7) (a) Dick, A. R.; Hull, K. L.; Sanford, M. S. J. Am. Chem. Soc. 2004,
126, 2300. (b) Dudnik, A. S.; Chernyak, N.; Huang, C.; Gevorgyan,
V. Angew. Chem. Int. Ed. 2010, 49, 8729.
3,3′-Di(pyridin-2-yl)-2,2′-binaphthalene (2g)14
White solid: yield: 28 mg (68%).
1H NMR (400 MHz, CDCl3): δ = 8.30 (d, J1 = 4.8 Hz, 2 H), 8.14 (s, 2 H),
8.03 (s, 2 H), 7.96 (d, J = 7.8 Hz, 2 H), 7.91 (d, J = 7.8 Hz, 2 H), 7.50–7.55
(m, 4 H), 7.27–7.19 (m, 2 H), 7.08–6.93 (m, 2 H), 6.71 (d, J = 7.9 Hz, 2
H).
13C NMR (100 MHz, CDCl3): δ = 157.8, 149.2, 138.5, 135.5, 133.6,
133.1, 130.8, 129.7, 128.6, 127.9, 126.9, 126.6, 124.6, 121.5.
(8) Schröder, N.; Wencel-Delord, J.; Glorius, F. J. Am. Chem. Soc.
2012, 134, 8298.
(9) Giri, R.; Chen, X.; Yu, J. Q. Angew. Chem. Int. Ed. 2005, 44, 2112.
(10) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(11) Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439.
(12) Hull, K. L.; Lanni, E. L.; Sanford, M. S. J. Am. Chem. Soc. 2006, 128,
14047.
(13) Desai, L. V.; Malik, H. A.; Sanford, M. S. Org. Lett. 2006, 8, 1141.
(14) Chen, X.; Dobereiner, G.; Hao, X.-S.; Giri, R.; Maugel, N.; Yu, J.-Q.
Tetrahedron 2009, 65, 3085.
(15) Guo, X.; Deng, G.; Li, C.-J. Adv. Synth. Catal. 2009, 351, 2071.
(16) (a) Liu, W.; Li, L.; Li, C.-J. Nat. Commun. 2015, 6, 6526. (b) Liu,
W.; Li, L.; Chen, Z.; Li, C.-J. Org. Biomol. Chem. 2015, 13, 6170.
(c) Li, L.; Liu, W.; Zeng, H.; Mu, X.; Cosa, G.; Mi, Z.; Li, C.-J. J. Am.
Chem. Soc. 2015, 137, 8328. (d) Liu, W.; Chen, Z.; Li, L.; Wang, H.;
Li, C.-J. Chem. Eur. J. 2016, in press; DOI: 10.1002/chem.201600219.
(17) Based on our research, higher temperature, longer reaction time
and higher concentration produced a higher reaction yield.
However, to make a comprimse on these three parameters, we
decided to use 110 °C, 0.4 M, and 24 h to optimize the solvent
and additive effects.
2,2′-Bis(5-methylpyridin-2-yl)biphenyl (2h)15
White solid: yield: 21 mg (63%).
1H NMR (400 MHz, CDCl3): δ = 8.18 (s, 2 H), 7.54–7.56 (m, 2 H), 7.31–
7.41 (m, 6 H), 7.13 (d, J = 8.0 Hz, 2 H), 6.70 (d, J = 8.0 Hz, 2 H), 2.25 (s, 6
H).
13C NMR (100 MHz, CDCl3): δ = 155.4, 149.4, 139.9, 139.7, 135.8,
131.4, 130.5, 130.0, 128.2, 127.6, 123.8, 18.2.
2,2′-(5,5′-Dimethoxybiphenyl-2,2′-diyl)dipyridine (2j)15
White solid: yield: 26 mg (70%).
1H NMR (400 MHz, CDCl3): δ = 8.28 (dd, J1 = 5.1 Hz, J2 = 0.9 Hz, 2 H),
7.49 (dd, J1 = 6.6 Hz, J2 = 2.7 Hz, 2 H), 7.29 (dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 2
H), 6.93–6.98 (m, 6 H), 6.72 (d, J = 7.8 Hz, 2 H), 3.81 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 159.6, 157.5, 148.7, 141.0, 135.1,
132.6, 131.4, 124.1, 120.7, 116.0, 113.5, 55.2.
(18) Teskey, C. J.; Lui, A. Y. W.; Greaney, M. F. Angew. Chem. Int. Ed.
2015, 54, 11677.
(19) Park, J.; Chang, S. Angew. Chem. Int. Ed. 2015, 54, 14103.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–F