Palladium-catalyzed decarboxylative cross-coupling of 3-pyridyl and 4-pyridyl carboxylates with aryl bromides

Article abstract of DOI:10.1016/j.tetlet.2015.01.131

Decarboxylative cross-coupling of 3-pyridyl and 4-pyridyl carboxylates with aryl bromides is reported. Using a bimetallic system of Cu₂O and Pd(PPh₃)₄, the scope of the reaction is demonstrated by the synthesis of 27 pyridine-containing biaryls in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2015.01.131

Tetrahedron Letters 56 (2015) 1293–1296
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Palladium-catalyzed decarboxylative cross-coupling of 3-pyridyl and
4-pyridyl carboxylates with aryl bromides
⇑
Lohitha Rao Chennamaneni , Anthony D. William, Charles W. Johannes
Institute of Chemical and Engineering Sciences (ICES), Agency for Science, Technology, and Research (A⁄STAR), 11 Biopolis Way, Helios Block, #03-08, Singapore 138667, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
Decarboxylative cross-coupling of 3-pyridyl and 4-pyridyl carboxylates with aryl bromides is reported.
Using a bimetallic system of Cu2O and Pd(PPh3)4, the scope of the reaction is demonstrated by the syn-
thesis of 27 pyridine-containing biaryls in moderate to good yields.
Received 10 September 2014
Revised 22 December 2014
Accepted 20 January 2015
Available online 3 February 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Decarboxylative coupling
3-Pyridyl and 4-pyridyl carboxylates
Aryl bromides
Palladium catalysis
Copper
O
Pyridine-containing heterobiaryls represent privileged struc-
tural units and are frequently found in pharmaceuticals, natural
products, bioactive molecules, and organic ligands.1 The 3- or 4-
aryl-substituted pyridine motifs are a subclass of heterobiaryls
and are present in a number of important pharmaceuticals and
small molecules (Fig. 1).
O
F
O
N
HN
O
N
N
O
N
O
N
N
N
N
antibiotic
O
F3C
N
N
RO4491533
O
N
Stoichiometric pyridyl organometallic reagents have been
extensively employed to prepare pyridine-containing biaryl motifs.
In this context, 3- and 4-pyridyl organometallics used in cross-
coupling reactions have proven to be more challenging than simple
aryl organometallics. This difficulty is presumably due to the insta-
bility and slow rate of transmetalation,1b attributed to the electron
deficiency of the pyridine ring. In spite of these hurdles, transition-
metal-catalyzed cross-coupling methods such as Suzuki,2 Stille,3
and others4–6 exist for the use of these 3- and 4-pyridyl organome-
tallics in coupling reactions. A major limitation with the aforemen-
tioned approaches is the stoichiometric synthesis of a reactive
metal species. Notable alternative methods have recently emerged
such as direct arylation of pyridine through C–H bond activation.7
While this approach would be ideal from an atom economy per-
spective, the regioselectivity remains a significant limitation.
Decarboxylative cross-coupling provides a catalytic approach to
the synthesis of biaryls, which would additionally obviate the reg-
ioselectivity issue. The extrusion of carbon dioxide is not as atom
economical, but it is a gaseous waste that does not need to be
N
N
H
OH
N
O
a7 nAChR agonist
(WAY-317,538)
NH
Me
3
N
5-HT receptor antagonist
(GR55562)
N
N
H
H
N
N
OH
O
N
H
N
H
natural product
(complanadine A)
H
H
ROCK inhibitor
(AS1892802)
Me
Figure 1. Bioactive 3-aryl and 4-aryl pyridine derivatives.
separated from the desired product.8 Several groups such as those
of Goossen,9 Forgione,10 and others11 have demonstrated the
synthesis of biaryls and heterobiaryls via decarboxylative cross-
coupling. Studies by Myers12 and others13 also highlight the
synthetic utility of related decarboxylative reactions. Although
decarboxylative coupling has been utilized in organic synthesis,
only a few reports are available which employ pyridine carboxylic
acids as coupling partners. More recently, Wu14a and Stoltz14b
⇑
Corresponding author. Tel.: +65 67998510; fax: +65 68745870.
E-mail address: lohitha_rao@ices.a-star.edu.sg (L.R. Chennamaneni).
http://dx.doi.org/10.1016/j.tetlet.2015.01.131
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

1294
L. R. Chennamaneni et al. / Tetrahedron Letters 56 (2015) 1293–1296
more general method for the decarboxylative cross-coupling of
Previous work:
both 3-pyridyl and 4-pyridyl carboxylates with aryl bromides for
the synthesis of 3- or 4-arylpyridines (Scheme 1, Eq. 4), which
are of interest in medicinal chemistry (Fig. 1).
[Pd]/ligand
Cu2O/base
COOR
N
Ar
Ar
N
(1)
(2)
Ar-Br
Our study began by testing the Pd-catalyzed decarboxylative
coupling of potassium pyridine-3-carboxylate with 4-bromotolu-
ene (Table 1). Initial results using a similar bimetallic catalyst sys-
tem reported by Wu and co-workers,14a PdCl2 and Cu2O with
BINAP as a ligand in DMA under microwave irradiation, provided
a 22% yield of the desired product (Table 1, entry 1). Switching
the palladium precatalyst (PdCl2) to the palladium catalyst
[Pd(PPh3)4] improved the yield to 30% (Table 1, entry 2). Interest-
ingly, decreasing the Pd-catalyst loading from 5 mol % to
2.5 mol % did not alter significantly the yield (Table 1, compare
entries 2 and 3). Other bidentate and monodentate phosphine
ligands such as Xantphos and X-phos were evaluated but failed
to improve the yields (Table 1, entries 4 and 5). Although phos-
phines such as BINAP are known to be effective ligands for cop-
per(I),14a,16 and the exact mechanism of the reaction is not
clearly understood, we hypothesized that nitrogen-containing
ligands might help to facilitate decarboxylation.17 Both mono and
bidentate ligands were screened. The monodentate ligand pyridine
gave a comparable yield to the phosphine ligands (35% yield,
Table 1, entry 6). Bidentate N-ligands such as 2,20-bipyridine and
1,10-phenanthroline provided a marked improvement with yields
of 53% and 72%, respectively (Table 1, entries 7 and 8). This result
indicates that the bite angle plays a critical role in the decarboxyl-
ation. To explore the potential effect of the phosphine ligand on
these optimized conditions, other Pd(0) and Pd(II) sources in com-
bination with a phosphine ligand (10 mol %) as an additive were
screened. No improvement was observed providing a range of
yields of 30–58% (Table 1, entries 9–13). Replacing Cu2O with other
Cu salts such as CuI or CuBr gave much lower yields (Table 1,
compare entries 8 with 14 and 15). The influence of several polar
R= H (or) K
Only 2-pyridinecarboxylic acid (or)
potassium carboxylate
COOK
[Pd]/P-ligand
Cu2O/N-ligand
p-tolyl-OTf or Naph-OTs
N
N
No Aryl Halides
Only 3-pyridinecarboxylate
Ar= p-tolyl or naphthyl
COOH
Ar
[Pd]/P,N-ligand
Cu2O/base
(3)
Ar-Br
N
N
Only 4-pyridinecarboxylic acid
Our work:
COOK
Ar
Pd(PPh3)4/Cu2O,
1,10-phenanthroline
(4)
X
X
Ar-Br
Y
R
Y
R
if X=N then Y=CH (or)
if X=N then Y=CH (or)
if Y=N then X=CH
if Y=N then X=CH
3- and 4-pyridinecarboxylates
Scheme 1. Decarboxylative cross-coupling reactions of pyridine carboxylic acids.
independently reported the decarboxylative cross-coupling
between pyridine-2-carboxylic acid (or) potassium pyridine-2-car-
boxylate and aryl bromides (Scheme 1, Eq. 1). Goossen et al.
demonstrated the decarboxylative cross-coupling of potassium
pyridine-3-carboxylate with an aryl triflate9c or aryl tosylate9h
(Scheme 1, Eq. 2). However, to the best of our knowledge, an exam-
ple of the decarboxylative cross-coupling of pyridine-3-carboxylic
acid with aryl halides has not been reported, and that of pyridine-
4-carboxylic acid is rare (Scheme 1, Eq. 3).15 Herein, we report a
Table 1
Optimization of the reaction conditionsa
CH3
Br
COOK
Pd source, Cu source
ligand, solvent,
180 oC,
+
N
60 oC
N
3a
1
2a
µ
W, 4 h
CH3
Entry
Additive
Pd source
Ligand
Solvent
Yieldb (%)
1c
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
Cu2O
CuI
PdCl2
BINAP
BINAP
BINAP
Xantphos
XPhos
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
NMP
DMF
22
30
28
17
12
35
53
72
30
55
35
58
30
15
24
36
48
28
12
2c
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd2(dba)3+PPh3
PdCl2+PPh3
Pd(OAc)2+PPh3
Pd(acac)2+PPh3
Pd(acac)2+XPhos
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
3
4
5
6
7
8
Pyridine
2,20-Bipyridine
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
1,10-Phenanthroline
9d
10d
11d
12d
13d
14
15
16
17
18
19
CuBr
Cu2O
Cu2O
Cu2O
Cu2O
Pd(PPh3)4
Pd(PPh3)4
Diglyme
DMSO
Values in bold face indicate best optimized reaction conditions employed to study substrate scope.
a
Reaction conditions: 1 (0.5 mmol), 2a (0.75 mmol), Cu (0.15 mmol), Pd (2.5 mol %), ligand (10 mol %), solvent (3.0 mL), 60–180 °C, lw, 4 h.
b
c
Isolated yield based on 1.
5 mol % palladium catalyst.
10 mol % P-ligand.
d

L. R. Chennamaneni et al. / Tetrahedron Letters 56 (2015) 1293–1296
1295
Table 2
Decarboxylative cross-coupling of potassium pyridine-3-carboxylates with aryl bromide
substratesa,b
Br
COOK
Pd(PPh3)4, Cu2O,
+
R
R
1,10-phenanthroline, DMA,
N
60 o
C
180 oC, W, 4 h
µ
N
3a-p
1
2a-p
3a,
72%
N
N
3b,
3f,
3j,
64%
N
N
3c,
46%
51%
3d,
33%
N
OMe
CF3
OMe
48%
F
N
N
3e,
N
42%
3g,
3h,
55%
NHCOCH3
CHO
CN
CN
N
N
N
N
3i,
50%
45%
3k,
3l,
42%
52%
N
N
N
N
N
N
N
3n,
25%
3o,
3p,
29%
31%
3m,
60%
a
Reaction conditions:
1 (0.5 mmol), 2a–p (0.75 mmol), Cu2O (0.15 mmol), Pd(PPh3)4
(2.5 mol %), 1,10-phenanthroline (10 mol %), DMA (3.0 mL), 60–180 °C,
Isolated yield based on 1.
lw, 4 h.
b
Table 3
Scope with regard to various potassium pyridine-3-carboxylatesa,b
expect a trend where 3a is in between 3f and 3i, but is in fact
noticeably better (72% vs 42% and 50%). This electronic difference
was not observed in relation to the ortho position (3c vs 3g vs
3k) where the yields were similar indicating that steric effects
remained the overriding factor. Under the same conditions, the
reaction with 2-bromonaphthalene delivered the corresponding
product 3m in good yield. Reactions with ortho-, meta-, and para-
bromopyridines afforded the corresponding bipyridines (3n, 3o,
and 3p) in lower yields. The effect of substituents on the potassium
methyl pyridine-3-carboxylate substrates was also briefly sur-
veyed using 4-bromotoluene as the electrophilic coupling partner.
As can be seen from Table 3, decarboxylative cross-coupling reac-
tions of 6-methylnicotinate and 5-methylnicotinate potassium
salts gave products 5a and 5b in yields of 60% and 58%, but the
4-methylnicotinate potassium salt gave a slightly lower yield (5c,
48%), consistent with the trend that sterically hindered substrates
are more challenging. Less obvious is the decrease in yield from the
2-methyl-substituted pyridine 5a vs. 3a (60% vs 72%).
Br
COOK
Pd(PPh3)4, Cu2O,
R
+
R
1,10-phen anthroline , DMA,
N
o
60 oC
180 C, W, 4 h
N
µ
2a
4a-c
5a-c
N
N
N
5a, 60%
5b, 58%
5c, 48%
a
Reaction conditions: 4a–c (0.5 mmol), 2a (0.75 mmol), Cu2O (0.15 mmol),
Pd(PPh3)4 (2.5 mol %), 1,10-phenanthroline (10 mol %), DMA (3.0 mL), 60–
180 °C,
l
w, 4 h.
b
Isolated yield based on 4a–c.
aprotic solvents other than DMA was investigated, however, no
further improvement in the yield was observed (Table 1, entries
16–19). A slight trend in the dielectric constant was observed
DMA > DMF > NMP (Table 1, entries 8, 17, and 16) with the
noticeable exception of DMSO, which was even worse as a solvent
than diglyme with respect to the yield, 12% versus 28% (Table 1,
entries 18 vs 19).
The decarboxylative cross-coupling reaction between potas-
sium pyridine-4-carboxylate and
a variety of aryl bromides
affording products (7a–h) is summarized in Table 4. Generally,
the trends observed for the pyridine-3-carboxylates were also
observed with the pyridine-4-carboxylate. At this time it is unclear
why the yields are reduced with respect to the 4-position (compare
Tables 2 and 4).
In summary, we have developed a microwave-assisted Pd-cata-
lyzed method for the decarboxylative cross-coupling of both pyri-
dine-3- and pyridine-4-carboxylates with aryl bromides. The
methodology has also been successfully applied in the decarboxy-
lative cross-coupling of substituted pyridine-3- carboxylates. Low
catalyst and additive loadings, and short reaction times are some
of the promising features of this methodology.
To test the substrate scope, the optimized conditions18 were
employed in decarboxylative cross-coupling reactions of potas-
sium pyridine-3-carboxylate with different aryl bromides. The
effect of substitution on the aryl bromide in the coupling of potas-
sium pyridine-3-carboxylate was explored with various bromotol-
uenes, which indicated that ortho substitution was less effective
(Table 2, entries 3a–d). Electronic influences are more subtle as
indicated by 3a, 3f, and 3i. From inductive effects, one would

1296
L. R. Chennamaneni et al. / Tetrahedron Letters 56 (2015) 1293–1296
Table 4
Decarboxylative cross-coupling of potassium pyridine-4-carboxylate with aryl bromide substratesa,b
Br
COOK
Pd(PPh3)4, Cu2O,
+
N
R
R
1,10-phen anthroline , DMA,
N
o
60 oC
180 C, W, 4 h
µ
6
7a-h
2a-c, f, i, j, l, q
OMe
O
N
N
N
N
7a,
7e,
N
68%
45%
7c,
7g,
7d,
7h,
44%
40%
7b,
7f,
58%
CHO
NHCOCH3
42%
CN
N
N
N
38%
26%
a
Reaction conditions:
6 (0.5 mmol), 2a–c,f,i,j,l,q (0.75 mmol), Cu2O (0.15 mmol), Pd(PPh3)4
(2.5 mol %), 1,10-phenanthroline (10 mol %), DMA (3.0 mL), 60–180 °C,
Isolated yield based on 6a.
lw, 4 h.
b
10. (a) Forgione, P.; Brochu, M. C.; Stonge, M.; Thesen, K. H.; Bailey, M. D.; Bilodeau,
F. J. Am. Chem. Soc. 2006, 128, 11350; (b) Bilodeau, F.; Brochu, M. C.; Guimond,
N.; Thesen, K. H.; Forgione, P. J. Org. Chem. 2010, 75, 1550.
11. (a) Shang, R.; Fu, Y.; Wang, Y.; Xu, Q.; Yu, H.-Z.; Liu, L. Angew. Chem., Int. Ed.
2009, 48, 9350; (b) Hu, P.; Zhang, M.; Jie, X. M.; Su, W. P. Angew. Chem., Int. Ed.
2012, 51, 227; (c) Hu, P.; Shang, Y.; Su, W. P. Angew. Chem., Int. Ed. 2012, 51,
5945; (d) Zhao, H. Q.; Wei, Y.; Xu, J.; Kan, J. A.; Su, W. P.; Hong, M. C. J. Org.
Chem. 2011, 76, 882; (e) Cornella, J.; Lahlali, H.; Larrosa, I. Chem. Commun. 2010,
8276; (f) Cornella, J.; Larrosa, I. Synthesis 2012, 44, 653; (g) Zhang, F.; Greaney,
M. F. Org. Lett. 2010, 12, 4745.
12. (a) Myers, A. G.; Tanaka, D.; Mannion, M. R. J. Am. Chem. Soc. 2002, 124, 11250;
(b) Tanaka, D.; Myers, A. G. Org. Lett. 2004, 6, 433; (c) Tanaka, D.; Romeril, S. P.;
Myers, A. G. J. Am. Chem. Soc. 2005, 127, 10323.
13. (a) Duan, Z. Y.; Ranjit, S.; Zhang, P. F.; Liu, X. G. Chem. Eur. J. 2009, 15, 3666; (b)
Luo, Y.; Pan, X. L.; Wu, J. Tetrahedron Lett. 2010, 51, 6646; (c) Bhadra, S.; Dzik,
W. I.; Goossen, L. J. J. Am. Chem. Soc. 2012, 134, 9938.
Acknowledgment
We acknowledge the Institute of Chemical and Engineering
Sciences - A STAR, for financial support (ICES/12-242A02).
Supplementary data
Supplementary data (characterization of the products and cop-
ies of spectras) associated with this article can be found, in the
online version, at http://dx.doi.org/10.1016/j.tetlet.2015.01.131.
References and notes
14. (a) Li, X.; Zou, D.; Leng, F.; Sun, C.; Li, J.; Wu, Y.; Wu, Y. Chem. Commun. 2013,
312; (b) Haley, C K.; Gilmore, C. D.; Stoltz, B. M. Tetrahedron 2013, 69, 5732.
15. He, R. T.; Wang, J. F.; Wang, H. F.; Ren, Z. G.; Lang, J. P. Dalton Trans. 2014, 43,
9786.
16. Blue, E. D.; Davis, A.; Conner, D.; Gunnoe, T. B.; Boyle, P. D.; White, P. S. J. Am.
Chem. Soc. 2003, 125, 9435.
17. In entries 1–5 (Table 1), after completion of the reaction, LCMS analysis
indicated the presence of unreacted carboxylic acid.
18. General procedure for the decarboxylative cross-coupling of 3-pyridyl and 4-
pyridyl carboxylates with aryl or heteroaryl bromides: In an argon-filled glove
1. (a) Henry, G. D. Tetrahedron 2004, 60, 6043; (b) Campeau, L. C.; Fagnou, K.
Chem. Soc. Rev. 2007, 36, 1058; (c) Kobayashi, J.; Hirasawa, Y.; Yoshida, N.;
Morita, H. Tetrahedron Lett. 2000, 41, 9069; (d) Morita, H.; Ishiuchi, K.;
Haganuma, A.; Hoshino, T.; Obara, Y.; Nakahata, N.; Kobayashi, J. Tetrahedron
2005, 61, 1955; (e) Arena, C. G.; Arico, G. Curr. Org. Chem. 2010, 14, 546.
2. (a) Ishikura, M.; Kamada, M.; Terashima, M. Synthesis 1984, 936; (b) Bouillon,
A.; Lancelot, J.-C.; Collot, V.; Bovy, P. R.; Rault, S. Tetrahedron 2002, 58, 2885; (c)
Cioffi, C. L.; Spencer, W. T.; Richards, J. J.; Herr, R. J. J. Org. Chem. 2004, 69, 2210;
(d) Kudo, N.; Perseghini, M.; Fu, G. C. Angew. Chem., Int. Ed. 2006, 45, 1282; (e)
Billingsley, K. L.; Anderson, K. W.; Buchwald, S. L. Angew. Chem., Int. Ed. 2006,
45, 3484; (f) Billingsley, K. L.; Buchwald, S. L. J. Am. Chem. Soc. 2007, 129, 3358.
3. (a) Yamamoto, Y.; Azuma, A. Y.; Mitoh, H. Synthesis 1986, 564; (b) Fujita, M.;
Oka, H.; Ogura, K. Tetrahedron Lett. 1995, 36, 5247; (c) Wittenberg, R.; Srogl, J.;
Egi, M.; Liebeskind, L. S. Org. Lett. 2003, 5, 3033; (d) Ma, G.; Leng, Y.; Wu, Y.;
Wu, Y. Tetrahedron 2013, 69, 902.
box,
a 10 mL microwave vial was charged with Pd(PPh3)4 (14.35 mg,
0.0125 mmol), Cu2O (21.3 mg, 0.15 mmol), 1,10-phenanthroline (8.95 mg,
0.05 mmol), the potassium pyridylcarboxylate (0.50 mmol), aryl bromide
(0.75 mmol) and anhydrous DMA (3.0 mL). The resulting solution was
irradiated in a microwave reactor (Biotage Initiator Eight EXP) with a 2 min
prestirring period, followed by 10 min at 60 °C. The reaction was then heated
at 180 °C for 3 h 50 min. The maximum pressure noted was 3 bar. After
completion of the reaction, H2O was added to the mixture which was then
extracted with EtOAc (3 ꢀ 10 mL). The combined organic layers were washed
with brine (5 mL), dried over Na2SO4, filtered, and the volatiles removed in
vacuo. The residue was purified by column chromatography on silica gel,
yielding the corresponding biaryl product.
4. (a) Stanetty, P.; Schnurch, M.; Mihovilovic, M. D. Synlett 2003, 1862; (b) Kim, S.-
H.; Slocum, T. B.; Rieke, R. D. Synthesis 2009, 3823; (c) Kim, S.-H.; Rieke, R. D.
Tetrahedron 2010, 66, 3135.
5. (a) Bonnet, V.; Mongin, F.; Trecourt, F.; Breton, G.; Marsais, F.; Knochel, P.;
Quequiner, G. Synlett 2002, 1008; (b) Furstner, A.; Leitner, A.; Mendez, M.;
Krause, H. J. Am. Chem. Soc. 2002, 124, 13856.
Characterization data for selected compounds: Compound 3a (3-(p-
tolyl)pyridine): Colorless oil; 1H NMR (600 MHz, CDCl3) d 8.84 (dd, J = 2.4,
0.9 Hz, 1H), 8.57 (dd, J = 4.8, 1.6 Hz, 1H), 7.86 (dt, J = 8.0, 2.1 Hz, 1H), 7.48 (d,
J = 8.1 Hz, 2H), 7.38–7.33 (m, 1H), 7.32–7.27 (m, 2H), 2.41 (s, 3H); 13C NMR
(150 MHz, CDCl3) d 148.2, 138.2, 136.7, 135.0, 134.3, 129.9, 127.1, 123.6, 21.3;
HRMS (ESI-TOF) m/z Calcd for C12H12N [M+H]+ 170.0964, found 170.0968.
Compound 5a (2-methyl-5-(p-tolyl)pyridine): White Solid; mp 84–85 °C; 1H
NMR (600 MHz, CDCl3) d 8.72 (s, 1H), 7.76 (dd, J = 8.0, 2.4 Hz, 1H), 7.46 (d,
J = 8.1 Hz, 2H), 7.27 (d, J = 7.8 Hz, 2H), 7.21 (d, J = 8.0 Hz, 1H), 2.60 (s, 3H), 2.40
(s, 3H); 13C NMR (150 MHz, CDCl3) d 156.9, 147.4, 137.8, 135.1, 134.7, 129.9,
6. (a) Seganish, W. M.; DeShong, P. J. Org. Chem. 2004, 69, 1137; (b) Tang, S.;
Takeda, M.; Nakao, Y.; Hiyama, T. Chem. Commun. 2011, 307.
7. (a) Kobayashi, O.; Uraguchi, D.; Yamakawa, T. Org. Lett. 2009, 11, 2679; (b) Li,
M.; Hua, R. Tetrahedron Lett. 2009, 50, 1478; (c) Ye, M.; Gao, G.-L.; Edmunds, A.
J. F.; Worthington, P. A.; Morris, J. A.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 19090.
8. Nilsson, M. Acta Chem. Scand. A 1966, 20, 423.
9. (a) Goossen, L. J.; Deng, G.; Levy, L. M. Science 2006, 313, 662; (b) Goossen, L. J.;
Rodriguez, N.; Melzer, B.; Linder, C.; Deng, G.; Levy, L. M. J. Am. Chem. Soc. 2007,
129, 4824; (c) Goossen, L. J.; Rodriguez, N.; Linder, C. J. Am. Chem. Soc. 2008, 130,
15248; (d) Goossen, L. J.; Zimmermann, B.; Knauber, T. Angew. Chem., Int. Ed.
2008, 47, 7103; (e) Goossen, L. J.; Zimmermann, B.; Linder, C.; Rodriguez, N.;
Lange, P. P.; Hartung, J. Adv. Synth. Catal. 2009, 351, 2667; (f) Goossen, L. J.;
Linder, C.; Rodriguez, N.; Lange, P. P. Chem. Eur. J. 2009, 15, 9336; (g) Goossen, L.
J.; Lange, P. P.; Rodriguez, N.; Linder, C. Chem. Eur. J. 2010, 16, 3906; (h)
Goossen, L. J.; Rodriguez, N.; Lange, P. P.; Linder, C. Angew. Chem., Int. Ed. 2010,
49, 1111; (i) Rodriguez, N.; Goossen, L. J. Chem. Soc. Rev. 2011, 40, 5030; (j)
Fromm, A.; Wüllen, C. V.; Hackenberger, D.; Goossen, L. J. J. Am. Chem. Soc. 2014,
136, 10007.
126.9, 123.3, 24.2, 21.3; HRMS (ESI-TOF) m/z Calcd for
184.1121, found 184.1124.
C13H14N
[M+H]+
Compound 7a (4-(p-tolyl)pyridine): White solid; mp 92-94 °C; 1H NMR
(600 MHz, CDCl3) d 8.67–8.61 (m, 2H), 7.59–7.52 (m, 4H), 7.33–7.28 (m, 2H),
2.42 (s, 3H); 13C NMR (150 MHz, CDCl3) d 149.48, 149.17, 139.83, 134.84,
130.07, 127.03, 121.78, 21.39; HRMS (ESI-TOF) m/z Calcd for C12H12N [M+H]+
170.0964, found 170.0971.
See Supporting information for analytical data on the other products.