Palladium-Catalyzed Divergent Arylation with Triazolopyridines: One-Pot Synthesis of 6-Aryl-2-α-styrylpyridines

Article abstract of DOI:10.1002/adsc.201500967

We have developed a new strategy for palladium-catalyzed arylation reactions with triazolopyridines, wherein two different chemical transformations (C-3 vs. C-7) are observed by differentiating the substrates using different bases. The reactive palladium carbenoids were directly generated from triazolopyridines and underwent denitrogenative arylations with aryl bromides. Intriguingly, when potassium carbonate was replaced with potassium tert-butoxide, direct C-H arylation occurred at the most acidic position (C-7). Moreover, two different catalytic arylation events were successfully performed in a one-pot sequence, providing a convenient access to 6-aryl-2-α-styrylpyridines.

Full text of DOI:10.1002/adsc.201500967

FULL PAPERS
DOI: 10.1002/adsc.201500967
Very Important Publication
Palladium-Catalyzed Divergent Arylation with Triazolopyridines:
One-Pot Synthesis of 6-Aryl-2-a-styrylpyridines
Youngtaek Moon,a,b Soonhyung Kwon,a,b Dahye Kang,a,b Honggu Im,a,b
and Sungwoo Honga,b,*
a
Department of Chemistry, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea
Fax: (+82)-42-350-2810; phone: (+82)-42-350-2811; e-mail: hongorg@kaist.ac.kr
Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon 305-701, Korea
b
Received: October 17, 2015; Revised: November 25, 2015; Published online: January 25, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500967.
À
Abstract: We have developed a new strategy for pal- oxide, direct C H arylation occurred at the most
ladium-catalyzed arylation reactions with triazolopyr- acidic position (C-7). Moreover, two different cata-
idines, wherein two different chemical transforma- lytic arylation events were successfully performed in
tions (C-3 vs. C-7) are observed by differentiating a one-pot sequence, providing a convenient access to
the substrates using different bases. The reactive pal- 6-aryl-2-a-styrylpyridines.
ladium carbenoids were directly generated from tri-
azolopyridines and underwent denitrogenative aryla-
tions with aryl bromides. Intriguingly, when potassi- Keywords: arylation; carbenes; one-pot reaction;
um carbonate was replaced with potassium tert-but- palladium; triazolopyridines
Introduction
mechanism; subsequent transfer of an aryl group
could then afford C-7 arylated products.[7] Herein, we
The utilization of the 1,2,3-triazole group as a versatile report a new strategy for the Pd-catalyzed arylation
reactive platform for a variety of useful synthetic with triazolopyridines, wherein divergent reaction
transformations has been a field of intense re- pathways between positions C-3 and C-7 are observed
search.[1,2] Based on the ability of the triazole moiety by differentiating substrates using different bases.
to exist in a closed/open form, triazolopyridines can Moreover, despite the mechanistic dichotomy, two
serve as versatile pyridyl carbene precursors for the different catalytic arylation events could be success-
construction of nitrogen-containing heterocyclic com- fully linked in a one-pot sequence with a single Pd
pounds via transition metal catalyzed denitrogenative catalyst to afford valuable 6-aryl-2-a-styrylpyridine
transformations.[3] Important advances have been compounds (Scheme 1).
made with the use of triazolopyridines as precursors
of rhodium or copper carbenes to afford valuable pyr-
idine-containing compounds.[4,5] Despite the advances
reported thus far, the direct introduction of (hetero)-
arenes via the Pd-catalyzed migratory insertion of an
aryl group into triazoles has not been reported previ-
ously.
We envisioned that a variety of (hetero)aryl groups
could be installed for the synthesis of 2-a-styrylpyri-
dines by trapping the pyridyl carbenes derived from
triazolopyridines with a Pd catalyst,[6] if the Lewis ba-
sicity of the pyridine nitrogen is attenuated via coor-
dination of a Lewis acid to the pyridyl nitrogen atom.
We also hypothesized that the reaction site could be
switchable to the most acidic position (C-7) in the tri-
azolopyridines via
a
base-assisted deprotonation Scheme 1. Pd-catalyzed arylation with triazolopyridines.
958
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 958 – 964

FULL PAPERS
Palladium-Catalyzed Divergent Arylation with Triazolopyridines
Results and Discussion
experiments verified that no reaction occurred with-
out a Pd catalyst, which indicated that Ni-catalyzed
First, the feasibility of the denitrogenative arylation coupling was unlikely to be operative (entry 11).
of triazolopyridines was tested using the Pd-catalyzed After determining the optimal reaction conditions,
cross-coupling reaction with aryl bromides for the we set up a series of experiments to investigate the
synthesis of 2-a-styrylpyridines (Table 1).[8] After sur- scope of the triazolopyridines (Table 2). The present
veying some potential catalytic systems, the use of methodology was amenable to the presence of a varie-
a catalytic system consisting of Pd(OAc)2, Xphos, and ty of both electron-donating and electron-withdrawing
K2CO3 was found to initiate the denitrogenative ary- groups, affording the desired products (3a–l). In case
lation to afford the desired product 3a but only in an of the C-7 CF3-substituted triazolopyridine, the result-
8% yield (Table 1, entry 2). Thorough ligand screen- ing a-styrylpyridine product underwent further the
ing was conducted and we found that Cy3P exhibited Mizoroki–Heck reaction,[10] leading to 1,2-diphenyl
a much better perfomance (50%, entry 3). No produc- product 3m.[11] Expanding the scope from the pyridine
tive reaction was observed with the Rh or Cu catalytic to the pyrimidyl and pyrazinyl motifs, which are
systems, which were employed previously in the deni- useful for medicinal chemistry, was also possible, lead-
trogenative transformations of triazolopyridines.[4,5] ing to the formation of 3o and 3p. Substrates bearing
The base source was also critical for the coupling effi- ethyl, and phenyl groups at the R2 position were suc-
ciency, and K2CO3 was the most effective for promot- cessfully converted into the E-selective adducts (3q–
ing the reactions. Diminished yields were observed, 3s).
except under reaction conditions that employed tolu-
Subsequently, we examined the scope of this new
ene as the solvent. Among the Pd sources tested, method with respect to the aryl bromides (Table 3).
(Cy3P)2PdCl2 (5 mol%) was found to be an optimal We observed that the coupling of the triazolopyridine
catalyst with minimal formation of side products worked well with a wide range of aryl bromides bear-
(entry 6). Considering the potential interference of ing electron-neutral, electron-donating, and electron-
the Lewis basic N-atom of the pyridine moiety with
the Pd catalyst,[9] we screened a variety of additives to
Table 2. Substrate scope of triazolopyridines.
diminish the Lewis basicity of the pyridine or triazole
moiety. During optimization of the reaction condi-
tions, we discovered that Ni(OAc)2·4H2O (0.1 equiv.)
was critical for optimal results (81%, entry 8). Control
Table 1. Optimization of Pd-catalyzed denitrogenative aryla-
tion conditions.[a]
Entry Pd (5 mol%) Base
Ligand or Additive Yield
(2 equiv.) (0.1 equiv.)
[%]
1
2
3
4
5
6
7
8
9
10
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(TFA)2
(Cy3P)2PdCl2 K2CO3
(Cy3P)2PdCl2 K2CO3
(Cy3P)2PdCl2 K2CO3
(Cy3P)2PdCl2 K2CO3
K2CO3
K2CO3
K2CO3
Cs2CO3
K2CO3
–
–
8
50
6
48
53
60
81
71
70
XPhos
Cy3P
Cy3P
Cy3P
–
Zn(OAc)2
Ni(OAc)2·4H2O
Mn(OAc)2·4H2O
Cy3P/
Pd(OAc)2
K2CO3
Ni(OAc)2·4H2O
Ni(OAc)2·4H2O
11
–
K2CO3
0
[a]
1a, (0.1 mmol), 2a (0.2 mmol), Pd (5 mol%), base
(0.2 mmol), and additive (10 mol%) in PhMe (1.5 mL) at
1308C under N2 for 24 h; isolated yields. XPhos=2-dicy-
clohexylphosphino-2’,4’,6’-triisopropylbiphenyl,
tricyclohexylphosphine, TFA =trifluoroacetate.
Cy3P=
[a]
4 equiv. of PhBr were used.
Adv. Synth. Catal. 2016, 358, 958 – 964
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
959

FULL PAPERS
Youngtaek Moon et al.
Table 3. Substrate scope of aryl bromides.
Scheme 2. Plausible mechanism for Pd-catalyzed denitroge-
native arylation.
withdrawing groups that are commonly encountered
in organic synthesis. The 2-bromonaphthalene sub-
strate was also suitable for this transformation, and
the desired product 4t was obtained in good yield. In
view of the frequency of heterocyclic analogs within
biologically active molecules, we further investigated
heteroaryl substrates and were pleased to observe
that this method was further extended using a series
of heteroaryl groups, including thiophene (4u), pyri-
dines (4v and 4w), pyrimidine (4x), benzothiazole
(4y), and chromone (4z).
A plausible mechanism for the Pd-catalyzed deni-
trogenative arylation of triazolopyridines with aryl
bromides is shown in Scheme 2. Oxidative addition
initiates the catalytic cycle, generating an organopalla-
dium species. Next, a reactive Pd-carbene complex I
is formed via the reaction of an arylpalladium species
with the in situ-generated diazo imine 1a’. Nickel ions
may coordinate to the pyridyl nitrogen atom in
a diazo form and facilitate Pd-carbene formation. The
resulting complex I can undergo migratory insertion
of the aryl group to give the alkylpalladium species
II. Subsequent b-hydride elimination provides the de-
sired coupled product 4 and regenerates the Pd(0)
catalyst with the aid of the base.
Unexpectedly, the endo-olefin products 5a–5d were
obtained with the C-7 methoxy-substituted triazolo-
Scheme 3. Reactions of 7-MeO-substituted triazolopyridine
pyridine 1b (Scheme 3a).
A control experiment with aryl bromides.
960
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 958 – 964

FULL PAPERS
Palladium-Catalyzed Divergent Arylation with Triazolopyridines
Scheme 4. Synthesis of LG100268.
Scheme 5. a) Calculated B3LYP/6-311+ +G(2df,2p) free en-
ergies for the deprotonation of each C H bonds of sub-
strate. b) H/D exchange experiment.
À
showed that the mixture of alkene 1b’ and cycloprop-
yl product 6 could be detected in the absence of Pd
and aryl bromide (Scheme 3b). The cyclopropyl prod-
uct 6 is presumably generated from the reaction of
the in situ generated carbene with an alkene inter-
mediate. The introduction of a methoxy group at C-7
appears to facilitate the formation of the reactive
diazo form,[4a,12] thus spontaneously generating the
carbene and alkene intermediates.[13] These observa-
tions suggest that the alkene intermediate 1b’, which
is rapidly formed in situ via the 1,2-H shift of the car-
bene intermediate, reacts with the arylpalladium spe-
cies to afford Heck-type products 5a–5d (Scheme 3d).
To further showcase the synthetic applicability, this
method was employed as a straightforward synthetic
route to the selective retinoid X receptor agonist
LG100268.[14] Thus, a key intermediate 7 of LG100268
was efficiently prepared (82%), via Pd-catalyzed deni-
trogenative cross-coupling (Scheme 4).
Table 4. Discovery and optimization of Pd-catalyzed C-7 ar-
ylation.[a]
Entry Base (2 equiv,) Temp. [oC] Time [h] Yield [%]
1
2
3
4
5
6
7
8
9
LiOEt
130
130
130
130
80
130
130
130
130
1.5
1.5
1.5
1.5
7
1.5
1.5
1.5
1.5
NR
NR
62
88
70
NR
72
63
t-BuONa
KHMDS
t-BuOK
t-BuOK
LiHMDS
Cs2CO3
NaH
K2CO3
NR
[a]
After successfully achieving the Pd-catalyzed deni-
trogenative arylation, we speculated that the direct
1a, (0.1 mmol), 2a (0.2 mmol), Pd (5 mol%), base
(2 equiv.), in PhMe (1.5 mL) at 1308C under N2; isolated
yields.
À
C H arylation of the triazolopyridine could be ach-
ieved by taking advantage of the inherent electronic
characteristics of this core.[7] Thus, we performed
computational studies with density functional theory icant effect on the reactivity, and t-BuOK was the
calculations, showing that the Gibbs free energy for most effective for promoting the reactivity (88%
À
the deprotonation of C-7 H is particularly low yield, entry 4). Interestingly, usage of other bases led
(Scheme 5a).[13] Additionally, the H/D exchange ex- to lower yields presumably as a result of competitive
periment revealed that the most acidic site of the tri- ring-opening decomposition.[12] Moreover, no forma-
azolopyridines is the C-7 position.
tion of C-3 denitrogenative arylation by-product was
These observations prompted us to explore the fea- observed under the reaction conditions. A diminished
sibility of the installation of an aryl group at the C-7 conversion rate was observed when the reaction tem-
position in the triazolopyridines via the presumed perature was decreased to 100 or 808C (entry 5).
base-assisted deprotonation mechanism. We investi-
gated a possible collection of C H arylation condi- dine and aryl bromide substrates by conducting direct
tions using the Pd catalytic system and phenyl bro- C-7 H arylation reactions (Table 5). We found that
mide by evaluating the effect of different bases this catalytic system was amenable to a range of func-
(Table 4). We found that the C-7 arylated product tional groups such as alkyl, methoxy, trifluoromethyl,
could be obtained in a 62% yield using KHMDS dimethylamino, phenyl, and chloro groups under the
(entry 3). As predicted, the choice of base had a signif- optimized conditions, leading to the formation of
Next, we explored the scope of both triazolopyri-
À
À
Adv. Synth. Catal. 2016, 358, 958 – 964
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
961

FULL PAPERS
Youngtaek Moon et al.
Table 5. Substrate scope for C-7 arylation of triazolopyri-
Table 6. One-pot reaction.[a]
dine.
[a]
1a, (0.1 mmol), Ar1Br (0.11 mmol), (Cy3P)2PdCl2
(10 mol%), and t-BuOK (0.2 mmol) in PhMe (1.5 mL) at
1308C under N2 for 1.5 h; Ar2Br (0.2 mmol), KHCO3
(0.2 mmol), and Ni(OAc)2·4H2O (10 mol%) for 24 h.
a series of C-7 arylated triazolopyridines in good to
excellent yields.
We next preliminarily investigated the utility of this process, in which two different aryl groups are intro-
approach for the controlled installation of two differ- duced for the construction of diversely functionalized
ent aryl groups in a one-pot procedure because the 6-aryl-2-a-styrylpyridines.
resulting C-7 aryltriazolopyridines are prone to under-
A plausible mechanism for the one-pot reaction is
go the Pd-catalyzed denitrogenative arylation reaction shown in Scheme 6. The initial addition of Pd(II) to
À
(e.g., 3l in Table 2). Indeed, we were delighted to ob- C-7 would proceed via a base-assisted C H deproto-
serve that the one-pot catalytic process was facile nation–palladation mechanism, leading to the C-7 pal-
under slightly modified reaction conditions in which ladated species I. The subsequent reductive elimina-
KHCO3 was employed to remove the reactive tert- tion of II delivered the C-7 arylated triazolopyridine,
butoxide anion. The second half event operates se- which was then engaged in the Pd-catalyzed denitro-
quentially via the in situ generated K2CO3 from t- genative arylation event in the second catalytic cycle.
BuOK and KHCO3.[15] As demonstrated in Table 6,
a series of substrates effectively underwent a one-pot
962
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 958 – 964

FULL PAPERS
Palladium-Catalyzed Divergent Arylation with Triazolopyridines
The mixture was monitored by TLC using EtOAc and n-
hexane=1:2 as the mobile phase and stirred until starting
material disappeared. After cooled to room temperature,
the mixture solvent was removed under reduced pressure.
The reaction mixture was diluted with CH2Cl2 and the resi-
due was extracted with aqueous NH4Cl (3”30 mL). The or-
ganic layer was dried over MgSO4. After removal of solvent,
the residue was purified by flash chromatography on silica
gel to give desired product.
Full characterization data and copies of relevant spectra
are provided in the Supporting Information.
General Procedure for One-Pot Synthesis of 6-
Phenyl-2-a-styrylpyridines
Scheme 6. Proposed reaction pathways for one-pot catalysis.
Triazolopyridine
(Cy3P)2PdCl2 (10 mol%), and KO-t-Bu (2 equiv.) were com-
bined in anhydrous PhMe (1.5 mL) under nitrogen
a sealed tube. The reaction mixture was stirred at 1308C for
1.5 h. The mixture was monitored by TLC using EtOAc and
(0.1 mmol),
Ar1Br
(0.11 mmol),
Conclusions
n
In summary, we have developed a new and versatile
synthetic strategy for the Pd-catalyzed arylation with n-hexane=1:2 as the mobile phase and stirred until the
starting material disappeared. After being cooled to room
temperature, KHCO3 (0.2 mmol), Ni(OAc)2·4H2O
triazolopyridines. The synthetic utility of this ap-
proach has been verified via two different chemical
transformations (C-3 vs. C-7) from the same set of
substrates, which were achieved by differentiating
each event using different bases. Moreover, two con-
current arylation events successfully proceeded in the
one-pot process with a single Pd catalyst, providing
a new straightforward route to 6-aryl-2-a-styrylpyri-
dines of high synthetic utility.
(0.1 equiv.), and Ar2Br (0.2 mmol) were added. The reaction
mixture was stirred at 1308C for 24 h under nitrogen. The
mixture was monitored by TLC using EtOAc and n-
hexane=1:5 as the mobile phase and stirred until the inter-
mediate disappeared. After being cooled to room tempera-
ture, the mixture solvent was removed under reduced pres-
sure. The reaction mixture was diluted with CH2Cl2 and the
residue was extracted with aqueous NH4Cl (3”30 mL). The
organic layer was dried over MgSO4. After removal of sol-
vent, the residue was purified by flash chromatography on
silica gel to give desired product.
Experimental Section
Full characterization data and copies of relevant spectra
are provided in the Supporting Information.
General Procedure for Synthesis of 2-(1-Phenylvinyl)-
pyridine Derivatives
Triazolopyridine (0.1 mmol), aryl bromide (0.2 mmol),
(Cy3P)2PdCl2
(5 mol%),
K2CO3
(2 equiv.),
and
Acknowledgements
Ni(OAc)2·4H2O (0.1 equiv.) were combined in anhydrous
PhMe (1.5 mL) under nitrogen condition in a sealed tube.
The reaction mixture was stirred at 1308C for 24 h. The mix-
ture was monitored by TLC using EtOAc and n-hexane=
1:2 as the mobile phase and stirred until the starting materi-
al disappeared. After being cooled to room temperature, the
mixture solvent was removed under reduced pressure. The
reaction mixture was diluted with CH2Cl2 and the residue
was extracted with aqueous NH4Cl (3”30 mL). The organic
layer was dried over MgSO4. After removal of the solvent,
the residue was purified by flash chromatography on silica
gel to give desired product.
This research was supported financially by the Institute for
Basic Science (IBS-R010-G1).
References
[1] For selected recent reviews, see: a) S. R. Chemler, P. H.
Fuller, Chem. Soc. Rev. 2007, 36, 1153; b) M. Schlosser,
F. Mongin, Chem. Soc. Rev. 2007, 36, 1161; c) J.
Wencel-Delord, T. DrÅge, F. Liu, F. Glorius, Chem. Soc.
Rev. 2011, 40, 4740; d) S. H. Cho, J. Y. Kim, J. Kwak, S.
Chang, Chem. Soc. Rev. 2011, 40, 5068; e) J. Yamagu-
chi, A. D. Yamaguchi, K. Itami, Angew. Chem. 2012,
124, 9092; Angew. Chem. Int. Ed. 2012, 51, 8960; f) J.
Wencel-Delord, F. Glorius, Nat. Chem. 2013, 5, 369.
[2] For selected recent reviews, see: a) A. V. Gulevich, V.
Gevorgyan, Angew. Chem. 2013, 125, 1411; Angew.
Chem. Int. Ed. 2013, 52, 1371; b) H. M. L. Davies, J. S.
Alford, Chem. Soc. Rev. 2014, 43, 5151; c) B. Chatto-
padhyay, V. Gevorgyan, Angew. Chem. 2012, 124, 886;
Angew. Chem. Int. Ed. 2012, 51, 862.
Full characterization data and copies of relevant spectra
are provided in the Supporting Information.
General Procedure for 7-Arylation of Triazolo-
pyridine
Triazolopyridine (0.1 mmol), aryl bromide (0.2 mmol),
(Cy3P)2PdCl2 (5 mol%), and KO-t-Bu (2 equiv.) were com-
bined in anhydrous PhMe (1.5 mL) under nitrogen condition
in a seal tube. The reaction was stirred at 1308C for 1.5 h.
Adv. Synth. Catal. 2016, 358, 958 – 964
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
963

FULL PAPERS
Youngtaek Moon et al.
[3] For selected examples, see: a) D. J. Lee, H. S. Han, J.
Shin, E. J. Yoo, J. Am. Chem. Soc. 2014, 136, 11606;
b) H. J. Jeon, D. J. Jung, J. H. Kim, Y. Kim, J. Bouffard,
S. Lee, J. Org. Chem. 2014, 79, 9865; c) J. E. Spangler,
H. M. L. Davies, J. Am. Chem. Soc. 2013, 135, 6802;
d) B. T. Parr, S. A. Green, H. M. L. Davies, J. Am.
Chem. Soc. 2013, 135, 4716; e) M. Zibinsky, V. V.
Fokin, Angew. Chem. 2013, 125, 1547; Angew. Chem.
Int. Ed. 2013, 52, 1507; f) N. Selander, B. T. Worrell, S.
Chuprakov, S. Velaparthi, V. V. Fokin, J. Am. Chem.
Soc. 2012, 134, 14670; g) T. Miura, T. Biyajima, T. Fujii,
M. Murakami, J. Am. Chem. Soc. 2012, 134, 194; h) T.
Miura, Y. Funakoshi, M. Morimoto, T. Biyajima, M.
Murakami, J. Am. Chem. Soc. 2012, 134, 17440; i) N.
Selander, B. T. Worrell, V. V. Fokin, Angew. Chem.
2012, 124, 13231; Angew. Chem. Int. Ed. 2012, 51,
13054; j) N. Grimster, L. Zhang, V. V. Fokin, J. Am.
Chem. Soc. 2010, 132, 2510; k) T. Miura, M. Yamauchi,
A. Kosaka, M. Murakami, Angew. Chem. 2010, 122,
5075; Angew. Chem. Int. Ed. 2010, 49, 4955; l) I. Bae,
H. Han, S. Chang, J. Am. Chem. Soc. 2005, 127, 2038;
m) S. H. Cho, E. J. Yoo, I. Bae, S. Chang, J. Am. Chem.
Soc. 2005, 127, 16046.
Angew. Chem. 2010, 122, 7008; Angew. Chem. Int. Ed.
2010, 49, 6856; d) X. Zhao, J. Jing, K. Lu, Y. Zhang, J.
Wang, Chem. Commun. 2010, 46, 1724; e) Y.-T. Tsoi, Z.
Zhou, A. S. C. Chan, W.-Y. Yu, Org. Lett. 2010, 12,
4506.
[7] a) R. B. Bedford, S. J. Durrant, M. Montgomery,
Angew. Chem. 2015, 127, 8911; Angew. Chem. Int. Ed.
2015, 54, 8787; b) Y. Boutadla, D. L. Davis, S. A. Mac-
gregor, A. I. Poblador-Bahamonde, Dalton Trans. 2009,
5820; c) S. Liu, J. Sawicki, T. G. Driver, Org. Lett. 2012,
14, 3744.
[8] See the Supporting Information for more details. Note
that the transformation was not successful when ArCl
was used as an arylating reagent.
[9] a) H. A. Malik, B. L. H. Taylor, J. R. Kerrigan, J. E.
Grob, K. N. Houk, J. Du Bois, L. G. Hamanna, A. W.
Patterson, Chem. Sci. 2014, 5, 2352; b) Y.-J. Liu, H. Xu,
W.-J. Kong, M. Shang, H.-X. Dai, J.-Q. Yu, Nature
2014, 515, 389.
[10] a) T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. Soc.
Jpn. 1971, 44, 581; b) R. F. Heck, J. P. Nolley Jr, J. Org.
Chem. 1972, 37, 2320.
[11] S. Oi, K. Sakai, Y. Inoue, Org. Lett. 2005, 7, 4009.
[12] B. Abarca, R. Ballesteros, F. Mojarred, G. Jones, D. J.
Mouat, J. Chem. Soc. Perkin Trans. 1 1987, 1865.
[13] For details of the computational studies, see the Sup-
porting Information.
[4] For selected recent reviews, see: a) I. V. Seregin, V. Ge-
vorgyan, Chem. Soc. Rev. 2007, 36, 1173; b) A. V. Gule-
vich, A. S. Dudnik, N. Chernyak, V. Gevorgyan, Chem.
Rev. 2013, 113, 3084.
[5] J. H. Kim, T. Gensch, D. Zhao, L. Stegemann, C. A.
Strassert, F. Glorius, Angew. Chem. 2015, 127, 11126;
Angew. Chem. Int. Ed. 2015, 54, 10957.
[6] For selected examples of Pd-catalyzed arylation reac-
tions with diazo compounds, see: a) J. Barluenga, P.
Moriel, C. ValdØs, F. Aznar, Angew. Chem. 2007, 119,
5683; Angew. Chem. Int. Ed. 2007, 46, 5587; b) C. Peng,
Y. Wang, J. Wang, J. Am. Chem. Soc. 2008, 130, 1566;
c) J. Barluenga, M. Escribano, F. Aznar, C. ValdØs,
[14] a) D. S. Lala, R. Mukherjee, I. G. Schulman, S. S. C.
Koch, L. J. Dardashti, A. M. Nadzan, G. E. Croston,
R. M. Evans, R. A. Heyman, Nature 1996, 383, 450;
b) H. Yoshida, Y. Takemoto, K. Takaki, Chem.
Commun. 2014, 50, 8299.
[15] Removal of the reactive tert-butoxide anion was crucial
for the Pd-catalyzed denitrogenative arylation reaction
and the addition of K2CO3 was not effective for a one-
pot procedure.
964
asc.wiley-vch.de
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 958 – 964