Palladium-Catalyzed Arylation of Benzylic C-H Bonds of Azaarylmethanes with Aryl Sulfides

Article abstract of DOI:10.1055/s-0036-1589098

Benzylic C-H arylation of azaarylmethanes with aryl sulfides has been developed by using a Pd-NHC catalyst and an amide base. Various azaarylmethanes and aryl sulfides were involved in the reaction to afford the corresponding diarylmethanes in good to excellent yields. Moreover, triarylmethane synthesis was accomplished through iterative arylations of 2- or 4-methylpyridine with two different aryl sulfides.

Full text of DOI:10.1055/s-0036-1589098

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
©
Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
letter
A
en
Synlett
K. Gao et al.
Letter
Palladium-Catalyzed Arylation of Benzylic C–H Bonds of Azaaryl-
methanes with Aryl Sulfides
Ke Gao
cat. Pd-NHC
Keita Yamamoto
Keisuke Nogi
SMe
Me
N
Ar2
KN(SiMe3)2
N
Ar2
Ar1
+
Ar1
Hideki Yorimitsu*
15 examples
70–96%
Department of Chemistry, Graduate School of Science, Kyoto
University, Sakyo-ku, Kyoto 606-8502, Japan
yori@kuchem.kyoto-u.ac.jp
Dedicated to Professor Victor Snieckus in celebration of his 80th
birthday
Received: 26.06.2017
Accepted after revision: 17.07.2017
Published online: 17.08.2017
erocyclic carbene (NHC) catalyst and sterically congested
6h
amide base. Later, we adapted this methodology for
3
6j
DOI: 10.1055/s-0036-1589098; Art ID: st-2017-r0514-l
C(sp )–H arylation to invent α-arylation of ketimines.
We envisioned that benzylic C–H bonds of azaarylmeth-
anes such as 2-methylpyridine would also undergo aryla-
tion with aryl sulfides to afford diarylmethanes. Although
benzylic C–H arylation of azaarylmethanes has been
Abstract Benzylic C–H arylation of azaarylmethanes with aryl sulfides
has been developed by using a Pd-NHC catalyst and an amide base. Var-
ious azaarylmethanes and aryl sulfides were involved in the reaction to
afford the corresponding diarylmethanes in good to excellent yields.
Moreover, triarylmethane synthesis was accomplished through iterative
arylations of 2- or 4-methylpyridine with two different aryl sulfides.
7–9
achieved by employing aryl halides as aryl donors,
aryl
sulfides have never been utilized in the transformation.
Here, we report benzylic C–H arylation of azaarylmethanes
with aryl sulfides with the aid of a Pd-NHC catalyst and
strongly basic KN(SiMe ) as a base, affording diarylmeth-
Key words C–H arylation, palladium catalyst, aryl sulfides
3
2
Transition-metal-catalyzed cross-coupling to construct
C–C bonds is a mainstay in the field of organic chemistry,1
and expansion of the scope of electrophilic coupling part-
ners is an ongoing issue for synthetic organic chemists.
While C–I and C–Br bonds have conventionally served as
electrophilic coupling partners, transformations of inert
anes as the products.
Phenylation of 2-methylpyridine (2a) with methyl phe-
nyl sulfide (1a) in octane was chosen as a model reaction. In
the presence of three equivalents of KN(SiMe ) as a base,
3
2
we screened a series of palladium precatalysts (Table 1).
Palladium NHC complexes were again found to be effective;
bonds such as C–Cl,2 C–F, and C–O bonds have been
3
4
SingaCycle-A1 (Figure 1) gave 73% yield of 2-benzylpyri-
10
emerging as new areas to expand the scope.
dine (3aa) accompanied by a small amount of doubly phe-
nylated triarylmethane 4aa (entry 1). The total yield of 3aa
and 4aa was increased when SingaCycle-A310 was employed
(entry 2). By shortening the reaction time from 24 h to 12 h,
the yield of 3aa was improved to 83%, and 3aa was isolated
in 78% yield (entry 3).11 Two equivalents of 2a were indis-
pensable for smooth arylation, and the yield of 3aa was sig-
nificantly decreased with one equivalent of 2a (entry 4).
The yield of 4aa was significantly increased when 2a was
used as the limiting substrate and treated with two equiva-
lents of 1a (entry 5). Moderate yields of 3aa were obtained
with Pd-PEPPSI-NHC precatalysts12 (entries 6–8). Phos-
phine-ligated palladium complexes showed lower reactivi-
ties (entries 9 and 10).
Catalytic C–S bond transformations of aryl sulfides have
also been investigated for a long time because of their ver-
5
satility as well as ubiquity. Although rather strong C–S
bonds and catalyst-poisonous sulfur-containing leaving
groups often lower the efficiency of the catalysis, efficient
transformations have been emerging with the aid of coordi-
natively unsaturated and highly electron-rich metal cata-
lysts.
As a part of our research interest in the invention of cat-
alytic C–S bond transformations of aryl sulfides,6 we re-
cently developed arylation of relatively acidic C–H bonds
6h,6j
with aryl sulfides through deprotonation in situ.
For in-
2
stance, C(sp )–H arylation of polyfluoroarenes and het-
eroarenes was accomplished by using a palladium N-het-
We then tested the effect of bases. Alteration of the
counter cation from potassium to sodium drastically
changed the selectivity of the reaction; 4aa was obtained in
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

B
Synlett
K. Gao et al.
Letter
8
0% yield as the major product when NaN(SiMe ) was used
3 2
NHC
IPr
IPr
(
Table 1, entry 11). On the other hand, LiN(SiMe3)2 im-
Pd Cl
Pd Cl
O
Cl Pd Cl
N
proved the yield of 3aa while the selectivity and efficiency
of the reaction were low (entry 12). Other potassium bases,
KOtBu and K CO , were totally ineffective (entries 13 and
N
Me
Me
N
H
Me
Cl
Pd-PEPPSI-NHC
2
3
SingaCycle-A1
SingaCycle-A3
1
4). Octane was indispensable as the solvent, and 3aa was
obtained in low yields when toluene or 1,4-dioxane was
used instead (entries 15 and 16).
i-Pr
NH2 i-Pr
Pd
i-Pr
NH2 MeO
Pd
OMe
Table 1 Optimization of Reaction Conditions
P
P
Cl Cy Cy
Cl Cy Cy
Ph SMe
catalyst (5 mol%)
Ph
1a
base (3 equiv)
N
XPhos Pd G2
SPhos Pd G2
+
Ph
N
+
Ph
Me
N
octane
Figure 1 Ligands and palladium precatalysts used in Table 1 (IPr = 1,3-
bis(2,6-diisopropylphenyl)imidazol-2-ylidene, IMes = 1,3-bis(2,4,6-
trimethylphenyl)imidazol-2-ylidene, SIPr = 1,3-bis(2,6-diisopropylphe-
nyl)imidazolidin-2-ylidene
100 °C, 24 h
3aa
4aa
2a (2 equiv)
Entry
Catalyst
Base
Yield of
Yield of
4aa (%)
a
a,b
3
aa (%)
methyl anion but also less reactive phenyl(2-pyridyl)methyl
anion can expel the benzenethiolate anion on the palladium
catalyst, resulting in the higher yield of 4aa.
1
Singacycle-A1
Singacycle-A3
Singacycle-A3
Singacycle-A3
Singacycle-A3
Pd-PEPPSI-IPr
Pd-PEPPSI-IMes
Pd-PEPPSI-SIPr
XPhos Pd G2
SPhos Pd G2
KN(SiMe
KN(SiMe
KN(SiMe
KN(SiMe
KN(SiMe
KN(SiMe
KN(SiMe
KN(SiMe
KN(SiMe
KN(SiMe
3
3
3
3
3
3
3
3
3
3
)
2
2
2
2
2
2
2
2
2
2
73
72
16
28
17
12
32
20
0
2
)
)
)
)
)
)
)
)
)
3c
4c,e
5c,f
6
83 (78)d
68
51
67
45
54
13
18
13
31
0
SingaCycle-A3 (5 mol%)
KN(SiMe3)2 (3 equiv)
Ph
Ph SR
+
N
N
Ph
+
Ph
octane, 100 °C, 12 h
2a
(2 equiv)
3aa
4aa
7
R = C12H25
R = Ph
(1a'):
90%
68%
0%
8
0
(1a''):
32%a
9
0
Scheme 1 Effect of sulfanyl leaving groups (NMR yields). a Yield was
calculated based on the molar amount of the phenyl rings of 4aa.
1
1
1
1
1
1
1
0
0
1c
Singacycle-A3
Singacycle-A3
Singacycle-A3
Singacycle-A3
Singacycle-A3
Singacycle-A3
NaN(SiMe
)
80
38
0
3
2
2c
3 2
LiN(SiMe )
3c
With the optimal conditions established (Table 1, entry
KOt-Bu
3), we investigated the scope of the reaction with respect to
4c
K
CO
0
0
2
3
azaarylmethanes 2 with 1a (Scheme 2). 4-Methylpyridine
5c,g
6c,h
KN(SiMe
)
)
37
22
54
6
3
2
2
(
2b) successfully reacted to provide 3ab in 96% yield. Nota-
KN(SiMe
3
bly, 1.2 equivalents of 2b were sufficient to obtain diaryl-
methane 3ab in excellent yield without the formation of the
corresponding doubly phenylated product. Owing to the
lower acidity of its C–H bond, 3-methylpyridine (2c) gave
a
NMR yield.
b
Yield was calculated based on the molar amount of the phenyl rings of
aa.
4
c
For 12 h.
Isolated yield.
1
d
e
f
13
the product in only 4% yield. Both 2- and 4-methylquino-
equiv of 2a.
Ratio of 1a/2a = 2:1. Yields were determined based on the molar amount
of 2a.
Toluene as solvent.
line 2d and 2e furnished diarylmethane 3ad and 3ae in
good yields. 1-Methylisoquinoline (2f) also underwent the
reaction to afford a 83% yield of 3af. In these cases, toluene
was effective as the solvent because of the poor solubility of
methylquinoline 2d–f in octane. By using two equivalents
of 2,6-dimethylpyridine (2g), monophenylated 3ag was se-
lectively obtained. When 2,4-dimethylpyridine (2h) was
employed, a mixture of 2- and 4-phenylated products 3ah
and 3ah′ were obtained with low selectivity. Fortunately,
the two isomers could be separated by silica gel chromatog-
raphy to afford 3ah and 3ah′ in 34% and 50% yields, respec-
tively.
g
h
1
,4-Dioxane as solvent.
The methylsulfanyl moiety of 1a was not a requisite as
the leaving group. Indeed, dodecyl phenyl sulfide (1a′) fur-
nished 3aa in 90% yield (Scheme 1). Diphenyl sulfide (1a′′)
also provided 3aa while the yield was moderate and 4aa
was formed in 32% yield. Considering that the benzenethio-
late anion derived from 1a′′ would be less Lewis basic than
alkanethiolate anions, we presume that not only 2-pyridyl-
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

C
Synlett
K. Gao et al.
Letter
SingaCycle-A3 (5 mol%)
KN(SiMe3)2 (3 equiv)
SingaCycle-A3 (5 mol%)
KN(SiMe3)2 (3 equiv)
N
N
N
N
Ph SMe
Me
Ar
Ph
Ar
Ar SMe
Me
+
Ar
Ar
Ar
+
1a
octane, 100 °C, 12 h
1b–g
octane, 100 °C, 12 h
2b–h
3ab–ah
2a or 2b
3ba–3gb
(1.2 equiv)
(1.2 equiv)
N
N
N
N
N
N
Ph
MeO
Me
3da: 70%a
Ph
3
ba: 78%a
Ph
ab: 96%
Ph
3ac: (4%)a,b
3ad: 94%c
3ae: 74%c,d
N
N
N
3
Ph
Me
N
N
Ph
N
Me
Ph
N
+
MeO
Me3Si
Me
Me
3ah: 34%b
Ph
3ah': 50%b
3bb: 90%
3cb: 89%
3db: 73%
3
af: 83%c
3ag: 87%b
N
N
N
Scheme 2 Scope of the reaction with respect to azaarylmethanes.
a
NMR yield is shown in parenthesis. b 2 equiv of 2. Toluene was used
c
instead of octane. d For 24 h.
We then surveyed the scope of the reaction with respect
to aryl sulfides with 2a or 2b (Scheme 3). Electron-rich 4-
methoxyphenyl methyl sulfide (1b) smoothly reacted to af-
ford diarylmethanes 3ba and 3bb in good yields. Despite
the strongly basic reaction conditions, the trimethylsilyl
moiety of 3cb survived. The methyl moiety at the ortho-
position of aryl sulfide 1d did not hamper the reaction,
yielding 3da and 3db in good yields. Even more sterically
hindered ortho-phenyl-substituted aryl sulfide 1e was
smoothly converted into 3eb in 84% yield.
3
eb: 84%
3fb: 80%
3gb: 79%
Scheme 3 Scope of the reaction with respect to aryl sulfides. a 2 equiv
of 2a.
furnishing an 88% yield of 5 (Scheme 4a). On the other
hand, 4-benzylpyridine (3ab) was reluctant to undergo the
coupling reaction under similar conditions, and desired tri-
arylmethane 6 was obtained in only 10% NMR yield. Fortu-
nately, we found that employing NaN(SiMe3)2 instead of
KN(SiMe3)2 improved the yield of 6 to 60% (Scheme 4b).
This is consistent with the result of the initial screening in
which NaN(SiMe ) promoted double arylation more effec-
We next turned our attention to synthesis of triaryl-
methanes by using the present benzylic C–H arylation with
aryl sulfides (Scheme 4). 2-Benzylpyridine (3aa) reacted
smoothly with two equivalents of methyl p-tolyl sulfide
3
2
tively than KN(SiMe ) (Table 1, entries 3 and 11).
3
2
(
1h) with the combination of SingaCycle-A3/KN(SiMe3)2
Me
4
-MeC6H4SMe (2 equiv) (1h)
SingaCycle-A3 (5 mol%)
KN(SiMe3)2 (3 equiv)
SingaCycle-A3 (5 mol%)
Me
N
N
KN(SiMe3)2 (3 equiv)
Ph SMe
Ph
(a)
+
1a
octane, 100 °C, 12 h
(in Table 1, entry 3)
toluene, 100 °C, 24 h
N
Ph
2a
3
aa: 78%
5: 88%
69% overall
N
4
-MeC6H4SMe (2 equiv) (1h)
SingaCycle-A3 (5 mol)
MN(SiMe3)2 (3 equiv)
SingaCycle-A3 (5 mol%)
KN(SiMe3)2 (3 equiv)
N
N
Ph SMe
(b)
+
1a
octane, 100 °C, 12 h
toluene, 100 °C, 24 h
Ph
(in Scheme 2)
Ph
Me
Me
2b
3ab: 96%
6
a
M = K: (10%)
Na: 60%, 58% overall
Scheme 4 Triarylmethane synthesis through iterative arylations with aryl sulfides. a NMR yield shown in parentheses.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

D
Synlett
K. Gao et al.
Letter
In conclusion, we have developed benzylic C–H aryla-
tion of azaarylmethanes with aryl sulfides by using a Pd-
NHC catalyst and an amide base. A range of azaarylmeth-
anes and aryl sulfides were converted into the correspond-
ing diarylmethanes in good to excellent yields. We have also
accomplished triarylmethane synthesis through iterative
arylations of 2- and 4-methylpyridine with two different
aryl sulfides. Further studies on the development of novel
C–S bond-cleaving transformations are under way in our
group.
3674. (h) Wang, L.; He, W.; Yu, Z. Chem. Soc. Rev. 2013, 42, 599.
(
i) Modha, S. G.; Mehta, V. P.; Van der Eycken, E. V. Chem. Soc.
Rev. 2013, 42, 5042. (j) Pan, F.; Shi, Z.-J. ACS Catal. 2014, 4, 280.
k) Gao, K.; Otsuka, S.; Baralle, A.; Nogi, K.; Yorimitsu, H.; Osuka,
(
A. J. Synth. Org. Chem., Jpn. 2016, 74, 1119.
(
6) (a) Kanemura, S.; Kondoh, A.; Yorimitsu, H.; Oshima, K. Synthe-
sis 2008, 2659. (b) Ookubo, Y.; Wakamiya, A.; Yorimitsu, H.;
Osuka, A. Chem. Eur. J. 2012, 18, 12690. (c) Murakami, K.;
Yorimitsu, H.; Osuka, A. Angew. Chem. Int. Ed. 2014, 53, 7510.
(d) Sugahara, T.; Murakami, K.; Yorimitsu, H.; Osuka, A. Angew.
Chem. Int. Ed. 2014, 53, 9329. (e) Otsuka, S.; Fujino, D.;
Murakami, K.; Yorimitsu, H.; Osuka, A. Chem. Eur. J. 2014, 20,
13146. (f) Baralle, A.; Otsuka, S.; Guérin, V.; Murakami, K.;
Yorimitsu, H.; Osuka, A. Synlett 2015, 26, 327. (g) Gao, K.;
Yorimitsu, H.; Osuka, A. Eur. J. Org. Chem. 2015, 2678.
Funding Information
(
1
2
h) Otsuka, S.; Yorimitsu, H.; Osuka, A. Chem. Eur. J. 2015, 21,
4703. (i) Baralle, A.; Yorimitsu, H.; Osuka, A. Chem. Eur. J. 2016,
2, 10768. (j) Gao, K.; Yorimitsu, H.; Osuka, A. Angew. Chem. Int.
This work was supported by JSPS KAKENHI Grant Numbers
JP16H01019, JP16H04109, JP16H06887, as well as JST ACT-C Grant
Number JPMJCR12ZE, Japan. H.Y. thanks the Japan Association for
Chemical Innovation, the Tokuyama Science Foundation, and The Nai-
to Foundation for financial support. G.K. acknowledges a JSPS Post-
Ed. 2016, 55, 4573.
(
7) For recent reviews on transition-metal-mediated synthesis of
diarylmethanes and triarylmethanes, see: (a) Houwer, J. D.;
Maes, B. U. W. Synthesis 2014, 46, 2533. (b) Nambo, M.;
Crudden, C. M. ACS Catal. 2015, 5, 4734.
doctoral Fellowship for Foreign Researchers.
a
Jp
an
S
o
ecity
o
f
r
hte
P
or
m
o
itn
of
Secince
P
J(1
6
H
0
1
0
1
9aJ)p
a
n
S
o
ecity
o
f
r
hte
P
or
m
o
itn
of
S
ecin
c
e
P
J(1
6
H
0
4
1
0
9aJ)p
a
n
S
o
ecity
o
f
r
hte
Pro
m
o
itn
of
Secince
P
J(1
6
H
0
6
8
8
7aJ)p
a
n
Secince
a
n
d
Tech
n
o
lg
y
A
g
e
n
c
y
P
J(M
C
J
R
1
2
Z
E)
Supporting Information
(8) For diarylmethane synthesis through C–H arylation with aryl
electrophiles, see: (a) Campeau, L.-C.; Schipper, D. J.; Fagnou, K.
J. Am. Chem. Soc. 2008, 130, 3266. (b) Mousseau, J. J.; Larivee, A.;
Charette, A. B. Org. Lett. 2008, 10, 1641. (c) Schipper, D. J.;
Campeau, L.-C.; Fagnou, K. Tetrahedron 2009, 65, 3155.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1589098.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
(
d) Burton, P. M.; Morris, J. A. Org. Lett. 2010, 12, 5359. (e) Duez,
References and Notes
S.; Steib, A. K.; Manolikakes, S. M.; Knochel, P. Angew. Chem. Int.
Ed. 2011, 50, 7686. (f) Duez, S.; Steib, A. K.; Knochel, P. Org. Lett.
2
(
1) (a) de Meijere, A.; Diederich, F. Metal-Catalyzed Cross-Coupling
Reactions; Wiley-VCH: Weinheim, Germany, 2004.
b) Nishihara, Y. Applied Cross-Coupling Reactions; Springer:
012, 14, 1951.
(
9) For triarylmethane synthesis through C–H arylation of diaryl-
methanes with aryl electrophiles, see: (a) Inoh, J.-I.; Satoh, T.;
Pivsa-Art, S.; Miura, M.; Nomura, M. Tetrahedron Lett. 1998, 39,
(
Heidelberg, 2013. (c) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz,
E.; Lemaire, M. Chem. Rev. 2002, 102, 1359. (d) Alberico, D.;
Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (e) Suzuki, A.
Angew. Chem. Int. Ed. 2011, 50, 6722.
4
2
673. (b) Niwa, T.; Yorimitsu, H.; Oshima, K. Org. Lett. 2007, 9,
373. (c) McGrew, G. I.; Temaismithi, J.; Carroll, P. J.; Walsh, P. J.
Angew. Chem. Int. Ed. 2010, 49, 5541. (d) Song, G.; Su, Y.; Gong,
X.; Han, K.; Li, X. Org. Lett. 2011, 13, 1968. (e) Zhang, J.; Bellomo,
A.; Creamer, A. D.; Dreher, S. D.; Walsh, P. J. J. Am. Chem. Soc.
(2) (a) Herrmann, W. A. Angew. Chem. Int. Ed. 2002, 41, 1290.
(
(
b) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41, 4176.
c) Bedford, R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem. Rev.
2
012, 134, 13765. (f) Chen, J.-J.; Onogi, S.; Hsieh, Y.-C.; Hsiao, C.-
C.; Higashibayashi, S.; Sakurai, H.; Wu, Y.-T. Adv. Synth. Catal.
012, 354, 1551. (g) Bellomo, A.; Zhang, J.; Trongsiriwat, N.;
2
004, 248, 2283.
3) (a) Amii, H.; Uneyama, K. Chem. Rev. 2009, 109, 2119.
b) Ohashi, M.; Ogoshi, S. Catalysts 2014, 4, 321. (c) Ahrens, T.;
Kohlmann, J.; Ahrens, M.; Braun, T. Chem. Rev. 2015, 115, 931.
d) Ohashi, M.; Ogoshi, S. J. Synth. Org. Chem., Jpn. 2016, 74,
047.
4) (a) Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Acc. Chem. Res. 2010, 43, 1486.
b) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
Resmerita, A.-M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111,
(
2
(
Walsh, P. J. Chem. Sci. 2013, 4, 849. (h) Zhang, J.; Bellomo, A.;
Trongsiriwat, N.; Jia, T.; Carroll, P. J.; Dreher, S. D.; Tudge, M. T.;
Yin, H.; Robinson, J. R.; Schelter, E. J.; Walsh, P. J. J. Am. Chem.
Soc. 2014, 136, 6276. (i) Ji, X.; Huang, T.; Wu, W.; Liang, F.; Cao,
S. Org. Lett. 2015, 17, 5096. (j) Cao, X.; Sha, S.-C.; Li, M.; Kim, B.-
S.; Morgan, C.; Huang, R.; Yang, X.; Walsh, P. J. Chem. Sci. 2016, 7,
(
1
(
(
6
11. (k) Zhang, J.; Sha, S.-C.; Bellomo, A.; Trongsiriwat, N.; Gao,
F.; Tomson, N. C.; Walsh, P. J. J. Am. Chem. Soc. 2016, 138, 4260.
10) (a) Kantchev, E. A. B.; Ying, J. Y. Organometallics 2009, 28, 289.
b) Peh, G.-R.; Kantchev, E. A. B.; Er, J.-C.; Ying, J. Y. Chem. Eur. J.
010, 16, 4010.
1346. (c) Tobisu, M.; Chatani, N. Top. Organomet. Chem. 2013,
44, 35. (d) Han, F.-S. Chem. Soc. Rev. 2013, 42, 5270. (e) Li, W.-N.;
(
Wang, Z.-L. RSC Adv. 2013, 3, 25565. (f) Cornella, J.; Zarate, C.;
Martin, R. Chem. Soc. Rev. 2014, 43, 8081. (g) Tobisu, M.;
Chatani, N. Acc. Chem. Res. 2015, 48, 1717. (h) Tollefson, E. J.;
Hanna, L. E.; Jarvo, E. R. Acc. Chem. Res. 2015, 48, 2344.
(
2
(
11) C–H Arylation of 2a with 1a; Typical Procedure: A Schlenk
tube was charged with SingaCycle-A3 (10 mg, 0.015 mmol),
potassium bis(trimethylsilyl)amide (KN(SiMe ) ; 0.18 g, 0.90
(
5) For reviews, see: (a) Sugimura, H.; Okamura, H.; Miura, M.;
Yoshida, M.; Takei, H. Nippon Kagaku Kaishi 1985, 416. (b) Naso,
F. Pure Appl. Chem. 1988, 60, 79. (c) Luh, T.-Y.; Ni, Z.-J. Synthesis
3
2
mmol) and octane (1.0 mL). Methyl phenyl sulfide (1a; 38 mg,
.30 mmol) and 2-methylpyridine (2a; 59 μL, 0.60 mmol) were
0
1
(
990, 89. (d) Luh, T.-Y. Acc. Chem. Res. 1991, 24, 257.
e) Fiandanese, V. Pure Appl. Chem. 1990, 62, 1987. (f) Dubbaka,
S. R.; Vogel, P. Angew. Chem. Int. Ed. 2005, 44, 7674.
g) Prokopcová, H.; Kappe, C. O. Angew. Chem. Int. Ed. 2008, 47,
added, and the resulting mixture was stirred at 100 °C for 12 h.
After the addition of H O, the mixture was passed through pads
of Na SO and silica gel, and concentrated under reduced pres-
sure. The residue was purified by silica gel column chromatog-
2
2
4
(
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

E
Synlett
K. Gao et al.
Letter
raphy (toluene/EtOAc, 5:1) to give 3aa (40 mg, 0.23 mmol, 78%)
Valente, C. Synthesis 2008, 2776. (c) Valente, C.; Çalimsiz, S.; Hoi,
K. H.; Mallik, D.; Sayah, M.; Organ, M. G. Angew. Chem. Int. Ed.
2012, 51, 3314.
1
13
as a yellow oil. All the resonances in H and C NMR spectra
were consistent with reported values, see: Niwa, T.; Yorimitsu,
H.; Oshima, K. Angew. Chem. Int. Ed. 2007, 46, 2643.
(13) Isomeric 2-, 3-, and 4-methylpyridines have pKa values of 34,
37.7, and 32.3 in THF, respectively, see: Fraser, R. R.; Mansour, T.
S.; Savard, S. J. Org. Chem. 1985, 50, 3232.
(
12) For reviews of Pd-PEPPSI-NHC catalysts, see: (a) Kantchev, E. A.
B.; O’Brien, C. J.; Organ, M. G. Aldrichimica Acta 2006, 39, 117.
(b) Organ, M. G.; Chass, G. A.; Fang, D.-C.; Hopkinson, A. C.;
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E