Acid-Free Silver-Catalyzed Cross-Dehydrogenative Carbamoylation of Pyridines with Formamides

Article abstract of DOI:10.1055/s-0035-1561975

Primary pyridylcarboxamides are prevalent parent structures in bioactive molecules and have the apparent advantages over N-protected derivatives as synthetic building blocks. However, no practical methods have been developed for direct synthesis of this compound class from unfunctionalized pyridines. We herein present a general, safe, concise, acid-free, and highly selective method for the C2-carbamoylation of pyridines with unprotected formamide and N-methyl formamide through the cleavage of two C-H bonds.

Full text of DOI:10.1055/s-0035-1561975

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©
Georg Thieme Verlag Stuttgart · New York
2016, 27, A–F
A
letter
Synlett
W. Han et al.
Letter
Acid-Free Silver-Catalyzed Cross-Dehydrogenative Carbamoyla-
tion of Pyridines with Formamides
Wei Han*a,b
Fengli Jina
Qian Zhaoa
Hongyan Dua
Lifang Yaoa
O
O
N
H
AgNO3
N
R1
+
NHR2
NHR2
H
HCO2Na
K2S2O8
H2O, 80 °C
R1
R2 = H, Me
up to 95% yield
acid-free
a
mild conditions
excellent regioselectivity
ligand- and additive-free
Jiangsu Key Laboratory of Biofunctional Materials, Key Laboratory
of Applied Photochemistry, School of Chemistry and Materials
Science, Nanjing Normal University, Wenyuan Road NO.1, Nanjing
210023, P. R. of China
whhanwei@gmail.com
Jiangsu Collaborative Innovation Center of Biomedical Functional
Materials, Nanjing 210023, P. R. of China
b
Received: 29.01.2016
Accepted after revision: 14.03.2016
Published online: 06.04.2016
cessible to direct synthesis of primary pyridylcarboxam-
ides. Up to date, there are limited examples for the direct
synthesis of primary pyridylcarboxamides via palladium-
catalyzed aminocarbonylations of aryl halides with ammo-
nia equivalents. Recently, Bhanage et al. reported methoxyl-
amine hydrochloride undergoing sequential carbonylation
DOI: 10.1055/s-0035-1561975; Art ID: st-2016-w0059-l
Abstract Primary pyridylcarboxamides are prevalent parent structures
in bioactive molecules and have the apparent advantages over N-pro-
tected derivatives as synthetic building blocks. However, no practical
methods have been developed for direct synthesis of this compound
class from unfunctionalized pyridines. We herein present a general,
safe, concise, acid-free, and highly selective method for the C2-carba-
moylation of pyridines with unprotected formamide and N-methyl for-
mamide through the cleavage of two C–H bonds.
and demethoxylation in the presence of PdCl (10 mol%)
2
6
and CO (5 atm) to construct amide groups. Furthermore,
the Skrydstrup group employed ammonium carbamate as
ammonia synthon and 9-methyl-9H-fluorene-9-carbonyl
chloride (COgen) as CO source to synthesize primary pyr-
7
idylcarboxamides by a two-chamber system. Recently, Ba-
Key words pyridylcarboxamides, pyridines, C–H bonds functionaliza-
tion, carbamoylation, formamides
burajan and co-workers used nongaseous precursors NH Cl
4
8
and Co (CO) for both ammonia and CO, respectively. These
2
8
Primary pyridylcarboxamides are widely used as versa-
protocols are attractive as both the NH and CO sources can
3
tile building blocks for pharmaceuticals and herbicides ow-
ing to the innate advantages of these free N–H groups over
N-protected derivatives in synthetic manipulations and
readily be handled. However, these more sophisticated syn-
thons cause higher cost and lower atom efficiency (Scheme
1, eq. 1: conditions B). Noteworthy progress is that forma-
1
their unique biological activity. As a result, numerous
mide acts both as the NH and CO surrogate for carbamoy-
3
methodologies have been developed for primary pyridyl-
carboxamides. Generally, these compounds are constructed
by reacting carboxylic acids or benzoic acid derivatives
lation of aryl halides, although a high temperature (120–
180 °C) and a strong base are required to ensure the decom-
position of the formamide into CO and ammonia. In all
9
(
e.g., acyl chlorides, anhydrides, and esters) with ammonia,
above-mentioned methods, the use of preactivated starting
materials (often aryl iodides/bromides), thus adding multi-
step procedures towards the construction of one desired
chemical bond, make this protocol unfavorable in both the
environment and large-scale applications (Scheme 1, eq. 1).
The ideal way to address those issues is to direct func-
tionalization of pyridyl C–H bonds via cross-dehydrogena-
tive coupling (CDC) approach.10 However, unlike various re-
liable means for the C–H carbamoylation of other (hete-
2
albeit producing stoichiometric amounts of waste. To over-
come these disadvantages, the atom-economic palladium-
catalyzed aminocarbonylation of aromatic halides with am-
monia has utilized as an alternative and attractive strategy
(
Scheme 1, eq. 1: conditions A).3 However, the required
handling of two toxic, flammable, and/or corrosive gases
carbon monoxide (CO) and ammonia] and high-pressure
[
equipments restrict their large-scale applications. Although
aqueous ammonia and some sophisticated ammonia
equivalents have been demonstrated to prepare aromatic
primary amides, such as hexamethyldisilazane (HMDS), N-
tert-butylamine, benzylamine, allyl amine, hydroxylamine,
and a titanium–nitrogen complex; these methods are inac-
4
11
ro)arenes, the methods for introducing amido groups into
5
pyridine rings through pyridyl C–H decoration suffer from
the following inherent difficulties:12 (1) the low reactivity
of pyridine rings because of their poor electron density,
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

B
Synlett
W. Han et al.
Letter
a
Pd-catalyzed aminocarbonylations
of aryl halides
Table 1 AgNO -Catalyzed Carbamoylation of 1a with Formamide
3
Previous work:
N
N
N
[Pd]
2
CO Me
R
R
CONH2
(
1)
2
CO Me
R
X
conditions A: CO and NH3
conditions B: CO and/or NH3 synthons
[Ag]
X = I, Br
+
HCONH2
oxidant, additive
N
N
CONH2
This work: CDC protocol
1a
2
3a
O
N
[Ag]
CONH2 (2)
R
H
+
H
NH2
Entry
[Ag]
Oxidant
Base
Yield of 3a (%)
acid-free
1
2
3
4
5
6
7
8
9
AgNO
–
3
K
K
–
K
K
K
K
K
2
S
2
O
O
8
8
Na
Na
Na
–
2
2
2
CO
CO
CO
3
3
3
52
0
Scheme 1 Strategies for the construction of primary pyridylcarboxam-
ides
2
S
2
AgNO
AgNO
3
3
0
2
2
2
2
2
S
S
S
S
S
2
2
2
2
2
O
O
O
O
O
8
8
8
8
8
8
8
0
particularly, at the C-2 and C-6 positions; (2) the strong
tendency of pyridines to bind to transition-metal centers
leading to metal catalysts sequestration and deactivation;
and (3) the regiocontrol of pyridine C–H functionalization.
A seminal work reported by Li and co-workers described
the palladium-catalyzed twofold C–H cross-dehydrogena-
tive coupling of preactivated isoquinoline N-oxides or quin-
AgOAc
AgBF
AgOTf
Na
Na
Na
2
2
2
CO
CO
CO
3
3
3
43
39
41
55
4
AgNO
3
2 3
Cs CO
AgNO3
K S O
2
2
2
NaHCO3
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
AcONa
67
95 (79)b
10
11
12
13
AgNO
AgNO
AgNO
AgNO
AgNO
3
3
3
3
3
K
2
S
O
13
oline N-oxides with formylamides. Unfortunately, this ap-
proach has been totally unsuccessful with pyridyl C–H
bonds.
TBHP
BPO
0
5
DTBP
41
89
95
91
<5
78
80
83
Among the known NH and CO equivalents, formamide
3
14c
15
is an ideal carbamoylation reagent only if its C–H bond can
be functionalized effectively, since it is inexpensive, stable,
easily to handle, and almost no waste formation after cross-
dehydrogenative coupling. While a number of reports are
available on direct activation of N-protected formamide C–
2 2
K S O
8
8
8
8
8
8
8
d
AgNO3
K S O
2
2
2
2
2
2
2
2
2
2
2
2
1
6
7
AgNO
AgNO
AgNO
AgNO
AgNO
3
3
3
3
3
K
K
K
K
K
S
S
S
S
S
O
O
O
O
O
1
t-BuONa
14
18
Et
i-Pr
DBU
3
N
H bond, catalytic C–H functionalization of formamide has
met with no success to date, probably because of uncom-
19
2
NEt
15
patibility of free N–H groups. Although few examples re-
ported direct carbamoylation of pyridines with formamide,
these contributions suffer from some limitations, such as
low yields (often less than 50%), low chemoselectivity, nar-
row scope of pyridine substrates, and/or the use of severely
20
a
Reaction conditions (unless otherwise stated): 1a (0.5 mmol), 2 (2 mL),
(1 atm), 120 °C, 4 h.
[
Ag] (20 mol%), oxidant (1.5 mmol), base (1.0 mmol), O
2
b
3
Conditions: AgNO (10 mol%).
Conditions: 8 h in air.
Conditions: 5 h at 80 °C.
c
d
16
corrosive acids.
Recently, we reported a novel combination of palladi-
um-silver-copper-mediated dehydrogenative cross-cou-
1
7
plings of benzazoles with azoles, and uncovered silver
played a critical role in regiocontrol of C–H bonds activa-
tion in both substrates. Herein, we reveal the first silver-
catalyzed dual C–H oxidation–cross-coupling of pyridines
with formamide to a library of primary pyridylcarboxam-
ides (Scheme 1, eq. 2). Notably, this method offers an oper-
ationally simple, inherently safe, highly efficient, and regio-
selective conversion process without the requirement of
preactivated substrates, designed ligands, and a huge excess
of pyridines.
component in the combination was necessary to the reac-
tion. We also examined other silver catalysts, such as
AgOAc, AgBF , and AgOTf (Table 1, entries 5–7), and found
4
that these catalysts provided a little bit lower yields than
AgNO . Other bases such as Cs CO and NaHCO resulted in
3
2
3
3
moderate yields of 3aa (Table 1, entries 8 and 9). To our de-
light, a weak base HCOONa was found to be the most effec-
tive, affording the product 3a in 95% isolated yield (Table 1,
entry 10). Additionally, AcONa, Et N, i-Pr NEt, and DBU
3
2
were also good bases for this transformation (Table 1, en-
tries 16 and 18–20). However, a strong base t-BuONa was
completely ineffective in the reaction (Table 1, entry 17).
TBHP, BPO (dibenzoyl peroxide), and DTBP (di-tert-butyl
peroxide) as the oxidants did not enable the reaction to
perform well (Table 1, entries 11–13). In the air atmo-
sphere, the reaction also proceeded effectively, providing
Initially, we started our investigation by examining sil-
ver-catalyzed carbamoylation of methyl isonicotinate (1a)
with formamide (2, Table 1). Gratifyingly, a carbamoylated
product 3a was obtained in 52% yield with perfect C2 regio-
selectivity (no appreciable amount of isomers in our crude
product was found) in the presence of Na CO . And each
2
3
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

C
Synlett
W. Han et al.
Letter
the desired product in 89% yield in eight hours (Table 1, en-
try 14). Gratifyingly, decreasing the reaction temperature to
partner, surprisingly, only the C2-selective carbamoylated
product was obtained (3q) and nitrogen atom-directed
product was not observed. For other substrates, di(pyridin-
2-yl)methanone afforded a low yield (3r) and quinoline was
unsuitable for this system to result in a complex mixture. To
highlight the applicability of this method, the model reac-
tion was scaled up to 5 mmol under normal conditions,
which furnished the desired product 3a in 88% yield.
80 °C had little impact on the transformation (Table 1, entry
15).
Under the optimized conditions, we next set out to ex-
plore the scope of the AgNO -catalyzed carbamoylation of
3
pyridines with formamide. We initially investigated the car-
bamoylation of 2-ethylpyridine (1b), However, to our disap-
pointment, a 70/28 (C2/C4) mixture of isomers was ob-
served (see the Supporting Information). According to pre-
O
AgNO3
R1
R1
18
+
NH2
vious reports,
solvent played an important role in
H
NH2
K2S2O8, HCO2Na
H2O, O2, 80 °C
N
N
influencing the regioselectivity of pyridines. Water is an
ideal solvent and was chosen to regulate regioselectivity.
Much to our delight, an excellent C2 regioselectivity (Table
S1, entry 3) could be achieved when the volume ratio of
water to formamide was increased to 2:10, whereas when
the amount of water was further raised, the C2 regioselec-
tivity would decrease accordingly (Table S1, entries 4 and
O
1
2
3
CO2Me
NH2
N
NH2
NH2
N
NH2
N
N
O
O
O
O
3a, 5 h, 95%
3b, 4 h, 91%
3c, 3 h, 89%
3d, 6 h, 80%
5).
Subsequently, under the newly established optimal con-
ditions, we conducted carbamoylative reactions on a vari-
ety of commercially available pyridines (Scheme 2).19 Gen-
erally, both electron-donating and electron-withdrawing
groups at the ortho, meta, or para position of pyridines
were compatible, affording the corresponding carbamoylat-
ed products in satisfactory yields with high levels of C2 se-
lectivity (minor C4-products: <10%). High substituent com-
patibility was also observed: for instance, Me, Et, MeO, EtO,
COMe, COOMe, COOEt, aryl, and n-pentyl groups, on the
pyridine moiety were tolerated well. 2-Ethylpyridine and 2-
pentylpyridine provided C2-selective pyridylcarboxamides
in 91% and 80% yields (3b and 3d), respectively. It was
found that a pyridine with a methyl at C4 position gave the
desired product in a higher yield of 89% (3c). Pyridines hav-
ing two methyl substituents at different positions on the
pyridine ring could undergo the expected C2 carbamoyla-
tion in excellent yields (3e–g), and the positions of two
methyl substituents had negligible impact on these reac-
tions. A pyridine substrate with three methyl groups was
quite reactive toward formamide 3h. Furthermore, alkoxy-
substituted pyridines were also surveyed: pyridine with a
methoxy at C4, C3, or C2 position gave a higher yield than
that with an ethoxy at C2 position (3i–l); it was worth not-
ing that 3-methoxypyridine just provided 5-methoxypico-
linamide in 89% yield (3j), suggesting that less steric hin-
drance position was far more reactive. Gratifying, a simple
pyridine with multiple reactive sites with no steric hin-
drance still proceeded in excellent C2 selectivity (3m). No-
tably, electron-withdrawing ester and ketone groups on the
pyridine ring that usually reduces reactivity and selectivity
NH2
NH2
NH2
NH2
N
N
N
N
O
O
f, 4 h, 90%
O
O
3e, 4 h, 89%
3
3g, 4 h, 89%
3h, 4 h, 96%
O
O
NH2
NH2
NH2
O
N
NH2
O
N
N
N
O
O
O
O
3
i, 4 h, 88%
3j, 4 h, 89%
3k, 4 h, 83%
3l, 4 h, 76%
Ac
NH2
NH2
NH2
NH2
Ac
N
N
EtO2C
N
N
O
O
O
O
3n, 6 h, 76%
3o, 4 h, 90%
3p, 4 h, 86%
3
m, 4 h, 94%
NH2
N
NH2
N
N
NH2
N
O
O
O
O
3
q, 4 h, 51%
3r, 12 h, 29%
3r', 12 h, –
Scheme 2 Ag-catalyzed carbamoylation of pyridines with formamide.
Reagents and conditions (unless otherwise stated): 1 (0.5 mmol), 2 (2
mL), AgNO (20 mol%), HCOONa (1.0 mmol), K S O (1.5 mmol), H O
3
2
2
8
2
(
0.4 mL), O (balloon), and 80 °C. Yields are of isolated product after
2
column chromatography.
Next, the carbamoylation of other formamides was in-
vestigated. Applying the optimized conditions to N-methyl-
formamide resulted in pyridylcarboxamide 3m′ in 85% yield
within five hours (Equation 1). However, when the forma-
mide substrate was switched to DMF, its reaction with pyri-
dine (1m) did not occur (Equation 2).
20
significantly were tolerated and resulted in high yields
with high selectivity in our case (3a and 3n–p), and these
groups are versatile handles for further transformations.
While employing 3-methyl-2-phenylpyridine as a coupling
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

D
Synlett
W. Han et al.
Letter
AgNO3 (20 mol%)
K2S2O8 (3 equiv)
HCO2Na (2 equiv)
(k /k = 1.0) for C2 position of 1m indicated that the rate-
H
D
limiting step does not involve the C–H cleavage of the pyri-
dine. Furthermore, the reaction of 1a was totally inhibited
in the presence of the radical scavenger TEMPO (see the
Supporting Information). This evidence supports that the
present transformation proceeds by a radical process,
which is consistent with the mechanism of metal-catalyzed
oxidation reactions involving persulfates.
O
+
NHMe
H
N
H
H2O, O2 (1 atm), 5 h
N
N
80 °C
O
1m
3
m', 85%
Equation 1
AgNO3 (20 mol%)
K2S2O8 (3 equiv)
HCO2Na (2 equiv)
Based on the above observations and previous re-
21–23
O
search,
the following mechanism is proposed (Scheme
+
no product
3). It is known23 that the silver(I) salt can be oxidized to a
silver(II) species by peroxydisulfate, and meanwhile, the
peroxydisulfate disproportionates into a sulfate dianion
and a sulfate radical anion. Subsequently, the sulfate radical
anion oxidizes formamide to form acyl radical A. It is proba-
ble that the acyl radical A reacts with pyridine to give im-
portant intermediate B. Finally, the intermediate B is reoxi-
dized by silver(II) and provides the carbamoylative product
C and meanwhile, regeneration of the silver(I) species com-
pletes the catalytic cycle.
H
N
H2O, O2 (1 atm), 4 h
0 °C
N
8
1m
Equation 2
Considering that the above substrates proceeded in ex-
cellent C2 selectivity, we also briefly surveyed other pyri-
dines where C2 positions were blocked by substituents.
When 2-methoxy-6-methylpyridine (1s) was subjected to
the normal conditions, only the C4-selective carbamoylated
product 3s was detected (Equation 3), demonstrating the
strong preference for pyridines without C2 positions to re-
act at the C4 position in this transformation. Furthermore,
O
SO42–
H
NH2
S2O82–
SO4–
SO42–, H+
2
,4,6-trimethylpyridine, lacking of C2 and C4 positions, did
AgI
AgII
not furnish desired product (Equation 4); instead it deliv-
ered an unidentifiable side product. In conjunction with all
the above results, a conclusion can be made that in the car-
bamoylation C2 and C4 positions of pyridines are ready to
react and reactivity of C2 position has much greater prefer-
ence than that of C4 position, as is observed in the Chichib-
O
A
O
O
H
N
N
N
NH2
NH2
NH2
B
C
base·H+
base
21
abin reaction.
Scheme 3 Possible mechanism of oxidative carbamoylation of pyridine
with formamide
AgNO3 (20 mol%)
K2S2O8 (3 equiv)
HCO2Na (2 equiv)
CONH2
O
H
+
H
N
H
In summary, we presented the first example of a ligand-
less silver-catalyzed direct oxidative C–H/C–H carbamoyla-
tion of pyridines with unprotected formamide for the
preparation of primary pyridylcarboxamides. Advantages of
our procedure include the concise and safety of operation,
and in fact it is a carbon monoxide and ammonia-free route,
avoiding the use of toxic and flammable, or corrosive re-
agents. Moreover, an excellent selectivity was achieved in
the presence of water. Although excess formamide is re-
quired, it can be readily recycled for the next reactions. Pri-
mary pyridylcarboxamides are prevalent parent structures
in druglike and/or pharmaceutically relevant molecules and
have the clear advantages over N-protected derivatives as
synthetic building blocks.
O
N
H2O, O2 (1 atm)
O
N
80 °C
1
s
2
3s, 8 h, 87%
Equation 3
AgNO3 (20 mol%)
K2S2O8 (3 equiv)
HCO2Na (2 equiv)
O
H
+
no product
H
N
N
H2O, O2 (1 atm), 4 h
H
80 °C
1t
2
Equation 4
To gain preliminary insight into the mechanism of the
transformation, we carried out a kinetic isotope effect (KIE)
study (see the Supporting Information). The KIE value
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

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Synlett
W. Han et al.
Letter
Acknowledgment
(10) For recent reviews and highlights on oxidative cross dehydroge-
native couplings, see: (a) Li, C.-J. Acc. Chem. Res. 2009, 42, 335.
The work was sponsored by the Natural Science Foundation of China
21302099), the SRF for ROCS, SEM, and the Priority Academic Pro-
(b) You, S.-L.; Xia, J.-B. Top. Curr. Chem. 2010, 292, 165. (c) Lyons,
(
T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. (d) Newhouse,
T.; Baran, P. S. Angew. Chem. Int. Ed. 2011, 50, 3362. (e) Yeung, C.
S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. (f) McMurray, L.;
O’Hara, F.; Gaunt, M. J. Chem. Soc. Rev. 2011, 40, 1885. (g) Han,
W.; Ofial, A. R. Synlett 2011, 1951. (h) Bugaut, X.; Glorius, F.
Angew. Chem. Int. Ed. 2011, 50, 7479. (i) Liu, C.; Zhang, H.; Shi,
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Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112, 5879.
gram Development of Jiangsu Higher Education Institutions
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561975.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
(
k) Girard, S. A.; Knauber, T.; Li, C.-J. Angew. Chem. Int. Ed. 2014,
3, 74.
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5
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3) For a few examples of the use of CO and ammonia in palladium-
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5) (a) Takács, A.; Abreu, A. R.; Peixoto, A. F.; Pereira, M.; Kollár, L.
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18) For studies on the solvent effect in the α and γ regioselectivity
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(19) General Procedure
A 25 mL Schlenk flask was charged with AgNO3 (17.2 mg, 20
mol% Ag), K S O (408 mg, 1.5 mmol), and HCOONa (129 mg, 1.0
8460. (j) Appukkuttan, P.; Axelsson, L.; Van der Eycken, E.;
2
2
8
Larhed, M. Tetrahedron Lett. 2008, 49, 5625. (k) Wu, X.;
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mmol) before standard cycles of evacuation and back-filling
with dry and pure oxygen (three times). Corresponding pyri-
dine 1m (40 μL, 0.5 mmol), formamide (2, 2 mL), and H O (0.4
2
(6) Gadge, S. T.; Bhanage, B. M. Synlett 2014, 25, 85.
mL) were added successively. The mixture was stirred at 80 °C
for the indicated time (monitored by TLC). At the end of the
reaction, the reaction mixture was cooled to room temperature,
poured into a sat. aq NaCl solution (15 mL), and extracted with
EtOAc (3 × 15 mL). The organic phases were combined, and the
volatile components were evaporated in a rotary evaporator.
The residue was purified by flash column chromatography on
(
7) Nielsen, D. U.; Tanning, R. H.; Lindhardt, A. T.; Gogsig, T. M.;
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9) (a) Wan, Y.; Alterman, M.; Larhed, M.; Hallberg, A. J. Comb.
Chem. 2003, 5, 82. (b) Schnyder, A.; Beller, M.; Mehltretter, G.;
Nsenda, T.; Studer, M.; Indolese, A. F. J. Org. Chem. 2001, 66,
silica gel (eluent: PE–EtOAc–Et N) to afford the corresponding
3
4311.
product 3m as white solid (57 mg, 94%); mp 102–103 °C. 1
H
NMR (400 MHz, DMSO-d ): δ = 8.62 (m, 1 H), 8.11 (br s, 1 H),
6
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

F
Synlett
W. Han et al.
Letter
8
.06 (dt, J = 7.6, 0.8 Hz, 1 H), 8.0 (td, J = 7.6, 1.6 Hz, 1 H), 7.64 (br
(22) (a) Fier, P. S.; Hartwig, J. F. Science 2013, 342, 956. (b) Fier, P. S.;
Hartwig, J. F. J. Am. Chem. Soc. 2014, 136, 10139.
13
s, 1 H), 7.61–7.57 (m, 1 H) ppm. C NMR (100 MHz, DMSO-d ):
6
δ = 166.5, 150.7, 148.9, 138.1, 126.9, 122.4 ppm.
20) Wen, P.; Li, Y. M.; Zhou, K.; Ma, C.; Lan, X. B.; Ma, C. W.; Huang,
G. S. Adv. Synth. Catal. 2012, 354, 2135.
(23) (a) Xu, P.; Guo, S.; Wang, L. Y.; Tang, P. P. Angew. Chem. Int. Ed.
2014, 53, 5955. (b) Anderson, J. M.; Kochi, J. K. J. Am. Chem. Soc.
1970, 92, 1651.
(
(
21) Mcgill, C. K.; Rappa, A. Adv. Heterocycl. Chem. 1988, 44, 1.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F