Palladium-catalyzed C-H aminations of anilides with N - fluorobenzenesulfonimide

Article abstract of DOI:10.1021/ja1101695

The first amide-directed, palladium-catalyzed, intermolecular, highly selective C-H aminations with the non-nitrene-based nitrogen source N-fluorobenzenesulfonimide have been developed. This methodology might provide a new pathway for directed metal-catalyzed aromatic C-H amination.

Full text of DOI:10.1021/ja1101695

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pubs.acs.org/JACS
Palladium-Catalyzed C-H Aminations of Anilides with
N-Fluorobenzenesulfonimide
Kai Sun, Yan Li, Tao Xiong, Jingping Zhang, and Qian Zhang*
Department of Chemistry, Northeast Normal University, Changchun 130024, China
S Supporting Information
b
Similar to oxime ester, an active FPdN(SO2Ph)2 species was
suggested to be formed via the oxidative addition of Pd(0) to the
N-F bond of NFSI,10 and therefore, as a starting point we
sought to use NFSI as a nitrogen source to perform palladium-
catalyzed intermolecular C-H amination reactions. As shown in
Scheme 1, we supposed that a novel electrophilic palladation of
in situ-generated FPdN(SO2Ph)2 with arene might form a
dearomatized spiro-cyclopalladium intermediate C, which could
undergo nucleophilic amination followed by hydrogen elimina-
tion to provide ortho-amination products D (path I) or para-
amination products E (path II) depending on the electronic and
steric effect of the arene substituents. In the present work, the
first amide-directed, palladium-catalyzed, intermolecular, highly
selective C-H aminations with the non-nitrene nitrogen source
NFSI were efficiently realized.
Initially, we found that N-phenylacetamide failed to undergo
the amination reaction upon treatment with Pd(OAc)2 (10 mol %)
and NFSI at 80 °C, and N-phenylacetamide was recovered
after 24 h. Starting from N-p-tolylacetamide, a benzylic amina-
tion product was obtained in 71% yield.4 Surprisingly, when
N-(40-methylbiphen-4-yl)acetamide 1a was employed, o-C-H
amination product 2a11 was obtained in 87% yield (Table 1,
entry 1). No reaction occurred in the absence of the palladium
catalyst (entry 2). KF was as effective as NaHCO3 (entry 3).
With solvents such as acetonitrile, N,N-dimethylformamide
(DMF), and dimethyl sulfoxide (DMSO), no desired 2a was
obtained (entries 7-9). Other solvents, such as nitroethane,
dichloromethane, nitrobenzene, and chlorobenzene were not as
effective as dichloroethylene (DCE) (entries 10-13). In addi-
tion, the use of Pd(TFA)2 and Pd(dba)2 as the catalyst gave 2a in
84 and 70% yield, respectively (entries 14 and 15). It should be
noted that the transformation from 1a to 2a represents the first
palladium-catalyzed intermolecular aromatic C-H amination
with a non-nitrene nitrogen source.
ABSTRACT: The first amide-directed, palladium-catalyzed,
intermolecular, highly selective C-H aminations with the
non-nitrene-based nitrogen source N-fluorobenzenesulfon-
imide have been developed. This methodology might
provide a new pathway for directed metal-catalyzed aro-
matic C-H amination.
ransition-metal-catalyzed direct carbon-hydrogen bond
T
functionalization appears to be highly appealing, especially
if high selectivity for a unique C-H bond can be achieved.1
Accordingly, directed metalation1,2 is a powerful approach for the
selective functionalization of C-H bonds in complex substrates.
However, all previously reported directed palladium-catalyzed
C-H functionalizations of arenes provided o-C-H functiona-
lized products. Therefore, the development of new methodolo-
gies that override the popular o-C-H selectivity to realize meta
or para aromatic and benzylic C-H functionalization remains a
great challenge.3 Recently, an amide-group-directed, copper-
catalyzed m-C-H arylation reaction was reported by Gaunt
and co-workers.3a Yu and co-workers3b studied the palladium-
catalyzed m-C-H olefination of electron-deficient arenes using
2,6-dialkylpyridine ligands. In addition, our group developed an
amide-directed, palladium-catalyzed benzylic C-H amination
with N-fluorobenzenesulfonimide (NFSI).4 However, to date,
directed, metal-catalyzed, highly selective p-C-H functionaliza-
tion has not been realized.
Direct aromatic C-N bond formation is of immense interest
because aromatic amines and their derivatives are common in
pharmaceuticals, agrochemicals, dyes, herbicides, and conduct-
ing polymers.5 Accordingly, the area of catalytic C-H amination
has led to significant results arising both from the discovery of
simple, efficient nitrene transfers and the combination of transi-
tion-metal-catalyzed C-H activation with C-N bond form-
ation.6 Although intramolecular oxidative aminations of arenes
with amine derivatives had been reported,7 intermolecular aro-
matic C-H amination could not be realized unless in situ-
generated, highly active nitrene intermediates were employed as
nitrogen sources (Scheme 1, amination product B).8 Recently, a
remarkably interesting work by Hartwig and co-workers9 showed
that intramolecular C-H amination via a Pd0/PdII manifold can
be achieved using a non-nitrene-based nitrogen source, oxime
ester, which contains a N-O bond as a built-in oxidant. How-
ever, the analogous intermolecular C-H amination remains a
challenge.
With the optimized conditions in hand (Table 1, entry 1), we
turned to an examination of the generality of this C-H amina-
tion reaction. As described in Table 2, the tested biphenyl
derivatives 1b-h were smoothly reacted with NFSI to afford
2b-h in moderate to good yields. In addition, with various acyl
group substrates 1i-l, 2i-l could also be obtained. Moreover,
the reaction worked with carbamate, although the yield was only
moderate. The 4-OR-substituted substrates 1m-q were also
successfully reacted with NFSI to afford 2m-q in good to
excellent yields. Starting from 4-amide-substituted substrate 1r,
2r could be obtained in 74% yield within 1.5 h. However, starting
Received: November 12, 2010
Published: January 20, 2011
r
2011 American Chemical Society
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|

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Scheme 1. Directed Palladium-Catalyzed Aromatic C-H
Amination
Table 2. o-C-H Amination of 1b-w with NFSIa,b
Table 1. C-H Amination of 1a with NFSIa
additive
yield of
2a (%)b
entry
catalyst
solvent
DCE
(2.0 equiv)
time (h)
1
2
Pd(OAc)2
none
NaHCO3
NaHCO3
KF
2.5
10.0
2.5
87
0
DCE
3
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(TFA)2
Pd(dba)2
DCE
87
81
88c
0d
0
4
DCE
none
4.0
5
DCE
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
NaHCO3
2.5
a Reactions were carried out with 1 (0.5 mmol), Pd(OAc)2 (10 mol %),
NFSI (2.0 equiv), and NaHCO3 (2.0 equiv) in DCE (4 mL) at 80 °C.
b Yields of isolated products are shown. c The reaction was performed at
110 °C.
6
DCE
2.5
7
CH3CN
DMF
10.0
10.0
10.0
10.0
10.0
2.5
8
0
9
DMSO
C2H5NO2
CH2Cl2
PhNO2
PhCl
0
10
11
12
13
14
15
43e
54f
81
43
84
70
excellent yields. 4f and 4g could be obtained even starting from
substrates 3f and 3g having substituents at both ortho positions.
Notably, starting from cyclic substrate 3l, para-substituted pro-
duct 4l could also be obtained in 76% yield (eq 1):
3.0
DCE
3.0
DCE
3.0
a Reactions were carried out with 1a (0.5 mmol), Pd catalyst (10 mol %),
and NFSI (2.0 equiv) at 80 °C. b Yield of the isolated product. c The
reaction was performed at 110 °C. d The reaction was performed at 50
°C. e With recovery of 29% of 1a. f With recovery of 26% of 1a.
However, no reaction occurred from diacetamide substrate 3m
or 3n or from substrate 3o with a strongly electron-withdrawing
nitro group on the aromatic ring. Also, no reaction occurred
starting from substrate 3p. Surprisingly, instead of the p-C-H
amination product, the m-C-H amination product 5q was
obtained in 77% yield starting from 3q (eq 2),12 which might
be attributed to the steric effect.
To understand the mechanims of these aromatic C-H
amination reactions, ortho-substituted cyclopalladium(II) inter-
mediate F was prepared from 1m (eq 3).13 No desired 2m was
obtained when the reaction of F and NFSI was performed under
conditions identical to those described in Table 1, entry 1. In
addition, there was no obvious effect on the C-H amination of 1m
by addition of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO),
from 2-alkyl-substituted substrates 1s and 1t and 4-cyclohexyl-
substituted substrate 1u, no reactions occurred (Table 2). Start-
ing from 4-alkyl-substituted substrates 1v and 1w, unseparated
mixtures without main products were obtained (Table 2).
To our surprise, when 2-OMe-substituted substrate 3a was
tested under the optimal conditions (Table 1, entry 1), the para-
amination product 4a was obtained in 92% yield (Table 3).
Indeed, the transformation from 3a to 4a represents the first
directed palladium-catalyzed highly selective para aromatic C-H
amination. Gratifyingly, 2-OR-substituted substrates 3b-f pro-
vided 4b-f in good to excellent yields (Table 3).11 In addition,
starting from 2-OMe-substituted acetamide and benzamide
substrates 3g-k, 4g-k could also be obtained in good to
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COMMUNICATION
Table 3. p-C-H Amination of 3a-k and 3m-p with NFSIa,b
might provide a new pathway for directed metal-catalyzed
aromatic C-H functionalization.
In conclusion, an unprecedented amide-directed, palladium-
catalyzed, intermolecular, highly selective C-H amination
reaction using the non-nitrene-based nitrogen source NFSI
that might provide a new pathway for aromatic C-H amination
has been developed. Further investigations of the mecha-
nism for the formation of the novel key dearomatized spiro-
palladacycle intermediates and the application of this metho-
dology for directed C-H functionalization are ongoing in our
laboratory.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details, spectral
b
data for new compounds, and crystallographic data for 2a and 4b
(CIF). This material is available free of charge via the Internet at
http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
zhangq651@nenu.edu.cn
’ ACKNOWLEDGMENT
Financial support of this research was provided by the NCET
(08-0756), the NNSFC (20772015 and 20972028), the JLSDP
(20080547 and 20082212), and the Fundamental Research
Funds for the Central Universities (09ZDQD07).
a Reactions were carried out with 1 (0.5 mmol), Pd(OAc)2 (10 mol %),
NFSI (2.0 equiv), and NaHCO3 (2.0 equiv) in DCE (4 mL) at 80 °C.
b Yields of isolated products are shown. c With recovery of 11% of 3j.
’ REFERENCES
Scheme 2. Proposed Mechanism for the Formation of 4
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which suggests that a radical mechanism was not operating. Also,
on the basis of the result that p-C-H amination products 4f and
4g (Table 3) could also be obtained starting from substrates 3f
and 3g (without ortho aromatic hydrogens), we propose a
possible catalytic cycle for the formation of 4 (Scheme 2). The
suggested initial step is the formation of intermediate G with a
N-Pd(II) bond via the oxidative addition of Pd(0) to the N-F
bond of NFSI.10 The electrophilic palladation of intermediate H
would provide dearomatized spiro-palladacycle intermediate I,
which would undergo an amination reaction to give intermediate
J. The next hydrogen elimination would provide the amination
product 4. Notably, for the spiro-palladacycle intermediate I in
the above proposed mechanism (Scheme 2), the carbons of the
functionalized C-H bond were not directly connected to
palladium as in the pattern for the widely accepted cyclopalla-
dium intermediate A (Scheme 1). Therefore, this methodology
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(11) Crystallographic details for 2a and 4b are provided in the
Supporting Information.
(12) In this reaction, 21% of 3q was recovered, and even when the
reaction time was prolonged to 20 h, the same result was obtained.
(13) Zhao, X.; Yeung, C. S.; Dong, V. M. J. Am. Chem. Soc. 2010, 132,
5837.
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