Gold-catalyzed hydroarylation of alkenes with dialkylanilines

Article abstract of DOI:10.1021/ja507788r

Anti-Bredt di(amino)carbene supported gold(I) chloride complexes are readily prepared in two steps from the corresponding isocyanide complexes. In the presence of KB(C₆F₅)₄as chloride scavenger, they promote the unprecedented hydroarylation reaction of alkenes with N,N-dialkylanilines with high para-selectivity. The latter are challenging arenes for Friedel-Craft reactions, due to their high basicity.

Full text of DOI:10.1021/ja507788r

Communication
pubs.acs.org/JACS
Gold-Catalyzed Hydroarylation of Alkenes with Dialkylanilines
Xingbang Hu,†,‡ David Martin,† Mohand Melaimi,† and Guy Bertrand*,†
†UCSD-CNRS Joint Research Laboratory (UMI 3555), Department of Chemistry and Biochemistry, University of California, San
Diego, La Jolla, California 92093-0343, United States
‡School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, P. R. China
S
* Supporting Information
The scope of the previously reported synthesis of pyrNHC-
ABSTRACT: Anti-Bredt di(amino)carbene supported
gold(I) chloride complexes are readily prepared in two
steps from the corresponding isocyanide complexes. In the
presence of KB(C6F5)4 as chloride scavenger, they
promote the unprecedented hydroarylation reaction of
alkenes with N,N-dialkylanilines with high para-selectivity.
The latter are challenging arenes for Friedel-Craft
reactions, due to their high basicity.
gold chloride complexes was limited by the scarcity of available
precursors, and the instability of free carbenes.13 Therefore, we
considered a new synthetic strategy, in which the ligand is built
in the coordination sphere of the metal.15,16 Isocyanide gold
chlorides 1a−e were reacted with 1 equiv of 3-piperidine
methanol, generating the corresponding acyclic di(amino)-
carbene gold complexes 2a−e (Scheme 1). Addition of triflic
Scheme 1. Synthesis of Precatalysts 3a−e
riedel−Crafts reactions1,2 typically require Lewis acid
F
catalysts and are therefore generally unsuitable for basic
substrates. Classical textbooks especially emphasize their
incompatibility with amines, which is a major limitation due
to the ubiquity of this organic functionality.3 The intermo-
lecular hydroarylation of alkenes,4 a powerful atom-economic
method for the alkylation of arenes, is no exception. Besides a
few examples with the parent aniline (C6H5)NH2,5−7 there are
only two reports of hydroarylation of styrene with the more
basic N-methylaniline; with Ru3(CO)12,5d or a rhodium-based
catalytic system,5c the reaction occurs at 140−150 °C. Under
similar conditions, only 17% conversion was observed with the
challenging N,N-dimethylaniline.5c Similarly to hydroarylation
reactions, metal-catalyzed hydroaminations8 are often inhibited
by nucleophilic amines, which strongly bind the metal to form
inert Werner-complexes.9 However, our group has demon-
strated that cationic gold(I) complexes supported by (alkyl)-
(amino)carbenes (CAACs)10 (Chart 1) can catalyze the
anhydride, in the presence of base, triggered the cyclization, and
gold chloride complexes 3a−e were isolated in good yields.
These organometallic compounds are air-stable and can be
stored for several months with no significant decomposition.
They were fully characterized, including by X-ray diffraction
analysis for 3a and 3e (Figure 1).
In a first experiment, a solution of α-methylstyrene and N,N-
diethylaniline in benzene was heated in a sealed ampule in the
Chart 1
hydroamination of alkynes and allenes with a variety of
amines,11 including ammonia11b and hydrazine.11g In 2013, we
reported that another type of electrophilic carbene, namely, the
“anti-Bredt NHCs” (pyrNHCs),12 allows for the gold-catalyzed
hydrohydrazination of terminal alkynes at room temperature.13
This was a significant improvement since CAAC-Au(I) systems
typically require temperatures of 70−110 °C for the same
transformation.11g Here we report that Au(I)/pyrNHC
complexes promote the hydroarylation of alkenes with N,N-
dialkylanilines with high para-selectivity.14
Figure 1. X-ray structure of 3a (left) and 3e (right) with thermal
ellipsoids drawn at 50% probability level. Hydrogen atoms and solvent
molecules are omitted for clarity.
Received: August 4, 2014
Published: September 15, 2014
© 2014 American Chemical Society
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presence of a catalytic amount (5 mol %) of 3a and KB(C6F5)4.
To our delight, we observed the clean formation of the
corresponding para-hydroarylation adduct 4a with complete
conversion after 24 h at 135 °C (Table 1, entry 1). Under the
substituted pyrNHC 3d as catalyst (entry 4). In the case of 3e,
the conversion reached a ceiling at 38%, suggesting a
decomposition of the catalyst. No reaction was observed with
3a in the absence of KB(C6F5)4 (entry 6), and even using silver
triflate, as an alternative chloride scavenger, led to poor
conversion (entry 7). These observations confirm the expected
involvement of a cationic gold complex in the catalytic cycle.
We also verified that simple systems, such as AuCl3/AgSbF6,17
Table 1. Hydroarylation of α-Methylstyrene with N,N-
a
Diethylaniline
18
FeCl3 or BiCl3,19 which are recognized as efficient catalysts
for the hydroarylation of alkenes, were poorly active for the
reaction of N,N-diethylaniline with α-methylstyrene (entries 8−
10). Not surprisingly, 1 mol % of our catalytic system [3a +
KB(C6F5)4] promotes the hydroarylation of styrene with
anisole, at room temperature, but this reaction is totally
inhibited by the presence of N,N-diethylaniline. These last
observations highlight the powerful deactivating role of anilines
(see Supporting Information (SI) for details).
Using 3a and KB(C6F5)4 as catalytic system, we explored the
scope of this unprecedented hydroarylation reaction. We found
that N,N-dialkylanilines react with a variety of styrenes and
norbornene, affording products 4a−q and 5l,q in fair to
excellent yields (Scheme 2). Not surprisingly, significantly
lower temperatures are required for the hydroarylation of 4-
methoxystyrene (80−110 °C) than for the less electron-rich
styrene and norbornene (145 °C). The high para-regioselec-
tivity observed in the reaction leading to 4a−h, 4j and 4m−p is
likely the consequence of the steric hindrance of the 1-phenyl-
entry
catalytic system
conversion (%)
1
2
[3a + KB(C6F5)4] (5 mol %)
[3b + KB(C6F5)4] (5 mol %)
[3c + KB(C6F5)4] (5 mol %)
[3d + KB(C6F5)4] (5 mol %)
[3e + KB(C6F5)4] (5 mol %)
3a (5 mol %)
97
98
89
69
38
0
3
4
5
6
7
[3a + AgOSO2CF3] (5 mol %)
[AuCl3 + 3 AgSbF6] (5 mol %)
FeCl3 (10 mol %)
12
10
3
8
9
10
BiCl3 (10 mol %)
4
a
After 24 h; determined by GC.
same conditions, 3b and 3c gave comparable results (entries 2
and 3), whereas a slower rate was observed with the nitro-
a
Scheme 2. Hydroarylation of Alkenes with N,N-Dialkylanilines
a
b
3a (5 mol %), KB(C6F5)4 (5 mol %), except for 4m−p (10 mol %). Solvent: C6H6. Isolated yields. See SI for details. GC conversion.
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Communication
1-(methyl)ethyl and 1,1-diphenylethyl groups. However,
electronic effects are also of importance since the para-
substituted products are selectively formed with 4-methox-
ystyrene (4f−j), but not with styrene (4k−l and 5k−l).
Interestingly, the selective formation of 4i shows that the
preference of 4-methoxystyrene for para-substitution does not
preclude the ortho-substitution when the para-position is
protected. Note that ortho-substitution is usually favored by
the few systems that are known to promote the hydroarylation
of alkenes with the parent aniline.5,6 Ackermann et al. have even
demonstrated that the hydroarylation product results from the
rearrangement of the initially formed hydroamination pro-
duct.6g
complexes, bearing stable electrophilic carbenes as the ancillary
ligand, to promote reactions that are usually hampered by
nucleophilic substrates.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
Full experimental details, H, 13C NMR and MS spectra for all
new compounds and X-ray crystallographic data for 3a and 3e.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
guybertrand@ucsd.edu
■
Although unactivated alkenes, such as 1-octene, 3-octene and
tetra(methyl)ethylene do not react with N,N′-dimethylaniline,
our catalytic system allowed for the hydroarylation of enones
(Scheme 3). This reaction is the atom economic equivalent of a
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Scheme 3. Hydroarylation of Enones with N,N-
Di(alkyl)anilines
a
The authors gratefully acknowledge financial support from the
DOE (DE-FG02-13ER16370). Thanks are due to the National
Natural Science Foundation of China (No. 21176110) and
Jiangsu Province Natural Science Foundation (BK20141311)
for a Fellowship (X.H.).
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