Cationic palladium(II) catalysis: C-H activation/suzuki-miyaura couplings at room temperature

Article abstract of DOI:10.1021/ja910973a

Cationic palladium(II) catalyst realized facile C?H activation of aryl urea with arylboronic acids at room temperature. This reaction is extremely mild to carry out aromatic CH activations through electrophilic substitution.

Full text of DOI:10.1021/ja910973a

Published on Web 03/22/2010
Cationic Palladium(II) Catalysis: C-H Activation/Suzuki-Miyaura Couplings at
Room Temperature
Takashi Nishikata, Alexander R. Abela, Shenlin Huang, and Bruce H. Lipshutz*
Department of Chemistry & Biochemistry, UniVersity of California, Santa Barbara, California 93106
Received December 30, 2009; E-mail: lipshutz@chem.ucsb.edu
Table 1. Solvent Effectsa
Notwithstanding the extraordinary progress being made in Pd-
catalyzed cross-couplings involving nitrogen- or oxygen-based directing
groups (DG) for C-H activation chemistry, Suzuki-Miyaura cou-
plings under very mild, room temperature conditions remain very
rare.1,2 Most of the highly successful approaches to date employ a
combination of neutral palladium acetate as catalyst and high temper-
atures (>120 °C) in aromatic C-H activations.3 The increased
nucleophilicity of reaction partners along with acidic conditions often
run
solvent
yield (%)
run
solvent
yield (%)
assist in the desired bond constructions.4 Mechanistic studies indicate
that aromatic C-H bonds, independent of temperature, are activated
with the aid of carboxylate or carbonate anions.5,6 Alternatively,
electrophilic C-H activation1,5,7 with cationic palladium at room
temperature has been advanced (Scheme 1). While not yet of general
applicability, it does raise the intriguing notion of tuning cationicity
of the catalyst,8,9 potentially leading to far milder conditions for C-H
1
2
3
4
hexane
THF
acetone
EtOH
50
80
38
70
5
6
7
8
DMF
2% surfactant/water
EtOAc
31
trace
96
EtOAc
94b
a Conducted at rt for 20 h with 10 mol % [Pd(MeCN)4](BF4)2,
1,4-benzoquinone(BQ) (5 equiv), 1a (0.25 mmol), and 2a (3 equiv).
b 1.5 equiv of 2a and 3 equiv of BQ.
Scheme 1. Electrophilic C-H Activation with Cationic Pd(II)
Under optimized conditions, various arylboronic acids having
electron-donating or -withdrawing groups reacted smoothly with
aromatic ureas in high yields (Table 2).13 Indications that functional
group tolerance appears to be good can be found from products 3d-3f
and 3k-3m, likely reflecting the mildness of the C-H activation event.
Especially noteworthy is the general trend of selective directed
monoarylation (3w-3bb), which is typically not the case with
symmetrical coupling partners.2,3
Pd(OAc)2 is also reactive in this reaction but undergoes C-H
Suzuki-Miyaura coupling only in the presence of an additional
strong acid, HBF4 (Scheme 3). Under such acidic conditions,
Pd(OAc)2 may release an acetate anion to generate cationic Pd(II)
species.14
activation/coupling with arylboronic acids. Herein, we report Suzuki-
Miyaura couplings with aryl ureas catalyzed by a preformed cationic
palladium(II) complex, which provide aniline derivatives at room
temperature in the absence of metal oxidants or added acid (Scheme
2).
Scheme 2. C-H Activation/Suzuki-Miyaura Coupling Catalyzed by
Cationic Pd(II)
Scheme 3. C-H Activation Catalyzed by Pd(OAc)2
The dimethylurea moiety was easily removed under general
hydrolysis conditions to produce the corresponding amine quanti-
tatively (Scheme 4).
Initially, a study was conducted of several neutral palladium
catalysts, such as Pd(OAc)2, PdCl2, and Pd2(dba)3, but none were
effective (<1% biaryl). On the other hand, the combination of anilide
1a and phenylboronic acid (2a, 3 equiv) in the presence of
[Pd(MeCN)4](BF4)2 (10 mol %) and 1,4-benzoquinone (BQ, 5 equiv)
dramatically improved the extent of product formation (Table 1). While
several solvents under otherwise identical conditions gave the desired
biaryl in low-to-moderate yields (runs 1-6), C-H activation in EtOAc
led to 3a in 96% isolated yield (run 7). Decreased amounts of both
phenylboronic acid (2a) and BQ could be used with equal success;
lower catalyst loading, however, led to far slower reactions. Thus, this
cationic palladium(II) catalyst enhances not only the rate of C-H
activation10 but also that for transmetalation with an arylboronic acid,
which otherwise requires ate formation.11 The BQ present is known
to promote reductive elimination in metal-catalyzed couplings.12
Scheme 4. Deprotection
In summary, the dramatic effect of cationic palladium in Suzuki-
Miyaura reactions has been uncovered, which enables facile aromatic
C-H activation and subsequent cross-couplings at room temperature.
Mechanistic studies on these highly reactive cationic complexes are
ongoing to further elucidate the nature of the active catalyst formed
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4978 J. AM. CHEM. SOC. 2010, 132, 4978–4979
10.1021/ja910973a  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Representative Couplingsa
a Conducted at rt for 20 h with 10 mol % [Pd(MeCN)4](BF4)2, BQ (2 or 5 equiv), 1 (0.25 mmol), and 2 (1.5 or 3 equiv). The ratios of single/double
arylation determined by H NMR are shown in the parentheses. b Run for 48 h. c 2 equiv of BQ. d 1.5 equiv of 2.
1
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Acknowledgment. Financial support provided by the NIH (GM
86485) is warmly acknowledged as is Johnson Matthey for providing
catalyst [Pd(MeCN)4](BF4)2 used in this study.
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Supporting Information Available: Experimental details. This
material is available free of charge via the Internet at http://pubs.acs.org.
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(14) In the absence of Pd(OAc)2, no reaction takes place.
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