Oxygen and base-free oxidative heck reactions of arylboronic acids with olefins

Article abstract of DOI:10.1021/ja0782955

A mild and efficient protocol for palladium-catalyzed oxidative Heck reactions of arylboronic acids with both electron-rich and -deficient olefins is described. In contrast to the normal oxidative Heck coupling, this new method works in the absence of a base, oxygen, or other external oxidants. With a wide variety of substrates tolerated, the method broadens the scope of palladium-catalyzed coupling reactions. Copyright

Full text of DOI:10.1021/ja0782955

Published on Web 01/31/2008
Oxygen and Base-Free Oxidative Heck Reactions of Arylboronic Acids with
Olefins
Jiwu Ruan, Xinming Li, Ourida Saidi, and Jianliang Xiao*
Department of Chemistry, LiVerpool Centre for Materials and Catalysis, UniVersity of LiVerpool,
LiVerpool L69 7ZD, U.K.
Received October 30, 2007; E-mail: j.xiao@liv.ac.uk
Scheme 1
The palladium-catalyzed Mizoroki-Heck reaction is now one
of the most important tools for constructing C-C bonds.1 After
the first report of Heck2 and further development by Uemura3 and
Mori,4 the transition metal-catalyzed coupling of organoboronic
acids and olefins, known as the oxidative Heck reaction, had been
extensively investigated,5 particularly by the groups of Jung,5c,d,m
Larhed,5b,e,h,i Lautens,5j and Brown,5f mainly because boronic acids
Table 1. Oxidative Coupling with Electron-Rich Olefinsa
are comparatively stable, nontoxic, and easily available. The
methods developed thus far require the presence of an oxidant to
reoxidize Pd(0), for example, Cu(OAc)2, quinone, or O2, producing
stoichiometric amounts of metal waste or being associated with
potentially hazardous handling and not suitable for air-sensitive
conditions. Herein we disclose a new method that allows efficient
oxidative Heck coupling of arylboronic acids with both electron-
rich and -deficient olefins, with no need for external oxidants.
Previous studies suggest that the regeneration of Pd(II) after each
catalytic cycle is the key step for the Pd-catalyzed oxidative Heck
reaction.5,6 We thought that following the release of the coupling
product from Pd(II), the X-Pd-H intermediate might be inter-
cepted by a hydrogen acceptor, such as acetone, thus regenerating
the Pd(II) without forming Pd(0) and so circumventing the need
for traditional oxidants or base (Scheme 1).7
With this hypothesis in mind we set out to examine the reaction
of arylboronic acids with olefins in acetone under nitrogen.
Delightfully, our initial study of 4-methoxy-phenylboronic acid (1j)
coupling with the benchmark electron-rich olefin n-butyl vinyl ether
(2a) catalyzed by Pd-dppp was met with very encouraging results
under base-free conditions and with no extra oxidant (Table S1,
Supporting Information). We then tested a range of different
conditions in the hope to optimize the reaction. The results show
that the use of acetone as solvent and dppp as ligand affords the
best yield of ketone 3j, obtained from the olefin product after in
situ hydrolysis. The reaction was highly regioselective, with no
linear olefin detected. Very low yields were obtained with PPh3,
2,2′-bipyridine, or no ligand. When the reaction was run under an
O2 atmosphere, the yield decreased from 89% to 71%. We note
that nitrogen ligands have been most successful when the reaction
is run under oxygen.5b-e,g-i
entry
R
R
′
, R′′
product
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
H 1a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
H, nBu 2a
CH3, Et 2b
CH3, Et 2b
CH3, Et 2b
Et, Et 2c
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
89
85
74
70
61
90
93
92
92
91
84
94
89
81
75
92
87
85
90
91
85
84
82
81
84
80
o-CH3 1b
o-OCH3 1c
o-Cl 1d
o-F 1e
m-CH3 1f
m-Cl 1g
m-NO2 1h
p-CH3 1i
p-OCH3 1j
p-F 1k
p-Cl 1l
p-Br 1m
p-NO2 1n
p-COCH3 1o
p-OH 1p
p-SCH3 1q
p-CH2OH 1r
1-naph 1sc
2-naph 1td
H 1a
p-OCH3 1j
p-Br 1m
H 1a
p-OCH3 1j
p-Br 1m
3t
3u
3v
3w
3x
3y
3z
Et, Et 2c
Et, Et 2c
a All reactions were carried out with 1 (1.0 mmol), 2a-c (2.0 equiv),
Pd(OAc)2 (2 mol %), and dppp (3 mol %) in 3 mL acetone at 70 °C for
15 h. b Isolated yields. c 1-Naphthylboronic acid. d 2-Naphthylboronic acid.
Using the optimized conditions, we then examined the reaction
of various arylboronic acids 1a-t with olefins 2a-c. The results
are summarized in Table 1. As can be seen, the reactions afforded
good to excellent yields of ketones 3. Ortho substitution appears
to lower the yield, so do electron-withdrawing groups (e.g., entries
3 vs 10; 10 vs 14 and 15). The observation is reminiscent of that
found in the Heck reaction of aryl halides with 2a.8 Gratifyingly
but unsurprisingly, the reaction works excellently for oxygen-
sensitive substrates (entries 16-18).9 To gain understanding of the
reaction pathway, we studied an intramolecular competition reaction
by coupling 4-bromophenylboronic acid (1m) with 2a. As may be
expected in the absence of a base, the oxidative Heck reaction
product was exclusively produced in 89% yield; no other coupling
products were detected (entry 13). Very good results were also
obtained when the substituted vinyl ethers 2b,c were used (entries
21-26), providing an alternative for preparing different aryl alkyl
ketones.
9
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10.1021/ja0782955 CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Oxidative Coupling with Electron-Deficient Olefinsa
The catalysis also worked for other electron-deficient olefins.
An example is seen in the coupling of acrylonitrile 2i, affording
exclusively the linear olefins in good isolated yields (eq 3).
The reaction mechanism is yet to be fully studied. However, it
is clear that the solvent acetone is not a hydrogen acceptor in the
coupling of either electron-rich or deficient olefins on the basis of
1H NMR investigations.11 In the case of electron-deficient olefins,
it is the substrate that acts as the hydrogen acceptor. Thus, 1H NMR
monitoring of the coupling of 1a and 2f in acetone-d6 showed that
5a and methyl propionate were formed concomitantly in a molar
ratio of 2:1 during the entire reaction, and no hydrogen from the
-B(OH)2 group was incorporated into the propionate (eq 4).
However, in the case of the electron-rich olefins, for example, 2a,
reduction of the substrates was not detected with either NMR or
GC. The mechanism is under investigation in our lab.
entry
R
R
′
, R′′
product
yield (%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
H 1a
o-CH3 1b
o-Cl 1d
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
H, OCH3 2f
CH3, OCH3 2g
CH3, OCH3 2g
CH3, OCH3 2g
H, N(CH3)2 2h
H, N(CH3)2 2h
H, N(CH3)2 2h
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
82
94
81
80
85
94
93
95
86
96
94
80
78
83
82
75
79
80
o-F 1e
m-CH3 1f
m-Cl 1g
m-NO2 1h
p-CH3 1i
p-OCH3 1j
p-Cl 1l
p-Br 1m
1-naph 1sc
H 1a
p-OCH3 1j
p-Br 1m
H 1a
p-OCH3 1j
p-Br 1m
In conclusion, we have developed an efficient protocol for the
oxidative Heck coupling of arylboronic acids with both electron-
rich and -deficient olefins. The method requires neither oxygen nor
base to operate, broadening the scope of palladium-catalyzed
coupling reactions.
a All reactions were carried out with 1 (1.0 mmol), 2f-h (2.0 equiv),
Pd(OAc)2 (2 mol %), dppp (3 mol %), and TFA (30 mol %) in 3 mL acetone
at 70 °C for 20 h. b Isolated yields. c 1-Naphthylboronic acid.
The catalysis also worked for the electron-rich olefins 2d,e (eq
1). The products are again branched olefins. However, isomerization
of the CdC bond occurred, affording a mixture of olefins, probably
due to palladium or acid catalysis.10
Acknowledgment. We thank the DTI (JR), Zhongkai University
of Agriculture and Technology (XL), and the Department of
Chemistry of Liverpool University (JR) for financial support.
With the success in electron-rich olefins, we then turned attention
to a benchmark electron-deficient olefin methyl acrylate (2f).
Unfortunately, using the same conditions, the coupling of 1j with
2f afforded only ca. 20% yield of 5i. We then searched conditions
to promote the reaction and to our delight, acids were found to
significantly accelerate the reaction. In particular, 5i could be
obtained in over 60% isolated yield in the presence of 30 mol %
trifluoroacetic acid (TFA) under otherwise similar reaction condi-
tions (eq 2). The amount of the TFA had no significant effect on
the yield when more than 30 mol % was used. Other acids were
proven to be less effective, for example, acetic acid, benzoic acid,
triflic acid, and p-toluenesulfonic acid. The effects of other variables
echoed those found for 2a.
Supporting Information Available: Experimental details and
spectroscopy data (1H and 13C NMR). This material is available free
of charge via the Internet at http://pubs.acs.org.
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