Lindh et al.
SCHEME 1
increase catalytic stability and to control the regioselectivity with
electron-rich olefins.13,14 In addition, with dmphen, palladium
loadings could be reduced and atmospheric air could be used
as the sole reoxidant. Very recently, Jung’s research group
published the first base-free oxidative Heck reaction,15 including
a plausible catalytic mechanism for the transformation.15-17 This
method employed oxygen gas for the essential Pd(II) recycling.
The use of pure oxygen gas is, however, inconvenient,
expensive, and associated with dangerous handling, reducing
the utility of the procedure, especially for large-scale applica-
tions.
microwave-assisted transformations only a limited number of
pressurized medium- and large-scale reactions are avail-
able.14,33,34
This report addresses the base-free Pd(II)-dmphen-catalyzed
oxidative Heck reaction and the impact of microwave-accelera-
tion on it. We report herein (1) a new room-temperature method
for chemo- and regioselective vinylation of arylboronic acids
under air, (2) a small-scale microwave-accelerated oxidative
Heck protocol using p-benzoquinone as reoxidant and dmphen
as the regiocontrolling ligand, and (3) an oxidative Heck
arylation performed on a 50 mmol scale using air and microwave
energy to drive the reaction.
Arylboronic acids or esters are commonly employed sub-
strates in the oxidative Heck reaction,11,13-15,18,19 but other
arylating agents have also been reported, e.g., arylstannanes,20
arylsilanes,21 arylmercury,22 arylphosphonic acids,23 arylbis-
muth,24 and arylantimony25 compounds. Many of these alterna-
tive organometallic or organometalloid reagents are unstable
and produce byproducts that are often highly toxic and difficult
to remove.26 In contrast, arylboronic acids are comparatively
air and moisture stable, relatively nontoxic, and easily acces-
sible.11,13,14,18,19,27,28 Another reason for the rising interest in the
oxidative Heck transformation stems from the advancements
made in environmentally benign reoxidation systems, mainly
driven by the development of novel Pd(II)-catalyzed oxidation
protocols.17,29,30
Results and Discussion
Reactions under Air. In previous work by our group in the
field of the oxidative Heck chemistry there were indications
that the choice of base had a distinct impact both on the product
yield and the amount of detected homocoupled byproduct
(Suzuki biaryl product).35 To further investigate these observa-
tions, a model reaction was chosen and a series of different
bases were screened at room temperature in open vessels using
atmospheric air as the reoxidant (Scheme 1). The reaction system
contained the olefin n-butyl acrylate (1a, 1 mmol), p-tolylboronic
acid (2c, 2 equiv) as arylating agent, Pd(OAc)2 (2 mol %) as
Pd(II) source, dmphen (2.4 mol %) as the ligand, and a base (2
equiv) in acetonitrile (3 mL). The selected bases were all
previously known to promote either Suzuki or oxidative Heck
reactions, providing a wide span in base strength and structure.36
Sodium hydroxide and cesium carbonate gave very little vinylic
substitution product 3c but predominantly homocoupled bitolyl,
which under oxidative Heck reaction conditions is the expected
product from a competing Suzuki-type pathway.37-39 In ac-
cordance with literature data,13 previously used oxidative Heck
bases such as tertiary amines gave predominantly arylated olefin
3c. Interestingly, a weak base such as sodium acetate worked
almost as well as the commonly employed N-methylmorpholine
(NMM), furnishing a slightly slower but higher yielding reaction
without any concomitant biaryl formation.40 This observation
prompted us to run an experiment under air without addition
of a base, and the result exceeded our expectations. The base-
free process was even faster (18 h) than the corresponding
In modern synthetic organic chemistry laboratories, protocols
for convenient and rapid transformations are highly desired. To
meet these demands, dedicated microwave reactors have been
developed for fast processing of sealed small-scale reaction
mixtures.31,32 However, among the large number of published
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2002, 67, 7127-7130.
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Hiyama, T. Bull. Chem. Soc. Jpn. 2000, 73, 1409-1417.
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