Aerobic oxidative coupling of arenes and olefins through a biomimetic approach

Article abstract of DOI:10.1002/chem.201300100

Arenes and electron-deficient olefins can be oxidatively coupled through a biomimetic Pd(OAc)₂-catalyzed transformation. C-H activation of the arene partner is effected under reaction conditions of low catalyst loading, normal oxygen pressure,

Full text of DOI:10.1002/chem.201300100

DOI: 10.1002/chem.201300100
Aerobic Oxidative Coupling of Arenes and Olefins through a Biomimetic
Approach
Beneesh P. Babu, Xu Meng, and Jan-E. Bꢀckvall*[a]
An important challenge in synthetic organic chemistry is
the design and development of new environmentally friend-
ly synthetic methods that are efficient, selective, and cost ef-
fective. As the demand for green chemical approaches is in-
creasing, simple and short synthetic routes that produce a
minimal amount of waste are called for.[1] Biomimetic
metal-catalyzed aerobic oxidation reactions are of interest
in this respect because they are simple to carry out and they
give essentially no side products.[2] In these aerobic oxida-
tion reactions, catalytically active, oxidized forms of the
metal are maintained in the catalytic cycle through reoxida-
tion of the reduced metal by using air (O2) as the terminal
oxidant. In the biomimetic approach,[2] the high activation
energy of direct oxidation by O2 is circumvented by the use
of electron-transfer mediators (ETMs), which ultimately
divide the overall oxidation reaction into several intercon-
nected redox cycles. This leads to low-energy electron trans-
fer, which significantly reduces the activation energy. An
oxygen-activating metal-containing macrocycle and a p-ben-
zoquinone derivative have been used as ETMs in combina-
tion with an active metal catalyst and air (O2). During the
past two decades, our laboratory has explored this approach
in detail and we have developed a range of biomimetic sys-
tems[2b,3–5] for the aerobic oxidation of dienes,[3] alkenes,[3b]
enallenes,[4a] azaenallenes,4b dieneallenes,[4c] alcohols,[5a] ami-
nes,[5b,c,d] diols,[5e] and amino alcohols.[5f]
styrene to yield stilbene,[8] the DHR has become the focus
of intensive research and has found widespread application
in organic synthesis.[9] Even though the inherent stability of
À
the C H bond and the lack of selectivity are often challeng-
ing, attempts to increase the selectivity and productivity of
this reaction has attracted much interest. These protocols re-
quire stoichiometric amounts of an oxidant to reoxidize the
palladium(0) species back into the active palladium(II) spe-
cies, the most commonly used oxidants being copper(II), sil-
ver(I), benzoquinone, polyoxometalates, peroxides, and air/
O2.[9,10] By using substrates with a directing group, high
levels of site selectivity can be obtained in these olefination
reactions.[11]
Among the different oxidants mentioned above, molecu-
lar oxygen is the ideal oxidant for oxidative couplings
(Scheme 1). However, the aerobic DHR suffers from severe
limitations such as the need for relatively high catalyst load-
Scheme 1. General scheme for aerobic oxidative coupling.
Encouraged by our previous results, we considered the
possibility of expanding the scope of the biomimetic ap-
ing, high pressure of oxygen, high concentration of arene
(often used as the solvent), and stoichiometric amounts of
various additives.[7,8,9b] We considered the possibility of using
a biomimetic approach for this oxidative coupling in which
the aerobic reoxidation of the metal is facilitated by catalyt-
À
proach towards intermolecular C C bond-forming reactions.
Palladium-catalyzed arylation of olefins (Heck reaction) is
[6]
À
one of the fundamental reactions for C C bond formation.
À
À
However, a limiting factor in these reactions is the required
prefunctionalization of the arene partner, a requirement
that increases the synthetic steps and produces extra salt
waste. The dehydrogenative Heck reaction (DHR), in which
ic ETMs (Scheme 2). Herein, we report a direct C H/C H
coupling of arenes and electron-deficient olefins through a
biomimetic approach that employs relatively low catalyst
À
À
arylation of an olefin proceeds through direct C H/C H
coupling, circumvents this problem.[7] Ever since, Fujiwara
and Moritani first reported the coupling of benzene and
[a] Dr. B. P. Babu, X. Meng, Prof. J.-E. Bꢀckvall
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University, 106 91 Stockholm (Sweden)
Fax : (+46)8-154-908
E-mail: jeb@organ.su.se
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201300100.
Scheme 2. Biomimetic aerobic dehydrogenative coupling.
4140
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 4140 – 4145

COMMUNICATION
À
Table 1. Biomimetic aerobic C H olefination of 1,4-dimethoxy-
loading and can be conducted under oxygen at atmospheric
pressure.
benzene.[a]
The dehydrogenative coupling between n-butyl acrylate
(1a) and 1,4-dimethoxybenzene (2) was chosen as the test
reaction, and after some initial trials we found that heating
a mixture of 1a (1 mmol) and 2 (5 mmol) in the presence of
catalytic amounts of PdACTHNUTRGNE(UGN OAc)2 (2.5 mol%), p-benzoquinone
(BQ; 20 mol%) and iron phthalocyanine ([Fe(Pc)], Pc=
phthalocyanine; 2 mol%) in acetic acid (0.5 mL) at 908C
under molecular oxygen (1 atm) for 24 h afforded coupling
product 3a in 69% yield as a pale brown viscous liquid. n-
Butyl 3-acetoxyacrylate (4) was the major side product with
trace amount of b,b-diarylated acrylate [Eq. (1)].
Entry
Olefin
Product
Yield [%][b,c]
1
2
3
R=nBu, 1a
R=CH3, 1b
R=tBu, 1c
R=nBu, 3a
R=CH3, 3b
R=tBu, 3c
69
66
61
65[d]
AHCTUNGTRENN(GUN E/Z=3:1)
4
5
35
6
7
56[d] (1:1)
67[d]
AHCTUNGTRENN(GUN E/Z=7:1)
Encouraged by this result, we repeated the reaction using
various palladium salts, ETMs, and acids to find the best re-
action conditions for this coupling and the results are sum-
marized in Table S1 (see the Supporting Information).[12] Pd-
63
AHCTUNGTRENN(GUN E/Z=7:1)
8
9
55[e]
(OAc)2 (2.5 mol%), BQ (20 mol%),
ACHTUNGTRENNUNG
[a] Olefin (1 mmol), 2 (5 mmol), Pd
G
A
ACHTUNGTRENNUNG
[Fe(Pc)] (2 mol%), AcOH (0.5 mL), O2 (1 atm), 908C, 24 h. [b] Yield of
isolated product. [c] Product ratio determined using NMR analysis of iso-
lated mixtures. [d] The assignment of E stereochemistry to the major
forded the product in lower yields, 45 and 51%, respectively.
On the other hand, PdCl2 was not effective at all. 2,6-Dime-
thoxy-1,4-benzoquinone and chloranil were also tested in
place of p-benzoquinone (BQ). However, both of these qui-
nones were less effective than BQ and only gave the prod-
ucts in yields ranging from 20 to 24%. Interestingly, the role
of [Fe(Pc)] was quite unique in the coupling as attempts to
substitute it with either cobalt(phthalocyanine), [Co(Pc)], or
isomer was supported by NOE analysis. [e] 5 mol% of Pd
used.
ACHTUNGRTEN(NUNG OAc)2 was
mate derivatives, 3b and 3c, in 66 and 61% yield, respec-
tively (Table 1, entries 2 and 3). Both a- and b-substituted
acrylates were effective in this aerobic coupling. Thus,
whereas the use of methyl cinnamate (1d) afforded the cou-
pled product as a mixture of E/Z isomers in 65% yield
(Table 1, entry 4), the use of ethyl crotonate (1e) gave a
single isomer in a moderate yield of 35% (Table 1, entry 5).
When n-butyl a-methacrylate (1 f) was used, two different
arylated products were obtained, namely the normal prod-
uct, 3 f1, and its double bond isomer, 3 f2, which were ob-
tained in a combined yield of 56% (Table 1, entry 6). Nota-
bly, in addition to acrylates, conjugated aldehydes and ke-
tones are also suitable olefins to couple with 2 in this reac-
tion. Thus, cinnamaldehyde (1g) and chalcone (1h) were
successfully coupled with 2 and the corresponding products,
3g and 3h, were isolated in 67 and 63% yield, respectively,
as a 7:1 mixture of E/Z isomers in each case (Table 1, en-
tries 7 and 8). In addition, the reaction of phenyl vinyl sul-
fone (1i) with 2 also gave the desired product in 55% yield
(Table 1, entry 9). Even though the stereochemistry of the
cobaltACHTUNGTRENNUNG(salophen) were less successful and afforded coupling
product 3a in low yield (12 and 28%, respectively). The
presence and identity of acid was also crucial: the coupling
was inefficient in the absence of acetic acid and although tri-
fluoroacetic acid promoted the reaction to some extent
(31% yield), the use of methane sulfonic acid was not effec-
tive at all. The reaction completely failed in the absence of
PdACHTUNGTRENNUNG(OAc)2, and the absence of an ETM in the coupled cata-
lytic system resulted in less than 10% yield. Decreasing the
loading of BQ and [Fe(Pc)] to 5 mol% and 1 mol%, respec-
tively, afforded the cinnamate derivative in only 38% yield.
With optimized reaction conditions established, we next
examined the scope of the oxidative coupling reaction by
using various olefins in conjunction with 2. As summarized
in Table 1, a wide range of electron-deficient olefins could
be employed as the coupling partners. Thus, other acrylates
such as methyl acrylate (1b) and tert-butyl acrylate (1c) also
coupled smoothly with 2 to afford the corresponding cinna-
Chem. Eur. J. 2013, 19, 4140 – 4145
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4141

J.-E. Bꢀckvall et al.
b,b-disubstituted products can be predicted by the well-ac-
cepted mechanism of the Heck reaction, NOE experiments
were carried out on the major isomer obtained from repre-
sentative reactions to confirm the assignment.
ingly, 2,3-benzofuran was also reactive under these reaction
conditions and afforded a mixture of 2- and 3-substituted
isomers in a ratio of 4:1. When 1-bromo-3,5-dimethoxyben-
zene was subjected to the reaction conditions, the expected
product 11 was isolated as a white crystalline solid in a mod-
erate yield of 40%, the bromine atom remaining in the
product. Alkyl-substituted benzenes, p-xylene, o-xylene, and
toluene could also undergo oxidative coupling, thus giving
the corresponding cinnamate derivatives. The use of p-
xylene afforded product 12 in 54% yield, whereas the use of
o-xylene and toluene gave products 13 and 14, respectively,
each being isolated as a mixture of isomers. However, 10
equivalents of alkyl benzenes was used for good conversion.
This protocol was not limited to electron-rich arenes; elec-
tronically neutral arenes such as benzene and naphthalene
also coupled with 1a to give the corresponding cinnamates,
15 and 16, in 56 and 64% yields, respectively. A catalyst
À
As summarized in Scheme 3, the C H olefination of a
number of arenes with n-butyl acrylate was quite successful.
In the case of electron-rich arenes such as alkoxy- and alkyl-
substituted arenes, this biomimetic aerobic coupling pro-
loading of 5 mol% PdACHTNUGTRNEUNG(OAc)2 and 10 equivalents of arene
were required in the case of benzene and naphthalene to
achieve the best results. Moderately electron-deficient
arenes such as chlorobenzene and bromobenzene also func-
tioned as successful arene partners in this coupling when
5 mol% PdACTHNURGTNEUNG(OAc)2 and 10 equivalents of arene were em-
ployed. The cinnamate derivatives 17 and 18 were isolated
as mixtures of isomers in 54 and 45% yield, respectively.
Interestingly, careful monitoring of the reaction revealed
that the course of the coupling of electron-rich arenes with
acrylates depends on the amount of catalyst and it is possi-
ble to switch between mono- and diarylated products by
changing the catalyst loading. Thus, for the coupling of 1a
and 2, when the catalyst loading was increased from 2.5 to
4 mol% and the reaction time was 24 hours, a mixture of
mono- (b) and diarylated (b,b) products in a ratio of 1:4 was
obtained. By increasing the catalyst loading further to
5 mol%, diarylated product 19 was obtained exclusively in
55% yield as a brown viscous liquid. The product yield was
increased to 70% when 10 equivalents of 2 was used in
1 mL of acetic acid, reaction conditions that turned out to
be optimal for this diarylation reaction (Table 2, entry 1).
This protocol was found to be applicable to other electron-
rich arenes and acrylates and the results are shown in
Table 2. The use of tert-butyl acrylate with 2 led to diarylat-
ed product 20 being isolated in 61% yield (Table 2, entry 2).
The use of 1,4-dimethylbenzene was also successful in the
aerobic diarylation reaction with n-butyl acrylate, yielding
the corresponding product 21 in 66% yield (Table 2,
entry 3). Finally, the use of 1,2-dimethoxybenzene and 1,2-
dimethylbenzene afforded the corresponding diarylated
products 22 and 23 in 63 and 62% yield, respectively, a mix-
ture of isomers being isolated in each case (Table 2, in en-
tries 4 and 5).
À
Scheme 3. Biomimetic aerobic C H olefination of arenes with n-butyl
acrylate. Unless otherwise noted, 1a (1 mmol), arene (5 mmol), Pd-
ACHTUNGTRENNUNG(OAc)2 (2.5 mol%), BQ (20 mol%), [Fe(Pc)] (2 mol%), and AcOH
(0.5 mL), were stirred under O2 (1 atm) at 908C for 24 h. Yields of prod-
ucts isolated by chromatography are reported. Product ratios were deter-
mined from 1H NMR analysis of isolated mixtures. [a] Arene (10 mmol)
and AcOH (1.0 mL) were used. [b] Arene (10 mmol), PdACTHNUTRGNEUNG(OAc)2
(5 mol%) and AcOH (1.0 mL) were used. [c] Reaction at 808C.
ceeded smoothly with low catalyst loading, PdACTHNUTRGNEUNG(OAc)2
(2.5 mol%), and with only 5–10 equivalents of excess arene,
thus providing the corresponding mono-olefinated products
in moderate to good yields. The use of 1,4-dimethoxyben-
zene, 1,3-dimethoxybenzene, and 1,4-dimethoxynaphthalene
gave the corresponding cinnamate derivatives, 3a, 5, and 6,
respectively, as single isomers. The use of 1,2-dimethoxyben-
zene gave 7 as a 7:1 mixture of isomers, whereas the use of
1,2,3-trimethoxybenzene afforded 8 as a 5:1 mixture of iso-
mers. The use of anisole provided a mixture of ortho, meta,
and para isomers 9 in a ratio of 4:1:7, respectively. Interest-
Notably, the mono- and diarylation of acrylate was quite
sensitive towards the Pd
ACHTUNGTRENNUNG
tion between 1a and 2 with 2.5 mol% Pd
AHCTUNGTRENNUNG
forded monoarylated acrylate 3a as the major product (even
after 40 h), was relatively slow (44% conversion after 8 h),
when 5 mol% of PdACTHNUTRGNE(UNG OAc)2 was used, the same reaction was
4142
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 4140 – 4145

Biomimetic Oxidative Coupling of Arenes and Olefins
Table 2. Biomimetic aerobic diarylation of acrylates with arenes.[a]
COMMUNICATION
Entry
1
Arene
Product
Yield [%][b]
70
Scheme 4. Determination of deuterium isotope effects. (i) 1a (1 mmol),
C6H6/C6D6 (10 mmol), PdACTHNUGTRNEUNG(OAc)2 (5 mol%), BQ (20 mol%), [Fe(Pc)]
(2 mol%), AcOH (1 mL), 908C, O2 (1 atm), 2 h.
2
3
61
66
ments a kinetic isotope effect (kH/kD) of 3.9 was obtained.
In addition, when a 1:1 mixture of benzene and [D6]benzene
was subjected to the same reaction condition (Scheme 4,
[Eq. (4)]), ESI mass spectrometric analysis of the reaction
mixture, after a reaction time 2 h, showed the presence of
15 and [D5]-15 in a ratio of 4.1:1, thus representing a kinetic
isotope effect of 4.1.[15]
A possible mechanism for the reaction is presented in
Scheme 5, it being similar to the well-known Fujiwara–Mori-
tani reaction.[8] As depicted in path 1, s-aryl-PdII intermedi-
4
5
63[c] (6:1)
62[c] (3:1)
[a] Acrylate (1 mmol), arene (10 mmol), PdACTHNURTGNENG(U OAc)2 (5 mol%), BQ
(20 mol%), [Fe(Pc)] (2 mol%), AcOH (1.0 mL), O2 (1 atm), 908C, 24 h.
[b] Yield of isolated product. [c] Combined yield of isomeric products.
fast and afforded, after 6 hours, a mixture of mono- and dia-
rylated acrylates in an approximate ratio of 2:1 ratio and
with 80% conversion. We therefore monitored the progress
of the reaction between 1a and 1,4-dimethoxybenzene
(Table 2, entry 1). At reaction times of up to 3 hours, the
monoarylated product, 3a, was formed almost exclusively
(69%) with only trace amount of diarylated product 19. For
reaction times longer than 3 hours, the diarylation reaction
becomes competitive and the yield of 19 gradually increases,
at the expense of 3a, the yield of which decreases with
longer reaction times, thus leading to 19 being the exclusive
product after a reaction time of 24 hours.[12]
There are not many reports in the literature for selective
b,b-diarylation of acrylates.[9j,13] The one-pot aerobic double
dehydrogenative coupling described herein is noteworthy
because it allows symmetrical b,b-diarylated conjugated
esters to be formed exclusively by using acrylates as the sub-
strate and a relatively low catalyst loading of 5 mol% under
ambient oxygen pressure as reaction conditions. b,b-Diary-
lated a,b-unsaturated esters and their derivatives are impor-
tant moieties in organic synthesis because they are structural
elements in many natural products and can function as pre-
cursors in synthesis.[14]
Scheme 5. Plausible mechanism for the aerobic dehydrogenative cou-
pling.
ate I is formed first through electrophilic substitution and
then coordinates the olefin to form p-complex II. Migratory
insertion gives III and subsequent b-hydride elimination
generates the product, IV. The hydride species. HPdACHTUNGTRENNUNG(OAc),
which is formed as an intermediate, is subsequently reduced
to Pd0. However, the acidity of the reaction medium and the
coordination of BQ to the metal gives Pd0 a sufficient life-
time in solution.[16] These conditions prevent the precipita-
tion of Pd0 and enables reoxidation of Pd0 to PdII through a
biomimetic route, with O2 as the terminal oxidant and p-BQ
To obtain insight into the mechanism of the reaction, we
compared the initial rates of the reactions between both
benzene and [D6]benzene with 1a in two independent ex-
periments (Scheme 4, [Eqs. (2) and (3)]). From these experi-
Chem. Eur. J. 2013, 19, 4140 – 4145
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4143

J.-E. Bꢀckvall et al.
[6] a) R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5518; b) R. F. Heck, J.
Am. Chem. Soc. 1968, 90, 5538; c) T. Mizoroki, K. Mori, A. Ozaki,
Bull. Chem. Soc. Jpn. 1971, 44, 581; d) R. F. Heck, J. P. Nolley, J.
Org. Chem. 1972, 37, 2320–2322; e) I. P. Beletskaya, A. V. Chepra-
kov, Chem. Rev. 2000, 100, 3009–3066.
[7] For recent reviews, see: a) J. Le Bras, J. Muzart, Chem. Rev. 2011,
111, 1170–1214; b) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111,
1215–1292; c) X. Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew.
Chem. 2009, 121, 5196–5217; Angew. Chem. Int. Ed. 2009, 48, 5094–
5115.
and Fe(Pc) as electron-transfer mediators, as shown in
path 2.
In conclusion, we have developed a novel, biomimetic,
À
À
aerobic route for the dehydrogenative C H/C H coupling
between arenes and olefins. The reaction works well for
both electron-rich and moderately electron-deficient arenes.
Relatively low catalyst loading was required and this ap-
proach allowed the arene to be used in amounts that were
not too excessive. Importantly, the outcome could be switch-
ed between mono- and diarylation of acrylate by varying the
catalyst loading.
[8] a) I. Moritani, Y. Fujiwara, Tetrahedron Lett. 1967, 8, 1119–1122;
b) Y. Fujiwara, I. Moritani, M. Matsuda, S. Teranishi, Tetrahedron
Lett. 1968, 9, 3863–3865; c) C. Jia, W. Lu, T. Kitamura, Y. Fujiwara,
Org. Lett. 1999, 1, 2097–2100; d) C. Jia, D. Piao, J. Oyamada, W.
Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287, 1992–1995.
[9] a) T. Yokota, M. Tani, S. Sakaguchi, Y. Ishii, J. Am. Chem. Soc.
2003, 125, 1476–1477; b) M. Dams, D. E. De Vos, S. Celen, P. A.
Jacobs, Angew. Chem. 2003, 115, 3636–3639; Angew. Chem. Int. Ed.
2003, 42, 3512–3515; c) E. M. Beck, N. P. Grimster, R. Hatley, M. J.
Gaunt, J. Am. Chem. Soc. 2006, 128, 2528–2529; d) Y.-H. Zhang, B.-
F. Shi, J.-Q. Yu, J. Am. Chem. Soc. 2009, 131, 5072–5074; e) N. P.
Grimster, C. Gauntlett, C. R. A. Godfrey, M. J. Gaunt, Angew.
Chem. 2005, 117, 3185–3189; Angew. Chem. Int. Ed. 2005, 44, 3125–
3129; f) C. Aouf, E. Thiery, J. Le Bras, J. Muzart, Org. Lett. 2009, 11,
4096–4099; g) A. Garcꢆa-Rubia, R. G. Arrayꢇs, J. C. Carretero,
Angew. Chem. 2009, 121, 6633–6637; Angew. Chem. Int. Ed. 2009,
48, 6511–6515; h) M. Ye, G.-L. Gao, J.-Q. Yu, J. Am. Chem. Soc.
2011, 133, 6964–6967; i) D.-H. Wang, J.-Q. Yu, J. Am. Chem. Soc.
2011, 133, 5767–5769; j) S. Harada, H. Yano, Y. Obora, Chem-
CatChem. 2013, 5, 121–125.
[10] For some recent reports on Pd(II)-catalyzed DHR, see: a) A. Vas-
seur, J. Muzart, J. Le Bras, Chem. Eur. J. 2011, 17, 12556–12560;
b) A. Kubota, M. H. Emmert, M. S. Sanford, Org. Lett. 2012, 14,
1760–1763; c) Y. Zhang, Z. Cui, Z. Li, Z.-Q. Liu, Org. Lett. 2012,
14, 1838–1841; d) Y. Mizuta, Y. Obora, Y. Shimizu, Y. Ishii, Chem-
CatChem 2012, 4, 187–191; e) W.-L. Chen, Y.-R. Gao, S. Mao, Y.-L.
Zhang, Y.-F. Wang, Y.-Q. Wang, Org. Lett. 2012, 14, 5920–5923; for
recent ruthenium-catalyzed DHR, see: f) T. Ueyama, S. Mochida, T.
Fukutani, K. Hirano, T. Satoh, M. Miura, Org. Lett. 2011, 13, 706–
708; g) L. Ackermann, L. Wang, R. Wolfram, A. V. Lygin, Org. Lett.
2012, 14, 728–731; h) B. Li, J. Ma, N. Wang, H. Feng, S. Xu, B.
Wang, Org. Lett. 2012, 14, 736–739; i) K. Padala, M. Jeganmohan,
Experimental Section
PdACHTUNGTRENNUNG(OAc)2 (5.6 mg, 0.025 mmol), p-benzoquinone (21.6 mg, 0.2 mmol),
iron phthalocyanine (11.4 mg, 0.02 mmol), and 1,4-dimethoxybenzene
(690 mg, 5 mmol) were added to a Schlenk tube. The mixture was de-
gassed under reduced pressure for a few seconds and then oxygen gas
was introduced with a balloon. This exchange of atmosphere was repeat-
ed 3–4 times and olefin (1 mmol) was introduced into the tube (in the
case of olefins that were solids, these were introduced along with the
other reagents). Acetic acid (0.5 mL) was then added and the mixture
was stirred in an oil bath at 908C for 24 h under molecular oxygen. The
reaction mixture was then cooled to room temperature, diluted with
CH2Cl2, and filtered through a short pad of Celite. The filtrate was con-
centrated and the residue was subjected to silica-gel column chromatog-
raphy, eluting with pentane/ethyl acetate to afford the corresponding
product.
Acknowledgements
Financial support from the European Research Council (ERC AdG
247014) is gratefully acknowledged.
Org. Lett. 2012, 14, 1134–1137; for a recent rhodiumACHTUNTRGNEU(GN III)-catalyzed
DHR, see: j) Z. Shi, N. Schrçder, F. Glorius, Angew. Chem. 2012,
124, 8216–8220; Angew. Chem. Int. Ed. 2012, 51, 8092–8096.
À
Keywords: aerobic oxidation · biomimetic synthesis · C H
activation · dehydrogenative coupling · palladium
[11] a) D.-H. Wang, K. M. Engle, B.-F. Shi, J.-Q. Yu, Science 2010, 327,
315–319; b) M. Miura, T. Tsuda, T. Satoh, S. Pivsa-Art, M. Nomura,
J. Org. Chem. 1998, 63, 5211–5215; c) M. D. K. Boele, G. P. F. van
Strijdonck, A. H. M. de Vries, P. C. J. Kamer, J. G. de Vries,
P. W. N. M. van Leeuwen, J. Am. Chem. Soc. 2002, 124, 1586–1587;
d) G. Cai, Y. Fu, Y. Li, X. Wan, Z. Shi, J. Am. Chem. Soc. 2007, 129,
7666–7673; e) J.-R. Wang, C.-T. Yang, L. Liu, Q.-X. Guo, Tetrahe-
dron Lett. 2007, 48, 5449–5453; f) C. E. Houlden, C. D. Bailey, J. G.
Ford, M. R. Gagnꢈ, G. C. Lloyd-Jones, K. I. Booker-Milburn, J. Am.
Chem. Soc. 2008, 130, 10066–10067; g) B.-F. Shi, Y.-H. Zhang, J. K.
Lam, D.-H. Wang, J.-Q. Yu, J. Am. Chem. Soc. 2010, 132, 460–461;
h) K. M. Engle, D.-H. Wang, J.-Q. Yu, J. Am. Chem. Soc. 2010, 132,
14137–14151; i) K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew. Chem.
2010, 122, 6305–6309; Angew. Chem. Int. Ed. 2010, 49, 6169–6173;
j) J. W. Wrigglesworth, B. Cox, G. C. Lloyd-Jones, K. I. Booker-Mil-
burn, Org. Lett. 2011, 13, 5326–5329; k) P. Gandeepan, C.-H.
Cheng, J. Am. Chem. Soc. 2012, 134, 5738–5741; l) M. Yu, Y. Xie,
C. Xie, Y. Zhang, Org. Lett. 2012, 14, 2164–2167; m) G. Li, D.
Leow, L. Wan, J.-Q. Yu, Angew. Chem. 2013, 125, 1283—1284;
Angew. Chem. Int. Ed. 2013, 52, 1245–1247.
[1] R. A. Sheldon, I. W. C. E. Arends, G. J. ten Brink, A. Dijksman,
Acc. Chem. Res. 2002, 35, 774–781.
[2] a) A. Berkessel, Adv. Inorg. Chem. 2006, 58, 1; b) J. Piera, J.-E.
Bꢀckvall, Angew. Chem. 2008, 120, 3558–3576; Angew. Chem. Int.
Ed. 2008, 47, 3506–3523.
[3] a) J.-E. Bꢀckvall, A. K. Awasthi, Z. D. Renko, J. Am. Chem. Soc.
1987, 109, 4750–4752; b) J.-E. Bꢀckvall, R. B. Hopkins, H. Grenn-
berg, M. Mader, A. K. Awasthi, J. Am. Chem. Soc. 1990, 112, 5160–
5166; c) J. Wçltinger, J.-E. Bꢀckvall, ꢃ. Zsigmond, Chem. Eur. J.
1999, 5, 1460–1467.
[4] a) J. Piera, K. Nꢀrhi, J.-E. Bꢀckvall, Angew. Chem. 2006, 118, 7068–
7071; Angew. Chem. Int. Ed. 2006, 45, 6914–6917; b) A. K. ꢄ. Pers-
son, J.-E. Bꢀckvall, Angew. Chem. 2010, 122, 4728; Angew. Chem.
Int. Ed. 2010, 49, 4624; c) J. Piera, A. Persson, X. Caldentey, J. E.
Bꢀckvall, J. Am. Chem. Soc. 2007, 129, 14120–14121.
[5] a) G. Csjernyik, A. H. ꢅll, L. Fadini, B. Pugin, J.-E. Bꢀckvall, J. Org.
Chem. 2002, 67, 1657–1662; b) A. H. ꢅll, J. S. M. Samec, C. Brasse,
J.-E. Bꢀckvall, Chem. Commun. 2002, 1144–1145; c) J. S. M. Samec,
A. H. Ell, J.-E. Bꢀckvall, Chem. Eur. J. 2005, 11, 2327–2334; d) Y.
Endo, J.-E. Bꢀckvall, Chem. Eur. J. 2012, 18, 13609–13613; e) Y.
Endo, J.-E. Bꢀckvall, Chem. Eur. J. 2011, 17, 12596–12601; f) B. P.
Babu, Y. Endo, J.-E. Bꢀckvall, Chem. Eur. J. 2012, 18, 11524–11527.
[12] See the Supporting Information for details.
[13] a) J. Tsuji, H. Nagashima, Tetrahedron 1984, 40, 2699–2702; b) M.
Tani, S. Sakaguchi, Y. Ishii, J. Org. Chem. 2004, 69, 1221–1226; c) T.
Yamada, S. Sakaguchi, Y. Ishii, J. Org. Chem. 2005, 70, 5471–5474.
4144
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 4140 – 4145

Biomimetic Oxidative Coupling of Arenes and Olefins
COMMUNICATION
[14] a) J. G. Taylor, C. R. D. Correia, J. Org. Chem. 2011, 76, 857–869;
b) J. C. Pastrea, C. R. D. Correia, Adv. Synth. Catal. 2009, 351,
1217–1223; c) W. D. Ollis, B. T. Redman, R. J. Roberts, I. O. Suther-
land, O. R. Gottlieb, J. Chem. Soc. Chem. Commun. 1968, 1392–
1393; d) A. B. Alarcꢉn, O. Cuesta-Rubio, J. C. Perez, A. L. Piccinel-
li, L. Rastrelli, J. Nat. Prod. 2008, 71, 1283–1286; e) B. D. Gallagher,
R. Taft, B. H. Lipshutz, Org. Lett. 2009, 11, 5374–5377; f) R. Berni-
ni, S. Cacchi, I. D. Salve, G. Fabrizi, Synlett 2006, 2947–2952; g) Y.
Yamamoto, N. Kirai, Y. Harada, Chem. Commun. 2008, 2010–2012;
h) T. Ikemoto, T. Nagata, M. Yamano, T. Ito, Y. Mizuno, K. Tomi-
matsu, Tetrahedron Lett. 2004, 45, 7757–7760; i) F. Song, S. Lu, J.
Gunnet, J. Z. Xu, P. Wines, J. Proost, Y. Liang, C. Baumann, J. Len-
hard, W. V. Murray, K. T. Demarest, G.-H. Kuo, J. Med. Chem. 2007,
50, 2807–2817; j) X. Peng, P. Li, Y. Shi, J. Org. Chem. 2012, 77, 701–
703.
[15] See the Supporting Information for details. The deuterium isotope
effect obtained is in accordance with that obtained by Ishii and co-
workers (4.0), Ref [9a].
[16] H. Grennberg, A. Gogoll, J.-E. Bꢀckvall, Organometallics 1993, 12,
1790–1793.
Received: January 11, 2013
Published online: February 28, 2013
Chem. Eur. J. 2013, 19, 4140 – 4145
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
4145