Pd-catalyzed C-H olefination of (hetero)arenes by using saturated ketones as an olefin source

Article abstract of DOI:10.1002/anie.201208627

Tolerant: By using Pd(OAc)₂/PCy₃ as a catalyst, both electron-rich aromatic heterocycles and electron-deficient fluorobenzenes undergo the dehydrogenative cross-coupling with (hetero)aryl ethyl ketones in good yields. A broad range of functional groups is tolerated, thus providing a general method for the facile syntheses of chalcones or heterocyclic chalcone analogues. Furthermore, dialkyl ketones can also participate in this transformation. Copyright

Full text of DOI:10.1002/anie.201208627

Angewandte
Chemie
DOI: 10.1002/anie.201208627
Synthetic Methods
Pd-Catalyzed C–H Olefination of (Hetero)Arenes by Using Saturated
Ketones as an Olefin Source**
Yaping Shang, Xiaoming Jie, Jun Zhou, Peng Hu, Shijun Huang, and Weiping Su*
Chalcones and their heterocyclic analogues represent an
important class of naturally occurring and synthetic com-
pounds, which display a wide range of pharmacological
properties,[1] including cytotoxicity towards cancer cell
lines;[2a,b] antimitotic[2c] and antimutagenic[2d] activities; anti-
bacterial,[2e] antiviral,[2f] and anti-inflammatory activity.[2g]
Recently, several chalcone-based drug candidates have
entered into preclinical trial stages for the development of
antimalarial and antileishmanial drugs.[2h] Furthermore, these
compounds are of great importance as intermediates both in
the syntheses of a large number of heterocyclic systems[3] and
in functional materials.[4]
Traditionally, chalcones and their heterocyclic analogues
are synthesized by the aldol condensation between aromatic
aldehydes and ketones (Scheme 1a).[5] Because the aldol
condensation often requires strongly basic reaction condi-
tions, the functional groups sensitive to bases cannot be
tolerated in such a condensation reaction. To overcome this
limitation, the research groups of Mꢀller and Beller inde-
pendently developed a Pd-catalyzed Sonogashira coupling of
electron-deficient aryl halides with aryl 1-propargyl alcohols
(Scheme 1b)[6] and a Pd-catalyzed carbonylative Heck cou-
pling of aryl halides with styrenes (Scheme 1c)[7] for the
syntheses of chalcones, respectively.
À
The rapid development in the metal-catalyzed C H bond
functionalization reactions have demonstrated the great
potential of these chemical transformations to synthesize
valuable products from simple starting materials in concise
steps and therefore minimize waste formation in the synthesis
process.[8] Recently, we have achieved decarboxylative vinyl-
ation of aryl carboxylic acids with nitroethane[9a] or propio-
phenones.[9b] These encouraging achievements led us to
consider whether the dehydrogenative cross-coupling
between (hetero)arenes and saturated ketones could directly
afford chalcones or heterocyclic chalcone analogues. Herein,
we report a versatile method for the facile syntheses of
chalcone or heterocyclic chalcone analogues through Pd-
catalyzed dehydrogenative cross-coupling between (hetero)-
arenes and (hetero)aryl ethyl ketones (Scheme 1d) and
demonstrate that unsymmetrical dialkyl ketones also undergo
this coupling reaction with reaction occurring exclusively on
the less sterically hindered moiety. The mechanistic studies
revealed that this reaction proceeds through dehydrogenation
to form an olefin intermediate in situ and a subsequent C–H
olefination sequence.
Although transition-metal-catalyzed Heck coupling of
aryl halides or (hetero)arenes with (hetero)aryl vinyl ketones
would directly generate chalcones or their heterocyclic
analogues in principle, the examples of this type of reaction
are scarce, presumably because (hetero)aryl vinyl ketones are
not commercially available. Our protocol allows using
saturated ketones as equivalents of olefins for the direct
olefination of (hetero)arenes and thereby enhances trans-
formation efficiency, which is further illustrated by the
troublesome preparation of a,b-unsaturated carbonyl com-
pounds. Typically, the preparation of a,b-unsaturated carbon-
yl compounds require two or more than two steps starting
from the corresponding saturated carbonyl compounds;[10–13]
examples of such methods are Pd-mediated dehydrosilylation
of silyl enol ethers (Saegusa oxidation),[10] halogenation–
dehalogenation sequence,[11] and/or use of stoichiometric
reagents such as 2-iodoxybenzoic acid (IBX)[12] and 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).[13] The Pd-
catalyzed aerobic oxidative dehydrogenation of ketones
represents a promising method for the facile synthesis of
a,b-unsaturated ketones, but is still limited to cyclic enones or
b-arylated enones.[14] Consequently, the reactions that com-
bine in situ dehydrogenation to form reactive olefin inter-
mediates with secondary coupling process are attracting
attention from synthetic chemists.[15] In this context, pioneer-
Scheme 1. The syntheses of chalcones. EWG=electron-withdrawing
groups.
[*] Dr. Y. Shang,[+] X. Jie,[+] J. Zhou, P. Hu, S. Huang, Prof. Dr. W. Su
State Key Laboratory of Structural Chemistry
Fujian Institute of Research on the Structure of Matter
Chinese Academy of Sciences
Yangqiao west road 155#, Fuzhou, Fujian 350002 (China)
E-mail: wpsu@fjirsm.ac.cn
[+] These authors contributed equally to this work.
[**] Financial support from the 973 Program (2011CB932404,
2011CBA00501), NSFC (20925102) is greatly appreciated.
Supporting information (including full experimental details) for this
article is available on the WWW under http://dx.doi.org/10.1002/
anie.201208627.
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ing studies have emerged, including the Pd-catalyzed dehy-
drogenative b-arylation of alkyl aryl ketones with aryl
bromides,[15a] Ni-catalyzed dehydrogenative amination of
propiophenones,[15b] the Pd-catalyzed dehydrogenative
Diels–Alder reaction of terminal olefins with dienes,[15c] the
Pd-catalyzed dehydrogenative b’-functionalization of b-keto
esters with indoles,[15d] and the dehydrogenative cross-cou-
pling of cyclic b-heteroatom-substituted ketones with ben-
zenes.[15e] Despite these advances, the dehydrogenative cross-
coupling between (hetero)arenes and saturated ketones
through in situ dehydrogenation to generate olefin intermedi-
ates is an almost untouched area.
The challenge posed by our targeted reaction is the
identification of suitable reaction conditions that are compat-
ible with both the oxidative dehydrogenation of saturated
ketones to olefin intermediates and C–H olefination of
(hetero)arenes, and also allow these two processes to operate
À
in a tandem manner. Elegant studies on C H bond function-
alization of (hetero)arenes[16–18] provided useful starting
points for our investigation of dehydrogenative cross-cou-
pling of this type. The reaction of 2-methylthiophene (1a)
with propiophenone (2a; 3.0 equiv) in 1,2-dimethoxyethane
(DME; 2.0 mL) at 1008C was chosen as a model system for
the optimization studies using Pd(OAc)2 (10 mol%) as
a catalyst, and Ag2CO3 (2.5 equiv) as an oxidant (see the
Supporting Information for details).[19] The initial reaction
conditions did not give the desired cross-coupling product in
any detectable amount; instead a large amount of homocou-
pling product from thiophene was formed.[17a] Three critical
parameters were identified, the modification of which led to
a high-yielding reaction. First, the use of PCy3 as a ligand
efficiently suppressed the homocoupling of thiophene and
dramatically improved the efficiency of this reaction, prob-
ably because the strongly electron-donating PCy3 may reduce
the electrophilicity of palladium and thus inhibit further
electrophilic attack of palladium to the second thiophene
molecule after the palladation of thiophene. The second
critical parameter proved to be the additional base. Of the
examined bases, LiOAc provided the best result. The use of
TEMPO (0.4 equiv; TEMPO = 2,2,6,6-tetramethyl piperi-
dine-N-oxyl) as a cooxidant led to an increase in yield
presumably owing to its ability to accelerate reoxidation of
Pd0 to PdII.[20]
With the optimized reaction conditions in hand
(Pd(OAc)2 (10 mol%), PCy3 (20 mol%), TEMPO
(0.4 equiv), LiOAc (1.5 equiv), Ag2CO3 (3.0 equiv), DME
(2.0 mL), and 1008C), we first examined the substrate scope
of this reaction with respect to heterocycles. As shown in
Scheme 2, this reaction was applicable to a variety of
substituted thiophenes, furans, and indoles, and gave the
corresponding products in synthetically useful yields with
excellent selectivity (the reaction occurred exclusively at the
5-position of monosubstituted thiophene or furan rings, and at
the 3-position of indoles, E/Z > 99:1). In contrast, unsubsti-
tuted heteroarenes such as thiophene afforded the product in
poor yields (3w). A broad range of functional groups were
tolerable, including base-sensitive formyl and acetyl groups,
an acid-sensitive ketal group, and easily leaving acetate
groups, which provided useful handles for further trans-
Scheme 2. The scope of heterocycles. Conditions: Pd(OAc)2
(10 mol%), PCy3 (20 mol%), TEMPO (0.4 equiv), LiOAc (1.5 equiv),
Ag2CO3 (3.0 equiv), DME (2.0 mL). Yields of isolated products are
reported. [a] NaOAc (0.45 mmol) was used instead of LiOAc.
[b] Carried out at 1208C.
formations. Note that furans and N-methylindoles underwent
this reaction at elevated temperature (1208C) to afford the
corresponding products in synthetically useful yields. Inter-
estingly, the reaction of 2-formylfuran produced the desired
product along with a saturated by-product (3s’) with an 8:1
selectivity.
Next, we evaluated the scope of (hetero)aryl ethyl
ketones by using 2-methyl thiophene as a coupling partner
(Scheme 3). Both electron-withdrawing and electron-donat-
ing substituents on the benzene ring of (hetero)aryl ethyl
ketones furnished good to excellent yields with the exception
of the dimethylamino substitutent. Variations of substitution
positions did not much influence the product yields, as
illustrated by the reactions of three fluoro-substituted pro-
piophenone isomers. 1-(2-Naphthyl)-1-propanone also exhib-
ited excellent reactivity towards this reaction. For most of the
propiophenones bearing electron-withdrawing substituents,
reducing the amount of PCy3 to 10 mol% was required to
achieve satisfying yields. Notably, as exemplified by 1-(3-
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Scheme 5. The dehydrogenative cross-coupling between fluoroben-
zenes with propiophenones. Conditions: Pd(OAc)2 (10 mol%), KF
(3 equiv), TEMPO (0.2 equiv), Ag2CO3 (2.5 equiv), DME (2.0 mL),
TMSO (2 equiv). Yields of isolated products are reported. In all cases
the E/Z ratios were >99:1. [a] Without TMSO. [b] For the detailed
experimental process see the Supporting Information.
Scheme 3. The scope of (hetero)aryl ethyl ketones. Conditions:
Pd(OAc)2 (10 mol%), PCy3 (20 mol%), TEMPO (0.4 equiv), LiOAc
(1.5 equiv), Ag2CO3 (3.0 equiv), DME (2.0 mL). Yields of isolated
products are reported. Np=naphthyl. [a] PCy3 (10 mol%) was used.
[b] Carried out at 1208C.
There are three possible reaction pathways for the
dehydrogenative cross-coupling of aromatic heterocycles
with saturated ketones (Scheme 6). Path I involves the
carbonyl directed b-C–H palladation[21] followed by b-aryla-
tion with thiophene and dehydrogenation to form the target
product. However, path I cannot be supported by the
observation that ketones lacking an a-H atom, such as tert-
butyl phenyl ketone, did not participate in this dehydrogen-
ative cross-coupling. Path II comprises the initial b-C–H
palladation that occurs through the process proposed by
Baudoin and co-workers[22] (b-H elimination of Pd-enolate,
1808 rotation of the olefin coordinating to Pd, double bond
pyridinyl)-1-propanone, replacing the phenyl moiety of
propiophenone with a heterocyclic group has only a slight
effect on the reactivity of substrates.
À
reinsertion into the Pd H bond), the subsequent b-arylation
Scheme 4. Dehydrogenative cross-coupling of dialkyl ketones with
thiophenes. Conditions: Conditions: Pd(OAc)2 (10 mol%), PCy3
(20 mol%), TEMPO (0.4 equiv), LiOAc (1.5 equiv), Ag2CO3 (3.0 equiv),
DME (2.0 mL). Yields of isolated products are reported. [a] PCy3
(10 mol%) was used.
with thiophene, and dehydrogenation to form the product. If
path II operates, the hydrogen atom on the b-position of the
ketone would migrate from the b-position to the a-position.
Thus, b-deuterated ethyl phenyl ketone was prepared and
used for a deuterium-labeling experiment. The reaction of b-
deuterated ethyl phenyl ketone with 2-methylthiophene did
Gratifyingly, dialkyl ketones can par-
ticipate in this dehydrogenative cross-
coupling (Scheme 4). Although unsym-
metrical dialkyl ketones have two acces-
sible reaction sites, reactions occurred
exclusively on the less sterically hindered
ethyl group.
To show the generality of this reac-
tion, we further expanded the substrate
scope to electron-deficient benzenes
(Scheme 5). An array of polyfluoroben-
zenes exhibited good reactivity towards
this reaction, and afforded the desired
products in reasonable yields. Benzene
also participated in this reaction, albeit in
diminished yield. In this case, TMSO
(2.0 equiv; TMSO = tetramethylene sulf-
oxide) was used as ligand rather than
PCy3, and KF was the base of choice.
Scheme 6. Three possible reaction pathways.
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not generate any a-deuterated product,[19] thus eliminating
the possibility of path II. Path III involves in situ dehydrogen-
ation of a ketone to a reactive olefin, followed by C–H
olefination of a heterocycle or by the 1,4-conjugate addition
of a heterocycle to an a,b-unsaturated ketone and subsequent
oxidative dehydrogenation. The dehydrogenation to in situ
generate an olefin intermediate has independently been
proposed by Pihko,[15d] Kuwano,[15b] and White[15c] to ration-
alize the dehydrogenative cross-coupling reactions. To
explore the possibility of path III, we checked the behavior
of propiophenone under our standard conditions in the
absence of thiophenes, and observed that propiophenone
indeed underwent dehydrogenation to generate phenyl vinyl
ketone in 26% yield after 24 h.[19] Because three equivalents
of propiophenone were used in the reaction, the phenyl vinyl
ketone generated from dehydrogenation would be almost
equimolar to 2-methylthiophene. Furthermore, the standard
conditions allowed the direct olefination of thiophene with
Received: October 26, 2012
Published online: December 7, 2012
Keywords: C–C coupling · C–H functionalization ·
.
dehydrogenation · heterocycles · olefination
[1] For a review on the bioactivity of chalcones, see: J. R. Dimmock,
D. W. Elias, M. A. Beazely, N. M. Kandepu, Curr. Med. Chem.
1999, 6, 1125 – 1149.
[2] a) M. T. Konieczny, W. Konieczny, M. Sabisz, A. Skladanowski,
R, Wakiec, J. Med. Chem. 2007, 42, 729 – 733; b) D. Kumar,
N. M. Kumar, K. Akamatsu, E. Kusaka, H. Harada, T. Ito,
Bioorg. Med. Chem. Lett. 2010, 20, 3916 – 3919; c) S. Ducki, R.
Forrest, J. A. Hadfield, A. Kendall, N. J. Lawrence, A. T.
McGown, D. Rennison, Bioorg. Med. Chem. Lett. 1998, 8,
1051 – 1056; d) R. Edenharder, I. V. Petersdorff, R. Rauscher,
Mutat. Res. 1993, 287, 261 – 274; e) S. N. Pandeya, D. Sriram, G.
Nath, E. DeClercq, Eur. J. Med. Chem. 1999, 9, 25 – 31; f) J. K.
Buolamwini, H. Assefa, J. Med. Chem. 2002, 45, 841 – 852; g) Z.
Nowakowska, Eur. J. Med. Chem. 2007, 42, 125 – 137; h) V. J.
Ram, A. S. Saxena, S. Srivastava, S. Chandra, Bioorg. Med.
Chem. Lett. 2000, 10, 2159 – 2161.
[3] For selected reviews on the syntheses of heterocyclic compounds
from chalcones, see: a) L. Raimondi, M. Benaglia, Eur. J. Org.
Chem. 2001, 1033 – 1043; b) R. Carriꢁ, Heterocycles 1980, 14,
1529 – 1545; c) B. Stanovnik, Tetrahedron 1991, 47, 2925 – 2945;
d) H. M. I. Osborn, N. Gemmell, L. M. Harwood, J. Chem. Soc.
Faraday Trans. 1 2002, 2419 – 2438.
[4] For selected examples of the syntheses of organic functional
materials from chalcones, see: a) J.-C. Ribierre, G. Cheval, F.
Huber, L. Mager, A. Fort, R. Muller, S. Mery, J. F. Nicoud, J.
Appl. Phys. 2002, 91, 1710 – 1712; b) C. Melzer, M. Barzoukas,
A. Fort, S. Mery, J.-C. Nicoud, Appl. Phys. Lett. 1997, 71, 2248 –
2250.
[5] C. Thebtaranonth, Y. Thebtaranonth in The Chemistry of
Enones, Vol. 29 (Eds.: S. Patai, Z. Rappoport), Wiley, New
York, 1989, pp. 199 – 280.
phenyl vinyl ketone in 68% yield[19]
.
Path III is also consistent with the results of kinetic
experiments. The initial rate of dehydrogenative cross-cou-
pling between 2-methyl thiophene (1a) and propiophenone
(2a) was dependent on the concentration of 2a. The initial
rate increased with the concentration of 2a, reached max-
imum at six equivalents of 2a, and then decreased upon
increasing the concentration of 2a from six to eight equiv-
alents (Figure S2 in the Supporting Information).[19] When
excess 2a (3 equiv or more than 3 equiv) was used, the rate of
cross-coupling between 1a and 2a was almost constant during
the whole reaction course. These data obtained from kinetic
experiments could be rationalized if the dehydrogenation of
2a to the olefin is slower than the cross-coupling of the olefin
intermediate with 1a. Although the dehydrogenation of 2a to
the olefin intermediate is a kinetically significant event, the
kinetic isotope effect (KIE) values for a- and b-positions of
2a (1.69 and 1.16, respectively) indicated that the rate-
determining step does not involve the C–H cleavage of the
ketone.
[6] a) T. J. J. Mꢀller, M. Ansorge, D. Aktah, Angew. Chem. 2000,
112, 1323 – 1326; Angew. Chem. Int. Ed. 2000, 39, 1253 – 1256;
b) R. U. Braun, M. Ansorge, T. J. J. Mꢀller, Chem. Eur. J. 2006,
12, 9081 – 9094.
To distinguish between the C–H olefination and the
conjugate addition of 1a to vinyl ketone followed by
dehydrogenation in the late stage of path III, we investigated
the reaction of 2-methyl-5-deuterated thiophene with pro-
piophenone.[19] This reaction did not generate the deuterated
product, thereby allowing us to eliminate the possibility of the
conjugate addition.
In summary, a Pd-catalyzed dehydrogenative cross-cou-
pling reaction of (hetero)arenes with (hetero)aryl ethyl
ketones has been developed. This protocol offers good
yields and tolerates a broad range of functional groups, thus
presenting a versatile method for the facile syntheses of
chalcones or heterocyclic chalcone analogues. In addition,
dialkyl ketones can also participate in this transformation
with the reaction occurring exclusively on the less sterically
hindered moiety and subsequent coupling between (hetero)-
arenes and olefin intemediates. Since olefins are versatile
intermediates, diverse types of the dehydrogenative cross-
couplings via olefin intermediates can be designed and
developed.
[7] a) X.-F. Wu, H. Neumann, M. Beller, Angew. Chem. 2010, 122,
5412 – 5416; Angew. Chem. Int. Ed. 2010, 49, 5284 – 5288; b) X.-
F. Wu, H. Neumann, A. Spannenberg, T. Schulz, H. Jiao, M.
Beller, J. Am. Chem. Soc. 2010, 132, 14596 – 14602.
[8] For selected books and reviews, see: a) “C-H Activation”: Topics
in Current Chemistry, Vol. 292 (Eds.: J.-Q. Yu, Z.-J. Shi),
Springer, Berlin, 2010; b) F. Kakiuchi, N. Chatani, Adv. Synth.
Catal. 2003, 345, 1077 – 1101; c) T. Satoh, M. Miura, Chem. Lett.
2007, 36, 200 – 205; d) 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; e) C.-J. Li, Acc. Chem. Res. 2009, 42, 335 –
344; f) O. Daugulis, H.-D. Do, D. Shabashov, Acc. Chem. Res.
2009, 42, 1074 – 1086; g) L. Ackermann, R. Vicente, A. R. Kapdi,
Angew. Chem. 2009, 121, 9976 – 10011; Angew. Chem. Int. Ed.
2009, 48, 9792 – 9826; h) T. W. Lyons, M. S. Sanford, Chem. Rev.
2010, 110, 1147 – 1169; i) C. S. Yeung, V. M. Dong, Chem. Rev.
2011, 111, 1215 – 1292; j) X. Bugaut, F. Glorius, Angew. Chem.
2011, 123, 7618 – 7620; Angew. Chem. Int. Ed. 2011, 50, 7479 –
7481; k) C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 2011, 111,
˝
1780 – 1824; l) J. Wencel-Delord, T. Droge, F. Liu, F. Glorius,
Chem. Soc. Rev. 2011, 40, 4740 – 4761.
[9] a) M. Zhang, J. Zhou, J. Kan, M. Wang, W. Su, M. Hong, Chem.
Commun. 2010, 46, 5455 – 5457; b) J. Zhou, G. Wu, M. Zhang, X.
Jie, W. Su, Chem. Eur. J. 2012, 18, 8032 – 8036.
1302
www.angewandte.org
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Chemie
[10] For Pd-catalyzed dehydrosilylation of silyl enol ethers(Saegusa
oxidation), see: a) Y. Ito, T. Hirao, T. Saegusa, J. Org. Chem.
1978, 43, 1011 – 1013; b) R. C. Larock, T. R. Hightower, G. A.
Kraus, P. Hahn, D. Zheng, Tetrahedron Lett. 1995, 36, 2423 –
2426; c) J.-Q. Yu, H. C. Wu, E. J. Corey, Org. Lett. 2005, 7, 1415 –
1417.
[11] For the syntheses of a,b-unsaturated carbonyls through a halo-
genation–dehalogenation sequence, see: a) B. Miller, H.-S.
Wong, Tetrahedron 1972, 28, 2369 – 2376; b) A. E. Greene, J.-C.
Muller, G. Ourisson, Tetrahedron Lett. 1972, 13, 3375 – 3378;
c) P. L. Stotter, K. A. Hill, J. Org. Chem. 1973, 38, 2576 – 2578.
[12] For the methods using IBX, see the following leading references:
a) K. C. Nicolaou, Y. L. Zhong, P. S. Baran, J. Am. Chem. Soc.
2000, 122, 7596 – 7597; b) K. C. Nicolaou, T. Montagnon, P. S.
Baran, Angew. Chem. 2002, 114, 1035 – 1038; Angew. Chem. Int.
Ed. 2002, 41, 993 – 996; c) M. Uyanik, M. Akakura, K. Ishihara,
J. Am. Chem. Soc. 2009, 131, 251 – 262.
Angew. Chem. Int. Ed. 2009, 48, 3644 – 3647; h) S. Yanagisawa, T.
Sudo, R. Noyori, K. Itami, J. Am. Chem. Soc. 2006, 128, 11748 –
11749; i) H.-Q. Do, R. M. Kashif Khan, O. Daugulis, J. Am.
Chem. Soc. 2008, 130, 15185 – 15192; j) S. Kirchberg, S. Tani, K.
Ueda, J. Yamaguchi, A. Studer, K. Itami, Angew. Chem. 2011,
123, 2435 – 2439; Angew. Chem. Int. Ed. 2011, 50, 2387 – 2391;
k) P. Hu, M. Zhang, X. Jie, W. Su, Angew. Chem. 2012, 124, 231 –
235; Angew. Chem. Int. Ed. 2012, 51, 227 – 231; l) O. Renꢁ, D.
Lapointe, K. Fagnou, Org. Lett. 2009, 11, 4560 – 4563; m) N.
Kuhl, M. N. Hopkinson, F. Glorius, Angew. Chem. 2012, 124,
8354 – 8358; Angew. Chem. Int. Ed. 2012, 51, 8230 – 8234.
[18] a) F. Zhang, M. F. Greaney, Angew. Chem. 2010, 122, 2828 –
2831; Angew. Chem. Int. Ed. 2010, 49, 2768 – 2771; b) E. M.
Beck, R. Hatley, M. J. Gaunt, Angew. Chem. 2008, 120, 3046 –
3049; Angew. Chem. Int. Ed. 2008, 47, 3004 – 3007; c) E. M.
Beck, N. P. Grimster, R. Hatley, M. J. Gaunt, J. Am. Chem. Soc.
2006, 128, 2528 – 2529; d) A. Garcꢂa-Rubia, R. G. Arrayꢃs, J. C.
Carretero, Angew. Chem. 2009, 121, 6633 – 6637; Angew. Chem.
Int. Ed. 2009, 48, 6511 – 6515; e) Z. Wang, K. Li, D. Zhao, J. Lan,
J. You, Angew. Chem. 2011, 123, 5477 – 5481; Angew. Chem. Int.
Ed. 2011, 50, 5365 – 5369; f) J. Ryu, S. H. Cho, S. Chang, Angew.
Chem. 2012, 124, 3737 – 3741; Angew. Chem. Int. Ed. 2012, 51,
3677 – 3681; g) S. H. Kim, J. H. Yoon, S. Chang, Org. Lett. 2011,
13, 1474 – 1477; h) S. J. Hwang, H. J. Kim, S. Chang, Org. Lett.
2009, 11, 4588 – 4591; i) S. J. Hwang, S. H. Cho, S. Chang, J. Am.
Chem. Soc. 2008, 130, 16158 – 16159; j) P. Gandeepan, C. H.
Cheng, J. Am. Chem. Soc. 2012, 134, 5738 – 5741; k) S. Yang, C.
Sun, B. Li, Y. Li, Z. Shi, Angew. Chem. 2008, 120, 1495 – 1498;
Angew. Chem. Int. Ed. 2008, 47, 1473 – 1476; l) T.-J. Gong, B.
Xiao, Z.-J. Liu, J. Wan, J. Xu, D.-F. Luo, Y. Fu, L. Liu, Org. Lett.
2011, 13, 3235 – 3237; m) S. Ding, N. Jiao, J. Am. Chem. Soc.
2011, 133, 12374 – 12377.
[13] For the review on the method using DDQ, see: D. Walker, J. D.
Hiebert, Chem. Rev. 1967, 67, 153 – 195.
[14] a) J. Muzart, Eur. J. Org. Chem. 2010, 3779 – 3790; b) T. Diao,
S. S. Stahl, J. Am. Chem. Soc. 2011, 133, 14566 – 14569; c) W.
Gao, Z. He, Y. Qian, J. Zhao, Y. Huang, Chem. Sci. 2012, 3, 883 –
886; d) T. Diao, T. J. Wadzinski, S. S. Stahl, Chem. Sci. 2012, 3,
887 – 891.
[15] For the reactions that involve dehydrogenation to olefins
followed by a coupling process, see: a) Y. Terao, Y. Kametani,
H. Wakui, T. Satoh, M. Miura, M. Nomura, Tetrahedron 2001, 57,
5967 – 5974; b) S. Ueno, R. Shimizu, R. Kuwano, Angew. Chem.
2009, 121, 4613 – 4615; Angew. Chem. Int. Ed. 2009, 48, 4543 –
4545; c) E. M. Stang, M. C. White, J. Am. Chem. Soc. 2011, 133,
14892 – 14895; d) M. V. Leskinen, K.-T. Yip, A. Valkonen, P. M.
Pihko, J. Am. Chem. Soc. 2012, 134, 5750 – 5753; e) Y. Moon, D.
Kwon, S. Hong, Angew. Chem. 2012, 124, 11495 – 11498; Angew.
Chem. Int. Ed. 2012, 51, 11333 – 11336.
[16] a) K. Ueda, S. Yanagisawa, J. Yamaguchi, K. Itami, Angew.
Chem. 2010, 122, 9130 – 9133; Angew. Chem. Int. Ed. 2010, 49,
8946 – 8949; b) M. Steinmetz, K. Ueda, S. Grimme, J. Yamagu-
chi, S. Kirchberg, K. Itami, A. Studer, Chem. Asian J. 2012, 7,
1256 – 1260; c) Y. Huang, F. Song, Z. Wang, P. Xi, N. Wu, Z.
Wang, J. Lan, J. You, Chem. Commun. 2012, 48, 2864 – 2866.
[17] a) K. Masui, H. Ikegami, A. Mori, J. Am. Chem. Soc. 2004, 126,
5074 – 5075; b) P. Xi, F. Yang, S. Qin, D. Zhao, J. Lan, G. Gao, C.
Hu, J. You, J. Am. Chem. Soc. 2010, 132, 1822 – 1824; c) C.-Y. He,
S. Fan, X. Zhang, J. Am. Chem. Soc. 2010, 132, 12850 – 12852;
d) S. Pivsa-Art, T. Satph, Y. Kawamura, M. Miura, M. Nomura,
Bull. Chem. Soc. Jpn. 1998, 71, 467 – 473; e) J. Fournier Dit Ch-
abert, L. Joucla, E. David, M. Lemaire, Tetrahedron 2004, 60,
3221 – 3230; f) S. Yanagisawa, K. Ueda, H. Sekizawa, K. Itami, J.
Am. Chem. Soc. 2009, 131, 14622 – 14623; g) B. Join, T.
Yamamoto, K. Itami, Angew. Chem. 2009, 121, 3698 – 3701;
[19] See the Supporting Information for details.
[20] a) S. Kirchberg, T. Vogler, A. Studer, Synlett 2008, 2841 – 2845;
b) S. Kirchberg, R. Frçhlich, A. Studer, Angew. Chem. 2009, 121,
4299 – 4302; Angew. Chem. Int. Ed. 2009, 48, 4235 – 4238; c) E. J.
Yoo, M. Wasa, J.-Q. Yu, J. Am. Chem. Soc. 2010, 132, 17378 –
17380.
[21] For the first example of a palladium(0)-catalyzed directed b-
arylation, see: M. Wasa, K. M. Engle, J.-Q. Yu, J. Am. Chem. Soc.
2009, 131, 9886 – 9887. For a recent review, see: R. Jazzar, J.
Hitce, A. Renaudat, J. Sofack-Kreutzer, O. Baudoin, Chem. Eur.
J. 2010, 16, 2654 – 2672.
[22] a) A. Renaudat, L. Jean-Gꢁrard, R. Jazzar, C. E. Kefalidis, E.
Clot, O. Baudoin, Angew. Chem. 2010, 122, 7419 – 7423; Angew.
Chem. Int. Ed. 2010, 49, 7261 – 7265; b) P. Larini, C. E. Kefalidis,
R. Jazzar, A. Renaudat, E. Clot, O. Baudoin, Chem. Eur. J. 2012,
18, 1932 – 1944; c) S. Aspin, A.-S. Goutierre, P. Larini, P. Jazzar,
O. Baudoin, Angew. Chem. 2012, 124, 10966 – 10969; Angew.
Chem. Int. Ed. 2012, 51, 10808 – 10811.
Angew. Chem. Int. Ed. 2013, 52, 1299 –1303
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