Palladium-Catalyzed Cross-Coupling of Unactivated Aryl Sulfides with Arylzinc Reagents under Mild Conditions

Article abstract of DOI:10.1002/chem.201404380

Cross-coupling of general aryl alkyl sulfides with arylzinc reagents proceeds smoothly, even at room temperature or below, with a palladium-N-heterocyclic carbene (NHC) catalyst. When combined with reactions that are unique to organosulfurs, that is, the S_NAr sulfanylation or Pummerer reaction, the cross-coupling offers interesting transformations that are otherwise difficult to achieve. An alkylsulfanyl group is preferentially converted whilst leaving the tosyloxy and chloro intact, which expands the variety of orthogonal cross-coupling.

Full text of DOI:10.1002/chem.201404380

DOI: 10.1002/chem.201404380
Communication
&
Organic Synthesis
Palladium-Catalyzed Cross-Coupling of Unactivated Aryl Sulfides
with Arylzinc Reagents under Mild Conditions
Shinya Otsuka,[a] Daishi Fujino,[a] Kei Murakami,[a, b] Hideki Yorimitsu,*[a, c] and
Atsuhiro Osuka[a]
would be slow because of the high affinity between a cationic
Abstract: Cross-coupling of general aryl alkyl sulfides with
transition metal and a thiolate anion.
arylzinc reagents proceeds smoothly, even at room tem-
Since Takei’s and Wenkert’s pioneering work,[8] Grignard re-
perature or below, with a palladium–N-heterocyclic car-
agents are the choice of nucleophilic partners in the cross-cou-
bene (NHC) catalyst. When combined with reactions that
pling of aryl sulfides,[9] probably due to their high reactivity for
are unique to organosulfurs, that is, the SNAr sulfanylation
efficient transmetalation. Because Grignard reagents have low
or Pummerer reaction, the cross-coupling offers interest-
functional-group compatibility, organozinc, -stannane, and
ing transformations that are otherwise difficult to achieve.
-boron reagents are preferable. However, cross-coupling of aryl
An alkylsulfanyl group is preferentially converted whilst
sulfides with these mild organometallic species has severe limi-
leaving the tosyloxy and chloro intact, which expands the
tations: 1) The leaving group must be a neutral tetrahydrothio-
variety of orthogonal cross-coupling.
phene (aryltetramethylenesulfonium salts as substrates) or che-
lating thioglycolate derivatives that capture a zinc ion to facili-
tate transmetalation.[10] 2) Otherwise, aryl groups must be
either activated heteroaryls, such as thioester mimics[11,12] (2-
Cross-coupling reactions are among the most important
carbon–carbon bond formations in organic synthesis.[1] Aryl
bromides and iodides have played a central role as electrophil-
ic partners for cross-coupling reactions. Aryl sulfonates and
phosphates are also good substrates thanks to the high leav-
ing-group ability of their oxygen functionalities. Recent dra-
matic advances in transition-metal catalysts have been expand-
ing the scope of electrophiles. With very electron-rich transi-
tion-metal complexes that undergo smooth oxidative addition,
one can use less reactive aryl chlorides[2] and fluorides[2b,3] and
usually inert phenol derivatives, such as carbonates, esters, and
even ethers,[4,5] as electrophilic substrates.
pyridyl, 2-pyrimidyl, 2-pyrazinonyl, etc.) and 2-benzofuryl,[9i,13]
or aryls bearing ortho-directing groups (carbonyl or nitro).[14] To
the best of our knowledge, there are no reports on cross-cou-
pling reactions of unactivated aryl alkyl sulfides with organo-
zinc reagents despite their seeming simplicity. Here we report
the first examples of such cross-coupling reactions.
We chose the reaction of methyl p-tolyl sulfide with p-ethox-
ycarbonylphenylzinc iodide·lithium chloride complex[15] as
a model reaction. Our success heavily depends on the choice
of a palladium catalyst. We screened a variety of palladium
salts and ligands to find that commercially available [Pd-
PEPPSI-SIPr][16] is the best catalyst (see the Supporting Informa-
tion for the catalyst structure and optimization). Surprisingly,
the reaction proceeded at room temperature (208C). Palladium
complexes bearing phosphine ligand(s) were found to be
almost inactive. Other palladium–NHC complexes exhibited
moderate reactivities. The high activity of Pd–NHC complexes
was also the case for the cross-coupling reactions of 2-methyl-
sulfanylbenzofuran.[13b] A Ni–NHC complex [NiCl2(IPr)(PPh3)] is
not effective. Acetonitrile has proved to be the best solvent
and ethereal solvents, such as THF, 1,2-dimethoxyethane, and
diglyme also worked as well. Less polar toluene and diethyl
ether were inferior.
Less attention has been paid to the use of organosulfur
compounds in cross-coupling reactions.[6] Among them, aryl
sulfides bearing a divalent sulfur atom constitute the most
challenging substrates. Their C(sp2)ÀS bonds are rather
strong[7] to retard oxidative addition. Furthermore, starting aryl
sulfides can poison transition-metal catalysts and the resulting
thiolate anions can do much more. Naturally, transmetalation
[a] S. Otsuka, Dr. D. Fujino, Dr. K. Murakami, Prof. Dr. H. Yorimitsu,
Prof. Dr. A. Osuka
Department of Chemistry, Graduate School of Science
Kyoto University
Arylzinc reagents can contain electron-withdrawing ester,
cyano, trifluoromethyl, or electron-donating methoxy groups
(Table 1, entries 1–4).[17] Heteroaromatic 2-thienylzinc reagents
as well as sterically demanding 1-naphthylzinc reagents also
participated smoothly (entries 5 and 6) although the latter re-
quired a higher temperature. Alkenylzinc bromide·lithium chlo-
ride complex prepared from a-bromostyrene reacted to yield
alkenylated product 1g (entry 7).
Sakyo-ku, Kyoto 606-8502 (Japan)
E-mail: yori@kuchem.kyoto-u.ac.jp
[b] Dr. K. Murakami
The Hakubi Center for Advanced Research
Sakyo-ku, Kyoto 606-8502 (Japan)
[c] Prof. Dr. H. Yorimitsu
ACT-C, JST
Sakyo-ku, Kyoto 606-8502 (Japan)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201404380.
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compatible. A methyl group at the ortho position did not
retard the reaction (entry 13). Not only 2-alkylsulfanylpyridine
but also 3-alkylsulfanylpyridine, which is not a thioester mimic,
reacted smoothly (entries 15 and 16). As a protecting group of
NH2, succinimido protection is suitable (entry 17). Other protec-
tions that leave an acidic NH, such as acetoamido, inhibited
the reaction.
Table 1. Cross-coupling of aryl sulfides with arylzinc reagents.[a]
Entry
R1
R2
t [h]
Product
Yield [%]
1
2
3
4
5
6
7
8
H
H
H
H
H
4-Me
H
4-OMe
4-OBoc
4-CHO
4-COCH3
4-F
4-CO2Et
4-CN
4-CF3
4
16
24
4
1a
1b
1c
1d
1e
1 f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
99
83
85
91
The leaving sulfanyl moiety is not limited to a methylsulfanyl
group. Odorless dodecylsulfanyl[20] and phenylsulfanyl are
good leaving groups (99% yield of 1a in both cases). However,
the reaction of tert-butyl phenyl sulfide was sluggish to afford
1a in only 21% yield under the otherwise same conditions.
Alkanethiols are nucleophilic enough to react with electron-
deficient arenes by an SNAr mechanism. The SNAr reactions of
methyl 4-nitrobenzoate and 4-nitrobenzonitrile with dodecane-
thiol in the presence of cesium carbonate[21] resulted in cleanly
replacing the NO2 groups with dodecylsulfanyl (Scheme 2). The
4-OMe
(2-thienyl)
(1-naphthyl)
(CPh=CH2)[c]
4-CO2Et
4-CO2Et
H
4-CO2Et
4-CO2Et
4-CO2Et
4-CO2Et
4-CO2Et
4-CO2Et
4-CO2Et
5
91
4.5
24
22
16
4
4
2
4
5
95[b]
62
77[d]
73
9
10
11
12
13
14
15
16
17
96
89[d]
88
2-Me
87
93
91
91
(2-naphthyl)
(2-pyridyl)
(3-pyridyl)[e]
4-succinimido
16
4
5
75
[a] Conditions: aryl methyl sulfide (0.50 mmol), ArZnI·LiCl (1.0m in THF,
2 equiv), [Pd-PEPPSI-SIPr] (5 mol%), acetonitrile (1.5 mL). [b] 608C. [c] With
CH2=CPhZnBr·LiCl. [d] In diglyme. [e] 3-Dodecylsulfanylpyridine was used.
Interestingly, the presence of lithium chloride is crucial for
the success of the arylation (Scheme 1).[18] Gosmini’s arylzinc re-
agent,[19] prepared from ethyl 4-bromobenzoate and zinc
Scheme 2. SNAr displacement of NO2 with C12H25S followed by cross-cou-
pling.
sulfides thus generated underwent smooth cross-coupling
with an arylzinc reagent. These two-step transformations repre-
sent displacement of a nitro group with an aryl group taking
advantage of the high nucleophilicity of a thiolate anion,
which halide and alkoxide anions are unable to achieve.
Another unique transformation of organosulfur compounds
is the Pummerer reaction.[22] According to Procter’s protocol,[23]
methyl phenyl sulfoxide was converted to 2-propargylphenyl
sulfide 2 (Scheme 3). After this ortho-functionalization, which
the corresponding aryl halides and pseudohalides cannot
engage in, the following cross-coupling reaction afforded
products 3a–c. The overall transformations represent vicinal
propargylation/arylative substitution to synthesize o-propargyl-
Scheme 1. Reactions with arylzinc species prepared through other methods.
powder in the presence of cobalt(II) bromide, did not undergo
the coupling at all in the absence of lithium chloride. Dramati-
cally, an addition of lithium chloride accelerated the arylation
with Gosmini’s reagent to afford 1a in 92% yield. Deprotona-
tion of benzofuran and N-methylindole by butyllithium fol-
lowed by transmetalation with zinc chloride provided the cor-
responding benzoheteroarylzinc chloride·lithium chloride,
which underwent smooth cross-coupling with thioanisole.
The scope of aryl sulfides is broad. Although the electron-
donating methoxy and tert-butoxycarbonyloxy group slowed
down the arylation, the reactions completed in 24 h to afford
the corresponding products in high yields (Table 1, entries 8
and 9). Electron-withdrawing groups (EWG) facilitated the ary-
lation (entries 10–12). Notably, formyl and acetyl groups are
Scheme 3. Pummerer propargylation/arylation sequence.
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1.0 mmol, 1.0m in THF) at 208C under nitrogen. After 3 min, the
solution turned black. Acetonitrile (1.5 mL) and methyl phenyl sul-
fide (62.1 mg, 0.50 mmol) were added and the resulting mixture
was stirred at 208C for 4 h. Saturated NH4Cl aq. (10 mL) was added
and organic compounds were extracted with a mixture of n-
hexane/EtOAc (3:1, 10 mLꢁ3). The combined organic layer was
passed through pads of anhydrous sodium sulfate and activated
alumina. Concentration followed by purification on silica gel (n-
hexane/EtOAc=30/1) provided 1a (112.0 mg, 0.49 mmol, 99%).
biaryls, potent precursors of phenanthrenes under Lewis acid
catalysis,[24] from very simple building blocks.
The emergence of this new cross-coupling option raised
questions about orthogonality with other cross-coupling foot-
holds.[25] According to the procedure of Buchwald,[26] Suzuki–
Miyaura arylation of aryl tosylate 4 selectively substituted the
tosyloxy group to yield methylsulfanylbiphenyl 5. In contrast,
arylation of 4 under our conditions afforded 6 by replacing the
methylsulfanyl group and leaving the tosyloxy moiety intact
(Scheme 4). Similarly, 4-chlorothioanisole (7) underwent aryla-
tion under our conditions to yield 9 without touching the
chloro group at 08C[27,28] whereas selective arylation of 7 at the
chlorinated position was reported to form 8.[29] Our new proto-
col thus expands the variety of orthogonal functionalizations
of arenes.
Acknowledgements
This work was supported by Grants-in-Aid from MEXT (Nos.:
24106721 “Reaction Integration” and 25107002 “Science of
Atomic Layers”) and from JSPS (Nos.: 24685007 (Young Scien-
tists (A)) and 26620081 (Exploratory Research)). D.F. and K.M.
acknowledge JSPS for financial support.
Keywords: cross-coupling
organosulfur compounds · organozinc compounds · palladium
·
CÀS bond activation
·
[1] a) Cross-Coupling Reactions: A Practical Guide (Ed.: N. Miyaura), Springer,
Heidelberg, 2010; b) Metal-Catalyzed Cross-Coupling Reactions (Eds.: A.
de Meijere, F. Diederich), Wiley-VCH, Weinheim, 2004; c) Applied Cross-
Coupling Reactions, (Ed.: Y. Nishihara), Springer, Heidelberg, 2013; d) N.
Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457; e) E. Negishi, Bull. Chem.
Soc. Jpn. 2007, 80, 233; f) N. Miyaura, Bull. Chem. Soc. Jpn. 2008, 81,
1535; g) A. Suzuki, Y. Yamamoto, Chem. Lett. 2011, 40, 894; h) A. Suzuki,
Angew. Chem. 2011, 123, 6854; Angew. Chem. Int. Ed. 2011, 50, 6722;
i) E. Negishi, Angew. Chem. 2011, 123, 6870; Angew. Chem. Int. Ed. 2011,
50, 6738; j) C. C. C. J. Seechurn, M. O. Kitching, T. J. Colacot, V. Snieckus,
Angew. Chem. 2012, 124, 5150; Angew. Chem. Int. Ed. 2012, 51, 5062;
k) H. Li, C. C. C. J. Seechurn, T. J. Colacot, ACS Catal. 2012, 2, 1147.
[2] a) W. A. Herrmann, Angew. Chem. 2002, 114, 1342; Angew. Chem. Int. Ed.
2002, 41, 1290; b) A. F. Littke, G. C. Fu, Angew. Chem. 2002, 114, 4350;
Angew. Chem. Int. Ed. 2002, 41, 4176; c) R. B. Bedford, C. S. J. Cazin, D.
Holder, Coord. Chem. Rev. 2004, 248, 2283.
Scheme 4. Controllable cleavage.
[3] a) H. Amii, K. Uneyama, Chem. Rev. 2009, 109, 2119; b) N. Yoshikai, H.
Matsuda, E. Nakamura, J. Am. Chem. Soc. 2009, 131, 9590; c) M. Tobisu,
T. Xu, T. Shimasaki, N. Chatani, J. Am. Chem. Soc. 2011, 133, 19505.
[4] Reviews: a) D.-G. Yu, B.-J. Li, Z.-J. Shi, Acc. Chem. Res. 2010, 43, 1486;
b) B. M. Rosen, K. W. Quasdorf, D. A. Wilson, N. Zhang, A.-M. Resmerita,
N. K. Garg, V. Percec, Chem. Rev. 2011, 111, 1346; c) M. Tobisu, N. Chata-
ni, Top. Organomet. Chem. 2013, 44, 35; d) F.-S. Han, Chem. Soc. Rev.
2013, 42, 5270; e) W.-N. Li, Z.-L. Wang, RSC Adv. 2013, 3, 25565.
[5] Selected very recent examples: a) J. Cornella, R. Martin, Org. Lett. 2013,
15, 6298; b) F. Zhao, Y.-F. Zhang, J. Wen, D.-G. Yu, J.-B. Wei, Z. Xi, Z.-J.
Shi, Org. Lett. 2013, 15, 3230; c) X.-J. Li, J.-L. Zhang, Y. Geng, Z. Jin, J.
Org. Chem. 2013, 78, 5078; d) A. L. Silberstein, S. D. Ramgren, N. K. Garg,
Org. Lett. 2012, 14, 3796; e) G.-J. Chen, F.-S. Han, Eur. J. Org. Chem.
2012, 3575; f) C. Wang, T. Ozaki, R. Takita, M. Uchiyama, Chem. Eur. J.
2012, 18, 3482; g) R. Kuwano, R. Shimizu, Chem. Lett. 2011, 40, 913; h) F.
Zhao, D.-G. Yu, R.-Y. Zhu, Z. Xi, Z.-J. Shi, Chem. Lett. 2011, 40, 1001;
i) K. W. Quasdorf, A. Antoft-Finch, P. Liu, A. L. Silberstein, A. Komaromi, T.
Blackburn, S. S. D. Ramgren, K. N. Houk, V. Snieckus, N. K. Garg, J. Am.
Chem. Soc. 2011, 133, 6352; j) L.-G. Xie, Z.-X. Wang, Chem. Eur. J. 2011,
17, 4972; k) M. Tobisu, T. Shimasaki, N. Chatani, Angew. Chem. 2008, 120,
4944; Angew. Chem. Int. Ed. 2008, 47, 4866.
In summary, we have developed general and efficient proto-
col for accomplishing the cross-coupling of unactivated aryl
sulfides with arylzinc reagents under [Pd–PEPPSI–SIPr] catalysis.
Electronically and sterically diverse aryl sulfides undergo cross-
coupling, even at room temperature. Not only Knochel’s ArZ-
nI·LiCl but also other arylzinc species are employable with the
aid of lithium chloride. The cross-coupling can follow SNAr dis-
placement of a nitro group with an alkylsulfanyl or Pummerer
ortho-propargylation, which eventually offers otherwise diffi-
cult transformations by taking advantage of the unique reac-
tivity of organosulfurs. Our system exhibits intriguing orthogo-
nal reactivity, leaving the tosyloxy and chloro intact. Our cur-
rent studies are directed to disseminate CÀS-based organic
synthesis that complements CÀX-based synthesis.[30]
[6] Reviews: a) H. Sugimura, H. Okamura, M. Miura, M. Yoshida, H. Takei,
Nippon Kagaku Kaishi 1985, 416; b) F. Naso, Pure Appl. Chem. 1988, 60,
79; c) T.-Y. Luh, Z.-J. Ni, Synthesis 1990, 89; d) T.-Y. Luh, Acc. Chem. Res.
1991, 24, 257; e) V. Fiandanese, Pure Appl. Chem. 1990, 62, 1987; f) S. R.
Dubbaka, P. Vogel, Angew. Chem. 2005, 117, 7848; Angew. Chem. Int. Ed.
2005, 44, 7674; g) H. Prokopcovꢂ, C. O. Kappe, Angew. Chem. 2008, 120,
3732; Angew. Chem. Int. Ed. 2008, 47, 3674; h) L. Wang, W. He, Z. Yu,
Chem. Soc. Rev. 2013, 42, 599; i) S. G. Modha, V. P. Mehta, E. V. Van der
Experimental Section
The reaction of thioanisole with 4-ethoxycarbonyphenylzinc re-
agent is representative (Table 1, entry 1). To [Pd-PEPPSI-SIPr]
(17.0 mg, 0.025 mmol) in a 20 mL two-neck flask was added 4-
ethoxycarbonylphenylzinc iodide·lithium chloride complex (1.0 mL,
Chem. Eur. J. 2014, 20, 1 – 5
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&
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Communication
Eycken, Chem. Soc. Rev. 2013, 42, 5042; j) F. Pan, Z.-J. Shi, ACS Catal.
2014, 4, 280.
A. Osuka, Chem. Eur. J. 2012, 18, 12690; c) J.-X. Liu, Y.-J. Liu, W.-T. Du, Y.
Dong, J. Liu, M. Wang, J. Org. Chem. 2013, 78, 7293.
[7] Bond dissociation energies of PhÀSMe, PhÀCl, and PhÀBr were deter-
mined to be 357.3Æ6.3, 399.6Æ6.3, and 336.4Æ6.3 kJmolÀ1, respec-
tively: Y.-R. Luo, Comprehensive Handbook of Chemical Bond Energies,
CRC Press, Boca Raton, 2007.
[8] a) H. Okamura, M. Miura, H. Takei, Tetrahedron Lett. 1979, 20, 43; b) H.
Takei, M. Miura, H. Sugimura, H. Okamura, Chem. Lett. 1979, 1447; c) E.
Wenkert, T. W. Ferreira, E. L. Michelotti, J. Chem. Soc. Chem. Commun.
1979, 637.
[9] a) K. Itami, D. Yamazaki, J. Yoshida, J. Am. Chem. Soc. 2004, 126, 15396;
b) Y.-H. Cho, A. Kina, T. Shimada, T. Hayashi, J. Org. Chem. 2004, 69,
3811; c) J. Torres-Nieto, A. Arꢃvalo, P. Garcꢄa-Gutiꢃrrez, A. Acosta-Ramꢄr-
ez, J. J. Carcꢄa, Organometallics 2004, 23, 4534; d) S. Kanemura, A.
Kondoh, H. Yorimitsu, K. Oshima, Synthesis 2008, 2659; e) V. P. Mehta,
S. G. Modha, E. Van der Eycken, J. Org. Chem. 2009, 74, 6870; f) J. Ma, L.
Peng, X. Zhang, Z. Zhang, M. Campbell, J. Wang, Chem. Asian J. 2010, 5,
2214; g) L. Hintermann, M. Schmitz, Y. Chen, Adv. Synth. Catal. 2010,
352, 2411; h) A. J. Eberhart, J. E. Imbriglio, D. J. Procter, Org. Lett. 2011,
13, 5882; i) K. Murakami, H. Yorimitsu, A. Osuka, Angew. Chem. 2014,
126, 7640; Angew. Chem. Int. Ed. 2014, 53, 7510.
[14] a) J. F. Hooper, R. D. Young, I. Pernik, A. S. Weller, M. C. Willis, Chem. Sci.
2013, 4, 1568; b) F. Pan, H. Wang, P.-X. Shen, J. Zhao, Z.-J. Shi, Chem. Sci.
2013, 4, 1573; c) G. S. Creech, O, Kwon, Chem. Sci. 2013, 4, 2670.
[15] A. Krasovskiy, V. Malakhov, A. Gavryushin, P. Knochel, Angew. Chem.
2006, 118, 6186; Angew. Chem. Int. Ed. 2006, 45, 6040.
[16] PEPPSI is an abbreviation for pyridine-enhanced precatalyst preparation
stabilization and initiation. a) M. G. Organ, M. Abdel-Hadi, S. Avola, N.
Hadei, J. Nasielski, C. J. O’Brien, C. Valente, Chem. Eur. J. 2007, 13, 150;
b) E. A. B. Kantchev, C. J. O’Brien, M. G. Organ, Aldrichimica Acta 2006,
39, 97; c) C. Valente, M. Pompeo, M. Sayah, M. G. Organ, Org. Process
Res. Dev. 2014, 18, 180; d) M. G. Organ, G. A. Chass, D.-C. Fang, A. C.
Hopkinson, C. Valente, Synthesis 2008, 2776. For the Negishi reactions
with Pd-PEPPSI catalysts, see: e) M. G. Organ, S. Avola, I. Dubovyk, N.
Hadei, E. A. B. Kantchev, C. J. O’Brien, C. Valente, Chem. Eur. J. 2006, 12,
4749; f) C. Valente, M. E. Belowich, N. Hadei, M. G. Organ, Eur. J. Org.
Chem. 2010, 4343.
[17] We could reduce the amounts of the palladium catalyst and an arylzinc
reagent without significant decrease of yield. For instance, the reaction
of thioanisole with 4-ethoxycarbonylphenylzinc reagent (1.4 equiv) in
the presence of 3 mol% of [Pd-PEPPSI-SIPr] proceed to completion in
7 h to afford 1a in 87% yield.
[18] The success of Negishi coupling heavily depends on the nature of the
organozinc species (i.e., the presence or absence of LiCl). For details,
see: L. C. McCann, M. G. Organ, Angew. Chem. 2014, 126, 4475; Angew.
Chem. Int. Ed. 2014, 53, 4386, and references therein.
[19] a) H. Fillon, C. Gosmini, J. Pꢃrichon, J. Am. Chem. Soc. 2003, 125, 3867;
b) I. Kazmierski, C. Gosmini, J.-M. Paris, J. Pꢃrichon, Tetrahedron Lett.
2003, 44, 6417.
[20] a) M. Node, K. Kumar, K. Nishide, S. Ohsugi, T. Miyamoto, Tetrahedron
Lett. 2001, 42, 9207; b) K. Nishide, S. Ohsugi, T. Miyamoto, K. Kumar, M.
Node, Monatsh. Chem. 2004, 135, 189; c) K. Nishide, M. Node, J. Synth.
Org. Chem. Jpn. 2004, 62, 895.
[21] A. Kondoh, H. Yorimitsu, K. Oshima, Tetrahedron 2006, 62, 2357.
[22] Recent reviews: a) L. H. S. Smith, S. C. Coote, H. F. Sneddon, D. J. Procter,
Angew. Chem. 2010, 122, 5968; Angew. Chem. Int. Ed. 2010, 49, 5832;
b) S. Akai, Y. Kita, Top. Curr. Chem. 2007, 274, 35; c) K. S. Feldman, Tetra-
hedron 2006, 62, 5003; d) S. K. Bur, A. Padwa, Chem. Rev. 2004, 104,
2401; e) Sulfur-Mediated Rearrangements I (Ed.: E. Schaumann), Springer,
2007; f) H. Yorimitsu, J. Synth. Org. Chem. Jpn. 2013, 71, 341.
[23] A. J. Eberhart, D. J. Procter, Angew. Chem. 2013, 125, 4100; Angew.
Chem. Int. Ed. 2013, 52, 4008.
[10] a) J. Srogl, G. D. Allred, L. S. Liebeskind, J. Am. Chem. Soc. 1997, 119,
12376; b) J. Srogl, W. Liu, D. Marshall, L. S. Liebeskind, J. Am. Chem. Soc.
1999, 121, 9449; c) L. S. Liebeskind, J. Srogl, C. Savarin, C. Polanco, Pure
Appl. Chem. 2002, 74, 115.
[11] a) M. E. Angiolelli, A. L. Casalnuovo, T. P. Selby, Synlett 2000, 905; b) L. S.
Liebeskind, J. Srogl, Org. Lett. 2002, 4, 979; c) M. Egi, L. S. Liebeskind,
Org. Lett. 2003, 5, 801; d) C. Kusturin, L. S. Liebeskind, H. Rahman, K.
Sample, B. Schweitzer, J. Srogl, W. L. Neumann, Org. Lett. 2003, 5, 4349;
e) F.-A. Alphonse, F. Suzenet, A. Keromnes, B. Lebret, G. Guillaumet, Org.
Lett. 2003, 5, 803; f) S. Silva, B. Sylla, F. Suzenet, A. Tatibouꢅt, A. P.
Rauter, P. Rollin, Org. Lett. 2008, 10, 853; g) Q. Sun, F. Suzenet, G. Guil-
laumet, J. Org. Chem. 2010, 75, 3473; h) A. Lengar, C. O. Kappe, Org.
Lett. 2004, 6, 771; i) B. K. Singh, V. P. Mehta, V. S. Parmar, E. Van der Eyck-
en, Org. Biomol. Chem. 2007, 5, 2962; j) V. P. Mehta, A. Sharma, E. Van
der Eycken, Org. Lett. 2008, 10, 1147; k) V. P. Mehta, A. Sharma, K. Van
Hecke, L. Van Meervelt, E. Van der Eycken, J. Org. Chem. 2008, 73, 2382;
l) V. P. Mehta, A. Sharma, E. Van der Eycken, Adv. Synth. Catal. 2008, 350,
2174; m) S. G. Modha, J. C. Trivedi, V. P. Mehta, D. S. Ermolat’ev, E. V. Van
der Eycken, J. Org. Chem. 2011, 76, 846; n) Z.-J. Quan, W.-H. Hu, X.-D. Jia,
Z. Zhang, Y.-X. Da, X.-C. Wang, Adv. Synth. Catal. 2012, 354, 2939; o) Z.-J.
Quan, Y. Lv, F.-Q. Jing, X.-D. Jia, C.-D. Huo, X.-C. Wang, Adv. Synth. Catal.
2014, 356, 325; p) B. C. Shook, D. Chakravarty, P. F. Jackson, Tetrahedron
Lett. 2009, 50, 1013; q) K. Lee, C. M. Counceller, J. P. Stambuli, Org. Lett.
2009, 11, 1457; r) J.-M. Begouin, M. Rivard, C. Gosmini, Chem. Commun.
2010, 46, 5972; s) A. Metzger, L. Melzig, C. Despotopoulou, P. Knochel,
Org. Lett. 2009, 11, 4228; t) L. Melzig, A. Metzger, P. Knochel, J. Org.
Chem. 2010, 75, 2131; u) L. Melzig, A. Metzger, P. Knochel, Chem. Eur. J.
2011, 17, 2948; v) T. Higashino, M. S. Rodrꢄguez-Morgade, A. Osuka, T.
Torres, Chem. Eur. J. 2013, 19, 10353; w) S. Dahbi, P. Bisseret, Eur. J. Org.
Chem. 2012, 3759; x) A. A. Farahat, D. W. Boykin, Synthesis 2012, 120;
[24] a) Y. Kwon, H. Cho, S. Kim, Org. Lett. 2013, 15, 920; b) C. Shu, L. Li, C.-B.
Chen, H.-C. Shen, L.-W. Ye, Chem. Asian J. 2014, 9, 1525.
[25] a) A. F. Littke, C. Dai, G. C. Fu, J. Am. Chem. Soc. 2000, 122, 4020; b) M.
Tobisu, N. Chatani, Angew. Chem. 2009, 121, 3617; Angew. Chem. Int. Ed.
2009, 48, 3565.
[26] B. Bhayana, B. P. Fors, S. L. Buchwald, Org. Lett. 2009, 11, 3954.
[27] The same reaction at 208C was complicated due to undesired arylation
at the chlorinated position.
ˇ
ˇ
ˇ
´
´
y) P. Brehovꢂ, M. Cesnek, M. Dracꢄnsky, A. Holy, Z. Janeba, Tetrahedron
2011, 67, 7379; z) M. Koley, L. Wimmer, M. Schnꢆrch, M. D. Mihovilovic,
Eur. J. Org. Chem. 2011, 1972.
[28] 4-Bromothioanisole underwent arylation at the brominated carbon ex-
clusively.
[29] H. Xu, K. Ekoue-Kovi, C. Wolf, J. Org. Chem. 2008, 73, 7638.
[30] T. Sugahara, K. Murakami, H. Yorimitsu, A. Osuka, Angew. Chem. Int. Ed.
2014, 126, 9483; Angew. Chem. Int. Ed. 2014, 53, 9329.
[12] Thioesters are well known to undergo catalytic cross-coupling very
smoothly to afford the corresponding ketones, for example: a) H. To-
kuyama, S. Yokoshima, T. Yamashita, T. Fukuyama, Tetrahedron Lett.
1998, 39, 3189; b) T. Fukuyama, H. Tokuyama, Aldrichimica Acta 2004,
37, 87; c) L. S. Liebeskind, J. Srogl, J. Am. Chem. Soc. 2000, 122, 11260.
[13] a) T. Kobatake, D. Fujino, S. Yoshida, H. Yorimitsu, K. Oshima, J. Am.
Chem. Soc. 2010, 132, 11838; b) Y. Ookubo, A. Wakamiya, H. Yorimitsu,
Received: July 13, 2014
Published online on && &&, 0000
&
&
Chem. Eur. J. 2014, 20, 1 – 5
www.chemeurj.org
4
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Communication
COMMUNICATION
&
Organic Synthesis
S. Otsuka, D. Fujino, K. Murakami,
H. Yorimitsu,* A. Osuka
A palladium–carbene complex has
now made reluctant aryl sulfides reac-
tive in cross-coupling reactions with or-
ganozinc reagents. The cross-coupling is
broad in scope and proceeds even at
room temperature or below (see
scheme). When combined with sulfur-
specific reactions, the cross-coupling
offers useful transformations that are
otherwise difficult to achieve.
&& – &&
Palladium-Catalyzed Cross-Coupling of
Unactivated Aryl Sulfides with
Arylzinc Reagents under Mild
Conditions
Chem. Eur. J. 2014, 20, 1 – 5
www.chemeurj.org
5
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ