DOI: 10.1002/chem.201502101
Communication
&
Synthetic Methods |Hot Paper|
Palladium-Catalyzed Zinc-Amide-Mediated CÀH Arylation of
Fluoroarenes and Heteroarenes with Aryl Sulfides
Shinya Otsuka,[a] Hideki Yorimitsu,*[a, b] and Atsuhiro Osuka[a]
The transition-metal-catalyzed direct CÀH arylation of arenes
Abstract: CÀH arylation of polyfluoroarenes and heteroar-
with aryl halides has emerged as a promising alternative to
enes with aryl sulfides proceeds smoothly with the aid of
conventional cross-coupling reactions.[9] However, due to the
a palladium–N-heterocyclic carbene catalyst. A bulky zinc
aforementioned difficulties in transforming aryl sulfides catalyt-
amide, TMPZnCl·LiCl, plays a key role as an effective base
ically, only very recently Wang reported the first elegant exam-
to generate the corresponding arylzinc species in situ.
ple of a direct CÀH arylation with aryl sulfides in which a palla-
This arylation protocol is practically much easier to per-
dium–diphosphine catalyst and sodium tert-butoxide were em-
form than our previous method, which necessitates prepa-
ployed.[10] Nevertheless, the arylation lacks generality: electron-
ration of the arylzinc reagents in advance from the corre-
neutral and -rich aryl sulfides reacted moderately, even at
sponding aryl halides. Aryl sulfides that are prepared
1408C, and only oxazole derivatives smoothly underwent the
through sulfur-specific reactions, such as SNAr sulfanyla-
arylation. To expand the utility of aryl sulfides, we herein
tion and extended Pummerer reactions, undergo this
report efficient and general conditions for the CÀH arylation of
direct arylation, offering interesting transformations that
polyfluoroarenes[11,12] and heteroarenes[13] with aryl sulfides.
are otherwise difficult to achieve with conventional halo-
The reaction of methyl p-tolyl sulfide (1a) with pentafluoro-
gen-based organic synthesis.
benzene (2a) was chosen as a model reaction. We screened
palladium catalysts and bases (see the Supporting Information
for optimization studies) to find that Pd–PEPPSI-SIPr ([1,3-
Organosulfur compounds have played unique roles in organic
chemistry owing to their intriguing reactivities, biological activ-
ities, or physical properties.[1] Among them, aryl sulfides
occupy an important position, and, therefore, new methods
for the synthesis of aryl sulfides have been actively devel-
oped.[2] In contrast, the development of new reactions of aryl
sulfides has only been reported only scarcely. Transition-metal-
catalyzed cross-coupling reactions of aryl sulfides[3] are difficult
to achieve because sulfur species can permanently poison the
catalyst and C(sp2)ÀS bonds are rather strong and difficult to
cleave. To overcome these difficulties, reactive Grignard re-
agents were employed as nucleophiles[4] or aryl sulfides were
used that have special structures that facilitate efficient conver-
sion.[5–7] We are interested in catalytic transformations of orga-
nosulfur compounds[4e–g,8] and recently developed general
cross-coupling reactions of aryl sulfides with arylzinc reagents
by using a palladium–NHC complex as catalyst.[8b] Although
our Negishi-type cross-coupling shows a wide scope and pro-
ceeds under mild conditions, the reactions necessitate prepara-
tion of the arylzinc reagents from the corresponding haloar-
enes in advance.
bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene](3-chloropyridi-
ne)palladium(II) dichloride[14] and 2,2,6,6-tetramethylpiperidyl-
zinc chloride·lithium chloride complex[15,16] (TMPZnCl·LiCl) are
the best catalyst/base combination to afford 3a in 91% yield
(Scheme 1). As reported by us previously,[8] Pd–PEPPSI-SIPr,
a palladium–NHC complex, is again the key for success.
TMPZnCl·LiCl is known as an exquisite base for deprotonative
zincation of electron-deficient arenes or heteroarenes, tolerat-
ing various functional groups.[15] We were delighted to find
that TMPZnCl·LiCl generates a pentafluorophenylzinc species
[a] S. Otsuka, Prof. Dr. H. Yorimitsu, Prof. Dr. A. Osuka
Department of Chemistry, Graduate School of Science
Kyoto University, Sakyo-ku, Kyoto 606-8502 (Japan)
[b] Prof. Dr. H. Yorimitsu
ACT-C, JST, Sakyo-ku, Kyoto 606-8502 (Japan)
Supporting information for this article is available on the WWW under
Scheme 1. Scope of polyfluoroarenes.
Chem. Eur. J. 2015, 21, 14703 – 14707
14703
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