CL-190300
Received: April 10, 2019 | Accepted: April 26, 2019 | Web Released: May 31, 2019
Palladium-catalyzed One-step Synthesis of Symmetrical Diaryl Sulfones
from Aryl Halides and a Sulfur Dioxide Surrogate
Hiromichi Tanaka, Hideyuki Konishi, and Kei Manabe*
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
E-mail: manabe@u-shizuoka-ken.ac.jp
(a) Reported work
SO2 surrogate
A convenient method for the one-step synthesis of sym-
Ar
X
metrical diaryl sulfones from aryl halides has been developed. A
keystone of the method is the use of K2S2O5, which can be easily
and safely handled, as a sulfur dioxide surrogate. The palladium
catalyst bearing P(t-Bu)3 as a ligand enables formation of the
desired sulfones without significant formation of byproducts.
O
S
O O
S
Pd catalyst
Ar Li
Ar
Ar
Ar
O
O
(X = I, Br)
arylation
sulfinate formation
SO2 surrogate
Pd catalyst
reductant
Ar2I+Cl
Keywords: Sulfur dioxide
| Palladium catalyst | Sulfone
O
S
O O
S
Ar
I
Ar
Ar
Ar
Diaryl sulfones are an important class of compounds in
various fields, including pharmaceuticals, electronic devices,
and polymers.1 Traditionally, these sulfones are synthesized via
aromatic electrophilic substitution with arenesulfonyl halides or
the oxidation of diaryl sulfides.2 However, the former method
requires handling of unstable sulfonyl halides, and the latter
cannot be used for substrates with oxidation-sensitive functional
groups. In addition, the sulfonyl halides or sulfides must first be
prepared by methods in which the introduction of the sulfur
groups is often tedious. Arylation of arenesulfinates with aryl
halides is an alternative, emerging method that is useful for the
synthesis of various diaryl sulfones,3 although the preparation of
the starting arenesulfinates, in many cases, also requires the use
of sulfonyl halides or toxic sulfur dioxide (SO2) gas.4 Therefore,
there is still a need to develop a convenient method for the
synthesis of diaryl sulfones.
sulfinate formation
arylation
(b) This work
SO2 surrogate
Pd catalyst
reductant
O O
S
Ar
X
Ar
Ar
(X = I, Br)
one step
Scheme 1. (a) Reported work on two-step synthesis of diaryl
sulfones using an SO2 surrogate. (b) One-step synthesis of diaryl
sulfones (this work).
sulfones, the reaction can be conducted easily, and requires
neither an organometallic substrate nor an iodonium salt.
In the past decade, SO2 surrogates,5 such as DABSO
(DABCO•2SO2)6 and potassium metabisulfite (K2S2O5),7 have
been used for synthesis of sulfur-containing organic compounds.
These surrogates are stable solids that are easily handled: SO2 is
generated by heating in the reaction vessel. Thus, the reaction
can be set up without the need to handle toxic SO2 gas. The use
of SO2 surrogates has also been reported for the synthesis of
diaryl sulfones. In these reported examples, a two-step strategy
that consisted of sulfinate formation and subsequent arylation
was used (Scheme 1a).8 The strategy can be conducted in one
pot and applied for the synthesis of asymmetric sulfones, which
have two different aryl groups. However, there are some
drawbacks: strongly basic and nucleophilic organometals or
expensive diaryliodonium salts have to be used. If both the
sulfinate formation and the arylation steps are catalyzed by the
same catalyst, diaryl sulfones could be synthesized from aryl
halides in one step under relatively mild reaction conditions,
without the use of organometals or iodonium salts (Scheme 1b).
Recently, an excellent method for diaryl sulfone synthesis via
sulfonylative Suzuki-Miyaura coupling was reported;9 however,
boronic acids must be used in this reaction. No methods have yet
been reported for a one-step synthesis in which both the aryl
groups of the diaryl sulfones are introduced directly using aryl
halides. Herein, we report the Pd-catalyzed one-step synthesis
of diaryl sulfones from aryl halides, using K2S2O5 as an SO2
surrogate. Although this method produces only symmetrical
The reaction conditions of the sulfone synthesis were
optimized by using 4-iodoanisole (1) as a model substrate
(Table 1). Based on our previous work on the Pd-catalyzed
synthesis of sulfonamides and sulfinamides,13 we chose K2S2O5
as an SO2 surrogate and a tertiary amine as a reductant. When
the reaction was conducted by using Pd(OAc)2 as a catalyst, the
HBF4 salt of P(t-Bu)314 as a ligand, K2S2O5 as an SO2 surrogate,
and iPr2NEt as a reductant in toluene at 80 °C, a small amount
(<15% yield) of the desired sulfone 2 was obtained (Entry 1).
Among the solvents (Entries 2-5), DMSO and DMF were found
to be promising. At higher temperatures, DMF produced better
results than DMSO (Entry 6 vs. 7), and 100 °C was the optimal
temperature (Entry 7 vs. 8). When the amount of K2S2O5 was
reduced, 2 was still obtained in good yields (Entries 9 and 10),
suggesting that two equivalents of SO2 are available from one
equivalent of K2S2O5. The optimal amount of K2S2O5 was found
to be 0.75 equivalent (Entry 9). Next, the effects of ligands were
studied. In the absence of ligands, 2 was not obtained at all,
and a significant amount of biaryl 3 was formed (Entry 11),
indicating that the ligand plays an important role. Unexpectedly,
the other ligands tested also failed to yield the sulfone, and 3
was obtained as the major product (Entries 12-20). It is of note
that only P(t-Bu)3 was effective for sulfone synthesis. We also
tested other SO2 surrogates, but better results were not obtained
(Entries 21 and 22). Other reductants, such as NEt3 and
HCO2Na, resulted in poorer yields (Entries 23 and 24); the
© 2019 The Chemical Society of Japan
Tanaka, Hiromichi
