Rhodium-catalyzed substitution reaction of aryl fluorides with disulfides: P-orientation in the polyarylthiolation of polyfluorobenzenes

Article abstract of DOI:10.1021/ja8049996

In the presence of a catalytic amount of RhH(PPh₃)₄ and 1,2-bis(diphenylphosphino)benzene, an aromatic fluoride, an organic disulfide (0.5 equiv), and triphenylphosphine (0.5 equiv) reacted in refluxing chlorobenzene to give an aryl sulfide in high yield. Since triphenylphosphine trapped fluoride atoms forming phosphine difluoride, both organothio groups of the disulfide reacted effectively, and the fluoride substituent reacted more readily than the chloride and bromide. The reaction of hexafluorobenzene and a diaryl disulfide gave 1,4-diarylthio-2,3,5,6-tetrafluorobenzene, 1,2,4,5-tetraarylthio-3,6-difluorobenzene, and hexaarylthiobenzene in a stepwise manner; pentafluorobenzene gave 1-arylthio-2,3,5,6-tetrafluorobenzene; 1,2,3,4-tetrafluorobenzene gave 1,2-diarylthio-3,6-difluorobenzene; and 1,2,4,5-tetrafluorobenzene gave 1,4-diarylthio-2-5-difluorobenzene. The polyarylthiolation reaction of polyfluorobenzenes exhibited a strong tendency to form 1,4-difluorobenzenes. Copyright

Full text of DOI:10.1021/ja8049996

Published on Web 08/23/2008
Rhodium-Catalyzed Substitution Reaction of Aryl Fluorides with Disulfides:
p-Orientation in the Polyarylthiolation of Polyfluorobenzenes
Mieko Arisawa,† Takaaki Suzuki,† Tomofumi Ishikawa,† and Masahiko Yamaguchi*,‡
Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku UniVersity, Aoba,
Sendai, 980-8578, Japan and WPI AdVanced Institute for Materials Research, Tohoku UniVersity, Aoba, Sendai, Japan
Received May 2, 2008; E-mail: yama@mail.pharm.tohoku.ac.jp
Scheme 1
A variety of organofluorine compounds have become available
in recent years, and their reactivity difference with organochlorine,
organobromine, and organoiodine compounds can considerably
broaden the potential of organic synthesis.1 In this regard, the
development of aromatic CF substitution reactions is desirable, and
the use of transition metal catalysis has attracted much attention
for organometallic reagents containing magnesium,2 boron,3 sili-
con,4 tin,5 copper,6 or cesium,7 which possess reactive and polarized
metal-containing bonds. The reaction of less reactive reagents
possessing unpolarized bonds with organofluorides, however, is rare;
an exception is the hydrogenation reaction to convert CF bonds to
CH bonds.8 For the latter reactions to proceed, catalysts must be
able simultaneously to activate a CF bond and another single bond
of low polarity.
During our studies on the synthesis of organosulfur compounds
utilizing rhodium catalysis, single bond metathesis reactions have
become an important methodology. Rhodium complexes can cleave
the SS bond and exchange bonds with SS, HH, CH, PS, PP, and
CS bonds.9 Described in this study is the finding that this
methodology can be applied to the single bond metathesis of CF
and SS bonds: Rhodium-catalyzed aryl- and alkylthiolation reactions
of fluorobenzenes with disulfides. Synthesis of aryl sulfides using
thiolates and aryl fluorides possessing strong electron-withdrawing
substituents at the o- or p-positions has many precedents.10 The
present method employs disulfides without using strong bases.
In the presence of RhH(PPh3)4 (0.25 mol%) and 1,2-bis(diphe-
nylphosphino)benzene (dppBz) (0.5 mol%), bis(m-methoxyphenyl)
disulfide 2 (0.5 equiv), p-fluorobenzophenone 1, and PPh3 (0.5
equiv) were reacted in refluxing chlorobenzene for 3 h giving 4-(m-
methoxyphenylthio)benzophenone 3 in 89% yield (Scheme 1). The
rhodium complex is essential, and 3 was not detected when 1
and 2 were treated with dppBz and PPh3. Rh2(OAc)4 (70%),
Rh(acac)(C2H4) (84%), and RhH(CO)(PPh3)4 (71%) were active
under identical conditions, whereas RhCl(PPh3)3, [RhCl(cod)2]2,
[RhCl2Cp*]2 (Cp* ) pentamethylcyclopentadienyl), and RhCl3
showed essentially no activity. 3 was not obtained in the absence
of dppBz, and the use of other bidentate and monodentate ligands
revealed a high efficiency of dppBz in this reaction: dppe, dppp,
dppb, dpppentane, dpphexane, PPh3, (p-ClC6H4)3P, and (p-
MeOC6H4)3P were not effective at all. In these unreactive cases, 2
was recovered in more than 80% yield. Added PPh3 (0.5 equiv)
trapped the fluoride to form Ph3PF2, which was confirmed by 31P
and 19F NMR studies,11 and as a result both arylthio groups of 2
could be used for the arylthiolation. It is presumed that rapid fluoride
transfer from rhodium metal to phosphorus atom of the added PPh3
took place,12 or alternatively sulfenyl fluoride, which was formed
by single bond metathesis of 1 and 2, was rapidly converted to
Ph3PF2. Essentially no reaction occurred in the absence of PPh3.
Dialkyl disulfides underwent alkylthiolation with 1, when an
electron-rich tris(p-methoxyphenyl)phosphine was employed as the
fluoride trapping reagent.
The p- and o-derivatives of cyano- and nitrofluorobenzene reacted
with bis(p-methoxyphenyl) disulfide 4 in the presence of the
rhodium complex (0.25-2 mol%) to give the corresponding aryl
sulfides in high yields (Scheme 1). Fluorobenzene, however, was
inert under these conditions indicating the important role of electron-
withdrawing groups. It should be noted that m-cyano- and m-
nitrofluorobenzene reacted smoothly with 4, provided that a higher
catalyst loading (5 mol%) was employed. The reactivity of aryl
fluoride was higher than bromide and chloride as indicated by the
reaction of 1-bromo-4-chloro-3-fluorobenzene with di(p-tolyl) di-
sulfide 5 giving the fluorine substituted product.
Mechanistically, the rhodium complex should be involved in the
cleavage of the CF bond in aryl fluorides and the SS bond in
disulfides, and the mode of CF cleavage is a subject of interest.
Nucleophilic aromatic substitution of the aryl fluoride with rhodium
† Graduate School of Pharmaceutical Sciences.
‡ WPI Advanced Institute for Materials Research.
9
12214 J. AM. CHEM. SOC. 2008, 130, 12214–12215
10.1021/ja8049996 CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2
in the nucleophilic substitution reactions of polyfluorobenzenes with
sodium methoxide in a nonexplicit manner as shown here.15
The origin of the p-difluoride rule is an interesting subject. An
explanation is the minimization of the dipole moment by the
formation of the p-difluoride structure. Alternatively, it can be due
to an unusually high reactivity of p-arylthiolated fluorobenzenes
toward the rhodium catalyzed.
A rhodium complex catalyzes arylthiolation of aromatic fluorides.
The rhodium-catalyzed method contains a notable mode of CF
activation by a transition metal catalyst and may offer an extremely
broad scope for the manipulation of organosulfur compounds.
Scheme 3
Acknowledgment. This work was supported by JSPS (Nos.
16109001 and 17689001). M.A. expresses her thanks to the Grant-
in-Aid for Scientific Research on Priority Areas (Nos. 18037005
and 19020008) from MEXT.
Supporting Information Available: Detailed experimental proce-
dures and characterization data. This material is available free of charge
via the Internet at http://pubs.acs.org.
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