Rhodium-catalyzed interconversion between acid fluorides and thioesters controlled using heteroatom acceptors

Article abstract of DOI:10.1016/j.tetlet.2010.09.009

A rhodium complex catalyzed the equilibrium acyl transfer reaction between acid fluorides and thioesters. In the presence of fluoride or thiolate acceptors, the reaction could be shifted to either product. RhH(PPh ₃)₄-dppe catalyzed the reaction of acid fluorides and diorgano disulfides in the presence of triphenylphosphine giving thioesters, which was accompanied by triphenylphosphine difluoride. The same complex catalyzed the reaction of aryl thioesters and hexafluorobenzene giving acid fluorides, which was accompanied by 1,4-di(arylthio)-2,3,5,6- tetrafluorobenzenes.

Full text of DOI:10.1016/j.tetlet.2010.09.009

Tetrahedron Letters 51 (2010) 6090–6092
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Tetrahedron Letters
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Rhodium-catalyzed interconversion between acid fluorides and thioesters
controlled using heteroatom acceptors
Mieko Arisawa a, Toru Yamada a, Masahiko Yamaguchi a,b,
⇑
a Department of Organic Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Sendai 980-8578, Japan
b WPI Research Center, Advanced Institute for Materials Research, Tohoku University, Aoba, Sendai 980-8577, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A rhodium complex catalyzed the equilibrium acyl transfer reaction between acid fluorides and thioes-
ters. In the presence of fluoride or thiolate acceptors, the reaction could be shifted to either product.
RhH(PPh3)4-dppe catalyzed the reaction of acid fluorides and diorgano disulfides in the presence of tri-
phenylphosphine giving thioesters, which was accompanied by triphenylphosphine difluoride. The same
complex catalyzed the reaction of aryl thioesters and hexafluorobenzene giving acid fluorides, which was
accompanied by 1,4-di(arylthio)-2,3,5,6-tetrafluorobenzenes.
Received 5 August 2010
Revised 26 August 2010
Accepted 1 September 2010
Available online 21 September 2010
Ó 2010 Published by Elsevier Ltd.
1. Introduction
Benzoyl fluoride (1 equiv), di(p-tolyl) disulfide (0.5 equiv), and
triphenylphosphine (0.5 equiv)6 were reacted in refluxing THF for
A catalyst is a substance that changes the reaction course with-
out affecting the relative stability of substrates and products. The
development of an efficient catalyst, which decreases the activa-
tion energy of the reaction, results in equilibrium when the relative
thermodynamic stabilities of the substrates and products are close.
We found that a transition-metal complex could be used as a cat-
alyst in the synthesis and transformation of organosulfur and orga-
nophosphorus compounds,1 and that, in some cases, such reactions
exhibit equilibrium. For example, organothio groups are exchanged
among disulfides,2 thioalkynes,3 thioesters,4 and thioketones.5
Therefore, the control of equilibrium reactions to provide desired
products with high efficiency has become a subject of interest.
We found that the acyl transfer reaction between thioesters and
acid fluorides could be catalyzed by a rhodium catalyst. When S-(p-
tolyl) 3,5-dimethoxybenzothioate 1 and p-methoxybenzoyl fluo-
3 h in the presence of RhH(PPh3)4 (0.1 mol %) and dppe
(0.2 mol %), and S-(p-tolyl) benzothioate was obtained with a 88%
yield (Table 1, entry 1). The yield increased to 100% using
1 mol % of the rhodium complex. The formation of triphenylphos-
phine difluoride was confirmed by 19F NMR d ꢀ42.9 and 31P NMR
d ꢀ55.0 absorptions of the crude products.6
The method was applied to the synthesis of various acid fluo-
rides and disulfides (Table 1). For the reaction of aroyl fluorides
and diaryl disulfides, a small effect of the aromatic p-substituents
was observed for both aroyl and arylthio moieties (entries 1–4
and 8–10). The reaction of aliphatic disulfides also proceeded
smoothly (entries 5–7). Aliphatic acid fluorides could react with
di(p-tolyl) disulfide (entries 11–14). In some cases, the catalyst
loading could be reduced to 0.1 mol % (entries 1–5).
The synthesis of thioesters has generally been conducted using
acid chlorides or anhydrides and thiols in the presence of a base. It
is notable that the present method produces thioesters from acid
fluorides without using a strong base under transition-metal catal-
ysis.7 It was then considered interesting to compare the reactivities
of benzoyl fluoride and chloride, which revealed the notable
ride
2 were treated with RhH(PPh3)4 (5 mol %) and dppe
(10 mol %) in refluxing chlorobenzene for 3 h, a mixture of 3,5-dim-
ethoxybenzoyl fluoride 3 (37%) and S-(p-tolyl) p-dimethoxybenzo-
thioate 4 (40%) was obtained with the recovery of 1 (55%) and 2
(35%) (Scheme 1). No reaction occurred in the absence of the rho-
dium catalyst.
In order that thioesters or acid fluorides can be obtained effec-
tively, a device for shifting the equilibrium reaction is required. In
this work, it has been shown that acid fluorides could be converted
to thioesters in the presence of triphenylphosphine, and the re-
verse reaction could be conducted in the presence of hexafluoro-
benzene ( Scheme 2). The use of sulfur or fluoride acceptors
effectively shifted the equilibrium reaction.
MeO
MeO
COF
COSTol-p
RhH(PPh3)4 (5 mol%)
dppe (10 mol%)
3 37%
MeO
1 55%
MeO
MeO
+
+
C6H5Cl, refl., 3 h
COF 2 35%
MeO
COSTol-p
4 40%
⇑
Corresponding author.
E-mail address: yama@mail.pharm.tohoku.ac.jp (M. Yamaguchi).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2010.09.009

M. Arisawa et al. / Tetrahedron Letters 51 (2010) 6090–6092
6091
Table 3
F2PPh3
PPh3
F
Rhodium-catalyzed reaction of thioesters and hexafluorobenzene
O
RC F
RhH(PPh3)4 (2.5 mol%)
dppe (5 mol%)
O
+
R'S SR'
R'S
F
F
F
F
RC SC6H4X-p
p-XC6H4S
SC6H4X-p
C6H5Cl, refl., 3 h
+ C6F6
O
O
RC
F
RC SR'
Entry
R
X
Yield (%)
1
2
3
4
5
6
7
8
9
p-MeOC6H4
Me
OMe
H
Cl
Me
OMe
OMe
OMe
OMe
OMe
OMe
OMe
94
83
83
85
88
73
90
30
65
72
80
82
C6F6
C6F4(SR')2
Scheme 2.
p-EtOC6H4
3,5-(MeO)2C6H3
p-Me2NC6H4
p-ClC6H4
n-C9H19
PhCH2CH2
Table 1
Rhodium-catalyzed reaction of acid fluorides and disulfides
RhH(PPh3)4 (1 mol%)
dppe (2 mol%)
10
11
12
4-(t-Butyl)cyclohexyl
1-Adamantyl
O
O
PPh3 (0.5 eq)
+
(R'S)2
RC SR'
RC
F
THF, refl., 2 h
Entry
R
R0
Yield (%)
acceptor. The reaction of S-(p-tolyl) p-methoxybenzothioate 4
and hexafluorobenzene6 (2 equiv) in the presence of RhH(PPh3)4
(2.5 mol %) and dppe (5 mol %) in refluxing chlorobenzene for 3 h
gave p-methoxybenzoyl fluoride 2 and 1,4-di(p-tolylthio)-2,3,5,6-
tetrafluorobenzene7 with 94% and 99% yields, respectively (Table
3, entry 1). No reaction occurred in the absence of the rhodium
complex or dppe. Hexafluorobenzene is a reactive organosulfur
acceptor compared with p-fluoronitrobenzene, which gave 2 with
85% yield along with 4-(p-tolylthio)nitrobenzene (87%). The reac-
tion also proceeded under THF reflux conditions, that is, thioester
synthesis conditions, giving a modest yield (42%) of product 2.
A notable p-substituent effect of the aroyl moiety was shown by
a higher yield of p-methoxybenzothioate than that of p-chloro-
benzothioate (entries 2 and 6–8). The aromatic substituent effect
at the arylthio moiety was small in this reaction (entries 1–4). S-
Octyl p-methoxybenzoate gave a very small amount of acid fluo-
ride under the conditions used. The slightly different effects of
the substituents in the thioester formation (Table 1) and acid fluo-
ride formation (Table 3) may be due to the difference in efficiency
between the CO–S and CO–F bond cleavages. Acid fluorides were
generally synthesized from carboxylic acids by treating them with
reactive fluorinating reagents such as DAST or cyanuric fluoride;8,9
however, the transition-metal-catalyzed synthesis of acid fluorides
from thioesters using a stable fluorinating reagent may also be an
interesting approach.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Ph
p-Tol
p-ClC6H4
88,a 100
22,a 88b
85a
91a
89a
86c
63c
99
86
88
92
90
p-MeOC6H4
Ph
PhCONH(CH2)2
PhCOO(CH2)3
n-C8H17
p-Tol
p-Tol
p-Tol
p-Tol
p-Tol
p-ClC6H4
p-MeOC6H4
p-MeC6H4
n-C11H23
Ph(CH2)2
(n-Pr)2CH
n-PrMe2C
p-Tol
p-Tol
80
82
a
b
c
RhH(PPh3)4 (0.1 mol %), dppe (0.2 mol %), reaction time 5 h.
RhH(PPh3)4 (0.5 mol %), dppe (1 mol %).
RhH(PPh3)4 (5 mol %), dppe (10 mol %).
Table 2
Reaction of benzoyl fluoride and chloride with di(p-tolyl) disulfide
O
O
+
(p-TolS)2
PhC
X
PhC STol-p
THF, refl., 2 h
Entry Catalyst
PPh3
Temp
Yield (%)
X = F X = Cl
1
2
3
None
None
None
0.5 Equiv rt
0.5 Equiv rt
Refl.
ND
ND
45
ND
13
20
The rhodium catalyst equilibrated the acyl transfer reaction
between acid fluorides and thioesters, and the use of fluoride or
thiolate acceptors shifted the reaction for the synthesis of either
product. The use of triphenylphosphine promoted the formation
RhH(PPh3)4 (1 mol %) dppe
(2 mol %)
ND: Not detected.
reactivity of the acid fluoride under rhodium catalysis (Table 2). It
was first confirmed that no reaction occurred when benzoyl fluo-
ride or chloride was reacted with di(p-tolyl) disulfide under THF
reflux for 2 h (entry 1). In the presence of triphenylphosphine
(0.5 equiv), the acid chloride gave a small amount of thioester
(13%) at room temperature, but the acid fluoride did not, which re-
vealed the lower reactivity of the latter (entry 2). When
RhH(PPh3)4 (1 mol %) and dppe (2 mol %) were added to the mix-
tures, the reaction of the acid chloride slightly improved, giving a
thioester with 20% yield, whereas the acid fluoride gave the same
product with 45% yield. It was shown that the acid fluoride is spe-
cifically activated by the rhodium complex.
equilibrium
E
RCOSR'
RCOF
F acceptor
R'S acceptor
RCOF
(R'S)2
PPh3
E
E
RCOSR'
C6F6
RCOF
C6F4(SR')2
RCOSR'
F2PPh3
The reverse reaction for the synthesis of acid fluorides from
thioesters was then examined in the presence of an organothio
Scheme 3.

6092
M. Arisawa et al. / Tetrahedron Letters 51 (2010) 6090–6092
of thioesters, and hexafluorobenzene promoted that of acid fluo-
rides (Scheme 3). The acceptors were employed to change the rel-
ative thermodynamic stabilities of the substrates and products.
The conversion of triphenylphosphine to difluoride promoted the
formation of thioesters and that of hexafluorobenzene to aryl sul-
fide promoted the formation of acid fluorides.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.09.009.
References and notes
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In a two-necked flask equipped with a reflux condenser were
placed benzoyl fluoride (620 mg, 5.0 mmol), p-tolyl disulfide
(615 mg, 2.5 mmol), RhH(PPh3)4 (5.8 mg, 0.1 mol %), 1,2-
bis(diphenylphosphino)ethane (4.0 mg, 0.2 mol %), and triphenyl-
phosphine (655 mg, 50 mol %) in tetrahydrofuran (2 mL) under
an argon atmosphere, and the solution was stirred under reflux
for 2 h. The solvent was removed under reduced pressure, and
RhH(PPh3)4 was removed by short flash column chromatography
on silica gel. The eluents were concentrated under reduced pres-
sure, and the residue was purified by flash column chromatogra-
phy on silica gel giving S-(p-tolyl) benzothioate (1.006 g, 88%).
Acknowledgments
This work was supported by Grant-in-Aid for Scientific Re-
search (No. 21229001), GCOE program, and WPI Initiative from
JSPS. M.A. expresses her thanks to the Grant-in-Aid for Scientific
Research (No. 22689001) and the Asahi Glass Foundation.
9. Scattered examples of the reactions giving acid fluorides from thioesters.
Minato, H.; Miura, T.; Kobayashi, M. Chem. Lett. 1977, 609; Kremlev, M. M.;
Tyrra, W.; Naumann, D.; Yagupolskii, Y. L. Tetrahedron Lett. 2004, 45, 6101.