P. Guan et al. / Tetrahedron Letters 53 (2012) 5987–5992
5991
Table 4 (continued)
Entrya
Halide
Sulfide
Product
Yieldb (%)
Br
HS
S
10
95
O
O
a
All reactions were conducted with ArX (1 mmol), thiol (1.1 mmol), Ni(OAc)2 (0.1 mmol), IPr (0.05 mmol), and KOtBu (1.5 mmol) in DMF (2 mL).
Isolated yield.
b
same as that in the reaction with phenylthiol. Diarylation with
2.4 equiv of benzylthiol could not occur in one-pot process as the
same as that with phenylthiol. The catalytic system showed good
activities for deactivated electron-rich aryl bromides as well.
Studies on the scope of coupling more aliphatic thiols are sum-
marized in Table 4. The results showed high yield in short reaction
times with this catalytic system as well.
At present the mechanism of the Ni-catalyzed coupling reaction
is not completely clear. Nonetheless, Ni-NHC catalyst is assumed to
be undergoing the same oxidative addition and reductive elimina-
tion cycle as well established Pd-phosphine catalysts in coupling of
C–S bonds (Scheme 1).3a,9 Oxidative addition of the aryl halide
with the catalyst may provide intermediate A, which reacts with
thiol that can give intermediate B. The desired C-S coupling prod-
uct is provided by reductive elimination of B.
LnNi NHC
Ar-SR
Ar-X
NHC
NHC
LnNi
LnNi
X
Ar
Ar
SR
B
A
M-X
M-SR
Scheme 1. Catalytic cycle for C–S coupling reaction.
suitable base, whereas DMF was the best solvent. The influence of
temperature and Ni/NHC ratio was insignificant for the tested reac-
tion. Decrease in the yield was observed when the reaction tem-
perature was raised from 70 to 130 °C, which probably due to no
or little side reactions happened at 70 °C. Thus, the optimized reac-
tion conditions were 10 mol % Ni(OAc)2 as the catalyst, 5 mol % IPr
as the ligand, t-BuOK as a base, DMF as the solvent, and a reaction
temperature of 70 °C.
Conclusion
A simple and efficient procedure is described for the C–S cou-
pling reaction of aromatic and aliphatic thiols with aryl halides (io-
dides, bromides and chlorides) using anhydrous Ni(OAc)2 with
NHC under argon. This catalytic system showed good activities to-
ward various aryl halides in C–S coupling reactions. Reactions oc-
cur in excellent yields, broad scope, and high tolerance of
functional groups. They could be excellent candidates to replace
expensive palladium complexes for C–S coupling catalysis.
To probe the substrate scope of the reaction, two electroni-
cally different thiols were chosen (phenylthiol and benzylthiol)
to react with a variety of aryl halides under the optimized con-
ditions. The results for phenylthiol with various aryl halides are
given in Table 2. It shows that phenylthiol reacted with aryl io-
dide to form the corresponding sulfides in good to excellent
yield (Table 2, entries 1–4). Moreover, the coupling reaction with
relatively inexpensive aryl bromides could occur in moderate to
good yield. However, better yield was afforded in the reaction
with less reactive aryl bromides at high temperature, for exam-
ple, 89% of product was afforded with o-methoxyphenyl iodide
at 70 °C, rather than 79% with bromide at 110 °C (Table 2, en-
tries 2 vs 14). Due to the higher reactivity of the aryl halides
with electron-withdrawing group, their reactions with phenylth-
iol were completed in 2 h. The longer reaction time would lead
to the lower yield (Table 2, entries 7, 9, 11–12, 15 and 17). Ste-
rically demanding ortho-substituted aryl halides led to the lower
yield sometimes (Table 2, entries 2 vs 4). Only mono-arylated
product was obtained in the reaction of 1,4-dibromobezene,
and diarylation could not occur in one-pot process with
2.4 equiv of thiol (Table 2, entry 13). The coupling reaction could
only occur with aryl chlorides which are activated with electron
withdrawing substitution. Some interesting functional group tol-
erances were noticed.
Acknowledgments
We gratefully acknowledge the National Natural Science Foun-
dation of China (NSFC) (21071121 and 21172188), Scientific Re-
search Foundation (SRF) for the Returned Overseas Chinese
Scholars (ROCS), State Education Ministry (SEM), the Priority Aca-
demic Program Development of Jiangsu Higher Education Institu-
tions (PAPD), 333 project for the cultivation of high-level talents
(33GC10002) and Qing Lan Project of Jiangsu Education Committee
(08QLT001 and 08QLD006) for financial support of this work.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
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The results for the reaction of benzylthiol with aryl halides are
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yield (Table 2, entries 3, 6–8 and 10). Steric and electronic factors
still play an important role in the reaction with benzylthiol as the
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Guan, Pei
