Single-Electron Transfer between CuX2and Thiols Determined by Extended X-Ray Absorption Fine Structure Analysis: Application in Markovnikov-Type Hydrothiolation of Styrenes

Article abstract of DOI:10.1002/chem.201604086

Transition-metal mediated C?S bond formation using thiol compounds has been widely used in recent years. However, there has been less focus on the interaction between the metal and thiol compounds. In this work, we have successfully evidenced the single-e

Full text of DOI:10.1002/chem.201604086

DOI: 10.1002/chem.201604086
Communication
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Reaction Mechanisms |Hot Paper|
Single-Electron Transfer between CuX2 and Thiols Determined by
Extended X-Ray Absorption Fine Structure Analysis: Application
in Markovnikov-Type Hydrothiolation of Styrenes
Hong Yi+,[a] Chunlan Song+,[a] Yiying Li,[a] Chih-Wen Pao,[c] Jyh-Fu Lee,[c] and Aiwen Lei*[a, b]
excess strong acid, alkenes, or conjugated olefins are always
needed.[5] Recently, some examples have been accomplished
Abstract: Transition-metal mediated CÀS bond formation
using thiol compounds has been widely used in recent
years. However, there has been less focus on the interac-
tion between the metal and thiol compounds. In this
work, we have successfully evidenced the single-electron
transfer between CuX2 and thiophenol utilizing EXAFS.
The fitting EXAFS results reveal that two halide anions are
coordinated with the CuI center, whereas no sulfur atom is
observed in the first coordination sphere. This CuI ate
complex serves as the key intermediate for the proton
transfer in the application of Markovnikov-type hydrothio-
lation reactions.
using catalytic Pd or Cu to achieve the Markovnikov-type hy-
drothiolation.[6] In these reported examples, the olefins are
always alkenes bearing heteroatoms and the detailed mecha-
nism between metals and thiols remains unclear.[1g] Though in-
teraction between CuII species and thiols is a known process
and has been studied,[1g,j] a detailed mechanism and determi-
nation of the CuI species generated still remains unknown. In
this work, we employed extended X-ray absorption fine struc-
ture (EXAFS) and EPR analyses to study the single-electron
transfer between CuX2 and thiophenol, which provides direct
evidence of this reductive process. This formed CuI ate com-
plex serves as the key intermediate in unprecedented Markov-
nikov-type hydrothiolation of alkenes with thiophenols.
EPR spectroscopy has been used to probe the CuII species
present in different reactions.[7] Initially, we applied EPR spec-
troscopy to investigate this reaction between CuBr2 and p-Me-
PhSH. As shown in the EPR spectra (Figure 1), an EPR silent
species was generated after adding the p-toluenethiol in CuBr2
solution. These results may indicate that the CuII species can
be reduced by thiophenol compounds.
Thiol compounds widely exist in nature and occupy an impor-
tant role in organic synthesis.[1] The construction of CÀS bonds
using thiol compounds is a significant goal in synthetic
chemistry due to the widespread utility of numerous organo-
sulfur compounds as synthetic intermediates, bioactive com-
pounds, and functional materials.[1d,2] The addition reaction of
organosulfur compounds to unsaturated bonds presents
a very attractive strategy for CÀS bond formation, and great
progress has been achieved in recent decades.[3] The thiol–ene
“click” reaction is well established and has served as a powerful
tool in organic synthesis.[2d] The anti-Markovnikov addition of
thiols to alkenes was achieved in high selectivity.[4] A radical-
type mechanism was involved and promoted by initiators,
such as AIBN, peroxides, or photochemistry. However, Markov-
nikov-type hydrothiolation of alkenes is relatively less devel-
oped. Although several examples have been demonstrated,
To further probe this process, we used XAS spectroscopy,
which has served as a powerful tool for determination of the
local structure of metal species,[8] to investigate the reaction
between CuX2 (X=Br, Cl) and p-toluenethiol under nitrogen at-
mosphere. As shown in the XANES spectra (Figure 2A, black
[a] H. Yi,+ C. Song,+ Y. Li, Prof. Dr. A. Lei
College of Chemistry and Molecular Sciences
The Institute for Advanced Studies (IAS)
Wuhan University, Wuhan, Hubei 430072 (P.R. China)
E-mail: aiwenlei@whu.edu.cn
Homepage: http://aiwenlei.whu.edu.cn/Main Website/
[b] Prof. Dr. A. Lei
State Key Laboratory and Institute of Elemento-Organic Chemistry
Nankai University, Tianjin 300071 (P.R. China)
[c] Dr. C.-W. Pao, Prof. Dr. J.-F. Lee
National Synchrotron Radiation Research Center
Hsinchu 30076 (Taiwan)
[+] These authors contributed equally to this work.
Figure 1. EPR spectra of the reaction between CuBr2 (0.5 mmol) and p-tolue-
nethiol (1.0 mmol) in 5.0 mL DMF for 5 min. Red line: CuBr2 in DMF; black
line: reaction system.
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/chem.201604086.
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Table 1. Summary of EXAFS first shell-fitting results.[a]
edge energy OS
(eV)
coordination CN
atom
d
[ꢁ]
CuBr2 +p-toluenethiol 8981.6
+1 Br
2
2.24
2.11
(DMF solution)[b]
(edge)
CuCl2 +p-toluenethiol
(DMF solution)[c]
8981.6
(edge)
+1 Cl
2
[a] OS: oxidation state; CN: coordination number; d: bond length. [b] Fit-
ting results of the R-Space EXAFS spectrum of CuBr2 +p-toluenethiol in
DMF solution (FT: 3.00–13.98 ꢁÀ1, fitting range: 1.22–2.37 ꢁ, Debye–Waller
factor: 0.0034. [c] Fitting results of the R-Space EXAFS spectrum of
CuCl2 +p-toluenethiol in DMF solution (FT: 1.84–10.53 ꢁÀ1, fitting range:
1.34–2.04 ꢁ, Debye–Waller factor: 0.001.
(CuCl2)À H+ complex, in accordance with the single-crystal
structure reported in the literature.[9] Based on these results,
we think that the [X-Cu-X]À H+ ate complex is the most proba-
ble structure for the CuI species generated through the reduc-
tion process between CuX2 (X=Br or Cl) and thiols.
Based on the above results, thiophenol can serve as the re-
ductant to transfer one electron to CuII, furnishing the reduced
CuI complex and the thiyl radical. We hoped to add one olefin
to trap the formed thiyl radical. Initially, we used trans-anethole
1a as the trapping substrates (Scheme 1). However, no desired
anti-Markovnikov product was detected, whereas 70% yield of
Markovnikov-type product 3a was generated. A plausible
mechanism for this hydrothiolation process is proposed in
Scheme 2. As evidenced by EXAFS and EPR studies, the initial
step is the single-electron transfer between CuBr2 and thiophe-
nol, generating the [CuBr2]À H+ species. Almost quantitative
yield of the homocoupling product of thiophenol was formed
during this single-electron transfer (SET) process. The
[CuBr2]À H+ ate complex 6 then transfers one proton to the
olefin, forming the cation intermediate 7 and complex 8. Final-
ly, the p-toluenethiol attacks this intermediate 7 to form the
desired hydrothiolation product with the loss of one proton.
The [CuBr2]À H+ ate complex 6 can be regenerated through
the combination of complex 8 and proton. In this hydrothiola-
tion process, the [CuBr2]À H+ ate complex serves as the key in-
termediate for the proton transfer. In addition, we found that
the HBr acid could also promote this reaction, which is further
evidence that the CuI ate complex acted as a proton-transfer
intermediate.
Figure 2. XANES and EXAFS spectra. Black line: CuBr2 (0.5 mmol) and p-tol-
uenethiol (1.0 mmol); red line: CuCl2 (0.5 mmol) and p-toluenethiol
(1.0 mmol); blue line: CuBr2 (0.5 mmol) in DMF at room temperature.
line), the obtained copper species has an edge energy of
8981.6 eV. Therefore, it could be concluded that the obtained
Cu species is CuI. In addition, the reaction of CuCl2 and p-tolue-
nethiol was also demonstrated (Figure 2A, red line). A nearly
identical XANES spectrum revealed that the geometry and oxi-
dation specification of both generated CuI species were similar.
As shown in Figure 2B, the EXAFS spectrum of the reaction be-
tween CuBr2 and p-toluenethiol is very different from the reac-
tion between CuCl2 and p-toluenethion, indicating that the
halide ion with different bond length may coordinate with the
formed CuI species and no sulfur atom is coordinated. The fit-
ting results showed that two bromide ions coordinated with
CuI species (Figure S1 in the Supporting Information). The aver-
age distance of the CuÀBr bond is 2.24 ꢁ (Table 1). We also
fitted the data with a [CuBrSPh]À structure for comparison (Fig-
ure S2 in the Supporting Information). However, the Debye–
Waller factor of the CuÀS bond is relatively large. Furthermore,
we also isolated, in quantitative yield, the homocoupling prod-
uct of p-toluenethiol. Therefore, we determined the obtained
CuI complex to be (CuBr2)À H+.[7a] In addition, we also fitted the
EXAFS of the reaction between CuCl2 and p-toluenethiol (Fig-
ure S2). The fitting results revealed that two Cl ions coordinat-
ed with the CuI species and the average bond distance of the
CuÀCl bond is 2.11 ꢁ, which we proposed to be the
Scheme 1. The reaction between 4-methylbenzenethiol and p-toluenethiol
promoted by CuBr2.
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moderate to good yields (3c–3g). The thiols substituted with
-bromo, m-bromo, and o-bromo gave the desired products in
95, 76, and 85% yields, respectively, indicating that steric ef-
fects have little impact on this transformation. Moreover, 87%
yield was obtained when using a strong electron-withdrawing
substituent like nitro on the benzenethiols (3h).
Subsequently, the reaction was expanded for the synthesis
of sulfanes using different olefins (Scheme 4). Besides 3a,
other kinds of external alkene like indene could also tolerate
this transformation (3i). The terminal alkenes that included dif-
ferent substituent groups reacted effectively to afford the cor-
responding products in excellent yields (3j–3q). Styrenes sub-
stituted with methyl and methoxy groups were almost quanti-
tatively converted into the desired products (3j and 3k). How-
ever, the styrenes substituted with electron-withdrawing
groups such as F and CN did not produce the desired prod-
ucts.
Scheme 2. The proposed mechanism of single-electron transfer between
CuX2 4 and p-toluenethiol 2a, and application in hydrothiolation reaction.
We found that almost quantitative yield of the hydrothiola-
tion product was achieved when employing CH3CN as solvent
and CuBr2 as the catalyst (see the Supporting Information,
Table S1, entry 2). In addition, we investigated the effect of dif-
ferent copper salts on this hydrothiolation reaction. It was
found that CuBr2 showed the best catalytic activity. In the con-
trol experiments, no desired product was detected without the
addition of CuBr2, confirming that the copper salt was essential
to this transformation (Table S1, entry 7). With the optimized
conditions established, we turned to explore the generality of
this copper-promoted hydrothiolation reaction in the synthesis
of sulfanes. As shown in Scheme 3, the benzenethiols 2 with
different electron-withdrawing and electron-donating substitu-
ents reacted efficiently to afford the corresponding sulfanes
(3a–3h) in good to excellent yields. Benzenethiols with p-
methyl and o-methyl groups gave the desired product in good
yields (3a and 3b). Notably, halide substituents on the aromat-
ic ring were well-tolerated in this transformation and afforded
Scheme 4. Copper-promoted hydrothiolation reaction between p-toluene-
thiol 2a and different alkene derivatives 1. [a] Reactions were conducted at
RT for 2 h using 1 (0.50 mmol), 2a (1.0 mmol), and CuBr2 (15 mol%) in
CH3CN (2.0 mL) under N2 atmosphere. Isolated yields are shown. [b] The re-
action time is 12 h.
In conclusion, we have observed and provided evidence for
the single-electron transfer between CuX2 and thiophenol
using EXAFS and EPR spectroscopy. The formed CuI species
was assigned as the CuI ate complex, which serves as the key
intermediate for the proton transfer in the application of hy-
drothiolation reaction. These spectroscopic analyses for the ob-
servation of single-electron transfer between CuII and thiophe-
nol will not only be helpful for mechanistic understanding in
copper catalysis but will also benefit further reaction design.
Scheme 3. Copper-promoted hydrothiolation reaction between anethole 1a
and different thiophenol derivatives 2. [a] Reactions were conducted at RT
for 2 h using 1a (0.50 mmol), 2 (1.0 mmol), and CuBr2 (15 mol%) in CH3CN
(2.0 mL) under N2 atmosphere. Isolated yields are shown.
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Experimental Section
General procedure: A Schlenk tube equipped with a stir bar was
loaded with 16.7 mg (15 mol%, 0.75 mmol) of CuBr2, 0.5 mmol ole-
fins 1a and 1.0 mmol 4-methylbenzenethiol 2a in 2.0 mL degassed
acetonitrile under N2 atmosphere. The solution was then stirred at
room temperature for 2 h. After the completion of the reaction,
the products were determined by TLC. The solvent was removed
under reduced pressure by an aspirator, then the pure product
was obtained by flash column chromatography on silica gel
(eluent: petroleum ether/ethyl acetate=50:1) to afford 3a in
132.2 mg (97%, 0.5 mmol scale) as a pale yellow solid. 1H NMR
(400 MHz, CDCl3) d=7.16–7.12 (m, 4H), 6.98 (d, J=7.6 Hz, 2H),
6.77 (d, J=8.8 Hz, 2H), 3.95 (dd, J=9.0, 5.9 Hz, 1H), 3.72 (s, 3H),
2.25 (s, 3H), 2.09–1.644 (m, 2H), 0.87 ppm (t, J=7.2 Hz, 3H).
13C NMR (100 MHz, CDCl3) d=158.3, 136.9, 133.9, 132.8, 131.3,
129.3, 128.8, 113.5, 55.0, 54.9, 29.2, 21.0, 12.2 ppm. HRMS (EI+) m/z
calcd for C17H20OS: 272.1235 [M]+; found: 272.1239.
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Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21390400, 21520102003, 21272180,
21302148), the Hubei Province Natural Science Foundation of
China (2013CFA081), the Research Fund for the Doctoral Pro-
gram of Higher Education of China (20120141130002), and the
Ministry of Science and Technology of China (2012YQ120060).
The Program of Introducing Talents of Discipline to Universities
of China (111 Program) is also appreciated. We also thank all
the team members at the beamline 17C1 of the National Syn-
chrotron Radiation Research Center (NSRRC) in Taiwan.
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Keywords: copper catalysis · copper reduction · CÀS bond
formation · hydrothiolation · synchrotron
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Received: August 28, 2016
Published online on && &&, 0000
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COMMUNICATION
EXAFS lights up copper: The single-
electron transfer between CuX2 and thi-
ophenol is reported, based on extended
X-ray absorption fine structure (EXAFS)
analysis. The fitting EXAFS results reveal
that two halide anions are coordinated
with the CuI center, whereas no sulfur
atom is observed in the first coordina-
tion sphere. This CuI ate complex serves
as the key intermediate for the proton
transfer in the application of Markovni-
kov-type hydrothiolation reactions.
&
Reaction Mechanisms
H. Yi, C. Song, Y. Li, C.-W. Pao, J.-F. Lee,
A. Lei*
&& – &&
Single-Electron Transfer between CuX2
and Thiols Determined by Extended
X-Ray Absorption Fine Structure
Analysis: Application in Markovnikov-
Type Hydrothiolation of Styrenes
Chem. Eur. J. 2016, 22, 1 – 5
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