Metal-free sp3 C-H functionalization: A novel approach for the syntheses of selenide ethers and thioesters from methyl arenes

Article abstract of DOI:10.1039/c4cc04503c

A DTBP-promoted metal-free and solvent-free formation of C-Se and C-S bonds through sp³ C-H functionalization of methyl arenes with diselenides and disulfides is described. the Partner Organisations 2014.

Full text of DOI:10.1039/c4cc04503c

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Metal-free sp3 C–H functionalization: a novel
approach for the syntheses of selenide ethers
and thioesters from methyl arenes†
Cite this: Chem. Commun., 2014,
50, 11374
Received 13th June 2014,
Accepted 29th July 2014
Satpal Singh Badsara, Yi-Chen Liu, Ping-An Hsieh, Jing-Wen Zeng, Shao-Yi Lu,
Yi-Wei Liu and Chin-Fa Lee*
DOI: 10.1039/c4cc04503c
www.rsc.org/chemcomm
Table 1 Optimization of the reaction conditionsa
A DTBP-promoted metal-free and solvent-free formation of C–Se
and C–S bonds through sp3 C–H functionalization of methyl arenes
with diselenides and disulfides is described.
From an atom-economy point of view, the construction of carbon–
carbon1,2 and carbon–heteroatom3 bonds through C–H function-
alization has been an attractive research area in organic synthesis.1–3
Regarding the carbon–heteroatom bond formation, the synthesis of
aryl chalcogenides4,5 has been less studied when compared with
other carbon–heteroatom bond forming processes. Although the
direct C–S and C–Se bond formation through C–H functionalization
of arenes is known with6 or without7 transition metals, the C–S and
C–Se bond formations through the C–H functionalization of sp3
carbon are not documented. Organo-selenium compounds are
important motifs in organic synthesis and in the chemical industry8
as well as serve as potential drug candidates.9,10 In recent years, the
preparation of thioesters have also received much attention due to
the importance of thioesters as acyl transfer reagents in organic
synthesis11 and chemical biology.12 Traditionally, thioesters have
been prepared through the condensation reaction of carboxylic acid
derivatives such as acyl chlorides and anhydrides. For example, acyl
chlorides are moisture-sensitive, and this approach will produce an
equal amount of halide anion when an acyl halide is used.13
Recently, the coupling reaction of thiols or disulfides with aldehydes
has been reported for the preparation of thioesters.14 Notably,
coupling of methyl arenes with thiol surrogates would be the most
attractive approach from an atom-economy point of view. Here, we
report the DTBP-promoted syntheses of selenide ethers and thio-
esters from methyl arenes for the first time.
Entry
Oxidant (equiv.)
Yield (%)
1b
2c
3
4
5
TBHP (3.0)
TBHP (3.0)
H2O2 (3.0)
BPO (3.0)
TBPB (3.0)
DTBP (3.0)
DTBP (5.0)
DCP (5.0)
DTBP (5.0)
DTBP (5.0)
DTBP (5.0)
DTBP (5.0)
Trace
Trace
Trace
14
Trace
38
68
58
60
37
6
7
8
9d
10e
11f
12g
69
71
a
Reaction conditions: mesitylene (1.0 mL), diphenyl diselenide (0.5 mmol)
b
and oxidant (5.0 mmol) were reacted at 120 1C for 24 h. TBHP solution in
c
d
e
decane. TBHP solution in water. 140 1C. 0.5 mL mesitylene was used.
f
g
1.5 mL mesitylene was used. 2.0 mL mesitylene was used. (TBHP = tert-
butyl hydroperoxide, TBPB = tert-butyl peroxybenzoate, BPO = benzoyl
peroxide, DTBP = di-tert-butyl peroxide, DCP = dicumyl peroxide).
Screening other oxidants (Table 1, entries 3–6) showed that di-tert-
butyl peroxide (DTBP) is the best and gives the product in 38% yield
(Table 1, entry 6). To our delight, 68% yield of the product was
obtained when a higher amount of DTBP was employed (Table 1,
entry 7). 58% of the product was obtained when dicumyl peroxide
(DCP) was used as the oxidant (Table 1, entry 8).2 It was found that a
higher reaction temperature (Table 1, entry 9) and lower amount of
mesitylene (Table 1, entry 10) diminished the yield of 3a. Increasing
the amount of mesitylene provided little enhancement in the
chemical yields (Table 1, entries 11 and 12, respectively). Notably,
no selenoxide was formed during the reaction.
With the optimized reaction conditions in hand, we then studied
the scope of this system for a variety of substrates. As demonstrated
in Table 2, various methyl arenes 1 were worked smoothly with
diaryl diselenides 2 to provide selenide ethers (3b–3s) in good yields.
This system shows good functional group tolerance, and functional
groups including chloro (3c, 3h–3l), bromo (3m, 3n), iodo (3o, 3p)
Initially, mesitylene (1a) was selected as the model, and treated
with diphenyl diselenide (2a) under the influence of tert-butyl hydro-
peroxide (TBHP)14a at 120 1C for 24 h (Table 1, entries 1 and 2);
however, only a trace amount of 3a was detected using GC-MS.
Department of Chemistry, National Chung Hsing University, Taichung, Taiwan 402,
Republic of China. E-mail: cfalee@dragon.nchu.edu.tw; Fax: +886 4 2286 2547;
Tel: +886 4 2284 0411 ext. 810
† Electronic supplementary information (ESI) available: Experimental details,
spectral data for new products. See DOI: 10.1039/c4cc04503c
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Table 2 DTBP-promoted C–Se bond formation between methyl arenes
and diselenides via sp3 C–H functionalizationa,b
formation of a thioester to various methyl arenes with disulfides
under the influence of DTBP at 110 1C for 36 h to give thioesters in
good yields. Remarkably, both diaryl- and dialkyl disulfides were
coupled with methyl arenes. Functional groups including bromo
(6c, 6g, 6n–6q), chloro (6l–6n and 6r) and methoxy (6b and 6f) were
tolerated under the reaction conditions employed. 2-Methyl-
thiophene was also coupled with diphenyl disulfide to provide 6s
in 56% yield. The coupling of ethyl benzene with diphenyl disulfide
provided the thioether 6t instead of the thioester (Table 3).7d
The control experiment showed that dimerization of mesitylene
and trace amounts of aldehyde were detected when mesitylene (1a)
was treated with DTBP at 110 1C for 24 h without diselenide or
disulfide (eqn (2)). Based on this result, we proposed a plausible
mechanism for this reaction (Scheme 1). In the case of C–Se
formation, the benzyl radical A was coupled with diselenide to
provide a selenide ether (3), and no selenide ester was determined
in this reaction even when the reaction was performed for 48 h.
Two potential reaction pathways are involved in the case of C–S
coupling. First, the benzyl radical A reacted with disulfide to
Table 3 DTBP-promoted synthesis of thioesters from methyl arenes 1
and disulfides 4a,b
a
Reaction conditions: methyl arenes (1.0 mL), diselenide (0.5 mmol)
b
and DTBP (5.0 mmol) were reacted at 120 1C for 24 h. Yields are based
on diselenides. Trace amount of isomer was also observed.
c
and trifluoromethyl (3n) are tolerated under the reaction conditions.
Not only diaryl diselenide but also dialkyl diselenide could be used
as the coupling partner (3q, 3r). 2-Methylpyridine was also coupled
with diphenyl diselenide to form selenide ether 3s. The coupling
reaction of ethyl benzene with diphenyl diselenide could give
selenide ether 3t as the major product along with the isomer
(at the position of the methyl carbon).
Based on the promising results for C–Se bond formation, we
then turned our attention towards C–S bond formation via sp3
C–H functionalization of methyl arenes. The thioether (5) was
obtained along with the formation of a thioester (6a) when
mesitylene (1a) was treated with diphenyl disulfide (4a) by using
DTBP as the oxidant at 120 1C for 24 h (eqn (1)).
(1)
a
Reaction conditions: methyl arene (1.0 mL), disulfide (0.5 mmol) and
b
To our delight, 65% yield of 6a was obtained when the reaction
DTBP (5.0 mmol) were reacted at 110 1C for 36 h. Yields are based on
was carried out at 110 1C for 36 h. We have extended this selective disulfides. 48 h. Thioester was not obtained.
c
d
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1
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(2)
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The National Science Council, Taiwan (NSC 101-2113-M-005-
008-MY3), the National Chung Hsing University and the Center
of Nanoscience and Nanotechnology (NCHU) are gratefully
acknowledged for financial support. We also thank Prof. Fung-E
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Golden-Jade Fellow of Kenda Foundation, Taiwan.
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