A nickel-catalyzed silylation reaction of alkyl aryl sulfoxides with silylzinc reagents

Article abstract of DOI:10.1039/d1ob00840d

Ni(PEt₃)Cl₂-catalyzed silylation of alkyl aryl sulfoxides with silylzinc reagents was carried out. This protocol allows alkyl aryl sulfoxides to convert to arylsilicon compounds under mild reaction conditions, tolerates a range of functional groups and is suitable for a wide scope of substrates.

Full text of DOI:10.1039/d1ob00840d

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A nickel-catalyzed silylation reaction of alkyl aryl
sulfoxides with silylzinc reagents†
Cite this: Org. Biomol. Chem., 2021,
19, 5082
Wei-Ze Lia and Zhong-Xia Wang
*
a,b
Received 29th April 2021,
Accepted 18th May 2021
DOI: 10.1039/d1ob00840d
rsc.li/obc
Ni(PEt3)Cl2-catalyzed silylation of alkyl aryl sulfoxides with silylzinc appropriate silylation reagents is worth exploring more widely.
reagents was carried out. This protocol allows alkyl aryl sulfoxides Aryl sulfoxides are more reactive than aryl sulfides owing to
to convert to arylsilicon compounds under mild reaction con- the electron deficiency of the sulfoxide unit and are potentially
ditions, tolerates a range of functional groups and is suitable for a promising electrophiles.10 However, most examples concen-
wide scope of substrates.
trated upon the reaction of diaryl sulfoxides.10b,c,11 More
general and easily accessible alkyl aryl sulfoxides have been
rarely used because their reactions often led to low
yields.10b,11c,d Up to now, only two systematic studies employ-
ing alkyl aryl sulfoxides as electrophiles in the cross-coupling
reactions have been reported, namely nickel-catalyzed cross-
coupling of aryl methyl sulfoxides with arylzinc reagents
(Scheme 1(b))10a and transition-metal-free cross-coupling of
aryl methyl sulfoxides with alcohols.12 The former reaction
gave good product yields via the use of excess arylzinc reagents
which consume the catalyst-oxidizing methanesulfenate anion
formed in the process of reaction. Enthaler et al. reported a
reaction example of methyl phenyl sulfoxide with
p-MeOC6H4MgBr under nickel catalysis.11b We intended to
explore the silylation of alkyl aryl sulfoxides using silylzinc
reagents as nucleophiles (Scheme 1(c)) because silylzinc
reagents have better compatibility with functional groups than
silyllithium or silylpotassium reagents and better nucleophilic
ability than silylboron reagents and disilanes.3–5 Herein, we
report the results.
Arylsilanes are important intermediates or building blocks
and are widely applied in the field of organic synthesis, medic-
inal chemistry and materials science.1 A range of method-
ologies for the synthesis of arylsilanes have been developed,
mainly including (a) the reaction of silicon halides with
organometallic reagents;2 (b) the reaction of aromatic electro-
philes with silylation reagents such as silyllithium reagents,3
silylboron reagents,4 silylzinc reagents,5 and hydrosilanes;6 (c)
direct C–H silylation of arenes.7 Among the methods, the reac-
tion of silyl nucleophiles with appropriate aromatic electro-
philes is still attractive because of the wide availability of elec-
trophilic aromatic substrates such as aryl halides and various
phenol derivatives. In recent years, sulfur-containing aromatic
compounds including aryl sulfides, thiophenols, sodium aryl-
sulfinates, arylsulfinic acids, arylsulfonyl chlorides, arylsulfo-
nyl hydrazides, aryl sulfoniums, and aryl sulfoxides have been
employed as electrophiles via C–S bond cleavage in cross-coup-
ling reactions. They were used to construct C–C bonds and C–
heteroatom bonds with or without transition metal catalysis.8
However, it is rare to see C–Si bond construction using sulfur-
containing electrophiles.9 A representative example is shown
in Scheme 1(a).9a In view of the importance of organosilicon
compounds and the accessibility of organosulfur compounds,
the silylation of sulfur-containing aromatic substrates with
aCAS Key Laboratory of Soft Matter Chemistry and Department of Chemistry,
University of Science and Technology of China, Hefei, Anhui 230026, P. R. China..
E-mail: zxwang@ustc.edu.cn; Tel: +86 551 63603043
bCollaborative Innovation Center of Chemical Science and Engineering, Tianjin
300072, P. R. China
†Electronic supplementary information (ESI) available: Experimental details and
the copies of the NMR spectra of the coupling products. See DOI: 10.1039/
d1ob00840d
Scheme 1 Reaction of aryl sulfoniums or aryl alkyl sulfoxides.
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A
reaction of methyl phenyl sulfoxide (1a) with This oxidizing species might lead to the formation of disilanes
PhMe2SiZnCl (2a) was used to screen catalysts and optimize in our reaction system. We did observe the formation of disi-
reaction conditions (Table 1). In the absence of a catalyst, the lanes. Hence, a larger amount of silylzinc reagent should be
reaction cannot occur in THF at 80 °C (entry 1). It has been required. Indeed, when 3 equiv. of 2a were employed, the reac-
reported that nickel complexes were effective in the catalytic tion gave 82% yield of the cross-coupling product. A higher
cleavage of the C–S bonds of sulfoxides.10a Hence, we also loading of 2a cannot further improve the yield. Conversely, the
chose nickel compounds for the test. NiF2 was demonstrated yield markedly decreased compared with that employing 3
to be ineffective in THF at 80 °C. NiBr2 can catalyze the reac- equiv. of 2a (entries 9 and 10). Reducing the dosage of 2a to 1
tion, leading to the desired product in 33% yield (entries 2 equiv. resulted in only 14% product yield (entry 11). Screening
and 3). It was reported that Ni(dppe)Cl2 effectively catalyzed of reaction time and temperature proved that 12 h and 80 °C
the cross-coupling of aryl sulfoxides with arylzinc reagents.10a were suitable (entries 12–16). Examination of the loading
Hence, we examined the catalysis of nickel complexes with amount of catalyst showed that 10 mol% Ni(PEt3)2Br2 loading
bidentate phosphine ligands including Ni(dppe)Cl2, Ni(dppp) hardly increased the product yield of the reaction and
Cl2 and Ni(dppf)Cl2 (entries 4–6). Both Ni(dppe)Cl2 and Ni 2.5 mol% Ni(PEt3)2Br2 loading caused a marked decrease in
(dppf)Cl2 showed a similar catalytic capability to NiBr2 and Ni the yield (entries 17 and 18). Finally, the solvent effect was
(dppp)Cl2 exhibited a little higher catalytic activity than NiBr2. examined and the results showed that 1,4-dioxane, CPME
Next, we examined the catalysis of monodentate phosphine (cyclopentyl methyl ether), DCM (dichloromethane), and
coordinated nickel complexes such as Ni(PPh3)2Cl2 and Ni DMSO (dimethyl sulfoxide) were less effective than THF
(PEt3)2Br2. Ni(PEt3)2Br2 showed higher activity than the other (entries 19–22).
nickel compounds tested. The Ni(PEt3)2Br2-catalyzed reaction
Next, we examined the substrate scope under the optimized
gave the desired product in 66% yield (entries 7 and 8). It was conditions. The reaction of various aryl methyl sulfoxides with
reported that R–S(vO)–M formed in the reaction process can PhMe2SiZnCl (2a) was tested (Scheme 2). Both 1-methoxy-4-
isomerize to R–S–O–M and the latter is an oxidizing species.10a (methylsulfinyl)benzene and 1-(methylsulfinyl)-4-phenoxy-
benzene reacted smoothly with PhMe2SiZnCl, resulting in the
corresponding products 3b and 3c in 68% and 70% yields,
Table 1 Optimization of reaction conditionsa
respectively. The reaction of 5-(methylsulfinyl)benzo[d][1,3]
dioxole gave 3d in lower yield. This is ascribed to the electron-
donating effect of the substituents. The reaction of N-(4-
(methylsulfinyl)phenyl)acetamide and N-methyl-N-(4-(methyl-
sulfinyl)phenyl)acetamide formed the corresponding products
3e and 3f in almost the same yields. Surprisingly, the presence
of the acidic proton in N-(4-(methylsulfinyl)phenyl)acetamide
did not affect the reaction result. Sulfoxides with conjugated
aromatic systems and fused aromatic systems also showed a
good reactivity. Their reaction gave the products (3g–3k) in
51–80% yields. A range of aryl methyl sulfoxides with electron-
withdrawing groups such as CF3, RC(O) and COOR on the aro-
matic rings were demonstrated to react smoothly with
PhMe2SiZnCl. Their reaction gave the corresponding products
(3l–3r) in 65–89% yields. Steric hindrance of the ortho-substitu-
ent on the phenyl ring did not seem to affect the reaction (3q
vs. 3o and 3p). Several heteroaryl methyl sulfoxides including
Entry
Catalyst
X
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
—
NiF2
NiBr2
2
2
2
2
2
2
2
2
3
4
1
3
3
3
3
3
3
3
3
3
3
3
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
None
Trace
33
35
47
36
40
66
82
Ni(dppe)Cl2
Ni(dppp)Cl2
Ni(dppf)Cl2
Ni(PPh3)2Cl2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
Ni(PEt3)2Br2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
59
14
79c
68d
79e
80f
85g
85h
50i
68
2-(methylsulfinyl)pyridine,
2-(methylsulfinyl)-5-(tri-fluoro-
methyl)pyridine, 2-(methylsulfinyl)benzo[b]thiophene and 2-
(methylsulfinyl)benzofuran were also tested. Their reaction
gave the desired products (3s–3v) in 68–93% yields. In most
cases, the reaction of electron-poor (hetero)aryl methyl sulfox-
ides led to higher product yields (e.g. 3i vs. 3g, 3t vs. 3s).
The reaction of Ph2MeSiZnCl and Ph3SiZnCl with (hetero)
aryl methyl sulfoxides was also tested (Scheme 3). For example,
the reaction of Ph2MeSiZnCl with various aryl methyl sulfox-
ides afforded the desired products (4a–4e) in 50–80% yields.
Aryl methyl sulfoxides with electron-rich and electron-poor
aryl groups, extended aromatic systems, and heteroaromatic
systems can be used. The reaction of Ph3SiZnCl with isopropyl
4-(methylsulfinyl)benzoate or 2-(methylsulfinyl)pyridine gave
THF
THF
1,4-Dioxane
CPME
DCM
DMSO
27
31
Trace
a Unless otherwise specified, the reactions were performed on a
0.2 mmol scale; PhMe2SiZnCl was prepared by the reaction of
PhMe2SiLi with an equimolar amount of ZnCl2 in THF. b NMR yields
using C2H2Cl4 as an internal standard. c The reaction time was 14 h.
d The reaction time was 8 h. e The reaction time was 10 h. f The reaction
temperature was 60 °C. g The reaction temperature was 100 °C.
h 10 mol% Ni(PEt3)2Br2 was employed. i 2.5 mol% Ni(PEt3)2Br2 was
employed.
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Scheme 3 Reaction of (hetero)aryl methyl sulfoxides with Ph2MeSiZnCl
or Ph3SiZnCl. The reactions were carried out on a 0.2 mmol scale
according to the conditions indicated by the above equation; isolated
yields were reported.
Scheme 4 Reaction of alkyl phenyl sulfoxides with PhMe2SiZnCl.
Preliminary experiments to evaluate the plausible reaction
mechanism were performed. One equiv. of 1,1-diphenylethene
additive did not markedly affect the reaction result of methyl
phenyl sulfoxide with PhMe2SiZnCl under the standard con-
ditions (Scheme 5a). Hence, the reaction might not proceed
via a free radical process. The MeS− ion can be trapped by
adding BnBr to the reaction system of methyl phenyl sulfoxide
with PhMe2SiZnCl (Scheme 5b). The silylation product and dis-
ilane were also obtained in the same reaction. No benzyl
methyl sulfoxide was observed. These experimental results
showed that an oxidation–reduction reaction between MeS(O)
ZnCl and PhMe2SiZnCl did occur besides the normal cross-
coupling reaction. Intermolecular competition experiments
between 1-methanesulfinyl-4-methoxybenzene and 1-methane-
Scheme 2 Reaction
of
(hetero)aryl
methyl
sulfoxides
with
PhMe2SiZnCl. The reactions were carried out on a 0.2 mmol scale
according to the conditions indicated by the above equation; unless
otherwise specified, isolated yields were reported. aNMR yield using
C2H2Cl4 as an internal standard.
the corresponding products (5a and 5b) in 50% and 57% sulfinyl-4-trifluoromethylbenzene proved the latter to be more
yields, respectively. From the reaction results of different silyl- reactive (Scheme 5c). These results are also similar to those of
zinc reagents, it can be seen that the product yields of the reac- the reaction of aryl methyl sulfoxides with arylzinc reagents.10a
tion of PhMe2SiZnCl, Ph2MeSiZnCl, and Ph3SiZnCl with the Unexpectedly, we found that BnBr markedly accelerated the
same aryl methyl sulfoxides gradually decreased. This may be reaction. As seen in Scheme 5d, in the absence of BnBr, the
ascribed to the steric hindrance of the silylzinc reagents.
reaction of methyl phenyl sulfoxide with PhMe2SiZnCl led to
We also examined the reactivity of other alkyl phenyl sulfox- only a trace amount of the silylation product under the same
ides including ethylsulfinylbenzene, benzylsulfinylbenzene reaction conditions as shown in Scheme 5b. It was reported
and isobutylsulfinylbenzene (Scheme 4). The reaction of ethyl- that iPrI can accelerate the palladium-catalyzed cross-coupling
sulfinylbenzene and benzylsulfinylbenzene with PhMe2SiZnCl of arylmagnesium or arylzinc reagents with aryl bromides via
afforded the desired products in 70% and 61% yields, respect- a free radical process.13 In our reaction system, the 1,1-diphe-
ively. However, the reaction of isobutylsulfinylbenzene gave nylethene additive did not inhibit the accelerating effect of
only 28% yield of the product. This might be due to the steric BnBr (Scheme 5e). Hence, the reaction did not seem to be a
hindrance of the alkyl groups.
free radical process in the presence of BnBr. We guessed that
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tion conditions. This method is suitable for a wide scope of
sulfoxides including electron-rich and electron-poor aryl
methyl sulfoxides and heteroaryl methyl sulfoxides, and it tol-
erates a range of functional groups such as F, CF3, RO, C(O)R,
COOR, C(O)NEt2, MeC(O)NH, and MeC(O)N(Me) groups, pro-
viding the desired (hetero)arylsilanes in moderate to high
yields. PhMe2SiZnCl, Ph2MeSiZnCl and Ph3SiZnCl can be used
as nucleophiles. However, the product yields decreased with
the increase of the steric hindrance of the silylation reagents.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The financial support from the National Basic Research
Program of China (Grant No. 2015CB856600) is gratefully
acknowledged.
Notes and references
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