Direct oxidation of the C(sp2)-C(sp3) bond from benzyltrimethylsilanes to phenols

Article abstract of DOI:10.1039/c7cc01868a

A novel pathway for direct conversion of benzylsilanes to phenols by oxidation with Na₂S₂O₈ and oxygen is efficiently developed under mild and neutral conditions. The reaction shows good functional group tolerance to afford phenols in moderate yields. The possible mechanism is proposed based on the isotopic labeling trials.

Full text of DOI:10.1039/c7cc01868a

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Direct oxidation of C(sp2)-C(sp3) bond from
benzyltrimethylsilanes to phenols
Received 00th January 20xx,
Accepted 00th January 20xx
Wei Li,ab Guolin Gao,a Yuan Gao,c Chao Yang*a and Wujiong Xia * a
DOI: 10.1039/x0xx00000x
www.rsc.org/
A novel pathway for direct conversion of benzylsilanes to phenols phenol (Scheme 1a). Benzaldehyde derivatives as precursors
by oxidation with Na2S2O8 and oxygen is efficiently developed which can be transformed to phenols by Dakin oxidation or
(a) Hock process
under mild and neutral conditions. The reaction shows good
functional group tolerance to afford phenols in moderate yields.
The possible mechanism is proposed based on the isotopic
labeling trials.
H2O2, H+
OH
R
R
(b) Baeyer-Villiger or Dakin oxidation
The development of novel methods for the preparation of
phenols draw interest of organic chemists because of great
importance of these compounds in natural products,1
pharmaceuticals,2 and polymers.3 Phenols are traditionally
prepared by displacement of other functional groups, such as
aryl halides,4 sulphonic acids,5 nitrogen derivatives.6 Although
some of the above methods have been applied in industry,
high temperature and strong base are ineluctable.
Consequently the drawbacks of the harsh reaction conditions
were overcome by virtue of metal-based catalytic systems,
such as Pd,7 Cu8 and others9. However, preparation of phenols
under metal-free conditions was more charming and practical
meaning, which was generally realized through C-C / C-Si bond
insertion reaction by oxygen atom of peroxyacids or peroxides.
Among which there are three common routes as shown in
scheme 1. The cumene hydroperoxide route namely hock
process.10 was the general phenol production technology
mostly, which is based on oxidation of cumene to cumene
hydroperoxide and then rearrangement in acidic medium to
O
Peracids, H+
OH
OH
or H2O2, OH-
R
R
(c)
Tamao-Fleming oxidation
X
Si
H2O2
R
R
or [M] and [O]
X = hydrogen, methyl, heteroatoms
(d) This work
Si
R1
R2
OH
Na2S2O8
O2
R3
R3
Scheme 1. Preparation of phenols via oxygen atom insertion
Baeyer-Villiger (BV) oxidation,11 the mechanism involves
nucleophilic attack on carbonyl carbon by peroxide ion and
aryl migrates onto the peroxygen, following hydrolysis
produced the expected phenol (Scheme 1b). Similarly, this
trick can also be applied in arylsilanes namely Tamao−Fleming
oxidation,12 in which the aryl group undergoes 1, 2-migration
from the silicon to the oxygen atom,13 or C-Si bond is activated
by virtue of metal-catalyzed reaction and then oxidized to
insert oxygen atom (Scheme 1c).14
Despite the above advances, room still exists for developing
new protocol for the synthesis of phenols under benign
conditions and with wider substrate scope. Herein, we present
an unprecedented formation of phenol through C(sp2)-C(sp3)
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bond cleavage using Na2S2O8 and oxygen as oxidants under benzene ring was not tolerated but to give eliminated product.
mild and neutral conditions (Scheme 1d).
It was noteworthy substituents located on benzyl position
didn’t restrain the formation of phenol, in contrast which
accelerated this
Table 1. Optimization of reaction conditionsa
Table 2. Synthesis of phenols from benzylsilanesa
Entry R1
R2
H
R3
Time (h) Yieldb(%)
Entry Oxidant
Solvent
CH3CN
Gas Time (h) Yieldb (%)
1
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
4-CH3O
9
57 (1a
64 (2a
33 (3a
46 (4a
71 (5a
56 (6a
70 (7a
45 (8a
70 (9a
0
)
)
)
)
)
)
)
)
)
1
Na2S2O8
Air
Air
Air
Air
Air
Air
O2
12
24
24
24
24
24
9
36
2
H
2-CH3O
9
2
(NH4)2S2O8 CH3CN
20
3c
4c
5
H
4-(CH3)2CH
4-(CH3)3C
2-CH3CH2O
2-(CH3)2CHO
2-CH3(CH2)2O
2-CH2=CHCH2O
2-PhO
20
20
12
9
3c
TBHQ
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
0
H
4
Oxone
Trace
0
H
5
BPO
6
H
6
m-CPBA
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Na2S2O8
Trace
57
7
H
12
18
18
24
12
7
8
H
8
CH3CN/H2O(10:1) O2
18
18
18
18
18
Trace
N.R
Trace
N.R
N.R
9
H
9
DMF
O2
O2
O2
O2
10
11
12d
13
14
15d
16
17
18
19
20
H
H
10
11
12
CH3OH
Dioxane
Toluene,
H
2-CH3O, 5-tBu
2-CH3O, 3,5-di-tBu 18
63 (10a
65 (11a
54 (12a
68 (13a
)
)
)
)
H
a Reaction conditions: substrate (0.2 mmol), Oxidant (1.5 equiv. 0.26 mmol),
Solvent, stirred at 55
b Isolated yields. c TBHQ = tert-Butyl hydroperoxide,
H
2-CH3O, 5-Cl
4-CH3O, 3-Br
12
9
H
℃.
CH3
CH3
nBu
Ph
4-Cl-Ph
2-CH3O, 5-(CH3)3Si 10
72 (2a
62 (1a
77 (2a
73 (1a
71 (1a
65 (1a
)
)
)
)
)
)
stored in decane. Oxone = Potassium monopersulfate triple salt; BPO =
4-CH3O
2-CH3O
4-CH3O
2-CH3O
4
benzoyl peroxide; m-CPBA = 3-Chloroperoxybenzoic acid.
4
4
The investigation was carried out on the reaction of (4-
12
3
methoxybenzyl)trimethylsilane
2-
℃, a temperature that S2O8 could be converted to SO4
1 with Na2S2O8 in MeCN at
·−
Ph 4-CH3O-Ph 4-CH3O
55
a Reaction conditions: substrate (0.2 mmol), Na2S2O8 (1.5 equiv, 0.3 mmol),
under atmosphere, which was initially assumed to hydroxylate
on the phenyl ring. However, 4-methoxyphenol was obtained
instead in 36% yield (Table 1, entry 1). Such a result reveals the
direct oxidative cleavage of C(sp2)-C(sp3) bond to provide an
easy access to phenols that encourages us to further explore
the reaction. Other oxidants exhibited little efficiency such as
c
CH3CN (2.0 mL), stirred at 55
℃
.
b Isolated yields. Na2S2O8 (3.0 equiv. 0.6
mmol), at 65
℃
.
d Na2S2O8 (3.0 equiv. 0.6 mmol)
reaction probably due to the stabilization of radical
intermediates (Entries 15-19, see mechanism discussion).
When the benzyl group was substituted with two groups, the
4-methoxyphenol also was obtained with 65% yield (Entry 20).
To reveal the source of phenolic oxygen, we performed the
oxidative cleavage reaction of 19 in the presence of H2O18
which gave 18O-unlabelled 2-methoxyphenol 2a and 4-
chlorobenzaldehyde (eq.1). Subsequently, we have performed
the reaction in the presence of 18O2 gas which afforded 18O-
labelled 2-methoxyphenol 2a based upon GCMS analysis (eq.2).
These experimental results indicate that the phenolic oxygen
might originate from O2.
(NH4)2S2O8, H2O2, Oxone and m-CPBA, BPO only oxidize
1 to 4-
methoxybenzaldehyde (Table 1, entries 2 - 6). It is noteworthy
oxygen can accelerate the reaction and produce phenol in 57%
yield (Table 1, entry 7). Various solvents such as CH3CN/H2O,
DMF, MeOH, dioxane and toluene were screened (Table 1,
entries 8 - 12) and the results showed that MeCN was most
suitable for this reaction owing to the fact that MeCN might
act as a nucleophile in assisting the C-Si bond cleavage.15
With the optimized conditions in hand, we applied this
strategy to investigate the scope under synergistic effect of
Na2S2O8 and oxygen. Use of benzylsilanes bearing an electron-
donating group on para- or ortho- benzene ring afforded the
corresponding products in moderate yields. Alkoxyl groups
showed more effective on this reaction (Entries 1, 2, 5 - 9),
whereas iso-propyl and tert-butyl led to decreased yields
(Entries 3 - 4), Benzylsilane bearing electron-neutron group
was inactive (Entry 10) and mostly recovered. Electron-
withdrawing groups such as Cl and Br also could be tolerated
in case of methoxyl group located in para- or ortho- position of
benzene ring (Entries 13-14). Interestingly trimethylsilyl on
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On the basis of all the results mentioned above, a possible
reaction pathway was proposed as depicted in Scheme 2.
Notes and references
‡ Footnotes relating to the main text should appear here. These
might include comments relevant to but not central to the
matter under discussion, limited experimental and spectral data,
and crystallographic data.
·−
Initially, SO4 is generated through hemolytic cleavage of
2-
S2O8 under heating.16 Benzylsilane
1 is oxidized to
·−
intermediate A stabilized by
single electron transfer (SET) which was then transformed to
β
-silicon effect17 by SO4 via the
1
(a) Z. Mao, W. Sun, L. Fu, H. Luo, D. Lai and L. Zhou,
Molecules., 2014, 19 5088; (b) T. Bunyapaiboonsri, S.
,
·−
benzyl radical
generates monosulfate anion
Following adsorption of O2 on
component combination radical
rearrangement causes cleavage of C(sp2)-C(sp3) bond and
affords peroxyl radical , which abstracts a hydrogen atom and
B
after desilyl process. Coupling of
, which is oxidized to
lead to formation of a three -
electron transfer
B and SO4
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,
this reaction, benzylsilane 21 was synthesized for the purpose
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.
In summary, we have developed a novel synthetic approach
to phenols by direct oxidation of benzyltrimethylsilanes using
Na2S2O8 and oxygen as the oxidant. This method was found to
be potential useful for the preparation of diphenols from
designed benzyltrimethylsilanes in combination with Baeyer-
Villiger reaction.
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We are grateful for the financial supports from China NSFC
(Nos. 21372055, 21472030 and 21672047), SKLUWRE (No.
2017DX03) and the Fundamental Research Funds for the
Central Universities (Grant No. HIT.BRETIV.201310).
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Direct oxidation of C(sp2)-C(sp3) bond from benzyltrimethylsilanes to phenols
Wei Li, Guolin Gao, Yuan Gao, Chao Yang* and Wujiong Xia *
A novel pathway for direct conversion of benzylsilanes to phenols by oxidation with Na2S2O8 and oxygen is efficiently developed under
mild and neutral conditions.
1