Silylative aromatization of: P -quinone methides under metal and solvent free conditions

Article abstract of DOI:10.1039/d1ra03193g

A base-mediated silylation reaction leading to benzyl silanes has been developed. Under transition-metal and solvent free conditions, the silylation of a wide array of p-quinone methides is achieved using a Cs2CO3 catalyst in yields up to 96%. Carboxylati

Full text of DOI:10.1039/d1ra03193g

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Silylative aromatization of p-quinone methides
under metal and solvent free conditions†
Cite this: RSC Adv., 2021, 11, 17860
b
a
Tingting Li,a Yuzhu Wu,a Wenzeng Duan
and Yudao Ma
*
*
Received 24th April 2021
Accepted 12th May 2021
A base-mediated silylation reaction leading to benzyl silanes has been developed. Under transition-metal
and solvent free conditions, the silylation of a wide array of p-quinone methides is achieved using
a Cs2CO3 catalyst in yields up to 96%. Carboxylation of the as-obtained organosilane with gaseous CO2
provides a new synthetic protocol for the preparation of carboxylic acid.
DOI: 10.1039/d1ra03193g
rsc.li/rsc-advances
reactions,5 ring-opening C(sp3)–Si bond-forming reactions,6
deuorosilylation of uoroalkenes,7 carbosilylation of unsatu-
rated hydrocarbons,8 silylation of aldehydes9 and conjugate silyl
addition to unsaturated carbonyl compounds10 and dienes,11
etc. Among these available approaches to organosilicon
compounds, silyl transfer from silylboranes (e.g., PhMe2Si-
Bpin)12 to unsaturated acceptors, especially transition metal-
free organocatalytic silylation is becoming increasingly attrac-
tive to organic chemists (Scheme 1a).13
With the development of the Si–B bond activation,14 Tortosa
and co-workers rstly reported an efficient and general cop-
per(I)-catalyzed protocol for the addition of nucleophilic silicon
species to p-quinone methides (Scheme 1b).15 Due to the low-
abundance and high toxicity of the transition metal, the
development of environmentally friendly and transition metal-
free methods for chemical biology studies and pharmaceutical
synthesis has been highly desirable. As part of our continuing
efforts in metal-free catalytic C–Si bond-formations,16 we herein
disclose a new entry of Cs2CO3-catalyzed transition metal-free
silylative aromatization of p-quinone methides.
Introduction
Organosilicon compounds are of particular interest owing to
their plentiful applications in materials science and pharma-
ceutical chemistry.1,2 Organosilanes are versatile intermediates
in organic synthesis,3 since the C–Si bond can be readily
transformed into C–O bonds and C–C bonds. Thus, various
synthetic methods for obtaining organosilicon compounds
have been developed, including silyl addition to carboxylate
derivatives,4
radical-mediated
C(sp3)–Si
cross-coupling
As a further benet, the resulting benzylic silane acts as bench-
stable carbanion for preparation of the corresponding carboxylic
acid through addition of gaseous CO2 under mild reaction
conditions. This synthetic protocol is very attractive not only for
the utilization of CO2, an inexpensive and sustainable C1 source,
but also for decreasing the CO2, the most signicant long-live
greenhouse gas in the atmosphere. To the best of our knowl-
edge, the use of dibenzylic anion from a silane for the addition
reaction of carbon dioxide has not previously been reported.
Scheme 1 Catalytic nucleophilic addition to unsaturated acceptors.
Results and discussion
It is well established that water as an additive has a benecial
effect on organocatalytic silyl transfer reaction.13,16 Thus, we
commenced the study of silylative aromatization reaction by
aDepartment of Chemistry, Shandong University, Shanda South Road No. 27, Jinan
250100, P. R. China. E-mail: ydma@sdu.edu.cn
bSchool of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng
using
4-benzylidene-2,6-di-tert-butylcyclohexa-2,5-dien-1-one
(1a) as the model substrate, Me2PhSi-Bpin as the silylating
reagent and water as the additive (Table 1). As reported by
Tortosa,15 using THF as the solvent, the transition metal-free
252000, P. R. China. E-mail: duanwenzeng@lcu.edu.cn
† Electronic supplementary information (ESI) available: Experiment procedures,
and copies of NMR spectra. See DOI: 10.1039/d1ra03193g
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silyl transfer reactions did not take place to any appreciable suitable reaction temperature for further investigation. Again,
extent aer 24 hours (entries 1–3).
the impact of water at 80 ꢀC was tested, and 0.5 equiv. of water
Disappointed by these results, we moved attention to our was found to be more competitive (entries 10–11). To improve
previous research ndings,17 in which azidative aromatization the yield, we then examined the inuence of the base with
of p-quinone methides was achieved with cesium carbonate as a particular emphasis on the effect of escorting counterion. It
a catalyst and water as an effective additive under transition was found that carbonate was superior to trimethylsilanolate,
metal and solvent free conditions. We anticipated a solvent-free uoride, acetate, tert-butoxide as well as DBU, thus indicating
reaction condition might be a viable option so as to compensate that these variables was incompetent to improve the yield
for the lack of reactivity. We therefore decided to run this (entries 12–17). Notably, unreacted substrate 1a was observed in
1
reaction under solvent-free conditions, in an attempt to accel- the H NMR spectrum of the crude product, but the silylating
erate reaction rate by means of efficient and environmentally reagent (Me2PhSi-Bpin) could not be found in all the reaction
friendly procedures. Although the silylation was sluggish, the mixtures at higher reaction temperature (entries 5–17). These
desired product 3a was obtained in 14% yield aer 24 hours at results showed that the adding quantity of Me2PhSi-Bpin did
room temperature (entry 4). The low yield could be attribute to not meet the needs of the reaction due to its high reactivity and
the low reaction temperature because most of the substrate 1a low stability, so more silaborane reagent might be needed to ll
as a yellow solid remained unchanged.
in the gaps resulted from thermal decomposition. As expected,
In line with our expectation, the silyl addition reaction pro- complete conversion of 1a was achieved in 95% yield by
ceeded smoothly providing the product 3a in 55% yield by increasing the amount of 2 from 1.5 to 2.5 equiv. (entry 18).
heating the reaction mixture to 60 ꢀC for 24 h (entry 5). As Furthermore, two different disilanes were also tested under the
a comparative illustration, the efficiency of water to promote optimized reaction conditions (Scheme 2). Unfortunately, both
addition was evident as a 47% yield was obtained in the absence hexamethyldisilane and hexaphenyldisilane failed to give the
of water (entry 6). Encouragingly, the yield was increased to 67% desired products.
by raising the reaction temperature to 80 ꢀC (entries 7–8).
With the optimized reaction conditions in hand, the
However, a further increase in the reaction temperature proved substrate scope of the silylative aromatization of p-quinone
ꢀ
to be almost ineffective (entry 9), so 80 C was chosen as the methides was investigated (Table 2). A wide range of p-quinone
methides bearing electron-decient groups at different posi-
tions on the phenyl ring were well compatible with the reaction
conditions, and afforded the silyl transfer products in 79–96%
yields (3h–3l). However, the substrate containing an electron-
donating group at the benzene ring such as methyl and
methoxy proved to be less reactive, so the reaction time had to
be prolonged to 48 h (3b–3g). Similarly, the p-quinone methide
having a naphthalene ring was not a good substrate and
provided the corresponding product 3m in lower yield (78%). It
was found that an electron-rich heteroaromatic ring such as
thiophene was also amenable to the aforementioned protocol,
and gave the desired product 3n in 84% yield. In contrast, an
electron-decient heteroaromatic ring like pyridine was very
suitable for the reaction and the silyl addition product 3o was
obtained in 83% yield, even though the reaction was conducted
at 40 ꢀC for 24 h. In line with our expectation, the scope was also
extended to aliphatic-substituted p-quinone methide, which
furnished the desired product in good yield (83%).
Table 1 Optimization of reaction conditions
Entry
T/ꢀC
Base (mol%)
Additive (equiv.)
Yielda (%)
1b
2c
3c
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18d
rt
rt
rt
rt
NaOt-Bu (20)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
Cs2CO3 (5)
K2CO3 (5)
KOSi(CH3)3 (5)
KF (5)
MeOH (4)
H2O (1)
—
H2O (1)
H2O (1)
—
H2O (1)
H2O (1)
H2O (1)
H2O (0.5)
H2O (2)
H2O (0.5)
H2O (0.5)
H2O (0.5)
H2O (0.5)
H2O (0.5)
H2O (0.5)
H2O (0.5)
—
<5
<5
14
55
47
63
67
69
73
71
70
64
57
67
62
51
95
60
60
70
80
90
80
80
80
80
80
80
80
80
80
A tentative catalytic cycle for the silylative aromatization of p-
quinone methides is depicted in Scheme 3. The formation of
benzylic silanes is assumed to involve an active complex A, the
adduct of Cs2CO3 with Me2PhSi-Bpin, which undergoes
KOAc (5)
KOt-Bu (5)
DBU (5)
Cs2CO3 (5)
a
Yields were determined by 1H NMR analysis. b Reaction conditions: 1a
(0.2 mmol), 2 (0.22 mmol), NaOt-Bu (20 mol%), MeOH (0.8 mmol), THF
c
(0.1 M), 12 h. Reaction conditions: 1a (0.1 mmol), 2 (0.15 mmol),
Cs2CO3 (5 mol%), THF (0.1 M). d 2 (0.25 mmol) used.
Scheme 2 Screening of disilanes.
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Table 2 Substrate scopea,b
Scheme
4
Scale-up experiment and synthetic application of
compound 3a.
addition of the exocyclic double bond of p-quinone methide 1 to
generate the intermediates B and C. The intermediates B is then
protonated by H2O to release the nal product 3, and by-product
D which involves another circle to form E. Such a catalytic cycle
explains why the mole ratio between 1 and H2O is 2 : 1 under
the optimized reaction conditions.
To demonstrate the synthetic utilities of this catalytic
process, a gram-scale reaction was performed under the stan-
dard reaction conditions. As anticipated, the reaction was
completed in 36 h and afforded the corresponding benzylic
silane 3a in 93% yield (Scheme 4a). Furthermore, organosilane
3a as a bench-stable carbanion enabled the incorporation of
gaseous CO2 into a value-added carboxylic acid under mild
reaction conditions (Scheme 4b).
a
Reaction conditions: 1 (0.2 mmol), 2 (2.5 equiv.), Cs2CO3 (5 mol%),
b
c
H2O (0.5 equiv.), 80 ꢀC, 24 h. Yield of isolated 3. Reaction time was
d
48 h. 40 ꢀC, 24 h.
Experimental
General information
Commercially available reagents were used without further
purication unless otherwise noted. Solvents were reagent
grade and puried by standard techniques. Purication of the
reaction products was carried out by chromatography on silica
1
gel (200–300 mesh). H NMR and 13C NMR spectra were recor-
ded in CDCl3 on a Bruker AVANCE-400 or Bruker AVANCE-500
spectrometer at 298 K. Mass spectra were recorded on an Agi-
lent Technologies 6510 Q-Tof LC/MS. All melting points were
recorded on a melting point apparatus and were uncorrected.
All reactions were monitored by TLC with silica gel-coated
plates and visualized with a UV light at 254 nm.
General procedure for synthesis of dibenzylic silanes (3)
To an oven-dried vial was charged 1.8 ml H2O, Cs2CO3 (3.2 mg,
0.01 mmol), the indicated para-quinone methide 118 (0.2 mmol)
and a stir bar. Me2PhSi-Bpin (145 ml, 0.5 mmol) was taken under
an N2 atmosphere and added into the vial by syringe. Aer the
mixture was stirred under 80 ꢀC for 24 h or 48 h, the mixture was
diluted by petroleum ether and a few drops of CH3COOH was
added. The solvent was removed in vacuum and the crude
Scheme 3 Proposed catalytic cycle.
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product was puried by ash column chromatography (petro-
leum ether/chloroform ¼ 5 : 1–1 : 2) to afford the correspond-
ing product 3.
Acknowledgements
Financial support from the Shandong Province Natural Science
Foundation (ZR2019MB044) is gratefully acknowledged.
General procedure for the gram-scale synthesis of dibenzylic
silanes (3a)
Notes and references
To an oven-dried vial was charged 22.5 ml H2O, Cs2CO3 (40.8 mg,
0.125 mmol), the indicated para-quinone methide 1a (0.74 g, 2.5
mmol) and a stir bar. Me2PhSi-Bpin (1.8 ml, 6.25 mmol) was
taken under an N2 atmosphere and added into the vial by
syringe. Aer the mixture was stirred under 80 ꢀC for 36 h, the
mixture was diluted by petroleum ether and a few drops of
CH3COOH was added. The solvent was removed in vacuum and
the crude product was puried by ash column chromatog-
raphy (petroleum ether/chloroform ¼ 5 : 1) to afford the corre-
sponding product 3a (998 mg, 93% yield).
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ꢀ
Aer the displacement with CO2 gas, 3a (86 mg, 0.2 mmol, 1.0
equiv.) dissolved in dry DMF (4.0 ml) was added to the vial. The
resulting reaction mixture was stirred at rt for 48 h under CO2
atmosphere (1 atm, balloon). Water was added to the reaction
mixture followed by the acidication (pH ¼ ca. 2) using 1 M
HCl. The mixture was extracted with dichloromethane for 3
times, then the organic layers were combined and washed with
water for 3 times, nally dried over anhydrous MgSO4. The
solvent was then removed under reduced pressure and the
residue was puried by ash column chromatography (petro-
leum ether/ethyl acetate ¼ 10 : 1–5 : 1) to afford the corre-
sponding product 4 (37 mg, 54% yield).
Conclusions
In conclusion, we have developed a base-mediated silylation
reaction which can be effectively performed on a gram scale.
The present study exhibits that the silylative aromatization of
a wide array of p-quinone methides is achieved by Cs2CO3
catalyst without the needs for any harmful organic solvents and
an air- and moisture-sensitive copper(I) salt. To the best of our
knowledge, this is the rst example which enables the silyl
transfer from silylborane (e.g., PhMe2Si-Bpin) to unsaturated
acceptors under transition metal and solvent-free conditions.
Furthermore, carboxylation of the as-obtained organosilane
with gaseous CO2 provides a new synthetic protocol for prepa-
ration of a value-added carboxylic acid. The study of an asym-
metric variant of this silylative aromatization is in progress.
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