Mild synthesis of silyl ethers: Via potassium carbonate catalyzed reactions between alcohols and hydrosilanes

Article abstract of DOI:10.1039/c8ob00464a

A method has been developed for the silanolysis of alcohols using an abundant and non-corrosive base K₂CO₃ as a catalyst. Reactions between a variety of alcohols and hydrosilanes generate silyl ethers under mild conditions. The use of hydrosilanes leads to the formation of H₂ as the only byproduct thus avoiding the formation of stoichiometric strong acids. The mild conditions lead to a wide scope of possible alcohol substrates and good functional group tolerance. Selective alcohol silanolysis is also observed in the presence of reactive C-H bonds, lending this method for extensive use in protection group chemistry.

Full text of DOI:10.1039/c8ob00464a

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Mild Synthesis of Silyl Ethers via Potassium Carbonate Catalyzed Reactions between
Alcohols and Hydrosilanes
Nicholas A. DeLucia, Nivedita Das, and Aaron K. Vannucci*
University of South Carolina, Department of Chemistry and Biochemistry, Columbia, SC USA 29208
Abstract
A method has been developed for the silanolysis of alcohols using the abundant and non-
corrosive base K2CO3 as the catalyst. Reactions between a variety of alcohols and hydrosilanes generate
silyl ethers under mild conditions. The use of hydrosilanes lead to the formation of H2 as the only
byproduct thus avoiding the formation of stoichiometric strong acids. The mild conditions lead to a wide
scope of possible alcohol substrates and good functional group tolerance. Selective alcohol silanolysis is
also observed in the presence of reactive C–H bonds, lending this method for extensive use in protection
group chemistry.
Introduction
The protection of reactive functional groups, such as alcohols, amines, and thiols, is highly
prevalent throughout organic syntheses. In particular, the silylation of alcohols to form silyl ethers is an
important reaction in protecting group chemistry.1 Hydroxy group protection via Si–O bonds has also
extensively been used to alter the steric and electronic properties of substrates.1 Silyl ethers have also
played a large role in the development of organic semiconducting materials,2 been used in the synthesis of
medical compounds,3 and utilized as directing groups for C–H activation reactions.4, 5
Sterically bulky silyl groups have exhibited a desired balance between protecting group abilities
and ease of desilylation to reform the alcohol.1 Much of the initial reports on the formation of silyl ethers
with sterically bulky silyl groups focused on the treatment of alcohols with chlorosilanes, as shown in
Scheme 1 A.6 In addition to the moisture sensitivity of the chlorosilanes, this procedure requires an excess
of base, such a pyridine or imidazole to neutralize the HCl byproduct.7-9 The formation of HCl as a
byproduct can also prevent the use of acid sensitive alcohol substrates and limits the practicality of
scaling up the reaction to industrial levels. More recently, silanolysis of alcohols has focused on the use of
hydrosilanes in the general form R3SiH (Scheme 1 B). This procedure avoids the production of unwanted
acid, as H2 is the only byproduct generated. Hydrosilanes are also less sensitive to moisture compared to
chlorosilanes. Dehydrogenative silylation of alcohols with hydrosilanes, however, does require a catalyst
to promote the reaction.
Scheme 1. Comparison of silanolysis of alcohols
using chlorosilanes versus hydrosilanes.

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pyridine/
imidazole
A.
B.
O
O
O
O
+ R3Si Cl
+ R3Si H
+ HCl
R
R
H
H
R
R
SiR3
catalyst
+ H H
SiR3
A variety of catalysts have been explored for the formation of O–Si bonds from alcohols and
hydrosilanes.10-21 Transition metal catalysts have been used to successfully construct O–Si bonds.10-14
These catalysts, which range from rare earth metals such as ruthenium and iridium to earth abundant
metals such as nickel and titanium, are not commercially available and have exhibited limited reactivity
with tertiary alcohols and bulky hydrosilanes. Lewis acid catalysts, such as B(C6F5)3, are commercially
available and avoid use of transition metal catalysts.15-17 These Lewis acid catalysts have also shown the
ability to catalyze reactions involving secondary and tertiary alcohols and bulky hydrosilanes under mild
conditions. Lewis acid catalysts, however, are commonly incompatible with Lewis basic functional
groups such as pyridine. Alternatively, base-catalyzed dehydrosilylation of alcohols have also been
explored.18-20 Many of these base-catalyzed studies report harsh conditions such as high temperatures,
strong bases, and excess of additives to promote reactivity and are more commonly employed for
hydrosilylation reactions. A recent report, however, showed that the dehydrosilylation of alcohols with
hydrosilanes can be achieved under more mild conditions with a catalytic amount of NaOH.21 The
strength of the base catalyst, however, could limit functional group tolerance.21 There remains a need,
therefore, for a mild, catalytic route for the dehydrosilylation of alcohols with a wide functional group
tolerance.
The Oestreich group has shown that Cs2CO3 is an effective, mild catalyst for the dehydrogenative
coupling of diols with hydrosilanes.22 The authors showed that with 10 mol% base catalyst and excess
hydrosilane, the protection of 1,3- and 1,4-diols could be achieved at room temperature in THF. Utilizing
K2CO3 or Na2CO3 as the catalyst resulted in much lower reaction efficiency. In addition, alcohol
substrates beyond diols were not reported.
Herein we report the K2CO3 catalyzed dehydrosilylation of a variety of alcohol substrates. The
catalyst operates at conditions as mild as room temperature, and the relatively weak base catalyst is
compatible with a wide range of functional groups. Alcohols that are sensitive to Lewis acid and strong
Lewis base catalysts were successfully silylated. Substrates containing halogen, alkene, and alkyne
functional groups all resulted in high yields of dehydrosilylated products without observation of unwanted
side products from hydrosilylation. In addition, a variety of hydrosilanes were compatible with this
catalytic approach.
Results and Discussion
Reactions were prepared by adding the chosen silane to a minimal amount of a DMF:THF solvent
mixture (1:1, 1mL) containing the alcohol substrate and 20 mol% K2CO3 catalyst. A 1:1 DMF:THF ratio

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proved to be the optimized solvent over just DMF, just THF, or acetonitrile. Furthermore, a lesser
concentration of K2CO3 resulted in diminished yields, while a greater concentration of the base catalyst
did not improve yields beyond what is reported below. A small excess of silane was required to achieve
optimized yields, as has been previously observed.15, 21, 22 All solvents were purchased anhydrous and
used without further purification. All glassware and the K2CO3 catalyst were dried in an oven to remove
residue water. While water does not fully prevent product formation, the presence of water does result in
formation of a siloxane.15, 21 After the reaction, products were separated using flash chromatography and
purity was determined by NMR spectroscopy.
Figure 1 shows that this method efficiently dehydrosilylates phenolic alcohols. Triethylsilane
(TES) was chosen as a readily available and bulky silane that has not been extensively explored for
silylation reactions. The moderately bulky nature of TES balances the ease of silylation with the ability to
later remove the silane protecting group.15 Triethylsilylation of unsubstituted phenol occurred with a 95%
yield (entry 1). Phenolic alcohols with substitutions of both electron donating and withdrawing groups at
the para position (2c – 4c, 5) all resulted in excellent yields. Substrates with functional groups at the
ortho- and meta- positions also were successfully silylated with yields between 62% and 98%.
Figure 1. K2CO3 catalyzed triethylsilylation of phenolic
alcohols.
OH
OSi(Et)3
K2CO3 (20 mol%)
DMF:THF 1:1
R
+
HSi(Et)3
OH
R
+
H2
OH
OH
OH
OH
H3C
Br
MeO
O2N
2a o- 72%
3a o- 84%
4a o- 87%
1
95%
5
98%
2b
2c
3b
3c
o
4b
4c
m- 87%
p- 99%
m- 91%
p- 99%
m- 98%
p- 99%
Reactions performed at 60 C expect for substrates 2a-c which were
performed at 25 oC. 3 equiv of TES. 18 hrs.
With knowledge that K2CO3 is an efficient catalyst for the triethylsilylation of phenolic alcohols,
we looked to show that this procedure was applicable for a range of different silanes. The steric and
electronic character of silanes will have an effect on the reactivity. The ease of silylation and subsequent
deprotection of alcohols is dependent on the identity of the silane.1 Figure 2 illustrates that K2CO3 is a
compatible catalyst for various silylation reactions. Yields for the protection of phenol with silanes that
vary in steric bulk and electronic character were nearly quantitative with the exception of tri-isopropyl
silane. For product 8 excess silane dimer was observed in the mass spectrum, which is what likely led to
the lower (67%) yield.
Figure 2. K2CO3 catalyzed silylations of phenols.

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OH
OSiR3
K2CO3 (20 mol%)
DMF:THF 1:1
R
SiR3
+
R
+
H2
OSi(Et)3
OSi(Me)2Ph
OSi(Ph)3
1
6
7
95%
99%
99%
OSi(i-Pr)3
OSi(Me)2t-Bu
8 67%
9 99%
Reactions performed at 60 oC. 3 equiv of SiR3. 18 hrs.
To further explore the scope of the K2CO3 catalyzed dehydrosilylation of alcohols, a range of
alcohol substrates were examined. Both triethyl- and triphenylsilane (TPS) were used to achieve high
yields of the desired silyl ethers. Unsubstituted and 4-substituted benzyl alcohols were successfully
silylated (products 10 and 11). Substrates containing unsaturated carbon atoms, such as cinnamyl alcohol
(product 13) were also successfully dehydrosilylated without observing any hydrosilation products. This
catalytic procedure was also successful with both secondary (product 14) and primary (product 15)
aliphatic alcohols. Lewis acid sensitive groups such as pyridine (product 16) and furan (product 17) also
underwent efficient dehydrogenative silylation. The functional group tolerance of this catalytic approach
was further shown with the nearly quantitative dehydrogenative silylation of phthalimide (product 18),23
which is a substrate that has previously been shown to be unsuitable for Lewis base catalyzed silylation.24
To demonstrate the ability of this approach to selectively generate silyl ethers in the presence of
reactive C–H bonds, we performed the dehydrosilylation of 3-ethynylphenol. Facile hydrosilylation of
alkynes has been reported,25, 26 including a report on the base catalyzed hydrosilylation of alkynes.27 In
that recent report, an attempt to selectively silylate alcohols or alkynes led to only doubly silylated
product. Our K2CO3-catalyzed silylation reaction, however, was selective for the dehydrosilylation of
alcohol over the hydrosilylation of the alkyne moiety. The previously unreported (3-
ethynylphenoxy)triethylsilane product (19) was obtained in 81% isolated yield, with a minor amount of
the doubly silylated product being observed using mass spectrometry.
Table 1. K2CO3 Catalyzed Silylation of Alcohols.
%
Yield
Product
(oC)
OSi(Ph)3
25
99
10
11
60
60
98
99
OSi(Ph)3
12

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OSi(Et)3
25
94
99
99
13
14
15
60
60
60
60
83
56
16
17
60
60
99
81
18
19
3 equiv of TES/TPS. 18 hrs.
A mechanistic pathway for the base catalyzed dehydrogenative silylation of alcohols has
previously been prosposed.22, 28 The mechanism proceeds via the base catalyst interacting with silicon
atom to generate a more hydridic hydrosilane. This interaction promotes reactivity with alcohols to
produce H2 and form the Si–O bond. A similar mechanism has been assumed for NaOH catalyzed
silylation of alcohols.21 It is likely that the K2CO3 catalyzed silylation reactions in this report operate
under a related mechanism, but a detailed mechanism will require future studies. This study has shown,
however, that the relatively weak nature of the K2CO3 base compared to previous studies has led to
exceptional functional group tolerance and operates through dehydrogenative silylation, and avoids acidic
salt byproducts.
CONCLUSIONS
In summary, the K2CO3 catalyzed dehydrogenative silylation of a wide variety of alcohols has
been achieved. The catalyst is readily commercially available, operates under mild conditions, and
exhibits wide functional group tolerance. Substrates that had previously shown incompatibility with both
Lewis acid and base catalyzed reactions were successfully silylated with high yields. The catalyst also
exhibited selectivity for hydroxyl groups, allowing for protection chemistry during reactions involving C–
H bonds. Overall, the ease of use and breadth of reactivity makes this an appealing approach for the
formation of silyl ethers.
EXPERIMENTAL SECTION

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General Information
All starting materials were obtained from commercial sources and used without further
1
13
purification. Yields refer to isolated compounds through column chromatography. H and C
obtained using a Bruker Avance III-HD 300 MHz spectrometer in CDCl3;
NMR spectra were
chemical shifts are reported in parts
per million (ppm) relative to chloroform-d (7.27 ppm) for
1H NMR. For C NMR, chloroform-d (77.0 ppm, center peak). Multiplicity is indicated using
the following abbreviations: s (singlet), d (doublet), dd (doublet of doublets), t (triplet), q
(quartet), m (mulitplet). 29Si NMR spectra were obtained using a Bruker Avance III-HD 400
MHz spectrometer in CDCl3.
13
General procedure for the dehydrogenative silylation of alcohols: products 1-19
Reaction vessels were dried under vacuum and the reactions carried out under an inert
atmosphere using standard Schlenk line techniques. The silane (1.5 mmol) was added at room
solution of the alcohol (0.5 mmol) and K2CO3 (20 mol%, 12 mg) in DMF:
temperature to a
o
THF (1:1, 1 mL). After
stirring at 25 – 60 C for 18 h, the reaction mixture was filtered through
celite and the residue was analyzed with GC-MS. Further purification by column
chromatography using ethyl acetate:hexane 90:10 solvent mixture gave the isolated silyl ether
product. All products were characterized by the usual spectroscopic techniques or compared
with data reported in the literature.
AUTHOR INFORMATION
Corresponding Author
*vannucci@mailbox.sc.edu
ACKNOWLEDGMENTS
The support of the National Science Foundation through the EPSCoR R-II Track-2 grant number
1539150 is gratefully acknowledged.
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