Direct Dehydrogenative Coupling of Alcohols with Hydrosilanes Promoted by Sodium tri( sec -butyl)borohydride

: Alkoxysilanes ﬁnd application in many areas of chemistry ranging from research-scale organic synthesis to multi-ton production of materials. Classically, they are obtained in stoichiometric reaction of alcoholysis of chlorosilanes, however, recent years brought development in the ﬁeld of direct dehydrogenative coupling of hydrosilanes with alcohols, which is a more atom-economic and benign alternative to the former process. In this paper, we report the use of sodium tri( sec -butyl)borohydride as a convenient promoter of this reaction. Exemplary syntheses carried out under mild conditions and without additional solvents, followed by very easy work-up procedure, show excellent potential for application of so devised catalytic system.


Introduction
Alkoxysilanes constitute a group of compounds widely used in materials science as precursors of polymers [1], silica-based mesoporous materials [2][3][4], and surface coatings [5,6], in particular as silane coupling agents [7][8][9]. In organic chemistry, alkoxysilanes are often referred to as silyl ethers and are a widely used class of protecting groups for alcohols [10,11], while silyl ethers of enolates are a set of convenient nucleophilic reagents [12].
Our interest in this reaction stems from the observation made during a previous study on trialkylborohydride-catalyzed hydrosilylation, especially as triethylborohydrides are widely used as additives in various other catalytic systems [37]. Then, we noticed that attempts to hydrosilylate 2-allyloxyethanol were unsuccessful, leading only to complete transformation of hydroto alkoxysilanes (Scheme 1). Scheme 1. The reaction of phenylsilane with 2-allyloxyethanol in the presence of sodium triethylborohydride.
An interesting point was if this side reaction could be further exploited and applied to a wider range of silanes and alcohols as possible method in organic synthesis.
The initial trial with sodium triethylborohydride (entry 1) turned out to be not as successful as the ones with the other trialkylborohydrides among which sodium tri(sec-butyl)borohydride has proven to be the best, giving complete conversion of 2 even in 1 h (entry 10). Further, we decided to use no solvent, as at room temperature the reaction carried out in solution was slower (entries 5 vs. 7 & 8).
In the above-optimized conditions, we investigated the scope of this reaction, using various aliphatic and aromatic alcohols as well as selected primary, secondary and tertiary silanes. The results are presented in Table 2. An interesting point was if this side reaction could be further exploited and applied to a wider range of silanes and alcohols as possible method in organic synthesis.

Results and Discussion
At first, the usability of different alkali metal trialkylborohydrides was examined in a model reaction of benzyl alcohol 1 with dimethylphenylsilane 2 (Table 1). This reaction leads to one possible alkoxysilane 3. Table 1 summarizes the results of optimization ran on 1-mmol scale. An interesting point was if this side reaction could be further exploited and applied to a wider range of silanes and alcohols as possible method in organic synthesis.
The initial trial with sodium triethylborohydride (entry 1) turned out to be not as successful as the ones with the other trialkylborohydrides among which sodium tri(sec-butyl)borohydride has proven to be the best, giving complete conversion of 2 even in 1 h (entry 10). Further, we decided to use no solvent, as at room temperature the reaction carried out in solution was slower (entries 5 vs. 7 & 8).
The initial trial with sodium triethylborohydride (entry 1) turned out to be not as successful as the ones with the other trialkylborohydrides among which sodium tri(sec-butyl)borohydride has proven to be the best, giving complete conversion of 2 even in 1 h (entry 10). Further, we decided to use no solvent, as at room temperature the reaction carried out in solution was slower (entries 5 vs. 7 & 8).
In the above-optimized conditions, we investigated the scope of this reaction, using various aliphatic and aromatic alcohols as well as selected primary, secondary and tertiary silanes. The results are presented in Table 2.                  As follows from the results presented in Table 2, all used silanes and alcohols can be efficiently coupled with the aid of sodium tri(sec-butyl)borohydride, however, some substrates require either higher reaction temperatures or prolonged reaction time, which indicates a visible steric effect mostly of the silane. Simple aliphatic alcohols such as ethanol and methanol reacted efficiently with diphenylsilane and dimethylphenylsilane to give the corresponding alkoxysilanes in good yields (86-96%) in a few minutes at room temperature ( Table 2, entry 2-3, 10), even with reduced NaHB(s-Bu)3 loading ( Table 2, entry 10), however, silylation of ethanol by more sterically hindered methyldiphenylsilane required a longer reaction time (48 h). Similarly, diphenylmethylsilane seems to be less reactive in the reactions with benzyl alcohol derivatives than dimethyphenylsilane. Allyl-( Table 2, entries 4, 16, 18) and propargyl alcohol derivatives (Table 2, entry 9) can be efficiently Osilylated by primary and tertiary aromatic silanes with excellent chemoselectivity, which is surprising in view of our recent reports on the reactivity of allyl glycidyl ether and terminal alkynes in sodium triethylborohydride-mediated hydrosilylation [37] or dehydrogenative silylation reactions [38]. All compounds were isolated by extremely simple protocol employing precipitation of the remainders of catalyst with hexane, filtration through a 0.45 µm syringe filter and evaporation of the solvent to give very high yields (up to 99%, average 91%). The structures of the products were confirmed by the 1 H and 13 C NMR spectra of isolated compounds (see Supporting Information). The limitation of this reaction system concerns its inapplicability to trialkylsilanes, such as triisopropylsilane, in whose presence a conversion of 67% was observed only in the reaction with methanol after 72 h of heating at 65 °C ( Table 2, entry 19). Other trialkylsilanes e. g. triethylsilane or (t-butyl)dimethylsilane appear to be unreactive in the reactions with aliphatic and aromatic alcohols in the conditions applied.
In general, this protocol provides very good chemoselectivity towards dehydrogenative coupling of alcohol with silane and no other processes were observed. Halogen substituents were also preserved, which is important from the point of view of possible subsequent functionalization. What is also remarkable, the nature of generated active catalyst must be milder than an alkoxide, as potentially dangerous redistribution of phenylsilane with evolution of gaseous pyrophoric SiH4 (Scheme 2) was not observed. This reaction was reported to occur in basic conditions [39,40], especially in the presence of alkoxides. On the basis of this observation, we postulate that tri(sec-butyl)borane, initially generated in the reaction of sodium tri(sec-butyl)borohydride with an alcohol, is formed as adduct and aids the catalytic reaction analogous to the one proposed by Schowen [41] in the form presented as example in Scheme 3. Another advantage of this system is the lack of external alkoxide which could lower the effective yield by contamination of products with other alkoxysilanes resulting from its presence. As follows from the results presented in Table 2, all used silanes and alcohols can be efficiently coupled with the aid of sodium tri(sec-butyl)borohydride, however, some substrates require either higher reaction temperatures or prolonged reaction time, which indicates a visible steric effect mostly of the silane. Simple aliphatic alcohols such as ethanol and methanol reacted efficiently with diphenylsilane and dimethylphenylsilane to give the corresponding alkoxysilanes in good yields (86-96%) in a few minutes at room temperature ( Table 2, entry 2-3, 10), even with reduced NaHB(s-Bu)3 loading ( Table 2, entry 10), however, silylation of ethanol by more sterically hindered methyldiphenylsilane required a longer reaction time (48 h). Similarly, diphenylmethylsilane seems to be less reactive in the reactions with benzyl alcohol derivatives than dimethyphenylsilane. Allyl-( Table 2, entries 4, 16, 18) and propargyl alcohol derivatives (Table 2, entry 9) can be efficiently Osilylated by primary and tertiary aromatic silanes with excellent chemoselectivity, which is surprising in view of our recent reports on the reactivity of allyl glycidyl ether and terminal alkynes in sodium triethylborohydride-mediated hydrosilylation [37] or dehydrogenative silylation reactions [38]. All compounds were isolated by extremely simple protocol employing precipitation of the remainders of catalyst with hexane, filtration through a 0.45 µm syringe filter and evaporation of the solvent to give very high yields (up to 99%, average 91%). The structures of the products were confirmed by the 1 H and 13 C NMR spectra of isolated compounds (see Supporting Information). The limitation of this reaction system concerns its inapplicability to trialkylsilanes, such as triisopropylsilane, in whose presence a conversion of 67% was observed only in the reaction with methanol after 72 h of heating at 65 °C ( Table 2, entry 19). Other trialkylsilanes e. g. triethylsilane or (t-butyl)dimethylsilane appear to be unreactive in the reactions with aliphatic and aromatic alcohols in the conditions applied.
In general, this protocol provides very good chemoselectivity towards dehydrogenative coupling of alcohol with silane and no other processes were observed. Halogen substituents were also preserved, which is important from the point of view of possible subsequent functionalization. What is also remarkable, the nature of generated active catalyst must be milder than an alkoxide, as potentially dangerous redistribution of phenylsilane with evolution of gaseous pyrophoric SiH4 (Scheme 2) was not observed. This reaction was reported to occur in basic conditions [39,40], especially in the presence of alkoxides. On the basis of this observation, we postulate that tri(sec-butyl)borane, initially generated in the reaction of sodium tri(sec-butyl)borohydride with an alcohol, is formed as adduct and aids the catalytic reaction analogous to the one proposed by Schowen [41] in the form presented as example in Scheme 3. Another advantage of this system is the lack of external alkoxide which could lower the effective yield by contamination of products with other alkoxysilanes resulting from its presence. As follows from the results presented in Table 2, all used silanes and alcohols can be efficiently coupled with the aid of sodium tri(sec-butyl)borohydride, however, some substrates require either higher reaction temperatures or prolonged reaction time, which indicates a visible steric effect mostly of the silane. Simple aliphatic alcohols such as ethanol and methanol reacted efficiently with diphenylsilane and dimethylphenylsilane to give the corresponding alkoxysilanes in good yields (86-96%) in a few minutes at room temperature ( Table 2, entry 2-3, 10), even with reduced NaHB(s-Bu) 3 loading ( Table 2, entry 10), however, silylation of ethanol by more sterically hindered methyldiphenylsilane required a longer reaction time (48 h). Similarly, diphenylmethylsilane seems to be less reactive in the reactions with benzyl alcohol derivatives than dimethyphenylsilane. Allyl- (Table 2, entries 4, 16, 18) and propargyl alcohol derivatives (Table 2, entry 9) can be efficiently O-silylated by primary and tertiary aromatic silanes with excellent chemoselectivity, which is surprising in view of our recent reports on the reactivity of allyl glycidyl ether and terminal alkynes in sodium triethylborohydride-mediated hydrosilylation [37] or dehydrogenative silylation reactions [38]. All compounds were isolated by extremely simple protocol employing precipitation of the remainders of catalyst with hexane, filtration through a 0.45 µm syringe filter and evaporation of the solvent to give very high yields (up to 99%, average 91%). The structures of the products were confirmed by the 1 H and 13 C NMR spectra of isolated compounds (see Supporting Information). The limitation of this reaction system concerns its inapplicability to trialkylsilanes, such as triisopropylsilane, in whose presence a conversion of 67% was observed only in the reaction with methanol after 72 h of heating at 65 • C ( Table 2, entry 19). Other trialkylsilanes e. g. triethylsilane or (t-butyl)dimethylsilane appear to be unreactive in the reactions with aliphatic and aromatic alcohols in the conditions applied.
In general, this protocol provides very good chemoselectivity towards dehydrogenative coupling of alcohol with silane and no other processes were observed. Halogen substituents were also preserved, which is important from the point of view of possible subsequent functionalization. What is also remarkable, the nature of generated active catalyst must be milder than an alkoxide, as potentially dangerous redistribution of phenylsilane with evolution of gaseous pyrophoric SiH 4 (Scheme 2) was not observed. This reaction was reported to occur in basic conditions [39,40], especially in the presence of alkoxides. As follows from the results presented in Table 2, all used silanes and alcohols can be efficiently coupled with the aid of sodium tri(sec-butyl)borohydride, however, some substrates require either higher reaction temperatures or prolonged reaction time, which indicates a visible steric effect mostly of the silane. Simple aliphatic alcohols such as ethanol and methanol reacted efficiently with diphenylsilane and dimethylphenylsilane to give the corresponding alkoxysilanes in good yields (86-96%) in a few minutes at room temperature ( Table 2, entry 2-3, 10), even with reduced NaHB(s-Bu)3 loading ( Table 2, entry 10), however, silylation of ethanol by more sterically hindered methyldiphenylsilane required a longer reaction time (48 h). Similarly, diphenylmethylsilane seems to be less reactive in the reactions with benzyl alcohol derivatives than dimethyphenylsilane. Allyl-( Table 2, entries 4, 16, 18) and propargyl alcohol derivatives (Table 2, entry 9) can be efficiently Osilylated by primary and tertiary aromatic silanes with excellent chemoselectivity, which is surprising in view of our recent reports on the reactivity of allyl glycidyl ether and terminal alkynes in sodium triethylborohydride-mediated hydrosilylation [37] or dehydrogenative silylation reactions [38]. All compounds were isolated by extremely simple protocol employing precipitation of the remainders of catalyst with hexane, filtration through a 0.45 µm syringe filter and evaporation of the solvent to give very high yields (up to 99%, average 91%). The structures of the products were confirmed by the 1 H and 13 C NMR spectra of isolated compounds (see Supporting Information). The limitation of this reaction system concerns its inapplicability to trialkylsilanes, such as triisopropylsilane, in whose presence a conversion of 67% was observed only in the reaction with methanol after 72 h of heating at 65 °C ( Table 2, entry 19). Other trialkylsilanes e. g. triethylsilane or (t-butyl)dimethylsilane appear to be unreactive in the reactions with aliphatic and aromatic alcohols in the conditions applied.
In general, this protocol provides very good chemoselectivity towards dehydrogenative coupling of alcohol with silane and no other processes were observed. Halogen substituents were also preserved, which is important from the point of view of possible subsequent functionalization. What is also remarkable, the nature of generated active catalyst must be milder than an alkoxide, as potentially dangerous redistribution of phenylsilane with evolution of gaseous pyrophoric SiH4 (Scheme 2) was not observed. This reaction was reported to occur in basic conditions [39,40], especially in the presence of alkoxides. On the basis of this observation, we postulate that tri(sec-butyl)borane, initially generated in the reaction of sodium tri(sec-butyl)borohydride with an alcohol, is formed as adduct and aids the catalytic reaction analogous to the one proposed by Schowen [41] in the form presented as example in Scheme 3. Another advantage of this system is the lack of external alkoxide which could lower the effective yield by contamination of products with other alkoxysilanes resulting from its presence. On the basis of this observation, we postulate that tri(sec-butyl)borane, initially generated in the reaction of sodium tri(sec-butyl)borohydride with an alcohol, is formed as adduct and aids the catalytic reaction analogous to the one proposed by Schowen [41] in the form presented as example in Scheme 3. Another advantage of this system is the lack of external alkoxide which could lower the effective yield by contamination of products with other alkoxysilanes resulting from its presence. Scheme 3. Proposed mechanism of tri(sec-butyl)borohydride-catalyzed direct dehydrogenative coupling of dimethylphenylsilane with methanol.
It seems very unlikely that any kind of hydride is effectively engaged in this catalysis in the presence of great excess of alcohol, contrary to what was proposed by Panda [32].

General Remarks
All reactions were performed under inert atmosphere. Oxygen does not seem to influence the performance, however, moisture is decreasing reactivity. Solvents were purified by distillation over sodium/benzophenone. Reagents (Sigma-Aldrich/Merck) were used as supplied, however, methanol, ethanol and benzyl alcohol were stored over molecular sieves.
Gas chromatography was performed on a Bruker Scion 436-GC with a 30 m Agilent VF5-ms 0.53 mm Megabore column and a thermal conductivity (TCD) detector. The temperature program was as follows: 60 °C (3 min), 20 °C/min, 280 °C (20 min). NMR spectra were recorded on a Bruker Fourier 300 spectrometer and referenced to the solvent residual peak.

Dehydrogenative Coupling of Alcohols with Silanes
In a typical reaction, 1 mmol of silane, and 1 mmol of alcohol were placed in a Schlenk bomb flask dried and filled with argon. Next, 0.1 mL of 1M solution of sodium tri(sec-butyl)borohydride in THF was carefully added. Reaction vessel was closed and placed in a preheated oil bath at given temperature and stirred. Samples were taken at time intervals and analyzed using gas chromatography. After detection of complete conversion of substrates, reaction mixture was cooled down, dosed with approximately 3 mL of hexane, and left for 15 min to precipitate. The suspension was filtered and the resulting clear solution was evaporated to yield pure alkoxysilane.

Conclusions
Direct dehydrogenative coupling of alcohols with hydrosilanes can be efficiently promoted by sodium tri(sec-butyl)borohydride in solvent-free conditions, which enable almost quantitative isolation of desired alkoxysilane product.
Supplementary Materials: Spectral data of products are available online at www.mdpi.com/xxx/s1. 1. Analytical data of isolated products, 2. Spectra of products.

Conflicts of Interest:
The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. It seems very unlikely that any kind of hydride is effectively engaged in this catalysis in the presence of great excess of alcohol, contrary to what was proposed by Panda [32].

General Remarks
All reactions were performed under inert atmosphere. Oxygen does not seem to influence the performance, however, moisture is decreasing reactivity. Solvents were purified by distillation over sodium/benzophenone. Reagents (Sigma-Aldrich/Merck) were used as supplied, however, methanol, ethanol and benzyl alcohol were stored over molecular sieves.
Gas chromatography was performed on a Bruker Scion 436-GC with a 30 m Agilent VF5-ms 0.53 mm Megabore column and a thermal conductivity (TCD) detector. The temperature program was as follows: 60 • C (3 min), 20 • C/min, 280 • C (20 min). NMR spectra were recorded on a Bruker Fourier 300 spectrometer and referenced to the solvent residual peak.

Dehydrogenative Coupling of Alcohols with Silanes
In a typical reaction, 1 mmol of silane, and 1 mmol of alcohol were placed in a Schlenk bomb flask dried and filled with argon. Next, 0.1 mL of 1M solution of sodium tri(sec-butyl)borohydride in THF was carefully added. Reaction vessel was closed and placed in a preheated oil bath at given temperature and stirred. Samples were taken at time intervals and analyzed using gas chromatography. After detection of complete conversion of substrates, reaction mixture was cooled down, dosed with approximately 3 mL of hexane, and left for 15 min to precipitate. The suspension was filtered and the resulting clear solution was evaporated to yield pure alkoxysilane.

Conclusions
Direct dehydrogenative coupling of alcohols with hydrosilanes can be efficiently promoted by sodium tri(sec-butyl)borohydride in solvent-free conditions, which enable almost quantitative isolation of desired alkoxysilane product.