Organophosphonic acid catalyzed dehydrogenative coupling of hydrosilanes with alcohols under solvent-free conditions

: There is a strong need for exploring the new preparation methods for silyl ethers due to their great potential in synthetic chemistry and materials. At present, the catalytic dehydrogenative coupling of silane and alcohol has been proven to be an attractive way to prepare silyl ethers. In this work, we used a non-metallic and inexpensive phenyl phosphonic acid as a catalyst, which can directly generate corresponding silyl ethers from alcohols and silanes in high yields under relatively mild conditions such as metal-free, no solvents, demonstrating its enormous application potentials.


Introduction
Silyl ethers serve the crucial role as polymer monomers in silicon-containing material [1], protecting groups in organic synthetic chemistry [2], electron donors in Ziegler-Natta catalyst [3], and so on.Indeed, these various applications benefit from the great progress in the synthesis of silyl ethers in recent years.In general, there are some routes involved in the preparation of silyl ethers at present.One is the traditionally elegant method of removing hydrogen chloride from chlorosilanes and alcohols with base agents [4].Despite bringing numerous practical applications, such procedure always suffering from the drawbacks of the corrosion of hydrogen chloride byproduct on equipment remains an unsolved problem.Some other methods include the direct synthesis of metallurgical silicon with selected alcohols performed on an industrial scale [5].Other approaches are based on reactions of metal alcoholates with halogenosilanes or silanes with Si-Si-bonds [6].Trans-silylation of chlorosilanes with (trimethyl)silylated alcohols is another route, forming volatile trimethylchlorosilane as a side product, which can be easily isolated [7].Overall, the most attractive protocol is the directly dehydrogenative cross-coupling reactions between the alcohols and hydrosilanes.Because of inherently atom-economy and environmentally benign, the method has become an attractive alternative in silyl ethers synthesis.To date, a large number of dehydrogenative cross-coupling catalytic systems toward silyl ethers have been developed including transition-metal [8][9][10][11][12][13][14][15], Lewis bases [16][17][18][19][20][21], Brønsted [22][23][24], and Lewis acids [25,26].Among them, Lewis acid/base catalysis has attracted much attention due to their many advantages, such as metal free, cheap and easily available, environmentally friendly, highly efficient, and selective in recent years.
As an elegant acid catalyst, organophosphonic acid has developed rapidly and efficiently catalyzed multiple reactions during the last few decades [27][28][29][30].In this work, we report the use of the commercially available organophosphonic acid as a catalyst for the dehydrogenative cross-coupling between alcohols and hydrosilanes.This method has the fascinating characteristics of mild and solvent-free conditions, high catalytic efficiency, broad substrate scope, and good functionality tolerance.All these demonstrate the considerable potential of the method in the synthesis of silyl ethers (Scheme 1).

Results and discussion
At first, we used some common organophosphonic acids including etidronic acid (1), ethylenediamine tetramethylenephosphonic acid (2), phenylphosphinic acid (3), phenylphosphonic acid (4), p-nitrophenyl phosphonic acid (5), and p-methoxyphenyl phosphonic acid (6) to catalyze the representative dehydrogenative cross-coupling between the triethoxysilane and isobutanol (1:1).As displayed in Table 1, when using 5 mol% hydroxyethylenediphosphate (60% aqueous solution) as a catalyst in tetrahydrofuran (TFT) at 50°C, the corresponding product isobutyloxy-triethoxysilane was obtained in the yield of 72%.Under the same conditions, the other organophosphonic acid catalysts 2-6 also showed good to excellent catalytic activities.In particular, all three phenylphosphonic acids 4-6 exhibited the impressive catalytic performance.Among them, phenylphosphonic acid 4 demonstrated the best catalytic performance with 91% catalytic conversion after 8 h of reaction at 50°C.Accordingly, the final reaction conditions were optimized as that phenylphosphonic acid was selected as the catalyst for the dehydrogenative cross-coupling reaction of triethoxysilane and isobutanol in a 1:1 ratio in THF at 50°C.
To further explore the catalytic performance of some other inorganic acids, several representative inorganic, such as like hydrochloric acid, phosphoric acid, sulfuric acid, and acetic acid, Table 1, entries 7-10, were used to catalyze the dehydrogenative cross-coupling reaction of triethoxysilane and isobutanol.The experimental results indicated that all these inorganic acids showed lower catalytic activities.This might be due to that inorganic acids contain water and are directly incompatible with organic silanes.
After screening the catalysts, we continued to study the effect of temperature on the dehydrogenative crosscoupling reaction of triethoxysilane and isobutanol using phenylphosphonic acid as the catalyst (Table 1).Afterwards, the reactions were performed under different temperatures 25(r.t.), 50°C, 60°C, 80°C, and 100°C, respectively (Table 1, entries [11][12][13][14][15].The results disclosed that the higher the temperature, the faster the reaction.However, when the temperature rose to 60°C, there was no significant improvement in the yield.Considering the mildness of the reaction conditions, the optimal temperature was ultimately chosen at 60°C. Then, we tested the effects of different solvents and selected n-hexane, tetrahydrofuran, dichloromethane (DCM), and solvent-free conditions for the reaction (Table 1, entries 13, 16-18).It was found that the solvent effect could be ignored for such a dehydrogenative cross-coupling reaction.Therefore, a solvent-free condition was selected due to being green, safe, and environmentally friendly.Afterwards, we optimized the ratio of the reactant and catalyst.As shown in Table 1, entries 18-21, the reactions were carried out with the catalyst loadings of 5.0, 2.5, 1.3, and 1.0 mol% in sequence.When the catalyst loadings were reduced to 1.3 mol%, the catalytic performance was still relatively high.While it decreased to 1.0 mol%, the catalytic performance began to decrease.Therefore, the final catalyst loading was optimized as 1.3 mol%.With the optimized reaction conditions in hand, we explored the dehydrogenative coupling reactions between triethoxysilane (EtO) 3 SiH and different primary, secondary, and tertiary alcohols (Table 2, entries 1-14).The results demonstrated that triethoxysilane and most alcohols could generate the corresponding silyl ethers with excellent yields (>90%) under the optimal reaction conditions.Compared with primary alcohols, the secondary and tertiary alcohols with higher steric hindrances featured lower yields for this reaction (Table 2, entries 1-3).Impressively, as for 1,2-ethylene glycol monoacetate and 5-hydroxy-2-pentanone containing double functional groups (Table 2, entries 4-5), only the hydroxyl groups took place in the dehydrogenative coupling reactions, and the ester or carbonyl groups made  Dehydrogenative coupling of hydrosilanes  3

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Dehydrogenative coupling of hydrosilanes  5 no changes.This phenomenon indicates that the reaction possessed a good functional group tolerance.To test the selectivity, alcohol substrates with unsaturated functional groups, such as olefin group and alkyne group (Table 2, entries 6-7), were investigated as well.The results showed that all these alcohols were highly converted into the corresponding silyl ethers without affecting the saturation of compounds.Afterwards, we also tested organic heterocyclic pyridine (Table 2, entries 10), and the result confirmed that the reaction could proceed smoothly with a high yield of 94%.Meanwhile, alcohols containing the oxirane group also had a good conversion (95% yield, Table 2, entries 11).
To further explore the selectivity and electronic effect, we carried out the dehydrogenation coupling reactions for alcohol substrates containing electron donor and acceptor substituents.It was discovered that both alcohols with electron-withdrawing (-F, -NO 2 ) groups and electrondonating (-OCH 3 ) groups exhibited excellent reactivities toward (EtO) 3 SiH (Table 2, entries [12][13][14].It should be noted that electron-withdrawing nitro-substituted alcohol was more advantageous for such dehydrogenative coupling reactions. To further confirm the catalytic range of phenylphosphonic acid, we chose to replace triethoxysilane with other silane compounds, such as triethylsilane and triisopropylsilane.As depicted in Table 3, both triethylsilane and triisopropylsilane could react with n-butanol with high yields.When reacting triethylsilane with tert-amyl alcohol containing a higher steric hindrance, the corresponding yield would decrease slightly from 87% to 82% (Table 3, entries 1-3).When using dimethylphenylsilane, methyldiphenylsilane, and triphenylsilane with a π-conjugated structure (Table 3, entries 4-7), it was found that only dimethylphenylsilane could react with n-butanol with a relatively lower yield (47%).However, no product was detected for the reaction between methyldiphenylsilane and triphenylsilane with n-butanols.The phenomenon revealed that the larger π-conjugated electronic effect might decrease the reactivity of silanes, thereby inhibiting this reaction.
On the basis of experimental results as well as some related literatures [6,7,9], we proposed the possible mechanism.As displayed in Figure 1, first, the catalyst phenylphosphonic acid could form a hydrogen bond with the substrate alcohol, thereby achieving to activate the alcohol.Second, the phosphorus oxygen double bond on the catalyst phenyl phosphate exhibited Lewis basicity, which could coordinated to the electrophilic silicon atom of the Si-H unit.This would enhance the reactivity of the hydrogen atom and catalyze the H 2 formation.Subsequently, an intramolecular reaction in the generated transition state complex occurred to eliminate hydrogen.Finally, the desired product silyl ethers would be obtained and the catalytic cycle was completed.

Conclusion
In summary, a highly efficient dehydrogenative coupling reaction was established for the synthesis of silyl ethers via organic phosphate catalysis.This method featured many advantages like non-metal catalysts, solvent-free, mild reaction conditions, good group toleration, and high yields, indicating great potential for the preparation of silyl ethers.This work not only provided a facile method for the synthesis of silyl ethers but also expanded the catalytic range of organic phosphoric acid.Further investigation of this new strategy and the application of such products is underway in our laboratory.

Experimental Materials and measurements
All commercially available experimental materials were obtained from commercial suppliers and were not further purified during use.Some silyl ethers were separated and purified on silica gel (200-300 mesh) using petroleum ether and ethyl acetate as eluents.The nuclear magnetic resonance (NMR) data ( 1 H NMR and 13 C NMR) was collected from a Bruker NMR spectrometer with tetramethylsilane as an internal reference.The mass spectra (MS) were obtained on a Shimadzu LCMS-2010EV mass spectrometer (ESI).The structures of products were well-confirmed by NMR and MS methods.

Synthetic route for silyl ethers
The synthesis procedure of silyl ether isobutyloxy-triethoxysilane: add (1.3 mol%, 0.019 g) of phenylphosphonic acid to a dry circular bottom flask with magnetic particles, followed by isobutanol (0.01 mol, 0.92 mL) and triethoxysilane (0.01 mol, 1.84 mL).After stirring for 10 h at 60°C under solvent-free conditions, the phosphonic acid catalyst was removed from the system by filtering to obtain the crude product.Afterwards, the crude product was purified by column chromatography with petroleum ether/ethyl acetate (50:1) to obtain the final product isobutyloxy-triethoxysilane as colorless liquid (2.31 g, 98% yield).
The synthesis routes of product silyl ethers were similar to that of isobutyloxy-triethoxysilane using other silanes and alcohols instead of triethoxysilane and isobutanol, respectively.

Scheme 1 :
Scheme 1: Strategies for the synthesis of silyl ethers.

Table 2 :
Dehydrogenative coupling reactions of triethoxysilane with various alcohols

Table 3 :
Dehydrogenative coupling reactions of different silanes with n-butanol