Potassium Trimethylsilanolate: Catalysis & Structural Insights

Potassium trimethylsilanolate is a versatile chemical compound widely recognized for its applications in various industries, particularly in the fields of organic synthesis and materials science. This compound serves as an effective silane coupling agent, enhancing the adhesion between organic materials and inorganic substrates. Its unique structure allows it to function as a precursor in the synthesis of silicone polymers, which are utilized in sealants, adhesives, and coatings. Researchers appreciate its ability to improve the mechanical properties and thermal stability of composite materials, making it a valuable addition to formulations in the automotive and aerospace sectors. Potassium trimethylsilanolate can be used as a reagent in the: Hydrolysis of nitriles to primary amides; conversion of esters to carboxylic acids, and dialkyl phosphonates to their monoalkyl phosphonates; synthesis of E-alkenes, and nitrocefin.

Potassium Trimethylsilanolate Enables Cross-Coupling of Boronic Esters

The Suzuki–Miyaura reaction is one of the premier methods for the formation of carbon-carbon bonds. Advances in ligand design have allowed for successful cross-coupling at room-temperature, cross-coupling of substrates bearing a poor nucleofuge, as well as those involving sterically hindered partners. However, competitive protodeboronation often necessitates the use of the organometallic coupling partner in excess, and multiple strategies have been developed to mitigate this issue. Extensive investigations on silicon-based, cross-coupling reactions from this laboratory suggested the use of potassium trimethylsilanolate (TMSOK) because of its low cost and high solubility in ethereal solvents. Initial results were encouraging; in a survey of three solvents and four catalysts for the coupling of 4-bromobenzotrifluoride with neopentyl 4-fluorophenylboronic ester, the combination of Pd-P(t-Bu)3-G3 and THF was uniquely effective. With optimized conditions fully developed, the generality of the Potassium trimethylsilanolate-promoted cross-coupling was explored with a series of neopentyl boronic esters and 9a. In general, reactions were complete in 5 min affording product in excellent (>90%) yield. Reactions using electron-rich partners such as 4-methoxyphenyl-, 3,4,5-trimethoxyphenyl-, and 3,4-methylenedioxyphenylboronic ester or electronically neutral partners such as 4-fluorophenyl-, 2-naphthyl-, and 1-naphthylboronic ester furnished the respective products in >90% yield in under 5 min.[1]

By substituting the neopentyl ester for the boronic acid and using Potassium trimethylsilanolate as the base, 10xx was produced in 91% yield after only 16 h. The cross-coupling of pyridyl bromide 9y and phenylboronic acid catalyzed by Pd(PPh3)4 is run for 72 h to obtain 10yy in 51% yield. With the modifications described above, the product was obtained in 92% yield after 5 h. Finally, the coupling of bromide 9z with cyclopropylboronic acid was investigated under catalysis by Pd(OAc)2/P(c-Hex)3, which furnished product 10zz in 73% yield after 50 h. Substituting with TMSOK and neopentyl cyclopropylboronic ester gave a lower yield owing to competitive protodehalogenation. These examples demonstrate that by simply using a boronic ester in place of the acid, using Potassium trimethylsilanolate as a base, and a compatible solvent system (ethereal, anhydrous solvents), the rate of cross-coupling is increased in a variety of catalytic systems; the catalyst/ligand for each system has not been changed. As such, we posit that this is a general advance that can provide benefits complementary to other improvements in ligand design. In conclusion, we have demonstrated that the use of an organic soluble base, Potassium trimethylsilanolate, allows for a homogeneous, anhydrous reaction that improves reproducibility and ease of use. Additionally, boronic ester structure represents a powerful new point of optimization in the Suzuki–Miyaura reaction which can complement recent advances in ligand and precatalyst design.

Potassium Trimethylsilanolate-Promoted Suzuki-Miyaura Reaction

The development of transition-metal catalyzed, cross-coupling reactions has fundamentally changed the way chemists construct C–C bonds. Because the formation of C–C bonds is central to synthetic organic chemistry, cross-coupling reactions are routinely applied in nearly every field in which organic chemistry is relevant, including polymer and materials chemistry, medicinal chemistry, small-molecule synthesis performed on small scale and large, and natural products synthesis.  Inspired by prior work in the Denmark laboratory on cross-coupling reactions of organosilicon reagents, potassium trimethylsilanolate (TMSOK) was identified as a base to promote the homogeneous, anhydrous Suzuki-Miyaura cross-coupling of boronic esters. It was demonstrated that the reaction time for several example reactions could be shortened from days to hours, without changing the ligand or precatalyst, simply by employing an appropriate boronic ester as the nucleophile, TMSOK as the base, and anhydrous, ethereal solvent. The homogeneous, anhydrous reaction conditions have also been adapted to the cross-coupling of heteroaryl nucleophiles with heteroaryl electrophiles, wherein the use of aqueous conditions can facilitate protodeboronation. Next, a rate equation for the Potassium trimethylsilanolate-promoted Suzuki-Miyaura reaction of neopentyl boronic esters was determined to identify the species that are involved between the resting state and turnover-limiting transition state. Furthermore, such experiments could reveal whether complex represented an artifact of the stoichiometric reaction conditions or a relevant catalytic intermediate.[2]

In support of the oxo-palladium pathway, Hartwig and Carrow demonstrated that transmetalation from potassium triolboronates is very slow at −40 °C. In contrast, the rate of transmetalation from Potassium trimethylsilanolate-ligated boronic esters is rapid at −40 °C. We hypothesize that in this system, the viability of boronate transmetalation pathway (path A) from Potassium trimethylsilanolate-complexes of boronic esters is related to the solubility of the potassium boronate and the insolubility of the inorganic salt byproduct, KBr. The solubilized potassium cation could bind as a Lewis acid to the bromide in complexes such, activating the arylpalladium bromide complex to transmetalation. The mechanism of the Potassium trimethylsilanolate-promoted, anhydrous Suzuki-Miyaura cross-coupling reaction has been elucidated through kinetic analysis and the study of reactivity of isolated reaction intermediates. Stoichiometric studies show that in contrast to prior results, transmetalation through the boronate pathway (path A) can proceed quickly under appropriate reaction conditions. Furthermore, it was demonstrated that saturation of both palladium and boronate with base (Path C) precludes transmetalation, giving rise to base inhibition in homogeneous, anhydrous Suzuki-Miyaura reactions. During the course of the investigation, a novel, binuclear palladium complex containing an μ-arene ligand was characterized and implicated as a catalytic intermediate.

Validation of the Existence of Tetrameric Species of Potassium Trimethylsilanolate

A considerable number of recent studies deal with the synthesis and structural characterization of different metallic alkylsilanolates. Although extensively studied experimentally (mainly by NMR and X-ray diffraction techniques), theoretical investigations on these structures are rare. In recent years, however, there has been a growing interest in combined theoretical and experimental studies that deal with the bonding properties and molecular structures of compounds containing highly polar bonds of the type M−X (where M = metal and X = C, O, ...).  The system studied in the present work, potassium trimethylsilanolate, belongs to this family of compounds. We have investigated, theoretically, the structural properties of potassium trimethylsilanolate in the gas phase at a B3LYP/6-31+G* level. For this purpose, a simplified ionic cluster model based on potassium trimethylsilanolate tetramers, proposed in the literature as the structural units of this compound in the solid state, was developed. The developed ionic cluster model was found to be best in reproducing the experimental structure of potassium trimethylsilanolate, supporting, at the same time, the existence of such tetrameric species (previously identified experimentally from mass spectrometry data by Weiss et al.) in the gas phase. Finally, NBO calculations highlighted the important role of the potassium counterion as a charge localizer in the structure of these chemical species.[3]

References

[1]Delaney CP, Kassel VM, Denmark SE. Potassium Trimethylsilanolate Enables Rapid, Homogeneous Suzuki-Miyaura Cross-Coupling of Boronic Esters. ACS Catal. 2020 Jan 3;10(1):73-80. doi: 10.1021/acscatal.9b04353. Epub 2019 Dec 2. PMID: 33585070; PMCID: PMC7880502.

[2]Delaney CP, Marron DP, Shved AS, Zare RN, Waymouth RM, Denmark SE. Potassium Trimethylsilanolate-Promoted, Anhydrous Suzuki-Miyaura Cross-Coupling Reaction Proceeds via the "Boronate Mechanism": Evidence for the Alternative Fork in the Trail. J Am Chem Soc. 2022 Mar 16;144(10):4345-4364. doi: 10.1021/jacs.1c08283. Epub 2022 Mar 1. PMID: 35230833; PMCID: PMC8930609.

[3]Montejo, Manuel et al. “Validation of the existence of tetrameric species of potassium trimethylsilanolate in the gas phase with a theoretical cluster model: role of the counterion as charge localizer in the structure.” The journal of physical chemistry. A vol. 111,13 (2007): 2629-33. doi:10.1021/jp0686240

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