Trialkoxysilane Exchange: Scope, Mechanism, Cryptates and pH‐Response

Abstract

The dynamic covalent chemistry (DCvC) of the Si−O bond holds unique opportunities, but has rarely been employed to assemble discrete molecular architectures. This may be due to the harsh conditions required to initiate exchange reactions at silicon in aprotic solvents. Herein, we provide a comprehensive experimental and computational account on the reaction of trialkoxysilanes with alcohols and identify mild conditions for rapid exchange in aprotic solvents. Substituent, solvent and salt effects are uncovered, understood and exploited for the construction of sila‐orthoester cryptates. A sharp, divergent pH‐response of the obtained cages renders this substance class attractive for future applications well beyond host‐guest chemistry, for instance, in drug delivery.

The Dynamic Chemistry of Orthoesters and Trialkoxysilanes: Making Supramolecular Hosts Adaptive, Fluxional, and Degradable

“… 2023 62 . 4 We report a detailed understanding of trialkoxysilane exchange and the first example of a self-assembled trialkoxysilane host–guest complex.…”

“…For instance, a conversion of only 3% was found in benzene after 20 min, whereas in DMSO the equilibrium was reached after only 7 min. 4 The basic solvents pyridine and HMPA represented outliers: reactivity was higher than expected from their dielectric constants. Because these solvents form salts with the acid catalyst TFA, we proceeded to study the influence of salt additives on the reaction kinetics (trifluoroacetate salts, triflate salts, and various salts comprising weakly coordinating ions).…”

“…DFT calculations carried out by Lutz Greb revealed a specific effect of the TFA acid catalyst, namely, that it generates a pentacoordinated adduct (Figure 8a), which lowers the barrier for ethanol exchange. 4 To study the influence of the solvent on the reaction kinetics, we chose seven aprotic solvents spanning a vast range of dielectric constants as well as two basic solvents (hexamethylphosphoric triamide (HMPA) and pyridine). The kinetic data obtained by 1 H NMR spectroscopy revealed a linear dependence of the solvent polarity on the reaction rate.…”

“…The difference stems from the mechanism of the exchange reaction, which in the case of trialkoxysilanes features a penta-coordinated intermediate, where sterics play a more important role than electronics (in contrast to orthoester exchange). DFT calculations carried out by Lutz Greb revealed a specific effect of the TFA acid catalyst, namely, that it generates a penta-coordinated adduct (Figure a), which lowers the barrier for ethanol exchange …”

“…Representative single crystal X-ray structure of [Na + ⊂ o -Si-(mesityl) 2 -1.1.1] (Mes = mesityl; omitted for clarity). (c) Half-lives t 1/2 for the hydrolysis of phenyltrimethoxysilane (red) and trimethyl orthoacetate (blue) …”