Mechanistic Investigations of Selective Alkoxysilane Substitutions by Primary Lithium Amides: From Mono- to Di- and Trisubstituted Si–N-Functionalized Silanes

Selective substitution of methoxy groups in organosilanes by lithium amides provides a direct route to amino-functionalized silanes. While chlorosilanes are commonly used in such transformations, their high reactivity and low selectivity limit synthetic control. Here, we focus on methoxysilanes and evaluate their substitution behavior toward primary lithium amides. Using a combination of in situ Fourier-transform infrared spectroscopy (FTIR) and density functional theory (DFT) calculations, we elucidate the mechanism of the monosubstitution and identify key kinetic parameters such as overall reaction order and activation energy. Based on these findings, reaction conditions were developed to achieve controlled di- and trisubstitution. The distinct substitution outcomes could be rationalized by different underlying mechanistic pathways. Solvent effects and lithium amide aggregation states were found to play a critical role. This work provides a mechanistic framework for designing selective Si-O to Si-N-substitution strategies with synthetic relevance.