Silicon Mimics of Unstable Carbon

Quest for Novel Chemical Entities through Incorporation of Silicon in Drug Scaffolds

“…Bioisosteric replacements are commonly practiced in medicinal chemistry to modulate the properties of a molecule and for creating intellectual property (IP) space. − Due to the similarity of silicon to carbon, over the years there has been growing interest in biological evaluation of organosilanes. Silicon can be considered a bioisostere of carbon and offers an innovative avenue in drug discovery. − The substitution of carbon with silicon in biologically active compounds is also known as the “silicon switch”.…”

“…The utility of organosilanes in drug discovery has been reviewed in the past, as well. − In 2013, a very useful Perspective on medicinal applications of organosilicon compounds by Franz and Wilson was published in this journal and attracted the attention of many research groups . We are writing this Perspective considering the importance and interest in the medicinal chemistry fraternity.…”

Breaking Conventional Site Selectivity in C–H Bond Activation: Selective sp3 versus sp2 Silylation by a Pincer-Based Pocket

“…Transition metal-catalyzed dehydrogenative silylation, a process that integrates C–H and Si–H activations into a dehydrogenative coupling reaction, has emerged as a valuable tool for C–Si bond formations . The intramolecular version of this transformation provides a straightforward approach to Si-containing heterocycles, which are not naturally occurring, but have demonstrated importance in drug discovery and material sciences . While most known intramolecular C­(sp 3 )–H silylation reactions involved benzylic C–H bonds and moderately activated C­(sp 3 )–H bonds attached to heteroatoms, a few disclosed the silylations of unactivated δ-C–H bonds (δ to the Si atom) in alkyl chains to form five-membered Si-containing heterocyle cyclopentane. , Surveying these examples reveal that none of the catalysts effect selective silylation of unactivated δ-C­(sp 3 )–H over spatially and geometrically unbiased ortho δ-C­(sp 2 )–H bonds.…”

Ruthenium-Catalyzed Dual Dehydrogenative Silylation of C(sp3)–H Bonds: Access to Diverse Silicon-Centered Spirocycles

“…While great success has been achieved for the synthesis and application of carbon-centered spirocycles, silicon-centered analogues have received much less attention. Given the fundamental difference between the C and Si atom in covalent radius and electronegativity, the “C-to-Si switch” strategy has been widely explored for the discovery of new bioactive heterocycles, luminescent materials, odorant compounds, and novel ligands . Thus, silicon-centered spirocycles have the potential to combine the properties of a spirocycle scaffold and those induced by the Si atom, which may lead to altered physicochemical and biological properties compared with those of the parent carbon-centered spirocycles …”