Secondary silylium ion drives one-pot ketone sulfonamidation, reaching 95% yields

Secondary silylium ion drives one-pot ketone sulfonamidation, reaching 95% yields Lisa Lock Scientific Editor Andrew Zinin Lead Editor A research team has developed a novel organocatalysis method based on a silylium Lewis acid. This technology employs an ion-pair catalyst combining a diethylsilylium ion with a weakly coordinating anion, enabling the direct installation of sulfonamide groups into functionalized ketone compounds, including β-ketoesters, which had previously been difficult to react using conventional catalytic methods. The team was led by Professor Han-Yong Bae of the Department of Chemistry at Sungkyunkwan University, in collaboration with Professor Junsuk Huh of the Department of Chemistry and Institute of Quantum Information Technology at Yonsei University. Their study is published in the journal Advanced Science. The catalytic system they developed represents a major advance in the field of reductive sulfonamidation, which enables precise control over nitrogen-carbon bond formation in the synthesis of complex molecular structures. Instead of conventional transition-metal catalysts or high-pressure hydrogen gas, the researchers implemented new catalytic reaction conditions in which a powerful silylium ion pair is generated in situ by combining trityl tetrakis(pentafluorophenyl)borate with diethylsilane. Diethylsilane simultaneously serves dual roles as both a reductant and a silylium precursor, while the resulting catalyst precisely controls not only the reaction rate but also substrate activation and selectivity. Notably, this study achieved, in a single reaction vessel, a series of steps—including the reduction of ketimine intermediates—for which conventional tertiary silylium catalysts had shown very low conversion rates. Through this reaction, alkyl β-amino ester derivatives were successfully synthesized in yields of up to 95%, realizing a sustainable process in which scale-up reactions proceed smoothly without solvent, metal, hydrogen gas or other additives. In addition to experimental results, the research team elucidated in detail how this new catalytic system operates through density functional theory (DFT) calculations, nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry (HR-MS). Beyond merely developing a new reaction, the team scientifically demonstrated that secondary silylium ions exhibit stronger Lewis acidity than tertiary silylium ions because of lower steric hindrance, and that they activate substrates more effectively in ion-pair formation with weakly coordinating anions. Professor Han-Yong Bae said, "This study is highly significant in that it proposes a new approach of in situ catalytic system based on secondary silylium ions." He added, "We expect it to find broad application in various carbon-heteroatom bond-forming reactions going forward." Professor Junsuk Huh said, "Validated through both experimental and theoretical approaches, this technology will serve as a fundamental platform applicable to the synthesis of high-value compounds, including natural products, pharmaceuticals and diverse organic materials—as exemplified by the antidiabetic drug sitagliptin." Publication details Woo Hee Kim et al, A Strong Lewis Acidic Diethylsilylium Catalyst for Direct Sulfonamidation of Challenging Ketones, Advanced Science (2026). DOI: 10.1002/advs.75783 Journal information: Advanced Science Provided by Sungkyunkwan University