A Strong Lewis Acidic Diethylsilylium Catalyst for Direct Sulfonamidation of Challenging Ketones

초록

Low-substitution-order silylium ions (R2HSi+), as less sterically congested analogs of carbenium ions, exhibit exceptionally high Lewis acidity and distinctive reactivity compared with tertiary counterparts. Herein, we present a strong Lewis acidic diethylsilylium catalysis that enables efficient reductive sulfonamidation of functionalized ketones, including beta-ketoesters, to access alkyl beta-amino esters. The active diethylsilylium ion pair ([Et2HSi](+)[B(C6F5)(4)](-)), in situ generated via hydride abstraction from diethylsilane by trityl tetrakis(pentafluorophenyl)borate, displays a remarkably enhanced catalytic performance. Diethylsilane functions dually as the reductant and precursor of the silylium species. Operating under solvent-, metal-, hydrogen-, and additive-free conditions, the protocol offers broad substrate scope and excellent scalability, exemplified by a concise three-step, multi-gram synthesis of the antidiabetic drug sitagliptin (> 4 g). Combined computational, NMR, and HR-MS analyses reveal that the remarkable Lewis acidity of the secondary silylium ion enables activation of challenging substrates and affords exceptional selectivity. A mechanistic understanding of this process provides the foundation for a practical and sustainable catalytic system that expands the frontier of silylium-mediated C & horbar;N bond formation.

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