Catalytic Electrophilic CH Silylation of Pyridines Enabled by Temporary Dearomatization

• Published in: Angewandte Chemie International Edition Vol. 54; no. 52; pp. 15876 - 15879
• Main Authors: Wübbolt, Simon, Oestreich, Martin
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 21.12.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Catalysts; Chemistry; Chemistry, Multidisciplinary; CH activation; Dehydrogenation; Dihydropyridine; electrophilic substitution; Hydrides; Hydrogen bonds; Hydrosilylation; Intermediates; Magnetic resonance spectroscopy; N-heterocycles; NMR; NMR spectroscopy; Nuclear magnetic resonance; Physical Sciences; Pyridines; Science & Technology; Silicon; SiH bond activation; RU-S BONDS; ACTIVATION; MECHANISM; HYDROSILANES; COMPLEXES; ARENES; 1,4-BIS(TRIMETHYLSILYL)-1,4-DIHYDROPYRIDINE; CLEAVAGE; electrophilic substitution; INDOLES; C-H activation; ANILINES; hydrosilylation; Si-H bond activation; N-heterocycles; CH activation; SiH bond activation
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201508181

A CH silylation of pyridines that seemingly proceeds through electrophilic aromatic substitution (SEAr) is reported. Reactions of 2‐ and 3‐substituted pyridines with hydrosilanes in the presence of a catalyst that splits the SiH bond into a hydride and a silicon electrophile yield the corresponding 5‐silylated pyridines. This formal silylation of an aromatic CH bond is the result of a three‐step sequence, consisting of a pyridine hydrosilylation, a dehydrogenative CH silylation of the intermediate enamine, and a 1,4‐dihydropyridine retro‐hydrosilylation. The key intermediates were detected by 1H NMR spectroscopy and prepared through the individual steps. This complex interplay of electrophilic silylation, hydride transfer, and proton ion is promoted by a single catalyst. Breaking the Law: Reversible 1,4‐hydrosilylation of substituted pyridines was used to break and reestablish its aromaticity. The intermediate 1,4‐dihydropyridine reacts as an enamine with a catalytically generated silicon electrophile, followed by deprotonation. The whole sequence is promoted by a single catalyst. This strategy addresses the CH bond at C5 of the electron‐deficient arene rather than the CH bond in proximity to the nitrogen donor.