Ionic and Neutral Mechanisms for C–H Bond Silylation of Aromatic Heterocycles Catalyzed by Potassium tert-Butoxide

Abstract

Exploiting C-H bond activation is difficult, although some success has been achieved using precious metal catalysts. Recently, it was reported that C-H bonds in aromatic heterocycles were converted to C-Si bonds by reaction with hydrosilanes under the catalytic action of potassium t-butoxide alone. The use of Earth-abundant potassium cation as a catalyst for C-H bond functionalization seems to be without precedent, and no mechanism for the process was established. Using ambient ionization mass spectrometry, we are able to identify crucial ionic intermediates present during the C-H silylation reaction. We propose a plausible catalytic cycle, which involves a pentacoordinate silicon intermediate consisting of silane reagent, substrate, and the t-butoxide catalyst. Heterolysis of the Si-H bond, deprotonation of the heteroarene, addition of the heteroarene carbanion to the silylether, and dissociation of t-butoxide from silicon lead to the silylated heteroarene product. The steps of the silylation mechanism may follow either an ionic route involving K + and t BuOions or a neutral heterolytic route involving the [KO t Bu] 4 tetramer. Both mechanisms are consistent with the ionic intermediates detected experimentally. We also present reasons why potassium t-butoxide is an active catalyst whereas sodium t-butoxide and lithium t-butoxide are not, and we explain the relative reactivities of different (hetero)arenes in the silylation reaction. The unique role of potassium t-butoxide is traced, in part, to the stabilization of crucial intermediates through cation-π interactions. ASSOCIATED CONTENT Supporting Information Mass spectra, NMR spectra. DFT calculations. This material is available free of charge via the Internet at http://pubs.acs.org.

Electron‐Transfer and Hydride‐Transfer Pathways in the Stoltz–Grubbs Reducing System (KOtBu/Et3SiH)

“…A number of intermediates likely arise from reaction of these two reagents, and spectroscopic evidence has resulted in informed proposals being made for their structures. These reactions have proved puzzling, but a recent coordinated study by synthetic, mechanistic, and computational chemists has allowed significant advances to be made 1e,1f. The conclusions are: 1) the combination of Et 3 SiH and KO t Bu leads to triethylsilyl radicals which have a major role to play in the reductive cleavage of the C−O and C−S bonds,1d 2) triethylsilyl radicals are also likely to be involved in the silylation reactions, although nonradical routes to the silylation have also been considered in depth and may also play a central role 1e,1f.…”

“…These reactions have proved puzzling, but a recent coordinated study by synthetic, mechanistic, and computational chemists has allowed significant advances to be made 1e,1f. The conclusions are: 1) the combination of Et 3 SiH and KO t Bu leads to triethylsilyl radicals which have a major role to play in the reductive cleavage of the C−O and C−S bonds,1d 2) triethylsilyl radicals are also likely to be involved in the silylation reactions, although nonradical routes to the silylation have also been considered in depth and may also play a central role 1e,1f. The mechanistic details are not fully in place, for example, on how formation of the silyl radicals occurs, but rational working hypotheses have been advanced 1e…”

N‐Silylation of Amines Mediated by Et3SiH/KOtBu

“…[24] The most intriguing recent development in silicon chemistry may well be the use of the Et 3 SiH/KO t Bu system, which has been extensively developed by Stoltz, Grubbs et al to address a number of remarkable reactions, such as the conversion of arenes and heteroarenes into regioselectively silyl-substituted products and the reductive cleavage of CÀ S and CÀ O bonds in aryl thioethers and aryl ethers, respectively. [25][26][27][28][29][30] The combination of Et 3 SiH and KO t Bu leads to triethylsilyl radicals which are very likely to play a major role in these reactions, although nonradical routes may also contribute, especially in the silylation process. Although a broad network of reactions involving several intermediates and mechanisms has been proposed, the mechanistic diversity of this pair of reagents is still puzzling.…”

C−C Bond Formation of Benzyl Alcohols and Alkynes Using a Catalytic Amount of KOtBu: Unusual Regioselectivity through a Radical Mechanism

“…[2] Recently, Stoltz, Grubbs,a nd co-workers have reported the transition-metal-free silylation of C À Hb onds of aromatic heterocycles catalyzed by KO t Bu. [3] Among several C À Cb ond-forming reactions,t he formation of a-alkylated ketones is important because of their interesting pharmacological and physiological properties. [4] In particular,d ihydrochalcones (a class of a-alkylated ketones) are found in natural products,s uch as naringin dihydrochalcone and aspalathin, and are used as artificial sweeteners and antioxidants.…”