Potassium tert-Butoxide-Catalyzed Dehydrogenative C–H Silylation of Heteroaromatics: A Combined Experimental and Computational Mechanistic Study

Abstract

We recently reported a new method for the direct dehydrogenative C-H silylation of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we report a systematic experimental and computational mechanistic investigation of this transformation. Our experimental results are consistent with a radical chain mechanism. A trialkylsilyl radical may be initially generated by homolytic cleavage of a weakened Si-H bond of a hypercoordinated silicon species as detected by IR, or by traces of oxygen which can generate a reactive peroxide by reaction with [KOt-Bu] as indicated by density functional theory (DFT) calculations. Radical clock and kinetic isotope experiments support a mechanism in which the C-Si bond is formed through silyl radical addition to the heterocycle followed by subsequent β-hydrogen scission. DFT calculations reveal a reasonable energy profile for a radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversible, with an equilibrium favoring products due to the generation of H gas. In situ NMR experiments with deuterated substrates show that H is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates.

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…”

“…Because of their subsequent importance in this paper, we mention here that the radical anions 12 may be formed in a number of ways, two of which are shown (inset) in Scheme 2 (see Figure 14 in Ref. 1e for an additional route). For these studies, we used the computationally less costly trimethylsilyl group instead of the triethylsilyl group 1d,1e.…”

“…1e for an additional route). For these studies, we used the computationally less costly trimethylsilyl group instead of the triethylsilyl group 1d,1e. To these, we add the triethylsilyl anion 14 b as another putative intermediate.…”

Radical‐Initiated Dismutation of Hydrosiloxanes by Catalytic Potassium‐Graphite

“…[5] Although the ionic pathway seems favored, Stoltz et al have detailed the three possible pathways (ionic, radical or neutral) for the KO t Bu-catalyzed dehydrogenative coupling of indoles with triethylsilane. [38,39] Their studies showed that a radical mechanism seemed favored, via the generation of a silyl radical. Electron-donors may also be used as radical initiators.…”