Silylation of Aryl and Alkyl Chlorides by a Seven-Membered Dialkoxysilyl Group Si(pan)Me via an In Situ Generated Silylpotassium

Abstract

Silicon-containing compounds are increasingly vital in pharmaceutical and agrochemical applications, yet existing silylation methods face critical limitations: poor reactivity of unactivated silanes and instability of activated silylation reagents and their products. Here, we present a seven-membered dialkoxysilyl unit, dioxasilepane, abbreviated as Si(pan), that combines exceptional stability with controllable reactivity. We demonstrate a versatile method for Si(pan)Me incorporation into organic molecules through reactions with diverse aryl, alkenyl, and alkyl chlorides. Notably, we have isolated and structurally characterized the key silylpotassium intermediate as its 18-crown-6 complex through X-ray crystallography. Experimental mechanistic studies reveal that this silylpotassium species mediates the transformation primarily through halogen-metal exchange (HME). Computational investigations confirm the HME pathway while suggesting a concurrent S_N2 mechanism for specific primary alkyl chlorides. This methodology establishes Si(pan) as a robust building block for constructing silicon-containing molecular frameworks, addressing a longstanding challenge in organic synthesis.

Keywords: Alkoxysilane; Dioxasilepane; Halogen‐metal exchange; Silylation; Silylpotassium.

Figure 1

Overview of the current study. 18‐C‐6 = 18‐crown‐6 ether.

Scheme 1

Scope with Respect to Disilane Reagents.

Scheme 2

Substrate Scope with Respect to Aryl Chlorides.^a) a) isolated yields.

Scheme 3

Substrate Scope with Respect to Alkyl Chlorides.^a) a) Isolated yields. b) NMR yield determined by ¹H NMR using mesitylene as an internal standard. c) 3.0 equiv 2a and 4.0 equiv KOtBu were used. d) 2.0 equiv KOtBu was used. e) Hexane as solvent.

Figure 2

Mechanistic insight for generation of silylpotassium species. a) Energy profile for Si–Si bond cleavage of (Si(pan)Me)₂ (2a) upon treatment with KOtBu to generate silylpotassium species SiK1 at the ωB97X‐D/def2‐TZVPPD in benzene (SMD)//ωB97X‐D/def2‐SVP level of theory at 323.15 K. b) X‐ray crystal structure of 18‐C‐6·K–Si(pan)Me (10) complex. c) Kohn‐Sham HOMO of 18‐C‐6·K–Si(pan)Me (10) computed at the ωB97X‐D/def2‐TZVPPD level of theory using benzene as an implicit solvent; isovalue = 0.03. d) Silylpotassium 10 mediates the silylation reaction of aryl chloride 1b.

Figure 3

Mechanistic investigation: possible mechanisms for silylation of aryl chlorides. a) Four possible mechanisms for silylpotassium‐mediated silylation. b) Silylation of aryl chloride involves arylpotassium intermediate. c) Energy profile for silylation of aryl chloride from the complex INT0_Ar to generate an arylsilane at the ωB97X‐D/def2‐TZVPPD in benzene (SMD)//ωB97X‐D/def2‐SVP level of theory at 323.15 K. HME = Halogen‐Metal Exchange.

Figure 4

Mechanistic investigation: silylation of alkyl chlorides. a) Silylation of a chiral secondary alkyl chloride indicates negligible S_N2 reaction involvement for a secondary alkyl chloride. b) The formation of a cyclized product suggests an anionic or radical intermediate. c) Anionic intermediate is inferred by the formation of the phenylsilane. d) Plausible anion‐mediated mechanism. e) Energy profile for the silylation of neophyl chloride through S_N2 reaction (brown, left) from INT0_SN2 and through the sequence of HME reaction from INT0_HME followed by the silylation of neophylpotassium (blue, right) at the ωB97X‐D/def2‐TZVPPD in benzene (SMD)//ωB97X‐D/def2‐SVP level of theory at 323.15 K. TFA = trifluoroacetic acid.