Strategic Applications of the β‐Silicon Effect

Abstract

Organosilicon reagents are highly versatile and privileged scaffolds in modern synthetic chemistry, largely due to the range of transformations the groups are amenable to. The β‐Silicon effect is one of the fundamental phenomena underpinning the inherent reactivity of organosilicon reagents, allowing unsaturated organosilanes to undergo a range of electrophilic substitutions with a variety of nucleophiles. The application of the β‐Silicon effect in a range of organic transformations is reviewed with the discussion divided up based on the class of silane. The reactivity of these compounds towards carbon, heteroatom and metallic electrophiles is discussed from classical applications such as the Sakurai allylation to contemporary applications such as cross‐coupling chemistry. In addition, examples of these transformations in the context of methodology development and natural product synthesis are provided.

β-Boron Effect Enables Regioselective and Stereospecific Electrophilic Addition to Alkenes

“…This effect has been reflected in the reactions of a wide variety of silylated alkenes, alkynes, and allenes, leading to many useful site-selective transformations. 15 However, due to the propensity of the silyl group to be attacked by nucleophiles, desilylative S E 2′ reactions are typically observed. 16 Inspired by the silyl group's activating and directing effects, we envisioned that the allylic B(MIDA) (N-methyliminodiacetic acid) moiety could impose regiocontrol on the adjacent double bond toward electrophilic addition.…”

“…The well-known β-silicon effect, or σ­(C–Si)-π hyperconjugation, makes the alkenyl carbon distal to the silyl group more nucleophilic, resulting in a selective outcome (Scheme A). This effect has been reflected in the reactions of a wide variety of silylated alkenes, alkynes, and allenes, leading to many useful site-selective transformations . However, due to the propensity of the silyl group to be attacked by nucleophiles, desilylative S E 2′ reactions are typically observed …”

Regioselective Fluorohydrin Synthesis from Allylsilanes

“…22 We attribute the rate acceleration, along with control of regioselectivity, to the beta-silyl effect, similar to rate enhancements observed for other reactions involving cationic intermediates with a silicon group at the β-position. 23 Scheme 2. Explanation of regioselectivity observed and structures of byproducts.…”

Diastereoselective access to substituted oxetanes via hydrosilylation–iodocyclisation of homopropargylic alcohols

“…We subsequently aimed to explore the cyclisation of the resultant vinyl silanes into oxetanes through an electrophilic activation strategy by taking advantage of the well-established b-silicon effect. 24 We began our investigation using model substrate 1a employing 10 mol% of PtCl 2 (Scheme 1). Whilst we were pleased to observe consumption of the starting alkyne, 1 H NMR analysis of the crude reaction mixture indicated the presence of the branched alkene arising from chelate directed hydrosilylation.…”

“…We subsequently aimed to explore the cyclisation of the resultant vinyl silanes into oxetanes through an electrophilic activation strategy by taking advantage of the well-established β-silicon effect. 24…”