One-Pot Twofold Unsymmetrical C–Si Bond 2,6-Bifunctionalization of Arenes via Sequential [1,4]-Csp² to O-Silyl Migration

Abstract

Twofold unsymmetrical C−Si bond bifunctionalization of 2,6-di(trimethylsilyl) benzyl alcohols has been achieved in one pot via sequential [1,4]-Csp 2 to O-silyl migration. The hydroxyl group functions as an "on−off−on" switch to control two successive silyl migrations, and 4,7dimethyl-o-phenanthroline ligand favors cleavage of the endocyclic C−Si bond. Diverse Csp 3 /Csp 3 or Csp 2 /Csp 3 electrophiles can be installed at the 2-and 6-positions. This approach was used to chemoselectively functionalize the three C−Si bonds of 2,4,6-tri(trimethylsilyl) benzyl alcohol, transforming it into isochroman derivatives. The approach even works as a five-component reaction to construct complex symmetric structures.

Revisiting the Mg/TMSCl/Dipolar Solvent System for Dearomatic Silylation of Aryl Carbonyl Compounds: Substrate Scope, Transformations, and Mechanistic Studies

“…1 H NMR (400 MHz, CDCl 3 ): δ 7.52–7.50 (d, J = 8.0 Hz, 2H, Ar–H), 7.32–7.30 (d, J = 8.0 Hz, 2H, Ar–H), 3.53–3.51 (m, 2H, N–CH 2 ), 3.25–3.23 (m, 2H, N–CH 2 ), 1.24–1.20 (m, 3H, C–CH 3 ), 1.10–1.07 (m, 3H, C–CH 3 ), 0.25 (s, 9H, Si­(CH 3 ) 3 ). 1 H NMR is consistent with the literature …”

“…1 H NMR is consistent with the literature. 30 N,N-Diethyl-3-fluoro-4-(trimethylsilyl)benzamide (33). Purification of 33 by flash column chromatography (petroleum ether/ethyl acetate: 5/1) afforded the desired product as a yellow oil (60.2 mg, 45% yield).…”

“…trans-N,N-Dimethyl-4-(trimethylsilyl)cyclohexa-2,5-diene-1-carboxamide (30). Purification of 30 by flash column chromatography afforded the desired product as a yellow oil (1.4744 g, 44% yield).…”

Unveiling Novel Synthetic Pathways through Brook Rearrangement

“…More recently in 2019, Song and co-workers have successfully applied this strategy to the difunctionalization of arenes, through two successive [1,4]-silyl migrations of 2,6-bis(trimethylsilyl)benzyl alcohols in a one-pot process. 25 The Smith group furthered the development of the [1,4]-C(sp 2 )-O silyl migration by targeting o-(trimethylsilyl)benzaldehyde (20). 26 Following the addition of various metalated carbon nucleophiles and subsequent transmetalation with copper(I) salts, the resulting copper alkoxides underwent Brook rearrangement, generating arylcopper species capable of reacting with various electrophiles (Scheme 5C).…”

C(sp2)−Si Bond Functionalization through Intramolecular Activation by Alkoxides

“…The alkoxide thus formed is engaged in a second [1,4]‐C(sp 2 )→O trimethylsilyl migration, which gives the difunctionalized compounds 64 by reaction with E 2 X 2 . This method can also be combined with palladium cross‐coupling reactions to perform arylation and vinylation reactions [44] …”