ortho‐Selective Nucleophilic Addition of Primary Amines to Silylbenzynes: Synthesis of 2‐Silylanilines

Abstract

Cause and effect: The first ortho‐selective nucleophilic addition reaction of amines to 3‐substituted benzynes has been achieved. Despite a large trimethylsilyl substituent, primary amines attack the C2 position of 3‐silylbenzynes to produce 2‐silylanilines (see scheme). This outcome is likely to result from the inductive electron‐donating effect of the silyl group, which overrides its steric repulsion with the approaching amines.

An Alternative Method for Generating Arynes from ortho-Silylaryl Triflates: Activation by Cesium Carbonate in the Presence of a Crown Ether

“…In particular, activation of ortho-silylaryl triflates with a fluoride ion is one of the most widely-used methods for generating arynes [9]. Due to the increased availability of ortho-silylaryl triflates [10,11], numerous transformations via arynes have been developed based on this method [12][13][14][15][16][17][18][19][20][21][22][23][24].…”

4.09 Nucleophilic Coupling with Arynes

“…102,103 However, high ortho-selectivity toward the nucleophilic addition has been achieved with 3-(trimethylsilyl)arynes, showing that the electronic effect overrides the steric disadvantage, which results from increased polarization of the triple bond by the formation of silicate complex 25 with a fluoride used as an aryne generator (Scheme 18). 104 Regardless of the electron-donating character of the alkyl group, meta-selective addition is observed with cyclobutane-fused benzyne, being ascribable to an enhanced s character of an orbital bound to the a carbon, whereas cyclopentane-fused benzyne gives an equal amount of regioisomers (Scheme 19). 105…”

Experimental and Theoretical Studies on Regiocontrol of Benzyne Reactions Using Silyl and Boryl Directing Groups

“…13 Despite possible steric repulsion between the approaching 48 and the bulky trimethylsilyl group, the reaction occurred preferentially at the 2 position of 7A to furnish ortho 49A (Scheme 6). This unique ortho selectivity was widely demonstrated by the reactions of various 7A with 48, and a range of functional groups such as uoro, chloro, silyloxy, furyl, hydroxyl, amino, and carbamoyl groups, were tolerated.…”