Highly Functionalized Benzene Syntheses by Directed Mono or Multiple Magnesiations with TMPMgCl·LiCl

Abstract

The direct magnesiation of highly functionalized aromatics bearing an ester, a nitrile, or a ketone can be readily performed by using an OBoc as a directing group and TMPMgCl.LiCl as a base. It allows, for example, the preparation of a meta-magnesiated benzophenone in >95%. After quenching, highly functionalized and substituted benzenes are obtained. [reaction: see text].

Regio‐ und chemoselektive Metallierung von Arenen und Heteroarenen mit gehinderten Metallamidbasen

“…Infolgedessen konzentrierten sich jüngste Untersuchungen auf Dimetall-TMP-Basen, wie Magnesiate, [84][85][86][87][88] Zinkate, [89,90] Aluminate, [91,92] Cadmate, [93] Chromate, [94] Manganate [95] und Ferrate. [94] Das TMP-Anion in diesen Reagentien ist ausnahmslos der einzige oder zumindest der aktivste Basenligand, der die Metallierung des Substrats ermçglicht.…”

Modern Amination Reactions

“…[48] Aromatic rings bearing acidic protons can be magnesiated by treatment with TMPMgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidyl). [49] The use of two equivalents of the Grignard reagent was found to be crucial for obtaining complete conversion, as explained by considering the reaction mechanism (Scheme 15). [44,50] Addition of the first equivalent of Grignard reagent to the nitroarene leads, after elimination of a magnesium phenolate, to the intermediate formation of an arylnitroso derivative 32, which reacts with a second equivalent of Grignard reagent to provide the desired diarylamine after reductive workup.…”

General Preparation of Primary, Secondary, and Tertiary Aryl Amines by the Oxidative Coupling of Polyfunctional Aryl and Heteroaryl Amidocuprates

“…[13] We have extended and adapted this procedure to the preparation of various primary, secondary, and tertiary amines. Thus, for the synthesis of primary amines, the diester 2 a was magnesiated with TMPMgCl·LiCl [14] (1.1 equiv, 0 8C, 1 h) which led to the aryl magnesium derivative 3 a [15] (TMP = 2,2,6,6-tetramethylpiperidyl). This was treated with CuCl·2 LiCl [12,13] (1.2 equiv) at À50 8C followed by the addition of bis[2-(N,N-dimethylamino)ethyl]ether (1.2 equiv) [16] and lithium hexamethyldisilazide (LiHMDS (2 equiv); À50 8C, 90 min) to afford the amidocuprate 5 a.…”