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Updated: Jul 2, 2025

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Catalyst-Controlled Intermolecular Homobenzylic C(sp3)-H Amination for the Synthesis of β-Arylethylamines
Erwan Brunard1, Vincent Boquet1, Tanguy Saget1
1Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, 91198 Gif-sur-Yvette, France.
Abstract:
The combination of a tailored sulfamate with a C4-symmetrical rhodium(II) tetracarboxylate allows to uncover a selective intermolecular amination of unactivated homobenzylic C(sp3)-H bonds. The reaction has a broad scope (>30 examples) and proceeds with a high level of regioselectivity with homobenzylic/benzylic ratio of up to 35:1, thereby providing a direct access to β-arylethylamines that are of utmost interest in medicinal chemistry. Computational investigations evidenced a concerted mechanism, involving an asynchronous transition state. Based on a combined activation strain model and energy decomposition analysis, the regioselectivity of the reaction was found to rely mainly on the degree of orbital interaction between the [Rh2]-nitrene and the C-H bond. The latter is facilitated at the homobenzylic position due to the establishment of specific noncovalent interactions within the catalytic pocket.
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