Lewis Acid-Catalyzed Borono-Minisci Reactions of Arylboronic Acids and Heterocycles
Year: 2016
Type: article
Abstract: A Lewis acid-catalyzed Minisci reaction between arylboronic acids and heterocycles has been developed.This radical-coupling reaction was demonstrated employing several different heterocycles as well as electron-rich arylboronic acids.Quinoline substrates afforded modest regioselectivity for substitution at the 4-position under the reaction conditions, in contrast to previously reported Brønsted acid-mediated reactions with quinoline substrates that favored substitution at the 2-position.The Minisci reaction has been a powerful reaction for the derivatization of heterocycles. 1 The Minisci reaction is broadly defined as the addition of a radical to a heterocycle and subsequent rearomatization of the heterocycle.While many radical precursors have been demonstrated to work in this reaction, arylboronic acids have only recently been identified as convenient sources of aryl radical precursors. 2 One of the remaining drawbacks to the Minisci reaction is the lack of regioselectivity.The regioselectivity in these radical reactions is determined by the inherent reactivity of the substrate. 3We hypothesized that Lewis acids could promote regioselective Minisci reactions by sterically blocking access to the electrophilic 2-position of heterocycles.Alternative methods have been developed to provide heterocycle-aryl coupling. 4-7An approach that attracted our interest was precoordination of a Lewis acid to the heterocycle followed by addition of a Grignard or zinc ionic nucleophile that provided one regioisomer of the coupled product. 8Typically in a Minisci reaction the heterocycle is activated by a Brønsted acid.We sought to examine whether Lewis acids would be effective catalysts in radical Minisci reactions and to evaluate the regioselectivity in these reactions to determine if the Lewis acid coordination could overcome the inherent reactivity of the heterocycle.Lewis acids have previously been employed in Minisci reactions. 9,10These reactions occur under forcing thermal conditions, making the possibility for a regioselective reaction unlikely.The coupling between
Source: Heterocycles
DOI: 10.3987/com-16-13506
Institution: College of Charleston
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: diamond
Funder: National Science Foundation
OpenAlex ID: W2951423288