Palladium-catalyzed four-component cascade carbonylative cyclization to access carbonyl-bridged bisheterocycles?

Organic Chemistry Frontiers Pub Date: 2023-01-31 DOI: 10.1039/D2QO01761J

Abstract

An expedient and efficient approach for the synthesis of structurally diverse carbonyl-bridged bisheterocycles has been developed via a palladium-catalyzed four-component carbonylative cyclization of alkenyl-tethered aryl iodides, trifluoroacetimidoyl chlorides and propargyl amines. The reaction proceeds through a cascade intramolecular Heck reaction, carbonylation, nucleopalladation and reductive elimination sequence with the concurrent formation of up to five chemical bonds (two C–N bonds and three C–C bonds) under mild conditions. Control experiments indicate that carbon monoxide plays a critical role in the reaction. An in situ generated acylpalladium species, not σ-alkylpalladium species, triggers the subsequent intramolecular cyclization of alkynyl-tethered amidine, providing straightforward access to functionalized bisheterocycles with high efficiency and excellent chemo- and regioselectivities.

Graphical abstract: Palladium-catalyzed four-component cascade carbonylative cyclization to access carbonyl-bridged bisheterocycles
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