Synthesis and Photochemical Characterization of Indolizine Fluorophores Obtained by a Multicomponent Palladium Iodide−Catalyzed Oxidative Aminocarbonylation Approach

N,N-disubstituted 2-(indolizin-3-yl)acetamides with fluorescent properties are obtained in a multicomponent fashion starting from simple building blocks (2-(pyridin-2-yl)pent-4-yn-1-carbonyl compounds, CO, amines, and oxygen) through a sequential PdI₂/KI-catalyzed oxidative aminocarbonylation – cyclization – aromatization process. Initially formed 2-ynamide intermediates, ensuing from Pd-catalyzed triple bond oxidative aminocarbonylation, are converted in situ into the final products by amine-promoted intramolecular dearomative conjugate addition followed by rearomatization.

Abstract

A catalytic carbonylative method for the direct, multicomponent synthesis of indolizine fluorophores has been developed. The process is based on the PdI₂/KI-catalyzed oxidative aminocarbonylation of 2-(pyridin-2-yl)pent-4-yn-1-carbonyl compounds leading to the corresponding 2-ynamide intermediates, followed in situ by 5-exo-dig cyclization (by amine-promoted conjugate addition of the pyridine ring nitrogen) and aromatization, to give the finally isolated N,N-disubstituted 2-(indolizin-3-yl)acetamides. Reactions are carried out under relatively mild conditions (100 °C under 20 atm of a 4 : 1 mixture CO−air for 6–15 h) in MeCN as the solvent and with a low catalyst loading (0.33 mol% PdI₂), in the presence of 0.5 equiv. of KI and 3 equiv. of a secondary amine. The optical properties of representative 2-(indolizin-3-yl)acetamide products have also been investigated.

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