Palladium Iodide Catalyzed Multicomponent Carbonylative Synthesis of 2-(4-Acylfuran-2-yl)acetamides

Abstract

2-Propargyl-1,3-dicarbonyl compounds have been carbonylated under oxidative conditions and with the catalysis of the PdI₂/KI catalytic system to selectively afford previously unreported 2-(4-acylfuran-2-yl)acetamides in fair to good yields (54-81%) over 19 examples. The process takes place under relatively mild conditions and occurs via a mechanistic pathway involving Csp-H activation by oxidative monoamincarbonylation of the terminal triple bond of the substrates with formation of 2-ynamide intermediates, followed by 5-exo-dig O-cyclization (via intramolecular conjugate addition of the in situ formed enolate to the 2-ynamide moiety) and aromative isomerization.

Keywords: C–H activation; alkynes; amides; aminocarbonylation; carbonylation; conjugate addition; cyclization; furans; oxidative carbonylation; palladium.

Scheme 1

PdI₂/KI-catalyzed oxidative monoaminocarbonylation of: (a) Simple alkyl- and arylacetylenes to give 2-ynamides [27,28] and (b) This work: 2-propargyl-1,3-dicarbonyl compounds 1 with amines 2 to 2-(4-acylfuran-2-yl)acetamides 3.

Scheme 2

Mechanistic route leading to 2-(4-acylfuran-2-yl)acetamides 3 by PdI₂/KI-catalyzed oxidative aminocarbonylation of 2-propargyl-1,3-dicarbonyl compounds 1 with secondary amines 2 through the formation of 2-ynamide intermediates I and II.