RESUMEN

A novel synthesis strategy to access 2-alkoxyquinoline derivatives via a palladium-driven cascade reaction is disclosed. Unlike classic methods based on the alkylation of 2-quinolones with alkyl halides, the present method benefits from the de novo assembly of the quinoline core starting from 1,3-butadiynamides. Palladium-catalyzed reaction cascades with N-(2-iodophenyl)-N-tosyl-1,3-butadiynamides and primary alcohols as external nucleophiles proceed under mild reaction conditions and selectively deliver a variety of differently functionalized 4-alkenyl 2-alkoxyquinolines in a single batch transformation.

RESUMEN

1,3-butadiynamides-the ethynylogous variants of ynamides-receive considerable attention as precursors of complex molecular scaffolds for organic and heterocyclic chemistry. The synthetic potential of these C4-building blocks reveals itself in sophisticated transition-metal catalyzed annulation reactions and in metal-free or silver-mediated HDDA (Hexa-dehydro-Diels-Alder) cycloadditions. 1,3-Butadiynamides also gain significance as optoelectronic materials and in less explored views on their unique helical twisted frontier molecular orbitals (Hel-FMOs). The present account summarizes different methodologies for the synthesis of 1,3-butadiynamides followed by the description of their molecular structure and electronic properties. Finally, the surprisingly rich chemistry of 1,3-butadiynamides as versatile C4-building blocks in heterocyclic chemistry is reviewed by compiling their exciting reactivity, specificity and opportunities for organic synthesis. Besides chemical transformations and use in synthesis, a focus is set on the mechanistic understanding of the chemistry of 1,3-butadiynamides-suggesting that 1,3-butadiynamides are not just simple alkynes. These ethynylogous variants of ynamides have their own molecular character and chemical reactivity and reflect a new class of remarkably useful compounds.

Asunto(s)

Elementos de Transición , Técnicas de Química Sintética/métodos , Reacción de Cicloadición , Estructura Molecular , Plata

RESUMEN

Divergent Pd-catalyzed reaction cascades with various 1,3-diynamides yielding either 2-amino-3-alkynylindoles or 2-amino-4-alkenylquinolines were established. Omitting or adding TBAF (tetrabutylammonium fluoride) to the reaction of N,N-(2-iodophenyl)(4-toluenesulfonyl)-1,3-diynamides with secondary or primary amines in the presence of KOH in THF and catalytic amounts of Pd(PPh3 )4 completely changed the outcome of the reaction. In the absence of TBAF, 2-amino-3-alkynylindoles were the sole products, while the presence of TBAF switched the product formation to 2-amino-4-alkenylquinolines. Deuterium labeling proceeded selectively at the C3 and C11 positions of the 2-amino-4-alkenylquinoline products and this suggests the unprecedented formation of [4]cumulenimines from 1,3-diynamides as reactive key intermediates.