Search

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]