Palladium-Catalyzed Aerobic α,β-Dehydrogenation of Aliphatic Amides

Abstract

A Pd(II)-catalyzed α,β-dehydrogenation of substituted aliphatic amides assisted by a reusable bis-chelating 8aminoquinoline ligand is demonstrated. Broad spectra of βsubstituted including olefin-substituted aliphatic amides are well tolerated. The present protocol efficiently dehydrogenates the less acidic aliphatic amides via the chelation-assisted β-C−H bond activation and replaces the traditional enolate-based strategy.

Iron-Catalyzed Aerobic α,β-Dehydrogenation

“…Molecular oxygen is a clean and inexpensive oxidant that has been widely used in industrial oxidations as well as organic synthesis. Pioneered by Theisen and Kirschke et al, catalytic aerobic α,β-dehydrogenation has been well-established by Muzart, Wenzel, Fuchita, Li, Stahl, Huang, Wang, Jeganmohan, and our group, using palladium as a catalyst. − In 2013, Xu and co-workers developed a copper-catalyzed α,β-dehydrogenation of 4,5-dihydropyridazin-3­(2 H )-ones in the presence of excess Na 2 CO 3 and pyridine . In 2018, Huang and co-workers reported an efficient iridium-catalyzed aerobic α,β-dehydrogenation of γ,δ-unsaturated amides and acids.…”

“…Their preparation from the corresponding saturated substrates is the most convenient and straightforward process and is thus of great importance. Traditional methods normally required a multistep process or the involvement of stoichiometric halogen-containing oxidants. , Utilization of a transition metal as a catalyst has been proven to be the most efficient method for the single-step α,β-dehydrogenation of carbonyls, and significant advances have been achieved. − …”

Synthesis of conjugated dienes via palladium-catalysed aerobic dehydrogenation of unsaturated acids and amides

“…Recently, our group has reported a bidentate 8-aminoquinoline directing group-assisted selective aerobic dehydrogenation of substituted amides. 12 Furthermore, the bischelating 8-aminoquinoline ligand was cleaved to generate biologically relevant conjugated dienoic acids efficiently. However, the requirement of additional steps to install and remove the directing group limits the synthetic efficiency of the reaction.…”