A Fast and General Route to Ketones from Amides and Organolithium Compounds under Aerobic Conditions: Synthetic and Mechanistic Aspects

We report that the nucleophilic acyl substitution reaction of aliphatic and (hetero)aromatic amides by organolithium reagents proceeds quickly (20 s time), efficiently, chemoselectively with a broad substrate scope in environmentally responsible cyclopentyl methyl ether, at ambient temperature under air, to provide ketones up 93 % yield an effective suppression notorious over-addition reaction. Detailed DFT calculations NMR investigations support experimental results. The described methodology was proven be amenable scale-up recyclability protocols. Contrasting classical procedures carried out inert atmospheres, this work lays foundation for profound paradigm shift reactivity carboxylic acid organolithiums, being straightforwardly obtained simply combining aerobic conditions no need using previously modified or pre-activated amides, as recommended.