A journey into amide and alkylamine synthesis from CO

International audienceNitrogen containing molecules are essential for life. They are also key products in the chemical industry and areproduced at the megaton scale. Among these compounds, amides and alkylamines are of particular importance.Amides are indeed among the most ubiquitous functions in living systems and form important materials (nylon,hydrogels, etc.), solvents, or pharmaceutics. An analysis carried out by the three leading pharmaceuticalcompanies in 2006, revealed that amide bonds formation was used in the synthesis of 65% of the drugscandidates.Classically, amide compounds are synthesized from the reaction of an activated carboxylic acid derivative with anamine but traditional methods prove expensive with a poor atom economy. An appealing alternative wouldconsist in promoting the direct carbonylation of an amine with CO. During the last decade, a handful of catalystswere shown to facilitate the carbonylation of tertiary amines. However, they require harsh conditions (> 30 bar, >190°C), and use of precious and/or toxic metal (palladium, rhodium or cobalt). In this context, we have designed the first system able to promote the carbonylation of amines to amides with iron catalysts. Low valent iron carbonyl complexes, in combination with a promotor (MeI) and a Lewis acid, favor the carbonylation of a variety of aromatic and aliphatic amines at low CO pressures (P < 8bar