Two Iron Catalysts are Better than One: A General and Convenient Reduction of Aromatic and Aliphatic Primary Amides

Abstract

It takes two: For the reduction of amides to amines iron catalysts were developed. A combination of two different iron catalysts made possible the challenging reduction of primary amides (see picture).

Iron-catalyzed reduction of carboxylic and carbonic acid derivatives

“…Scheme 9: reduction of primary amides into amines with in situ generated iron complex [20]. combination [20].…”

“…Based on these previous results, the group of Beller investigated a combination of two different iron-catalyzed reactions to obtain the primary amines: one iron precursor to catalyze dehydration of amides to nitriles and a second one for the reduction step [20]. After a complete screening of the reaction parameters (iron salt pre-catalysts and loading, nature of the nitrogen-based ligands, solvent, silane), the scope was performed with 5 mol% of for the reduction of nitriles, in the presence of (EtO) 2 MeSiH (Scheme 9).…”

“…Proposed mechanism for the hydrosilylation of urea derivatives[34].After hydrosilylation of the carbonyl function and dehydrogenative amine silylation catalyzed by the iron complex, subsequent elimination of siloxane liberated the carbodiimide II. This transformation is reminiscent of the dehydration of primary amides to nitriles using hydrosilanes already discussed above[20]. It proceeds similarly through dehydrogenative silylation of both N-H bonds of the di-substituted urea and subsequent elimination of the siloxane product.…”

Direct Hydrosilylation of Tertiary Amides to Amines by an In Situ Formed Iron/N‐Heterocyclic Carbene Catalyst

“…[10] Beller showed that the iron-carbonyl complex [Fe 3 -(CO) 12 ] could be used together with polymethylhydrosiloxane (PMHS) for the direct reduction of tertiary amides to amines at 100°C. [16] We recently reported that a highly active, in situ formed iron/NHC complex formed from iron(II) acetate and 1-(2-hydroxyethyl)-3-methylimidazolium triflate [HEMIM]-[OTF] efficiently catalyzed the reduction of aldehydes and ketones under hydrosilylation conditions (Scheme 1). The reaction could be carried out under both thermal and photoassisted conditions by using either PMHS or 1,1,3,3-tetramethyldisiloxane (TMDS) as the reducing agent.…”

Ligand strategies for green chemistry. Catalysts for amide reduction and hydroamination

“…8 Primary amides were also reduced using a diiron system with methyldiethoxysilane and achieved yields from 49 to 70%. 9 Beller has reported zinc-catalyzed reduction of tertiary and secondary amides. 10 Mild conditions are reported and wide functional group tolerance is achieved (eq.…”