Metal‐Free Catalytic Reduction of Amides: Recent Progress

Abstract

Amines are one of the most important functional groups in organic synthesis, particularly in scaffolds constituting the active ingredients of natural products, pharmaceutical molecules, and agrochemicals. Among various transformations to access amines, amide reduction has been considered as the most facile and efficient strategy, but it is also one of the most problematic, often requiring the use of highly reactive stoichiometric reductants, such as lithium aluminum hydride, as well as rare transition metal catalysts, or both, and harsh reaction conditions. This review covers recent advances in the catalytic reduction of amides to amines without the need for metal catalysts, thus overcoming such problems.

Hydrogenation of amides to amines by heterogeneous catalysis: a review

“…6) for hydrogenation is as follows: tertiary amides < secondary amides < primary amides. 49 It is worth noting that the aforementioned reactivity is made under the assumption that these amides have similar alkyl substituents. However, in reality, the electron density of a specific secondary amide containing an electronegative group may be lower than that of tertiary amides without such groups, making them potentially easier to hydrogenate.…”

Titanium-Mediated Reduction of Carboxamides to Amines with Borane–Ammonia

“…The reduction of a carbonyl moiety is an extremely important transformation that occurs during organic syntheses [ 1 ]. While aldehydes, ketones, carboxylic acids, and esters provide the product alcohols, the reduction of carboxamides typically generates deoxygenated amines [ 2 , 3 ], an extremely important class of compounds due to their multifaceted functions [ 4 , 5 , 6 ]. Although they are efficient for carboxamide reduction, typical hydride reducing agents such as lithium aluminum hydride [ 7 ] are hazardous due to their air and moisture sensitivity.…”

“…We envisioned that the use of borane-ammonia would release only ammonia and provide pure product amines. On the basis of the reported reduction of amides using 2 equivalents of borane derivatives, such as BTHF and BMS [18,19], we aimed to achieve the reduction, if possible, using ≤2.0 equivalents of (2) As part of our ongoing projects on the synthesis [35,36] and application of boraneamines [37], we recently reported the conversion of ketones [38] and carboxylic acids [39] to alcohols (Equation ( 3)) with borane-ammonia in the presence of titanium tetrachloride as an activator of the carbonyls. During the latter project, we had carried out a competitive reduction of an acid and a nitrile or an amide, and described the exclusive reaction of the acids.…”