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

Abstract

In this study, the successful titanium tetrachloride-catalyzed reduction of aldehydes, ketones, carboxylic acids, and nitriles with borane–ammonia was extended to the reduction (deoxygenation) of a variety of aromatic and aliphatic pri-, sec- and tert-carboxamides, by changing the stoichiometry of the catalyst and reductant. The corresponding amines were isolated in good to excellent yields, following a simple acid–base workup.

TiF4-catalyzed direct amidation of carboxylic acids and amino acids with amines

“…We have recently reported the effect of catalytic titanium tetrachloride (TiCl 4 ) for the borane-amine mediated reduction of ketones, 29 acids, 30 amides, 31 and nitriles, 32 deoxygenation of esters to ethers 33 and deoxyhalogenation of carbonyl compounds. 34 During these projects, we undertook a systematic evaluation of the catalytic ability of several metal halides and established that the reaction depended on the Lewis acidity of these halides and TiCl 4 is a critical and superior catalyst.…”

Catalyst- and Stoichiometry-Dependent Deoxygenative Reduction of Esters to Ethers or Alcohols with Borane–Ammonia

“…33 We subsequently demonstrated that TiCl 4activated carboxamides can be conveniently reduced to the corresponding amines with 1a. 34 Systematic extension of this process to reduce carboxylic esters to alcohols has now led to a novel catalyst-dependent deoxygenative reduction to ethers or to alcohols (Scheme 1v).…”

“…During these projects, ketones or acids were selectively reduced in the presence of esters, which is not surprising given the fact that esters are poor substrates for reduction with BTHF or BMS . We subsequently demonstrated that TiCl 4 -activated carboxamides can be conveniently reduced to the corresponding amines with 1a . Systematic extension of this process to reduce carboxylic esters to alcohols has now led to a novel catalyst-dependent deoxygenative reduction to ethers or to alcohols (Scheme v).…”

Reduction of esters to alcohols and iodides using aminodiborane (μ-NH2B2H5): scope and mechanistic investigations

“…4 Very recently, Ramachandran and co-workers reduced nitriles, amides and carboxylic acids using AB and TiCl 4 . 5–7 Among the various B–N dehydrogenated species, 8 aminodiborane (μ-NH 2 B 2 H 5 , ADB) has received recent interest in organic and inorganic syntheses. 9–14 ADB is a strained molecule, which is sensitive to moisture and air.…”