Noncatalyzed Reduction of Nitriles to Primary Amines with Ammonia Borane

Abstract

The preparation of primary amines from nitriles has been a subject of continuing interest, and many different methods have been reported for this process. We report in this paper an alternative method for transforming nitriles into primary amines. In this work, a wide range of nitriles were reduced to primary amines by 1.2 equiv of ammonia borane under thermal decomposition conditions without any catalyst and the corresponding primary amines were isolated in good to excellent yields. The reactions are environmentally benign with H 2 and NH 3 generated as byproducts. The reactions are also tolerant of many functional groups. Nitriles are likely reduced by the in situ-generated aminodiborane, the application of which in organic synthesis has never been reported before. By using our protocol, primary amines containing multifluorinated aromatic rings, which are greatly important in pharmaceutical synthesis and have rarely been prepared via catalytic processes, were successfully prepared.

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

“…20,21 Using appropriate catalysts and activators, it has been applied for the reduction of carbonyls, 22,23 esters, 24,25 amides, 26,27 and a variety of other functional groups. 28,29 As part of our program on borane−amines for organic synthesis, we recently reported efficient room temperature (RT) reductions of ketones 30 and carboxylic acids 31 to alcohols with BH 3 −NH 3 using catalytic (10 mol %) TiCl 4 . 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 32 or BMS.…”

“…Borane–ammonia (BH 3 –NH 3 , 1a ) is an easily prepared, air and moisture stable alternative to borane–tetrahydrofuran (BTHF) and borane–dimethyl sulfide (BMS). A great deal of work has been performed exploring BH 3 –NH 3 as a hydrogen source, , but it is also gaining prominence as a useful reducing agent. , Using appropriate catalysts and activators, it has been applied for the reduction of carbonyls, , esters, , amides, , and a variety of other functional groups. , As part of our program on borane–amines for organic synthesis, we recently reported efficient room temperature (RT) reductions of ketones and carboxylic acids to alcohols with BH 3 –NH 3 using catalytic (10 mol %) TiCl 4 . 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 .…”

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

“…[5][6][7] Among the various B-N dehydrogenated species, 8 aminodiborane (m-NH 2 B 2 H 5 , ADB) has received recent interest in organic and inorganic syntheses. [9][10][11][12][13][14] ADB is a strained molecule, which is sensitive to moisture and air. The isolation of pure ADB as a reagent is cumbersome due to the high reactivity of the compound.…”

“…11,12 So, in situ generation of ADB has been found to be a better alternative for the reduction reactions of various organic functional groups. [12][13][14] The in situ generated ADB has been reported for reduction of carboxylic acids to alcohols 12 and nitriles to amines. 13 Very recently, our group reported that by combining iodine and AB, ADB can be in situ generated which can be used to reduce amides to amines (Scheme 1).…”

“…[12][13][14] The in situ generated ADB has been reported for reduction of carboxylic acids to alcohols 12 and nitriles to amines. 13 Very recently, our group reported that by combining iodine and AB, ADB can be in situ generated which can be used to reduce amides to amines (Scheme 1). 14 Mechanistic steps for generating ADB from catalytic iodine and AB was also proposed.…”