Nitrile Synthesis by Aerobic Oxidation of Primary Amines and in situ Generated Imines from Aldehydes and Ammonium Salt with Grubbs Catalyst

Abstract

Herein, a Grubbs‐catalyzed route for the synthesis of nitriles via the aerobic oxidation of primary amines is reported. This reaction accommodates a variety of substrates, including simple primary amines, sterically hindered β,β‐disubstituted amines, allylamine, benzylamines, and α‐amino esters. Reaction compatibility with various functionalities is also noted, particularly with alkenes, alkynes, halogens, esters, silyl ethers, and free hydroxyl groups. The nitriles were also synthesized via the oxidation of imines generated from aldehydes and NH4OAc in situ.

NH4Br‐Promoted Single‐Step and Transition‐Metal‐Free Conversion of Aldehydes to Nitriles in Ammonia Water

“…Ammonia salts are cheap, nontoxic and could be used as a “CN” source [3] for help in improving reaction yields [7c] . We began the initial study with 4‐nitrobenzaldehyde 1 a and a variety of ammonium salts.…”

“…Furthermore, nitriles can be applied to synthesize natural compounds, agrochemicals, materials and dyes. [3] Therefore, developing a general and efficient method for nitrile preparation has attracted intense interest in the organic synthesis field.…”

“…The cyano group (CN) is a motif that widely exists in the structure of many bioactive molecules and pharmaceutical drugs, [2] selective drug examples are shown in Figure 1. Furthermore, nitriles can be applied to synthesize natural compounds, agrochemicals, materials and dyes [3] . Therefore, developing a general and efficient method for nitrile preparation has attracted intense interest in the organic synthesis field.…”

A Concise Enantioselective Total Synthesis of (−)‐Deoxoapodine

“…The reaction with iodine and sodium bicarbonate in acetonitrile [12a] and oxidation conditions by using potassium ferricyanide [21] gave the desired product 23, although the yield was only 6 % (entries 3 and 4). Next, an electrochemical condition [22] and the aerobic oxidation with Grubbs catalyst developed by our group [23] were examined. In both cases, the starting material 6 was completely consumed, however, the desired product 23 was not obtained (entries 5 and 6).…”

Silver-Catalyzed Synthesis of Nitriles from Carboxylic Acids and Cyanamides

“…Another established nitrogen atom transfer reaction is transnitrilation (Scheme 1b). 18 Nevertheless, the harsh reaction conditions, such as high temperature (≥ 200 °C) as well as the requirement of an excess of Bro̷ nsted acids and sacrificial nitriles, restrict the functional This article is protected by copyright. All rights reserved.…”