Amide Synthesis From Alcohols And Amines By The Extrusion Of Dihydrogen

摘要

The amide bond is one of the most important linkages in organic chemistry and constitutes the key functional group in peptides, polymers, and many natural products and Pharmaceuticals. Amides are usually prepared by coupling of carboxylic acids and amines by the use of either a coupling reagent or by prior conversion of the carboxylic acid into a derivative. Alternative procedures include the Staudinger ligation, aminocarbonylation of aryl halides, and oxidative amidation of aldehydes. However, all these methods require stoichiometric amounts of various reagents and lead to equimolar amounts of byproducts. In special cases, amides can be formed by catalytic procedures as shown for the Schmidt reaction between ketones and azides, the Beckmann rearrangement, and the amidation of thioacids with azides.rnA more environmentally friendly protocol for amide synthesis is the direct amidation of amines with alcohols where two molecules of dihydrogen are liberated (Scheme 1). This unique transformation has only been described once before where a ruthenium pincer complex was used for the direct coupling of sterically unhindered primary amines and alcohols.