Reductive Functionalization of Amides in Synthesis and for Modification of Bioactive Compounds

In this review, applications of the amide reductive functionalization methodology for the synthesis and modification of bioactive compounds are covered. A brief summary of the different protocols is presented in the introduction, followed by the synthetic application of these in late-stage functionalization, leading to known pharmaceuticals or to their derivatives, including bioisosteres, with potential higher activity as the main axis of the article. The synthetic approach to natural products based on amide reduction is also discussed; however, this is given in a condensed form focusing on recent or as yet unexplored applications due to a number of recently published excellent reviews covering this topic. The aim of this review is to illustrate the potential of reductive functionalization of amides as an elegant and useful tool in the synthesis of bioactive compounds and inspire further work in this field.

The importance of the counter-cation in reductive rare-earth metal chemistry: 18-crown-6 instead of 2,2,2-cryptand allows isolation of [YII(NR2)3]1− and ynediolate and enediolate complexes from CO reactions

The use of 18-crown-6 (18-c-6) in place of 2.2.2-cryptand (crypt) in rare earth amide reduction reactions involving potassium has proven to be crucial in the synthesis of Ln(ii) complexes and isolation of their CO reduction products.

A comparative analysis of hydrosilative amide reduction catalyzed by first-row transition metal (Mn, Fe, Co, and Ni) N-phosphinoamidinate complexes

Screening reveals (PN)Ni(x) pre-catalysts to be effective for the hydrosilative reduction of amides under mild conditions.

Chemoselective reduction of carboxamides

This tutorial review presents the most prominent protocols developed for chemoselective amide reduction.