Control of atropoisomerism: an access to valuable compounds

Many natural, biologically active compounds are stereogenic with a unique tridimensional structure that is on the origin of the specific interactions with the active binding site. This concept of chirality goes beyond chiral stereocenters, englobing also atropoisomerism related to a hindered rotation around an axis with the isolation of atropostable conformers at room temperature. Atropoisomerism is well-known in biaryls, however this phenomenon is encountered in many pharmaceutically relevant compounds such as heterobiaryl, diarylamines, benzamides and anilides. Currently four FDA-approved drugs are atropostable and many others are in clinical trials. It is also important to note that almost 30% of recent FDA-approved small molecules are "proatropisomeric" and interact with a target in a specific chiral conformation. Given this vivid interest in C-C but also C-N atropisomerically stable compounds, this account will detail the new atropoisomeric strategies we developed and their applications in the synthesis of relevant molecules and ligands.