Enantioselective Synthesis of Heteroatom-Linked Non-Biaryl Atropisomers

Atropisomers hold significant fascination, not only for their prevalence in natural compounds but also for their biological importance and wide-ranging applications as chiral materials, ligands, and organocatalysts. While biaryl and heterobiaryl atropisomers are commonly studied, the enantioselective synthesis of less abundant heteroatom-linked non-biaryl atropisomers presents a formidable challenge in modern organic synthesis. Unlike classical atropisomers, these molecules allow rotation around two bonds, resulting in low barriers to enantiomerization through concerted bond rotations. In recent years the discovery of new configurationally stable rare non-biaryl scaffolds such as aryl amines, aryl ethers and aryl sulfones as well as innovative methodologies to control their configuration have been disclosed in the literature and constitute the topic of this minireview. The successful atroposelective synthesis of heteroatom-linked non-biaryl atropisomers marks a significant milestone in organic synthesis. Unlike conventional atropisomers, these unique molecules display generally lower enantiomerization barriers due to possible concerted bond rotations. Through innovative strategies, chemists have succeeded in controlling the atroposelectivity of these reactions, enabling the construction of original optically active molecular structures. image