Enantioselective Synthesis of Atropisomers with Multiple Stereogenic Axes

Abstract

Atropisomers possessing multiple stereogenic axes are intriguing molecules with huge uncovered potential. As compared with molecules with multiple stereogenic centers for which countless methods exist for their stereocontrolled synthesis, only few approaches have been developed for the enantioselective synthesis of this peculiar class of atropisomers. This is due to the still under developed field of axial chirality control and also the often‐low configurational stability of the stereogenic bond, rendering systems with more than one chiral axis even more difficult to assemble with high enantiocontrol. Besides these difficulties, innovative methods have emerged in recent years, opening unforeseen possibilities on future developments in the synthesis of this original class of atropisomeric compounds. This review will cover the history of the development in this field, based on a classification of the multi‐axis systems according to the distance between the stereogenic axes and the strategy used to build them [aryl‐aryl cross‐coupling, (2+2+2) cycloaddition, dynamic kinetic resolution, central‐to‐axial chirality conversion, trapping chiral vinylidene‐quinone methides and a very recent miscellaneous cycloisomerization strategy].