Strategies for the Synthesis of Enantiopure Mechanically Chiral Molecules

Mechanically interlocked molecules, such as rotaxanes and catenanes, are composed of two or more covalent subcomponents threaded through one another such that they cannot be separated without breaking a covalent bond. This arrangement can allow the covalent subcomponents to undergo large-amplitude relative motion, and this property of the mechanical bond has been widely exploited in the design and synthesis of molecular machines. Another less well-known property of the mechanical bond is that it can give rise to chirotopic stereogenic units that do not rely on covalent stereogenic elements. Although the study of such "mechanically chiral" molecules is expanding, their synthesis in enantiopure form remains challenging. In this Perspective, we review the strategies available, highlighting key examples along the way, and suggest future areas for development.