Facial Selectivity in Mechanical Bond Formation: Axially Chiral Enantiomers and Geometric Isomers from a Simple Prochiral Macrocycle

In 1971, Schill recognized that a prochiral macrocycle encircling an oriented axle led to geometric isomerism in rotaxanes. More recently, we identified an overlooked chiral stereogenic unit in rotaxanes that arises when a prochiral macrocycle encircles a prochiral axle. Here we show that both stereogenic units can be accessed using equivalent strategies, with a single weak stereo-differentiating interaction sufficient for reasonable stereoselectivity. Using this understanding, we were able to demonstrate the first direct enantioselective (70% ee) synthesis of a mechanically axially chiral rotaxane.