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

Peter R Gallagher; Andrea Savoini; Abed Saady; John R J Maynard; Patrick W V Butler; Graham J Tizzard; Stephen M Goldup

doi:10.1021/jacs.3c14329

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

J Am Chem Soc. 2024 Apr 3;146(13):9134-9141. doi: 10.1021/jacs.3c14329. Epub 2024 Mar 20.

Authors

Peter R Gallagher^{1

2}, Andrea Savoini^{1

2}, Abed Saady^{1

2}, John R J Maynard¹, Patrick W V Butler¹, Graham J Tizzard¹, Stephen M Goldup^{1

2}

Affiliations

¹ Chemistry, University of Southampton, University Road, Southampton, SO17 1BJ, U.K.
² School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.

Abstract

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 stereodifferentiating interaction sufficient for moderate to excellent stereoselectivity. Using this understanding, we demonstrated the first direct enantioselective (70% ee) synthesis of a mechanically axially chiral rotaxane.