Single-Step Enantioselective Synthesis of Mechanically Planar Chiral [2]Rotaxanes Using a Chiral Leaving Group Strategy

• Published in: Journal of the American Chemical Society Vol. 142; no. 21; pp. 9803 - 9808
• Main Authors: Tian, Chong, Fielden, Stephen D. P, Pérez-Saavedra, Borja, Vitorica-Yrezabal, Iñigo J, Leigh, David A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.05.2020
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c03447

We report a one-step enantioselective synthesis of mechanically planar chiral [2]­rotaxanes. Previous studies of such molecules have generally involved the separation of enantiomers from racemic mixtures or the preparation and separation of diastereomeric intermediates followed by post-assembly modification to remove other sources of chirality. Here, we demonstrate a simple asymmetric metal-free active template rotaxane synthesis using a primary amine, an activated ester with a chiral leaving group, and an achiral crown ether lacking rotational symmetry. Mechanically planar chiral rotaxanes are obtained directly in up to 50% enantiomeric excess. The rotaxanes were characterized by NMR spectroscopy, high-resolution mass spectrometry, chiral HPLC, single crystal X-ray diffraction, and circular dichroism. Either rotaxane enantiomer could be prepared selectively by incorporating pseudoenantiomeric cinchona alkaloids into the chiral leaving group.