Impact of Host Flexibility on Selectivity in a Supramolecular Host-Catalyzed Enantioselective aza-Darzens Reaction

• Published in: Journal of the American Chemical Society Vol. 144; no. 25; pp. 11425 - 11433
• Main Authors: Bierschenk, Stephen M., Pan, Judy Y., Settineri, Nicholas S., Warzok, Ulrike, Bergman, Robert G., Raymond, Kenneth N., Toste, F. Dean
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 29.06.2022; Amer Chemical Soc; American Chemical Society (ACS)
• Subjects: amides; catalysts; cavities; Chemistry; Chemistry, Multidisciplinary; condensation; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Physical Sciences; Science & Technology; selectivity; DESIGN; DIELS-ALDER REACTIONS; ENZYMES; STATE; NONCOVALENT INTERACTIONS; HYDROFORMYLATION; WATER
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.2c04182

A highly enantioselective aza-Darzens reaction (up to 99% ee) catalyzed by an enantiopure supramolecular host has been discovered. To understand the role of host structure on reaction outcome, nine new gallium­(III)-based enantiopure supramolecular assemblies were prepared via substitution of the external chiral amide. Despite the distal nature of the substitution in these catalysts, changes in enantioselectivity (61 to 90% ee) in the aziridine product were observed. The enantioselectivities were correlated to the flexibility of the supramolecular host scaffold as measured by the kinetics of exchange of a model cationic guest. This correlation led to the development of a best-in-class catalyst by substituting the gallium­(III)-based host with one based on indium­(III), which generated the most flexible and selective catalyst.