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

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

Polyamide–Polyamine Cryptand as Dicarboxylate Receptor: Dianion Binding Studies in the Solid State, in Solution, and in the Gas Phase

Polyamide–polyamine hybrid macrobicycle <b>L</b> is explored with respect to its ability to bind α,ω-dicarboxylate anions. Potentiometric studies of protonated <b>L</b> with the series of dianions from succinate (suc^2–) through glutarate (glu^2–), α-ketoglutarate (kglu^2–), adipate (adi^2–), pimelate (pim^2–), suberate (sub^2–), to azelate (aze^2–) have shown adipate preference with association constant value of <i>K</i> = 4900 M^–1 in a H₂O/DMSO (50:50 <i>v/v</i>) binary solvent mixture. The binding constant increases from glu^2– to adi^2– and then continuously decreases with the length of the anion chain. Further, potentiometric studies suggest that hydrogen bonding between the guest anions and the amide/ammonium protons of the receptor also contributes to the stability of the associations along with electrostatic interactions. Negative-mode electrospray ionization of aqueous solutions of host–guest complexes shows clear evidence for the selective formation of 1:1 complexes. Single-crystal X-ray structures of complexes of the receptor with glutaric acid, α-ketoglutaric acid, adipic acid, pimelic acid, suberic acid, and azelaic acid assist to understand the observed binding preferences. The solid-state structures reveal a size/shape complementarity between the host and the dicarboxylate anions, which is nicely reflected in the solution state binding studies