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

Abstract

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.

Catalysis of Synergistic Reactions by Host–Guest Assemblies: Reductive Carbonylation of Nitrobenzenes

“…For instance, the role of scaffold flexibility in promoting the reaction rate and selectivity of supramolecular systems has recently received considerable attention. 26 Previous studies by our group have also underlined the significance of flexible catalytic components in promoting the performance of heterogeneous catalysts by facilitating the activation of reagents. 27,28 composite whose performance is superior to that of the corresponding homogeneous systems.…”

“…Significant efforts have been made by synthetic chemists to mimic enzyme characteristics. For instance, the role of scaffold flexibility in promoting the reaction rate and selectivity of supramolecular systems has recently received considerable attention …”

Supramolecular Capsule-Catalyzed Highly β-Selective Furanosylation Independent of the SN1/SN2 Reaction Pathway

“…Supramolecular capsule and cage catalysis has started emerging as a novel tool for tackling current synthetic challenges in organic chemistry. − Recent examples − included the site-selective functionalization of terpenes, regioselective spirocyclization, asymmetric hydroformylation, selective reductions, , enantioselective aza-Darzens reaction, tail-to-head terpene cyclizations, and a short synthesis of a complex sesquiterpene natural product . Our group recently reported the β-selective pyranosylation of readily available α-pyranosyl chlorides and fluorides (Figure A) catalyzed inside the supramolecular resorcin[4]­arene capsule I (Figure B) .…”

Metallacages and Covalent Cages for Biological Imaging and Therapeutics

“…The development of functional materials with unique cavities and defined morphologies, such as metal–organic frameworks, covalent-organic frameworks, hydrogen-bonded organic frameworks, porous organic polymers, and cages, has always been a focus of synthetic chemists and materials scientists. Additionally, these materials are widely used in many fields, including separation, catalysis, − optoelectronic materials, biological diagnostics, and therapeutics. , Cages have developed relatively slowly compared to other materials, but their controllable three-dimensional cavity structure has attracted increasing attention. Depending on their synthesis method, cages can be generally divided into noncovalent cages and covalent cages, which are constructed by noncovalent interactions and covalent chemical bonds, respectively (Figure a).…”

“…The majority of noncovalent cages are currently constructed through metal coordination, , anion coordination, , π–π stacking, and hydrogen bonds, among which metal coordination cages (abbreviated metallacages) are the most extensively studied. Saalfrank and co-workers reported the first metallacage in 1988, and since then, the groups of Fujita, Stang, Raymond, Nitschke, Shionoya, Clever, Yoshizawa, and others − have successfully developed various coordination-based self-assembly protocols to build numerous metallacages.…”