Template‐Directed Quantitative One‐Pot Synthesis of Homochiral Helical Receptors Enabling Enantioselective Binding

Abstract

Template‐directed synthesis and dynamic covalent chemistry were implemented to achieve quantitative one‐pot syntheses of homochiral helical cavities inside aromatic foldamers. One‐handed helical receptors P‐1, M‐1, P‐2 and M‐2 were assembled from their precursors in the presence of appropriate templates (d‐ and l‐tartaric acid, and d‐ and l‐sorbitol, respectively) via three sequential steps in one pot: imine‐linked chain elongation, template‐induced folding and [4+2] cycloaddition between helical turns. These helical receptors were proven to enantioselectively bind chiral guests used as the templates, and the differences between the association constants of enantiomeric guests were up to more than two orders of magnitude. The structures and binding modes of the receptors were fully characterized by single‐crystal X‐ray crystallography and 1H NMR spectroscopy.

Enantioselective Recognition of Racemic Amino Alcohols in Aqueous Solution by Chiral Metal‐Oxide Keplerate {Mo132} Cluster Capsules

“…This is important as the specific stereochemistry of a molecule determines the chemical, physical and biological properties of the species. Structures including cyclodextrins, [1] calixarenes, crown ethers, porphyrins, [2] cucurbiturils, [3] and cages/cavities,[ 4 , 5 , 6 , 7 ] have been explored as hosts for probing chiral analytes by noncovalent interactions using solution‐state NMR, mostly in organic media. The development of extended chiral metal‐organic frameworks and their application to NMR chiral recognition methods has thus far been limited to solid‐state analyses.…”

Subtle Modification of Imine‐linked Helical Receptors to Significantly Alter their Binding Affinities and Selectivities for Chiral Guests

“…[4] Previously, we described the one-pot synthesis of covalently modified aromatic receptors 1 and 2 bearing homochiral helical cavities capable of accommodating chiral guests with high affinities and selectivities (Figure 1). [5] Specifically, receptor 1 was quantitatively formed in a 2 : 1 mixture of tetramer 3 and 1,3-diaminobenzene (5) in the presence of d-or l-tartaric acid. The reaction proceeded through the formation of a chainelongated intermediate foldamer with imine linkages, [6] followed by intramolecular [4 + 2] cycloaddition (Povarov reaction) [7] between iminobenzene and alkyne units in the helically folded backbone.…”

“…In addition, tartaric acid is an acid catalyst for both imine bond formation and intramolecular [4 + 2] cycloaddition. Similarly, another receptor 2 with a more spacious cavity was also assembled using tetramer 4, 1,3-diaminobenzene (5) and an acid catalyst, d-tartaric acid. In this case, d-or l-sorbitol was required to function as a template for the completion of the reaction and to control the helix orientation.…”

Template‐Directed Quantitative One‐Pot Synthesis of Homochiral Helical Receptors Enabling Enantioselective Binding

“…Racemic crystallization [12] was performed to obtain single crystals suitable for X-ray diffraction via vapor diffusion of pentane into a tetrahydrofuran solution containing a racemic mixture of two enantiomeric complexes of P-1 and M-1 with d/l-tartaric acid (3 equiv). As shown in Figure 1, and Figures S26 and S27, [13] P-1'd-TA and M-1'l-TA adopt helically folded conformations, and one end of the helices is severely distorted as a result of intramolecular [4+2] cycloaddition between helical turns. P-1 and M-1 are right-and left-handed helical receptors that can encapsulate d-and l-tartaric acid, respectively.…”

“…The structures of P-2 and M-2 were determined by the X-ray crystal structures of their complexes P-2'd-sorbitol and M-2'l-sorbitol ( Figure 3 b; Figures S28 and S29). [13] Single crystals were grown by vapor diffusion of hexane into Figure S30 and Table S9, d-and l-sorbitol are completely encapsulated inside the cavities through the formation of 10 H-bonds. Notably, bound sorbitol exhibits conformational features that are distinct from free sorbitol.…”