Size‐Induced Chiral Discrimination Switching by (S)‐(−)‐2(α‐Hydroxyethyl)Benzimidazole‐Derived Azacrowns

Abstract

(S)‐(−)‐2‐(α‐Hydroxyethyl)benzimidazole (1)‐derived diastereomeric monoaza‐[18]crown‐6 compounds 5 and 6 were synthesised with an additional chiral centre bearing a phenyl ring. The aim was to achieve enhanced enantioselective discrimination, compared with monoaza‐[15]crown‐5 (7). Surprisingly, reversal of enantioselective binding for chiral guest enantiomers between the two differently sized [15]crown‐5 and [18]crown‐6 azacrowns were discovered; all three were prepared from the same parent compound, 1. To complete the observations, another [18]crown‐6‐sized azacrown (10) without an additional chiral centre was synthesised from 1 and screened for its enantioselective binding abilities towards the chiral guest enantiomers investigated; these results corroborated the observations. Single‐crystal XRD analysis and molecular docking studies revealed that changes to the conformational aspects of [18]crown‐6 and [15]crown‐5 azacrowns were the major contributing factors to this peculiar behaviour.

Helicene-Based Chiral Auxiliaries and Chirogenesis

“…For example, (M)-140 was able to transport 6% of (S)-142, with optical purity of 75% in 6 h, comparatively better than (M)-141 with 2% transport of 26% optical purity of opposite enantiomer (R)-142 in the same time. The observed opposite enantioselectivity extraction using helicenes 140 and 141 with the same helical sense was rationalized by the phenomenon of changing the crown ether conformation [80]; this is evident in their CPK models. Additionally, the inner methyl groups also assist in the chiral recognition process, as suggested by the same models [78,79].…”

“…The scope of this HELOL host and its structural analogue were further extended towards other nucleophiles such as alcohols, phenols, amines, and carboxylic acids, also containing a remote chirality, under similar methodology to the 31 P NMR-based enantiodiscrimination [82]. opposite enantioselectivity extraction using helicenes 140 and 141 with the same helical sense was rationalized by the phenomenon of changing the crown ether conformation [80]; this is evident in their CPK models. Additionally, the inner methyl groups also assist in the chiral recognition process, as suggested by the same models [78,79].…”

Chiral Heterocycle-Based Receptors for Enantioselective Recognition

“…Symmetrical macrocycles can aslo be prepared using various spacer (Chart 4). Recently, our group [36] has synthesized the chiral benzimidazole-based receptors (Figure 13), mono aza-15-crown-5 181, monoaza- [18]crown-6 (S,R)-182,(S,S)-183, and [18]crown-6-sized aza-crown 184.…”

“…With these findings, an additional component of size-dependent pre-organization effects for the effective binding of enantiomeric guests was introduced. Recently, our group [36] has synthesized the chiral benzimidazole-based receptors (Figure 13 Recently, our group [36] has synthesized the chiral benzimidazole-based receptors (Figure 13), mono aza-15-crown-5 181, monoaza- [18]crown-6 (S,R)-182,(S,S)-183, and [18]crown-6-sized aza-crown 184.…”

“…The present review article presents a detailed account of the recent developments in the design and synthesis of various chiral receptors with heterocyclic motif such as pyridine [18], chromene [32,33], imidazole [34], benzimidazole [35,36], furan [37], thiophene [38], oxazole [22][23][24][25] etc. and its application in the enantioselective recognition of different classes of chiral analytes [39,40].…”