Enantioselective Complexation of Chiral Oxirane Derivatives by an Enantiopure Cryptophane in Water

Abstract

We show here that optically active cryptophane 1 bearing phenol functions can efficiently bind the two enantiomers of 2‐(chloromethyl)oxirane, ethyloxirane, and 2,2′‐bioxirane derivatives in aqueous solution. The binding process is characterized by high‐field 1H NMR signals that are specific to the encapsulated species. In all cases, an enantioselective effect was observed and a relationship between the molecular volume of the guest and the binding constant can be established, even though the flexibility of the guest molecule also seems to play a role. In this series, the 2,2′‐bioxirane guest is a particularly interesting example, because this compound possesses two stereogenic centers. Thus, in solution, three different pairs of enantiomers can be obtained in the presence of the optically active host 1. Electronic circular dichroism (ECD) spectroscopy has also been used to characterize these complexes; specific ECD spectra recorded in the 1Lb region were obtained for each diastereomer.

Enantiopure cryptophane derivatives: Synthesis and chiroptical properties

“…91 On the other hand, dimethyloxirane does not show any affinity for host 47, whereas the two enantiomers of ethyloxirane can access the cavity of this host. 92 As observed, in the case of methyloxirane, different ECD spectra have been obtained in the 1 L b region with the two enantiomers of chloromethyloxirane.…”

“…Small chiral oxiranes derivatives such as methyloxirane (called also propylene oxide (PrO), V vdw = 57 Å 3 ), chloromethyloxirane (called also epichlorohydrin, V vdw = 72 Å 3 ), ethyloxirane (V vdw = 74.2 Å 3 ) and bis-oxirane (V vdw = 70.6 Å 3 ) are also well recognized by cryptophane derivatives bearing ethylenedioxy linkers. [90][91][92] For instance, it has been shown that the two enantiomers of methyloxirane fit well the cavity of anti-47 in basic aqueous solution. Thanks to the strong shielding effect of the benzene rings surrounding the guest molecule, the proton signals in the 1 H NMR spectrum of the encapsulated guest are observed at lower frequencies than those of the free guest in solution.…”

“…Another original example has been reported with the bioxirane (Bo) derivative. 92 This compound is made of two covalently bonded oxirane cycles. Thus, this molecule contains two stereogenic centers, and three stereoisomers are possible for this molecule: (2R,2 0 R)-Bo, (2S,2 0 S)-Bo and the meso derivative (2S,2 0 R)-Bo = (2R,2 0 S)-Bo.…”

“…Small chiral oxiranes derivatives such as methyloxirane (called also propylene oxide (PrO), V vdw = 57 Å 3 ), chloromethyloxirane (called also epichlorohydrin, V vdw = 72 Å 3 ), ethyloxirane (V vdw = 74.2 Å 3 ) and bis‐oxirane (V vdw = 70.6 Å 3 ) are also well recognized by cryptophane derivatives bearing ethylenedioxy linkers 90–92 . For instance, it has been shown that the two enantiomers of methyloxirane fit well the cavity of anti ‐ 47 in basic aqueous solution.…”

Control and Transfer of Chirality Within Well-Defined Tripodal Supramolecular Cages

“…The propagation of the chirality along linkers and even to the opposite face of the cage could lead to highly efficient enantioselective sensors, due to the presence of a strongly controlled chiral environment around the guest-binding site. Indeed, although examples of C 3 -symmetrical cages displaying enantioselectivity in the recognition of chiral guests remain rare (Sambasivan et al, 2010 ; De Rycke et al, 2018 ), it has been recently shown that remarkable enantioselective recognition of chiral neurotransmitters or carbohydrates can be reached by hemicryptophane cages presenting a C 3 symmetrical axis (Long et al, 2018b ; Yang et al, 2020 ). Secondly, by controlling the chirality at both first and second coordination sphere levels of metal complexes, promising chiral confined catalysts for enantioselective transformations could be obtained.…”