Chiral Resorcin Research Articles

Absolute Configuration Assignment of Chiral Resorcin[4]arenes from ECD Spectra.

Racemates of five chiral resorcin[4]arenes, four tetra-O-substituted and one hepta-O-substituted, have been resolved by enantioselective HPLC, and their ECD spectra have been recorded online by stopped-flow measurements. The absolute configuration has been assigned by comparison of the experimental ECD spectra with DFT and semiempirical calculations. For the four tetra-O-substituted resorcin[4]arenes, the ECD exciton couplet at longer wavelength depends on the chirality induced in the arene scaffold by the substituents rather than on the precise nature of the substituents themselves. Accordingly, the exciton chirality model with excitons localized on the arene scaffold, here generalized to Cn symmetry, accurately describes the relationship between stereochemistry and chiroptical properties for this couplet, while its application at shorter wavelengths is unsafe. For the significantly larger hepta-O-substituted system the assignment particularly benefits from the use of the semiempirical ZINDO method.

Inherently Chiral Resorcin[4]arenes with Urea and Amide Side Arms: Synthesis, Structure and Chiral Recognition

AbstractStarting from an inherently chiral aminomethyl‐substituted resorcin[4]arene, a series of urea and amide derivatives were synthesized; these new functionalities extend the macrocycle cavity and introduce new opportunities for chiral recognition. A pair of diastereomeric macrocycles was obtained by introducing (S)‐(–)‐1‐phenylethyl‐urea functionalities. Chiral recognition capabilities of the diastereomeric hosts were investigated by circular dichroism spectral titration to reveal modest R/S selectivities of up to 1.4 for mandelic acid and other related carboxylic guests.

Chirality Effects on the IRMPD Spectra of Basket Resorcinarene/Nucleoside Complexes

The IRMPD spectra of the ESI-formed proton-bound complexes of the R,R,R,R- and S,S,S,S-enantiomers of a bis(diamido)-bridged basket resorcin[4]arene (R and S) with cytosine (1), cytidine (2), and cytarabine (3) were measured in the region 2800-3600 cm(-1). Comparison of the IRMPD spectra with the corresponding ONIOM (B3LYP/6-31(d):UFF)-calculated absorption frequencies allowed the assessment of the vibrational modes that are responsible for the observed spectroscopic features. All of the complexes investigated, apart from [R⋅H⋅3](+), showed similar IRMPD spectra, which points to similar structural and conformational landscapes. Their IRMPD spectra agree with the formation of several isomeric structures in the ESI source, wherein the N(3)-protonated guest establishes noncovalent interactions with the host amidocarbonyl groups that are either oriented inside the host cavity or outside it between one of the bridged side-chains and the upper aromatic nucleus. The IRMPD spectrum of the [R⋅H⋅3](+) complex was clearly different from the others. This difference is attributed to the effect of intramolecular hydrogen-bonding interactions between the C(2')-OH group and the aglycone oxygen atom of the nucleosidic guest upon repulsive interactions between the same oxygen atom and the aromatic rings of the host.

Inherently Chiral Resorcin[4]arenes: A New Concept for Improving the Functionality

A new reactive postion at the upper rim of inherently chiral resorcin[4]arenes was introduced through cleavage of an up to now unreactive methoxy group through the demethylating reagent 9-I-9-BBN. Conservation of the inherent chirality was warranted through the use of a protecting group at the free phenol group.

Unprecedented gas-phase chiroselective logic gates

The gas-phase encounters between 2-aminobutane and proton-bound chiral resorcin[4]arene/nucleoside complexes behave in the gas phase as supramolecular "chiroselective logic gates" by releasing the nucleoside depending on the resorcin[4]arene and the 2-aminobutane configurations.

A Chiral “Frozen” Hydrogen Bonding in C4‐Symmetric Inherently Chiral Resorcin[4]arenes: NMR, X‐ray, Circular Dichroism, and Theoretical Study

AbstractChiral C4‐symmetric resorcinarenes, substituted with l‐amino acid derivatives at upper rims, were synthesized by the modified Mannich reaction and subsequent N‐substitution reactions. Compounds of that type (5a–e) can exist in two relatively stable inherently chiral C4‐symmetric conformations, (M) and (P), stabilized by the formation of seams of hydrogen bonds. However, because of diastereomeric preferences the amino acid substituted resorcinarenes exhibit considerable diastereomeric excesses for the induced conformational inherent chirality (up to ≥95 %). The relatively slow exchange allowed the determination of the directions of the hydrogen bond ring closures through the combined application of NMR (ROESY) and X‐ray analysis. It was also possible to correlate the absolute conformation with the sign of the Cotton effects observed for the transitions within the resorcinol chromophore in the CD spectra (solution and solid state). The ab initio calculations (TDDFT/B3LYP/DZVP and TDDFT/CAMB3LYP/6‐31++G*) for model compounds showed that the chiral arrangement of the hydrogen bonding in resorcinarenes can produce substantial CD effects, which are amplified by exciton coupling. However, it was also shown that the neighboring urea, amide, or phenyl groups have crucial effects on the direction of electric transition dipoles and, as the result, on the signs of the exciton‐coupled bands.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Cavity‐Extended Inherently Chiral Resorcin[4]arenes: Synthesis and Chiroptical Properties of the Cycloenantiomers

AbstractInherently chiral resorcin[4]arenes 2 and 3 were prepared from enantiomerically pure C4‐symmetric rccc‐2,8,14,20‐tetraisobutyl‐4,10,16,22‐tetra‐O‐methylresorcin[4]arene (1). The four 2‐bromobenzyl ether residues in precursor 2 were introduced as halide moieties to partake in an intramolecular Pd‐catalysed C–C cross‐coupling reaction to give tetrabiaryl ether compound 3. The absolute configurations could be derived from the starting compounds and were assigned as (M,R)‐(–)‐2 and (P,S)‐(+)‐2 for the tetrakis(2′‐bromobenzyl) ether compounds as well as (M,R)‐(–)‐3 and (P,S)‐(+)‐3 for the cavity‐extended resorcinarenes. The carbon scaffold of 3 contains four new stereogenic axes whose configurations were assigned by single‐crystal X‐ray analysis. The simulation of the CD spectra by time‐dependent Pariser–Parr–Pople calculations (TDPPP) based on the X‐ray data gave very good images of the experimental spectra. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Cover Picture: Flattened Cone 2,8,14,20‐Tetrakis(L‐valinamido)[4]resorcinarene: An Enantioselective Allosteric Receptor in the Gas Phase (Angew. Chem. Int. Ed. 17/2006)

Protein allosterism is the basis for the molecular control of fundamental processes in living systems, but despite its importance, basic questions on the mechanisms involved remain unanswered. A gas‐phase approach to the problem is described by M. Speranza et al. in their Communication on page 2717 ff., in which they report the highly enantioselective, 2‐aminobutane‐induced loss of D‐ and L‐tryptophan from the achiral hydrophobic rim of a chiral resorcin[4]arene.

Enantioselective guest exchange in a chiral resorcin[4]arene cavity.

Gas-phase proton-bound complexes between a chiral resorcin[4]arene and some representative amino acids, that is, L- and D-alanine or L- and D-serine, were generated in the source of a Fourier transform ion cyclotron resonance mass spectrometer. Gas-phase exchange of the amino acid from the diastereomeric complexes with the enantiomers of 2-butylamine exhibits a significant enantioselectivity, which depends not only upon the configuration of the leaving guest but also on that of the incoming amine. These findings, coupled with molecular dynamic calculations, point to the observed gas-phase enantioselectivity as determined by the effects of the resorcin[4]arene chiral cavity upon the diastereomeric exchange transition structures.