Chiral Crystals from Dynamic Combinatorial Libraries of Achiral Macrocyclic Imines

Dynamic combinatorial chemistry (DCC) was initially introduced as a means to solve problems of effective synthesis of complex compounds in solution. It benefits from the use of reversible reactions to connect simple building blocks under thermodynamic control. We present an application of DCC to generate structurally diverse crystalline complexes of macrocyclic imines, some of which crystallized as chiral crystals, despite the use of achiral substrates only. Features of imine complexes such as easy synthesis of building blocks and a high tendency to crystallize make them good candidates for studying the relationship between molecular structure and crystallinity

Tetra‑(<i>meta</i>-butylcarbamoyl)azobenzene: A Rationally Designed Photoswitch with Binding Affinity for Oxoanions in a Long-Lived <i>Z</i>‑State

A new photoswitchable anion receptor <b>1</b> based on a tetra-<i>meta</i>-substituted azobenzene skeleton has been readily synthesized in two steps. Titration studies (¹H NMR) and theoretical predictions (DFT/­M06-2X/­6-31G­(d)/­DMSO-SM8) revealed that nonplanar <i>Z</i>-<b>1</b> is a better host for anions than <i>E</i>-<b>1</b>, which results from the greater ability of four amide NH protons in the <i>Z</i>-state to cooperatively bind oxoanions, in particular tetrahedral H₂PO₄^– and H₂AsO₄^–. Furthermore, the thermal decay of <i>Z</i>-<b>1</b> (τ_1/2 = 11 days) is not accelerated by anion binding

Sweet Anion Receptors: Recognition of Chiral Carboxylate Anions by d‑Glucuronic-Acid-Decorated Diindolylmethane

Anion receptors containing glucuronic acid were synthesized, and their anion binding ability studied. Chirality of anionic guests derived from mandelic acid and amino acids can be distinguished not only in terms of stability constants but also by significant differences in chemical shift changes for sugar moiety protons

Sweet Anion Receptors: Recognition of Chiral Carboxylate Anions by d‑Glucuronic-Acid-Decorated Diindolylmethane

Anion receptors containing glucuronic acid were synthesized, and their anion binding ability studied. Chirality of anionic guests derived from mandelic acid and amino acids can be distinguished not only in terms of stability constants but also by significant differences in chemical shift changes for sugar moiety protons

Trapping of Octameric Water Cluster by the Neutral Unclosed Cryptand Environment

Unclosed cryptands (UCs) are neutral and easily accessible compounds with precisely defined spatial arrangement of various functional groups. They readily form crystals with a unusually high packing efficiency (≥0.8), thus providing a well-suited 3D-framework for study of supramolecular assemblies. Herein, one example of the discrete eight-membered water cluster trapped in the matrix of UC 1 is presented. X-ray, ATR FT-IR, and DFT studies indicate extraordinary stability of this assembly, which originated from the cumulative interplay of many noncovalent interactionshydrogen bonds and London dispersion forces

Exploring the Chiral Recognition of Carboxylates by <i>C</i>₂‑Symmetric Receptors Bearing Glucosamine Pendant Arms

Two urea-based receptors containing a glucosamine derivative were synthesized and investigated in terms of their ability to recognize chiral and achiral anions. Both receptors demonstrated a high affinity toward carboxylates in very competitive DMSO/water mixtures. The chiral recognition properties of these compounds were studied using structurally differentiated guests derived from mandelic acid and α-amino acids. We found that receptor <b>1</b> exhibits significantly higher enantioselectivities than compound <b>2</b> for all anions investigated, with a <i>K</i>_<i>S</i>/<i>K</i>_<i>R</i> ratio of up to 2. This low enantiodiscrimination in the case of receptor <b>2</b> is attributed to a lack of interactions between its sugar moieties and the side chain of chiral anions, due to their inadequate spatial arrangement

Engineering Light-Mediated Bistable Azobenzene Switches Bearing Urea d‑Aminoglucose Units for Chiral Discrimination of Carboxylates

The symmetrical molecular receptors <b>1a</b> and <b>1b</b> consisting of a photochemically addressable azobenzene tether functionalized with urea hydrogen-bonding groups and d-carbohydrates as chiral selectors were developed to achieve control over the chiral recognition of α-amino acid-derived carboxylates. The photo- and thermally interconvertible planar <i>E</i>-<b>1</b> and concaved <i>Z</i>-<b>1</b> were found to exhibit different affinities, selectivities, and binding modes toward these biologically important anions in a highly polar medium (DMSO + 0.5% H₂O). Binding affinity for the same enantiomerically pure guest was up to 3 times higher for <i>E</i>-<b>1</b> than for <i>Z</i>-<b>1</b> (cf. parameter β). In addition, the rate of thermal <i>Z</i> → <i>E</i> isomerization was found to depend on the chiral binding ability of <i>Z-</i><b>1</b>, i.e., more strongly bound carboxylate enantiomer as well as higher enantiomer concentration caused faster relaxation to <i>E-</i><b>1</b>

Enantioselective Friedel–Crafts Reaction of Acylpyrroles with Glyoxylates Catalyzed by BINOL–Ti(IV) Complexes

We report the first efficient enantioselective Friedel–Crafts hydroxyalkylation of pyrroles having one electron<i>-</i>withdrawing group at the α, β or <i>N</i>-positions with alkyl glyoxylates catalyzed by readily available chiral BINOL–Ti(IV) complexes (1–5 mol %). The reaction regioselectively led to the desired pyrrole-hydroxyacetic acid derivatives with good yields (70–96%) and enantiomeric excesses up to 96%, and is applicable in multigram scale with low loading of the catalyst (1 mol %)

Enantioselective Liquid–Solid Extraction (ELSE)An Unexplored, Fast, and Precise Analytical Method

A novel method of evaluating the enantioselectivity of chiral receptors is investigated. It involves extraction of an ionic guest in racemic form from an ion-exchange resin to the organic solvent, where it is bound by a chiral receptor. The enantioselectivity of the examined receptor is determined simply by measuring the enantiomeric excess of the extracted guest. We show that the concept is viable for neutral receptors binding chiral organic anions extracted into acetonitile. This method was determined to be more accurate and far less time-consuming than the classical titrations. Multiple racemic guests can be applied to a resin in a single experiment, giving the method a very high throughput

8‑Propyldithieno[3,2‑<i>b</i>:2′,3′‑<i>e</i>]­pyridine-3,5-diamine (DITIPIRAM) Derivatives as Neutral Receptors Tailored for Binding of Carboxylates

The DITIPIRAM (8-propyldithieno­[3,2-<i>b</i>:2′,3′-<i>e</i>]­pyridine-3,5-diamine)-based receptors <b>11</b> and <b>12</b> were readily synthesized, and their anion-binding properties were studied both in solution and in the solid-state. ¹H NMR titrations revealed that receptor <b>12</b> equipped with two phenyl-urea groups preferentially binds carboxylates, even in the highly competitive DMSO<i>-d</i>₆/CD₃OH solvent mixture. X-ray analysis showed that receptor <b>12</b> exhibited great complementarity for benzoate, which is cooperatively bound by the means of four highly directional hydrogen bonds from the two urea groups. Comparison with the most effective acyclic receptors based on a structurally related rigid carbazole platform demonstrates that the DITIPIRAM motif provides a better suited geometry in the binding pocket, and consequently stronger anion binding