This critical review is dedicated to the anion complexation chemistry of amide- and urea-functionalized (benzo)pyrroles, such as pyrroles, indoles, carbazoles, isoindoles, naphthalenodipyrroles and benzodipyrroles. It provides a comprehensive overview of these simple and neutral anion sensors from the first examples up to very recent studies. There is a discussion of a gradual progress made over time, often based on careful analysis of the properties of former generations that have subsequently led to obtaining excellent effectivities and selectivities. The influence of these species on other fields of chemistry and their applications there are also discussed (57 references).

Catalytic reactions occur readily at sites of starting materials that are both innately reactive and sterically accessible or that are predisposed by a functional group amenable to direct a catalyst. However, selective reactions at unbiased sites of substrates remain challenging and typically require additional pre-activation steps or the use of highly reactive reagents. Herein, we report dual-catalytic transition metal systems that merge a reversible activation cycle with a functionalization cycle, together enabling functionalization of substrates at their inherently unreactive sites. By engaging the Ru-or Fe-catalyzed equilibrium between an alcohol and an aldehyde, Pd-catalyzed b-arylation of aliphatic alcohols and Rh-catalyzed g-hydroarylation of allylic alcohols were developed. The mild conditions, functional group tolerance and broad scope of the methodologies (81 examples) demonstrate the synthetic applicability of the dual-catalytic systems. In a broader context, this work highlights the potential of the multi-catalytic approach to address challenging transformations to circumvent the multi-step procedures and the use of highly reactive reagents in organic synthesis. File list (2)download file view on ChemRxiv Dydioetal_manuscript1.pdf (1.16 MiB) download file view on ChemRxiv Dydioetal-SI1.pdf (26.35 MiB)

Secondary benzylic alcohols (SBAs) and diarylmethanols (DAMs) are common structural motifs of biologically active and medicinally relevant compounds. Here we report their enantioselective synthesis by -arylation of primary aliphatic and benzylic alcohols under sequential catalysis integrating a Ru-catalyzed hydrogen-transfer oxidation and a Ru-catalyzed nucleophilic addition. The method is applicable to various alcohols and aryl nucleophiles tolerating a range of functional groups, including secondary alcohols, ketones, alkenes, esters, NH-amides, tertiary amines, aryl halides, and heterocycles.Secondary benzylic alcohols (SBAs) and diarylmethanols (DA Ms) constitute valuable synthetic intermediates and prevalent structural motifs of numerous natural products and bioactive compounds. 1,2 Therefore, protocols for their stereoselective synthesis from various accessible starting materials have attracted much attention over the years. Common approaches include potent asymmetric (transfer) hydrogenation of ketones 1,3,4 or 1,2-addition of aryl nucleophiles to aldehydes, 5,6 particularly useful for fine-chemical synthesis when such starting materials are available and do not require additional synthetic steps.Because aliphatic alcohols represent a class of abundant starting materials, increasing attention has been devoted to developing methods for their valorization through selective C−H bond functionalization. [7][8][9] In the context of SBAs, an elegant strategy for the enantioselective alkylation of -C−H bonds of primary benzylic alcohols with unsaturated hydrocarbons (e.g., dienes, enynes) was devised by Krische and co-workers (Scheme 1a). 10,11 The methods of the arylation of -C−H bonds of aliphatic alcohols in the Minisci-type reactions were also established. [12][13][14][15][16][17] (Scheme 1b). Unfortunately, these methods lead to racemic products, leaving the enantioselective -C−H arylation of alcohols unexplored.We have recently reported an enantioselective synthesis of SBAs from unsaturated alcohols and aryl boronic acids under sequential catalysis (Scheme 1c). 18 The one-pot sequence of an Ir-catalyzed isomerization of the starting material and a Ru-catalyzed nucleophilic addition of an aryl boronic acid to the aldehyde intermediate provided a convenient synthetic method with a broad scope and functional group tolerance.

The binding selectivity of structurally simple anion receptors is governed by the Hofmeister series (SO > HPO > carboxylates ∼ HPO > HCO > Cl), and exceptions to this rule are rare and require utilization of structurally sophisticated receptors. In this paper we examined a set of 48 structurally diverse anion receptors, barely one fourth of which exhibit selectivity for chloride over more basic dihydrogen phosphate (HPO) or carboxylates (MeCO and PhCO). Searching for regularities in the properties of these mainly macrocyclic-derived receptors across quite systematic changes in structure, combined with analysis of multiple crystal structures, allowed us to identify the crucial structural features that are likely required for the occurrence of the phenomenon of selective chloride binding. Examination of a subset of other 'case study' receptors reported in the literature as being particularly chloride-selective served as a confirmation of our hypotheses. As such, our findings are valid for all artificial receptors with exceptional selectivity for chloride, as well as for natural chloride channel proteins (ClC).

Herein we report the synthesis and detailed studies of the anion-binding properties of two 20-membered macrocyclic tetramide receptors: one symmetrical, containing two identical azulene-based bisamide units, the other a hybrid, containing a dipicolinic bisamide unit and an azulene-based bisamide unit. Analysis of the crystal structures of the macrocyclic receptors revealed their preference for adopting similar well-preorganized bent-sheet conformations, both as free receptors and in their complexes with anions. Studies of the optical properties of both receptors revealed abilities to selectively sense phosphate anions (H PO , HP O ), allowing for naked-eye detection of the presence of these guests in DMSO. Binding studies in solution confirmed that the receptors bind strongly to a series of anions even in highly demanding media, such as mixtures of DMSO with water or with methanol. Comparison of the anion affinity of linear analogues with that of the macrocyclic receptors evidenced the importance of macrocyclic topology. Quantitative analysis revealed that the macrocyclic receptors are selective for H PO over other anions. The affinity to H PO seen for the symmetrical receptor, containing two azulene-based subunits, is much higher than for the hybrid macrocycle containing both the azulene-based and pyridine-derived subunits. This highlights that the azulene-based building block serves efficiently as both a binding site and a structure-preorganizing motif.

One-pot multi-step procedures bear the potential to rapidly build up molecular complexity while avoiding the wasteful and costly isolations and purifications of consecutive intermediates. Here we report multi-catalytic protocols that convert alkenes, unsaturated aliphatic alcohols, and aryl boronic acids into secondary benzylic alcohols with high stereoselectivities under sequential catalysis that integrates alkene cross-metathesis, isomerization, and nucleophilic addition. Because each transformation of the sequence is executed by an independent catalyst, without any catalytic cross-reactivity, allylic alcohols bearing a prochiral double bond can be converted to any stereoisomer of the product with high stereoselectivity (>98:2 er and >20:1 dr). Overall, with the aid of up to four catalysts operating in a single vessel, the protocols directly convert simple starting materials into a range of value-added products with high stereocontrol and excellent material efficiency, demonstrating both the efficacy and the advantages of the one-pot synthesis employing multiple transition-metal catalysts.

The easy-to-make 7,7'-diamino-2,2'-diindolylmethane was used as a building block for the construction of anion receptors operating by hydrogen bonds. Its various bisamide and bisurea derivatives were designed and synthesised as acyclic as well as macrocyclic molecules, then their structural and anion binding properties were studied in solution and in the solid state. The bisamide receptors demonstrate high affinity towards oxoanions in highly polar and partially aqueous solutions (DMSO with up to 25 % H(2)O) with significant selectivity for dihydrogen phosphate. Remarkably, the bisurea-based molecules are able to bind anionic guests even in pure methanol and show selectivity toward tetrahedral oxoanions, that is, hydrogen sulphate and dihydrogen phosphate. X-ray analysis revealed that both classes of molecules adopt a similar conformation in the solid state: a bent sheet shape with a binding pocket equipped with hydrogen-bond donors (four for the amides and six for the bisureas), whose orientation is particularly tailored for oxoanions. The results of ROESY NMR experiments are in agreement with the findings for the solid state and confirmed that both bisamides and bisureas can easily adapt the conformation with convergent hydrogen-bond donors, which is highly suitable for anion binding.

An understanding of host-guest noncovalent interactions lies at the very heart of supramolecular chemistry. Often a minute change to the structure of a host molecule's binding site can have a dramatic impact on a prospective host-guest binding event, changing the relative selectivity for potential guest molecules. With the overall goal of aiding the rational design of selective and effective receptors for anions, we have studied the influence of small perturbations in binding site geometry for a series of five closely related 20-membered macrocyclic tetra-amide receptors, constructed from two building blocks from a pool of azulene-5,7-bisamide, azulene-1,3-bisamide, and dipicolinic bisamide units. The solid-state structures revealed that the conformational preferences of the free receptors are driven by the inherent preferences of the building blocks, yet in some cases the macrocyclic topology is able to over-ride these to promote pre-organized conformations favorable for anion binding. The solid-state structures of the chloride complexes of these receptors revealed that although all the receptors can adapt to binding to the challenging small Cl guest with all the NH groups, only receptors containing azulene-5,7-bisamide units form short and linear, and therefore strong, hydrogen-bonding interactions. These conclusions are further supported by studies in solution. Although all the receptors showed high affinities toward a series of anions (H PO , PhCO , Cl , and Br ), even in a highly competitive polar medium (DMSO/25 % MeOH), only receptors containing azulene-5,7-bisamide units exhibited non-inherent selectivity for Cl over PhCO , breaking the Hofmeister trend of selectivity. The data presented herein highlight the privileged properties of the azulene-5,7-bisamide building block for binding to chloride anions and provide guidelines for the construction of selective and efficient anion receptors with prospective practical applications.