Iridium-Catalyzed C-H Borylations: Regioselective Functionalizations of Calix[4]arene Macrocycles.

We report iridium-catalyzed C-H borylations for the regioselective synthesis of distally disubstituted calix[4]arene macrocycles. The atom- and step-economical method led to a broad family of calix[4]arenes in good yields and functional group tolerance. The synthetic utility of the C-H borylation protocol was finally illustrated with several late-stage modifications for the synthesis of elaborate calix[4]arenes frameworks, otherwise challenging to achieve with commonly employed procedures.

Iron-Catalyzed C-H Alkylation/Ring Opening with Vinylbenzofurans Enabled by Triazoles.

We report an unprecedented iron-catalyzed C-H annulation using readily available 2-vinylbenzofurans as the reaction pattern. The redox-neutral strategy, based on cheap, non-toxic, and earth-abundant iron catalysts, exploits triazole assistance to promote a cascade C-H alkylation, benzofuran ring-opening and insertion into a Fe-N bond, to form highly functionalized isoquinolones. Detailed mechanistic studies supported by DFT calculations fully disclosed the manifold of the iron catalysis.

Modern Organometallic C-H Functionalizations with Earth-Abundant Iron Catalysts: An Update.

Iron-catalyzed C-H activation has recently emerged as an increasingly powerful synthetic method for the step- and atom- economical direct C-H functionalizations of otherwise inert C-H bonds. Iron's low-cost and toxicity along with its catalytic versatility have encouraged the scientific community to elect this metal for the development of new C-H activation methodologies. Within this review, we aim to present a collection of the most recent examples of iron-catalyzed C-H functionalizations with a particular emphasis on modern synthetic strategies and mechanistic aspects.

Gold(I)-catalysed hydroarylations of alkynes for the synthesis of inherently chiral calix[4]arenes.

We describe the first gold(I)-catalysed intramolecular hydroarylation of alkynes for the straightforward synthesis of inherently chiral calix[4]arenes. This step- and atom-economical approach, which exploits a formal meta-functionalisation of the calix[4]arene macrocycle, is able to deliver an ample family of N-heterocyclic, chiral compounds in high yields and functional group tolerance.

Selective enhancement of organic dye properties through encapsulation in rotaxane orientational isomers.

We report the synthesis and characterisation of [2]rotaxanes based on a stilbazolium dye and a calix[6]arene macrocycle. Since both components are non-symmetric, two orientational isomers are obtained. The two isomers display distinct photophysical and photochemical properties in solution and solid state, superior to the unencapsulated dye.

A Multiresponsive Calix[6]arene Pseudorotaxane Empowered by Fluorophoric Dansyl Groups.

We report the synthesis and characterization, by means of NMR and UV-visible spectroscopy and electrochemical techniques, of a dansyl calix[6]arene derivative and of its pseudorotaxane complex with a bipyridinium-based axle. This novel macrocycle shows remarkable complexation ability, in analogy with parent compounds, while the dansyl moieties impart valuable features to the system. Indeed, these units: i) signal the state of the system by fluorescence; ii) can be reversibly protonated, enabling the modulation of the complexation abilities of the macrocycle; iii) participate in photoinduced electron transfer processes, which may be exploited to tune the stability of the supramolecular complex. Therefore, in this multiresponsive pseudorotaxane, the threading and de-threading motions of the molecular components can be modulated either by protonation of the calixarene host or by reduction of the bipyridinium guest, which can be accomplished both by electrochemical reduction and via photoinduced electron transfer. Overall, three orthogonal and reversible stimuli can be used to induce molecular movements of the pseudorotaxane components.

Calix[6]arene-Based [3]Rotaxanes as Prototypes for the Template Synthesis of Molecular Capsules.

In this work, the ability of several bis-viologen axles to thread a series of heteroditopic tris(N-phenylureido)calix[6]arene wheels to give interwoven supramolecular complexes to the [3]pseudorotaxane type was studied. The unidirectionality of the threading process inside these nonsymmetric wheels allows the formation of highly preorganised [3]pseudorotaxane and [3]rotaxane species in which the macrocycles phenylureido moieties, functionalised with either ester, carboxylic, or hydroxymethyl groups, are facing each other. As verified by NMR and semiempirical computational studies, these latter compounds possess the correct spatial arrangement of their subcomponents, which could lead, in principle, upon proper bridging reaction, to the realisation of upper-to-upper molecular capsules that are based on calix[6]arene derivatives.

Triazole-enabled, iron-catalysed linear/branched selective C-H alkylations with alkenes.

Iron-catalysed C-H alkylations with alkenes were achieved on benzamides by N-triazole assistance. A notable switch of the regioselectivity from linear to branched was observed depending on the nature of the olefin employed. The approach allowed for the synthesis of a family of decorated benzamides with ample scope and high levels of chemo-, regio- and site-selectivity.

Diametric calix[6]arene gold(I) catalysts for intramolecular cyclopropanations of 1,6-dienynes.

We report a solid-state structural investigation of diametric calix[6]arene-based phosphine gold(I) cavitands which are characterised by two specific, different 1,2,3-alternate conformations in solution and in the solid state. The effect of the specific orientation of phosphines, with respect to macrocycles, was studied in intramolecular cyclopropanation of 1,6-dienynes. The general applicability of these catalysts was disclosed, delivering a family of polycycles with high yields and functional group tolerance.

Diametric calix[6]arene-based phosphine gold(I) cavitands.

We report the synthesis and characterization, in low polarity solvents, of a novel class of diametric phosphine gold(I) cavitands characterized by a 1,2,3-alternate geometry. Preliminary catalytic studies were performed on a model cycloisomerization of 1,6-enynes as a function of the relative orientation of the bonded gold(I) nuclei with respect to the macrocyclic cavity.

Is Aromaticity a Driving Force in Catalytic Cycles? A Case from the Cycloisomerization of Enynes Catalyzed by All-Metal Aromatic Pd3+ Clusters and Carboxylic Acids.

The work details a mechanistic study based on density functional theory modeling on the cycloisomerization of polyunsaturated substrates catalyzed by all-metal aromatic tripalladium complexes and carboxylic acids. These clusters are an emerging class of catalysts for a variety of relevant transformations, including C-C forming processes that occur under mild conditions and display synthetic features complementary to those of established mononuclear complexes. This study is the first computational one devoted to the comprehension of the series of elementary steps involved in a synthetic transformation catalyzed by an all-metal aromatic complex. Present results confirm previous experimental hints on the striking mechanistic differences exerted by these clusters with respect to the usual cyclization pathways of related substrates. Moreover, the catalytic cycle involving present all-metal aromatic clusters closely parallels the mechanism of the aromatic substitution of regular arenes.

Inter/Intramolecular Cascade of 1,6-Enynes Catalyzed by All-Metal Aromatic Tripalladium Complexes and Carboxylic Acids.

Trinuclear all-metal aromatic clusters are an original class of molecules with a cyclic and planar metal core. Characterized by peculiar metal-metal delocalized bonds, they represent a new frontier in transition-metal catalysis. We report a study on C-C-forming reactions of polyunsaturated substrates catalyzed by trinuclear all-metal aromatic palladium clusters. The synthesis of two new families of tricyclic compounds was obtained with a broad functional group tolerance under mild reaction conditions. A peculiar regio- and diastereoselectivity characterized the method, demonstrating that trinuclear palladium complexes are complementary to their popular mononuclear peers. Furthermore, preliminary studies on the mechanism of these polycyclization reactions revealed unique features of the homogeneous catalytic system.

Selective access to constitutionally identical, orientationally isomeric calix[6]arene-based [3]rotaxanes by an active template approach.

Tris(phenylureido)calix[6]arene is endowed with unique properties that make it a valuable macrocyclic component for the synthesis of mechanically interlocked molecules. Its three-dimensional and intrinsically nonsymmetric structure is kinetically selective toward two processes: (i) in apolar media, the threading of bipyridinium based axle-like components takes place exclusively from the upper rim; (ii) SN2 alkylation reactions of a pyridylpyridinium precursor engulfed in the cavity occur selectively at pyridylpyridinium nitrogen atom located at the macrocycle upper rim (active template synthesis). Here we exploit such properties to prepare two series of [3]rotaxanes, each consisting of three sequence isomers that arise from the threading of two identical but nonsymmetric wheels on a symmetric thread differing only for the reciprocal orientation of the macrocycles. The features of the calix[6]arene and the active template synthetic approach, together with a careful selection of the precursors, enabled us to selectively synthesise the [3]rotaxane sequence isomers of each series with fast kinetics and high yields.

Calixarene-based artificial ionophores for chloride transport across natural liposomal bilayer: Synthesis, structure-function relationships, and computational study.

An amphiphilic calix[6]arene, alone or complexed with an axle to form a pseudo-rotaxane, has been embedded into liposomes prepared from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and the permeability of the membrane-doped liposomes towards Cl- ions has been evaluated by using lucigenin as the fluorescent probe. The pseudo-rotaxane promotes transmembrane transport of Cl- ions more than calix[6]arene does. Surprisingly, the quenching of lucigenin was very fast for liposomes doped with the positively charged axle alone. Molecular dynamics (MD) simulations and quantum-chemical calculations were also carried out for providing a semi-quantitative support to the experimental results.

Merging Molecular Recognition and Gold(I) Catalysis with Triphoscalix[6]arene Ligands.

We report the synthesis and characterization of novel triphosphine calix[6]arene ligands. These supramolecular wheels, with recognition features governed by the hydrogen-bonding domain, were employed to synthesize multitasking trinuclear gold(I) complexes as a new platform for the synthesis of interwoven (pseudo)rotaxane species. In parallel, the multivalent, metal-bonded upper rim displayed catalytic features promoting highly selective gold-catalyzed cycloisomerization reactions of 1,6-enynes.

Heteroditopic Calix[6]arene Based Intervowen and Interlocked Molecular Devices.

Since the dawn of supramolecular chemistry, calixarenes have been employed as platforms onto which functional groups and binding sites can be loaded in a regio- and stereocontrolled manner for the recognition of charged and neutral species. Despite their wider annulus, potentially suitable to bind larger guests, the larger members of the calixarene series have been relatively less employed, mainly because of the synthetic difficulties to control their conformational flexibility and their regioselective functionalization. In this account, we will present the achievements gained during the last two decades on the use of the calix[6]arene as a platform to build-up structures in which the macrocycle acts as a wheel for the synthesis of oriented (pseudo)rotaxanes. We also account on how these calix[6]arene hosts affect the reactivity or spectroscopic properties of their bound guests.

Calix[6]arene-based Brønsted acids for molecular recognition and catalysis.

We report the synthesis of a versatile trifluoromethylsulfonamide calix[6]arene derivative with Brønsted acid features which can influence both molecular recognition and catalytic application. Indeed, in low polarity media, the trifluoromethyl-containing supramolecular wheel is able to respond to the complexation with charged species as a function of its selective ion-pair recognition. In parallel, the enhanced acidity is the key to promote Michael additions of indoles to nitroalkenes under pseudo-physiological reaction conditions (H2O, 37 °C).

Trisulfonamide calix[6]arene-catalysed Michael addition to nitroalkenes.

We describe the application of a novel family of trisulfonamide (TSA) calix[6]arenes in general acid catalysis. Hydrogen-bonding interactions between acidic TSA and methanol boosted the reactivity of the Michael addition of indoles to nitroalkene derivatives. The transformation occurs at a low catalyst loading of 5 mol%, allowing for the synthesis of nitroalkanes with good yields and functional group tolerance.

Recent Advances in Asymmetric Iron Catalysis.

Asymmetric transition-metal catalysis represents a fascinating challenge in the field of organic chemistry research. Since seminal advances in the late 60s, which were finally recognized by the Nobel Prize to Noyori, Sharpless and Knowles in 2001, the scientific community explored several approaches to emulate nature in producing chiral organic molecules. In a scenario that has been for a long time dominated by the use of late-transition metals (TM) catalysts, the use of 3d-TMs and particularly iron has found, recently, a widespread application. Indeed, the low toxicity and the earth-abundancy of iron, along with its chemical versatility, allowed for the development of unprecedented and more sustainable catalytic transformations. While several competent reviews tried to provide a complete picture of the astounding advances achieved in this area, within this review we aimed to survey the latest achievements and new concepts brought in the field of enantioselective iron-catalyzed transformations.

Iron-Catalyzed C-H Functionalizations under Triazole-Assistance.

3d transition metals-catalyzed C-H bond functionalizations represent nowadays an important tool in organic synthesis, appearing as the most promising alternative to cross-coupling reactions. Among 3d transition metals, iron found widespread application due to its availability and benign nature, and it was established as an efficient catalyst in organic synthesis. In this context, the use of ortho-orientating directing groups (DGs) turned out to be necessary for promoting selective iron-catalyzed C-H functionalization reactions. Very recently, triazoles DGs were demonstrated to be more than an excellent alternative to the commonly employed 8-aminoquinoline (AQ) DG, as a result of their modular synthesis as well as the mild reaction conditions applied for their removal. In addition, their tunable geometry and electronics allowed for new unprecedented reactivities in iron-catalyzed C-H activation methodologies that will be summarized within this review.