Selective Monofunctionalization Enabled by Reaction‐History‐Dependent Communication in Catalytic Rotaxanes

Selective monofunctionalization of substrates with distant, yet equally reactive functional groups is difficult to achieve, as it requires the second functional group to selectively modulate its reactivity once the first functional group has reacted. We now show that mechanically interlocked catalytic rings can effectively regulate the reactivity of stoppering groups in rotaxanes over a distance of about 2 nm. Our mechanism of communication is enabled by a unique interlocked design, which effectively removes the catalytic rings from the substrates by fast dethreading as soon as the first reaction has taken place. Our method not only led to a rare example of selective monofunctionalization, but also to a “molecular if function”. Overall, the study presents a way to get distant functional groups to communicate with each other in a reaction‐history‐dependent manner by creating linkers that can ultimately perform logical operations at the molecular level.     

Strategies and tactics for the metal-directed synthesis of rotaxanes, knots, catenanes, and higher order links

More than a quarter of a century after the first metal template synthesis of a [2]catenane in Strasbourg, there now exists a plethora of strategies available for the construction of mechanically bonded and entwined molecular level structures. Catenanes, rotaxanes, knots and Borromean rings have all been successfully accessed by methods in which metal ions play a pivotal role. Originally metal ions were used solely for their coordination chemistry; acting either to gather and position the building blocks such that subsequent reactions generated the interlocked products or by being an integral part of the rings or "stoppers" of the interlocked assembly. Recently the role of the metal has evolved to encompass catalysis: the metal ions not only organize the building blocks in an entwined or threaded arrangement but also actively promote the reaction that covalently captures the interlocked structure. This Review outlines the diverse strategies that currently exist for forming mechanically bonded molecular structures with metal ions and details the tactics that the chemist can utilize for creating cross-over points, maximizing the yield of interlocked over non-interlocked products, and the reactions-of-choice for the covalent capture of threaded and entwined intermediates.     

Catenanes: Fifty Years of Molecular Links

Half a century after Schill and Lüttringhaus carried out the first directed synthesis of a [2]catenane, a plethora of strategies now exist for the construction of molecular Hopf links (singly interlocked rings), the simplest type of catenane. The precision and effectiveness with which suitable templates and/or noncovalent interactions can arrange building blocks has also enabled the synthesis of intricate and often beautiful higher order interlocked systems, including Solomon links, Borromean rings, and a Star of David catenane. This Review outlines the diverse strategies that exist for synthesizing catenanes in the 21st century and examines their emerging applications and the challenges that still exist for the synthesis of more complex topologies.     

水蒸气对褐煤原位气化半焦反应性能及微观结构的影响

为了揭示水蒸气对半焦反应性和微观结构的影响,在自制两段新型反应器上依次进行了褐煤干燥、热解及"热"焦的水蒸气原位气化研究。利用TGA、BET和Raman光谱仪,对原位气化半焦进行反应性和微观结构解析。结果表明,在反应温度为600 ℃时,水蒸气对半焦转化率、反应性及微观结构影响很小。温度达到700~900 ℃,在半焦与水蒸气接触的前2 min,虽然半焦转化率变化不大,但其反应性、小环(3~5个芳环)与大环(≥6个环)体系之比及含氧官能团却急剧降低;大于2 min,半焦转化率逐渐增大,反应性、小环与大环之比及含氧官能团缓慢降低;而半焦孔结构在2 min 前后却具有基本一致的变化趋势。半焦与水蒸气接触的前2 min,小环与大环之比和含氧官能团急剧降低是导致反应性显著降低的重要因素,大于2 min,芳环体系的变化是导致反应性进一步降低的原因。     

Synthesis of acyltrifluoroborates

Acylboranes are among the most elusive boron-containing organic functional groups, a fact that has impeded development of new reactions employing them as substrates. A new synthesis of acyltrifluoroborates from benzotriazole (Bt)-based N,O-acetals has been developed. Two other routes provide acyltrifluoroborates containing alcohols, aldehydes, and carbamates. The ketone-like reactivity of the acyltrifluoroborate functional group is demonstrated, and the first X-ray structure of an acyltrifluoroborate is reported.     

A General Light-Driven Organocatalytic Platform for the Activation of Inert Substrates

Due to their strong covalent bonds and low reduction potentials, activating inert substrates is challenging. Recent advances in photoredox catalysis offered a number of solutions, each of which useful for activating specific inert bonds. Developing a general catalytic platform that can consistently target a broad range of inert substrates would be synthetically useful. Herein, we report a readily available indole thiolate organocatalyst that, upon excitation with 405 nm light, acquires a strongly reducing power. This excited-state reactivity served to activate, by single-electron reduction, strong C−F, C−Cl, and C−O bonds in both aromatic and aliphatic substrates. This catalytic platform was versatile enough to promote the reduction of generally recalcitrant electron-rich substrates (E_red<−3.0 V vs SCE), including arenes that afforded 1,4-cyclohexadienes. The protocol was also useful for the borylation and phosphorylation of inert substrates with a high functional group tolerance. Mechanistic studies identified an excited-state thiolate anion as responsible of the highly reducing reactivity.     

Ostensible enzyme promiscuity: alkene cleavage by peroxidases

Enzyme promiscuity is generally accepted as the ability of an enzyme to catalyse alternate chemical reactions besides the 'natural' one. In this paper peroxidases were shown to catalyse the cleavage of a C=C double bond adjacent to an aromatic moiety for selected substrates at the expense of molecular oxygen at an acidic pH. It was clearly shown that the reaction occurs due to the presence of the enzyme; furthermore, the reactivity was clearly linked to the hemin moiety of the peroxidase. Comparison of the transformations catalysed by peroxidase and by hemin chloride revealed that these two reactions proceed equally fast; additional experiments confirmed that the peptide backbone was not obligatory for the reaction and only a single functional group of the enzyme was required, namely in this case the prosthetic group (hemin). Consequently, we propose to define such a promiscuous activity as 'ostensible enzyme promiscuity'. Thus, we call an activity that is catalysed by an enzyme 'ostensible enzyme promiscuity' if the reactivity can be tracked back to a single catalytic site, which on its own can already perform the reaction equally well in the absence of the peptide backbone.     

Front Cover: Dynamic Covalent Chemistry for Synthesis and Co-conformational Control of Mechanically Interlocked Molecules (Eur. J. Org. Chem. 8/2023)

Mechanically interlocked molecules have found extensive applications in areas all across the physical sciences, from materials to catalysis and sensing. However, introducing mechanical bonds and entanglements at the molecular level is still a significant challenge due to the inherent restriction in entropy needed to preorganize strands before interlocking. Over the last decade, dynamic covalent chemistry has emerged as one of the most efficient methods of forming rotaxanes, catenanes and molecular knots. By using reversible bonds such as imines, disulfides and boronate esters, one can use the inherent error-correction in these linkages to form interlocked architectures with high fidelity and often in excellent yields. This review reports on recent advances in the use of dynamic covalent chemistry to make mechanically interlocked molecules, systematically surveying clipping, capping and templating approaches with dynamic bonds. Furthermore, it is also discussed how dynamic bonds can be used to control motion, co-conformational expression and catalytic activity in mechanically interlocked molecular machinery.     

Architectures, mechanisms and molecular evolution of natural product methyltransferases

Covering: up to January 2012The addition of a methyl moiety to a small chemical is a common transformation in the biosynthesis of natural products across all three domains of life. These methylation reactions are most often catalysed by S-adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs). MTs are categorized based on the electron-rich, methyl accepting atom, usually O, N, C, or S. SAM-dependent natural product MTs (NPMTs) are responsible for the modification of a wide array of structurally distinct substrates, including signalling and host defense compounds, pigments, prosthetic groups, cofactors, cell membrane and cell wall components, and xenobiotics. Most notably, methylation modulates the bioavailability, bioactivity, and reactivity of acceptor molecules, and thus exerts a central role on the functional output of many metabolic pathways. Our current understanding of the structural enzymology of NPMTs groups these phylogenetically diverse enzymes into two MT-superfamily fold classes (class I and class III). Structural biology has also shed light on the catalytic mechanisms and molecular bases for substrate specificity for over fifty NPMTs. These biophysical-based approaches have contributed to our understanding of NPMT evolution, demonstrating how a widespread protein fold evolved to accommodate chemically diverse methyl acceptors and to catalyse disparate mechanisms suited to the physiochemical properties of the target substrates. This evolutionary diversity suggests that NPMTs may serve as starting points for generating new biocatalysts.     

Organoactinides promote the dimerization of aldehydes: scope, kinetics, thermodynamics, and calculation studies

Surprising catalytic activities have been found for the actinide complexes Cp*(2)ThMe(2) (1), Th(NEtMe)(4) (2), and Me(2)SiCp'(2)Th(C(4)H(9))(2) (3) toward oxygenated substrates. During the catalytic dimerization of benzaldehydes to their corresponding esters, complexes 1 and 2 gave 65 and 85% yield in 48 h, respectively, while the geometry-constrained complex 3 gave 96% yield in 24 h. Exploring the effect of substituents on benzaldehyde, it has been found that, in general, electron-withdrawing groups facilitate the reaction. Kinetic study with complexes 1 and 3 reveals that the rate of the reaction is first order in catalyst and substrate, which suggests the rate equation "rate = k[catalyst](1)[aldehyde](1)". The activation energy of the reaction was found to be 7.16 ± 0.40 and 3.47 ± 0.40 kcal/mol for complexes 1 and 3 respectively, which clearly indicates the advantage of the geometry-constrained complex. Astonishing are the reactivity of the organoactinide complexes with oxygen-containing substrates, and especially the reactivity of complex 3, toward the dimerization of substrates like p-methoxybenzaldehyde, m/p-nitrobenzaldehyde, and furanaldehyde and the reactivity toward the polymerization of terephthalaldehyde. Density functional theory mechanistic study reveals that the catalytic cycle proceeds via an initially four-centered transition state (+6 kcal/mol), followed by the rate-determining six-centered transition state (+13.5 kcal/mol), to yield thermodynamically stable products.     

A Cooperative Rhodium/Secondary Phosphine Oxide [Rh/P(O)nBu2] Template for Catalytic Hydrodefluorination of Perfluoroarenes

The selective activation of C−F bonds under mild reaction conditions remains an ongoing challenge of bond activation. Here, we present a cooperative [Rh/P(O)nBu₂] template for catalytic hydrodefluorination (HDF) of perfluoroarenes. In addition to substrates presenting electron-withdrawing functional groups, the system showed an exceedingly rare tolerance for electron-donating functionalities and heterocycles. The high chemoselectivity of the catalyst and its readiness to be deployed at a preparative scale illustrate its practicality. Empirical mechanistic studies and a density functional theory (DFT) study have identified a rhodium(I) dihydride complex as a catalytically relevant species and the determining role of phosphine oxide as a cooperative fragment. Altogether, we demonstrate that molecular templates based on these design elements can be assembled to create catalysts with increased reactivity for challenging bond activations.     

Quantitative active transport in [2]rotaxane using a one-shot acylation reaction toward the linear molecular motor

A rotaxane consisting of a crown ether wheel and a secondary ammonium salt axle, on which a neopentyl-type end-cap was placed close to the ammonium moiety, was prepared. When the rotaxane was treated by excess triethylamine, the wheel component thermodynamically moved over the proximate neopentyl group to deconstruct the interlocked structure. The wheel component in the rotaxane, however, quantitatively moved against the proximate end-cap by the action of trifluoroacetic anhydride in the presence of excess triethylamine. This motion, which was driven by the simple one-shot acylation reaction, can be referred as the active transport. When the distant end-cap is of the neopentyl-type, the axle can be thermally dethreaded from the distant end-cap after the acylative transport. The series of the wheel movement controlled by the neopentyl group can be the basic motion of the unidirectional linear molecular motor.     

Cerium‐Based M4L4 Tetrahedra as Molecular Flasks for Selective Reaction Prompting and Luminescent Reaction Tracing

The application of metal–organic polyhedra as “molecular flasks” has precipitated a surge of interest in the reactivity and property of molecules within well‐defined spaces. Inspired by the structures of the natural enzymatic pockets, three metal–organic neutral molecular tetrahedral, Ce‐TTS, Ce‐TNS and Ce‐TBS (H₆TTS: N′,N′′,N′′′‐nitrilotris‐4,4′,4′′‐(2‐hydroxybenzylidene)‐benzohydrazide; H₆TNS: N′,N′′,N′′′‐nitrilotris‐6,6′,6′′‐(2‐hydroxybenzylidene)‐2‐naphthohydrazide; H₆TBS: 1,3,5‐ phenyltris ‐4,4′,4′′‐(2‐hydroxybenzylidene)benzohydrazide), which exhibit different size of the edges and cavities, were achieved through self‐assembly by incorporating robust amide‐containing tridentate chelating sites into the fragments of the ligands. They acted as molecular flasks to prompt the cyanosilylation of aldehydes with excellent selectivity towards the substrates size. The amide groups worked as trigger sites and catalytic driven forces to achieve efficient guest interactions, enforcing the substrates proximity within the cavity. Experiments on catalysts with the different cavity radii and substrates with the different molecular size demonstrated that the catalytic performance exhibited enzymatical catalytic mechanism and occurred in the molecular flask. These amides were also able to amplify guest‐bonding events into the measurable outputs for the detection of concentration variations of the substrates, providing the possibility for metal–organic hosts to work as smart molecular flasks for the luminescent tracing of catalytic reactions.     

Investigating the imidazolium–anion interaction through the anion-templated construction of interpenetrated and interlocked assemblies

The interaction between imidazolium cations and coordinating anions is investigated through the anion‐templated assembly of interpenetrated and interlocked structures. The orientation of the imidazolium motif with respect to anion binding, and hence the hydrogen bond donor arrangement, was varied in acyclic receptors, interpenetrated assemblies, and the first mono‐imidazolium interlocked systems. Their anion recognition properties and co‐conformations were studied by solution‐phase ¹H NMR investigations, solid‐state structures, molecular dynamics simulations, and density functional theory calculations. Our findings suggest that the imidazolium‐anion binding interaction is dominated by electrostatics with hydrogen‐bonding contributions having weak orientational dependence.     

Advances in bridged 1,2,4-trioxane-based chemistry. A divergent approach to oxa-heterocycles based on ambident reactivity

Heterogeneous catalytic hydrogenation of unsaturated 1,2,4-trioxanes derived from β-ionone-type dienones has been investigated. Our studies revealed a versatile reactivity of trioxanic substrates that led to the development of reaction methodology for the selective manipulation of the alkene and peroxide functionalities. Depending on the catalytic system used, divergent reaction pathways can be controlled to afford either the corresponding saturated 1,2,4-trioxanes or furan structures. A mechanistic rationalisation, which accounts for the reductive behaviour of these heterocycles, is proposed.     

Insight into the Folding and Cooperative Multi-Recognition Mechanism in Supramolecular Anion-Binding Catalysis

H-bond donor catalysts able to modulate the reactivity of ionic substrates for asymmetric reactions have gained great attention in the past years, leading to the development of cooperative multidentate H-bonding supramolecular structures. However, there is still a lack of understanding of the forces driving the ion recognition and catalytic performance of these systems. Herein, insight into the cooperativity nature, anion binding strength, and folding mechanism of a model chiral triazole catalyst is presented. Our combined experimental and computational study revealed that multi-interaction catalysts exhibiting weak binding energies (≈3–4 kcal mol⁻¹) can effectively recognize ionic substrates and induce chirality, while strong dependencies on the temperature and solvent were quantified. These results are key for the future design of catalysts with optimal anion binding strength and catalytic activity in target reactions.     

Theoretical investigation of the mechanism of primary amines reacting with hexamolybdate: an insight into the organoimido functionalization and related reactions of polyoxometalates

The functionalization of polyoxometalates (POMs), especially with an amino group to yield organonitrogenous derivatives of POMs, is an efficient approach to the enrichment of their structures and the diversification of their properties for various applications. The mechanism for the formation of organonitrogenous-derivatized hexamolybdates was explored by investigating the monofunctionalization of the [Mo(6)O(19)](2-) ion with methylamine using the density functional theory (DFT) method. The calculations show that the direct imidoylization of hexamolybdate with methylamine is both kinetically and thermodynamically unfavorable. However, this imidoylization was found to take place readily in the presence of dimethylcarbodiimide (DMC), for which the free-energy barrier was calculated to be +32.5 kcal mol(-1) in acetonitrile. Moreover, various factors controlling the efficiency of the imidoylization were examined. The calculations show that [W(5)MoO(19)](2-) has a relatively lower reactivity than [Mo(6)O(19)](2-), and that the imidoylization of [W(6)O(19)](2-) is an unfavorable process. With respect to the effect of carbodiimides, it is found that the catalytic activity is directly proportional to the electron-withdrawing effects of the substituents. As to the reactivity of R-NH(2) , the computation results indicate that the free-energy barriers of the substitution reactions are linearly correlated with the basicity constants (pK(b)) of the amino groups. It is noteworthy that the introduction of the proton dramatically decreases the free-energy barrier of the imidoylization of [Mo(6)O(19)](2-) catalyzed by DMC to 24.3 kcal mol(-1) in acetonitrile.     

Transient Directing Groups in Metal−Organic Cooperative Catalysis

The direct functionalization of C−H bonds is among the most fundamental chemical transformations in organic synthesis. However, when the innate reactivity of the substrate cannot be utilized for the functionalization of a given single C−H bond, this selective C−H bond functionalization mostly relies on the use of directing groups that allow bringing the catalyst in close proximity to the C−H bond to be activated and these directing groups need to be installed before and cleaved after the transformation, which involves two additional undesired synthetic operations. These additional steps dramatically reduce the overall impact and the attractiveness of C−H bond functionalization techniques since classical approaches based on substrate pre-functionalization are sometimes still more straightforward and appealing. During the past decade, a different approach involving both the in situ installation and removal of the directing group, which can then often be used in a catalytic manner, has emerged: the transient directing group strategy. In addition to its innovative character, this strategy has brought C−H bond functionalization to an unprecedented level of usefulness and has enabled the development of remarkably efficient processes for the direct and selective introduction of functional groups onto both aromatic and aliphatic substrates. The processes unlocked by the development of these transient directing groups will be comprehensively overviewed in this review article.     

Experimental and theoretical study of the adsorption of fumaramide [2]rotaxane on Au(111) and Ag(111) surfaces

Thin films of fumaramide [2]rotaxane, a mechanically interlocked molecule composed of a macrocycle and a thread in a "bead and thread" configuration, were prepared by vapor deposition on both Ag(111) and Au(111) substrates. X-ray photoelectron spectroscopy (XPS) and high-resolution electron-energy-loss spectroscopy were used to characterize monolayer and bulklike multilayer films. XPS determination of the relative amounts of carbon, nitrogen, and oxygen indicates that the molecule adsorbs intact. On both metal surfaces, molecules in the first adsorbed layer show an additional component in the C 1s XPS line attributed to chemisorption via amide groups. Molecular-dynamics simulation indicates that the molecule orients two of its eight phenyl rings, one from the macrocycle and one from the thread, in a parallel bonding geometry with respect to the metal surfaces, leaving three amide groups very close to the substrate. In the case of fumaramide [2]rotaxane adsorption on Au(111), the presence of certain out-of-plane phenyl ring and Au-O vibrational modes points to such bonding and a preferential molecular orientation. The theoretical and experimental results imply that the three-dimensional intermolecular configuration permits chemisorption at low coverage to be driven by interactions between the three amide functions of fumaramide [2]rotaxane and the Ag(111) or Au(111) surface.