Synthesis of [3]Rotaxanes that Utilize the Catalytic Activity of a Macrocyclic Phenanthroline–Cu Complex: Remarkable Effect of the Length of the Axle Precursor

[3]Rotaxanes, which consist of one macrocyclic phenanthroline compound and two axle components, were prepared by the oxidative dimerization of an alkyne compound with bulky tris[4′‐cyclohexyl‐(1,1′‐biphenyl)‐4‐yl]methyl blocking group. The catalytic activity of a macrocyclic phenanthroline–Cu complex was utilized to thread the two axle components inside the ring. The alkyne compound with chain of 15 or 20 methylene groups gave [3]rotaxanes in high yields, whereas the axle with a chain of six methylene groups afforded a [3]rotaxane in very poor yield. We also examined the effect of the ring size on the synthesis of [3]rotaxanes. [3]Rotaxanes were not isolated when a macrocyclic phenanthroline compound with a smaller ring size was used.     

Synthesis of bastadin-6 trimethyl ether,a novel 28-membered ring lactam

Bastadin-6 trimethyl ether, a 28-membered ring lactam, was synthesized by means of phenolic exidation of dibromobastadin-2 trimethyl ether with thallium (III0 nitrate (TTN) leading to the formation of the corresponding macrocyclic biphenyl ether as a key step. From bastadin-2 trimethyl ether, a 26-membered ring compound was also synthesized.     

Highly effective and reversible control of the rocking rates of rotaxanes by changes to the size of stimulus-responsive ring components

We have designed and synthesized rotaxanes whose rates of rocking motion (pendular motion) were switched reversibly through changes to the size of the ring component in response to external stimuli. The ring molecules of the rotaxanes incorporate a metaphenylene unit, which swings like a pendulum, and a dianthrylethane unit, which undergoes reversible isomerization in response to photo- and thermal stimuli and changes the size of the ring component. The rocking rates were estimated quantitatively by variable-temperature (VT) NMR spectroscopy and saturation transfer experiments, which revealed substantial changes in the rates between the open and closed forms, particularly in the case of rotaxanes with an isopropoxy group attached to a phenylene unit.     

Synthesis of [2]rotaxanes by the catalytic reactions of a macrocyclic copper complex

We synthesized [2]rotaxanes by the reactions catalyzed by a macrocyclic Cu(I)-phenanthroline complex. The catalytic site was located inside the ring component so that the rotaxane could be selectively formed. A C-S bond-forming reaction and oxidative dimerization of alkyne was utilized for the efficient synthesis of a new series of [2]rotaxanes. [reaction: see text]     

Sequential O- and N-acylation protocol for high-yield preparation and modification of rotaxanes: synthesis, functionalization, structure, and intercomponent interaction of rotaxanes

A pseudorotaxane consisting of a 24-membered crown ether and secondary ammonium salt with the hydroxy group at the terminus was quantitatively acylated by bulky acid anhydride in the presence of tributylphosphane as catalyst to afford the corresponding rotaxane in high yield. Large-scale synthesis without chromatographic separation was easily achieved. The ammonium group in the resulting rotaxane was quantitatively acylated with excess electrophile in the presence of excess trialkylamine. Various N-functionalized rotaxanes were prepared by this sequential double-acylation protocol. 1H NMR spectra and X-ray crystallographic analyses of the rotaxanes showed that the crown ether component was captured on the ammonium group in ammonium-type rotaxane by strong hydrogen-bonding intercomponent interaction. The conformation around the ammonium group was fixed by the hydrogen-bonding interaction. Meanwhile, the conformation of the amide-type rotaxane was determined by the weak CH/pi interaction between the methylene group in crown ether and the benzene ring of the axle component. The N-acylation of ammonium-type rotaxane is useful for the preparation of both functionalized rotaxanes and weak intercomponent interaction-based rotaxanes.     

Self-assembly of novel [3]- and [2]rotaxanes with two different ring components: donor-acceptor and hydrogen bonding interactions and molecular-shuttling behavior

Three of the first kind of hetero[3]rotaxanes, which comprise one linear component and one neutral and one tetracationic ring component, have been assembled by using the intermolecular hydrogen bonding and donor-acceptor interactions. Three neutral [2]rotaxanes and three tetracationic [2]rotaxanes have also been synthesized as intermediate products or for the sake of property comparison. The linear molecules are incorporated with two glycine subunits, for templating the formation of the neutral tetraamide cyclophane, and one or two hydroquinone subunits, for inducing the formation of the tetracationic cyclophane. Variable-temperature (1)H NMR investigation reveals that the shuttling behavior of the tetracationic ring component along the linear component is substantially influenced by the existence of the neutral ring component. The spatial repelling interaction of the neutral ring on the electron-deficient tetracationic ring simultaneously weakens the latter's "positioning" tendency at both electron-rich hydroquinone sites of the linear component. As a result, the activation energy associated with the shuttling process of the tetracationic ring between the two hydroquinone sites is remarkably reduced in comparison to that of the shuttling process of the corresponding neutral ring-free [2]rotaxanes. For the first time, the rotation of the dipyridinium subunit around the axis formed by the two methylene groups connecting them within the tetracationic cyclophane has been investigated by variable-temperature (1)H NMR spectroscopy and the associated kinetic data have also been successfully obtained. Furthermore, the UV-vis and fluorescent properties of the new [2]- and [3]rotaxanes have been studied. The results demonstrate that [3]rotaxanes with different ring components possess unique kinetic features that are not available in [3]rotaxanes with identical ring components.     

Switchable neutral bistable rotaxanes

Two switchable neutral bistable [2]rotaxanes have been synthesized, and their chemically induced mechanical switching has been studied in solution by 1H NMR spectroscopy. One of the rotaxanes was prepared by a thermodynamically controlled slippage mechanism, while the other rotaxane was obtained by a dynamic covalent chemistry protocol involving the assembly of its dumbbell component by olefin metathesis. The recognition sites present in the rod section of the dumbbell component, namely, naphthodiimide (NpI) and pyromellitic diimide (PmI) residues, were chosen in the knowledge that the ring component, 1,5-dinaphtho[38]crown-10 (1/5DNP38C10), will bind preferentially to the NpI site. However, upon introduction of Li+ ions into the solution, a 1:2 complex is formed between the PmI site, encircled by the 1/5DNP38C10 ring and two Li+ ions. Since this complex is more stable overall than the binding between the 1/5DNP38C10 ring and the NpI site, the ring component moves from the NpI site to the PmI one. This mechanical movement can be reversed by adding an excess of [12]crown-4 to the solution to act as a sequestering agent for the Li+ ions.     

Total synthesis of plagiochin G and derivatives as potential cancer chemopreventive agents

A new and efficient total synthesis has been developed to obtain plagiochin G (22), a macrocyclic bisbibenzyl, and four derivatives. The key 16-membered ring containing biphenyl ether and biaryl units was closed via an intramolecular S_NAr reaction. All synthesized macrocyclic bisbibenzyls inhibited Epstein–Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells and, thus, are potential cancer chemopreventive agents.     

Equilibrating dynamic [2]rotaxanes

Upon mixing and dehydration, 2,6-diformylpyridine and 2,2'-oxybis(ethylamine) form a dynamic combinatorial library of at least nine members. Through hydrogen bonding and other intermolecular interactions, templating dumbbell molecules select one macrocyclic member of the library, at the expense of all the others, to create [2]rotaxanes. These rotaxanes, however, retain the dynamic character of the library, since a diformylpyridine analogue can exchange with the macrocyclic component in solution. In addition, crystallization of the mixture surprisingly furnishes only the [24]crown-8-like macrocycle on its own--evidence of a kinetic selection process occurring between phase transitions.     

Foldamers in pseudo[2]rotaxanes and [2]rotaxanes: tuning the switching kinetics and metastability

Hydrogen bonded arylamide foldamers have been introduced in switchable pseudo[2]rotaxanes and [2]rotaxanes, which also include a cyclobisparaquat(p-phenylene) (CBPQT⁴⁺) ring and a ‘dumbbell’ containing tetrathiafulvalene (TTF) and 1,5-dioxynaphthalene (DNP, for rotaxanes). The foldamer size changes through folding and unfolding serve as a steric handle to modulate the mechanical movement of the CBPQT⁴⁺ ring along the dumbbell of the pseudo[2]rotaxanes and [2]rotaxanes. By varying the number of the repeating units in the foldamer, the kinetics of the solvent-dependent slippage/deslippage of pseudo[2]rotaxanes and the switching of the ring between TTF and DNP of the [2]rotoxanes can be tuned remarkably, with the time scope ranging from several minutes to several days, in twelve solvents of varying polarity, which have been confirmed by the ¹H NMR, UV–vis spectroscopy, and cyclic voltammogram experiments.     

Synthetic studies toward sarain A. Formation of the western macrocyclic ring

Starting with the tricyclic core 2b, annulation to form the 13-membered western ring of sarain A has been achieved to afford the macrocycle 30a by initial construction of the sterically congested quaternary center at C-3, followed by elaboration of the C-3 side-chain and ring-closing olefin metathesis. Also included is a parallel conversion of tricycle 2c to macrocycle 30b containing a functionalized side-chain at N-1 suitable for attachment of the eastern macrocyclic ring.     

Explorations on the total synthesis of the unusual marine alkaloid chartelline A

In work directed toward a total synthesis of chartelline A (1a), a strategy was investigated to construct the 10-membered ring of this marine alkaloid via an intramolecular aldehyde/beta-lactam cyclocondensation to form the macrocyclic enamide functionality. Therefore, spiro-beta-lactam and imidazole fragments were first prepared. Tribromooxindole beta-lactam 24 was synthesized from commercially available 5-nitroisatin (18) in seven steps and 30% overall yield via a Staudinger ketene-imine [2 + 2]-cycloaddition strategy. The requisite 2-bromoimidazole subunit 40 bearing a terminal alkyne and a masked aldehyde was efficiently prepared from the readily available imidazole ester 25 in 10 steps. With both advanced intermediates available, the addition of the lithium acetylide generated from 2-bromoimidazole subunit 40 to the gamma-lactam carbonyl group of N-Boc-tribromooxindole 24 was investigated, affording the desired N-Boc-aminal 41. Hydrolysis of the acetonide moiety of 41, followed by oxidative cleavage of the resulting diol, gave the aldehyde 42. Unfortunately, treatment of aldehyde 42 with p-toluenesulfonic acid did not give the desired 10-membered macrocyclic (Z)-enamide 46, but rather the highly unsaturated seven-membered ring compound 44.     

Light-harvesting in multichromophoric rotaxanes

Two rotaxanes with benzyl ether axles and tetralactam wheels were synthesized through an anion template effect. They carry naphthalene chromophores attached to the stopper groups and a pyrene chromophore attached to the wheel. The difference between the two rotaxanes is represented by the connecting unit of the naphthyl chromophore to the rotaxane axle: a triazole or an alkynyl group. Both rotaxanes exhibit excellent light-harvesting properties: excitation of the naphthalene chromophores is followed by energy transfer to the pyrene unit with efficiency higher than 90% in both cases. This represents an example of light-harvesting function among chromophores belonging to mechanically interlocked components, that is, the axle and the wheel of the rotaxanes.     

Photoswitchable rotaxanes on gold nanoparticles

We studied rotaxanes that consisted of a molecular axle, with a photoactive 9-Aryl-9-methoxy-acridane moiety at one end, and a tetracationic ring of cyclobis(paraquat-p-phenylene) (CBQT(4+)). The aim of the study was to deposit the axle ends onto gold nanoparticles (AuNPs). First, we introduced thioctic acid into the axle molecules. Then, rotaxanes were deposited on AuNPs by two methods: 1) Pseudorotaxanes were deposited on the gold surface by forming rotaxanes with the AuNP as a terminator to prevent unthreading of the ring structure; and 2) a chain containing the thioctic ester was introduced into a complete rotaxane, and then it was deposited on the AuNP with the aid of an exchange process. The photoheterolysis of the acridane unit resulted in formation of the corresponding acridinium methoxide; this, in turn, could thermally react to return to the acridane moiety. Due to the creation of a positive charge, the ring moved from the acridane station to a second, evasive station within the axle. This switching cycle could also take place when deposited on the gold surface. However, on the gold surface, the ring movement associated with the switching process was unidirectional.     

Structure-function relationship of amino acid-[2]rotaxanes

Synthetic methodology was developed to construct amino acid-[2]rotaxanes that have phenylalanine and 3,5-di-tert-butylbenzene as blocking groups and dibenzo-24-crown-8, derivatized with either N-acetylargininyl or a carboxylic group, as the ring. A relative measure of the intramolecular interaction energies between the functional groups in DMSO/water mixtures is obtained by comparing their pK(a) values. Rotaxane structures were investigated through 2D NMR analysis and molecular dynamics simulations. Association constants for complexes of amino acids and rotaxanes in various protonation states were determined in a variety of solvent systems by (1)H NMR analysis. The unique intracomponent interactions that exist in the rotaxanes and their ability to act as artificial receptors are discussed.     

Degenerate [2]rotaxanes with electrostatic barriers

A synthetic approach to the preparation of [2]rotaxanes (1-5·6PF(6)) incorporating bispyridinium derivatives and two 1,5-dioxynaphthalene (DNP) units situated in the rod portions of their dumbbell components that are encircled by a single cyclobis(paraquat-p-phenylene) tetracationic (CBPQT(4+)) ring has been developed. Since the π-electron-deficient bispyridinium units are introduced into the dumbbell components of the [2]rotaxanes 1-5·6PF(6), there are Coulombic charge-charge repulsions between these dicationic units and the CBPQT(4+) ring in the [2]rotaxanes. Thus, the CBPQT(4+) rings in the degenerate [2]rotaxanes exhibit slow shuttling between two DNP recognition sites on the (1)H NMR time-scale on account of the electrostatic barrier posed by the bispyridinium units, as demonstrated by variable-temperature (1)H NMR spectroscopy. Electrochemical experiments carried out on the [2]rotaxanes 1·6PF(6) and 2·6PF(6) indicate that the one-electron reduced bipyridinium radical cation in the dumbbell components of the [2]rotaxanes serves as an additional recognition site for the two-electron reduced CBPQT(2(˙+)) diradical cationic ring. Under appropriate conditions, the ring components in the degenerate rotaxanes 1·6PF(6) and 2·6PF(6) can shuttle along the recognition sites--two DNP units and one-electron reduced bipyridinium radical cation--under redox control.     

Functionally rigid bistable [2]rotaxanes

Two-station [2]rotaxanes in the shape of a degenerate naphthalene (NP) shuttle and a nondegenerate monopyrrolotetrathiafulvalene (MPTTF)/NP redox-controllable switch have been synthesized and characterized in solution. Their dumbbell-shaped components are composed of polyether chains interrupted along their lengths by (i) two pi-electron-rich stations-two NP moieties or a MPTTF unit and a NP moiety-with (ii) a rigid arylethynyl or butadiynyl spacer situated between the two stations and terminated by (iii) flexibly tethered hydrophobic stoppers at each end of the dumbbells. This modification was investigated as a means to simplify both molecular structure and switching function previously observed in related bistable [2]rotaxanes with flexible spacers between their stations and incorporating a cyclobis(paraquat-p-phenylene) (CBPQT4+) ring. The nondegenerate MPTTF-NP switch was isolated as near isomer-free bistable [2]rotaxane. Utilization of MPTTF removes the cis/trans isomerization that characterizes the tetrathiafulvalene (TTF) parent core structure. Furthermore, only one translational isomer is observed (> 95 < 5), surprisingly across a wide temperature range (198-323 K), meaning that the CBPQT4+ ring component resides, to all intents and purposes, predominantly on the MPTTF unit in the ground state. As a consequence of these two effects, the assignment of NMR and UV-vis data is more simplified as compared to previous donor-acceptor bistable [2]rotaxanes. This development has not only allowed for much better control over the position of the ring component in the ground state but also for control over the location of the CBPQT4+ ring during solution-state switching experiments, triggered either chemically (1H NMR) or electrochemically (cyclic voltammetry). In this instance, the use of the rigid spacer defines an unambiguous distance of 1.5 nm over which the ring moves between the MPTTF and NP units. The degenerate NP/NP [2]rotaxane was used to investigate the shuttling barrier by dynamic 1H NMR spectroscopy for the movement of the CBPQT4+ ring across the new rigid spacer. It is evident from these measurements that the rigid spacer poses a much lower barrier to the 1.0 nm movement of the CBPQT4+ ring from one station to another as compared with previous systems-a finding that is thought to be a result of the combination of fewer favorable interactions between the spacer and the CBPQT4+ ring and a relatively unimpeded path between the two NP stations. This example augers well for exploiting rigidity during the development of well-defined bistable [2]rotaxanes, which are unencumbered by the excesses of structural conformations that have characterized the first generations of molecular switches based on the donor-acceptor recognition motif.     

Synthesis of Cucurbituril-spermine-[2]rotaxanes of the Amide-type

Abstract

[2]Rotaxanes with the macrocyclic ligand cucurbituril were prepared in yields between 10 and 90% from the reaction of the spermine complex with cucurbituril and different carboxylic acid chlorides in a two phase Schotten-Baumann reaction. This reaction type offers the possibility to synthesize a lot of different [2]rotaxanes. They are characterised by elemental analysis, ¹H-NMR spectroscopy and mass spectrometry.     

Preparation of a variety of macrocyclic Di- and tetraamides and their peraza-crown analogs using the crab-like cyclization reaction

Twelve new macrocyclic di- and tetraamides have been synthesized from the reaction of a bis(α-chloroamide) with a primary amine or with a diamine. Some of these cyclic di- and tetraamides contained pendant aminoalkyl groups attached on one or more ring nitrogen atoms. Two macrocyclic dithiadiamides were prepared from the reaction of a bis(α-chloroamide) and a dimercaptan. In every case, 12-, 14- and 15-membered cyclic di- and tetraamides were isolated in good yields. The 9-, 17- and 18-membered macrocycles were prepared in lower yields. Four of the amide-containing macrocycles were reduced by diborane to the perazacrown compounds.     

Molecular shuttles based on tetrathiafulvalene units and 1,5-dioxynaphthalene ring systems

Six different degenerate [2]rotaxanes were synthesized and characterized. The rotaxanes contained either two tetrathiafulvalene (TTF) units or two 1,5-dioxynaphthalene (DNP) ring systems, both of which serve as recognition sites for a cyclobis(paraquat-p-phenylene) (CBPQT4+) ring. Three different spacer units were incorporated into the dumbbell components of the [2]rotaxanes between the recognition sites. They include a polyether chain, a terphenyl unit, and a diphenyl ether linker, all of which were investigated in order to probe the effect of the spacers on the rate of the shuttling process. Data from dynamic 1H NMR spectroscopy revealed a relatively small difference in the DeltaG++ values for the shuttling process in the [2]rotaxanes containing the three different spacers, in contrast to a large difference between the TTF-containing rotaxanes (18 kcal mol(-1)) and the DNP-containing rotaxanes (15 kcal mol(-1)). This 3 kcal mol(-1) difference is predominantly a result of a ground-state effect, reflecting the much stronger binding of TTF units to the CBPQT4+ ring in comparison with DNP ring systems. An examination of the enthalpic (DeltaH++) and entropic (DeltaS++) components for the shuttling process in the DNP-containing rotaxanes revealed significant differences between the three spacers, a property which could be important in designing new molecules for incorporation into molecular electronic and nanoelectromechanical (NEMs) devices.