Positive cooperativity in the template-directed synthesis of monodisperse macromolecules.

Two series of oligorotaxanes R and R' that contain -CH(2)NH(2)(+)CH(2)- recognition sites in their dumbbell components have been synthesized employing template-directed protocols. [24]Crown-8 rings self-assemble by a clipping strategy around each and every recognition site using equimolar amounts of 2,6-pyridinedicarboxaldehyde and tetraethyleneglycol bis(2-aminophenyl) ether to efficiently provide up to a [20]rotaxane. In the R series, the -NH(2)(+)- recognition sites are separated by trismethylene bridges, whereas in the R' series the spacers are p-phenylene linkers. The underpinning idea here is that in the former series, the recognition sites are strategically positioned 3.5 Å apart from one another so as to facilitate efficient [π···π] stacking between the aromatic residues in contiguous rings in the rotaxanes and consequently, a discrete rigid and rod-like conformation is realized; these noncovalent interactions are absent in the latter series rendering them conformationally flexible/nondiscrete. Although in the R' series, the [3]-, [4]-, [8]-, and [12]rotaxanes were isolated after reaction times of <5-30 min in yields of 72-85%, in the R series, the [3]-, [4]-, [5]-, [8]-, [12]-, [16]-, and [20]rotaxanes were isolated in <5 min to 14 h in 88-98% yields. It follows that while in the R' series the higher order oligorotaxanes are formed in lower yields more rapidly, in the R series, the higher order oligorotaxanes are formed in higher yields more slowly. In the R series, the high percentage yields are sustained throughout, despite the fact that up to 39 components are participating in the template-directed self-assembly process. Simple arithmetic reveals that the conversion efficiency for each imine bond formation peaks at 99.9% in the R series and 99.3% in the R' series. This maintenance of reaction efficiency in the R series can be ascribed to positive cooperativity, that is, when one ring is formed it aids and abets the formation of subsequent rings presumably because of stabilizing extended [π···π] stacking interactions between the arene units. Experiments have been performed wherein the dumbbell is starved of the macrocyclic components, and up to five times more of the fully saturated rotaxane is formed than is predicted based on a purely statistical outcome, providing a clear indication that positive cooperativity is operative. Moreover, it would appear that as the R series is traversed from the [3]- to the [4]- to the [5]rotaxane, the cooperativity becomes increasingly positive. This kind of cooperative behavior is not observed for the analogous oligorotaxanes in the R' series. The conventional bevy of analytical techniques (e.g., HR-MS (ESI) and both (1)H and (13)C NMR spectroscopy) help establish the fact that all the oligorotaxanes are pure and monodisperse. Evidence of efficient [π···π] stacking between contiguous arene units in the rings in the R series is revealed by (1)H NMR spectroscopy. Ion-mobility mass spectrometry performed on the R and R' series yielded the collisional cross sections (CCSs), confirming the rigidity of the R oligorotaxanes and the flexibility of the R' ones. The extended [π···π] stacking interactions are found to be present in the solid-state structures of the [3]- and [4]rotaxanes in the R series and also on the basis of molecular mechanics calculations performed on the entire series of oligomers. The collective data presented herein supports our original design in that the extended [π···π] stacking between contiguous arene units in the rings of the R series of oligorotaxanes facilitate an essentially rigid rod-like conformation with evidence that positive cooperativity improves the efficiency of their formation. This situation stands in sharp contrast to the conformationally flexible R' series where the oligorotaxanes form with no cooperativity.

Molecular gauge blocks for building on the nanoscale.

Molecular gauge blocks, based on 1-7, 9-11 paraxylene rings, have been synthesized as part of a homologous series of oligoparaxylenes (OPXs) with a view to providing a molecular tool box for the construction of nano architectures-such as spheres, cages, capsules, metal-organic frameworks (MOFs), metal-organic polyhedrons (MOPs) and covalent-organic frameworks (COFs), to name but a few-of well-defined sizes and shapes. Twisting between the planes of contiguous paraxylene rings is generated by the steric hindrance associated with the methyl groups and leads to the existence of soluble molecular gauge blocks without the need, at least in the case of the lower homologues, to introduce long aliphatic side chains onto the phenylene rings in the molecules. Although soluble molecular gauge blocks with up to seven consecutive benzenoid rings have been prepared employing repeating paraxylene units, in the case of the higher homologues it becomes necessary to introduce hexyl groups instead of methyl groups onto selected phenylene rings to maintain solubility. A hexyl-doped compound with seven substituted phenylene rings was found to be an organogelator, exhibiting thermally reversible gelation and a critical gelation concentration of 10 mM in dimethyl sulfoxide. Furthermore, control over the morphology of a series of hexyl-doped OPXs to give microfibers, microaggregates, or nanofibers, was observed as a function of their lengths according to images obtained by scanning electron microscopy. The modular syntheses of the paraphenylene derivatives rely heavily on Suzuki-Miyaura cross-coupling reactions. The lack of π-π conjugation in these derivatives that is responsible for their enhanced solubilities was corroborated by UV/Vis and fluorescent spectroscopy. In one particular series of model OPXs, dynamic (1)H NMR spectroscopy was used to probe the stereochemical consequences of having from one up to five axes of chirality present in the same molecule. The Losanitsch sequence for the compounds with 1-3 chiral axes was established, and a contemporary mathematical way was found to describe the sequence. The development of the ways and means to make molecular gauge building blocks will have positive repercussions on the control of nanostructures in general. Their incorporation into extended structures with the MOF-74 topology provides an excellent demonstration of the potential usefulness of these molecular gauge blocks.

Solution-phase counterion effects in supramolecular and mechanostereochemical systems.

The self-assembly of molecular components into complex superstructures involves the subtle interplay of various noncovalent forces. Charged species are often utilised in self-assembly processes as a result of the favorable π-π, cation-π, electrostatic, and hydrogen bonding interactions that form between these species. Although the counterions associated with these charged species can exert significant effects on the synthesis, stability, and operation of superstructures in solution, rarely are the counterions considered, leading to misinterpretations and misunderstandings of the studied systems. In this tutorial review, we discuss a variety of solution-phase counterion effects, from the fundamental origins to innovative ways in which these effects are exploited for useful functions.

The development of bulky palladium NHC complexes for the most-challenging cross-coupling reactions.

Palladium-catalyzed cross-coupling reactions enable organic chemists to form C-C bonds in targeted positions and under mild conditions. Although phosphine ligands have been intensively researched, in the search for even better cross-coupling catalysts attention has recently turned to the use of N-heterocyclic carbene (NHC) ligands, which form a strong bond to the palladium center. PEPPSI (pyridine-enhanced precatalyst preparation, stabilization, and initiation) palladium precatalysts with bulky NHC ligands have established themselves as successful alternatives to palladium phosphine complexes. This Review shows the success of these species in Suzuki-Miyaura, Negishi, and Stille-Migita cross-couplings as well as in amination and sulfination reactions.

Optical and vibrational properties of toroidal carbon nanotubes.

Toroidal carbon nanotubes (TCNTs), which have been evaluated for their potential applications in terahertz communication systems, provide a challenge of some magnitude from a purely scientific perspective. A design approach to TCNTs, as well as a classification scheme, is presented based on the definition of the six hollow sections that comprise the TCNT, slicing each of them to produce a (possibly creased) planar entity, and projecting that entity onto a graphene lattice. As a consequence of this folding approach, it is necessary to introduce five- and seven-membered rings as defect sites to allow the fusing together of the six segments into final symmetric TCNTs. This analysis permits the definition of a number of TCNT geometry families containing from 108 carbons up to much larger entities. Based on density functional theory (DFT) calculations, the energies of these structural candidates have been investigated and compared with [60]fullerene. The structures with the larger tube diameters are computed to be more stable than C(60) , whereas the smaller diameter ones are less stable, but may still be within synthetic reach. Computational studies reveal that, on account of the stiffness of the structures, the vibrational frequencies of characteristic low-frequency modes decrease more slowly with increasing ring diameter than do the lowest optical excitation energies. It was found that this particular trend is true for the "breathing mode" vibrations when the diameter of the tubes is small, but not for more flexible toroidal nanotubes with larger diameters.

Microcontact click printing for templating ultrathin films of metal-organic frameworks.

The controlled growth of metal-organic frameworks (MOFs) over surfaces has been investigated using a variety of surface analytical techniques. The use of microcontact printing to prepare surfaces, patterned with regions capable of nucleating the growth of MOFs, has been explored by employing copper-catalyzed alkyne-azide cycloaddition (CuAAC) to pattern silicon wafers with carboxylic acids, a functional group that has been shown to nucleate the growth of MOFs on surfaces. Upon subjecting the patterned silicon surfaces to solvothermal conditions, MOF thin films were obtained and characterized subsequently by AFM, SEM, and grazing-incidence XRD (GIXRD). Large crystals (∼0.5 mm) have also been nucleated, as indicated by the presence of a bas-relief of the original pattern on one surface of the crystal, suggesting that it is possible to transfer the template surface pattern onto a single crystal of a MOF.

Chromatography in a single metal-organic framework (MOF) crystal.

Millimeter-sized single MOF-5 crystals are used as "chromatographic columns" to effectively separate mixtures of organic dyes. Remarkably, owing to the nanoscopic pore dimensions and the molecular-level interactions between the migrating molecules and the MOF scaffold, the separations occur over a distance of only a few hundred micrometers which is unambiguously confirmed by fluorescence confocal microscopy.

High yielding alkylations of unactivated sp3 and sp2 centres with alkyl-9-BBN reagents using an NHC-based catalyst: Pd-PEPPSI-IPrf.

High yielding, room temperature cross couplings of unactivated alkyl bromides and aryl bromides/chlorides with alkyl-9-BBN reagents has been achieved using an NHC-based catalyst (Pd-PEPPSI-IPr) via a general, functional-group tolerant and easily implemented protocol.

Large-pore apertures in a series of metal-organic frameworks.

We report a strategy to expand the pore aperture of metal-organic frameworks (MOFs) into a previously unattained size regime (>32 angstroms). Specifically, the systematic expansion of a well-known MOF structure, MOF-74, from its original link of one phenylene ring (I) to two, three, four, five, six, seven, nine, and eleven (II to XI, respectively), afforded an isoreticular series of MOF-74 structures (termed IRMOF-74-I to XI) with pore apertures ranging from 14 to 98 angstroms. All members of this series have noninterpenetrating structures and exhibit robust architectures, as evidenced by their permanent porosity and high thermal stability (up to 300°C). The pore apertures of an oligoethylene glycol-functionalized IRMOF-74-VII and IRMOF-74-IX are large enough for natural proteins to enter the pores.

On the role of additives in alkyl-alkyl Negishi cross-couplings.

An additives study for the alkyl-alkyl Negishi reaction using an NHC-Pd catalyst revealed that bromide salts promote coupling while the cation is mechanistically benign. A double titration revealed that the cross-coupling begins at a 1 : 1 ratio of LiBr : (n)BuZnBr, suggesting that a higher-order zincate, presumably Li(m)Zn((n)Bu)Br(3)((2-m)-), is the active transmetalating agent.

Metal-organic frameworks with designed chiral recognition sites.

Linking struts containing Cram-like bisbinaphthyl[22]crown-6 with Zn(4)O(CO(2))(6) joints affords metal-organic frameworks with chiral recognition sites that are highly designed, ordered and placed in a precise manner throughout the entire crystal.

pH-responsive mechanised nanoparticles gated by semirotaxanes.

A [2]pseudorotaxane-based mechanised nanoparticle system, which operates within an aqueous acidic environment, has been prepared and characterised; this integrated system affords both water-soluble stalk and ring components in an effort to improve the biocompatibility of these promising new drug delivery vehicles.

Assessing synthetic strategies: total syntheses of (+/-)-neodolabellane-type diterpenoids.

Two strategies, namely a cross-metathesis/ring-closing metathesis and Pd-catalyzed Stille allylation/Nozaki-Hiyama-Kishi coupling, are examined for the preparation of neodolabellane-type diterpenoids 1 and 2. Whereas the first approach possessed synthetic limitations, the latter was successfully employed to provide compounds 1 and 2 in 8.8% (14 steps) and 8% (15 steps) overall yields, respectively.

Pd-catalyzed aryl amination mediated by well defined, N-heterocyclic carbene (NHC)-Pd precatalysts, PEPPSI.

Pd-N-heterocyclic carbene (NHC)-catalyzed Buchwald-Hartwig amination protocols mediated by Pd-PEPPSI precatalysts is described. These protocols provide access to a range of hindered and functionalized drug-like aryl amines in high yield with both electron-deficient and electron-rich aryl- and heteroaryl chlorides and bromides. Variations in solvent polarity, base and temperature are tolerated, enhancing the scope and utility of this protocol. A mechanistic rationalization for base strength (pKb) requirements is also provided.

Biaryls made easy: PEPPSI and the Kumada-Tamao-Corriu reaction.

An easily employed, highly versatile Kumada-Tamao-Corriu (KTC) protocol utilizing the PEPPSI (Pyridine, Enhanced, Precatalyst, Preparation, Stabilization and Initiation) precatalysts 1 and 2 is detailed. The ease-of-use of these catalysts and the synthesis of a wide range of hindered biaryls, large coupling partners and drug-like heterocycles, in high yield, makes the PEPPSI-KTC protocol very attractive. The high reactivity of the PEPPSI system allowed a tetra-ortho-substituted heterocycle, 11 to be synthesized at room temperature for the first time using any protocol. The PEPPSI protocols also tolerated the Boc protecting group and phenols required no protection in modified conditions. A relatively large scale (10 g) reaction was also performed with no loss in performance. Furthermore, PEPPSI-IPr, 1, was compared to previously reported highly active phosphine ligands 42, 43, and 44 and was shown to result in significantly better yields under identical conditions. Finally, we demonstrated that the PEPPSI catalyst system is very adept at performing sequential KTC coupling reactions, analogous to multicomponent reactions, which allow complex polyaryl and polyheteroaryl architectures to be produced in one single operation.

A user-friendly, all-purpose Pd-NHC (NHC=N-heterocyclic carbene) precatalyst for the negishi reaction: a step towards a universal cross-coupling catalyst.

We have developed the first user-friendly Negishi protocol capable of routinely cross-coupling all combinations of alkyl and aryl centers. The use of an easily synthesized, air stable, highly active, well-defined precatalyst PEPPSI-IPr (1; PEPPSI=pyridine-enhanced precatalyst preparation, stabilization and initiation; IPr=diisopropylphenylimidazolium derivative) substantially increases the scope, reliability, and ease-of-use of the Negishi reaction. All organohalides and routinely used pseudohalides were excellent coupling partners, with the use of chlorides, bromides, iodides, triflates, tosylates, and mesylates resulting in high yield of the coupled product. Furthermore, all reactions were performed by using general laboratory techniques, with no glove-box necessary as the precatalyst was weighed and stored in air. Utilization of this methodology allowed for the easy synthesis of an assortment of sterically encumbered biaryls and druglike heteroaromatics, demonstrating the value of the PEPPSI-IPr system. Furthermore, this is also the first time Pd-NHC (NHC=N-heterocyclic carbene) methodology has surpassed the related phosphine-ligated Negishi processes both in activity and use.

Easily prepared air- and moisture-stable Pd-NHC (NHC=N-heterocyclic carbene) complexes: a reliable, user-friendly, highly active palladium precatalyst for the Suzuki-Miyaura reaction.

The synthesis of NHC-PdCl(2)-3-chloropyridine (NHC=N-heterocyclic carbene) complexes from readily available starting materials in air is described. The 2,6-diisopropylphenyl derivative was found to be highly catalytically active in alkyl-alkyl Suzuki and Negishi cross-coupling reactions. The synthesis, ease-of-use, and activity of this complex are substantial improvements over in situ catalyst generation and all current Pd-NHC complexes. The utilization of complex 4 led to the development of a reliable, easily employed Suzuki-Miyama protocol. Employing various reaction conditions allowed a large array of hindered biaryl and drug-like heteroaromatic compounds to be synthesized without difficulty.