Examination of nature's favorite molecules reveals a striking preference for making carbon-heteroatom bonds over carbon-carbon bonds-surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon-heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C-C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C-X-C), an approach we call "click chemistry". Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect "spring-loaded" reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010601%2940%3A11%3C2004%3A%3AAID-ANIE2004%3E3.0.CO%3B2-5

Click Chemistry: Diverse Chemical Function from a Few Good Reactions.

The Conservation of Orbital Symmetry

Fascination with supramolecular chemistry over the last few decades has led to the synthesis of an ever-increasing number of elegant and intricate functional structures with sizes that approach nanoscopic dimensions Today, it has grown into a mature field of modern science whose interfaces with many disciplines have provided invaluable opportunities for crossing boundaries both inside and between the fields of chemistry, physics, and biology This chemistry is of continuing interest for synthetic chemists; partly because of the fascinating physical and chemical properties and the complex and varied aesthetically pleasing structures that supramolecules possess For scientists seeking to design novel molecular materials exhibiting unusual sensing, magnetic, optical, and catalytic properties, and for researchers investigating the structure and function of biomolecules, supramolecular chemistry provides limitless possibilities Thus, it transcends the traditional divisional boundaries of science and represents a highly interdisciplinary field

In the early 1960s, the discovery of ‘crown ethers’, ‘cryptands’ and ‘spherands’ by Pedersen,1 Lehn,2 and Cram3 respectively, led to the realization that small, complementary molecules can be made to recognize each other through non-covalent interactions such as hydrogen-bonding, charge-charge, donor-acceptor, π-π, van der Waals, etc Such ‘programmed’ molecules can thus be self-assembled by utilizing these interactions in a definite algorithm to form large supramolecules that have different physicochemical properties than those of the precursor building blocks Typical systems are designed such that the self-assembly process is kinetically reversible; the individual building blocks gradually funnel towards an ensemble that represents the thermodynamic minimum of the system via numerous association and dissociation steps By tuning various reaction parameters, the reaction equilibrium can be shifted towards the desired product As such, self-assembly has a distinct advantage over traditional, stepwise synthetic approaches when accessing large molecules

It is well known that nature has the ability to assemble relatively simple molecular precursors into extremely complex biomolecules, which are vital for life processes Nature’s building blocks possess specific functionalities in configurations that allow them to interact with one another in a deliberate manner Protein folding, nucleic acid assembly and tertiary structure, phospholipid membranes, ribosomes, microtubules, etc are but a selective, representative example of self-assembly in nature that is of critical importance for living organisms Nature makes use of a variety of weak, non-covalent interactions such as hydrogen–bonding, charge–charge, donor–acceptor, π-π, van der Waals, hydrophilic and hydrophobic, etc interactions to achieve these highly complex and often symmetrical architectures In fact, the existence of life is heavily dependent on these phenomena The aforementioned structures provide inspiration for chemists seeking to exploit the ‘weak interactions’ described above to make scaffolds rivaling the complexity of natural systems

The breadth of supramolecular chemistry has progressively increased with the synthesis of numerous unique supramolecules each year Based on the interactions used in the assembly process, supramolecular chemistry can be broadly classified in to three main branches: i) those that utilize H-bonding motifs in the supramolecular architectures, ii) processes that primarily use other non-covalent interactions such as ion-ion, ion-dipole, π–π stacking, cation-π, van der Waals and hydrophobic interactions, and iii) those that employ strong and directional metal-ligand bonds for the assembly process However, as the scale and degree of complexity of desired molecules increases, the assembly of small molecular units into large, discrete supramolecules becomes an increasingly daunting task This has been due in large part to the inability to completely control the directionality of the weak forces employed in the first two classifications above Coordination-driven self-assembly, which defines the third approach, affords a greater control over the rational design of 2D and 3D architectures by capitalizing on the predictable nature of the metal-ligand coordination sphere and ligand lability to encode directionality Thus, this third strategy represents an alternative route to better execute the “bottom-up” synthetic strategy for designing molecules of desired dimensions, ranging from a few cubic angstroms to over a cubic nanometer For instance, a wide array of 2D systems: rhomboids, squares, rectangles, triangles, etc, and 3D systems: trigonal pyramids, trigonal prisms, cubes, cuboctahedra, double squares, adamantanoids, dodecahedra and a variety of other cages have been reported As in nature, inherent preferences for particular geometries and binding motifs are ‘encoded’ in certain molecules depending on the metals and functional groups present; these moieties help to control the way in which the building blocks assemble into well-defined, discrete supramolecules4

Since the early pioneering work by Lehn5 and Sauvage6 on the feasibility and usefulness of coordination-driven self-assembly in the formation of infinite helicates, grids, ladders, racks, knots, rings, catenanes, rotaxanes and related species,7 several groups - Stang,8 Raymond,9 Fujita,10 Mirkin,11 Cotton12 and others13,14 have independently developed and exploited novel coordination-based paradigms for the self-assembly of discrete metallacycles and metallacages with well-defined shapes and sizes In the last decade, the concepts and perspectives of coordination-driven self-assembly have been delineated and summarized in several insightful reviews covering various aspects of coordinationdriven self-assembly15 In the last decade, the use of this synthetic strategy has led to metallacages dubbed as “molecular flasks” by Fujita,16 and Raymond and Bergman,17 which due to their ability to encapsulate guest molecules, allowed for the observation of unique chemical phenomena and unusual reactions which cannot be achieved in the conventional gas, liquid or solid phases Furthermore, these assemblies found applications in supramolecular catalysis18,19 and as nanomaterials as developed by Hupp20 and others21,22

This review focuses on the journey of early coordination-driven self-assembly paradigms to more complex and discrete 2D and 3D supramolecular ensembles over the last decade We begin with a discussion of various approaches that have been developed by different groups to assemble finite supramolecular architectures The subsequent sections contain detailed discussions on the synthesis of discrete 2D and 3D systems, their functionalizations and applications

Supramolecular coordination: self-assembly of finite two- and three-dimensional ensembles.

The advent of well-defined catalysts for olefin metathesis which combine high activity, durability, and excellent tolerance towards polar functional groups has revolutionized the field. The past decade has seen the rapid embrace of these reagents as tools for advanced organic and polymer chemistry and the success of this development is witnessed by a plethora of elegant applications to the synthesis of natural and nonnatural products. This review article provides an overview of these developments and intends to familiarize the reader with some very recent advances which hold the promise to expand the scope of the reaction even further. Moreover, the positive impact of metathesis on the fundamental logic of retrosynthetic planning is demonstrated by means of typical examples. Finally, it will be shown that metathesis is by no means restricted to alkenes as substrates, and some comments on metathesis reactions following unconventional mechanistic pathways will also be presented.

Olefin Metathesis and Beyond

Tetrathiafulvalenes, oligoacenenes, and their buckminsterfullerene derivatives: the brick and mortar of organic electronics.

Die thermochemische Analyse von Cyclobutanderivaten, die keine wechselwirkungsfreien 1,4-Diradikale bilden konnen, liefert quantitative Evidenz fur einen symmetrieverbotenen, konzertierten Mechanismus ihrer [2 + 2]-Cycloreversion mit antiaromatischem Ubergangszustand.



Forbidden Reactions. — [2 + 2] Cycloreversion of Rigid Cyclobutanes



Cyclobutane derivatives, severely restrained from generating noninteractive 1,4-diradicals, are examined thermochemically to provide quantitative evidence to support a forbidden-concerted, antiaromatic mechanism for their [2 + 2] cyclorevision.

Verbotene Reaktionen. — [2 + 2]-Cycloreversion starrer Cyclobutane

Putting Helium Inside Dodecahedrane

The original concept for the synthesis of pentagonal dodecahedranes by the conversion of structurally similar, high-energy [1111]pagodanes relied on catalytic dehydrocyclizations As a consequence, preparative limitations were preprogrammed With multiple functionalization of these pagodanes, alternative cyclization methods became viable These efficient processes allowed access to a multitude of pentagonal and nonpentagonal, carba- and heterocyclic dodecahedral skeletons with widely variable substitution patterns Such a roundabout route provided the (CH)20 basic framework with high efficiency, and long-lacking thermochemical data could be ascertained calorimetrically In spite of the unusually pronounced pyramidalization of their olefinic centers, singly and doubly unsaturated dodecahedranes with isolated CC bonds proved to be kinetically quite stable, but underwent dimerization on thermal activation Dodecahedranes with a higher degree of unsaturation (trienes–decaenes, C20 fullerene?) have been found so far only in the gas phase Higher fullerenes, including C60, have been identified by mass spectrometry after exposure of halogenated dodecahedranes and pagodanes to a 248-nm excimer laser Transannular electron delocalization has been verified for the “slender” pagodane/isopagodane and even for the “spherical” dodecahedrane cages

From an Insecticide to Plato's Universe—The Pagodane Route to Dodecahedranes: New Pathways and New Perspectives

Electron-impact ionization in a time-of-flight mass spectrometer of C20H0–3Br14–12 probes—secured from C20H20 dodecahedrane by a “brute-force” bromination protocol—provided bromine-free C20H0–2(3) anions in amounts that allowed the clean mass-separation of the hydrogen-free C20− ions and the photoelectron (PE) spectroscopic characterization as C20 fullerene (electron affinity (EA)=2.25±0.03 eV, vibrational progressions of 730±70). The extremely strained C20 fullerene ions surfaced as kinetically rather stable entities (lifetime of at least the total flight time of 0.4 ms); they only very sluggishly expel a C2 unit. The HOMO and LUMO are suggested to be almost degenerate (ΔE=0.27 eV). The assignment as a fullerene was corroborated by the PE characterization of the C20 bowl (EA=2.17±0.03 eV, vibrational progression of 2060±50 cm−1) analogously generated from C20H10 corannulene (C20H1–3Br9–8 samples) and comparably stable. Highly resolved low-temperature PE spectra of the known C20 ring (EA=2.49±0.03 eV, vibrational progressions 2022±45 and 455±30 cm−1), obtained from graphite, display an admixture of, most probably, a bicyclic isomer (EA=3.40±0.03 eV, vibrational progression 455±30 cm−1). The C20+(−) and C20H2+(−) cluster ions generated from polybrominated perylene (C20H0–2Br12–10) have (most probably) retained the planar perylene-type skeleton (sheet, EA=2.47±0.03 eV, vibrational progressions of 2089±30 and 492±30 cm−1 and EA=2.18±0.03 eV, vibrational progressions of 2105±30 and 468±30 cm−1).

Horst Prinzbach

Papers

Verbotene Reaktionen. — [2 + 2]-Cycloreversion starrer Cyclobutane

Putting Helium Inside Dodecahedrane

From an Insecticide to Plato's Universe—The Pagodane Route to Dodecahedranes: New Pathways and New Perspectives

C20 Carbon Clusters: Fullerene–Boat–Sheet Generation, Mass Selection, Photoelectron Characterization

cis‐Trioxa‐tris‐σ‐homobenzol (cis‐„Benzol‐trioxid”︁)