Synthetic macrocycle chemistry

Resulting from the widespread interest in macrocyclic ligand chemistry, an impressive array of synthetic procedures for macrocyclic systems has been developed. In spite of this, the synthesis of a new ring system frequently turns out to be far from trivial. Indeed, synthetic macrocyclic chemistry is often very challenging and, as well as a thorough knowledge of any metal-ion chemistry involved, skill in the subtle art of organic synthesis is also a valuable asset for those involved in the preparation of new cyclic systems. 

Pedersen, Cram and Lehn received the Nobel Prize in Chemistry in 1987 for their work on synthetic macrocyclic compounds. In their Nobel lectures, Pedersen (1988) described the discovery of crown ethers, Cram (1988) and Lehn (1988) the further development of work on new synthetic macrocycles and their host-guest properties. 

Since 1960, a very large number of other synthetic macrocycles has been prepared and this has resulted in a great increase in interest in all aspects of the chemistry of macrocyclic systems. From about this time there has also been enhanced interest in the role of metal ions in biological systems and many such bioinorganic studies have involved complexes of both natural and synthetic macrocycles. Thus there has been an element of cross-fertilization between these two developing areas, viz ... 

Synthetic macrocycles - Natural macrocycles Bioinorganic chemistry ... 

Emphasis in the early years of macrocyclic chemistry was given to the synthesis of a large number of N4-donor cyclic systems but synthetic procedures were subsequently developed for obtaining larger-ring species incorporating more than four donors [such as (38) and (39)]. 

Metathesis is the most useful reaction in recent synthetic organic chemistry.In this reaction, bond fission of two double bonds occurs and two new double bonds are simultaneously formed after exchange (Equation (1)). Ring-closing olefin metathesis is now used for the synthesis of five-membered to macrocyclic ring compounds. 

Although some scattered examples of binding of alkali cations (AC) were known (see [2.13,2.14]) and earlier observations had suggested that polyethers interact with them [2.15], the coordination chemistry of alkali cations developed only in the last 30 years with the discovery of several types of more or less powerful and selective cyclic or acyclic ligands. Three main classes may be distinguished 1) natural macrocycles displaying antibiotic properties such as valinomycin or the enniatins [1.21-1.23] 2) synthetic macrocyclic polyethers, the crown ethers, and their numerous derivatives [1.24,1.25, 2.16, A.l, A.13, A.21], followed by the spherands [2.9, 2.10] 3) synthetic macropolycyclic ligands, the cryptands [1.26, 1.27, 2.17, A.l, A.13], followed by other types such as the cryptospherands [2.9, 2.10]. 

In Section 2.2.1-2.2.3, a brief discussion on the chemistry, properties and structure of contracted, isomeric, and inverted porphyrins has been presented. Here, a brief sketch of the structural diversity in expanded porphyrins is given. Expanded porphyrins represent those synthetic macrocycles in which pyrrole or heterocyclic rings possess connectivity through mcso-carbon bridges. The conjugation of the porphyrin has been... 

The construction of macrocyclic compounds continues to be an important topic of synthetic organic chemistry [52-60], A bifunctional molecule may undergo either intramolecular or intermolecular reactions. A intramolecular reaction gives... 

Additionally to the theoretical data and synthetic techniques for various metal complexes presented in Chaps. 2-A, we would like to pay special attention to three kinds of coordination compounds (complexes of phthalocyanines, quinones, and radioactive elements), whose syntheses, in our opinion, have been insufficiently generalized in monographs and textbooks on synthetic coordination chemistry. This choice is caused by the facts that phthalocyanines, as n-aromatic macrocyclic compounds, possess unusual thermal stability (nonstandard for organic and organometallic species) the quinone complexes have free-radical properties and coordination and organometallic compounds of radioactive elements are interesting at least for the reasons of necessity of special precautions in their syntheses and applications in the nuclear industry and nuclear medicine. So, this chapter is dedicated to the peculiarities of structure and properties and the main synthetic procedures for the complexes above. 

Since the pioneering work of Pedersen (1), Lehn (2), and Cram (3) on synthetic macrocyclic and macropolycyclic host systems such as the crown ethers, cryptands, and spherands, there has been an enormous development of the field of host-guest or supramolecular chemistry. Molecular hosts designed to bind inorganic and organic, charged and neutral guest species via cumulative, noncovalent interactions have all been reported and extensive reviews on this subject have appeared (4-8). 

A large number of PET photocyclizations have appeared in the literature. Since the synthesis of complex polycyclic or macrocyclic ring-system is still a challenge in synthetic organic chemistry [10,17], we have tried to select recent examples of preparative value for this paragraph. Specific target-structures are highlighted in chapter 10.6 (vide infra). 

Again at the beginning of the 1970 s, other classes of synthetic macrocycles were being investigated, not necessarily in connection with biological problems. For instance, the rich chemistry of Schiff base derivatives (Fig. 4.8) was being developed and yielded the first macrocyclic complexes in 1979 (Fig. 4.9). Another type of interesting macrocyclic molecules are the calixarenes (Fig. 4.8) the history of which can be traced back to the first experiments, in Berlin in 1872, of Adolf von Baeyer (Nobel prize in chemistry in 1905) who treated p-substituted phenols with formaldehyde in the presence of acid or base. 

The synthesis of some coronands and cryptands involve several synthetic steps and, sometimes, high dilution techniques to avoid unwanted polymerisation, which considerably adds to the cost of the synthesis. In some instances, it is possible to simplify the synthetic procedure by using a templating agent, that is, a metal ion which pre-organizes the reactants in such a way that they do not polymerise and have the right orientation to yield the desired compound. One of the first examples of such template reaction in lanthanide macrocyclic chemistry was demonstrated by Wanda Radecka-Paryzek who isolated via a one-pot pro-... 

Nearly all iron complexes of synthetic macrocyclic ligands contain nitrogen either as the only ligand atom or as the major donor present. Moreover, most macrocyclic ligands are tetradentate usually presenting a roughly planar N4 donor set to the centrally complexed metal ion. The comprehensive review by Melson390 of the coordination chemistry of macrocyclic compounds should be consulted for work published up until 1978. 

There is a particularly extensive and rich coordination chemistry associated with iron(II) N donor macrocycles. The coordination chemistry of the biologically important iron porphyrin complexes has been of interest since the classic studies of Fischer, and over recent years there has been a resurgence of work on these and also on a wide range of related synthetic macrocyclic complexes. This section concentrates on their coordination chemistry, and where appropriate highlights enhanced ligand reactivity specifically induced by the iron(II) centre. First saturated ligands are discussed and then the unsaturated systems, with the particularly well-studied porphyrins and phthalocyanines being dealt with in separate subsections. 

As macrocyclic chemistry has developed, the variety and scope of the applications of these molecules have continued to multiply. This concluding section is an attempt to provide an overview of only three of the applications of synthetic macrocycles. A particularly insightful treatment can be found in the Nobel Lecture of Jean-Marie Lehn, which describes the concept of supramolecular chemistry from simple recognition, to cation and anion receptors, multiple recognition, catalysis, transport, and molecular devices. 

Related to transport capabilities is the use of synthetic macrocycles in analytical chemistry. Because of their selective complexation of a variety of cations, the crown ethers and related macrocycles have been widely used for separations and analyses. ... 

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