Chemistry of Thioether Macrocyclic

The coordination chemistry of thioether macrocycles has expanded greatly only since the mid-1980s, as seen by a number of reviews. The macrocychc effect is also noted for... 

Virtually all types of metal ions have been complexed with macrocyclic ligands.2-7 Complexes of transition metal ions have been studied extensively with tetraaza macrocycles (Chapter 21.2). Porphyrin and porphyrin-related complexes are of course notoriously present in biological systems and have been receiving considerable investigative attention (Chapter 22).8 Macrocyclic ligands derived from the Schiffbase and template-assisted condensation reactions of Curtis and Busch also figure prominantly with transition metal ions.6,7 The chemistry of these ions has been more recently expanded into the realm of polyaza, polynucleating and polycyclic systems.9 Transition metal complexes with thioether and phosphorus donor macrocycles are also known.2... 

In recent years, thioethereal macrocycles have attracted considerable interest in the chemical community. A variety of ring sizes have been prepared and their metal ion chemistry studied, yielding a diverse range of structures and unexpected electronic and redox responses. 

Thioether coordination chemistry has undergone a renaissance with the development of general syntheses of poly-thioether macrocyclic hgands. Scheme 29 illustrates some of the ligands that have been reported. The tridentate ligand... 

Another impetus for the study of the coordination chemistry of crown thioethers stems from the role of thioether binding in biological systems such as d-biotin (involving tetrahydrothiophene) (145, 208) and blue copper proteins such as plastocyanin and azurin (involving methionine) (4,13, 73,109,124,185). The binding of Cu(II) and Cu(I) centers to macrocyclic thioethers has led to a greater understanding of Cu-S(thioether) interactions and the stereochemical preferences of these metal centers (91, 95, 99,121,180,181). 

The aim of this chapter is to summarize critically the coordination chemistry of homoleptic thioether macrocycles, with emphasis on likely future developments and uses. The chemistry of mixed-donor ligands is not included. The literature is reviewed up to mid-1989 with particular emphasis on the literature since 1980. Some unpublished results, mainly crystallographic data from our own laboratories, are included. Recent reviews on aspects of thioether chemistry include those by Murray and Hartley (149), Kuehn and Isied (125), Cooper (74), Schroder (188), and Muller and Diemann (148). 

The low affinity of sulfur for alkali metal ions, however, renders template effects of less consequence in the synthesis of polythia macrocycles. Thus, the competition between cycli-zation and linear polymerization is more statistically defined, with cyclization kinetically favored only at high dilution 64,65,66). Consequently, most of the synthetic methods for the synthesis of polythia rings involve high-dilution techniques coupled with relatively long reaction times. Historically, the study of the coordination chemistry of macrocyclic thioethers has been hindered by difficulties in the synthesis of the free ligands. The synthesis of [BJaneSa, first reported by Ochrymowycz and co-workers in 1977 101), illustrates this well. 

A range of the macrocyclic thioethers whose coordination chemistry has been most studied in recent years is illustrated in Figure 1, and references to their synthesis are given in Table 1. 

For several reasons we further restrict consideration to those compounds that comprise solely thioethers as donor groups. First, complexes of such compounds most clearly evince the electronic consequences of thioether coordination. Second, homogeneity of donor group simplifies analysis of conformation. Such studies provide the trends and general principles for interpretation of the coordination chemistry of mixed donor macrocycles. Third, the surge of research effort in all-thioether macrocycles has yielded sufficient information to permit detailed comparisons between complexes of closely related Ugands inclusion of mixed-donor macrocycles contributes little to such discussion. 

In addition to the success just described with the well-known named processes, a number of other macrocyclization reactions mediated by palladium complexes have been reported. The first of these approaches exploits the established chemistry of palladium Jt-allyl complexes for use in activation towards reaction with nucleophiles. This reaction was employed by Harran et al. as a critical step in the construction of a series of macrocycles such as 116 via 115) designed to significantly reduce the peptidic character of known active peptides (Scheme 11.14). " The approach tolerates a variety of functionality, including alcohols, amides, thioethers and selected heteroaromatics, and was also successfully conducted on solid support. 

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