Macrobicycles lateral

An attractive feature of this route is that the macrobicyclic intermediate 40a can be readily N-alkylated without affecting the masked thiolate functions (209). Thus, reductive methylation of 40a with formaldehyde and formic acid under Eschweiler-Clarke conditions, followed by deprotection of 40b with Na/NH3 provides the otherwise inaccessible N6S2 ligand H2L19 in nearly quantitative yield (Scheme 1). Several other aza-thioethers 40c-p and their corresponding thiophenolate ligands were prepared by this route (see Fig. 30 and Table I) and some of them will be discussed further in later sections (210-215). 

Although two cations are often observed to complex in a dinuclear fashion in the axial macrobicycles, as noted in the previous paragraphs, lateral macrobicycles (Figure 1) are clearly designed for incorporation of two metal ions.9,171,172 These two metal ions are by construction necessarily in chemically different environments, which can greatly affect both chemical and physical properties. For example, in the bis-copper(II) complex of (49b) the two copper ions exhibit greatly different redox potentials (+ 550 and + 70 mV vs. NHE in propylene carbonate).9... 

Lateral macrobicycles are dissymmetric by design thus, monoelectronic reduction of the Cu(ll) ion bound to the [12]-N2S2 macrocyclic subunit in the bis-Cu(ll) cryptate 45, gives a mixed valence Cu(i)-Cu(ll) complex [4.6]. Macrotricycle 46 forms a dinuclear Cu(ll) cryptate that acts as a dielectronic receptor and exchanges two electrons in a single electrochemical wave [4.7]. Complexes of type 47 combine a redox centre and a Lewis acid centre for the potential activation of a bound substrate [4.8]. 

The high-dilution method (for technical details see for example Ref. 21) has been used not only to form simple cryptands, but also in the syntheses of more complex systems — cylindrical macrotricyclic molecules24), lateral macrobicycles 25), spherical macrotetracyclic systems 26), and speleands 27). Nevertheless, the important drawback of the method is the last step, e.g. reduction with diborane. That means only compounds which do not interfere with this reagent can be formed in this manner. Also, even a small contamination of the solvents and reactants with water has a significant influence on the yield. 

An ingenous method for the preparation of the lateral macrobicycles has been developed by Newkome and co-workers 30). The method consists on bis-quatemization of the macrocycles 25 with bis(2-iodoethoxy)ethane (26) in boiling acetonitrile to afford the bis-quaternary salts 27 in ca. 40% yield. Those were not isolated, but directly demethylated with L-selectride to form the desired macrobicycles 28 in a 40 % overall yield (Scheme 4). 

Undoubtly, cryptands remain the class of macrobicyclic and macropolycyclic receptors looking forward to a great future. The number of possible structures is practically unlimited and depends on a researcher imagination and creativity. Initially, the chemistry of cryptands had focused on the development of new synthetic strategies, either to improve the yields or to built up more complicated molecular architectures, like cylindrical, spherical or lateral macropolycycles, bi- or polynucleating, with hard and soft binding sites, etc. 

Lehn120) has also reported the synthesis of a lateral macrobicyclic molecule, 193, where a macrocyclic unit is bridged by a chelating unit which contains a... 

Gunter and coworkers have synthesized a lateral macrobicyclic molecule 197 where a phorphyrin ring is capped by a bridging unit which contains a pyridino subunit. This model system for cytochrome c oxidase is in fact a heterodinuclear complex with iron(III) complexed to the porphyrin unit and copper(II) complexed to the lateral pyridino bridge. A series of these complexes have been made with... 

Figure L Dijferent types of binucleating macrocycles a) large rings, b) bis-macrocycles, c) axial macrobicycles, d) lateral macrobicycles, and e) cylindrical macrobicycles.

A similar effect occurs with the cryptates. Comparing the stability constants of c 2.2.2] and its one-strand opened analogue (54) (known as a lariat ether , see later) the stability increases by a factor of 10 (Figure 2.16), and this is known as the cryptate effect or as the macrobicyclic cryptate effect (47). After comparing the thermodynamic quantities associated with formation of the [K c 2.2.2] complex to those for the K -dicyclohexyl-18-crown-6 (2) complex, Kauffmann and co-workers concluded that the cryptate effect is of enthalpic origin (52). 

---