The Spherands

By way of comparison, acyclic podand hosts analogous to compound 3.33 have been produced in order to assess the importance of the rigid preorganisation afforded by a cyclic host. Comparison of the closely related podand 3.36 (which is estimated to possess over 10 000 possible conformations, only two of which can bind cations in a convergent manner) and 3.33 (which is locked in only one conformation) shows that the spherand binds Li more than 10 times more effectively. This highlights the importance of preorganisation effects in host design. 

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The spherand prepared by Cram and coworkers was designed to have a relatively small molecular cavity and appeared to prefer complexation with Li and Na over larger cations like K", Rb, etc. Tlie spheroidal cryptand prepared by Lehn ° involved strategy employed previously but the spherand 24 was prepared by quite a different approach. 

The hemispherands, spherands, calixarenes, and related derivatives. A number of hosts for which the pre-organization criterion is half met (the hemispherands) (Cram et al., 1982) or fully met (the spherands) (Cram, Kaneda, Helgeson Lein, 1979) have been synthesized. An example of each of these is given by (251) and (252), respectively. In (251), the three methoxyl groups are conformationally constrained whereas the remaining ether donors are not fixed but can either point in or out of the ring. This system binds well to alkali metal ions such as sodium and potassium as well as to alkylammonium ions. The crystal structure of the 1 1 adduct with the f-butyl ammonium cation indicates that two linear +N-H - 0... 

It is of interest to compare the cyclodextrins with the spherands, since each consists of cyclic oligomers composed of rigid structural units such that enforced cavities result. However, they differ in that the spherands... 

The synthesis of pyridine analog to the spherands has also been reported as shown for ligand (39).119,120 Corey-Pauling-Kotun (CPK) molecular models of cyclosexipyridine molecules indicate a cavity size appropriate for Rb+ and K+ incorporation.120... 

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]. 

AC and AEC complexation is also effected efficiently by other macrocyclic ligands such as the spherands 13, cryptospherands 14 [2.9, 2.10], calixarenes [2.38, A.6, A.23], torands [2.39], etc., some of them, for instance the spherands displaying particularly high stabilities. A special case is represented by the endohedral complexes of fullerenes in which the cation (Sr2, Ba2+, lanthanides) is locked inside the closed carbon framework [2.40],... 

The AMBER-based approach used to model cyclic polyethers and cryptands has also been applied to the study of the Li+, Na+, and K+ complexes of three spherands (Fig. 14.3)12641. Experimentally determined metal ion selectivities were successfully reproduced. A similar AMBER-based model, used for molecular mechanics and dynamics of a cyclic urea-based spherand, was also successful in reproducing its metal ion selectivity12651. A number of new conformations of the spherand, including the global energy minimum, were located using molecular dynamics12651. 

In order to achieve the final cyclisation step in the spherand syntheses, a new synthetic ring-closure procedure was developed, which proceeds according to Equation 3.2 (acac = acetylacetonato, CH(COMe)2 ). The aryl lithium compound produced by action of butyl lithium is oxidised by the Fe (III) complex to give an aryl biradical, which then undergoes a template cyclisation about the Li+ ion (see Section 3.9.1 for an explanation of the template effect). In the case of 3.33, this method resulted in the isolation of the complex in 28 % yield from the reaction shown in Scheme 3.9. 

As hosts for cations, the phenolic oxygen atoms at the calixarene lower rim (Figure 3.81) have the potential to act in a similar way to the anisole residues of the spherands, either in the original hydroxyl form or as alkyl ether derivatives. This kind of behaviour has been observed for the methyl ether of the parent /j-f-butylcalix[4] arene (compound 3.121) upon reaction with a mixture of sodium benzoate, one... 

Carcerand 6.97 was designed by Cram s group, just as they had designed the spherands, with the aid of CPK molecular models. In his Nobel Prize address, writing just two years after the preparation of 6.97, Cram describes his interest in the host-guest chemistry of this new capsule ... 

This preorganization principle not only affects the thermodynamic stability of the complex but also has a pronounced effect on the kinetic stability of the alkali complexes of the spherands. The anisyl groups in the spherands provide the preorganized ligating donor sites, and they shield the cavity from solvent molecules. As a result, the rates of complexation by the spherands are decreased and the rates of decomplexation are decreased even more when compared with related flexible crown ethers. 

In addition to the spherands, Cram synthesized compounds in which at least half of the binding sites may be considered to be preorganized, the so-called hemispherands.6 In the parent molecule 2, the molecular cavity is composed of a rigid m-teranisyl moiety in which the oxygen binding sites are conformationally organized prior to complexation, and a flexible polyether... 

The same is true for the spherand-type calixarene 47, for which six singlets for OH and t-Bu are found at -150 °C Biali, S. Bohmer, V. Thondorf, I., unpublished results. 

Fig. 1,1, Preorganization does matter. A comparison of 18-crown-6 and the spherand on the right with respect to alkali metal ion binding reveals that the spherand has an up to 10 orders of magnitude higher binding constant.

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