Synthesis The Template Effect and High Dilution

The one-pot synthesis of 9 described above appears to afford only modest yields of azacrowns. One might wonder why any crown at all would be formed under non-high dilution conditions intended to yield only open-chained material. Vogtle suggests that this can be explained in terms of template, steric and entropy effects . These factors are of doubtless significance, but it is interesting to note that in the synthesis of poly-azamacrocycles, Richman and Atkins found that there was no significant template effect observed. The question of the template effect in Ihe syntheses of 9 has recently been addressed by Kulstad and Malmsten They conclude that the formation of 9 is assisted by the presence of alkali metal cations. 

Make brief explanatory notes on the following concepts. Source material may be found in both Chapters 1 and 3 (a) the template effect (b) the chelate and macrocyclic effects (c) the high dilution technique in macrocyclic synthesis and (d) preorganisation and complementarity. 

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. 

Greene observed that the formation of 18-crown-6 from a ditosylate and a diol in the presence of f-butoxide salts was enhanced when a potassium cation was used (Greene, 1972). This template effect was operative for the synthesis of other polyether crown compounds using alkali or alkaline-earth metal cations. Template effects have also been observed for the preparation of aza-crown ethers, although the effect is less pronounced because the softer A-donor atoms form weaker complexes with the alkali metal cations (Frens-dorff, 1971). Richman and Atkins reported that high-dilution techniques were not required for the cyclization reaction of the disodium salt of a pertosylated oligoethylenepolyamine with sulfonated diols to form medium and large polyaza-crown compounds (Richman and Atkins, 1974 Atkins et al., 1978). 

The one-pot synthesis of polymers via Ugi-4CR can only be performed if either two bifunctional AA-type components or one AB-type component are used. Moreover, highly concentrated reaction mixtures are needed because otherwise ring formations occur, as thoroughly investigated by Wessjohann and coworkers. Here, the directed synthesis of macrocycles or cryptands under classic or pseudo high dilution conditions, or even without dilution exploiting metal template effects were demonstrated [66, 67]. 

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