Equilibrium Macrocylizations

Equilibrium effective molarity (EM,), 2—3 Equilibrium macrocylizations. See also... 

Solutions of the alkali elements, in a range of polar solvents, have been shown to contain M , M ", e, and the unusual anion, M , in equilibrium. Early studies were hindered by solubility and decomposition problems. The addition of a macrocylic chelate to these solutions provided a means of increasing the solubility of the metal as well as controlling what species predominate in solution. A metal chelate mole ratio of 2 1 leads to formation of the alkalides [M -i- L] M while a ratio of 1 1 leads to the electrides (see 10.2.2.5), [M -t- L] e (where M and M = Li, Na, K, Rb, Cs (not always the same) and L = two crown ethers (combinations of 12-C-4, 15-C-5, 18-C-6) or one cryptand [2.2.2]). Furthermore, these unique compounds could be isolated as solids and fully characterized. A wider range of alkalides than electrides is known including those with other chelates such as ethylenediamne , and aza crown ethers . Some representative examples are [Na -t- crypt]Na"(the first to be structurally characterized) , and [Cs + 18-C-6)(15-C-5)]Na- . 

An ingenious method of altering the distribution of cyclic oligomers in the EO-BF3 system was developed by Dale20). This method involves formation of insoluble complexes of macrocylics with metal ions shifting the equilibrium to the direction of the desired macrocyclic products. Under typical conditions a mixture of 5 g EO (71 % wt) and 2 g 1,4-dioxane (29 % wt) was converted into products containing 8 % wt EO, 85% wt 1,4-dioxane, 1 % wt cyclic trimer, 4%wt cyclic tetramer and 1 % wt... 

The macrocyles formed depend on the overall proportions of 1 and 2, the diamine chain length and the type of cation used as the template. Of importance is the fact that the imine formation is a reversible reaction. Expressed in the DCC sense, one can say that all products, the macrocycies and the nonrepresented oligomers and polymers, are in constant equilibrium, and that all the species represented in Fig. 22 constitute a virtual combinatorial library (VCL). From this library, the high proportion of a specific macrocycle can be obtained by the use of the appropriate conditions (type of metal template, relative proportion of reactants). 

The fourth class of olefin metathesis in Scheme 21.1 is ring-closing metathesis (RCM). RCM is now used commonly in complex molecule synthesis. The thermodynamics for the ring-closing process are favored by the entropic benefit of generating two molecules from one. Moreover, these reactions are often conducted in an open system under non-equilibrium conditions that release gaseous ethylene. Some of the most favorable RCM reactions form five- and six-membered rings, but RCM has also been used to form macrocylic units in natural products and pharmaceutical candidates. 

In principle, the equilibrium between the /m(macrocylic) compound shown overleaf and the folded form shown above it, would be driven inter alia by entropy. The credibility of such a proposition would be enhanced if a cholesteryl lariat ether, a compound having the macroring and spacer portions of the system shown, could be prepared. Such a structure has been synthesized [10] and its self-assembly into... 

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