Metal-induced cyclization macrocycles

Two major strategies have been considered in order to obtain metallocorrolates the first one consists of the reaction of the preformed macrocycle with metal ions, while the second involves the oxidative, base induced cycliz-ation of the open-chain tetrapyrrolic precursor dihydrobilin (1,19-dideoxybiladiene-a,c) in buffered alcoholic solution in the presence of metal salts. By proper tuning of the experimental conditions (reaction time, solvent, metal carrier) several metal complexes have been obtained and characterized. 

There are two main approaches to the corrin system. One of them completes the macrocycle by ring closure between C-l and C-19. This is the main route and quite versatile. The first example was reported for the octadehydrocorrin synthesis.239 Biladienes-a,c were cyclized in the presence of metal salts and air to 1,19-frms-ODC complexes, and radical Yin and cationic 16m conrotatory mechanisms have been suggested. The cyclization is also induced by light (Scheme 85). Similarly 1-ethoxy-2,3-dihydro-19-methyl-b-bilene is cyclized to l-ethoxy-19-methyl-7,8,12,13,17,18-HDC (M = Ni).239-249... 

Another celebrated example of the template effect is the synthesis of crown ethers by Pedersen [11], but it was Busch who first intentionally used templates in synthesis and who first articulated the concept of the template effect in the 1960s [12]. Busch used the reaction of a nickel(Il) dithiolate complex 7 with l,2-bis(bromomethyl)benzene 8 to illustrate his ideas (Scheme 1-3) [13]. Once one end of the l,2-bis(bromomethyl)ben-zene has reacted with the nickel complex, the nickel template induces the reactive ends of the intermediate 9 to come into close proximity and favors cyclization. The metal template allows the synthesis of a metallated macrocycle 10 the free ligand cannot be prepared by the reaction of l,2-bis(bromomethyl)benzene with the unbound thiol (in the absence of a template other cyclic and acyclic products are formed). 

The simplest type of template directed cyclization is metal cation induced macrocycliza-tion, as discussed in Section 1.1. Mandolin and co-workers [37] have made a detailed study of the influence of alkali and alkaline earth metal cations on the cyclization of 2-hydroxyphenyl-3,6,9,12-tetraoxa-14-bromotetradecyl ether 28 in methanol and in dimethyl sulfoxide (Scheme 1-8). They studied different sizes of macrocycle and metal cation to determine the most effective combination for cyclization the results from this study will be summarized in Section 1.4.2.3. 

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