Cyclic Ligands and the Template Effect

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). 

An early demonstration of the template effect in the synthesis of macrocyclic ligands was the metal-ion-controlled cyclic condensation of 2,6-diacetylpyridine with 3,3 -diaminodipropylamine to give complexes of the 14-membered N4 ring (118), usually abbreviated (Me2pyo[14]triene i ). Effective template ions include Ni", Co" and Cu". Well-characterized iron complexes have not been... 

Condensation reactions between carbonyl compounds and primary amines have played a central role in the synthesis of new macrocyclic ligands [28-34]. Usually, though not in all cases, such reactions are conducted in the presence of metal ions which can serve to direct the condensation preferentially to cyclic rather than oligomeric/polymeric products and to stabilize the macrocycle once formed. The relative atomic radius of the templating ion has a considerable effect on the size of the macrocycle formed. For instance, in what is now classic work, cations such as Mg(Il) (r = 0.72 A) were found to stabilize the formation of macrocycles such as 60 from 1 1 condensations [35], while larger cations such as Sr(II)... 

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