Macrocycles linker length

The low yield achieved for the first dicopper knotted 86-membered macrocycle was improved significantly by changing the length of the linker connecting the two chelates and the long functionalised linker used in the cyclisation step [31-33]. The best yields for the cyclisation reaction were around 8%. The use of a 1,3-phenylene spacer between the coordinating units caused a great improvement [34]. 

The length of the tether is crucial for a successful macrocycle formation. When 51 was attached to acryUc acid through a three carbon linker, no intramolecular cycloaddition was observed to compete with the thermal polymerization of the diene (for other examples of macrocyclic formation through intramolecular Diels-Alder addition, see e.g., [195-200]). 

One direction for the development in this area is looking for more active and stable complex. In 2011, Hapke and coworkers prepared CpCo(H2C = CHSiMc3)2 complex and was found active in [2 + 2 + 2] cycloaddition reactions [26], The other direction is the exploration of applications. In 2005, Maryanoflf and coworkers applied [2 + 2 + 2] cycloaddition reaction in the preparation of macrocycles [27]. In the presence of CpCo(CO)2, pyridine containing macrocycles were prepared from long-chain a,cr-diyne and nitriles, cyanamides, or isocyanates (Scheme 3.11). The regioselectivity of these reactions was affected by the length and type of linker unit between the alkyne groups, as well as by certain stereoelectronic factors. 

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