Macrocyclic preorganization

This difficulty has been circumvented by the introduction of a modified concept [100]. Here, flexible alkyl chains are used as tethers that are incorporated in macrocyclic cyclo-[n]-malonates. In this way, the regioselectivity is not based on steric preorganization but on the avoidance of unequal strain in the alkyl chains. This has very important consequences for the symmetry of the product addition pattern and dictates selection rules (1) Cyclo-[n]-malonates containing alkyl chains... 

Hemispherands like 66 [37] and 239 [38] are macrocycles in which at least halfofthe ligating heteroatoms is preorganized prior to complexation (another part being crown ether) while in cryptahemispherands like 240 [39] there are two crown type bridges. The latter are very strong binders of alkali metal ions. 

SCHEME 8 A STEPWISE ROUTE TO UNSYMMETRICAL MACROCYCLES. WITH 2,6-PYRIDINE DICARBOXYLIC ACID DICHLORIDE BUILDING BLOCK 17 IS FORMED WHICH IS PREORGANIZED FOR MACROCYCLIZATION AND THUS GIVES HIGHER YIELDS OF MACROCYCLE 18 AS COMPARED TO 13. THE INSET SHOWS THE HYDROGEN BONDING PATTERN IN THE PYRIDINE BUILDING BLOCKS AND THE EFFECTS IT HAS ON CONFORMATIONAL EQUILIBRIA AND... 

A successful synthesis of a rotaxane of this type is shown in Figure 5. First, one tiityl aniline stopper is reacted with the terephthaloyl chloride to from semiaxle 9. This semiaxle threads into the tetralactam macrocycle 3 and is held by the amide template. Then, the preorganized complex is reacted with the second stopper 11 to yield rotaxane 12. Figure 5 shows three hydrogen bonds to form, which is in accord with AMI calculations on this system [19] and X-Ray crystal structure analysis [22],... 

---