Benzylic amide macrocycle

The templated syntheses of amide-based rotaxanes discussed until now have made use of the threading-followed-by-capping method. However there are also examples in which the clipping approach has been employed. Leigh, for example, has used a five-component clipping method to prepare [2]rotaxanes. Isophthalamide and peptide-based threads were shown to template the formation of benzylic amide macrocycles about them in non-polar solvents [69, 70]. When the peptide-based threads (49) contain bulky stoppers at their ends, the [2]rotaxanes (50) can be prepared in high yields (see Scheme 24) [71]. 

Scheme 15.9 Reversible shuttling of the benzylic amide macrocycle in [2]rotaxane 53 by redox reactions.

The rotaxane is composed of a glycylglycine chain, a simple dipeptide, bearing two diphenylmethane blocking groups, which prevent the dethreading of the benzylic amide macrocycle. The synthesis of the rotaxane structure is based on... 

In a study of chiral dipeptide [2]rotaxanes it was found that the presence of an intrinsically achiral benzylic amide macrocycle near to the chiral center could induce an asymmetric response in the aromatic ring absorption bands [62], This induced circular dichroism (ICD) effect was stronger in apolar solvents (Fig. 9), where intercomponent interactions are maximized, showing a direct relationship to the tightness with which the macrocycle binds the chiral thread. Computer simulations showed that chirality is transmitted from the amino acid asymmetric center on the thread via the achiral macrocycle to the aromatic rings of the achiral C-terminal stopper. 

Fig. 27 Examples of thermodynamically controlled reactions employed in the near-quantitative synthesis of MIMs. (a) Disulfide-exchange reaction permits equilibration between a bis(ammo-nium) disulfide dumbbell and a crown ether macrocycle to yield a mixture of [2]- and [3]rotaxanes quantitatively [194], (b) Olefin metathesis at high concentration on a benzylic amide macrocycle greatly favors the catenated species [196]. (c) Self-correcting imine bonds allow for nearly quantitative selection of a [2]rotaxane from an appropriate dynamic combinatorial library [76], (d) A weak nucleophile (E) equilibrates the components of a donor-acceptor [2]catenane in a dynamic Sn2 reaction [205]...

A bistable porphyrin-containing [2]rotaxane R3 is synthesized with a shuttling benzylic-amide macrocycle mechanically locked onto the thread subunit via hydrogen bonding with two potential stations, as shown in Figure 5. This macrocycle consists of two pyridine groups, which would be easily coordinated with zinc porphyrin. The Zn(n) coordination of porphyrin moiety on the thread... 

Leigh. D.A. Troisi. A. Zesbetto. F. A quantum-mechanical description of macrocyclic ring rotation in benzylic amide [2]catenanes. Chem. Eur. J. 2002. 7. 1450-1454. 

Other types of rotary motors can be constructed using catenanes, that is, species minimally composed of two mechanically interlocked macrocycles. In appropriately designed systems, the rotation of one ring around the other can be achieved by external stimulation. If suitable control elements are introduced in the structure, such a rotation can be performed unidirectionally. This concept was cleverly realized with benzylic amide catenanes by exploiting the isomerization of fumaramide to maleamide caused by UV light. Chiral C=N compounds such as imines also fulfill the criteria of two-step light-driven unidirectional molecular... 

In the final stages of the total synthesis of ustiloxin D, M.M. Joullie and co-workers had to install the amide side-chain onto the already assembled macrocycle.To achieve this goal, the macrocyclic primary alcohol was treated with the Dess-Martin periodinane to generate the corresponding aldehyde, which was subsequently treated with sodium chlorite to afford the carboxylic acid. The carboxylic acid was then coupled with the benzyl ester of glycine to complete the installation of the side-chain in 66% yield for three steps. 

The presence of the benzamide moiety appears essential for mesophase production. If the benzamides are reduced to the benzyl-amines [240], or straight-chain amides (C,, Hi3CO) [241] are used, all mesophase behaviour disappears. Some smaller ring azamacrocycles 66-68 have been prepared and found to give discotic phases. Their synthesis is wholly similar to that of the hex-acyclens. Benzamides of larger macrocycles (e.g. [30] N,o [241]) have also been synthesized, but these show only monotropic mesophases. 

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