Concave reagents

Luning U. Concave Reagents and Catalysts from Lamps to Selectivity in Mol. Recognit. Inclusion, Proc. Int. Symp., 9th. 1998 203, Ed. Coleman A. W., Pb. Kluwer, Dordrecht... 

On the other hand, in concave reagents, the reactive group is located within the cavity [7]. The concave geometry of enzymes is translated into artificial reagents. The concave shape is retained but the reactive group in the active site is replaced by a standard reagent of organic chemistry. Furthermore the concave... 

The structural components are not limited to one group of compounds (amino acids). Therefore the construction of a concave reagent becomes more variable. 

By using groups other than amino acids, concave reagents will be stable under... 

In the case of catalytic systems, the tedious and expensive synthesis of a concave catalyst is compensated by its (theoretically) unlimited recyclability. Reagents, in contrast, are used up in a reaction. Therefore, concave reagents will only be attractive when, after the reaction, the used functional groups can be returned into the active original functionality. They must be rechargeable . This is trivial for acids and bases but in principle should also be realizable for redox reagents. 

Which tasks have to be accomplished to obtain a concave reagent ... 

Section 2 discusses the syntheses of different classes of concave acids and bases. Convergent synthetic strategies were chosen for an easy structural variation of the reagents (modular assembly). Section 3 characterizes the concave acids and concave bases and checks whether the acid/base properties of the parent compounds benzoic acid, pyridine and 1,10-phenanthroline are conserved in the bimacrocyclic structures. In Section 4, the influence of the concave shielding on the reactivity and selectivity of the concave reagents is measured in model reactions. In principle, the concave shielding should be able to influence inter- and intramolecular competitions as well as chemoselectivity and (dia)stereoselectivity. If the reagent is chiral, enantioselectivity should also be observable. 

The synthetic strategies discussed above are not restricted to pyridines, 1,10-phenanthrolines and benzoic acids. Therefore a large numter of other concave reagents may be synthesized in the future. 

These conformers do not only complicate the NMR spectra, they also make it difficult to discuss the reactive conformation of the concave reagent. Furthermore, the existence of the conformer mixture slows down the crystallization of... 

Based on the X-ray data (see above), the accessibility of the concave functional group was studied. By computer modelling (Connolly-routine [34]), spheres of varying sizes were rolled over the van der Waals-surfaces of the concave reagents which were calculated from the X-ray data, and the resulting contact surface was monitored. 

When the concave reagents are compared to other reactions in Supramole-cular Chemistry a distinct difference must be noted Most other approaches try to bind the substrate in a host first. Then this complex reacts with a reagent which either is present in solution or attached to the host. For concave reagents and concave catalysts, however, there is no need for binding of the educt. In contrast, the protonation reactions can be interpreted as a reagent (H ) host complex. 

Besides concave pyridines, concave 1,10-phenanthrolines and concave benzoic acids, a large number of other concave adds and bases are conceivable containing other acidic or basic groups in the concave position. The central question for such new concave reagents is how can the new functionality be incorporated into the bimacrocyclic structure, and how can a concave orientation be assured ... 

The central benzene ring of cuppedophane 1 can be replaced by various other aromatic or heteroaromatic rings (for example, 9,10-phenanthroline) as in general representation 6. Cuppedophanes of this type possess basic sites in their concave cup. Various members of this class have recently been synthesized and studied by Liining and co-workers as a part of their effort to design concave reagents [8]. 

Phenanthroline-Based Cappedophanes as Selective Concave Reagents... 

While stoichiometric amounts of base were used in the nitronate anion protonations, catalytic amounts of concave macrocycles 156,157 and 159 were found to influence the addition of alcohols to diphenylketene. The chiral concave macrocycle 161 catalyzed the addition of l -l-phenylethanol 20% faster than the addition of the S-enantiomer to the ketene thus demonstrating the enantioselectivity of the concave reagent [8]. 

For a reagent or a catalyst, a reactive functional group is needed. Inspired by the structure of enzymes, the functional group must be located in the concave region. The challenge is an enc(o-functionalization. In 1987, we presented the concept of concave reagents... 

Figure 7.2 The geometry of a concave reagent resembles that of a light bulb in a lamp shade. The shade is the concave shielding. The (re)active site, the light bulb, is located on its inside and can only be touched by a molecule with matching size and shape...

Concave reagents have been employed in many reactions but for the reasons mentioned above, most of the reactions were catalyses. Besides acid or base catalyses, especially transition metal ion catalysed reactions are of interest and have been investigated. The following chapters will hrst present major classes of concave reagents and will then discnss some reactions and catalyses and the influence of the concave shielding on rate and especially selectivity. 

The first examples for concave reagents were bimacrocyclic concave pyridines with the general strnctnre shown in Figure 7.8. A 2,6-disubstitution of the pyridine was chosen in order to ensure the endo-position of the pyridine nitrogen atom s lone pair. Later, the framework of the bimacrocycle has been changed, and in principle, several approaches to concave pyridines, and to concave reagents in general, can be envisioned. 

Figure 7.8 The first class of concave reagents were bimacrocyclic 2,6-disubstituted pyridines with amide bridgeheads building up the bimacrocycle. The bridges X and Y were polymethylene but also polyethylene glycol chains, the basicity of the pyridine could be tuned by respective substituents R in 4-position ...

If the two-step syntheses for bimacrocyclic concave reagents are compared with one another, the use of a pyridine-free macrocycle as the starting material seems to be attractive because numerous macrocycles are easily available, some of which can even be purchased. Consequently, for instance calixarenes have been spanned with pyridine (and other) bridges. Although a very powerful ligand for a copper(I) catalyst has been found... 

Thus a pool of concave reagents has been made available using one or another of these three general strategies. Some of these molecules have been attached to dendrimers or polymers to allow easier recovery. ... 

The field of dynamic combinatorial chemistry takes advantage of the template effect, and numerous macrocycles have been stabilized by a proper tanplate. Also for the construction of macrocycles for concave reagents, the template effect is very valuable. 

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