Macrocycles synthetic catalysts

In this complex, enhanced rate of H-transfer to the bound pyridinium salt substrate is observed. This represents the first example of accelerated 1,4-dihydropyridine to pyridinium H-transfer (transreduction) in a synthetic molecular macrocyclic receptor-substrate complex. Therefore, such a synthetic catalyst displays some of the characteristic features which molecular catalysts should possess. It provides both a receptor site for substrate binding and a reactive site for transformation of the bound substrate. Consequently it is of interest as both as enzyme model, and as a new type of efficient and selective chemical reagent (278). 

The intramolecular version for synthesizing cyclic and polycyclic compounds offers a powerful synthetic method for naturally occurring macrocyclic and polycyclic compounds, and novel total syntheses of many naturally occurring complex molecules have been achieved by synthetic designs based on this methodology. Cyclization by the coupling of an enone and alkenyl iodide has been applied to the synthesis of a model compound of l6-membered car-bomycin B 162 in 55% yield. A stoichiometric amount of the catalyst was used because the reaction was carried out under high dilution conditions[132]. 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

The preparation of novel triazole-containing 20-22 membered macrocyclic azacrown ether-thioethers was reported <96JCR(S)182> and the first selective synthetic method fra the synthesis of dicyanotriazolehemiporhyrazines was published <96JOC6446>. 1,2,4-Triazole-containing polyimide beads were prepared and employed as Mo(VI) epoxidation catalyst supports, liie 1,2,4-nitronyl nitroxide 29 was also synthesized and found to have remarkable magnetic properties <96AM60>. 

The simple porphyrin category includes macrocycles that are accessible synthetically in one or few steps and are often available commercially. In such metallopor-phyrins, one or both axial coordinahon sites of the metal are occupied by ligands whose identity is often unknown and cannot be controlled, which complicates mechanistic interpretation of the electrocatalytic results. Metal complexes of simple porphyrins and porphyrinoids (phthalocyanines, corroles, etc.) have been studied extensively as electrocatalysts for the ORR since the inihal report by Jasinsky on catalysis of O2 reduction in 25% KOH by Co phthalocyanine [Jasinsky, 1964]. Complexes of all hrst-row transition metals and many from the second and third rows have been examined for ORR catalysis. Of aU simple metalloporphyrins, Ir(OEP) (OEP = octaethylporphyrin Fig. 18.9) appears to be the best catalyst, but it has been little studied and its catalytic behavior appears to be quite distinct from that other metaUoporphyrins [CoUman et al., 1994]. Among the first-row transition metals, Fe and Co porphyrins appear to be most active, followed by Mn [Deronzier and Moutet, 2003] and Cr. Because of the importance of hemes in aerobic metabolism, the mechanism of ORR catalysis by Fe porphyrins is probably understood best among all metalloporphyrin catalysts. 

Protonated forms of the large-ring macrocycle [24]Ng02 (5) and related compounds have been shown to be active as synthetic phosphorylation catalysts in ATP synthesis. It is likely that in this case the substrate enters the macrocyclic cavity to some extent, or is enveloped by it. Evidence for this possibility comes from the crystal structure of the chloride salt of 5-6H (Figure 1) in which a chloride ion is enveloped within a cleft formed by the boat-shaped conformation of the macrocy-cle. The crystal structure of the nitrate salt of 5-4H has also recently been determined and the host again adopts a boat-like conformation as it interacts with the anion. The hydrochloride salt of the smaller [22]Ng binds two chloride anions above and below the host plane in a similar way to 1. Molecular dynamics simulations indicate that the pocket-like conformation for 5-6H is maintained in solution, although Cl NMR experiments demonstrate that halide ions are in rapid exchange between the complexed and solvated state. 

We have also synthesized a catalyst related to 131 in which the cyclodextrin rings were replaced with synthetic macrocyclic binding groups [196], Also, we have examined catalysts related to 131 in which substrate binding involved metal ion coordination, not hydrophobic binding into cyclodextrins or macrocycles [198]. 

Given the observation of catalysis of alkene epoxidation by iron N-alkyl porphyrins, it is likely that these complexes may yield synthetically useful catalysts (32, 65). The possibility of chiral induction by using either a chiral N-alkyl group (66) or a chiral macrocycle such as N-Me etioporphyrin (67) is an area that should prove fruitful in the near future. 

Recently, the group of Deffieux181 presented the synthesis and solution properties of macrocyclic poly-(styrene-/rethylene oxide). The synthetic route involved the preparation of a linear a-diethylacetal-a -styrenyl poly(styrene-b-ethylene oxide) precursor and cyclization by cationic activation with SnCh catalyst. The a-diethylacetal-poly(styrene-/rethyl-ene oxide) precursor was synthesized by using a-di-ethylacetalpropyllithium as initiator of styrene. The functional living PS was end-capped with ethylene oxide, and the resulted cu-hydroxyl group was reacted with diphenylmethylpotassium. The potassium alkox-... 

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