Metal-catalyzed macrocyclizations, examples

The transition metal catalyzed synthesis of seven membered and larger heterocycles attracted considerably less attention than the preparation of their five and six membered analogues. Typical examples in this chapter include the formation of heterocycles in insertion reactions, or through carbon-heteroatom bond formation. Although the formation of some macrocyclic natural products was also achieved in cross-coupling reactions they will not be discussed in detail. 

There are a few examples of 02 oxidations catalyzed by zeolite-encapsulated complexes. Encapsulated CoPc was active in the oxidation of propene to aldehyde, whereas the free complex was inactive.76 A triple catalytic system, Pd(OAc)2, benzoquinone, and a metal macrocycle, was used to oxidize alk-enes with molecular oxygen at room temperature.77,78 Zeolite-encapsulated FePc79-81 and CoSalophen80,82 complexes were used as oxygen-activating catalysts. 

Perhaps the best-characterized example of this mechanism involves the synthesis of heme cofactors and their subsequent incorporation into various hemoproteins (see Iron Heme Proteins Electron Transport). Succinctly, enzyme-catalyzed reactions convert either succinyl-CoA or glutamate into 5-ammolevulinic acid. This molecule is further converted through a series of intermediates to form protoporphyrin IX, the metal-ffee cofactor, into which Fe is inserted by ferrochelatase. Analogous reactions are required for the synthesis of other tetrapyrrole macrocycles such as the cobalamins (see Cobalt Bu Enzymes Coenzymes), various types of chlorophylls, and the methanogen coenzyme F430 (containing Co, Mg, or Ni, respectively). Co- and Mg-chelatases have been described for insertion of these metals into the appropriate tetrapyrrolic ring structures. ... 

An example of this approach is demonstrated in an antibody mimic of the enzyme ferrochetalase (39). Ferrochelatase catalyzes the insertion of Fe + into protoporphyrin IX (3) as the last step in the heme biosynthetic pathway (40). Interestingly, N-alkylporphyrins are known to be potent inhibitors of this enzyme, because alkylation at one pyrrole lutrogen distorts the planarity of the porphyrin macrocycle (41). This finding was used in the design of hapten 4 to catalyze the incorporation of metal ions into mesoporphyrin IX (5) by eliciting an antibody that binds the substrate in a ring-strained conformation. 

If one moves in the periodic table or in the volcano plot of Figure 2.13 in the direction of metals that have more electrons in the d-orbitals, the activity decreases Ni, Cu, and Zn macrocyclics have low activity and catalyze the reduction of O2 only to peroxide. The lowest activity is shown by CuPc and CuTSPc. Ni, Cu, and Zn complexes do not exhibit the M(IIF(II) transition because between the energy levels of the HOMO and the LUMO of the ligand, they have no energy levels with d-character like for example Cr, Mn, Fe, and Co complexes "-So the low activity is associated to the fact that for these complexes the frontier orbitals have no d-character, so O2 cannot bind to the metal center or the interaction is not favorable. This is clearly illustrated for CuPc in Figures 2.14 and 2.15. Their catalytic activity is then always lower than that found for iron and cobalt chelates Pt, Rh, and Os macrocyclics show some activity but they give peroxide as the main product of the reaction. ... 

Complexation of triynes to Pd(0) has been reported to give homoleptic palladium alkyne complexes that show a trigonal-planar arrangement with all of the alkyne carbons and Pd in the same plane. Complex 73 is a macrocyclic complex synthesized by reaction of the triyne with Pd(PPh3)4- Due to coordination to the metal, the alkyne carbons are shifted to the center of the cycle and their substituents deviate from linearity by about 22°. Complex 74 undergoes clean intramolecular cyclization at room temperature upon addition of PPh3 (Equation (24)). No intermediate complexes were detected in the course of this reaction, which is an example of the important cycloisomerization of alkynes and enynes catalyzed, among other transition metal complexes, by Pd(0) derivatives. 

Non-pendant-arm macrocycles can also react with, and dissociate from, metal ions remarkably slowly when geometric conditions are appropriate, as for example in the classic example of th Ni /cyclam system. Similarly slow release of Ni from its A -cetylcyclam, (11), complex has an adverse effect on liquid-liquid extraction. Even the diazamacrocycle (12) (1,5-diazacyclooctane or daco) dissociates remarkably slowly from Ni " (fc = 2x 10 s for the non-acid-catalyzed path) and from Cu ( = 0.2 s is exceptionally slow for dissociation from this cation). ... 

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