Copper complex catalysis, oxidative

Oxidative coupling polymerization provides great utility for the synthesis of high-performance polymers. Oxidative polymerization is also observed in vivo as important biosynthetic processes that, when catalyzed by metalloenzymes, proceed smoothly under an air atmosphere at room temperature. For example, lignin, which composes 30% of wood tissue, is produced by the oxidative polymerization of coniferyl alcohol catalyzed by laccase, an enzyme containing a copper complex as a reactive center. Tyrosine is an a-amino acid and is oxidatively polymerized by tyrosinase (Cu enzyme) to melanin, the black pigment in animals. These reactions proceed efficiently at room temperature in the presence of 02 by means of catalysis by metalloenzymes. Oxidative polymerization is observed in vivo as an important biosynthetic process that proceeds efficiently by oxidases. 

The d-d absorption of the copper complex differs in each step of the catalysis because of the change in the coordination structure of the copper complex and in the oxidation state of copper. The change in the visible spectrum when phenol was added to the solution of the copper catalyst was observed by means of rapid-scanning spectroscopy [68], The absorbance at the d-d transition changes from that change the rate constants for each elementary step have been determined [69], From the comparison of the rate constants, the electron transfer process has been determined to be the rate-determining step in the catalytic cycle. 

Copper(I) catalysis is very well established to promote intramolecular [2+2] photocycloaddition reactions of l,n-dienes (review [351]). The methodology recently enjoyed a number of applications [352-354], It is assumed that CuOTf, which is commonly applied as the catalyst, coordinates the diene and in this way mediates a preorganization. The Ghosh group recently reported a number of CuOTf-catalyzed photochemical [2+2] cycloaddition reactions, in which an organocopper radical complex was proposed as a cyclization intermediate (which should, however, have a formal Cu(II) oxidation state) (selected references [355-357]). A radical complex must, however, not be invoked, since the process may either proceed by a [2+2] photocycloaddition in the coordination sphere of copper without changing the oxidation state or according to a cycloisomerization/reductive elimination process. 

Addition can also occur to the formal ring double bonds of a nitrogen heteroaromatic compound. The usual preference is for addition adjacent to the nitrogen (equation 41), but this may be modified by substitution, cryptand complexation, quatemization, or copper salt catalysis. Pyridine N-oxides may yield deoxygenated product. 

Experimental antitumor agents such as streptonigrin, bisthiosemicarbazones, and perhaps monothiosemicarbazones must form iron or copper complexes to become biologically active as catalysts of oxidant damage to cells. In sum, metal-based catalysis of redox reactions in cells describes a major topic in cancer therapeutics. Nevertheless, it has remained underdeveloped as a theme for study and application. The sections below provide a coordinated review and perspective on the subject of redox-active, metal-dependent drugs in cancer chemotherapy. 

Multicopper oxidases are typically active in the catalytic one-electron oxidation of a variety of diphenolic, polyphenolic, enediolic, and aminophe-nolic substrates 1,53,166,167). The mechanism of these reactions is complex and, as discussed in Section I, it involves a sequence of four one-electron oxidations of substrate molecules. The radical products of these reactions undergo dismutation, as shown in Scheme 21 for the oxidation of ascorbate to semidehydroascorbate radical 168,169). The substrate binds to the enzymes close to type 1 Cu, whereas the trinuclear cluster is only accessible to dioxygen, or other small molecules. This situation is clearly difficult to reproduce in a model system and for this reason the type of model oxidation reactions that have been studied so far using synthetic trinuclear copper complexes is more related to the activity of type 3 Cu enzymes than multicopper oxidases. Nevertheless, such trinuclear complexes open new perspectives in stereoselective catalysis, because one of the metal centers... 

The process of choice for acetaldehyde production is ethylene oxidation according to the so-called Wacker-Hoechst process [route (c) in Topic 5.3.2]. The reaction proceeds by homogeneous catalysis in an aqueous solution of HQ in the presence of palladium and copper chloride complexes. The oxidation of ethylene occurs in a stoichiometric reaction of PdQ2 with ethylene and water that affords acetaldehyde, metallic palladium (oxidation state 0), and HQ [step (a) in Scheme 5.3.5). The elemental Pd is reoxidized in the process by Cu(II) chloride that converts in this step into Cu(I) chloride [step (b) in Scheme 5.3.5). The Cu(II) chloride is regenerated by oxidation with air to finally close the catalytic cycle [step (c) in Scheme 5.3.5). 

An alternative route with rapid formation of an outer-sphere complex [Fe(phen)3 Si followed by reaction with a second mole of sulphur(iv) is also consistent with the rate law. No evidence was found for copper(u) catalysis in the reactions. The oxidation of hydroxide ion by [Fe(phen)3] + and [Fe(bipy)3] + [Fe(LL)3] + according to the reaction... 

The major problem of these diazotizations is oxidation of the initial aminophenols by nitrous acid to the corresponding quinones. Easily oxidized amines, in particular aminonaphthols, are therefore commonly diazotized in a weakly acidic medium (pH 3, so-called neutral diazotization) or in the presence of zinc or copper salts. This process, which is due to Sandmeyer, is important in the manufacture of diazo components for metal complex dyes, in particular those derived from l-amino-2-naphthol-4-sulfonic acid. Kozlov and Volodarskii (1969) measured the rates of diazotization of l-amino-2-naphthol-4-sulfonic acid in the presence of one equivalent of 13 different sulfates, chlorides, and nitrates of di- and trivalent metal ions (Cu2+, Sn2+, Zn2+, Mg2+, Fe2 +, Fe3+, Al3+, etc.). The rates are first-order with respect to the added salts. The highest rate is that in the presence of Cu2+. The anions also have a catalytic effect (CuCl2 > Cu(N03)2 > CuS04). The mechanistic basis of this metal ion catalysis is not yet clear. 

Additions of suifinic acids to polyenes ( hydrosulfonylation ), however, proceed with very strong acids or under catalysis of Pd complexes (equation 17). With copper(Il) arenesulfinates, azulene has been oxidatively sulfonylated in the 1- and 2-positions of the five-membered ring (equation 18). The sulfonylmercuration has also been applied with success to conjugated dienes (equation 19). 

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