Homogeneous Copper-Catalyzed Oxidations

Stahl et al. reported a continuous homogeneous copper-catalyzed aerobic oxidation method for primary alcohols [32]. A modified tube reactor was used (Figure 23.3). A dilute oxygen source (9% O2 in Nj) was controlled by a mass flow controller and mixed with the substrate and catalyst solution, respectively, by... 

Figure 23.3 Schematic diagram of the tube reactor setup for homogeneous copper-catalyzed oxidation of primary alcohols.

There are many ways to produce acetaldehyde. Historically, it was produced either hy the silver-catalyzed oxidation or hy the chromium activated copper-catalyzed dehydrogenation of ethanol. Currently, acetaldehyde is obtained from ethylene hy using a homogeneous catalyst (Wacker catalyst). The catalyst allows the reaction to occur at much lower temperatures (typically 130°) than those used for the oxidation or the dehydrogenation of ethanol (approximately 500°C for the oxidation and 250°C for the dehydrogenation). 

Like BINOL, salicylaldehyde imines have become very important in asymmetric catalysis and a variety of polydentate ligands prepared from chiral monoamines and diamines are employed in oxidation reactions, carbenoid reactions and Lewis acid catalyzed reactions. As in the previous section, this section emphasizes the effect of the phenol moiety on the asymmetric catalysis. An imine derived from a chiral 1-phenethylamine and salicylaldehyde was employed in the copper catalyzed asymmetric cyclopropanation by Nozaki, Noyori and coworkers in 1966, which is the first example of the asymmetric catalysis in a homogeneous system . Salicylaldehyde imines with ethylenediamine (salen) have been studied extensively by Jacobsen and Katsuki and their coworkers since 1990 in asymmetric catalysis. Jacobsen and coworkers employed the ligands prepared from chiral 1,2-diamines and Katsuki and coworkers sophisticated ligands possess chirality not only at the diamine moiety but also at the 3,3 -positions. 

The copper-catalyzed cyclopropanation of alkenes with diazoalkanes is a particularly important synthetic reaction (277). The reaction of styrene and ethyl diazoacetate catalyzed by bis[/V-(7 )- or (5)-a-phenyl-ethylsalicylaldiminato]Cu(II), reported in 1966, gives the cyclopropane adducts in less than 10% ee and was the first example of transition metal-catalyzed enantioselective reaction of prochiral compounds in homogeneous phase (Scheme 90) (272). Later systematic screening of the chiral Schiff base-Cu catalysts resulted in the innovative synthesis of a series of important cyclopropane derivatives such as chrysanthemic acid, which was produced in greater than 90% ee (Scheme 90) (273). The catalyst precursor has a dimeric Cu(II) structure, but the actual catalyst is in the Cu(I) oxidation state (274). (S)-2,2-Dimethylcyclopropanecar-boxylic acid thus formed is now used for commercial synthesis of ci-lastatin, an excellent inhibitor of dehydropeptidase-I that increases the in vivo stability of the caibapenem antibiotic imipenem (Sumitomo Chemical Co. and Merck Sharp Dohme Co.). Attempted enantioselective cyclopropanation using 1,1-diphenylethylene and ethyl diazoacetate has met with limited success (211b). A related Schiff base ligand achieved the best result, 66% optical yield, in the reaction of 1,1-diphenylethylene and ethyl diazoacetate (275). 

Copper compounds catalyze an exceedingly varied array of reactions, hetereogeneously, homogeneously, in the vapor phase, in organic solvents and in aqueous solutions. Many of these reactions, particularly if in aqueous solutions, involve oxidation-reduction systems and a Cu -Cu11 redox cycle. Molecular oxygen can often be utilized as oxidant, e.g., in copper-catalyzed oxidations of ascorbic acid and in the Wacker process (page 798) for conversion of alkenes into aldehydes. 

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