Oxidation using organocatalysts

The third subsection of this chapter discusses the a-funtionalisation of aldehydes and ketones. a-Oxidation, amination and halogenation have recently been achieved with high levels of enantioselectivity using enantiopure Lewis acids, or by generation of chiral nonracemic metal enolates, in the presence of a suitable electrophilic heteroatom source. Similar levels of selectivity in this transformation are obtained via the intermediacy of chiral enamines generated using organocatalysts. 

Recently, great advancement has been made in the use of air and oxygen as the oxidant for the oxidation of alcohols in aqueous media. Both transition-metal catalysts and organocatalysts have been developed. Complexes of various transition-metals such as cobalt,31 copper [Cu(I) and Cu(II)],32 Fe(III),33 Co/Mn/Br-system,34 Ru(III and IV),35 and V0P04 2H20,36 have been used to catalyze aerobic oxidations of alcohols. Cu(I) complex-based catalytic aerobic oxidations provide a model of copper(I)-containing oxidase in nature.37 Palladium complexes such as water-soluble Pd-bathophenanthroline are selective catalysts for aerobic oxidation of a wide range of alcohols to aldehydes, ketones, and carboxylic acids in a biphasic... 

More recently, a series of sol-gel hydrophobized nanostructured silica matrices doped with the organocatalyst TEMPO (SiliaCat TEMPO) entered the market as suitable oxidation catalysts for the rapid and selective production of carbonyls and carboxylic acids. In the former case, SiliaCat TEMPO selectively mediates the oxidation of delicate primary and secondary alcohol substrates into valued carbonyl derivatives (Scheme 5.2), retaining its potent activity throughout several reaction cycles (Table 5.2).33 Using this catalyst, for example, enables the synthesis of extremely valuable a-hydroxy acids with relevant selectivity enhancement by coupling of SiliaCat TEMPO with rapid Ru04-mediated olefin dihydroxylation (Scheme 5.3).34... 

A related N-oxide organocatalyst of type 178, developed by Maikov and Kocovsky et al., has been used for successful asymmetric allylation of aldehydes [178]. It is worthy of note that the corresponding N,N -dioxide gave less satisfactory results. In the presence of 7 mol% N-monoxide 178, aromatic aldehydes have been con-... 

Researchers at Degussa AG focused on an alternative means towards commercial application of the Julia-Colonna epoxidation [41]. Successful development was based on design of a continuous process in a chemzyme membrane reactor (CMR reactor). In this the epoxide and unconverted chalcone and oxidation reagent pass through the membrane whereas the polymer-enlarged organocatalyst is retained in the reactor by means of a nanofiltration membrane. The equipment used for this type of continuous epoxidation reaction is shown in Scheme 14.5 [41]. The chemzyme membrane reactor is based on the same continuous process concept as the efficient enzyme membrane reactor, which is already used for enzymatic a-amino acid resolution on an industrial scale at a production level of hundreds of tons per year [42]. 

The use of neutral coordinate organocatalysts such as DMF, sulfoxides, and phosphine oxides to activate allyltrichlorosilane in allylation of acylhydrazones has been reviewed 94... 

Nedelec and coworkers reported a manganese(III)-initiated cyanoacetate-catalyzed atom-transfer radical addition of polyhalomethanes or dibromomalonate 172 to alkenes 126 (Fig. 48) [272]. Since neither Mn(II) nor Mn(III) is useful to initiate Kharasch-type additions, an organocatalyst served this purpose. Thus, a short electrolysis of a mixture of 126,172,10 mol% of Mn(OAc)2, and 10 mol% of methyl cyanoacetate 171 led to initial oxidation of Mn(II) to Mn(III), which served to form the cyanoacetate radical 171A oxidatively. The latter is able to abstract a halogen atom from 172. The generated radical 172A adds to 126. The secondary... 

In 2004, Jorgensen and coworkers disclosed a-hydroxylation of 1,3-dicarbonyl systems 104 (Scheme 6.31) [59]. They used hydroquinine (106) as the organocatalyst and cumyl hydroperoxide as the oxidant for the enantioselective a-hydroxylation of various P-keto esters 104 with enantioselectivities up to 80% ee. Optimization studies revealed that the 0(9)-OH group of 106 is critical for good stereoselectivity, and the best enantioselectivity was obtained under CH2Br2 solvent at room temperature. 

Aqueous hydrogen peroxide, as a cheap and commercially available reagent, is an ideal oxidant because it can be safely stored and handled, contains effective oxygen, and produces water as the only by-product. Due to the low standard redox potential of hydrogen peroxide in neutral or weak acidic media, it has been usually used in the presence of inorganic acids or organocatalysts. 

In Section 10.5.2 we considered in detail the use of poly(amino acids) as oxidation catalysts for the epoxidation of chalcones. Rather surprisingly, such materials, as homopolymers or anchored to different supports, have been less studied as organocatalysts for other processes. Perhaps the poor results obtained for the enantioselective addition of thiols to unsaturated ketones in the pioneering work by Inoue are responsible for this situation [346]. 

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