Cinchona Alkaloids as Chiral Ligands in Asymmetric Oxidations

Cinchona Alkaloids as Chiral Ligands in Asymmetric Oxidations 

For oxidation reactions, the cinchona alkaloids have been mainly employed to control the osmium-catalyzed conversion of an alkene to give a 1,2-diol or vicinal functionalized alcohol. As these are important asymmetric reactions, they have been the subject of a number of reviews [1-18]. This chapter discusses the uses of these alkaloids as chiral ligands in asymmetric oxidation reactions. Oxidation reactions where an alkaloid is used in a phase-transfer sense are discussed in Chapter 5. 

The use of osmium tetroxide for the conversion of an alkene to a 1,2-diol is a well-established reaction [19-22]. The formation of an intermediate cyclic ester accounts for the cis-stereochemistry [21, 23-32] as reaction occurs on the least hindered face of the alkene [21, 30, 33-38]. This steric effect is amplified in cyclic substrates [39, 40]. The reaction conditions have to be carefully controlled to avoid oxidative cleavage of the diol product [28]. 

There is a marked rate acceleration in the presence of a tertiary amine or pyridine [19, 41]. This finding provided the background for the asymmetric dihy-droxylation (AD) and, later, the asymmetric aminohydroxylation (AA) reactions as it is this ligand acceleration effect (LAE) that ensures the reaction pathway involving the ligand. 

The use of a cooxidant can reduce the amount of osmium required for a complete reaction of an alkene from stoichiometric to catalytic some examples of oxidants that can achieve this are peroxides [20, 22, 35, 37, 42-44] including hydrogen peroxide [20, 42], chlorates [45], periodate [46, 47], hypochlorite [48], N-methyl-morpholine-N-oxide (NMMO) [22, 34, 35, 37, 49], potassium ferricyanide [50, 51], and even air [52, 53]. 

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SO 3 Cinchona Alkaloids as Chiral Ligands in Asymmetric Oxidations... 

A solid-phase sulfur oxidation catalyst has been described in which the chiral ligand is structurally related to Schiff-base type compounds (see also below). A 72% ee was found using Ti(OPr-i)4, aqueous H2O2 and solid-supported hgand 91 . More recently, a heterogeneous catalytic system based on WO3, 30% H2O2 and cinchona alkaloids has been reported for the asymmetric oxidation of sulfides to sulfoxides and kinetic resolution of racemic sulfoxides. In this latter case 90% ee was obtained in the presence of 92 as chiral mediator. ... 

Sharpless and co-workers first reported the aminohydroxyIation of alkenes in 1975 and have subsequently extended the reaction into an efficient one-step catalytic asymmetric aminohydroxylation. This reaction uses an osmium catalyst [K20s02(OH)4], chloramine salt (such as chloramine T see Chapter 7, section 7.6) as the oxidant and cinchona alkaloid 1.71 or 1.72 as the chiral ligand. For example, asymmetric aminohydroxylation of styrene (1.73) could produce two regioisomeric amino alcohols 1.74 and 1.75. Using Sharpless asymmetric aminohydroxylation, (IR)-N-ethoxycarbonyl-l-phenyl-2-hydroxyethylamine (1.74) was obtained by O Brien et al as the major product and with high enantiomeric excess than its regioisomeric counterpart (R)-N-ethoxycarbonyl-2-phenyl-2-hydroxyethylamine (1.75). The corresponding free amino alcohols were obtained by deprotection of ethyl carbamate (urethane) derivatives. 

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