Cinchona asymmetric oxidations

Another useful method for the asymmetric oxidation of enol derivatives is osmium-mediated dihydroxylation using cinchona alkaloid as the chiral auxiliary. The oxidation of enol ethers and enol silyl ethers proceeds with enantioselectivity as high as that of the corresponding dihydroxylation of olefins (vide infra) (Scheme 30).139 It is noteworthy that the oxidation of E- and Z-enol ethers gives the same product, and the E/Z ratio of the substrates does not strongly affect the... 

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. ... 

WO3-3O % H2O2-CINCHONA ALKALOIDS A NEW HETEROGENEOUS CATALYTIC SYSTEM FOR ASYMMETRIC OXIDATION OF SULFIDES AND KINETIC RESOLUTION... 

Chiral sulfoxides have emerged as versatile building blocks and chiral auxiliaries in the asymmetric synthesis of pharmaceutical products. The asymmetric oxidation of prochiral sulfides with chiral metal complexes has become one of the most effective routes to obtain these chiral sulfoxides.We have recently developed a new heterogeneous catalytic system (WO3-30% H2O2) which efficiently catalyzes both the asymmetric oxidation of a variety of thioethers (1) and the kinetic resolution of racemic sulfoxides (3), when used in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR], Optically active sulfoxides (2) are produced in high yields and with good enantioselectivities (Figure 9.3). ... 

Table 9.4 Asymmetric oxidation of prochiral sulfides ArSR by aq. H2O2 catalyzed by W03-cinchona alkaloids at 0°C...

Table 9.4 presents results of different sulfides that underwent asymmetric oxidation using catalytic WO3 in the presence of cinchona alkaloids such as hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQD)2-PYR] with 30 % H2O2 as oxidant. 

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 chiral ligands has allowed the asymmetric oxidation of alkenes with osmium reagents in catalytic amounts [61-66], The cinchona alkaloids have played, and continue to play, a significant role in this useful synthetic methodology. 

Figure 3.1 Common cinchona alkaloid derived ligand systems for asymmetric oxidations.

The cinchona alkaloids have opened up the field of asymmetric oxidations of alkenes without the need for a functional group within the substrate to form a complex with the metal. Current methodology is limited to osmium-based oxidations. The power of the asymmetric dihydroxylation reaction is exemplified by the thousands (literally) of examples for the use of this reaction to establish stereogenic centers in target molecule synthesis. The usefulness of the AD reaction is augmented by the bountiful chemistry of cyclic sulfates and sulfites derived from the resultant 1,2-diols. 

Cinchona-Based Organocatalysts for Asymmetric Oxidations and Reductions... 

On the contrary, to achieve a successful cinchona-catalyzed asymmetric oxidation chemistry, cinchona-catalyzed asymmetric reduction has been explored very little despite the importance of this reaction. Previous reports on this subject are restricted to the reduction of aromatic ketones and, moreover, the enantioselectivities achieved to date remain far from satisfactory when compared with metal catalysis. 

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