Enantioselective oxygenations

The enantioselective oxygenation procedures, epoxidation and dihydroxylation, developed by Barry Sharpless have dominated single-enantiomer organic synthesis. Recently, several additional methods for enantioselective oxidation have been developed, based on the a-functionalization of carbonyl compounds. 

Casella L, Gullotti M, Ghezzi R et al (1992) Mechanism of enantioselective oxygenation of sulfides catalyzed by chloroperoxidase and horseradish peroxidase. Spectral studies and characterization of enzyme-substrate complexes. Biochemistry 31 9451-9459... 

Enantioselective Oxygenation of Prostereogenic Enolates with Enantiomerically Pure (Camphorsulfonyl)oxaziridines... 

Peroxidases are synthetically important enzymes that can catalyze the enantioselective oxygenation of sulfides to sulfoxides, alkenes to epoxides, alkyl benzenes to benzylic... 

The most attractive aspect of cytochrome P450 monooxygenases is that they are able to perform chiral recognitions and enantioselective oxygenations which are induced by the protein around the active site. This aspect can be mimicked using synthetic chiral catalysts. 

Oxaziridines, prepared by the oxidation of imines, are selective oxygen-transfer reagents. In particular, the camphor-derived reagent is widely nsed for enantioselective oxygenation of enolates and other nucleophiles. 

Such reactions have not yet found their way into the arsenals of synthetic organic chemists instead, multistep sequences such as the chiral base-mediated method shown in Scheme 8.29c are usually used to achieve the net result of enantioselective oxygen insertion [129]. 

Fig. 3. Top Diastereospecific formation of bromohydrin. Center Regiospecific bromina-tive oxidation of 1,3-di-tert.butyl-indol. Bottom Enantioselective oxygenation of thioanisol by bromoperoxidase from the brown alga A nodosum (left) and the red alga C. pilulifera (right). The VClPO from the fungus C. inaequalis produces a racemate.

For the activation of a substrate such as 19a via coordination of the two carbonyl oxygen atoms to the metal, one should expect that a hard Lewis acid would be more suitable, since the carbonyl oxygens are hard Lewis bases. Nevertheless, Fu-rukawa et al. succeeded in applying the relative soft metal palladium as catalyst for the 1,3-dipolar cycloaddition reaction between 1 and 19a (Scheme 6.36) [79, 80]. They applied the dicationic Pd-BINAP 54 as the catalyst, and whereas this type of catalytic reactions is often carried out at rt or at 0°C, the reactions catalyzed by 54 required heating at 40 °C in order to proceed. In most cases mixtures of endo-21 and exo-21 were obtained, however, high enantioselectivity of up to 93% were obtained for reactions of some derivatives of 1. 

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