Phthalazine ligands, olefin dihydroxylation

Subsequently, stoichiometric asymmetric aminohydroxylation was reported.78 Recently, it was found by Sharpless79 that through the combination of chloramine-T/Os04 catalyst with phthalazine ligands used in the asymmetric dihydroxylation reaction, catalytic asymmetric aminohydroxylation of olefins was realized in aqueous acetonitrile or tert-butanol (Scheme 3.3). The use of aqueous rerr-butanol is advantageous when the reaction product is not soluble. In this case, essentially pure products can be isolated by a simple filtration and the toluenesulfonamide byproduct remains in the mother liquor. A variety of olefins can be aminohydroxylated in this way (Table 3.1). The reaction is not only performed in aqueous medium but it is also not sensitive to oxygen. Electron-deficient olefins such as fumarate reacted similarly with high ee values. 

The combination of K2[0s02(0H)4] or 0s04 with chiral alkaloid ligands affords highly recyclable systems for the dihydroxylation of olefins. Bis-Chinona alkaloid ligands containing phthalazine or pyrimidine backbones, as shown in Figure 5.8, provide superb enantioselectivity and different models have been devised to rationalise the chirality transfer/71,721... 

The Sharpless group is best known for development of a method for the asymmetrical dihydroxylation of olefins.104 A typical oxidation uses 1 mol% of potassium osmate dihydrate, 1 mol% ligand, potassium carbonate, potassium ferricyanide, and methylsulfonamide in aqueous tert-butyl alcohol. Other oxidants such as A-melhylmor pholine N oxide can be used in place of the potassium ferricyanide. One of the preferred ligands is a bis(dihydro-quinidine ether) of phthalazine (10.46). 

Enantioselective syn dihydroxylation (also aminohydroxylation)8 of olefins using AD-mix-a and AD-mix-p from phthalazine-dihydroquinidine or phthalazine- dihydroquinine and 0s04 or by a new ligand (DHQ)2 PYR or (DHQD)PYR respectively (see 1st edition). 

The product in this particular reaction (naproxen) is a high-value antiinflammatory drug. Even a simple microcapsulation of OSO4 into acrylonitrile-butadiene-styrene (ABS) polymer along with addition of a chiral ligand (N-methyl-morpholine A-oxide or l,4-bis(9-0-dihidroquinidinyl)phthalazine led to a considerable increase in the rate and in the chiral yield during the asymmetric dihydroxylation of olefins (Table 12-7) [64]. 

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