Dihydroquinine p-chlorobenzoate

Figure 6D.1. Structureof the dioxo[(3.S,4 )-2,2,5,5-tetramethyl-3,4-hexanediolato]osmium(VI) complex with dihydroquinine p-chlorobenzoate (DHQ-CLB).

After the "asymmetric epoxidation" of allylic alcohols at the very beginning of the 80 s, at the end of the same decade (1988) Sharpless again surprised the chemical community with a new procedure for the "asymmetric dihydroxylation" of alkenes [30]. The procedure involves the dihydroxylation of simple alkenes with N-methylmorpholine A -oxide and catalytic amounts of osmium tetroxide in acetone-water as solvent at 0 to 4 °C, in the presence of either dihydroquinine or dihydroquinidine p-chlorobenzoate (DHQ-pClBz or DHQD-pClBz) as the chiral ligands (Scheme 10.3). 

Preparative Methods the acetate is prepared from dihydroquinine and the p-chlorobenzoate is commercially available. The phthalazine-derived bis(dihydroquinine) ligand is commercially available. A formulation of the standard reactants for the asymmetric dihydroxylation (AD-mix-a) on the small scale has been developed and is commercially available. AD-mix-a (1 kg) consists of potassium osmate (0.52 g), the phthalazine-derived ligand (5.52 g), K3pe(CN)6 (700 g), and powdered K2CO3 (294 g). 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

---