Sharpless asymmetric dihydroxylation

The Asymmetric dihydroxylation has been developed by Barry Sharpless catalytic asymmetric oxidation of an olefin to a cis- vicinal diol. The high enantioselectivity of the reaction to take place through the use of a chiral ligand.

Reagents

The reaction is carried out with a catalytic amount of osmium (VIII ) oxide, the most as an OS ( VI ) salt is added and in the course of the reaction by a Kooxidans - K3Fe (CN) 6 or NMO - to Os (VIII ) species is oxidized.

The chiral ligands often dihydroquinine or dihydroquinidine derivatives are added to what is offered commercially as AD- mix. AD- mix α contains K2OsO2 (OH ) 4, K3Fe (CN) 6 and K2CO3 ligand ( DHQ ) 2PHAL in a catalytic amount, while AD- mix β ligands ( DHQD ) 2PHAL contains. Both ligands are diastereomorph. As the solvent, a two -phase mixture - for example, tert -butanol and water - used to prevent premature reoxidation of the cyclic osmate and the concomitant loss of enantioselectivity. Also often methanesulfonamide is used, which accelerates the hydrolysis and acts as a phase transfer catalyst.

The osmium (VIII ) oxide is bonded via a lone pair of electrons in the sp3 orbital of the nitrogen atom of a Dihydrochinidins (see chart ), which has a ligand acceleration result and can run the entire reaction on the reaction path of the chiral complex. This in turn has the high enantioselectivity. Because of the conformation of the ligand and the bound thereto osmium (VIII ) oxide is formed a " chiral pocket ", similar to the active site of an enzyme, in which the olefin is oriented only in a specific conformation.

Reaction mechanism

Of the olefin and the osmium (VIII ) oxide -ligand complex passes through a [3 2] cycloaddition reaction produced a five -membered cyclic intermediate, which is hydrolyzed and the liberated diol. In addition, the reduced osmate, which is reoxidized by the hyperstoichiometrically added Kooxidans arises.