Dihydroxylation is the process by which an alkene is converted into a vicinal diol. Although there are many routes to accomplish this oxidation, the most common and direct processes use a high-oxidation-state transition metal (typically osmium or manganese). The metal is often used as a catalyst, with some other stoichiometric oxidant present. In addition, other transition metals and non-transition metal methods have been developed and used to catalyze the reaction. Mechanism In the dihydroxylation mechanism, a ligand first coordinates to the metal catalyst (depicted as osmium), which dictates the chiral selectivity of the olefin. The alkene then coordinates to the metal through a [3+2] cycloaddition, and the ligand dissociates from the metal catalyst. Hydrolysis of the olefin then yields the vicinal diol, and oxidation of the catalyst by a stoichiometric oxidant regenerates the metal catalyst to repeat the cycle. The concentration of the olefin is crucial to the enantiomeric excess of the diol since higher concentrations of the alkene can associate with the other catalytic site to produce the other enantiomer. Osmium catalyzed reactions Osmium tetroxide (OsO4) is a popular oxidant used in the dihydroxylation of alkenes because of its reliability and efficiency with producing syn-diols. Since it is expensive and toxic, catalytic amounts of OsO4 are used in conjunction with a stoichiometric oxidizing agent. The Milas hydroxylation, Upjohn dihydroxylation, and Sharpless asymmetric dihydroxylation reactions all use osmium as the catalyst as well as varying secondary oxidizing agents. Milas The Milas dihydroxylation was introduced in 1930, and uses hydrogen peroxide as the stoichiometric oxidizing agent. Although the method can produce diols, overoxidation to the dicarbonyl compound has led to difficulties isolating the vicinal diol. Therefore, the Milas protocol has been replaced by the Upjohn and Sharpless asymmetric dihydroxylation. Upjohn Upjohn dihydroxylation was reported in 1973 and uses OsO4 as the active catalyst in the dihydroxylation procedure. It also employs N-Methylmorpholine N-oxide (NMO) as the stoichiometric oxidant to regenerate the osmium catalyst, allowing for catalytic amounts of osmium to be used. The Upjohn protocol yields high conversions to the vicinal diol and tolerates many substrates. However, the protocol cannot dihydroxylate tetrasubstituted alkenes. The Upjohn conditions can be used for synthesizing anti-diols from allylic alcohols, as demonstrated by Kishi and coworkers. Sharpless asymmetric The Sharpless asymmetric dihydroxylation was developed by K. Barry Sharpless to use catalytic amounts of OsO4 along with the stoichiometric oxidant K3[Fe(CN)6]. The reaction is performed in the presence