Dihydroxylation

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).

Osmium tetroxide (OsO4) is a popular oxidant used in the dihydroxylation of alkenes because of its reliability and efficiency with producing syn-diols.

AD-mix-α contains the chiral auxiliary (DHQ)2PHAL, which positions OsO4 on the alpha-face of the olefin; AD-mix-β contains (DHQD)2PHAL and delivers hydroxyl groups to the beta-face.

[1][10] The Sharpless asymmetric dihydroxylation has a large scope for substrate selectivity by changing the chiral auxiliary class.

[11] In the dihydroxylation mechanism, a ligand first coordinates to the metal catalyst (depicted as osmium), which dictates the chiral selectivity of the olefin.

[3] As mentioned above, the ability to synthesize anti-diols from allylic alcohols can be achieved with the use of NMO as a stoichiometric oxidant.

[6] The use of tetramethylenediamine (TMEDA) as a ligand produced syn-diols with a favorable diastereomeric ratio compared to Kishi’s protocol; however, stoichiometric osmium is employed.

[17][18] Manganese is also used in dihydroxylation and is often chosen when osmium tetroxide methods yield poor results.

In both the Prévost and Woodward reactions, iodine is first added to the alkene producing a cyclic iodinium ion.

A second benzoate anion reacts with the intermediate to produce the anti-substituted dibenzoate product, which can then undergo hydrolysis to yield trans-diols.

This can then readily react with water to give the monoacetate, which can then be hydrolyzed to give a cis-diol [22] To eliminate the need for silver salts, Sudalai and coworkers modified the Prévost-Woodward reaction; the reaction is catalyzed with LiBr, and uses NaIO4 and PhI(OAc)2 as oxidants.

Then, the alkene chain on the D ring was dihydroxylated to yield the second cis-diol using OsO4 and NMO as the stoichiometric oxidant.