Dihydroxylation of C = C Bond


The dihydroxylation of alkenes provides 1,2-diol products, present in a great many natural products and biologically active molecules.

The transformation has, therefore, received considerable interest and methods are now well developed for catalytic, racemic and asymmetric dihydroxylation.

The most common of these is syn (or cis) dihydroxylation, in which the two hydroxy groups are added to the same side of the double bond.

The best methods involve reaction with osmium tetroxide; other reagents include potassium permanganate or iodine with silver carboxylates.

To prepare the anti (or trans) diol product, ring-opening of epoxides is most convenient, although the Pr´evost reaction (iodine and silver acetate under anhydrous conditions) is also useful.

The alkene may, of course, have either the E- or Z-configuration and syn dihydroxylation gives rise to isomeric diols Treatment of alkenes either with osmium tetroxide or with alkaline potassium perrnanganate results in syn-dihydroxylation of the double bond.

1.1) Dihydroxylation of Olefins with OsO4

The dihydroxylation of olefins with OsO4 provides a reliable method for the preparation of cis-1,2-diols.

Although osmium tetroxide is expensive, it is the reagent of choice for syn-dihydroxylation because yields of diols obtained are usually high.

The reaction can be depicted as a concerted syn-addition of the reagent to the double bond, forming the cyclic osmate ester, which upon hydrolysis or reduction (H2S, Na2HSO3, or Na2O3) produces the cis- 1,2-diol.

1.2) Dihydroxylation of Cis Olefins

The reaction is stereospecific in that Z-alkenes give the anti-1,2-diols.

i.e. Meso, Erythreo,(R,S/S,R) compound.

1.3) Dihydroxylation of Trans olefins

where as (E)-alkenes furnish the syn-1,2-diols

i.e. Recimic, Threo, DL, (R,R/S,S) Compound

1.4) In a cyclic ring system Dihydroxylation

In a cyclic ring system Dihydroxylation always cis and always prefers from less hindered site

Osmium-tetroxide-catalyzed dihydroxylation of sterically hindered olefins proceeds more efficiently with trimethylamine N-oxide in the presence of pyridine.

The base appears to catalyze not only formation of the osmate ester, but also its hydrolysis.

1.5) Selectivity if more than one double bond

Under controlled conditions, the osmium-tetroxide-mediated dihydroxylation is also chemoselective, reacting preferentially with the more nucleophilic double bond in the presence of a triple bond.

1.6) Dihydroxyltion by Chelation control

In contrast, dihydroxylation of allylic alcohols using stoichiometric osmium tetroxide in the presence of tetramethylethylene diamine (TMEDA) as a ligand provides predominantly the syn product.

The diamine TMEDA coordinates to the osmium atom of OsO4, thereby increasing the electronegativity of the oxo ligands and favouring hydrogen bonding to the allylic hydroxy group.

1.7) Dihydroxyltion by epoxide opening

Payne rearrangement by treatment of 2,3-epoxy alcohol A with aqueous NaOH in the presence of a cosolvent to form a anti dihydroxy compound.

1.8) Combine Dihydroxylation

Epoxidation of olefins followed by ring opening with OH- provides 1,2 diols with Trans stereochemistry from that observed with osmiumtetroxide- mediated reaction syn-dihydroxylation.

1.9) Potassium Permanganate

The reaction of alkenes with alkaline potassium permanganate proceeds rapidly via formation of a cyclic manganese ester, which is hydrolyzed to the 1,2-diol.

To avoid overoxidation to an acyloin (a-ketol), the pH of the reaction medium has to be monitored.

Although the yields of cis-diols obtained are usually modest (-50%), the procedure is less hazardous and much less expensive than using osmium tetroxide and thus is well suited for large-scale preparations.

Improved yields of diols are obtained when the oxidation is carried out in water in the presence of a phase transfer agent such as benzyltriethylammonium chloride.

1.10) Asymmetric Dihydroxylation

Reagent-controlled asymmetric dihydroxylation (AD) of prochiral alkenes is feasible using chiral auxiliaries.

Sharpless and coworkers showed that treatment of prochiral alkenes with catalytic amounts of the solid, nonvolatile dipotassium osmate dehydrate (K2[OsVIO2(OH)4]), potassium ferricyanide (K3Fe(CN)6, a stoichiometric oxidant, and a chiral ligand results in enantioselective syn-dihydroxylation.

The required enantiomerically pure ligands are readily available from the cinchona alkaloids dihydroquinine (DHQ) and dehydroquinidine (DHQD).

Since use of the phthalazine spacer (PHAL) outperformed the monomeric alkaloid ligands, the (DHQ)2PHAL and (DHQD)2PHAL analogs have become the first-choice ligands for most AD reactions.

Mechanistic studies of the origin of enantioselectivity for the cinchona alkaloidcatalyzed AD of alkenes have been reported.

1.11) Prevost's conditions

The formation of 1,2-diol products from alkenes can be achieved using Prevost’s reagent a solution of iodine in carbon tetrachloride together with an equivalent of silver(I) acetate or silver(I) benzoate.

Under anhydrous conditions, this oxidant yields directly the diacyl derivative of the anti-diol (Prevost conditions),

Mechanism :

1.10) Woodward conditions:

In the presence of water the monoester of the syn-diol is obtained (Woodward conditions).

Thus, treatment of a cis-alkene with iodine and silver benzoate in boiling carbon tetrachloride under anhydrous conditions gives the trans-dibenzoate.

With iodine and silver(I) acetate in moist acetic acid, however, the monoacetate of the cis-1,2-dihydroxy compound is formed.

Mechanism :

1.13) Amino-hydroxylation

Related to the dihydroxylation of alkenes with osmium tetroxide is the direct conversion of alkenes into 1,2-amino alcohols.

Treatment of an alkene with osmium tetroxide in the presence of N-chloramine-T (TsNClNa) provides the 1,2-hydroxy toluene-p-sulfonamide.