Алькендерді вициналды диолға түрлендіру реакциясы

Chemical reaction where an alkene is converted to a vicinal diol
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.

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 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. Although the method can produce diols, overoxidation to the dicarbonyl compound has led to difficulties isolating the vicinal diol. The Upjohn protocol yields high conversions to the vicinal diol and tolerates many substrates. However, the protocol cannot dihydroxylate tetrasubstituted alkenes.

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 of a chiral auxiliary. The selection of dihydroquinidine (DHQD) or dihydroquinine (DHQ) as a chiral auxiliary dictates the facial selectivity of the olefin, since the absolute configuration of the ligands are opposite. The catalyst, oxidant, and chiral auxiliary can be purchased premixed for selective dihydroxylation. 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. The Sharpless asymmetric dihydroxylation has a large scope for substrate selectivity by changing the chiral auxiliary class. This has since been applied to homoallylic systems.

Since osmium tetroxide is expensive and toxic, other metals have been used to prepare vicinal diols from olefins. Another popular metal used in dihydroxylation is ruthenium. Although it is highly oxidative, ruthenium has been used because of its short reaction time and its cost effectiveness. Typically, the ruthenium tetroxide is created in situ from ruthenium trichloride, and a secondary oxidant NaIO4 is used to regenerate the catalyst. The turnover limiting step of the reaction is the hydrolysis step; therefore, sulfuric acid is added to increase the rate of this step. Manganese is also used in dihydroxylation and is often chosen when osmium tetroxide methods yield poor results.

Unlike the other methods described that use transition metals as catalyst, the Prévost and Woodward methods use iodine and a silver salt. However, the addition of water into the reaction directs the cis and trans addition of the hydroxyl groups. The Prévost reaction typically uses silver benzoate to produce trans diols; the Woodward modification of the Prévost reaction uses silver acetate to produce cis diols. In both the Prévost and Woodward reactions, iodine is first added to the alkene producing a cyclic iodinium ion. The anion from the corresponding silver salt is then added by nucleophilic substitution to the iodinium ion. In the Prévost reaction, the iodinium ion undergoes nucleophilic attack by benzoate anion. The benzoate anion acts as a nucleophile again to displace iodide through a neighboring group participation mechanism. A second benzoate anion reacts with the intermediate to produce the anti substituted dibenzoate product, which can then undergo hydrolysis to yield trans diols. 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. LiBr reacts with NaIO4 and acetic acid to produce lithium acetate, which can then proceed through the reaction as previously mentioned. The protocol produced high dr for the corresponding diol, depending on the oxidant chosen.

The synthesis of highly substituted and stereospecific sugars is important since polysaccharides make up a large class of compounds found in nature. One specific example is in the biologically active molecule kakelokelose, which has been shown to have anti HIV activity. Research conducted by Harris et al. have worked on an enantiospecific synthesis of sugars pertaining to kakelokelose and other sugars, employing many different dihydroxylation reactions with osmium catalyst. Vinylfuran was reacted under Sharpless conditions with AD mix α to yield (R) diol. Later, a resulting dihydropyran was reacted under Upjohn conditions to yield the resulting sugar, mannose (where R represents either H or a protecting group). Brosa installed the hydroxyl groups in the steroid using both Woodward conditions to yield a cis diol to the A ring of the steroid. Then, the alkene chain on the D ring was dihydroxylated to yield the second cis diol using OsO4 and NMO as the stoichiometric oxidant.