Oxidation asymmetric alkene dihydroxylation

With this reaction, two new asymmetric centers can be generated in one step from an achiral precursor in moderate to good enantiomeric purity by using a chiral catalyst for oxidation. The Sharpless dihydroxylation has been developed from the earlier y -dihydroxylation of alkenes with osmium tetroxide, which usually led to a racemic mixture. 

One of the most exciting developments in asymmetric catalysis over the past 25 years has been the discovery of transition metal complexes that catalyze the oxidation of alkenes to chiral epoxides and 1,2-diols. Equations 12.16, 12.17, and 12.18 show examples of epoxidation and 1,2-dihydroxylation. 

The cinchona alkaloids have opened up the field of asymmetric oxidations of alkenes without the need for a functional group within the substrate to form a complex with the metal. Current methodology is limited to osmium-based oxidations. The power of the asymmetric dihydroxylation reaction is exemplified by the thousands (literally) of examples for the use of this reaction to establish stereogenic centers in target molecule synthesis. The usefulness of the AD reaction is augmented by the bountiful chemistry of cyclic sulfates and sulfites derived from the resultant 1,2-diols. 

Oxidation of Alkenes Syn 1,2-Dihydroxylation 368 THE CHEMISTRY OF... Catalytic Asymmetric Dihydroxylation 370... 

The catalytic asymmetric dihydroxylation reaction developed by Sharpless (Sharpless asymmetric dihydroxylation [SAD]) allows the straightforward oxidation of alkenes 76 to the corresponding cw-diols 77 with good to excellent yields and enantioselectivities without suffering from the presence of oxygen and moisture. The core of the catalytic system is based on an Os(VIII) metal center that coordinates the alkenes and transfers an oxygen atom to it using KsFe (CN)6 as terminal oxidant in the presence of enantiopure tertiary amines derived by dihydroquinidine 78 or... 

Also fifteen years of painstaking work and the gradual improvement of the system, the Sharpless team announced that asymmetric dihydroxylation (AD) of nearly every type of alkene can be accomplished using osmium tetraoxide, a co-oxidant such as potassium ferricyanide, the crucial chiral ligand based on a dihydroquinidine (DHQD) (21) or dihydroquinine (DHQ) (22) and metha-nesulfonamide to increase the rate of hydrolysis of intermediate osmate esters 1811. 

These cinchona esters also effect asymmetric dihydroxylation of alkenes in reactions with an amine N-oxide as the stoichiometric oxidant and 0s04 as the catalyst. Reactions catalyzed by 1 direct attack to the re-face and those catalyzed by 2 direct attack with almost equal preference for the 5i-face. 

In the case of prochiral alkenes the dihydroxylation reaction creates new chiral centers in the products and the development of the asymmetric version of the reaction by Sharpless was one of the very important accomplishments of the last years. He received the Nobel Price in Chemistry 2001 for the development of catalytic oxidation reactions to alkenes. 

Sharpless stoichiometric asymmetric dihydroxylation of alkenes (AD) was converted into a catalytic reaction several years later when it was combined with the procedure of Upjohn involving reoxidation of the metal catalyst with the use of N-oxides [24] (N-methylmorpholine N-oxide). Reported turnover numbers were in the order of 200 (but can be raised to 50,000) and the e.e. for /rara-stilbene exceeded 95% (after isolation 88%). When dihydriquinidine (vide infra) was used the opposite enantiomer was obtained, again showing that quinine and quinidine react like a pair of enantiomers, rather than diastereomers. 

After the "asymmetric epoxidation" of allylic alcohols at the very beginning of the 80 s, at the end of the same decade (1988) Sharpless again surprised the chemical community with a new procedure for the "asymmetric dihydroxylation" of alkenes [30]. The procedure involves the dihydroxylation of simple alkenes with N-methylmorpholine A -oxide and catalytic amounts of osmium tetroxide in acetone-water as solvent at 0 to 4 °C, in the presence of either dihydroquinine or dihydroquinidine p-chlorobenzoate (DHQ-pClBz or DHQD-pClBz) as the chiral ligands (Scheme 10.3). 

Other functionalized supports that are able to serve in the asymmetric dihydroxylation of alkenes were reported by the groups of Sharpless (catalyst 25) [88], Sal-vadori (catalyst 26) [89-91] and Cmdden (catalyst 27) (Scheme 4.13) [92]. Commonly, the oxidations were carried out using K3Fe(CN)g as secondary oxidant in acetone/water or tert-butyl alcohol/water as solvents. For reasons of comparison, the dihydroxylation of trons-stilbene is depicted in Scheme 4.13. The polymeric catalysts could be reused but had to be regenerated after each experiment by treatment with small amounts of osmium tetroxide. A systematic study on the role of the polymeric support and the influence of the alkoxy or aryloxy group in the C-9 position of the immobilized cinchona alkaloids was conducted by Salvadori and coworkers [89-91]. Co-polymerization of a dihydroquinidine phthalazine derivative with hydroxyethylmethacrylate and ethylene glycol dimethacrylate afforded a functionalized polymer (26) with better swelling properties in polar solvents and hence improved performance in the dihydroxylation process [90]. 

Unlike the impressive progress that has been reported with asymmetric catalysis in other additions to alkenes (i.e., the Diels-Alder cycloaddition, epoxidation, dihydroxylation, aminohydroxylation, and hydrogenation) so far this is terra incognita with nitrile oxide cycloadditions. It is easy to predict that this will become a major topic in the years to come. 

Transformation of alkene 9 into diol 30 is a Sharpless asymmetric dihydroxylation.8 Its catalytic cycle with K3Fe(CNV, as co-oxidant is shown below. 

Osmium-catalysed dihydroxylation has been reviewed with emphasis on the use of new reoxidants and recycling of the catalysts.44 Various aspects of asymmetric dihydroxylation of alkenes by osmium complexes, including the mechanism, acceleration by chiral ligands 45 and development of novel asymmetric dihydroxylation processes,46 has been reviewed. Two reviews on the recent developments in osmium-catalysed asymmetric aminohydroxylation of alkenes have appeared. Factors responsible for chemo-, enantio- and regio-selectivities have been discussed.47,48 Osmium tetraoxide oxidizes unactivated alkanes in aqueous base. Isobutane is oxidized to r-butyl alcohol, cyclohexane to a mixture of adipate and succinate, toluene to benzoate, and both ethane and propane to acetate in low yields. The data are consistent with a concerted 3 + 2 mechanism, analogous to that proposed for alkane oxidation by Ru04, and for alkene oxidations by 0s04.49... 

A variation within the osmium-catalysed asymmetric dihydroxylation (AD) of alkenes has been described that yields cyclic boronic esters from alkenes in a straightforward manner. A protocol based on the Sharpless AD conditions (for enantiose-lective oxidation of prochiral olefins) has been developed that gives cyclic boronic esters, rather than free diols, with excellent enantiomeric excesses. Some of the... 

Osmium-catalysed dihydroxylation of olefins is a powerful route towards enantioselective introduction of chiral centers into organic substrates [82]. Its importance is remarkable because of its common use in organic and natural product synthesis, due to its ability to introduce two vicinal functional groups into hydrocarbons with no functional groups [83]. Prof. Sharpless received the 2001 Nobel Prize in chemistry for his development of asymmetric catalytic oxidation reactions of alkenes, including his outstanding achievements in the osmium asymmetric dihydroxylation of olefins. 

Unlike epoxides, these five-membered heterocyclics have received scant attention from organic chemists. But the recent catalytic asymmetric dihydroxylation of alkenes (14, 237-239), which is now widely applicable (this volume), and the ready access to optically active natural 1,2-diols has led to study of these compounds, including a convenient method for synthesis. They are now generally available by reaction of a 1,2-diol with thionyl chloride to form a cyclic sulfite of a 1,2-diol, which is then oxidized in the same flask by the Sharpless catalytic Ru04 system, as shown in equation I.1... 

The aminocyclitol moiety was synthesized in a stereocontrolled manner from cis-2-butene-l,4-diol (Scheme 40)112 by conversion into epoxide 321 via Sharpless asymmetric epoxidation in 88% yield.111 Oxidation of 321 with IBX, followed by a Wittig reaction with methyl-triphenylphosphonium bromide and KHMDS, produced alkene 322. Dihydroxylation of the double bond of 322 with OSO4 gave the diol 323, which underwent protection of the primary hydroxyl group as the TBDMS ether to furnish 324. The secondary alcohol of 324 was oxidized with Dess-Martin periodinane to... 

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