Ester, osmate

In the laboratory vicinal diols are normally prepared from alkenes using the reagent osmium tetraoxide (OSO4) Osmium tetraoxide reacts rapidly with alkenes to give cyclic osmate esters... 

Osmate esters are fairly stable but are readily cleaved m the presence of an 0x1 dizing agent such as tert butyl hydroperoxide... 

Overall the reaction leads to addition of two hydroxyl groups to the double bond and IS referred to as hydroxylation Both oxygens of the diol come from osmium tetraox ide via the cyclic osmate ester The reaction of OSO4 with the alkene is a syn addition and the conversion of the cyclic osmate to the diol involves cleavage of the bonds between oxygen and osmium Thus both hydroxyl groups of the diol become attached to the same face of the double bond syn hydroxylation of the alkene is observed... 

The cleavage of the intermediate osmate ester has presented problems in the past, and a variety of procedures have been developed, including the use of mannitol and strong aqueous base, refluxing aqueous alcoholic sodium bisulfite,formaldehyde and ascorbic acid. A much milder method involves simply bubbling hydrogen sulfide into a solution of the osmate ester osmium dioxide is precipitated rapidly, and the desired organic... 

Because osmium tetroxide is expensive, and its vapors are toxic, alternate methods have been explored for effecting vic-glycol formation. In the aliphatic series, olefins can be hydroxylated with hydrogen peroxide with the use of only a catalytic amount of osmium tetroxide. Anhydrous conditions are not necessary 30% hydrogen peroxide in acetone or acetone-ether is satisfactory. The intermediate osmate ester is presumably cleaved by peroxide to the glycol with regeneration of osmium tetroxide. When this reaction was tried on a A -steroid, the product isolated was the 20-ketone ... 

Hydroxy-20-cyanohydrins can be oxidized to 3-ketones in good yield with chromic acid, and the osmate ester of the unsaturated nitrile is also stable to this oxidant. " After hydrolysis of the osmate ester, the new 17-hydroxy-20-cyanohydrin which is presumably formed cannot be isolated, but loses hydrogen cyanide during the hydrolysis, and only the 17a-hydroxy-20-ketone is obtained. 

Osmate esters are important intermediates in the reactions of 0s04 in the stereospecific m-hydroxylation of alkenes and other unsaturated molecules [182],... 

The most widely used reagent for oxidation of alkenes to glycols is osmium tetroxide. Osmium tetroxide is a highly selective oxidant that gives glycols by a stereospecific syn addition.39 The reaction occurs through a cyclic osmate ester that is formed by a [3 + 2] cycloaddition.40... 

The 1,2-diol is liberated easily from cyclic osmate ester by either reductive or oxidative hydrolysis.213 Importantly, the ligand acceleration has been utilized extensively for the production of chiral 1,2-diols from (achiral) olefins using optically active amine bases (such as L = dihydroquinidine, dihydroquinine and various chiral diamine ligands).215... 

Despite the extensive utility of osmylation reactions, the mechanism remains controversial - generally focusing on either a concerted [3 + 2] cycloaddition to directly yield the cyclic osmate ester or a two-step mechanism where [2 + 2] cycloaddition forms a 4-membered osmaoxetane which then undergoes a ligand-assisted ring expansion to yield the cyclic osmate ester216 (Scheme 21). 

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. 

Oxidation of maleic acid by NaC103-0s04 in aqueous solution involves the formation of the cyclic osmate ester, the oxidative clevage of which by chlorate gives mesotartaric acid with the regeneration of 0s04. 

Hydroxylation of alkenes by high-valent metal oxides occurs in two steps, firstly the formation of a metal dialkoxylate (or metallate ester) and secondly the hydrolysis of this species to a 1,2-diol and the low-valent metal hydroxide. The amine plays a role in the first step, the formation of the osmate ester, and Criegee added pyridine to 0s04 to accelerate the reaction. 

In Figure 14.14 we have depicted the most striking result from the 1980 paper involving /rara-stilbenc as the substrate and dihydroquinine acetate. After addition the osmate ester was decomposed by reduction with UAIH4, a common procedure in the early days, to give the threo-dio. A diastereomer of the ligand, dihydroquinidine acetate, gave similar e.e. but the opposite enantiomer. The enantioselectivity was 83%. 

One of the routes to epimestix>l begins with acylation of estradiol with benzoyl chloride to give the dibenzoate 5. Pyrolysis of the ester leads to formation of the 16,17-olefin. Hydroxylation by means of osmiiim tetroxide affords the cis-diol 7 due to the intermediacy of the cyclic osmate ester (6a)-, attack... 

Commercial cyclohexene was used (the purity was checked by refractive index). Addition of cyclohexene caused a darkening of the reaction mixture. This is caused by a finite concentration of the osmate ester. The reaction becomes lighter in color when complete. 

Most of the cr-bonded organometallics that have been characterized structurally (mainly by 13C NMR) involve bonding to the fullerene at adjacent carbon atoms, i.e., 1,2 addition. Such is the case for the osmate esters, ( 1)(1 ) (49) and C60S2Fe2(CO)6 (53), which are illustrated in Fig. 15. Occasionally 1,4 addition occurs as for C60 Re(CO)5 2 (50) and substitution of Li in C Bu Li) with bulky electrophiles. 

Optically active ds.vic-diofa.1 It is known that pyridine catalyzes the hydroxyl-ation of alkenes with Os04 and that the osmate ester intermediates form an isolable complex with pyridine (1, 760-761). Hentges and Sharpless reasoned that a similar chiral amine could induce chirality in the diol. And indeed addition of 1 equivalent of 1 or of the C8-diastereoisomer, dihydroquinidine acetate (2), does result in vic-diols in fair to high enantiomeric excess, particularly in reactions performed in toluene at —78°. Opposite stereoselectivities are exhibited by 1 and 2. Optical yields range from 25 to 85%. Use of an amine in which the chiral center is two carbon atoms removed from the coordination site lowers the optical yield to 3 18%. 

Olefins react directly at the electron-rich and rather electron-deficient oxygens. If the dimer is much more reactive toward olefins than the monomer, only a small fraction of the alkaloid-Os04 complex need be present as a dimer (94a). Houk developed a symmetrical five-membered transition-structure model on the basis of X-ray crystal structures of Os04-amine complexes and osmate ester products and ab initio transition structures of analogous reactions (Scheme 40). The MM2 calculations based on this [3 + 2] reaction model reproduce the stereoselectivities of the stoichiometric reactions observed with several chiral diamines (94b). The transition state may be stabilized by tt-tt interaction of the alkene substrate and the ligand aromatic ring (95). 

Two key improvements have been made very recently (96). Scheme 41 summarizes the current state of art, which has been marked by the discovery of the phthalazine class of ligands, (DHQD)2-PHAL and (DHQ)2-PHAL, and the acceleration of osmate ester hydrolysis in the presence of organic sulfonamides, the turnover-limiting step of the reaction of nonterminal olefins. 

An osmate ester formed from two unsaturated groups... 

Ornithine decarboxylase 342, 342s Ornithine mutases 871, 874 Oscillatoria 22 Osmate ester 393s Osmotic shock 417 Osteoarthritis 438 Osteoblasts 26, 441... 

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