Osmate esters, hydrolysis

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. 

When the secondary reaction cycle shown in Scheme 6D.3 was discovered, it became clear that an increase in the rate of hydrolysis of trioxogly colate 10 should reduce the role played by this cycle. The addition of nucleophiles such as acetate (tetraethylammonium acetate is used) to osmylations is known to facilitate hydrolysis of osmate esters. Addition of acetate ion to catalytic ADs by using NMO as cooxidant was found to improve the enantiomeric purity for some diols, presumably as a result of accelerated osmate ester hydrolysis [16]. The subsequent change to potassium ferricyanide as cooxidant appears to result in nearly complete avoidance of the secondary cycle (see Section 4.4.2.2.), but the turnover rate of the new catalytic cycle may still depend on the rate of hydrolysis of the osmate ester 9. The addition of a sulfonamide (usually methanesulfonamide) has been found to enhance the rate of hydrolysis for osmate esters derived from 1,2-disubstituted and trisubstituted olefins [29]. However, for reasons that are not yet understood, addition of a sulfon-amide to the catalytic AD of terminal olefins (i.e., monosubstituted and 1,1-disubstituted olefins) actually slows the overall rate of the reaction. Therefore, when called for, the sulfonamide is added to the reaction at the rate of one equivalent per equivalent of olefin. This enhancement in rate of osmate hydrolysis allows most sluggish dihydroxylation reactions to be mn at 0°C rather than at room temperature [29]. 

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. 

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... 

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. 

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. 

Asymmetric dihydroxylation of alkenes (14, 235-239). Further study1 of this reaction reveals that the optical yields of products can be markedly improved by slow addition (5-26 hours) of the alkene to the catalyst in acetone-water at 0° with stirring. The enantioselectivity can also be increased by addition of tetraethylam-monium acetate, which facilitates hydrolysis of osmate esters. The report suggests that the first product (1) of osmylation can undergo a second osmylation to provide 2, with reverse enantioselectivity of the first osmylation. 

Studies undertaken in connection with the amine-catalyzed asymmetric alkene osmylation have recently clarified the peculiar mechanism of the hexacyanoferrate/CO2 mediated osmium re-oxidation in biphasic conditions36. Reversal of the osmate oxidation/hydrolysis sequence with respect to the previously described R3NO-mediated conditions was noted with this system. Thus, the monodiolate(amine) osmium(VI) ester 9 appears to be first hydrolyzed, releasing the diol and the amine ligand to the organic phase, and the resulting [0s02(0H)4]2 into the aqueous phase. 

The subsequent oxidation of [0s02(0H)4]2" by hexacyanoferrate allows regeneration of 0s04 which migrates back to the organic phase. In this case, addition of methanesulfonamide has been found to enhance the rate of hydrolysis for osmate esters derived from 1,2-disubstitut-ed and trisubstituted alkenes41. 

The phthalazide bis(cinchona) derivatives [(DHQD)2-PHAL] are the best ligands for the asymmetric dihydroxyla-tion of trans, 1,1-disubstituted, and trisubstituted alkenes, enol ethers, a,p-unsaturated ketones, and a,p- and p,y-unsaturated esters, whereas the DHQD-IND ligand turns out to be superior for c/j -alkenes (Table 1). The bis(cinchona) alkaloid-substituted pyrimidine ligand was found to be the best for monosubstituted terminal alkenes. The addition of Methanesulfonamide to enhance the rate of osmate(VI) ester hydrolysis is recommended for all nonterminal alkenes. 

The reaction can be depicted as a concerted s yn-addition of the reagent to the double bond, forming the cyclic osmate ester, which upon hydrolysis or reduction (H2S, NaHSOj, or Na2S03) produces the cA-l,2-diol. 

Osmium-tetroxide-catalyzed dihydroxylation of sterically hindered olefins proceeds more efficiently with trimethylamine AA-oxide in the presence of pyridine. The base appears to catalyze not only formation of the osmate ester, but also its hydrolysis. 

The use of a sulfonamide aids the hydrolysis of the osmate esters, which improves the catalyst turnover. A sulfonamide, such as methanesulfonamide, can routinely be added to the reaction mixture. Only in the case of terminal alkenes, the presence of this additive slows down the reaction [23, 76, 84]. 

The presence of water in the reaction medium is required for the hydrolysis of the intermediate osmate esters. Although aqueous tert-butanol is the solvent system of choice, MTBE has been used in a large-scale application [2[. 

Another key development was the discovery that methane-sulfonamide MeS02NH2 accelerated the rate of hydrolysis of the intermediate osmate ester (not to be confused with the rate of the addition of osmium tetroxide to the olefin). Reaction times can be reduced by as much as 50 fold. After 3 days at 0 °C in the absence of methanesulfonamide, ra .v-5-dcccne had been only 70% converted to the corresponding diol but the diol was isolated in a 97% yield after just 10 h at 0 °C in the presence of methanesulfonamide. This improvement means that reactions can be run at 0 °C instead of room temperature. However methanesulfonamide slows down the reaction of terminal olefins. It is thus omitted from such reactions.16... 

A further improvement can be effected by addition of methanesulfonamide (1 cquiv. based on olefin), which accelerates hydrolysis of osmate ester intermediates. This catalyst is useful if the alkcnc is trisubstituted or 1,2-disubstitutcd, but is not useful in the case of terminal alkcncs. Addition of the sulfonamide permits osmylations at 0°, with enhances cnantioselectivity. 

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