Asymmetric dihydroxylations, alkenes, osmium tetroxide

The asymmetric dihydroxylation is much less fussy about the alkenes it will oxidize than Sharpless asymmetric epoxidation. Osmium tetroxide itself is a remarkable reagent, since it oxidizes more or less any sort of alkene, electron-rich or electron-poor, and the same is true of the asymmetric dihydroxylation reagent. The following example illustrates both this and a synthetic use for the diol product. 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

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. 

The history of asymmetric dihydroxylation51 dates back 1912 when Hoffmann showed, for the first time, that osmium tetroxide could be used catalytically in the presence of a secondary oxygen donor such as sodium or potassium chlorate for the cA-dihydroxylation of olefins.52 About 30 years later, Criegee et al.53 discovered a dramatic rate enhancement in the osmylation of alkene induced by tertiary amines, and this finding paved the way for asymmetric dihydroxylation of olefins. 

Since Sharpless discovery of asymmetric dihydroxylation reactions of al-kenes mediated by osmium tetroxide-cinchona alkaloid complexes, continuous efforts have been made to improve the reaction. It has been accepted that the tighter binding of the ligand with osmium tetroxide will result in better stability for the complex and improved ee in the products, and a number of chiral auxiliaries have been examined in this effort. Table 4 11 (below) lists the chiral auxiliaries thus far used in asymmetric dihydroxylation of alkenes. In most cases, diamine auxiliaries provide moderate to good results (up to 90% ee). 

Polymer-supported [e.g. 8, 9] and silica-supported [10] cinchona alkaloids have been used in the asymmetric dihydroxylation of alkenes using osmium tetroxide. Enantiomeric excesses >90% have been achieved for diols derived from styrene derivatives. 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

Asymmetric dihydroxylation of alkenes using osmium tetroxide... 

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). 

The work by E.J. Corey [37], M. Hirama [38] and K. Tomioka [39], and their associates, on asymmetric dihydroxylation of alkenes with chiral diamine-osmium tetroxide complexes also deserves to be mentioned. 

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]. 

The essential components of the catalyst for the asymmetric dihydroxylation process are osmium tetroxide (OSO4) and an ester of one or the other of the pseudoenantiomeiic cinchona alkaloids dihydro-quinidine (DH( D) and dihydroquinine (DHQ). An amine oxide, generally N-methylmorpholine N-oxide, serves as the oxidant for foe reaction. When an alkenic substrate is added very slowly to a... 

Asymmetric dihydroxylation of the side-chain of Z-1-(4-meth-oxyphenyl)-1-(tert-butyldimethylsiloxy)-1-propene to give (R)-l-hydroxyethyl 4-methoxyphenyl ketone in 94% yield (99% e.e.) was effected by addition of the alkene to a stirred mixture of osmium tetroxide, potassium ferricyanide, potassium carbonate, a 9-0-(9 -phenanthryl)ether(PHN) of dihydroquinidine and 1 mole of methanesulphonamide in aqueous tert-butanol (1 1), with reaction during 16 hours at ambient temperature. Then treatment with sodium sulphite prior to work-up to gave the product (ref. 130). Other best ligands were the 9-0-(4 -methyl-2 -quinolyl) ethers (MEQ) of dihydroquinine. 

This alternative asymmetric oxidation really is probably the best asymmetric reaction of all. It is an asymmetric version of the syn dihydroxylation of alkenes by osmium tetroxide. Here is an example—although the concept is quite simple, the recipe for the reactions is complicated so we need to approach it step by step. 

Abstract The oxidative functionalization of olefins is an important reaction for organic synthesis as well as for the industrial production of bulk chemicals. Various processes have been explored, among them also metal-catalyzed methods using strong oxidants like osmium tetroxide. Especially, the asymmetric dihydroxylation of olefins by osmium(Vlll) complexes has proven to be a valuable reaction for the synthetic chemist. A large number of experimental studies had been conducted, but the mechanisms of the various osmium-catalyzed reactions remained a controversial issue. This changed when density functional theory calculations became available and computational studies helped to unravel the open mechanistic questions. This mini review will focus on recent mechanistic studies on osmium-mediated oxidation reactions of alkenes. 

Later, Kobayashi and coworkers reported on a new type of microencapsulated osmium tetroxide using phenoxyethoxymethyl-polystyrene as support [40]. With this catalyst, asymmetric dihydroxylation of alkenes has been successfully performed using (DHQD)2PHAL as a chiral ligand and K3[Fe(CN)6] as a cooxidant in H20/acetone (Scheme 1.16). This dihydroxylation does not require slow addition of the alkene, and the catalyst can be recovered quantitatively by simple filtration and reused without loss of activity. With a divinylbenzene-cross-linked polystyrene microencapsulated OSO4 and a nonionic phase transfer catalyst (Triton X-405), this system can be run in an aqueous system [41]. 

We already know how to produce 1,2-diols from the reactions of alkenes we studied in Chapter 11. We can make cis-diols using osmium tetroxide-mediated dihydroxylation, tra s-diols by ring opening of epoxides, and chiral diols by Sharpless asymmetric dihydroxylation (Figure 20.1). tra s-l,2-Amino alcohols can be prepared by ring opening of epoxides, and there is a version of the Sharpless dihydroxylation that leads to chiral amino alcohols. 

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