Osmium tetroxide enantioselective

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 ... 

Osmium tetroxide oxidations can be highly enantioselective in the presence of chiral ligands. The most highly developed ligands are derived from the cinchona alkaloids dihydroquinine (DHQ) and dihydroquinidine (DHQD).45 The most effective... 

Enantioselective osmylotion of alkenes. Osmium tetroxide forms a 1 1 wine-red complex with the chiral diamine l2 that effects efficient enantioselective dihy-droxylation of monosubstituted, oww-disubstituted, and trisubstituted alkenes (83-99% ee) at -110° in THF. The enantioface differentiation in all cases corresponds to that observed with t/mr-3-hexene and the complex with (-)-l. Essentially complete asymmetric induction is observed with frans-l-phenylpropene (99% ee). 

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. 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

From the practical perspective of laboratory use, the catalytic AD process requires a minimum of concern over stoichiometry. The new osmium tetroxide-chiral ligand complexes are so efficient that for most olefins, 0.2 mol % of osmium will provide a satisfactory rate of reaction at 0°C [291. In the occasional case where hydroxylation is slow under these conditions, the quantity of osmium in the catalyst should be increased to 1 mol % and the reaction temperature kept at 0 °C. In the rare case where hydroxylation is still slow under these conditions, the temperature may be raised to 25°C and, to ensure no loss in enantioselectivity, the ligand concentration may be increased from 1 mol % to 2 mol %. 

Olefins of the /ranr-disubstituted type have given diols with excellent enantiomeric purities when dihydroxylated with the (DHQD)2-PHAL/(DHQ-PHAL pair of chiral ligands with osmium tetroxide (see Table 6D.3 [16,26,29,31,35,40,41,46-48]). All the entries but one in Column 9 for diols obtained with these ligands exceed 90% ee (or 90% de). From other entries in Table 6D.3, particularly those of Column 3 for earlier stoichiometric ADs with the DHQD-CLB ligand, good enantioselectivities are anticipated for the dihydroxylation of most trans-disubstituted olefins when the PHAL ligands are used. 

In 1975 Sharpless and coworkers discovered the stoichiometric aminohydrox-ylation of alkenes by alkylimido osmium compounds leading to protected vicinal aminoalcohols [1,2]. Shortly after, an improved procedure was reported employing catalytic amounts of osmium tetroxide and a nitrogen source (N-chlo-ro-N-metallosulfonamides or carbamates) to generate the active imido osmium species in situ [3-8]. Stoichiometric enantioselective aminohydroxylations were first reported in 1994 [9]. Finally, in 1996 the first report on a catalytic asymmetric aminohydroxylation (AA) was published [10]. During recent years, several reviews have covered the AA reaction [11-16]. 

Permanganate oxidation of 1,5-dienes to prepare f r-2,5-disubstituted tetrahydrofurans is a well-known procedure (Equation 80). The introduction of asymmetric oxidation methodology has revived interest in this area. Sharpless-Katsuki epoxidation has found widespread application in the catalytic enantioselective synthesis of optically active tetrahydrofurans and the desymmetrization of w ro-tetrahydrofurans <2001COR663>. A general stereoselective route for the synthesis of f-tetrahydrofurans from 1,5-dienes has been developed which uses catalytic amounts of osmium tetroxide and trimethyl amine oxide as a stoichiometric oxidant in the presence of camphorsulfonic acid <2003AGE948>. 

It has been known for decades that osmium tetroxide catalyzes the H2O2 oxidation of olefins to c -l,2-diols but the cost, toxicity and volatility of OSO4 have limited its use to the organic research laboratory. Industrial interest was aroused in the 1990 s by i) the invention of a system for vicinal hydro-xylation using an electrochemical device as the ultimate oxidant and ii) the discovery of conditions to carry out the reaction enantioselectively, mainly by Sharpless and his group. The reaction is currently carried out by Chirex to... 

The diastereoselective and enantioselective oxidation of alkenes with osmium tetroxide is considered in Section 3.3.2.1. 

In the second approach, a chiral nitrogen-containing compound has most often been used as the ligand to achieve enantioselectivity. Thus, oxidation of ( )-stilbene (22 equation 9) with a stoichiometric quantity of osmium tetroxide in toluene at room temperature, in the presence of dihydroquinine acetate (23), yielded r/ireo-hydrobenzoins (24) after reductive hydrolysis, with an enantiomeric excess of 83.2% in favor of the (15,25)-(-)-isomer performing the reaction at -78 C increased the eiuuitiomeric excess to 89.7%. 

Protected a,3-dihydroxy aldehydes have been prepared by oxidation of acetals of a,B-unsaturated aldehydes with osmium tetroxide in the presence of (23), and a remarkable level of enantioselection ee 2 90%) thereby achieved. Oxidation of chiral acetals of a,p-unsaturated aldehydes in which chirality resides in the noncarbonyl moiety with osmium tetroxide-t ydroquinine acetate (or dihydroquitudine acetate) may be regard as a process in which double stereoselection is at work and a high dia-stereoisomeric ratio of products may be obtained. 

Optically active 1,2-diol units are often observed in nature as carbohydrates, macrolides or polyethers, etc. Several excellent asymmetric dihydroxylation reactions of olefins using osmium tetroxide with chiral ligands have been developed to give the optically active 1,2-diol units with high enantioselectivities. However, there still remain some problems, for example, preparation of the optically active anti-1,2-diols and so on. The asymmetric aldol reaction of an enol silyl ether derived from a-benzyloxy thioester with aldehydes was developed in order to introduce two hydroxyl groups simultaneously with stereoselective carbon-carbon bond formation by using the chiral tin(II) Lewis acid. For example, various optically active anti-a,p-dihydroxy thioester derivatives are obtained in good yields with excellent diastereo-... 

Ujaque, G., Maseras, F., Lledos, A. Theoretical Study on the Origin of Enantioselectivity in the Bis(dihydroquinidine)-3,6-pyridazine.Osmium Tetroxide-Catalyzed Dihydroxylation of Styrene. J. Am. Chem. Soc. 1999, 121, 1317-1323. 

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