Osmylation Of alkene

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. 

Asymmetric osmylation of alkenes.3 In the presence of 1 equiv. each of 1 and 0s04, alkenes undergo highly enantioselective ris-dihydroxylation. Highest enantiofacial selectivity (90-99%) is shown in osmylation of trans-di- and trisub-... 

Greg Fu supervised the proofreading and provided the structural formula based on the x-ray data for the new Sharpless catalytic reagent for osmylation of alkenes. Martita F. Barsotti is the photographer for the picture of some present and former co-workers for Reagents. 

The first observation that RuO is usable for the reaction was made by Sharpless et al. in 1976 in a footnote to a paper on osmylation of alkenes. It was found that E- and Z-cyclododecene with stoich. RuO /EtOAc at -78°C gave the threo and erythro diols, but the procedure was not deemed viable owing to the low yields obtained and the necessity for working at low temperatures [157],... 

Recently, kinetic studies have shown that the catalytic osmylation of alkenes in the presence of cinchona derivatives as chiral amine catalysts (vide infra) is first order with respect to 0s04 and alkene, but shows saturation behavior with respect to the amine ligand42. The influence of the reaction temperature on the enantioselectivity of these reactions has also been studied. Eyring plots according to the equation ... 

In summary, the asymmetric osmylation of alkenes catalyzed by derivatives of cinchona alkaloids represents a very elegant method which enables the enantioselective cis dihydroxylation of several types of alkenes in high enantiomeric excess and with predictable selectivities. The design of specific chiral ligands for substrates that still do not afford enantiomeric excesses over 90% would be desirable for the near future. 

Table 8. Osmylation of Alkenes Mediated by Chiral 1,2- or 1,4-Diaminesa...

Table 9. Osmylation of Alkenes with Double Stereodifferentiation3...

The osmylation of alkenes incorporated into rigid frameworks reveals that reagent approach is usually determined by steric factors. However, in some cases, the dihydroxylation is apparently directed by a functional group which is located close by. 

Joergensen, K. A. A mechanistic approach to the asymmetric epoxidation of allylic alcohols and osmylation of alkenes. Tetrahedron Asymmetry 99, 2, 515-532. 

Osmylation. A review of recent works on osmylation of alkenes has been published. Erancais, A., Bedel, O., Haudrechy, A. T 64, 2495 (2008). 

Dihydroxylation of Alkenes. The cis dihydroxylation (osmylation) of alkenes by osmium tetroxide to form d5-l,2-diols (vic-glycols) is one of the most reliable synthetic transformations (eq l).i... 

The [2+2] Mechanism Already in 1977 Sharpless proposed a stepwise [2+2] mechanism for the osmylation of olefins in analogy to related oxidative processes with d°-metals such as alkene oxidations with CrO,Cl2 [23, 24], Metallaoxetanes [25] were suggested to be formed by suprafacial addition of the oxygens to the olefinic double bond. In the case of osmylation the intermediate osmaoxetane would be derived from an olefm-osmium(VIII) complex that subsequently would rearrange to the stable osmium(VI) ester. 

Enantioselective dihydroxy lotion.2 Highly enantioselective osmylation of rraiif-disubstituted and monosubstituted alkenes obtains with Os04 oxidations in the presence of 1 equiv. of this chiral 2,2 -bipyrrolidine ligand at —78°. Note, however, that the enantioselectivity for osmylation of cis-disubstituted alkenes is only —65%... 

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. 

Dihydroxylation of alkenes. C6H5B(OH)2 is useful for capture of the diols formed on osmylation with 0s04 and N-methylmorpholine N-oxide, particularly unstable or water-soluble diols. Osmylation with the borane can also be conducted in a nonaqueous medium with enhanced rates.1... 

Nitrophenylselenation of the primary alcohol in 291, followed by in situ oxidative elimination, furnished alkene 292 in 95% yield. Stereoselective osmylation of the exocyclic alkene in 292, using 0s04 -NM0 gave diol 293, which was additionally characterized as its pentaacetate 294, formed in 65% yield. Acid hydrolysis of 294 furnished the target aminocyclopentitol (+)-5 in 87% yield. 

The addition of the 0s04— N donor complex 3 to alkenes is a much faster process and accounts for the rate acceleration of alkene stoichiometric osmylations in the presence of this and other amines10. 

The asymmetric cis dihydroxylation of alkenes covalently bound to chiral fragments, which can be cleaved after the osmylation step, has been the subject of several reports2-5. The subsequent removal of the chiral auxiliary can be effected by various methods and allows the preparation of enantiomerically pure hydroxylated compounds. 

Table 4. Osmylation of Chiral Auxiliary Bound Alkenes pi OsO< / Method A catalytic q1...

Reactions E and F in Fig. 2 represent examples of the simultaneous creation of two stereocenters under the influence of an existing one. In general, a process like this could generate four diastereoisomers [13]. In this example, however, the stereospecificity [5]5 of the osmylation reaction makes the two syn diols accessible only from the (E)-alkene and the two anti diols only from the (Z)-one. Thus, both E and F reactions are at the same time stereoselective (as two diastereoisomeric products are obtained in unequal amounts from each one) and stereospecific (as the products of the osmylation of the (E)-alkene cannot be obtained from the (Z)-isomer, and vice versa). 

The relatively bulky osmium complex is sterically demanding and osmylation generally involves reaction at the less hindered face of an alkene. Osmylation of 254 to 255 by Rigby, in a synthesis of (+)-pancratistatin, shows the cis-delivery of the reagent and the selectivity for delivery from the less hindered face.357 in this case, the osmium complex formed on the top of the molecule despite the free hydroxyl group on the bottom face. A conformational drawing of 254 will show that the alkene unit and the lactam unit effectively flatten the two rings, and the top face is more accessible. 

When n = 3 or 4. these group, the enantioselectivity osmylation of mono- and < alkenes. 

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