Enantioselective osmylation

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%... 

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

Enantiomencally pure (+)- and (-)-diphenylethylenediamines have recently been used for highly stereoselective Dlels-Alder, aldol,8 allylation,9 osmylation,10 and epoxidafion11 reactions. Other synthetic applications involve enantioselective Michael addition12 and asymmetric hydrogenation.13... 

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-... 

According to Shaipless, two cycles operate in the catalytic reaction (Scheme 39) (88c, 9CF). The first cycle is highly enantioselective, whereas the second is poorly enantioselective. Hydrolysis of the key intermediate formed from B and oxidant is not very fast. The second osmylation of olefinic substrate occurs as the intermediate enters the undesired catalytic cycle. Therefore, slow addition of olefinic substrates to minimize the second cycle is essential for obtaining high ee. Use of potassium hexacyanoferrate(III) as oxidant in a 1 1 tert-butyl alcohol-water two-layer system can suppress the second cycle and lead to high enantioselectivity (91). This procedure allows the convenient synthesis of 3-lactams from 2-octenoate. 

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. 

Enantioselective total syntheses of (-)-6-epitrehazolin and (+)-trehazolin were achieved by the synthesis of 275, which began with an asymmetric heterocycloaddition between [(benzyloxy)methyl]cyclopentadiene (263),108 prepared from thallous cyclopentadienide, and the acylnitroso compound arising from in situ oxidation of (,S )-mandelohydroxamic acid (264) with tetrabutylammonium periodate. Cycloaddition led to a mixture of 265 and its diastereomer (Scheme 35).109 The inseparable mixture was reduced to afford cyclopentenes 266 and 268 in 40% and 11 % overall yields, respectively, from thallous cyclopentadienide. Catalytic osmylation of 266 favored syn addition, while the osmylation of diacetate 267 was more selective and nearly quantitative, affording, after acetylation, compounds 270 and 269 in >5 1 ratio. 

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. 

Asymmetric osmylation. Chiral ligands of /V,/V -dialkyl bispiperazines linked by two carbons (I, n = 2) can effect highly enantioselective dihydroxylation of trans-disubstituted alkenes. 

Since cis-3, trans-3, and trans-2 bis-adducts of 50 with identical addends are chiral as a result of inherently chiral functionalization patterns [10, 44-46], it was of interest to explore whether Bingel macrocyclizations with bismalonates bridged by non-racemic tethers would provide an enantioselective synthesis of these compounds. An overall enantioselective synthesis of optically active Cgg bis-adducts had been achieved previously by asymmetric Sharpless bis-osmylation [77] however, this sequential bis-func-tionalization lacks the regioselectivity of the Bingel macrocyclization, and therefore requires tedious regioisomer separations. 

Support for a two-step mechanism of the osmylation reaction came from kinetic studies, which revealed a nonlinear correlation between the reciprocal of temperature and the enantioselectivity of the reaction [111]. However, experimental tests of the [3+2] and [2+2] pathways by means of kinetic isotope effects which were carried out by Corey et al. showed that the [3+2] mechanism is in accord with experimental results, while the [2+2] mechanism is not [ 112]. A kinetic study of Heller et al. showed that a nonlinear temperature behavior of product ratios in selection processes may be due to a distortion of the reactant equilibrium [113]. The experimental results did not give conclusive evidence about the alternative reaction mechanisms of the dihydroxylation... 

Asymmetric catalytic osmylation (14, 237-239 15, 240-241 16, 249). In the early versions of this reaction the asymmetry was obtained by use of esters of dihydroquinine and dihydroquinidine as ligands. Markedly higher enantioselectivity obtains by use of ligands 1 and 2, prepared by reaction of 1,4-dichlorophthalazine with dihydroquinidine (ligand 1) and dihydroquinine (ligand 2). ... 

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

Enantioselective Dihydroxylation. The acceleration of osmylation by tertiary amines brought about the use of chiral amines... 

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