Catalytic osmylation

Asymmetric catalytic osmylation.s Chiral cinchona bases are known to effect asymmetric dihydroxylation with 0s04 as a stoichiometric reagent (10, 291). Significant but opposite stereoselectivity is shown by esters of dihydroquinine (1) and of dihydroquinidine (2), even though these bases are diastereomers rather than enantiomers. 

Preliminary studies on catalytic osmylation were reported by Kokubo and co-workers who used bovine serum albumin, 0s04, and t-butylhydroperoxide as the oxidant. Turnover numbers up to 40 and an e.e. for 2-phenylpropene of 68% was achieved [23], Apparently the protein binds to osmium via nitrogen donors, but as different sites may be available this may lower the e.e. 

Cyclopentadiene undergoes catalytic osmylation to produce the bis(cyclic) boronate in good yield and with excellent selectivity for the a -product (Equation 61) <1998JOC7322>. The reaction was found to be effective for a range of dienes (see also Sections 10.21.9.3.4(iii)(b) and 10.21.9.4.4). 

In this report we describe the conversion of cyclohexene to cis-diol 2 in 90% yield in a catalytic osmylation using 1 mole equivalent of N-methylmorpholine N-oxide (1) to regenerate the less than 1 mole % of osmium tetroxide catalyst. This procedure avoids the a-ketol by-products encountered with the presently available catalytic processes, and provides the high yields of the stoichiometric reaction without the expense and work-up problems. 

Octoses.1 A new route to octoses involves catalytic osmylation (7, 256-257) of allylic alcohols derived from a hexose by Wittig olefination to introduce two... 

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 ... 

The rate-determining step in catalytic osmylations is usually the oxidation of the osmium(VI) esters 2 or 735t 37. Depending on the steric requirements of the alkene precursor, the trioxo(l,2-diolato)osmate(VIII) 4, formed in the amine TV-oxide promoted catalytic osmylation, can be further transformed following two different pathways. 

The role of amines in catalytic osmylations is therefore quite complex. They are promoters of the 0s04 addition step but they can inhibit osmium recycling through saturation of the coordination sites at the metal center of the osmate(VI) ester. 

Failure to achieve catalytic osmylation is usually attributable to difficulties in the oxida-tion/hydrolysis step. This problem can sometimes be overcome by addition of tetraethylammo-nium acetate which is believed to facilitate osmate hydrolysis29c. 

Potassium hexacyanoferrate in combination with l,4-diazabicyclo[2.2.2]octane has also been reported to promote catalytic osmylation of the otherwise unreactive double bond of cholesterol3 u. 

Similarly prepared by catalytic osmylation were cyclohexane derivatives54, tetrahydropyran derivatives55, several sugar derivatives56-57 and a tetrahydropiperidine derivative58,59. 

V-a./J-Enoylsultarns derived from camphor can be catalytically osmylated to the corresponding diols. Very high auxiliary-induced stereoselectivities are achieved with (E)- as well as (Z)-a,/l-enoyl substrates. Acetalization of the resulting 1,2-diols followed by flash chromatography or crystallization provides pure (>99% d.r.) acetonides. Subsequent nondestructive removal of the chiral auxiliary can be effected by basic hydrolysis or reductive treatment 5. 

Reagent-Induced Enantioface Differentiating Osmylations 4.4.4.1. Chiral Ligands for Catalytic Osmylations 4.4.4.I.I. Cinchona Alkaloid Derivatives as Chiral Ligands... 

Cinchona alkaloids have been extensively studied as chiral ligands for catalytic osmylations. This method, which has been much improved since its introduction, makes use of a complex generated in situ between 0s04 and a suitably 0-protected dihydroquinidine or dihydroquinine derivative using catalytic amounts of both these reagents at 0 or 25 °C1,2. 

In line with these results it has been recently noted that (CH3)3NO-based catalytic osmylation conditions, as opposed to stoichiometric conditions, efficiently oxidize sulfides to the corresponding sulfones94b. 

The combination of the chromatographic separation of enan-tiopure p-hydroxysulfoximine diastereomers and reductive elimination results in a method of ketone methylenation with optical resolution. The technique is illustrated in the synthesis of the ginseng sesquiterpene (—)-p-panasinsene and its enantiomer (eq 5). The addition of the enantiopure lithiosulfoximine to prochiral enones or the diastereoface selective addition to racemic enones results in the formation of two diastereomeric adducts. The hydroxy group in these adducts can be used to direct the Simmons-Smith cyclopropanation (eq 6 and eq 7). Catalytic osmylation of such adducts is directed by the anti effect of the hydroxy augmented by chelation by the methylimino group (eq 7). ... 

Poll and Sames [112] have converted L-serine into A -methylfucosamine (Scheme 13.63). The method relies on the diastereoselective addition of propenyllithium to the aldehyde derived from protected L-serine derivative 183, giving allylic alcohol 184. Catalytic osmylation of 184 gives a 6 1 mixture of anti,syn 185 and syn,syn-2iminotnols. Protection of the triol 185 as its triacetate, reductive methylation and desilylation provides 186. Successive Swern oxidation, methanolysis and benzhydryl group hydrogenation leads to A -methylfucosamine 187. 

In general, dihydroxylations are carried out in mixtures of aqueous and organic solvents, although catalytic osmylations have been performed under virtually anhydrous conditions in toluene [21] or dichloromethane [22]. In combination with water, organic solvents such as acetone, r-butanol, methyl /-butyl ether, and others are employed. 

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 dihydroqui-ninc and dihydroquinidine as ligands. Markedly higher enantiosclcctivity obtains by use of ligands 1 and 2, prepared by reaction of 1,4-dichlorophthalazinc with dihydroquinidine (ligand 1) and dihydroquininc (ligand 2). ... 

The A -allyllactam 119 was converted by RCM to 120, which on catalytic osmylation provided the polyhydroxylated indolizidine 121 <04OBC3128>. An analog 122 of the iminosugar siastatin B was prepared from the tetrahydropyridine 123. The relative configuration of the substitiuents in the latter were defined by the RCM reaction precursor 124 derived from a 2-azetidinone <04SL2776>. 

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