Reoxidants, dihydroxylations, osmium tetroxide

The osmium-catalyzed dihydroxylation reaction, that is, the addition of osmium tetr-oxide to alkenes producing a vicinal diol, is one of the most selective and reliable of organic transformations. Work by Sharpless, Fokin, and coworkers has revealed that electron-deficient alkenes can be converted to the corresponding diols much more efficiently when the pH of the reaction medium is maintained on the acidic side [199]. One of the most useful additives in this context has proved to be citric acid (2 equivalents), which, in combination with 4-methylmorpholine N-oxide (NMO) as a reoxidant for osmium(VI) and potassium osmate [K20s02(0H)4] (0.2 mol%) as a stable, non-volatile substitute for osmium tetroxide, allows the conversion of many olefinic substrates to their corresponding diols at ambient temperatures. In specific cases, such as with extremely electron-deficient alkenes (Scheme 6.96), the reaction has to be carried out under microwave irradiation at 120 °C, to produce in the illustrated case an 81% isolated yield of the pure diol [199]. 

Oxidative cleavage of the olefin is accomplished by the method of ijemieux-Johnson.12 The process begins with dihydroxylation of the double bond using osmium tetroxide (see Chapter 3)T leading to a cis diol and osmium(VI) oxide. The added periodate has two functions first, it reoxidizes the osmium(VI) species to os-mium(VIII), but it also cleaves the glycol oxidatively to an aldehyde. This is the reason for utilizing several equivalents of periodate. The periodate is in turn reduced from the +VH to the +V oxidation state. 

The stoichiometric asymmetric dihydroxylation obeys a rate law which is first order in osmium tetroxide and aikene, but shows saturation behavior in ligand (cf Fig. 2). The kinetic behavior of the reaction is shown in Scheme 7 and Eq. (2). This kinetic scheme is also vahd for a discussion of the factors governing the enantioselectivity in the catalytic asymmetric dihydroxylation, since the hydrolysis and reoxidation steps does not affect the selectivity of the AD reactions under the normal two-phase reaction using KjFelCNlg as cooxidant. 

Epoxidation and Dihydroxylation of Alkenes There are several ways to convert alkenes to diols. Some of these methods proceed by syn addition, but others lead to anti addition. An important example of syn addition is osmium tetroxide-catalyzed dihydroxylation. This reaction is best carried out using a catalytic amount of OSO4, under conditions where it is reoxidized by a stoichiometric oxidant. Currently, the most common oxidants are f-butyl hydroperoxide, potassium ferricyanide, or an amine oxide. The two oxygens are added from the same side of the double bond. The key step in the reaction mechanism is a [3 + 2] cycloaddition that ensures the syn addition. 

Photoinduced Charge Transfer Osmylation. The reaction of osmium tetroxide with benzenoid derivatives can only be accomplished by irradiation of the mixture. This reaction had previously been shown to work (with stoichiometric osmium tetroxide) by promotion of charge transfer between the two reactants to form an ion-pair this can then collapse to form an osmate ester of benzene diol. Subsequent dihydroxylation of this intermediate appears to follow a more conventional (and stereoselective) course. The use of catalytic osmium tetroxide (in conjunction with barium perchlorate as a reoxidant) for this reaction is noteworthy, as is the formation of both inositol and conduritol derivatives in one-pot (eq SS). The photoinduced osmylation of mono-substituted arenes was possible although the yields were lower and the amount of cyclitol-type products reduced. 

Osmium tetroxide is highly toxic, volatile, and very expensive. For these reasons, methods have been developed that permit OSO4 to be used catalytically in conjunction with a co-oxi-dant. A very small molar percentage of OSO4 is placed in the reaction mixture to do the dihydroxylation step, while a stoichiometric amount of co-oxidant reoxidizes the OSO4 as it... 

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