Osmium tetroxide alkenes, mechanism

Further supporting evidence for this type of a mechanism comes from the consideration of an analogous reaction, the oxidation of alkenes by osmium tetroxide, which also produces cis-diols. In this reaction the... 

Several oxidizing reagents react with alkenes under mild conditions to give, as the overall result, addition of hydrogen peroxide as HO—OH. Of particular importance are alkaline permanganate (MnO40) and osmium tetroxide (0s04), both of which react in an initial step by a suprafacial cycloaddition mechanism like that postulated for ozone. 

Osmium tetroxide is commonly used to add two OH groups to a double bond.15 The mechanism gives syn addition from the less hindered side of the alkene. Since 0s04 is expensive and highly toxic it is therefore mostly used in a catalytic fashion using stoichiometric cooxidants, like H202 or /V-methylmorpholine-/V-oxide (NMO). 

Now for the mechanism. We must admit before we start that this is a reaction about which there is still some controversy, and we give you the sibiplest reasonable view of the mechanism. Future results may show this mechanism to be wrong, but it will certainly do to explain any result you might meet. The first step is a cycloaddition between the osmium tetroxide and the alkene. You can treat the 0s04 like a dipole—it isn t drawn as one because osmium has plenty of orbitals to accommodate four double bonds. 

The resolution of the hot debate on the mechanism of metal-oxo mediated oxidations is one of the success stories of DFT calculations. An early publication by Sharpless on chromylchloride oxidations of alkenes10 started a long ongoing discussion11-25 on the mechanism of metal-oxo mediated oxidations. Sharpless proposed an interaction between the chromium metal and the alkene and generalized his proposal to include all metal-oxo compounds, especially osmium tetroxide and permanganate. Especially the mechanism of the reaction of osmium tetroxide with alkenes was the subject of an intense debate within the community of experimental organic chemists (Scheme 2). 

The oxidation of alkenes by permanganate is one of the frequently used examples in freshman chemistry. It is also well known as the Baeyer test for unsaturation. There are many reagents that add two hydroxyl groups to a double bond,44 but osmium tetroxide and permanganate are the most prominent ones. The mechanism of the permanganate oxidation is believed to be similar to the oxidation of alkenes by 0s0445 46... 

From the mechanism shown in Scheme 7.23, we would expect the dihydroxylation with syn-selectivity. The cyclic intermediate may be isolated in the osmium reaction, which is formed by the cycloaddition of OSO4 to the alkene. Since osmium tetroxide is highly toxic and very expensive, the reaction is performed using a catalytic amount of osmium tetroxide and an oxidizing agent such as TBHP, sodium chlorate, potassium ferricyanide or NMO, which regenerates osmium tetroxide. For example, Upjohn dihydroxylation allows the syn-selective preparation of 1,2-diols from alkenes by the use of catalytic amount of OSO4 and a stoichiometric amount of an oxidant such as NMO. 

Suggest a mechanism for the reaction between the osmium tetroxide and the alkene. 

The mechanism of the AD reaction, discussed in the limited context of what exact events take place during the chiral amine accelerated osmium tetroxide addition to alkenes, has been a subject of passionate debate for a number of years. The controversy is mostly concerned with two aspects of the alkene addition step in the AD process the exact mechanism of the amine-accelerated osmium... 

The key point of the Sharpless model is the two-step mechanism for the addition of osmium tetroxide to an alkene. The basis for this suggestion is the presence of inversion points in the Eyring plots (Sect. 4.1.1). The most viable proposal for this mechanism is outlined in Fig. 12. 

The Corey model, presented in Scheme 10, is based on the formation of an osmium tetroxide-chiral ligand ternary complex through a rapid and reversible equilibrium. Inside this complex, the osmium tetroxide is added to the alkene via a (3-1-2) addition mechanism forming the ligand-bound osmium (VI) glyco-late complex. 

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. 

The first theoretical study on the proposed reaction mechanisms of the dihydroxylation of alkenes by osmium tetroxide was performed in 1986 by Jorgensen and Hoffmann [ 17 ]. In that work, the authors carried out a theoretical study from a frontier orbital point of view. They used symmetry arguments and extended Hiickel [18] calculations to perform their analysis. 

The most popular method for dihydroxylation of alkenes uses osmium tetroxide. This reagent can be used stoichiometrically, although its expense and toxicity have led to the development of catalytic variants. There has been considerable debate over the mechanism of the reaction, which has been postulated to proceed by a direct [3 4-2] cycloaddition, or via a [2-1-2] cycloaddition followed by a rearrangement, to give the intermediate osmate ester.This osmium(Vl) species can be oxidized or reduced and hydrolysed to release the diol product (5.79). The reaction is accelerated by tertiary amine and other bases, such as pyridine, which co-ordinate to the osmium metal. 

Using osmium tetroxide to add two hydroxyl groups to the second alkene will give the diastereoisomer on the left, because the mechanism ensures both O atoms add to the same side of the alkene (p. 442 of the textbook). To get the trans diol, we can make an epoxide with m-CPBA and then open it with water, an Sn2 reaction that proceeds with inversion of configuration. 

Enantioselectivity in this process arises from reaction of the alkene and osmium tetroxide within an asymmetric environment created by the ligand. However, the precise shape of this binding pocket and the nature of the interactions between the substrate and ligand has been the subject of some debate. Corey has advanced a model based on a U-shaped ligand conformation initially derived from an inspection of molecular models while Sharpless has proposed an L-shaped active site based on the results of molecular mechanics studies. 

Abstract The oxidative functionalization of olefins is an important reaction for organic synthesis as well as for the industrial production of bulk chemicals. Various processes have been explored, among them also metal-catalyzed methods using strong oxidants like osmium tetroxide. Especially, the asymmetric dihydroxylation of olefins by osmium(Vlll) complexes has proven to be a valuable reaction for the synthetic chemist. A large number of experimental studies had been conducted, but the mechanisms of the various osmium-catalyzed reactions remained a controversial issue. This changed when density functional theory calculations became available and computational studies helped to unravel the open mechanistic questions. This mini review will focus on recent mechanistic studies on osmium-mediated oxidation reactions of alkenes. 

Once again, product stereochemistry provides key clues to the mechanism. Another important example of syn addition is osmium tetroxide-mediated cis-dihydroxylation of alkenes. Because of their limited relevance in this book, however, we won t discuss the mechanistic details of these reactions, but do consult your organic text if you are curious. 

Computations using density functional theory predict that the concerted permanganate hydroxylation of alkenes follows the 3 - - 2-cycloaddition mechanism established earlier for osmium tetroxide rather than a stepwise process involving a 2 -I- 2-cycloaddition. Calculated carbon and deuterium KIEs for a substituted case (frans-pentane-2,4-dienoic acid) are in good agreement with experimental data for frans-cinnamic acid." ... 

What is the mechanism of this transformation The initial reaction of the ir bond with osmium tetroxide constitutes a concerted (Section 6-4) addition in which three electron pairs move simultaneously to give a cyclic ester containing Os(VI). This process can be viewed as an electrophilic attack on the alkene Two electrons flow from the alkene onto the metal, which is reduced [Os(VIII) Os(VI)]. For steric reasons, the product can form only in a way that introduces the two oxygen atoms on the same face of the double bond—syn. This intermediate is usually not isolated but converted upon reductive work-up into the free diol. 

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