Alkenes by osmium tetroxide

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... 

It is a chiral version of the syn dihydroxylation of alkenes by osmium tetroxide. Here is an example— though the concept is quite simple, the recipe for the reactions is quite complicated so we need to approach it step by step. 

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. 

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... 

In Section 6.5A, we studied oxidation of alkenes by osmium tetroxide in the presence of peroxides. This oxidation results in syn stereoselective hydroxylation of the alkene to form a glycol. In the case of cycloalkenes, the product is a cis glycol. The first step in each oxidation involves formation of a cyclic osmate and is followed immediately by reaction with water to give a glycol. 

Another method for the hydroxylation of the etliylenic linkage consists in treatment of the alkene with osmium tetroxide in an inert solvent (ether or dioxan) at room temperature for several days an osmic ester is formed which either precipitates from the reaction mixture or may be isolated by evaporation of the solvent. Hydrolysis of the osmic ester in a reducing medium (in the presence of alkaline formaldehyde or of aqueous-alcoholic sodium sulphite) gives the 1 2-glycol and osmium. The glycol has the cis structure it is probably derived from the cyclic osmic ester ... 

With this reaction, two new asymmetric centers can be generated in one step from an achiral precursor in moderate to good enantiomeric purity by using a chiral catalyst for oxidation. The Sharpless dihydroxylation has been developed from the earlier y -dihydroxylation of alkenes with osmium tetroxide, which usually led to a racemic mixture. 

Since Sharpless discovery of asymmetric dihydroxylation reactions of al-kenes mediated by osmium tetroxide-cinchona alkaloid complexes, continuous efforts have been made to improve the reaction. It has been accepted that the tighter binding of the ligand with osmium tetroxide will result in better stability for the complex and improved ee in the products, and a number of chiral auxiliaries have been examined in this effort. Table 4 11 (below) lists the chiral auxiliaries thus far used in asymmetric dihydroxylation of alkenes. In most cases, diamine auxiliaries provide moderate to good results (up to 90% ee). 

Figure 8.15 The rate constant of a pseudo-order reaction varies with the concentration of the reactant in excess graph of k (as V) against [alkene]0 (as V). The data refer to the formation of a 1,2-diol by the dihydrolysis of an alkene with osmium tetroxide. The gradient of the graph yields k2, with a value of 3.2 x 10 2 dm3 mol-1 s-1...

Another familiar example of the reaction proceeding in cis fashion is the hydroxylation of alkenes which occurs by osmium tetroxide or by the action of KMn04. 

About a decade after the discovery of the asymmetric epoxidation described in Chapter 14.2, another exciting discovery was reported from the laboratories of Sharpless, namely the asymmetric dihydroxylation of alkenes using osmium tetroxide. Osmium tetroxide in water by itself will slowly convert alkenes into 1,2-diols, but as discovered by Criegee [15] and pointed out by Sharpless, an amine ligand accelerates the reaction (Ligand-Accelerated Catalysis [16]), and if the amine is chiral an enantioselectivity may be brought about. 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

Butyl hydroperoxide,37 barium chlorate,38 or potassium ferricyanide39 can also be used as oxidants in catalytic procedures. Scheme 12.6 provides some examples of oxidations of alkenes to glycols by permanganate and by osmium tetroxide. 

The conversion of alkenes to 1,2-diols by osmium tetroxide is also an olefin addition reaction. In this case a hydroxy group is added to each carbon of the olefin group, and the addition is termed an oxidative addition since the diol product is at a higher oxidation level than the alkene reactant. Oxidation of the carbon atoms of the alkene takes place in the first step, which is the reaction with 0s04 to produce the intermediate osmate ester. 

Sodium bisulfite, NaHS03. Reduces osmate esters, prepared by treatment of an alkene with osmium tetroxide, to yield 1,2-diols (Section 7.8). 

We now turn to the stereochemistry governed by a ring system, and we shall look at both nucleophilic and electrophilic attack, since usually they have similar stereochemical preferences rather than contrasting preferences. In addition to several reactions that are straightforwardly electrophilic attack, we shall see several which can be described as electrophilic in nature, like the reactions of alkenes with osmium tetroxide, with peracids, with some 1,3-dipoles, and with boranes, and of dienes with dienophiles in Diels-Alder reactions. Some of these reactions are pericyclic, the pericyclic nature of which we shall meet in Chapter 6. For now, it is only their diastereoselectivity that will concern us. 

In an extension of the cis dihydroxylation of alkenes with osmium tetroxide. Sharpless has developed a series of reactions, reviewed by Case et al., in which an osmium imine species is added to an alkene. 

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. 

Dihydroxylation of hindered double bonds.1 The tx-pinene derivative 1 (Nopol) is hydroxylated in low yield by osmium tetroxide and f-butyl hydroperoxide. Hydroxylation is effected in 62% yield by use of 0s04 in combination with trimethylamine N-oxide as oxidant and pyridine as base. This method is generally suitable for hindered alkenes (yields 78-93%). 

Gallc er and co-workers devised a formal enantioselective synthesis of ( — )-3 in wduch the stereogenic center at C-6 was derived fiom Cbz-protected (S)-2-amino-4-pentenoic acid (36) (44). Acylation of 3,3-dimethoxy-pyrrolidine (37) with this acid yielded amide 38, which was converted into aldehyde 39 by cleavage of the terminal alkene vnth osmium tetroxide and sodium periodate (Scheme 5). The indolizidine nucleus was constructed from 39 by a problematic intramolecular aldol condensation, which was eventually optimized by using 2,2,6,6-tetramethylpiperidine as base followed by adsorption onto, and elution from, silica gel (45). Diastereoselective reduction of the ketone group of the aldol product 40 was accomplished in better than 95% enantiomeric excess (ee) with the Corey... 

The Corey mechanistic proposal is founded on the ability of the alkene substrate to bind between the two quinohne ring walls which are spaced parallel with a separation of 7.2 A. When the substrate binds in this elongated cleft, the alkene complexes to the osmium center in the W-complexated osmium tetroxide through a donor-acceptor (d-Jt) interaction (Scheme 10). The interaction between the alkene and osmium tetroxide is also complemented with favorable van der Waals interactions between the alkene and the binding cleft. These interactions are implied by the Michaelis-Menten kinetics [72] observed in the process. The observation of Michaelis-Menten kinetics in the AD process has however been questioned as an experimental artifact by the Sharpless group [73]. The (3+2) addition takes place between the axial and one of the equatorial oxygen atoms in osmium tetroxide which are in close proximity with the alkene. This represents the minimum motion pathway in the formation of the pentacoordinate os-mium(VI) glycolate ester. In the Corey model the rate acceleration observed in... 

An alkene can be oxidized to a 1,2-diol either by potassium permanganate (KMn04) in a cold basic solution or by osmium tetroxide (OSO4). The solution of potassium permanganate must be basic, and the oxidation must be carried out at room temperature or below. If the solution is heated or if it is acidic, the diol will be oxidized further (Section 20.8). A diol is also called a glycol. The OH groups are on adjacent carbons in 1,2-diols, so 1,2-diols are also known as vicinal diols or vicinal glycols. 

Primary alcohols are oxidized to carboxylic acids by chromium-containing reagents and to aldehydes by PCC or a Swem oxidation. Secondary alcohols are oxidized to ketones. Tollens reagent can oxidize only aldehydes. A peroxyacid oxidizes an aldehyde to a carboxylic acid, a ketone to an ester (in a Baeyer-Villiger oxidation), and an alkene to an epoxide. Alkenes are oxidized to 1,2-diols by potassium permanganate (KMn04) in a cold basic solution or by osmium tetroxide (OSO4). 

Diol formation by reaction of alkenes with osmium tetroxide (sec. 3.5.B). 

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. 

Related to the dihydroxylation of alkenes with osmium tetroxide is the direct conversion of alkenes into 1,2-amino alcohols. Treatment of an alkene with osmium tetroxide in the presence of A -chloramine-T (TsNClNa) provides the 1,2-hydroxy toluene-/ -sulfonamide (5.94). The sulfonylimido osmium compound 94 is believed to be the active reagent, and is continuously regenerated during the reaction. The sulfonamide products can be converted to their free amines by cleavage of the tosyl group with sodium in liquid ammonia. 

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. 

Due to the electrophilic nature of osmium tetroxide, electron-withdrawing groups connected to the alkene double bond retard the dihydroxylation. This is in contrast to the oxidation of alkenes by Potassium Permanganate, which preferentially attacks electron-deficient double bonds. However, in the presence of a tertiary amine such as pyridine, even the most electron-deficient alkenes can be osmylated by osmium tetroxide (eq 4). The more highly substituted double bonds are preferentially oxidized (eq 5). 

Under stoichiometric and common catalytic osmylation conditions, alkene double bonds are hydroxylated by osmium tetroxide without affecting other functional groups such as hydroxyl groups, aldehyde and ketone carbonyl groups, acetals, triple bonds, and sulfides (see also Osmium Tetraxide-N-Methylmorpholine N-Oxide). 

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