Dihydroxylation osmium-mediated

Another useful method for the asymmetric oxidation of enol derivatives is osmium-mediated dihydroxylation using cinchona alkaloid as the chiral auxiliary. The oxidation of enol ethers and enol silyl ethers proceeds with enantioselectivity as high as that of the corresponding dihydroxylation of olefins (vide infra) (Scheme 30).139 It is noteworthy that the oxidation of E- and Z-enol ethers gives the same product, and the E/Z ratio of the substrates does not strongly affect the... 

Side Note 17.2. Alternatives to the Osmium-mediated cis-vt c-Dihydroxylation... 

An extended addition increases the effective mole ratio of reaction components, which can have a beneficial impact on reaction selectivity. This is particularly true for reactions using catalysts. In the dihydroxylations in Figure 8.7, olefin 13 was added over 6 hours in order to ensure high enantiomeric purity of the product [6], Excess olefin, which accumulates if the addition rate is faster than the reaction rate, is thought to coordinate with the catalyst in a fashion that leads to non-enantioselective dihydroxylation [6]. In the osmium-mediated dihydroxylation of... 

Fig. 10. Hammett plots of osmium mediated dihydroxylations of substituted stUbenes using pyridine left), quinuclidine (middle) and DHQD-CLB (right) as ligands... 

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. 

Osmium-mediated dihydroxylation of carbon-carbon double bonds with OsO is a classic reaction that can be made catalytic by using cooxidants such as r-butyl hydroperoxide or 8.30. For asymmetric dihydroxylation (ADH) reactions, the co-oxidant of choice is water-soluble potassium ferricyanide. 

Scheme 2. The osmium tetroxide mediated dihydroxylation reaction.

Scheme 4. Corey s synthesis of ( )-bilobalide [( )-l7], employing a stoichiometric osmium tetroxide mediated dihydroxylation reaction.

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). 

The cis dihydroxylation of olefins mediated by osmium tetroxide represents an important general method for olefin functionalization [1,2]. For the purpose of introducing the subject of this chapter, it is useful to divide osmium tetroxide mediated cis dihydroxylations into four categories (1) the stoichiometric dihydroxylation of olefins, in which a stoichiometric equivalent of osmium tetroxide is used for an equivalent of olefin (2) the catalytic dihydroxylation of olefins, in which only a catalytic amount of osmium tetroxide is used relative to the amount of olefin in the reaction (3) the stoichiometric, asymmetric dihydroxylation of olefins, in which osmium tetroxide, an olefinic compound, and a chiral auxiliary are all used in equivalent or stoichiometric amounts and (4) the catalytic, asymmetric dihydroxylation of olefins. The last category is the focus of this chapter. Many features of the reaction are common to all four categories, and are outlined briefly in this introductory section. 

Asymmetric induction also occurs during osmium tetroxide mediated dihydroxylation of olefinic molecules containing a stereogenic center, especially if this center is near the double bond. In these reactions, the chiral framework of the molecule serves to induce the diastereoselectivity of the oxidation. These diastereoselective reactions are achieved with either stoichiometric or catalytic quantities of osmium tetroxide. The possibility exists for pairing or matching this diastereoselectivity with the face selectivity of asymmetric dihydroxylation to achieve enhanced or double diastereoselectivity [25], as discussed further later in the chapter. 

This brief outline of historical developments in osmium tetroxide-mediated olefin hydroxy-lation brings us to our main subject, catalytic asymmetric dihydroxylation. The transition from stoichiometric to catalytic asymmetric dihydroxylation was made in 1987 with the discovery by Sharpless and co-workers that the stoichiometric process became catalytic when N-methyl-... 

Under controlled conditions, the osmium-tetroxide-mediated dihydroxylation is also chemoselective, reacting preferentially with the more nucleophilic double bond in the presence of a triple bond. ... 

It should also be noted that epoxidation of olefins followed by ring opening with OH provides 1,2 diols with different stereochemistry from that observed with osmium-tetroxide-mediated 5yn-dihydroxylation. Therefore, even when only one diastereomeric olefin is available, it is possible to prepare both diastereomeric 1,2-diols, as shown below. 

Osmium-catalyzed dihydroxylation of olefins involves an Os(VIII)/Os(VI) substrate-selective redox system [36c-gj. In this system, N-methylmorpholine N-oxide (NMMO) can be used for the reoxidation of Os(VI) to Os(VIII), with NMMO being reduced to NMM. In cyclohexene oxidation catalyzed by Os with HP, the yield to cis-1,2-cyclohexandiol can be improved remarkably by the use of specific mediators for NMM oxidation to NMMO, for instance by means of catalytic fiavin/HP. In this case, a yield to the cis-diol of 91% was obtained, as compared to 50% with the OSO4/HP system alone [36hj. Mixtures of aqueous HP and acetic acid or formic acid are also effective reagents for the dihydroxylation of olefins, but neutralization of the acid solvent is necessary for the recovery of the product. 

The Sharpless asymmetric hydroxylation can take one of two forms, the initially developed asymmetric dihydroxylation (AD)1 or the more recent variation, asymmetric aminohydroxylation (AA).2 In the case of AD, the product is a 1,2-diol, whereas in the AA reaction, a 1,2-amino alcohol is the desired product. These reactions involve the asymmetric transformation of an alkene to a vicinally functionalized alcohol mediated by osmium tetraoxide in the presence of chiral ligands (e.g., (DHQD)2-PHAL or (DHQ)2-PHAL). A mixture of these reagents (ligand, osmium, base, and oxidant) is commercially available and is sold under the name of AD-mix p or AD-mix a (vide infra). 

The discussion about the possible formation of metalla-2-oxetanes in transition metal-mediated oxidation reactions began with the ground breaking work of Sharpless in the field of enantioselective dihydroxylation of olefins with osmium tetraoxide using cinchona alkaloids as ligands [6]. The transfer of the stereochemical information of the chiral ligand to the substrate was explained by Sharpless with a two-step mechanism for the addition reaction, which should occur rather than a concerted [3+2] addition as originally proposed [110] (Fig. 15). 

The oxidative functionalization of olefins mediated by transition metal oxides leads to a variety of products including epoxides, 1,2-diols, 1,2-aminoalcohols, and 1,2-diamines [1]. Also the formation of tetrahydrofurans (THF) from 1,5-dienes has been observed, and enantioselective versions of the different reactions have been developed. Although a lot of experimental data has been available, the reaction mechanisms have been a subject of controversial discussion. Especially, osmium (VIII) complexes play an important role there, as the proposal of a stepwise mechanism [2] for the dihydroxylation (DH) of olefins by osmium tetroxide (OSO4) had started an intense discussion about the mechanism [2—11],... 

Dihydroxylated by-products might indeed result from dihydroxylation mediated by the imido osmium compound so2 Toig. l s a very low kinetic selectivity of only 0.9 kcal/mol (14.3-13.4 kcal/mol) has been obtained. In case of the methyl-substituted imido osmium, another pathway becomes more probable, which is the dihydroxylation by in situ formed OSO4 NH3. It was predicted to have a reaction barrier of only 17.0 kcal/mol and might be responsible for the experimental observation of a significant amount of dihydroxylated by-product in case of R = tert-Bu [18, 90]. 

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