Osmium tetroxide asymmetric dihydroxylation

Norrby, P.-O., Rasmussen, T., Haller, J., Strassner, T., Houk, K. N. Rationalizing the Stereoselectivity of Osmium Tetroxide Asymmetric Dihydroxylations with Transition State Modeling Using Quantum Mechanics-Guided Molecular Mechanics. J. Am. Chem. Soc. 1999, 121, 10186-10192. 

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. 

Norrby, P. O., Kolb, H. C., Sharpless, K. B. Calculations on the reaction of ruthenium tetroxide with olefins using density functional theory (DPT). Implications forthe possibility of intermediates in osmium-catalyzed asymmetric dihydroxylation. Organometallics 994,13, 344-347. 

We already know how to produce 1,2-diols from the reactions of alkenes we studied in Chapter 11. We can make cis-diols using osmium tetroxide-mediated dihydroxylation, tra s-diols by ring opening of epoxides, and chiral diols by Sharpless asymmetric dihydroxylation (Figure 20.1). tra s-l,2-Amino alcohols can be prepared by ring opening of epoxides, and there is a version of the Sharpless dihydroxylation that leads to chiral amino alcohols. 

A catalytic enantio- and diastereoselective dihydroxylation procedure without the assistance of a directing functional group (like the allylic alcohol group in the Sharpless epox-idation) has also been developed by K.B. Sharpless (E.N. Jacobsen, 1988 H.-L. Kwong, 1990 B.M. Kim, 1990 H. Waldmann, 1992). It uses osmium tetroxide as a catalytic oxidant (as little as 20 ppm to date) and two readily available cinchona alkaloid diastereomeis, namely the 4-chlorobenzoate esters or bulky aryl ethers of dihydroquinine and dihydroquinidine (cf. p. 290% as stereosteering reagents (structures of the Os complexes see R.M. Pearlstein, 1990). The transformation lacks the high asymmetric inductions of the Sharpless epoxidation, but it is broadly applicable and insensitive to air and water. Further improvements are to be expected. 

Another important reaction associated with the name of Sharpless is the so-called Sharpless dihydroxylation i.e. the asymmetric dihydroxylation of alkenes upon treatment with osmium tetroxide in the presence of a cinchona alkaloid, such as dihydroquinine, dihydroquinidine or derivatives thereof, as the chiral ligand. This reaction is of wide applicability for the enantioselective dihydroxylation of alkenes, since it does not require additional functional groups in the substrate molecule ... 

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. 

Amino-Hydroxylation. A related reaction to asymmetric dihydroxylation is the asymmetric amino-hydroxylation of olefins, forming v/c-ami noalcohols. The vic-hydroxyamino group is found in many biologically important molecules, such as the (3-amino acid 3.10 (the side-chain of taxol). In the mid-1970s, Sharpless76 reported that the trihydrate of N-chloro-p-toluenesulfonamide sodium salt (chloramine-T) reacts with olefins in the presence of a catalytic amount of osmium tetroxide to produce vicinal hydroxyl p-toluenesulfonamides (Eq. 3.16). Aminohydroxylation was also promoted by palladium.77... 

More than sixty years ago, Criegee reported that the dihydroxylation of olefins by osmium tetroxide was accelerated by the addition of a tertiary amine.165 166 Later, this discovery prompted the study of asymmetric dihydroxylation, because the use of an optically active tertiary amine was expected to increase the reaction rate (kc > k0) and to induce asymmetry (Scheme 41).167... 

The history of asymmetric dihydroxylation51 dates back 1912 when Hoffmann showed, for the first time, that osmium tetroxide could be used catalytically in the presence of a secondary oxygen donor such as sodium or potassium chlorate for the cA-dihydroxylation of olefins.52 About 30 years later, Criegee et al.53 discovered a dramatic rate enhancement in the osmylation of alkene induced by tertiary amines, and this finding paved the way for asymmetric dihydroxylation of olefins. 

The first attempt to effect the asymmetric cw-dihydroxylation of olefins with osmium tetroxide was reported in 1980 by Hentges and Sharpless.54 Taking into consideration that the rate of osmium(VI) ester formation can be accelerated by nucleophilic ligands such as pyridine, Hentges and Sharpless used 1-2-(2-menthyl)-pyridine as a chiral ligand. However, the diols obtained in this way were of low enantiomeric excess (3-18% ee only). The low ee was attributed to the instability of the osmium tetroxide chiral pyridine complexes. As a result, the naturally occurring cinchona alkaloids quinine and quinidine were derived to dihydroquinine and dihydroquinidine acetate and were selected as chiral... 

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). 

Polymer-supported [e.g. 8, 9] and silica-supported [10] cinchona alkaloids have been used in the asymmetric dihydroxylation of alkenes using osmium tetroxide. Enantiomeric excesses >90% have been achieved for diols derived from styrene derivatives. 

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. 

Asymmetric dihydroxylation can be achieved using osmium tetroxide in conjunction with a chiral nitrogen ligand. " The very successful Sharpless procedure uses the natural cinchona alkaloids dihydroquinine (DHQ) and its diastereomer dihy-droquinidine (DHQD), as exemplified in the epoxidation of imni-stilbene... 

Asymmetric dihydroxylation of alkenes using osmium tetroxide... 

After the "asymmetric epoxidation" of allylic alcohols at the very beginning of the 80 s, at the end of the same decade (1988) Sharpless again surprised the chemical community with a new procedure for the "asymmetric dihydroxylation" of alkenes [30]. The procedure involves the dihydroxylation of simple alkenes with N-methylmorpholine A -oxide and catalytic amounts of osmium tetroxide in acetone-water as solvent at 0 to 4 °C, in the presence of either dihydroquinine or dihydroquinidine p-chlorobenzoate (DHQ-pClBz or DHQD-pClBz) as the chiral ligands (Scheme 10.3). 

The work by E.J. Corey [37], M. Hirama [38] and K. Tomioka [39], and their associates, on asymmetric dihydroxylation of alkenes with chiral diamine-osmium tetroxide complexes also deserves to be mentioned. 

Asymmetric dihydroxylation ofalkenes using osmium tetroxide.283... 

Other functionalized supports that are able to serve in the asymmetric dihydroxylation of alkenes were reported by the groups of Sharpless (catalyst 25) [88], Sal-vadori (catalyst 26) [89-91] and Cmdden (catalyst 27) (Scheme 4.13) [92]. Commonly, the oxidations were carried out using K3Fe(CN)g as secondary oxidant in acetone/water or tert-butyl alcohol/water as solvents. For reasons of comparison, the dihydroxylation of trons-stilbene is depicted in Scheme 4.13. The polymeric catalysts could be reused but had to be regenerated after each experiment by treatment with small amounts of osmium tetroxide. A systematic study on the role of the polymeric support and the influence of the alkoxy or aryloxy group in the C-9 position of the immobilized cinchona alkaloids was conducted by Salvadori and coworkers [89-91]. Co-polymerization of a dihydroquinidine phthalazine derivative with hydroxyethylmethacrylate and ethylene glycol dimethacrylate afforded a functionalized polymer (26) with better swelling properties in polar solvents and hence improved performance in the dihydroxylation process [90]. 

Phthalazines are commonly used as ligands in transition metal cataysis since the structure provides a planar backbone with coordinating nitrogens. One of the most prevalent phthalazine-based ligands is known as (DHQD)2PHAL (154) <94CR2483>. A recent example of the use of 154 was in the catalytic asymmetric dihydroxylation by osmium tetroxide with air as the ultimate oxidant reported by Krief and co-worker <99TL4189>. 

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. 

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-... 

The focus of this chapter is to acquaint the reader with details of catalytic asymmetric dihydroxylation with osmium tetroxide and the scope of results that one can expect to achieve with current optimum conditions. The literature through mid-1992 has been reviewed in compiling this chapter. Osmium tetroxide catalyzed hydroxy]ations of olefins and acetylenes are the subject of an extensive review by Schroder published in 1980 [2a]. A comprehensive review of research and industrial applications of asymmetric dihydroxylations is in preparation [2b]. 

The ratio of diols 61 62 from dihydroxylation with osmium tetroxide alone is 2.8 1, whereas with (DHQD)2-PHAL the ratio is 39 1, and with (DHQ)2-PHAL the ratio is 1 1.3, which shows the cumulative effect that can be achieved by matching diastereoselectivities and also reveals that AD may not be as reliable as is asymmetric epoxidation (Chapter 6A) for attaining good results when diastereoselectivities are mismatched. 

This asymmetric dihydroxylation problem was first solved by the use of cinchona alkaloid esters (16 and 17 R = p-ClC6H4) together with a catalytic amount of osmium tetroxide.142143 The alkaloid esters act as pseudoenantiomeric ligands (Scheme 9.19).144 144 They can also be supported on a... 

Keywords Asymmetric dihydroxylation, Osmium tetroxide, Cinchona alkaloid, Ligand-accelerated catalysis, Immobilization... 

The first heterogeneous osmium catalyst applicable for asymmetric dihydroxylation reactions was described by Kobayashi and coworkers (Table 9, entry 1) [38, 39]. Osmium tetroxide was enveloped in a polymer capsule by microencapsulation techniques [40,41]. The asymmetric dihydroxylation of transmethylstyrene with poly(acrylonitrile-co-butadiene-co-styrene) microencapsulated (ABS-MC) osmium tetroxide as catalyst, NMO as the cooxidant, and (DHQD)2PHAL as the chiral ligand completed in 88% yield with 94% ee [38]. The catalyst and the chiral ligand were reused in five consecutive runs without loss of activity. However, the use of NMO as cooxidant required the slow... 

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