Dihydroxylation asymmetric, osmium

Reactions have been carried out adjacent to the epoxide moiety in order to examine the effects, if any, that the epoxide has on subsequent reactions with respect to the regio- and stereochemical outcome. Dihydroxylation using osmium tetraoxide and Sharpless asymmetric dihydroxylation reactions have been extensively studied using substrates 29 and 31. Initial studies centred on the standard dihydroxylation conditions using AT-methylmorpholine-AT-oxide and catalytic osmium tetraoxide. The diastereomeric ratios were at best 3 2 for 29 and 2 1 for 31, indicating that the epoxide unit had very little influence on the stereochemical outcome of the reaction. This observation was not unexpected, since the epoxide moiety poses minimal steric demands (Scheme 21). 

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 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. 

Asymmetric, osmium-catalysed dihydroxylation of 1,1-disubstituted and 1,3-disub stituted allenes has been employed to synthesize chiral a-hydroxy ketones, a,a - (g) Dihydroxy ketones were obtained from 1,3-disubstituted allenes with high enantio-... 

Fristrup, P., Tanner, D., Norrby, P.-O. Updating the asymmetric osmium-catalyzed dihydroxylation (AD) mnemonic Q2MM modeling and new kinetic measurements. Chirality 2003, 15, 360-368. 

We have spent some time in this chapter looking at the diastereoselectivity of some very important reactions. We shall be returning to the most important of these in chapter 25 where we discuss two of the most important reactions of the century - asymmetric versions of epoxidation and dihydroxylation by osmium. These developments were possible only because of the selectivities already established by the work described in this chapter and the selectivities we have discussed will be important in many syntheses. 

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. 

Chandrasekhar, S., Narsihmulu, C., Sultana, S.S., Reddy, N.R. (2003) Osmium Tetrox-ide in Poly(ethylene glycol) (PEG) A Recyclable Reaction Medium for Rapid Asymmetric Dihydroxylation Under Sharpless Conditions. Chemical Communications, 1716-1717. 

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... 

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... 

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... 

Figand acceleration (the so-called Criegee effect) is the important feature of asymmetric dihydroxylation using cinchona ligands.193 In particular, bis-cinchona ligands provide remarkable acceleration (Scheme 48). This enables high turnover rates of the osmium catalysts. 

In 1975, Sharpless et al. reported that imino-osmium trioxides underwent aminohydroxylation (Scheme 54).208,209 t0 perform aminohydroxylation with high efficiency, regio-, chemo-, and enantioselectivity must be addressed. This had made the practical realization of aminohydroxylation difficult. However, the development of asymmetric dihydroxylation, as described in the preceding section, propelled the study of asymmetric aminohydroxylatyion forward and, in 1996, Sharpless et al. reported a highly enantioselective version of catalytic aminohydroxylation... 

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). 

Also fifteen years of painstaking work and the gradual improvement of the system, the Sharpless team announced that asymmetric dihydroxylation (AD) of nearly every type of alkene can be accomplished using osmium tetraoxide, a co-oxidant such as potassium ferricyanide, the crucial chiral ligand based on a dihydroquinidine (DHQD) (21) or dihydroquinine (DHQ) (22) and metha-nesulfonamide to increase the rate of hydrolysis of intermediate osmate esters 1811. 

Sharpless asymmetric dihydroxylation procedure was applied to the synthesis of the side chain of azinomycin A (equation 26)43. Horner-Emmons condensation of phospho-nate 36 with a /J-aziridine substituted acrolein afforded dehydroamino acid diene 37. Treatment of the diene with catalytic amounts of an osmium reagent and dihydroquini-dine (DHQD) p-chlorobenzoate resulted in asymmetric dihydroxylation, producing diol 38. Diol 38 was further converted to the naphthyl ester. 

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]. 

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