Dihydroxylations, osmium tetroxide

DIHYDROXYLATION Osmium tetroxide-Dihydroquinine acetate. Osmium tetrox-ide-Diphenyl selenoxide. Osmium tetroxide-Trimethylamine N-oxide-Pyiidine. Thallium(l) acetate-iodine. Triphenylmethylphosphonium permanganate. 

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

ASYMMETRIC DIHYDROXYLATION Osmium tetroxide-Dihydroquinine acetate. 

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. 

Scheme 2. The osmium tetroxide mediated dihydroxylation reaction.

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

Dihydroxylation of 59a with osmium tetroxide in pyridine and epoxidation of 59a with m-chloroperbenzoic acid (mCPBA) both showed high syn preference of the addition (0 0 syn anti = 95 5 mCPBA synianti = 92 8). This preference is in sharp contrast to the anti preference of 60a (symanti = 12 88), observed under similar dihydroxylation conditions with osmium tetroxide in pyridine. 

Syn-Dihydroxylation. When the reaction was first discovered, the syn-dihydroxylation of alkenes was carried out by using a stoichiometric amount of osmium tetroxide in dry organic solvent.56 Hoffman made the observation that alkenes could react with chlorate salts as the primary oxidants together with a catalytic quantity of osmium tetroxide, yielding syn-vicinal diols (Eq. 3.11). This catalytic reaction is usually carried out in an aqueous and tetrahydrofuran solvent mixture, and silver or barium chlorate generally give better yields.57... 

Catalytic dihydroxylations using the osmium tetroxide-tm-butyl hydroperoxide system are largely due to Sharpless and co-workers. The aqueous 70%-i-butyl hydroperoxide is commercially available and ideal for direct use in this dihydroxylation process.60... 

A very effective way of carrying out syn-dihydroxylation of alkenes is by using an osmium tetroxide-tertiary amine N-oxide system. This dihydroxylation is usually carried out in aqueous acetone in either one-or two-phase systems, but other solvents may be required to overcome problems of substrate solubility.61... 

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... 

Ishikawa s endgame toward of 54 is shown in Scheme 3.12. First, the allylic alcohol function was oxidized by a substrate-directed dihydroxylation reaction, as developed by Donohoue and coworkers (66 % yield) [36]. This reaction is conducted using 1 equiv each of osmium tetroxide and tetramethylethylene diamine (TMEDA) and provides a method to obtain the syn-A i hydroxylation product in the... 

The osmium-catalyzed dihydroxylation reaction, that is, the addition of osmium tetr-oxide to alkenes producing a vicinal diol, is one of the most selective and reliable of organic transformations. Work by Sharpless, Fokin, and coworkers has revealed that electron-deficient alkenes can be converted to the corresponding diols much more efficiently when the pH of the reaction medium is maintained on the acidic side [199]. One of the most useful additives in this context has proved to be citric acid (2 equivalents), which, in combination with 4-methylmorpholine N-oxide (NMO) as a reoxidant for osmium(VI) and potassium osmate [K20s02(0H)4] (0.2 mol%) as a stable, non-volatile substitute for osmium tetroxide, allows the conversion of many olefinic substrates to their corresponding diols at ambient temperatures. In specific cases, such as with extremely electron-deficient alkenes (Scheme 6.96), the reaction has to be carried out under microwave irradiation at 120 °C, to produce in the illustrated case an 81% isolated yield of the pure diol [199]. 

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). 

In summary, the reaction of osmium tetroxide with alkenes is a reliable and selective transformation. Chiral diamines and cinchona alkakoid are most frequently used as chiral auxiliaries. Complexes derived from osmium tetroxide with diamines do not undergo catalytic turnover, whereas dihydroquinidine and dihydroquinine derivatives have been found to be very effective catalysts for the oxidation of a variety of alkenes. OsC>4 can be used catalytically in the presence of a secondary oxygen donor (e.g., H202, TBHP, A -methylmorpholine-/V-oxide, sodium periodate, 02, sodium hypochlorite, potassium ferricyanide). Furthermore, a remarkable rate enhancement occurs with the addition of a nucleophilic ligand such as pyridine or a tertiary amine. Table 4-11 lists the preferred chiral ligands for the dihydroxylation of a variety of olefins.61 Table 4-12 lists the recommended ligands for each class of olefins. 

The unsubstituted pyrrolo[l,2-f]oxazol-3-one 295 underwent a dihydroxylation with catalytic osmium tetroxide to exclusively give diol 296. This diol resulted from attack of the oxidizing agent from the concave face of the molecule due to the pseudoaxial protons that sterically hinder the /3-face to be attacked by the osmium reagent (Equation 51) <2004AJC669>. 

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