Osmium-catalyzed dihydroxylation

Scheme 12.7. Enantioselective Osmium-Catalyzed Dihydroxylation of Alkenes...

Dapprich, S., Ujaque, G., Maseras, F., Lledos, A., Musaev, D. G., Morokuma, K., 1996, Theory Does Not Support an Osmaoxetane Intermediate in the Osmium-Catalyzed Dihydroxylation of Olefins , J. Am, Chem. Soc., 118, 11660. 

A photo-induced dihydroxylation of methacryamide by chromium (VI) reagent in aqueous solution was recently reported and may have potential synthetic applications in the syn-dihydroxylation of electron-deficient olefins.63 Recently, Minato et al. demonstrated that K3Fe(CN)6 in the presence of K2C03 in aqueous rm-butyl alcohol provides a powerful system for the osmium-catalyzed dihydroxylation of olefins.64 This combination overcomes the disadvantages of overoxidation and low reactivity on hindered olefins related to previous processes (Eq. 3.14). 

Mono-, di-, and trisubstituted olefins undergo osmium-catalyzed enantioselective dihydroxylation in the presence of the (R)-proline-substituted hydroquinidine 3.9 to give diols in 67-95% yields and in 78-99% ee.75 Using potassium osmate(VI) as the catalyst and potassium carbonate as the base in a tm-butanol/water mixture as the solvent, olefins are dihydroxylated stereo- and enantioselectively in the presence of 3.9 and potassium ferricyanide with sodium chlorite as the stoichiometric oxidant the yields and enantiomeric excesses of 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]. 

Scheme 6.96 Osmium-catalyzed dihydroxylation of electron-deficient alkenes.

Wordy Over the past few years, we have encountered numerous examples of water as the perfect solvent. We observed this first in osmium-catalyzed dihydroxylation reactions and also in nucleophilic ring-opening reactions of epoxides. We also observed this in cycloaddition reactions and in most oxime ether, hydrazone, and aromatic heterocycle condensation processes.Finally, we observed it in formation reactions of an amide from a primary amine and an acid chloride using aqueous Schotten-Baumann conditions. ... 

Osmium-catalyzed oxidation is one of the most useful routes to dihydroxylation of alkenes to give the corresponding diols. This oxidation proceeds in the presence... 

The preparation described here is a slight modification of a route published by King and Sharpless via the osmium-catalyzed asymmetric dihydroxylation (AD) reaction of 1 -phenyl-1-cyclohexene. The major strengths of this process are that either enantiomer can be prepared in high optical purity (> 99.5% ee) v/ithout the need for chromatography. 

SCHEME 178. Osmium-catalyzed catalytic asymmetric dihydroxylation of olefins by H2O2 as terminal oxidant... 

D.2. GENERAL FEATURES OF OSMIUM-CATALYZED ASYMMETRIC DIHYDROXYLATION... 

In September 1997, Chemical and Engineering News summarized the ongoing discussion about the precise mechanism of the initial steps of the osmium-catalyzed olefin dihydroxylation in an... 

Moreover, the secondary cycle was utilized to develop a new procedure for racemic osmium-catalyzed dihydroxylation. Dihydroxylation with citric acid as... 

The Beller group was able to optimize the reaction conditions of the osmium-catalyzed dihydroxylation such that dioxygen or air could be used as cooxidants... 

Although the AD process has found widespread use on the lab scale, industrial applications are obstructed owing to the toxicity and the high cost of the osmium catalyst and the risk of contamination of the products by toxic osmium residues. To address this issue, several research groups have developed immobilized osmium catalysts for use in the osmium-catalyzed dihydroxylations [30]. 

Beller and coworkers [85] showed that osmium-catalyzed dihydroxylations can be performed successfully with dioxygen as the primary oxidant (Fig. 4.32). 

Fig. 4.31 Mechanism of osmium-catalyzed vicinal dihydroxylation of olefins.

After their leading publication on the osmium-catalyzed dihydroxylation of olefins in the presence of dioxygen [208], Beller et al. [209] recently reported that alcohol oxidations could also be performed using the same conditions. The reactions were carried out in a buffered two-phase system with a constant pH of 10.4. Under these conditions a remarkable catalyst productivity (TON up to 16 600 for acetophenone) was observed. The pH value is critical in order to ensure the reoxidation of Os(VI) to Os(VIII). The scope of this system seems to be limited to benzylic and secondary alcohols. 

When the Sharpless osmium-catalyzed dihydroxylation procedure is used in tandem with an aldolase-catalyzed addition, a rapid stereoselective entry to a variety of carbohydrates is achieved (Scheme 5.11).32 By judicious choice of hydroxylation and aldolase conditions, a number of the possible hexose... 

Conformationally constrained 2 -deoxy-4-thia /3-anomeric spirocyclic nucleosides have been synthesized by Dong and Paquette <2005JOC1580>. Osmium-catalyzed dihydroxylation of the spirocyclic dihydrothiophene 135 in the presence of DABCO gave the air-diol 136 in 53% yield which was protected as an acetonide hydrolysis using LiOH in aqueous THE and subsequent Meerwein-Ponndorf-Verley reduction of the keto compound 137 gave a diaster-eomeric mixture of alcohols (Scheme 36). 

The first successful osmium-catalyzed asymmetric aminohydroxylation and dihydroxylation of thiophene acrylates have been reported. The aminohydroxylation of 2-thienyl-, 5-bromo-2-thienyl-, and 3-thienylacrylates proceeds with high regio- and enantioselectivity (Equation 75) <1999SL1907. Yields were about 67-68%, with the regioselectivity of 151 over 152 being >15 1. The ee was 99%. 

Scheme 1 Proposed mechanism of the osmium-catalyzed asymmetric dihydroxylation of alkenes...

Eyrisch, O, Sinerius, G, Fessner, W-D, Eacile enzymic de novo synthesis and NMR spectroscopic characterization of D-tagatose 1,6-bisphosphate, Carbohydr. Res., 238, 287-306, 1993. Henderson, I, Sharpless, KB, Wong, C-H, Synthesis of carbohydrates via tandem use of the osmium-catalyzed asymmetric dihydroxylation and enzyme-catalyzed aldol addition reactions, J. Am. Chem. Soc., 116, 558-561, 1994. 

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