Oxidation with osmium tetraoxide

In a novel synthetic route involving the transformation of a tetrahydroproto-berberine nucleus to a pavine skeleton (Scheme 10) 119), canadine methiodide (67), was subjected to Hofmann degradation to yield styrene 68. This compound was successively oxidized with osmium tetraoxide-sodium periodate and the... 

Reaction of the unsaturated bromoethyl glycoside 216 in the foregoing manner gives the bicyclic product 217,218 and similar treatment of the propargyl ether 219 with a tributyltin radical results in carbon-radical generation and cyclization to afford the tin-containing adduct 220 in 90% yield. On oxidation with osmium tetraoxide and periodate ion, the Sn-C bond is cleaved, and the corresponding ketone 221 is produced in excellent yield.219... 

Dehydrobromination of compound 173 gave isomeric 2,5-dihydrofurans 174 and 175. Upon oxidation with osmium tetraoxide, the cis compound (174) gave exclusively 176, whereas the trans isomer (175) afforded approximately equal amounts of 177 and 178. The methyl esters 176-178 were reduced to die corresponding alcohols 179-181. A mixture of 179 and 180 was direcUy correlated wi compound 182 obtained from D-xylose, whereas hydrolysis of 181 in concentrated hydrochloric acid gave a,p-DL-dihydrostreptose. 

Oxidation of alkenes with osmium tetraoxide is much more moderate than similar oxidations with permanganate. This makes OSO4 a very reliable reagent for cis dihydroxylation. 

This problem may, however, be a special case because the oxidation of pteridine alkenes in the presence of sensitive substituents such as alkylthio was shown to be possible using ligand-assisted catalysis with osmium tetraoxide or DMDO (Scheme 10). In the case of pteridine 65, a clean series of transformations to afford the pterin 66 was possible <20030BC664, 2005PTR53004/04>. However, if oxidation was carried out under moist conditions, the corresponding 2-oxopteridine (lumazine) was always obtained as illustrated by the conversion of 67 into the epoxide 68. 

Compound 191 was transformed into the exo-alkene 193 via the respective spiro epoxide the enone 192 (11%) was obtained as a side product (Scheme 24).97 Compound 193 was deprotected, and the triol obtained was selectively mesylated at the allylic position to give, after acetylation, compound 194 (68%). Treatment of 194 with sodium acetate resulted in the inversion of configuration at C-l to give the tetra-N,O-acetyl derivative 195. Oxidation of 195 with osmium tetraoxide in aqueous acetone, followed by acetylation, afforded 196 (87%) and 197 (13%), whose acid hydrolysis provided the free bases 5 and 37, respectively. 

Alternatively, synthesis of compound 215 (4-epimer of 208) started by initial inversion of the OH group at C-l of 207 (Scheme 27).35,96,99 101 Acid hydrolysis of 207 gave the triol 209 (100%), which was identified as its tetraacetate 210, whose allylic hydroxyl group was selectively sulfonylated with mesyl chloride to afford 211, which was then converted into the acetate 212 (65%). On treatment with an excess of sodium acetate in DMF, 212 afforded 213 (60%). Oxidation of 213 with osmium tetraoxide gave, after acetylation, 214 and 216. Furthermore, epoxidation of 213 gave a single spiro epoxide 214 (64%), which was transformed exclusively into 216 (83%)... 

Dihydrooxazines of this type were essentially unknown previously, and studies were therefore undertaken to explore their potential as synthons in the stereoselective synthesis of 1,3-amino alcohols. For example, oxidations of the ring double bond were investigated. Thus, hydroxylation of 161 with osmium tetraoxide was stereoselective, affording diol 162 (Scheme 30) resulting from attack on the face of the double bound anti to the aryl sulfonyl group (cf. 160). This diol could be converted to an epimeric mixture of hydroxy nitriles 163 and 164 via an N- sulfonyl iminium intermediate. 

R = C5H90-0CH2).78 Methyl 5-0-trityl-/3-D-ribofuranoside was obtained with good specificity on oxidation of methyl 2,3-dideoxy-5-0-trityl-/3-D-gZi/cero-pent-2-enoside (41, R = OMe, R = CH2OTr) with osmium tetraoxide.78 ... 

Preparation of the corresponding cA-16a,17a-diol relies on the known propensity of many inorganic oxidizing agents to produce cA-diols. The sequence for synthesizing that isomer starts with heat-induced elimination of the elements of benzoic acid from estradiol 17-benzoate. The resulting 16-dehydro compound, 31-2, is then treated with osmium tetraoxide (Scheme 3.31). The stereochemistry of that transformation can be rationalized by positing the intermediacy of a complex such as that depicted in 31-3. The overall result is the formation of the c -diol 16a-hydroxy-a-estradiol (31-4). 

Oxidation of testosterone with osmium tetraoxide gives the corresponding 4,5-glycol (5-1) of undehned stereochemistry. By the method of formation, both hydroxyls probably have the same )8-conhguration. This product the undergoes spontaneous )8-dehydration to the enol hydroxide derivative formestane (5-2) (Scheme 5.5). 

Oxidation of polyDBOE with osmium tetraoxide leads to the cis-isomer ... 

Hydroboration of the methyl enol ether in (275) and subsequent oxidation provided crystalline (276). The selective hydrolysis of the protected lactol followed by treatment with methanesulfonyl chloride generated the sensitive dihydropyran (277), which was treated directly with osmium tetraoxide to give (278) and (279). 

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). 

This reaction was first reported by Lemieux and Johnson in 1956. It is a conversion of an olefin into two individual aldehydes by means of an oxidative cleavage of a carbon-carbon double bond with osmium tetraoxide-sodium periodate. Therefore, it is known as the Lemieux-Johnson oxidative cleavage, Lemieux-Johnson reaction, or simply Lemieux-Johnson oxidation." In addition, the combination of osmium tetraoxide and sodium periodate is referred to as Lemieux-Johnson reagent. It should be pointed out that a lactol may be obtained directly from the oxidation of the olefin with a hydroxyl group near the oleflnic bond." ... 

The products of dihydroxylation are vicinal diols, commonly called glycols. They are made with osmium tetraoxide (OsO ) as the oxidizing agent. 

The oxidation of alkenes with osmium tetraoxide gives excellent yields of vicinal diols. However, this reagent is both expensive and highly toxic. Therefore, it is used only in small-scale laboratory syntheses, not in industrial processes. Osmium tetraoxide can, however, be used in a catalytic process in which the oxidizing agent is recycled. For example, hydrogen peroxide can be used to oxidize the reduced osmium back to osmium tetraoxide, which continues to oxidize the alkene to a diol. This process allows the reaction to be carried out with only a small amount of the toxic OsO. A similar result can be obtained with A methylmorpholine-A -oxide (NMNO). 

From acrolein by oxidation with sodium chlorate and osmium tetraoxide. Neuberg, Biochem. Z. 255, i (1932). 

The reaction mechanisms of these transition metal mediated oxidations have been the subject of several computational studies, especially in the case of osmium tetraoxide [7-10], where the controversy about the mechanism of the oxidation reaction with olefins could not be solved experimentally [11-20]. Based on the early proposal of Sharpless [12], that metallaoxetanes should be involved in alkene oxidation reactions of metal-oxo compounds like Cr02Cl2, 0s04 and Mn04" the question arose whether the reaction proceeds via a concerted [3+2] route as originally proposed by Criegee [11] or via a stepwise [2+2] process with a metallaoxetane intermediate [12] (Figure 2). 

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). 

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