Osmium tetroxide-pyridine

Osmium Tetroxide-Pyridine. Osmium(VI) tetroxide is one of the most extensively used probes for DNA structure. It is an example of a high-valent transition metal complex which, due to its uniquely reactive center, is able to functionalize specific bonds on DNA. This powerful oxidant is known to form cisoid osmate esters upon attack of an electron-rich double bond. By tuning the reactivity of OSO4 and its esters with the addition of other ligands, it has been possible to generate a family of reactive probes for exposed pyrimidine bases. 

Preparation of dihydroxytiagabine (VII) was accomplished by the method shown in Scheme 29.19. Synthesis of the 9-0-(4 -Methyl-2 -quinolyl) ether of dihydroquinidinol proved difficult in that the central double bond is hindered and proved to be refractory to attack by reagents such as m-chloroperbenzoic acid and hydrogen peroxide. The putative epoxide was not detected under a variety of reaction conditions a complex mixture of products was always obtained. Reaction with osmium tetroxide/pyridine/V-methylmorpholine-V-oxide was slow and yielded the requisite diol in low yield, but extraction of the product from water proved to be a problem. 

Osmium tetroxide pyridine sodium hydrogen sulfite OsOJCfl N)NaHSO ... 

Cyclodecanediol has been prepared by the hydrogenation of sebacoin in the presence of Raney nickel or platinum, by the reduction of sebacoin with aluminum isopropoxide or lithium aluminum hydride, and by the oxidation of cyclodecene with osmium tetroxide and pyridine. ... 

Thus, Mathis et al. [1, 2] investigated oxidation reactions with 4-nitroperbenzoic acid, sodium hypobromite, osmium tetroxide and ruthenium tetroxide. Hamann et al. [3] employed phosphorus oxychloride in pyridine for dehydration. However, this method is accompanied by the disadvantages that the volume applied is increased because reagent has been added and that water is sometimes produced in the reaction and has to be removed before the chromatographic separation. 

Osmium Tetroxide Oxidation of a A -Cyanopregnene 20-Cyano-21-hydroxy-5j5-pregn-17(20)-ene-3,l l-dione21-methyl ether (8 g) isdissolved in 100 ml of benzene and 8 ml of pyridine. After the addition of 9.6 g of osmium tetroxide, the reaction mixture is stoppered and allowed to stand at room temperature for 5 days. The mixture is stirred for 24 hr with 160 ml of chloroform, 200 ml of methanol and 280 ml of an aqueous solution... 

Selective hydroxylation with osmium tetroxide (one equivalent in ether-pyridine at 0 ) converts (27) to a solid mixture of stereoisomeric diols (28a) which can be converted to the corresponding secondary monotoluene-sulfonate (28b) by treatment with /7-toluenesulfonyl chloride in methylene dichloride-pyridine and then by pinacol rearrangement in tetrahydrofuran-lithium perchlorate -calcium carbonate into the unconjugated cyclohepte-none (29) in 41-48 % over-all yield from (27). Mild acid-catalyzed hydrolysis of the ketal-ketone (29) removes the ketal more drastic conditions by heating at 100° in 2 hydrochloric acid for 24 hr gives the conjugated diketone (30). 

A solution of 1.0 g of A -3,11-diketo-20-cyano-21-acetoxy-pregnene in 10 cc of benzene is treated with 1.0 g of osmium tetroxide and 0.43 g of pyridine. After standing at room temperature for 18 hours, the resulting solution is treated successively with 50 cc of alcohol, and with 50 cc of water containing 2.5 g of sodium sulfite. The mixture is stirred for 30 hours, filtered, and the filtrate acidified with 0.5 cc of acetic acid and concentrated to small volume in vacuo. The aqueous suspension is then extracted four times with chloroform, the chloroform extracts are combined, washed with water and concentrated to dryness in vacuo. Recrystallization of the residue from acetone gives 3,11,20-triketo-17(a)-21-dihydroxy-pregnane MP 227° to 229°C. This compound is then treated with acetic anhydride and pyridine for 15 minutes at room temperature to produce 3,11,20-triketo-17(a)-hydroxy-21-acetoxy-pregnane or cortisone acetate. 

To a solution of 6.36 parts of 17(3-hydroxy-17a-methyl-5o -androst-Ten-3-one in 95 parts of acetic acid and 12 parts of water is added 40 parts of lead tetracetate and 0.6 part of osmium tetroxide. This mixture is stored at room temperature for about 24 hours, then is treated with 2 parts of lead tetracetate. Evaporation to dryness at reduced pressure affords a residue, which is extracted with benzene. The benzene extract is washed with water, and extracted with aqueous potassium bicarbonate. The aqueous extract is washed with ether, acidified with dilute sulfuric acid, then extracted with ethyl acetate-benzene. This organic extract is washed with water, dried over anhydrous sodium sulfate, and concentrated to dryness in vacuo. To a solution of the residual crude product in 20 parts of pyridine is added 10 parts of 20% aqueous sodium bisulfite and the mixture is stirred for about 20 minutes at room temperature. 

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. 

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... 

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. 

This new process has one unexpected benefit the rates and turnover numbers are increased substantially with the result that the amount of the toxic and expensive 0s04 is considerably reduced (usually 0.002 mole %). The rate acceleration is attributed to formation of an Os04-alkaloid complex, which is more reactive than free osmium tetroxide. Increasing the concentration of 1 or 2 beyond that of 0s04 produces only negligible increase in the enantiomeric excess of the diol. In contrast quinuclidine itself substantially retards the catalytic reaction, probably because it binds too strongly to osmium tetroxide and inhibits the initial osmylation. Other chelating tertiary amines as well as pyridine also inhibit the catalytic process. 

The stoichiometric enantioselective reaction of alkenes and osmium tetroxide was reported in 1980 by Hentges and Sharpless [17], As pyridine was known to accelerate the reaction, initial efforts concentrated on the use of pyridine substituted with chiral groups, such as /-2-(2-menthyl)pyridine but e.e. s were below 18%. Besides, it was found that complexation was weak between pyridine and osmium. Griffith and coworkers reported that tertiary bridgehead amines, such as quinuclidine, formed much more stable complexes and this led Sharpless and coworkers to test this ligand type for the reaction of 0s04 and prochiral alkenes. 

The method by which lactone 17 was obtained was not without its own implications for the synthesis. Treatment of 16 with dry tetra n-butylammonium fluoride in acetonitrile achieved desilylation. Not unexpectedly, this process triggered migration of the C5 benzoyl group to the newly unveiled C4 alcohol. The C5 alcohol thereby liberated underwent lactonization to the desired 17 (61% yield from 16). Indeed, reaction of 17 with stoichiometric osmium tetroxide in pyridine-THF afforded a single diol formulated as 18 in 97% yield (see Figure 4). 

Osmium tetroxide forms various complexes with donor molecules under varying conditions. For example, with pyridine(py) it forms a bridged complex, [(py)0s02(p-0)]2. ... 

Other methods for a-hydroxy ketone synthesis are addition of O2 to an enolate followed by reduction of the a-hydroperoxy ketone using triethyl phosphite 9 the molybdenum peroxide-pyridine-HMPA oxidation of enolates 10 photooxygenation of enol ethers followed by triphenylphosphine reduction 11 the epoxidation of trimethyl silyl enol ethers by peracid 1 - the oxidation of trimethylsilyl enol ethers by osmium tetroxide in N-methylmorpholine N-... 

Osmium tetroxide-Trimeth> lamine N-oxide-Pyridine... 

Certain tertiary amines such as pyridine or a-quinuclidine accelerate the stoichiometric reaction between osmium tetroxide and olefins (86). An asymmetric olefin osmylation using stoichiometric amounts of cinchona alkaloids as the chiral ligands was described in 1980 (87a). Optical yields of up to 90% were attained with frans-stilbene as substrate. 

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