Aldehydes Osmium tetroxide

Osmium tetroxide, reaction with alkenes, 235-236 toxicity of, 235 Oxalic add, structure of, 753 Oxaloacetic acid, structure of, 753 Oxetane, reaction with Grignard reagents, 680 Oxidation, 233, 348 alcohols, 623-626 aldehydes, 700-701 aldoses, 992-994 alkenes, 233-236 biological, 625-626 phenols, 631 sulfides, 670 thiols, 668... 

The crystalline material was shown to be modified sesquiterpinoid (5) containing two aldehyde functions, one of which is a,/3-unsat-urated (la). It analyzed for C13H22O2 and formed the dioxime. It readily took up oxygen on standing and was converted to the diol on treatment with lithium aluminum hydride. The bisdinitrobenzoate of this diol with osmium tetroxide yielded the tetraol, bisdinitrobenzoate, which was not readily acetylated. 

Osmium tetroxide used in combination with sodium periodate can also effect alkene cleavage.191 Successful oxidative cleavage of double bonds using ruthenium tetroxide and sodium periodate has also been reported.192 In these procedures the osmium or ruthenium can be used in substoichiometric amounts because the periodate reoxidizes the metal to the tetroxide state. Entries 1 to 4 in Scheme 12.18 are examples of these procedures. Entries 5 and 6 show reactions carried out in the course of multistep syntheses. The reaction in Entry 5 followed a 5-exo radical cyclization and served to excise an extraneous carbon. The reaction in Entry 6 followed introduction of the allyl group by enolate alkylation. The aldehyde group in the product was used to introduce an amino group by reductive alkylation (see Section 5.3.1.2). 

The total synthesis of ( )-geissoschizine (30) was reported by Yamada et al. (156) in 1974. The geometrically pure p-nitrophenyl ester 272 was condensed with tryptamine, and then the resulting amide 273 was transformed to lactam aldehyde 274 by hydroxylation with osmium tetroxide, metaperiodate oxidation, and Pictet-Spengler cyclization. 

Oxandrolone Oxandrolone, 17j3-hydroxy-17a-methyl-2-oxa-5-androstan-3-one (29.3.10), is made by oxidation of the C1-C2 double bond of 17j3-hydroxy-17a-methyl-l-androsten-3-one by a mixture of lead tetraacetate and osmium tetroxide with an opening of the A ring of the steroid system, which forms an aldehyde acid (29.3.9). Upon reducing the aldehyde group with sodium borohydride, intramolecular cyclization takes place, directly forming a lactone (29.3.10), which is the desired oxandrolone [31,32]. 

Furo[3,2-c][l]benzopyran-4-ones have been prepared either by acid catalyzed condensation of 4-hydroxycoumarin with a benzoin derivative (equation 11) (81IJC(B)614) or from 3-allyl-4-hydroxycoumarins on oxidation with osmium tetroxide/potassium periodate followed by cyclization of the intermediary aldehyde with PPA (equation 12) (79G109). 

In a first step, the TBS ether is subjected to acid cleavage with copper sulfate in acetone containing a catalytic amount of glacial acetic acid. The resulting diol is then protected as an acetunide. Next, the double bond is oxidatively cleaved with sodium periodate and a catalytic amount of osmium tetroxide to give aldehyde 5. 

Oxidative cleavage of the olefin is accomplished by the method of ijemieux-Johnson.12 The process begins with dihydroxylation of the double bond using osmium tetroxide (see Chapter 3)T leading to a cis diol and osmium(VI) oxide. The added periodate has two functions first, it reoxidizes the osmium(VI) species to os-mium(VIII), but it also cleaves the glycol oxidatively to an aldehyde. This is the reason for utilizing several equivalents of periodate. The periodate is in turn reduced from the +VH to the +V oxidation state. 

Dihydroxylation with catalytic osmium tetroxide and stoichiometric oxidant such as NMO (TV -methylmorpholine-A -oxide) gives diols that can be cleaved to the same aldehydes with sodium periodiate or lead tetra-acetate. It is also possible to combine either KMnC>4 or catalytic OSO4 with an excess of NaIC>4 and complete the operation in one pot. 

Protected a,3-dihydroxy aldehydes have been prepared by oxidation of acetals of a,B-unsaturated aldehydes with osmium tetroxide in the presence of (23), and a remarkable level of enantioselection ee 2 90%) thereby achieved. Oxidation of chiral acetals of a,p-unsaturated aldehydes in which chirality resides in the noncarbonyl moiety with osmium tetroxide-t ydroquinine acetate (or dihydroquitudine acetate) may be regard as a process in which double stereoselection is at work and a high dia-stereoisomeric ratio of products may be obtained. 

The conversion of tetrasubstituted double bonds to the corresponding ketones is easily achieved using a number of oxidants. However, if one or more of the alkenic carbons is secondary, the product will be either an aldehyde or a carboxylic acid Ozone and a combination of osmium tetroxide and sodium metaperiodate are recommended if the desired product is an aldehyde. Under carefully controlled conditions it is also possible to obtain good yields of the aldehyde when permanganate is used as the oxidant All methods that give aldehydes from secondary carbons can also be used to prepare ketones from tertiary carbons. 

The physical properties, preparation and reactions of ruthenium tetroxide have been reviewed by Lee and van den Engh, Rylander," Haines and Hetuy and Lange. A more vigorous oxidant than osmium tetroxide, its reaction with double bonds produces only cleavage products. " Under neutral conditions aldehydes are formed from unsaturated secondary carbons while carboxylic acids are obtained under alkaline or acidic conditions. For example, Shalon and Elliott" found that ruthenium tetroxide reacted with compound (11) to give the corresponding aldehyde under neutral conditions, but that a carboxylic acid was formed in acidic or alkaline solvents (equation 23). 

In a typical example, sodium periodate (18.2 g, 85 mmol) was added in small portions over a 45 min period to l,4-dioxa-6-acetyl-6-allylspiro[4.5]decane (8.9 g, 40 mmol) and osmium tetroxide (0.10 g, 0.39 mmol) in a solution of THF (126 mL) and water (42 mL) at room temperature. The mixture was stirred for 2 h at this temperature during which time the black slurry turned brown. Water (600 mL) was introduced, and the mixture was extracted with ether. The extract was dried over anhydrous magnesium sulfate and stripped of solvent to give 7.4 g of crude aldehyde. (Because osmium tetroxide is a toxic and volatile irritant, all preparations should be carried out in a fume hood with use of adequate personal protection, gloves and safety glasses.) Other examples of the use of this reagent have b n summarized in Table 5. 

An example is the acid-catalyzed condensation between the dimethyl acetal of an ot,/ -un-saturated aldehyde and a suitably AT-protected norephedrine which affords 2-alkenyloxazoli-dines 1 with a general kinetic as well as a thermodynamic preference for the diastereomer with the alkenyl moiety cis to the methyl and phenyl substituents1. Reaction with osmium tetroxide leads to the cw-diols 2 and 3 with a d.r. of 73 27. 

Optically active 1,2-diol units are often observed in nature as carbohydrates, macrolides or polyethers, etc. Several excellent asymmetric dihydroxylation reactions of olefins using osmium tetroxide with chiral ligands have been developed to give the optically active 1,2-diol units with high enantioselectivities. However, there still remain some problems, for example, preparation of the optically active anti-1,2-diols and so on. The asymmetric aldol reaction of an enol silyl ether derived from a-benzyloxy thioester with aldehydes was developed in order to introduce two hydroxyl groups simultaneously with stereoselective carbon-carbon bond formation by using the chiral tin(II) Lewis acid. For example, various optically active anti-a,p-dihydroxy thioester derivatives are obtained in good yields with excellent diastereo-... 

Although known for almost forty years, and in spite of a total synthesis of its racemate, the stereochemistry of doisynolic acid has remained in doubt. This problem has now been settled by a stepwise chemical conversion (Scheme 23) of 14)5-oestrone methyl ether (339), prepared from natural oestrone (114a), into c/s-doisynolic acid methyl ether (342). Osmium tetroxide oxidation of the enol acetate corresponding to (339) provided 16a-hydroxy-14)S-oestrone methyl ether. Subsequent periodic acid oxidation afforded the lactol (340), which upon treatment with diazomethane gave the aldehydo-ester (341). Electrochemical reduction of the aldehyde (341) afforded a methyl ester which by alkaline hydrolysis provided (-f )-ds-doisynolic acid 3-methyl ether (342), thus defining its complete stereochemistry. ... 

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