Woodward hydroxylation

Whipworm, 303 Willgerodt reaction, 68 Wittig condensation, 3, 6 Wittig reaction, 420 Woodward hydroxylation,... 

Woodward hydroxylation of 256 leads mainly to sterically disfavored products having cis-oriented substituents at C-2 and C-3, and C-2 and C-4. In fact, in this case also, the attack of I4 occurs from the less-hindered side. The iodonium ion (284) is then opened by the acetate anion, to afford iodo acetate 285 which, in the following substitution reaction with silver acetate, gives the more-hindered, c/.y-hydroxylation product 286. 

Vicinal iodo carboxylates may also be prepared from the reaction of olefins either with iodine and potassium iodate in acetic acid/ or with N-iodosuccinimide and a carboxylic acid in chloroform. " A number of new procedures for effecting the hydroxylation or acyloxylation of olefins in a manner similar to the Prevost or Woodward-Prevost reactions include the following iodo acetoxylation with iodine and potassium chlorate in acetic acid followed by acetolysis with potassium acetate reaction with iV-bromoacetamide and silver acetate in acetic acid reaction with thallium(III) acetate in acetic acid and reaction with iodine tris(trifluoroacetate) in pentane. ... 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

One of the first major pharmaceutical biotransformations was the development of the synthesis of hydrocortisone in the late 1940s by whole-cell hydroxylation (Figure 2.2). Up until then a 40-step synthetic route developed by the Noble Prize winning chemist R.B.Woodward was the only source of this important drug substance and intermediate. Nowadays, a biocatalyst exists for the selective hydroxylation of every position on the steroid nucleus. ... 

Only much later was the hydroxylation of pure trans-307 and cis-307 performed, and the corresponding ci.s-diols were obtained in 22-26% yield. The compound obtained from t ran 4-307 was converted199 into ert/fhro-pentopyranos-4-ulose hydrate by successive alkaline de-benzoylation, and hydrolysis of the acetal in the presence of Dowex W-50 resin. An attempt at direct tran.s--hydroxylation of trans-307 by Woodward s or Prevost s method failed, as have attempts at its epoxi-dation with peroxy acids.200 Nevertheless, a number of 3,4-epoxides... 

Hydrolysis of the ester does not change the configuration. Woodward s method is similar, but results in overall syn hydroxylation. The olefin is treated with iodine and silver acetate in a 1 1 molar ratio in acetic acid containing water. Here again, the initial product is a 3-... 

The Woodward Reaction (or Woodward c/s-Hydroxylation) allows the synthesis of syn-diols from alkenes by the addition of iodine followed by nucleophilic displacement with acetate in the presence of water. Hydrolysis of the intermediate ester gives the desired diol. The Prevost Reaction gives crn/z -diols. 

The desired diol can be isolated after hydrolysis. Woodward noted, that his modification of the Prevost reaction offers the opposite facial selectivity as compared to oxidations with 0s04 in the hydroxylation of synthetic steroid intermediates. Here, the steric approach factors first direct the stereochemistry of the iodination, which is followed by hydroxylation from the opposite face, whereas 0s04 leads to the isomeric cw-diol by direct attack from the most accessible face. 

Since Criegee s pioneering work in the late 1930s, the accepted mechanism for hydroxylation has been a concerted cycloaddition of alkene to the 0=0s=0 system.58 The development of the theory of pericyclic reactions in the 1960s and 1970s helped cement this proposal firmly in the minds of many workers.59 However, subsequent work has found few (if any) documented organometallic examples that followed the Woodward-Hoff-mann rules. 

Syn hydroxylation from the more hindered face of a ir-system can be effected using Woodward s pro-cedure in which an alkene is treated with iodine-silver acetate in acetic acid containing water. Variants of this method avoid the use of silver salts.A versatile pocedure by which syn hydroxyla-tion can be performed on either the more hindered or less hindered face of an alkene relies on stereoselective formation of the appropriate traru-bromohydrin from the alkene. ... 

Several related procedures for syn hydroxylation of alkenes involve a halohydrin ester (32) as the key intermediate. In Woodward s procedure an alkene in glacial acetic acid is treated with iodine and silver acetate. Acetyl hypoiodite, MeCOjI, formed by reaction of the latter two reagents attacks the alkene, R R 0=CR R in an electrophilic manner, from the less hindered side to give, by overall anti addition. 

Since silver salts are expensive, other cheaper reagents have been sought which can bring about the same type of conversion, and the iodine- tassium iodate- tassium acetate combination has been found to provide a useful alternative. Thallium(I) acetate may be used in place of silver acetate in the Woodward procedure, and syn hydroxylation of steroidal alkenes with dialliumflll) acetate in acetic acid has been performed. ... 

Both complexes are used in the hydroxylation of double bonds via diacetates or dibenzoates of vicinal diols. The reaction is stereospecific. In anhydrous medium (the Privost reaction [783]), the reaction takes place in the anti mode. In the presence of water (the Woodward modification [783]), the reaction results in a syn addition. The mechanisms of both reactions are shown in the section Hydroxylation of Alkenes and Cycloal-kenes in Chapter 3 see equation 78). 

Woodward, R. B., Brutcher, F. V., Jr. Cis hydroxylation of a synthetic steroid intermediate with iodine, silver acetate, and wet acetic acid. J. 

Prevost method The overall //7//-hydroxylation of an alkene achieved by treating the alkene with a 1 2 molar ratio of iodine and silver benzoate, followed by hydrolysis. Overall. syw-hy droxy 1 ation may be achieved by the method of Woodward. 

Woodward method The syn-hydroxylation of an alkene the first step involves treating the alkene with iodine and silver acetate in a 1 1 molar ratio in wet acetic acid. The hydrolysis of the intermediate c/////-P-halogenoester is via a normal SN2 reaction in which there is no neighbouring group effect because the ester function is solvated by the water. Overall //-addition may be achieved by the method of Prevost. 

Woodward and Brutcher developed a procedure for the cis-hydroxylation of olefins which combines halogenation with acetolysis in wet acetic acid. Thus the synthetic intermediate (1) on treatment in acetic acid with iodine (1.05 equiv.). 

Woodward cis-hydroxylation. The hydrox-ylation of an olefin with iodine and silver acetate in acetic acid to give cw-glycols. The method involves the trans addition of iodine and silver acetate to give a trans-iodo-acetoxy derivative. The latter is hydrolyzed to a cw-mono-glycol acetate with acetic acid and water. Alkaline hydrolysis results in the final cis-glycol. 

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