Woodward modification

The present procedure offers a convenient alternative to the Prevost reaction and the Woodward modification of the Prevost reaction in which silver carboxylates are used instead of thal-lium(I) carboxylates. Thallium(I) salts have the advantages of being generally stable crystalline solids that can be readily prepared in high yield by neutralization of the appropriate carboxylic acid with thallium(I) ethoxide. Silver salts, on the other hand, are frequently unstable and difficult to dry. Thallium and its compounds are, however, extremely toxic, and great care must therefore be taken in the use and disposal of thallium salts. ... 

The Woodward modification of the Oppenauer oxidation is occasionally used on substrates that fail to be oxidized under the standard protocol,27 although it possesses the serious limitation of the strongly basic medium generated by potassium f-butoxide. 

The Prevost Reaction allows the synthesis of anti-diols from alkenes by the addition of iodine followed by nucleophilic displacement with benzoate in the absence of water. Hydrolysis of the intermediate diester gives the desired diol.The Woodward Modification of the Prevost Reaction gives syn-diols. 

In the Woodward-Modification, added water decomposes the above benzoxonium intermediate directly to a -substituted diol. 

The use of expensive silver salts, the requirement for a stoichiometric amount of molecular halogen, and the formation of a relatively large amount of organic and inorganic wastes are definite drawbacks to this reaction. Sudalai recently reported on catalytic versions of both the Prevost Reaction and the Woodward-Modification. 

Hydrolysis of the ester does not change the configuration. The Woodward modification of the Prevost reaction is similar, but results in overall syn hydroxylation. The alkene 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-halo ester the addition is anti and a nucleophilic replacement of the iodine occurs. However, in the presence of water, neighboring-group participation is prevented or greatly decreased by solvation of the ester function, and the mechanism is the normal Sn2 process, ... 

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). 

A major trend in organic synthesis, however, is the move towards complex systems. It may happen that one needs to combine a steroid and a sugar molecule, a porphyrin and a carotenoid, a penicillin and a peptide. Also the specialists in a field have developed reactions and concepts that may, with or without modifications, be applied in other fields. If one needs to protect an amino group in a steroid, it is advisable not only to search the steroid literature but also to look into publications on peptide synthesis. In the synthesis of corrin chromophores with chiral centres, special knowledge of steroid, porphyrin, and alkaloid chemistry has been very helpful (R.B. Woodward, 1967 A. Eschenmoser, 1970). 

Comparatively few alterations have been made since 1989 in the structures accepted for well-known alkaloids. A slight but important change has been adopted in the formula of strychnine and contributions to the chemistry of that alkaloid and its associates are still being made, though the formula seems now so well established that Woodward has recently suggested and discussed a scheme for the biogenesis of strychnine on which Robinson has commented favourably. Robinson has also proposed a scheme for the biogenesis of emetine. This involves a modification in the formula of that alkaloid, which is supported by Dewar s interpretation of the results of recent chemical work on emetine by Karrer et al., by Spath and by Pailer. ... 

Haddock, P.S., Woodward, B., Hearse, D.J. and Dodds, R. (1991). Modification of the activity of bovine Na/K ATPase by reduced and oxidised glutathione and other sulphydryl compounds. Br. J. Pharmacol. 102, 54P. 

Johnson, A.R., and Dekker, E.E. (1996) Woodward s reagent K inactivation of Escherichia coli L-threo-nine dehydrogenase Increased absorbance at 340-350 nm is due to modification of cysteine and histidine residues, not aspartate or glutamate carboxyl groups. Protein Sci. 5, 382-390. 

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. 

The subsequent steps in the French and Czech modifications follow the Woodward synthesis in its broad lines, but it should be noted that Velluz already resolves Woodward s XXXV into optical isomers with the help of either brucine or ephedrine (185). In an analogous study, the Czech investigators resolve a hydroxy acid (XXXVIII), obtained by hydrolysis of the Velluz compound (XXXVII) (185), with the help of brucine (187). Also, another dihydroxy acid (XXXIX), obtained from Woodward s lactone acid (XXXVI), has been resolved, again by use of... 

Progesterone, a female sex hormone, has been prepared by total synthesis and by modifications of other steroids. Using established methodologies, such as Diels-Alder cycloadditions, Michael additions, Robinson annulations, aldol reactions, and ring contraction reactions, propose a total synthesis of progesterone. Discuss the merits of your approach in comparison with the total synthesis reported by Woodward, R. B., Sondheimer, R, Taub, D., Heusler, K., McLamore, W. M. J. Am. Chem. Soc. 1952, 74, 4223. 

The first step of the Provost reaction is the reaction of the alkene with iodine to form the cyclic iodonium ion. Next, the iodonium ion is stereospecifically opened by the silver carboxylate to form the corresponding frans-1,2-iodo carboxylate. The iodine is displaced intramolecularly by the carbonyl group of the carboxylate (anchimeric assistance) to form a cyclic cationic intermediate. In the absence of water, this cation is opened with the inversion of configuration by the second equivalent of silver carboxylate to afford the frans-1,2-dicarboxylate. However, in the presence of water Woodward-Brutcher modification) the common intermediate is converted to a c/s-orthocarboxylate which is hydrolyzed to the corresponding c/s-1,2-diol. 

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