Bis-oxygenated pregnanes

A classical method for the vicinal hydroxylation of a double bond involves treatment with osmium tetroxide to give a cyclic ester, followed by reductive cleavage to the glycol  

When applied to A -pregnenes, 17a,20-glycols are produced exclusively, because of rear-side attack by the reagent. 

The reaction is usually carried out in ether or benzene, but since pyridine markedly catalyzes the rate of the reaction,the use of this base as the sole solvent is recommended.  

The cleavage of the intermediate osmate ester has presented problems in the past, and a variety of procedures have been developed, including the use of mannitol and strong aqueous base, refluxing aqueous alcoholic sodium bisulfite,formaldehyde and ascorbic acid. A much milder method involves simply bubbling hydrogen sulfide into a solution of the osmate ester osmium dioxide is precipitated rapidly, and the desired organic 

Selectivity between A -olefins and other double bonds can often be excellent S-keto-A, A and A systems are relativelyunreactive, and functional groups at C-21 e.g., OH, OAc) or at C-20 e.g., CN, Br) normally do not interfere. With functional groups at C-20, the final products are 20-ketones rather than 20-aIcohols, the intermediate bromohydrin or cyanohydrin cleaving during workup to the ketone. 

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The 17-ethylidene steroids are extremely useful intermediates for the preparation of 17-oxygenated, 20-oxygenated, or 17,20-bis-oxygenated pregnanes (Chart I) and their further conversion will be discussed in later sections... 

Many of the reactions already discussed for the preparation of bis-oxygenated pregnanes can also be used for the synthesis of 17,20,21-tris-oxygenated pregnanes by proper choice of substrate. Thus, reaction of a 17-vinyl-17-hydroxy steroid or a A -21-hydroxypregnene with osmium tetroxide will give the 17,20,21-triol, and the Stork reaction can be applied to 17a-hydroxy-20-keto steroids. 

Preparation of 17,20-bis-oxygenated pregnanes by side-chain oxygenation of pregnanes... 

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