Bismethylenedioxy formation

The dihydroxyacetone side chain is conveniently protected by forming 17a,20 20,21-bismethylenedioxy compounds (BMD) (92). Formation of llf -ethers as by-products from 11 -hydroxycompounds (91) can be limited by using formalin with a low methanol content, or better with paraformaldehyde as a source of alcohol-free formaldehyde. ... 

In contrast to this, hydrolysis of 17a,20 20,21-bismethylenedioxy-19-nor-9y ,10a-pregn-4-en-3-one using aqueous 90% formic acid at reflux temperature for 3 min gives an overall yield of 17a,21-dihydroxy-19-nor-9, 10a-pregn-4-ene-3,20-dione 21-formate of 12%. 

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

A cortisone synthesis using remote functionalization at an unactivated carbon centre has been achieved.97 Cortexolone (224) was converted into the 5a-H,3j3-OH derivative (formation of the bismethylenedioxy-compound followed by lithium-ammonia-ethanol reduction). Inversion98 of 3)8- to 3 -OH followed by esterification with m-iodobenzoic acid produced (225), which on irradiation in methylene chloride containing phenyl iodide dichloride gave the 9 a -chloro-derivative (not isolated). This was dehydrohalogenated and saponified by methanolic potash to yield (226) (75%) and thence, by further known steps, cortisone acetate. 

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