Bismethylenedioxy acetal

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. 

This nitrite (5 g) is dissolved in 200 ml of toluene and photolyzed For 2 hr at 20° as described above. Without further treatment the solution is chromatographed on 100 g of alumina and eluted with methylene dichloride containing increasing proportions of methanol. The first fraction gives 0.6g prednisolone BMD. The latter fractions afford 17,20 20,21-bismethylenedioxy-llj5-hydroxy-18-oximinopregna-l,4-dien-3-one (3 g) mp 270-274° [oc]d 0°, after crystallization from ethyl acetate-hexane. 

A bismethylenedioxy group in a 4-chloro or 11-keto steroid is stable to cleavage by formic acid or glacial acetic acid (100°, 6 h). The tetramethyl derivative is readily hydrolyzed (50% AcOH, 90°, 3-4 h, 80-90% yield). ... 

The bismethylenedioxy group (BMD) [ (49)] represents the most suitable protecting group for the dihydroxyacetone side chain of corticosteroids. This group is stable to lead tetraacetate, brief heating with hydrochloric acid in acetic acid,108 or with sulfuric acid in methanol18 and to Jones oxidation.189... 

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. 

Miscellaneous Reactions.—Trity fluoroborate. previously reported as cleaving acetals by hydride abstraction, also cleaves benzylic ethers and a variety of related species, giving benzaldehydes. " Cholesteryl benzyl ethers afford cholesterol. The bismethylenedioxy protecting group for the corticosteroid side-chain is also cleaved with this reagent. 

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