A Synthesis of Aldosterone Acetate¹

The frequently overlooked importance of solvent in free radical syntheses

“…Barton exploited this fact in his ingenious synthesis of aldosterone by the UV photolysis of the nitrite of corticosterone acetate in toluene at room temperature. 8 The photo-generated alkoxyl radical performs an intramolecular H-atom abstraction from the 18 methyl group and the resulting primary alkyl radical is trapped by the photo-generated nitric oxide to form a C-nitroso compound, which tautomerises to the corresponding aldoxime (21% isolated yield). The aldoxime gave aldosterone acetate (B15%) on treatment with nitrous acid 8 (see Scheme 1).…”

“…8 The photo-generated alkoxyl radical performs an intramolecular H-atom abstraction from the 18 methyl group and the resulting primary alkyl radical is trapped by the photo-generated nitric oxide to form a C-nitroso compound, which tautomerises to the corresponding aldoxime (21% isolated yield). The aldoxime gave aldosterone acetate (B15%) on treatment with nitrous acid 8 (see Scheme 1). The low yield is partly due to abstraction from the 19-methyl group, the alkoxyl radical being equidistant from both methyl groups, so that H-atom abstraction occurs from both.…”

Recent developments in use of heteropolyacids, their salts and polyoxometalates in organic synthesis

“…Their synthesis from non-carbonyl compounds [154] provides an alternativeway to aldehydes and ketones. There has been great interest in the development of mild techniques for the conversion of oximes into their corresponding carbonyl compounds [155], but only a little attention has been paid for the regeneration of carbonyl compounds from hydrazones and semicarbazones [156].…”

Cleavage of Oximes, Semicarbazones, and Phenylhydrazones with Supported Potassium Permanganate

“…[3][4][5][6] Over the last two decades, the use of solid supports in synthetic chemistry has become popular and in recent years the use of supported reagents under solvent-free conditions has opened up new and surprisingly useful approaches to chemistry. 7 Among oxidants, supported potassium permanganate has proven to be a reagent whose reactions are easily adapted to solvent-free conditions.…”