Steroids and related products. XLVI. The regiospecific alpha-hydroxymethylation of saturated carbonyl compounds via preformed enolate ions. An improved synthesis of 17-hdyroxymethyl 20-keto steroids

As demonstrated for pregnenolone, saturated ketones are conveniently alpha-hydroxymethylated by their transformation into a lithium enolate and by the reaction of the latter with formaldehydr. The 17-hydroxymethylpregnenolone prepared by this method in very good yield was readily converted to 17-hydroxymethylprogesterone; either by selective acetylation in position 17(1) and subsequent Jones oxidation, followed by hydrolysis, or by conversion to the 4,5-dibromo 3-ketone - by bis(tri-n-butyltin)oxide-bromine oxidation or by dibromination and oxidation with N-bromoacetamde - and debromination with zinc and acetic acid.