Estrone acetate, hydroxylation

Pentafluorophenylhydrazones permit up to 0.1 ng of estrone to be determined with the ECD [381 ]. A hydroxyl group in position 3 is blocked by methylation with dimethyl sulphate and the reaction with pentafluorophenylhydrazine is performed in methanol in the presence of acetic acid. A column packed with 1% of XE-60 on Gas-Chrom Q at 205°C is suitable for the analysis. The determination of free estrone in blood plasma by this procedure provides good results provided that the measurement is corrected for the total recovery. 

Reaction of estrone methyl ether with 2,2-dimethylpropane-l, 3-diol in the presence of a catalytic amount of acid leads to derivative 26-1, in which the ketone at 17 is protected as an acetal (Scheme 3.26). Treatment of this intermediate with pyridinium chlorochromate leads to oxidation of the Cg benzylic carbon atom to a carbonyl group (26-2). Potassium tert-butoxide abstracts a proton from the adjacent methylene at C7 alkylation of the resulting anion with 4-(A, A -dimethyl)butyl iodide gives 26-3 as a mixture of diastereomers. The carbonyl group is next reduced to an alcohol by means of sodium borohydride (26-4). Dehydration of the newly introduced hydroxyl group is arguably facilitated by the adjacent aromatic ring (26-5). Aqueous acid removes the 17-acetal to afford 26-6, which is in essence an equilinin derivative. 

Oxidation of the 17-acetal of estrone (29-1, from estrone and propylene-1,3-glycol) with DDQ abstracts hydrogen from ring C to form the styrenoid derivative 29-2 (Scheme 3.29). The driving force behind this particular regiochemistry may be related to the more transoid nature of that compound compared with the 6,7 isomer. Hydroboration of the product followed by oxidative workup affords the 1 la-hydroxy derivative 29-3. Oxidation of the newly introduced hydroxyl group with chromium trioxide followed by hydrolysis of the 17-acetal yields... 

The nickel-catalyzed Suzuki-Miyaura-type C-O bond arylation has been successfully applied to steroidal architecture (Scheme 4). A hydroxyl moiety in estrone can readily be substituted by an array of aryl groups under nickel catalysis via conversion into pivalate instead of the typically used triflate [38]. The carbonyl moiety in estrone also serves as a suitable precursor for an alkenyl C-O electrophile. Treatment of estrone with 2-propenyl acetate affords the compounds bearing two acetate groups, both of which are potentially reactive toward nickel-catalyzed cross-coupling. However, selective arylation took place at the alkenyl position, and... 

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