Chromium trioxide cyclic acetal oxidation

In contrast to the usual reaction of aromatic aldehydes with cyclic ketones o-nitrobenzaldehyde condenses with 17-ketones to produce good yields of seco-acids, a reaction which has been applied to the preparation of 16-oxa-steroids. Thus, 3 -hydroxy-5a-androstan-17-one or its acetate affords the seco-steroid (153), which can be oxidised either as the free acid by ozone and alkaline hydrogen peroxide to the diacid (155) or, as its methyl ester (154), with chromium trioxide to the monomethyl ester (156). Diborane reduction of the diacid (155) or lithium aluminium hydride reduction of the dimethyl ester (157) gave the trans-diol (158), cyclised with toluene-p-sulphonic acid to 16-oxa-androstan-3)5-ol (159) or, by oxidation with Jones reagent to the lactone (152) (as 3-ketone) in quantitative yield. This lactone could also be obtained by lithium borohydride reduction of the monomethyl ester (156), whilst diborane reduction of (156) and cyclisation of the resulting (151) afforded the isomeric lactone (150). The diacid (155) reacted with acetic anhydride to afford exclusively the cis-anhydride (161) which was reduced directly with lithium aluminium hydride to the cis-lactone (160) or, as its derived dimethyl ester (162) to the cis-diol (163) which cyclised to 16-oxa-14)5-androstan-3) -ol (164). 

In 1952, Frank B. Colton (1923-2003) at Searle synthesised and later patented norethynodrel, an isomer of norethisterone. An improved synthesis emerged, in which both compounds were obtained, while the aromatisation and Birch reduction could be avoided. [41,42] As starting point serves 5-androsten-3/l-ol-17-one acetate, to which hypochlorous acid is added. Notable is the thermal or photochemical functionalisation of C-19 with lead tetraacetate/iodine, [43] under formation of a cyclic ether. Hydrolysis ofthe ester and oxidation with chromium trioxide leads to a A -enedione, while HCI is eliminated. Reductive opening ofthe ether gives the 19-hydroxy-compound, which can be oxidised with chromium trioxide to the lOjS-carboxylic acid and then decarboxylated in... 

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