Jr. Bull et al., CYCLOADDITION-FRAGMENTATION ROUTE TO 14-BETA-ALLYLESTRONE AND THE DERIVED 14-ALPHA,17-ALPHA-ETHANO ANALOG OF ESTRIOL, Tetrahedron, 50(21), 1994, pp. 6363-6376
3-Methoxyestra-1,3,5(10),14,16-pentaen-17-yl acetate (1) undergoes eff
icient baron trifluoride catalysed cycloaddition at 20 degrees C with.
acrolein to give the corresponding 17 beta-acetoxy 14 alpha,17 alpha-
etheno 16 alpha-carbaldebyde (2). The derived 16 alpha-tosyloxymethyl
intermediates are converted via Wharton fragmentation into 14 beta-all
yl derivatives of estrone. Oxidative cleavage of 14-allyl-3-methoxy-14
beta-estra-1,3,5(10)-trien-17-one (14) furnishes the 14 beta-formylme
thyl derivative (17). Intramolecular reductive cyclisation of 17, foll
owed by stepwise protection-deprotection of functionality provides an
efficient synthetic route to 14,17 alpha-ethanoestra-1,3,5(10)-triene-
3,16 alpha,17 beta-triol (23), the structure of which is confirmed wit
h the aid of X-ray crystallographic analysis of the derived triacetate
.