CYCLOADDITION MEDIATED SYNTHESIS AND REARRANGEMENT OF 16-FUNCTIONALIZED 14-ALPHA,17-ALPHA-ETHENO-19-NORSTEROIDS

Estra-1,3,5(10),14,16-pentaen-17-yl acetates (1) undergo cycloaddition with 2-acetoxyacrylonitrile to give the corresponding 16 alpha,17 bet a-diacetoxy 14 alpha,17 alpha-etheno 16 beta-carbonitriles (3), accomp anied by minor regio- and stereoisomers depending upon reaction condit ions. An X-ray crystal structure analysis of the major isomer derived from the reaction with 1b(3-OAc) confirmed the structure as 3,16 alpha ,17 beta-triacetoxy-14,17 beta-ethenoestratriene-16 beta-carbonitrile (3b). Hydrolysis of the 16 alpha-acetoxy 16 beta-cyano moiety of 3 fur nishes 17 beta-hydroxy 16-ketones which undergo stereoselective reduct ion to give mainly the corresponding 16 beta,17 beta-diols. Acid-media ted rearrangement of these diols or base treatment of the derived 17 b eta-hydroxy 16 beta-mesylates results in ready 17(1)(17 --> 16)abeo re arrangement, thus providing synthetic access to 14 alpha,16 alpha-etha no derivatives of estrone.