Synthesis Based on Cyclohexadienes. 5. A New Approach to the Synthesis of a-Ring Aromatic Steroids - a Formal Total Synthesis of (+/-)-Estrone

Abstract

A new strategy for the construction of A-ring aromatic steroids which resulted in the formal total synthesis of estrone is described. Thus reaction of the adduct (9), obtained from 1-methoxy-4-methylcyclohexa-1,4-diene and acrolein , with 3-(m-methoxypheny1) propyl -magnesium bromide followed by oxidation afforded the bicyclo [2.2.2] octene derivative (14). Acid-catalysed rearrangement of (14) followed by an intramolecular Michael addition resulted in the cis tetraenone (18) which was dehydrogenated with palladium chloride to the pentaenone (22). Li/NH3 reduction of (22) gave 3-methoxy-D-homoestra-1,3,5(10)-trien-16-one (31) which has been converted into the methyl ether (37) of marrianolic acid, and its methyl ester (38).