Annelation Reactions of Quinone Monoketals. Studies Directed at an Efficient Synthesis of Anthracyclinones

Article abstract of DOI:10.1021/jo00176a020

The annelation chemistry of quinone monoketals with dimethyl homophthalate, 7-methoxy-3-(phenylsulfonyl)-1(3H)-isobenzofuranone, and 7-methoxy-3-cyano-1(3H)-isobenzofuranone has been studied.The first two reagents mentioned above allowed the formation of oxygenated tri- and tetracyclic anthrone and anthraquinone systems in 40-50percent yields.While less extensively studied, the 7-methoxy-3-cyano-1(3H)-isobenzofuranone afforded a 75percent yield in an annelation reaction with a highly functionalized monoketal.These reactions, coupled with the unique effect of an allylic methoxylgroup on the regiochemistry of quinone bisketal hydrolysis, allowed a regiospecific preparation of certain tetracyclic anthraquinones.The work reported herein comprises a formal synthesis of racemic daunomycinone and forms a basis for an efficient, practical synthesis of fully functionalized anthracyclinones.