1,4-Dipole-Metalated Quinone Strategy to (+/-)-4-Demethoxydaunomycinone and (+/-)-Daunomycine. Annelation of Benzocyclobutenedione Monoketals with Lithioquinone Bisketals

Article abstract of DOI:10.1021/jo00337a002

A strategy for total synthesis of anthracyclinones is outlined in which a benzocyclobutenedione monoketal, serving as a 1,4-dipole equivalent, is reacted with a lithiated quinone bisketal, serving as a metalated quinone equivalent, to afford in one step a fully functionalized tetracyclic ring system.A convenient synthesis of the AB-ring system with the eventual C7 and C9 oxygen functions of the anthracyclinone present has been developed.In addition, a trimethylsilyl-mediated benzylic bromination serves as one of the key steps in a novel methylene-to-carbonyl transformation, resulting in a regiospecific route to benzocyclobutenedione monoketals.The potential general synthetic utility arising from trimethylsilyl-stabilized radical intermediates is noted.The chemistry described above resulted in a convergent, regiospecific route to (+/-)-4-demethoxydaunomycinone and (+/-)-daunomycinone