Regiocontrol by remote substituents. An enantioselective total synthesis of frenolicin B via a highly regioselective Diels-Alder reaction

Thequinone subunit is contained in a broad range of biologically important natural products.' This subunit is present in anticancer agents such as the anthracyclines, antibiotics such as the rifamycins, antifungal agents such as kalafungin, and antimidial agents such as frenolicin B.2 The latter two compounds are members of the pyranonaphthoquinone family. The diverse biological activity of quinones has led to the development of several new synthetic methods for quinones. A number of methods involving cycloadditions,3 carbanion-mediated annulations,4 and nucleophilic and electrophilic reactions5 have been reported. Among the pathways featuring a cycloaddition reaction, one of the most general methods for the regiospecific synthesis of substituted quinones was pioneered by Rapoport and others.6 This method involves the Diels-Alder reaction of a substituted quinone and is depicted below. The X group is usually chlorine or bromine, but nitriles and sulfoxides7 can also be employed.