SYNTHESIS OF ANTIBIOTICS WS-5995-A AND WS-5995-C AND RELATED-COMPOUNDS BY PALLADIUM-CATALYZED COUPLING OF 2-BROMONAPHTHOQUINONES WITH ORGANOSTANNANES

The synthesis of arylnaphthoquinones can be performed simply by using as the key reaction the Pd(0)- and Cu(I)-catalyzed coupling of arylsta nnanes with 2-bromonaphthoquinones as the electrophiles. The palladium -catalyzed coupling reaction is general and allows for the functionali zation of the unprotected quinone nucleus with alkyl, alkenyl, and ary l substituents. The coupling process tolerates the presence of a chela ted peri hydroxyl and steric crowding of a 2,6-disubstituted arylstann ane, although the preparation of a 2,6,2',6'-tetrasubstituted biaryl b y coupling of 2-bromo-3,5-bis(acetyloxy)-1,4-naphthoquinone as the ele ctrophile with 2,6-disubstituted arylstannanes was unsuccessful. The s yntheses of quinonoid antibiotics WS 5995 A and C was accomplished by using this method as the key step. Benz[b]phenanthridinone 1, hypothet ical intermediate in the biosynthesis of benz[b]phenanthridine alkaloi ds, was also prepared from antibiotic WS 5995 C or by addition of ammo nia to the 2-aryl-1,4-naphthoquinone 41 followed by heterocyclization.