The synthetic feasibility of a spiroannulation procedure involving a concerted 1,2-carbonyl migration will be demonstrated by its inclusion in the synthesis of the antitumor agent Fredericamycin A and related antibiotics incorporated in a spiro ring system. A variety of synthetic procedures leading to the isomeric dibenzospiro (4.4) ring skeleton have been outlined. This ring expansion methodology involving a 1,2-carbonyl migration of a cyclobutanone has been applied to the synthesis of various model analogues of Fredericamycin A. A method for constructing the contiguous six-membered rings adjoining the (4.4) spiro center has been proposed that utilizes the Diels-Alder cycloaddition reaction of o-quinodimethane and isobenzofuranone intermediates to the carbon-carbon double bond of the spiro dienophile, spiro(3- cyclopenten-2,5-dione-1,1'-indan). The isoquinolone portion of the molecule will be prepared by the acid or base catalyzed cyclization of a polyketide intermediate.
