Abstract
A unified synthetic strategy toward the oridamycin and xiamycin families of natural products was designed, aiming to access several natural products from a common synthetic intermediate readily prepared from geranyl acetate. Part of this strategy was successfully realized, culminating in the synthesis of oridamycin A and oridamycin B. Key steps include a Mn(III)-mediated oxidative radical cyclization to construct the trans-decalin ring, and a 6π-electrocyclization/aromatization sequence to produce the 2,3-fused carbazole. Oridamycin B was accessed through a late-stage, C-H oxidation that converted the C16 methyl to a hydroxymethyl. A variety of strategies were explored to form a chelated radical intermediate en route to xiamycin A, including enolate SET oxidation, oxo-vanadium oxidation, and atom-transfer cyclization. Unfortunately, none of these strategies provided the desired C16-epimeric trans-decalin. Exploratory studies on photoredox-catalyzed radical cyclizations yielded interesting results, including the formation of a bicyclic lactone arising from oxidative termination of the photoredox-catalyzed radical cyclization, and a double 6-endo cyclization with catalyst loadings as low as 0.01 mol%.