Regiodivergent Iodocyclizations for the Highly Diastereoselective Synthesis of syn- and anti-Hydroxyl-Isochromanones and -Isobenzofuranones: Concise Synthesis of the Isochromanone Core of the Ajudazols

Abstract

An efficient synthetic strategy to access hydroxyl-isochromanone and -isobenzofurans from readily available joint alkene precursors by a regiodivergent one-pot iodocyclization–substitution tandem process is reported. The cyclizations proceed with excellent diastereoselectivities, with <i>E</i>-alkenes giving <i>syn</i>-configured products and <i>Z</i>-alkenes giving <i>anti</i>-products. A strong influence of light on the regioselectivity of the reaction was observed. High yields were also observed under radical conditions. The protective-group-free method enables a highly concise synthesis of the authentic isochromanone core of the ajudazols, which are highly potent inhibitors of the mitochondrial respiratory chain.