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

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 E-alkenes giving syn-configured products and Z-alkenes giving anti-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. [ABSTRACT FROM AUTHOR]