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 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.

Key words

natural products - asymmetric synthesis - iodocyclisation - tandem reaction - diastereoselectivity

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