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

Sebastian Thiede; Peter Maria Winterscheid; Jan Hartmann; Gregor Schnakenburg; Sebastian Essig; Dirk Menche

doi:10.1055/s-0035-1561278

Synthesis, Table of Contents

Synthesis 2016; 48(05): 697-709
DOI: 10.1055/s-0035-1561278

paper

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

Sebastian Thiede

^aKekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany Email: dirk.menche@uni-bonn.de

,

Peter Maria Winterscheid

^aKekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany Email: dirk.menche@uni-bonn.de

,

Jan Hartmann

^bUniversität Heidelberg, Institut für Organische Chemie, INF 270, 69120 Heidelberg, Germany

,

Gregor Schnakenburg

^cInstitut für Anorganische Chemie, Universität Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany

,

Sebastian Essig

^bUniversität Heidelberg, Institut für Organische Chemie, INF 270, 69120 Heidelberg, Germany

,

Dirk Menche*

^aKekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany Email: dirk.menche@uni-bonn.de

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Abstract

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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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References

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